Research Trends and Evidence Gaps in Selected South/Central American Medicinal Plants: A Scientometric Review

Abstract

Medicinal plants from South and Central America are widely used, but the scientific literature remains fragmented and strongly concentrated in laboratory-based studies. This scientometric review mapped research trends and translational gaps for five focal species (Amburana cearensis, Libidibia ferrea, Justicia pectoralis, Lippia origanoides, and Spondias mombin). These species were selected because they combine ethnobotanical relevance, recurrent pharmacological and phytochemical interest, and sufficient representation in the retrieved corpus to support comparative scientometric analysis. Records indexed in the Web of Science Core Collection (1991–2024) were analyzed using VOSviewer and Bibliometrix within a transparent and reproducible workflow. Evidence was also organized across four domains, chemistry, preclinical, clinical, and safety, to support cross-species synthesis. A total of 183 publications were included. Brazil accounted for more than 60% of the records and concentrated the most productive authors and institutions. The Journal of Ethnopharmacology was the main publication outlet, followed by Industrial Crops and Products, indicating overlap between ethnopharmacological research and application-oriented development. Keyword networks were dominated by Spondias and Lippia, with recurring themes such as antioxidant activity, antimicrobial activity, and in vitro assays. Across species, preclinical evidence substantially exceeded controlled human studies and systematic safety reporting. Controlled trials were found only for Amburana and Justicia, whereas clinical and safety gaps remained evident for the other species despite the extensive experimental literature. Overall, the field is expanding, but its translational progress remains uneven. Future advances will depend on stronger chemical standardization, mechanism-driven study designs, and better integration of clinical and safety evidence.

1. Introduction

Medicinal plants have long been used worldwide in traditional health practices and remain especially important in low-income regions, while in recent decades they have also attracted renewed attention in industrialized countries due to the growing demand for natural therapies and phytotherapeutic products with pharmaceutical and commercial value [1,2]. Their therapeutic relevance is largely associated with a wide diversity of bioactive compounds, particularly secondary metabolites such as alkaloids, flavonoids, saponins, and tannins, which have been linked to antimicrobial, anti-inflammatory, antioxidant, and other pharmacological activities [3,4]. Extracts obtained through aqueous, ethanolic, methanolic, or essential oil-based processes have therefore become increasingly relevant in both health and agricultural applications [5,6,7].

Among these activities, antioxidant and antimicrobial effects stand out as especially recurrent in the literature. Phenolic compounds, for example, are widely recognized for their capacity to neutralize free radicals and contribute to cellular protection [8], while several medicinal plants have also been investigated as sources of natural antimicrobial agents and bioactive ingredients with therapeutic potential [3,5,6,7,8,9]. In biodiversity-rich contexts such as Brazil and other parts of Latin America, this research interest has been further strengthened by the diversity of native species and their ethnobotanical relevance [1,3,8,9].

Despite the broad and growing literature research on medicinal plants, there is still a limited synthesis of the most influential studies, major publication patterns, and evidence gaps in this field. Scientometric and bibliometric approaches offer a useful framework for this purpose, as they allow for the quantitative mapping of scientific production, leading contributors, institutional networks, and research trends through structured metrics and visualization tools [10,11]. These approaches have already been successfully applied in several areas of food science and related domains, including food packaging materials [12], exotic fruits [13], food additives [14], pesticide bioavailability in foods and wine [15], anthocyanin extraction and microencapsulation [16], pseudocereals and their applications in food manufacturing [17], medicinal and ethnomedical plants [1,18,19], and even concept building in emerging interdisciplinary areas such as Social Gastronomy [20].

In parallel, the study of medicinal plant bioactives is becoming increasingly aligned with the principles of green chemistry and the United Nations’ Sustainable Development Goals (SDGs), particularly when low-impact extraction methods, biodiversity conservation, and responsible use of plant resources are considered [21,22]. In this sense, the valorization of plant-based therapeutics may contribute not only to drug discovery and public health but also to broader sustainability-oriented agendas.

The five focal species (Amburana cearensis, Libidibia ferrea, Justicia pectoralis, Lippia origanoides, and Spondias mombin) were selected because they combine three attributes relevant to the scope of this review: (i) documented ethnobotanical relevance in South/Central American medicinal use contexts, (ii) recurrent pharmacological and phytochemical interest, particularly in studies related to antimicrobial and/or antioxidant activity, and (iii) sufficient representation in the retrieved Web of Science corpus to support comparative scientometric and evidence gap analysis. Thus, the scope was intentionally restricted to species that were not only regionally meaningful but also methodologically suitable for a cross-species synthesis of research trends and translational gaps.

Therefore, this scientometric review aims to examine and map the main trends in research on medicinal plant extracts, synthesize global contributions, and identify research gaps. The findings are expected to provide a comparative overview of the field and to help guide future studies toward areas of greater scientific and translational relevance.

2. Materials and Methods

The searches were conducted in Web of Science^® (Core Collection) for the period from 1991 to 2024, and the year 2025 is discussed in the section on challenges and future perspectives (Section 3.8), not being included in the scientometric analyses. Web of Science^® (Core Collection) was intentionally adopted as the sole database because it provides a curated and standardized metadata structure that is particularly suitable for reproducible scientometric analyses using Bibliometrix in R software (version 4.2.3) [23] and VOSviewer (version 1.6.20) [24]. Since the aim of this review was to map publication patterns, collaboration structures, and evidence gaps within a single internally consistent corpus, the use of one indexed database was considered methodologically appropriate for comparability across records. A specific search strategy was defined for the base database to retrieve records explicitly focused on five medicinal plants (Amburana cearensis, Libidibia ferrea, Justicia pectoralis, Lippia origanoides, and Spondias mombin), minimizing indexing noise; full details are provided in Figure 1. These five species were selected a priori because they represent medicinal plants with recognized ethnobotanical relevance, recurring scientific interest in antimicrobial and antioxidant applications, and sufficient indexed literature to enable robust scientometric comparison within a single, internally consistent corpus. To improve retrieval sensitivity and account for historical nomenclature in older records, synonymous or previously adopted species names (e.g., Lippia sidoides, Caesalpinia ferrea, and Dianthera pectoralis) were also considered during search design and keyword handling. Nevertheless, the current accepted taxonomy was adopted throughout the main text and synthesis tables. Records from the database were exported and processed as follows:

• Eligibility criteria: We included peer-reviewed original research articles that addressed at least one of the five medicinal plants researched associated with antimicrobial activity and/or antioxidant activity, including studies on the characterization of primary and secondary metabolites, industrial applications in the food, pharmaceutical, and cosmetic industries, as well as studies demonstrating new methods of extraction and purification of compounds from these medicinal plants, respecting the concepts of green chemistry. We excluded reviews, editorials, conference abstracts, patents, and book chapters. There were no language restrictions. Although the search strategy required the presence of “antioxidant activity” and/or “antimicrobial activity” in the Topic field, some retrieved records also reported additional pharmacological endpoints (e.g., antiviral or anti-inflammatory activity) because multi-endpoint studies and Topic indexing may capture broader thematic associations; these endpoints were treated as emergent themes within the eligible corpus.
• Data items and extraction: For each included study, bibliographic and general methodological information were extracted using a structured spreadsheet. Extracted items included publication year, journal, country, affiliation information, and study objective. Data were recorded in a standardized template (available upon request).

Figure 1. Scientometric search methodology used in the study (PRISMA).

Figure 1. Scientometric search methodology used in the study (PRISMA).

The analysis conducted with VOSviewer included the descriptors described as follows. Keyword (all keywords) co-occurrence charts: Keywords with a minimum of three co-occurrences were included, resulting in 57 distinct keywords. A Thesaurus file was applied to unify terms considered synonyms. Bibliographic coupling charts (source): journals were included on a minimum criterion of two documents per journal and at least 15 citations, totaling 23 journals.

On the other hand, in Bibliometrix, descriptors were applied as follows. Bradford’s law: zones were divided into primary and secondary zones to identify the distribution of core journals. Trend Topics: key topics within the journal were identified, with a Thesaurus file used to consolidate synonymous keywords. Sankey diagram: a three-field plot was created to illustrate relationships among authors, affiliations, and journals.

Because scientometric analyses also capture citation, coupling, and co-occurrence structures within the retrieved corpus, some broadly influential or peripheral records may appear in subsequent rankings and network visualizations even when they are not strictly centered on one of the five focal species. In such cases, these records were interpreted as part of the corpus’s citation architecture rather than as direct evidence for the five-species synthesis.

A semi-quantitative evidence-intensity matrix was developed to comparatively summarize the maturity of evidence across the five focal medicinal species.

3. Results and Discussion

3.1. Mapping Scientific Output, Disciplinary Scope, and Authorial Dynamics in the Studied Field

The first publication in this field appeared in 1991, focusing on phenolic acids from Spondias mombin, followed by another study in 1994 [25,26]. Both publications remain highly influential, ranking among the top ten most cited articles in the field, as shown in

Table 1. The top 10 most cited articles in medicinal plants from 1991 to 2024.

Class. *	Manuscript Titles	Journals	Country		NC **	IF ***	Reference
1st	Antimicrobial activity of the essential oil from Lippia sidoides, carvacrol and thymol against oral pathogens.	Brazilian Journal of Medical and Biological Research		Brazil	283	1.5	[5]
2nd	Composition and acaricidal activity of Lippia sidoides essential oil against two-spotted spider mite (Tetranychus urticae Koch).	Bioresource Technology		Brazil	118	9.0	[27]
3rd	Lippia origanoides chemotype differentiation based on essential oil GC-MS and principal component analysis.	Journal of Separation Science		Colombia	95	2.8	[28]
3rd	Chemical and antimicrobial analyses of essential oil of Lippia origanoides H.B.K.	Food Chemistry		Brazil	95	9.8	[29]
5th	Antiviral ellagitannins from Spondias mombin.	Phytochemistry		Belgium	90	3.4	[25]
6th	Synergistic antibiotic activity of volatile compounds from the essential oil of Lippia sidoides and thymol.	Phytotherapy		Brazil	79	2.6	[30]
7th	Ethnopharmacological study of plants sold for therapeutic purposes in public markets in Northeast Brazil.	Journal of Ethnopharmacology		Brazil	72	5.4	[31]
8th	Evaluation of antioxidant and free radical scavenging capacities of some Nigerian indigenous medicinal plants.	Journal of Medicinal Food		USA	69	2.0	[32]
9th	Antibacterial and molluscicidal phenolic acids from Spondias mombin.	Planta Medica		Belgium	65	2.0	[26]
10th	Antimicrobial potential of Spondias mombin, Croton zambesicus and Zygotritonia crocea.	Phytotherapy Research		Nigeria	63	6.3	[33]

* Ranks reflect citation ties (e.g., two papers share 3rd place); subsequent ranks may be skipped. ** NC = Number of citations. *** Impact Factor (2024 Journal Citations Report).

.

Figure 2a illustrates the temporal evolution of scientific output and citations in medicinal plant research. Until the mid-2000s, publication volume remained modest. However, from 2007 onward, a steady increase is observed, culminating in notable productivity peaks in 2016 and 2020, each with 16 publications. This upward trend reflects sustained and growing interest in the topic, with annual outputs consistently exceeding the historical average in subsequent years.

An analysis of thematic categories indexed by the Web of Science reveals the predominance of four key areas: Plant Sciences, Pharmacology Pharmacy, Chemistry Medicinal, and a grouped “Others” category. The consistent prominence of Plant Sciences underscores the foundational role of botany in the field, while the rising visibility of pharmaceutical and medicinal chemistry domains signals a deepening emphasis on therapeutic applications and natural product drug discovery.

The cumulative count across the four major thematic domains exceeds the total number of documents (183), with Plant Sciences alone accounting for 36 articles, followed by Pharmacology Pharmacy (36), Chemistry Medicinal (23), and Others (181) totaling 276 entries. This overlap indicates that many articles span multiple research areas. This interdisciplinary integration highlights the potential for cross-sector collaboration in addressing complex challenges, including sustainability and public health. However, this thematic diversity also presents coordination challenges, particularly in aligning research priorities across domains. While such convergence is promising, more integrated efforts among researchers, policymakers, and industry stakeholders may be required to effectively translate findings.

Citation data further reinforce this positive trajectory. Over the past five years (2020–2024), citation counts have consistently surpassed 300 annually. This growth reflects not only the accumulation of influential studies but also the field’s increasing relevance in addressing global health challenges. The publication and citation spike in 2020 may, in part, reflects intensified research in response to the COVID-19 pandemic, highlighting the potential of plant-based therapeutics in times of health crises [34,35].

Notably, the increasing convergence between “Plant Sciences” and “Pharmacology Pharmacy” also reflects a broader shift toward sustainable innovation in drug discovery. Research at this interface increasingly incorporates environmental impact assessments, favoring plant-based actives over synthetic alternatives. This aligns with global sustainability priorities and resonates with the core objectives of green chemistry: to reduce toxicity, increase efficiency, and utilize renewable raw materials [21,36]. As these thematic domains grow more interconnected, they present a valuable opportunity for framing phytochemical research as part of environmentally responsible therapeutic development.

Figure 2b explores author productivity and its alignment with Lotka’s Law. A key observation from this analysis is the concentration of scientific output among a small group of authors, as predicted by Lotka’s Law. According to Lotka [37] the number of authors producing “n” contributions is inversely proportional to the square of “n”, meaning a few prolific researchers dominate the literature.

The observed distribution closely mirrors the theoretical expectation: over 90% of authors contributed only one article, while progressively smaller groups authored two, three, or more publications. Notably, four authors published four articles each, twenty authors published three, and seventy-one contributed two. This highly skewed distribution reflects a hierarchical structure typical of maturing scientific domains, wherein a small core of prolific contributors plays a pivotal role in shaping the field.

While such a pattern is characteristic of established research communities, it also underscores structural barriers faced by early-career researchers, such as restricted access to funding, collaborative networks, and publishing opportunities. Addressing these challenges is vital for fostering equity and inclusivity. Targeted policies and support mechanisms for emerging scholars can expand participation, stimulate innovation, and enhance the global impact of medicinal plant research.

Figure 2c,d complement Figure 2a by treating the publication record as a growth process rather than only a year-by-year series. Annual counts in a collection of scientific documents (corpus) of this size naturally fluctuate with funding cycles, laboratory capacity, methodological fashions, special issues, and external events. For that reason, a cumulative model is useful because it reduces short-term noise and highlights the underlying trajectory. In Figure 2d, cumulative output was fitted with a logistic growth curve, and the implied annual growth pattern is shown in Figure 2c.

The cumulative model suggests a saturation level of about K = 257 publications for the corpus defined here, with a midpoint around 2018.2. This midpoint marks the period when growth shifts from rapid expansion to a slower and more incremental phase. The current dataset is consistent with that interpretation. By 2024, the corpus had reached 183 documents, which is about 71.2% of K. In practical terms, this means that much of the field’s expansion had already occurred, yet the topic has remained active and continues to generate new papers each year. The milestone years reinforce the same view. The model indicates that the field reached roughly 10% of its projected saturation around 2004.7, which matches the early period of low output described in Figure 2a, and crossed 50% near 2018.2, when annual output became consistently higher than the historical baseline. It then projects 90% around 2031.7 and 99% around 2046.4. These future values should be read as indicative markers, not as precise forecasts, because they depend on the stability of publication dynamics over time.

Figure 2c also helps reconcile the smoothed model with the observed peaks. The observed series shows strong bursts of productivity in 2016 and 2020, with 16 publications in each year. In contrast, the model derived from the cumulative curve points to a peak growth period around 2018.2, with a peak annual rate near 10 publications per year. These results are not contradictory. The model summarizes the central tendency of growth, while the observed points reflect year-to-year variability that can push some years above the long-run pattern. This is common in scientometric/bibliometric time series, especially when the corpus spans multiple plant species, multiple research domains, and different application goals, from phytochemical characterization to biological screening. The model fit is moderate (R² = 0.61), so it supports the interpretation of broad phases, but it does not justify strong claims about a future decline. Accordingly, the logistic growth model is used here as a descriptive approximation of publication dynamics and field maturation, and should not be interpreted as a predictive model of future research activity.

The forecasts shown in Figure 2c,d are therefore best viewed as scenario-based projections. Under the fitted curve, the corpus would reach about 219 cumulative papers by 2029 and 239 by 2034, with annual rates gradually decreasing from current levels. Importantly, a slowing growth rate does not mean that the topic is becoming less relevant. In many areas, a maturity stage is exactly when research standards rise and the agenda shifts from exploratory breadth to depth, consistency, and translation. In medicinal plant research, that usually means better standardization of plant material and extracts, clearer reporting of chemical markers and quality control, stronger links between chemistry and biological endpoints, and more explicit attention to safety, dosing, and clinical feasibility.

This life cycle view also aligns well with the citation pattern described above. Even if publication growth begins to slow, citations can remain high when a field consolidates around core methods, key compounds, and widely cited reference studies. In this corpus, citations remained consistently high from 2020 to 2024, which suggests that the literature is being actively reused and integrated, not merely accumulated. The publication and citation surge around 2020 may have been amplified by the pandemic context and the broader interest in plant-based therapeutics, but Figure 2d indicates that the acceleration of the field began earlier and follows a coherent long-term trajectory.

Finally, the life cycle framing provides a useful bridge to the next sections of the manuscript. If the field is interpreted as being in a maturity phase, the results suggest that future progress will likely depend on research designs that reduce heterogeneity and improve comparability across studies. This includes better studies and standardization of plant material and extracts, clearer linkage between chemical markers and biological endpoints, and more systematic attention to safety and clinical translation when claims move beyond preliminary screening. In this sense, Figure 2c,d do not merely describe growth; they also support a strategic interpretation of what the field now needs to progress from a large and active preclinical literature base toward more robust and clinically meaningful evidence.

3.2. Analysis of Highly Cited Publications

In research, the “most cited documents” often indicate studies that have strongly shaped the field’s agenda and methodological choices. In this corpus (1990–2024), Table 1 shows that the most cited publications are experimental and largely organized around two applied axes: (i) phytochemical characterization of plant-derived products (especially essential oils) and (ii) bioactivity-driven testing, with emphasis on antimicrobial, antioxidant, and antiviral endpoints relevant to public health and applied biotechnology.

The most cited article (274 citations) investigated the antimicrobial activity and chemical composition of Lippia essential oil, identifying thymol and carvacrol as major constituents with broad activity against Streptococcus spp. and Candida albicans [5]. This work has become a reference point because it links a defined chemical profile to reproducible antimicrobial outcomes, helping consolidate thymol and carvacrol as “reference actives” in the subsequent literature. However, its citation prominence should not be interpreted as translational closure: key aspects required for practical deployment—such as standardized quality control across batches, safety/toxicity framing, and longer-term risk considerations—are not addressed in depth in the study design [5].

The second ranked publication (115 citations) evaluated the acaricidal activity of Lippia essential oil against Tetranychus urticae, again highlighting thymol and carvacrol as primary constituents and reporting strong effects across doses and exposure times [27]. This study is influential because it extends the essential oil evidence base beyond human pathogens into agricultural relevance, supporting plant-derived volatiles as candidates for pest management. Nevertheless, the same evidence gap emerges: translation to field use depends on validating performance under realistic conditions and clarifying environmental and safety boundaries for large-scale application [27].

Two papers ranked third (each with 95 citations) are central to understanding the Lippia origanoides axis of the corpus. One differentiated chemotypes across Colombian regions based on essential oil composition, identifying three chemotypes with distinct primary components and showing that chemotype-specific profiles can modulate antioxidant performance [28]. The other reported the chemical composition and antimicrobial activity of Lippia origanoides oil, characterized by high concentrations of oxygenated monoterpenes, predominantly carvacrol and thymol, and activity against Candida guilliermondii and Fonsecaea pedrosoi [29]. Together, these studies are influential because they show that chemical variability (chemotypes, geographic origin) is not incidental; it is structurally linked to reproducibility and comparability across experiments, and therefore to the credibility of downstream applications [28,29].

Another highly cited study (90 citations) moved beyond broad screening by isolating and testing defined ellagitannins (geraniin and galloylgeraniin) from Spondias mombin, reporting antiviral activity against Coxsackie and Herpes simplex viruses [25]. This paper is influential because it provides compound-level specificity and mechanistic guidance for antiviral investigation, thereby expanding the evidence base beyond essential oil-centered antimicrobial screening [25].

Overall, the most cited literature reveals a field whose influence structure is dominated by essential oil chemistry, major volatile constituents (notably thymol and carvacrol), and preclinical bioactivity models [5,27,29]. Citation prominence, however, should be interpreted primarily as a marker of scientific influence and thematic consolidation rather than as a direct indicator of translational readiness. The recurrent emergence of chemotype variability and compound-driven activity underscores a central requirement for future progress: comparable evidence depends on standardized chemical reporting (markers and chemotype control) and on study designs that link bioactivity outcomes to reproducible composition and safety framing, particularly when translation to pharmaceutical, food, cosmetic, or agricultural applications is proposed [28,29].

3.3. Ethnobotanical and Phytochemical Studies of Medicinal Plants

Ethnobotanical and phytochemical studies are central for understanding why particular medicinal plants persist as research priorities: ethnobotany documents culturally embedded uses and therapeutic claims, while phytochemistry and pharmacological testing provide the basis for reproducible evaluation. Importantly, ethnobotanical relevance should be interpreted as a structured guide for hypothesis generation and prioritization, rather than as direct proof of efficacy; translational claims ultimately depend on standardized chemical characterization, appropriate dosing logic, and safety-oriented evidence.

The study ranked sixth (79 citations) reported that Lippia essential oil—rich in thymol and p-cymene—enhanced the activity of antibiotics such as gentamicin and amikacin against Pseudomonas aeruginosa and Staphylococcus aureus, outperforming thymol alone [30]. This contribution is influential because it supports the concept of mixture-driven effects and potential synergy in antimicrobial strategies. However, the study’s translational value remains constrained by limited mechanistic clarification and by the lack of longer-term safety framing necessary for clinically oriented applications of essential oil adjuvants [30].

The seventh-ranked article (72 citations) documented medicinal plants commercialized in Northeast Brazil markets and identified frequently used species for digestive disorders [31]. Its value lies in mapping real-world use patterns and community-level priorities. At the same time, ethnobotanical surveys are inherently limited for therapeutic inference because they rely on reported use and cultural persistence rather than controlled outcome evaluation. In this context, the findings primarily define research relevance and selection rationale, while validation requires phytochemical standardization and clinically meaningful study designs [31].

Ranked ninth (65 citations), the study on Spondias mombin phenolic acids reported antibacterial and molluscicidal activity and suggested potential disease control relevance [26]. This work is influential because it links defined phenolic scaffolds to bioactivity outcomes and proposes an applied pathway beyond general screening. Nonetheless, translation to intervention contexts depends on information that is typically underreported in early phytochemical studies, including bioavailability, safety margins, dose–exposure relationships, and environmental boundaries for deployment [26].

The studies ranked eighth (69 citations) and tenth (62 citations) further illustrate the evidence structure in this area. One evaluated Nigerian medicinal plants for antioxidant and free radical scavenging activity and classified them as potential chemopreventive agents [32]. The other evaluated the antimicrobial properties of Spondias mombin and other species and reported broad-spectrum antibacterial and antifungal activity consistent with narratives of gastrointestinal use [33]. Although these studies strengthen the preclinical evidence base, their reliance on in vitro endpoints limits direct inference to clinical or agricultural translation without subsequent standardized formulation, dosing, and safety programs [32,33].

Taken together, the ethnobotanical and phytochemical literature indicates strong traditional relevance and extensive preclinical bioactivity signals across key species such as Lippia and Spondias mombin, but it also reveals an evidence imbalance. The dominant trajectory remains anchored in screening-based outputs (in vitro assays and short-window animal models), whereas later-stage indicators of translation—standardized extract/oil specifications, reproducible marker-based reporting across chemotypes and regions, and controlled human validation—are less developed. Consequently, ethnobotanical continuity should be treated as a robust framework for prioritizing hypotheses and contexts of use, while translational conclusions should remain explicitly anchored to the level and quality of available pharmacological and safety evidence [26,30,31,32,33].

3.4. Scientometric Analysis

3.4.1. Authors, Affiliations, Journals, and Countries

This section characterizes the scientometric structure of research on bioactive compounds by identifying (i) the most visible authors and affiliations, (ii) the main journal ecosystem supporting publication and citation impact, and (iii) country-level leadership and collaboration patterns. Figure 3, Figure 4 and Figure 5 jointly show a field with a productive core centered in a limited set of institutions and outlets, alongside an uneven international collaboration profile.

Figure 3a summarizes the publication trajectories and citation performance of the ten most productive authors over the study period, where circle size reflects publication volume and shading represents annual citation averages [38,39,40]. Lucchese A. M. emerges as the most prolific author (four publications across multiple years) [41], whereas Botelho M. A. stands out for citation impact, with peaks that align with foundational Lippia research [5]. Overall, the author profile indicates a concentrated productivity core, with Brazilian researchers representing the majority of the top contributors. The presence of African authors such as Ayoka A. O. and Boadu A. highlights that Spondias mombin has also stimulated sustained research beyond Brazil, although the broader high-output network remains strongly anchored in Brazilian institutions.

The Sankey diagram (Figure 3b) complements this view by linking authors, affiliations, and journals and thereby clarifying how institutional centers channel output into specific publication outlets [42,43]. Several Brazilian universities and EMBRAPA-linked groups appear as recurrent hubs, reflecting both institutional continuity and thematic consolidation. At the same time, nodes such as Obafemi Awolowo University connect to multiple journals, suggesting a wider distribution of outlets across pharmacognosy, pharmaceutical biology, and applied biotechnology. Rather than being interpreted as a purely descriptive mapping, this structure has a direct implication for evidence consolidation: when production concentrates within a limited institutional core and a small set of journals, the field may gain continuity and cumulative expertise, but it may also require deliberate protocol harmonization and inter-laboratory validation to avoid methodological path dependence.

The journal ecosystem (Figure 4) further confirms a core set of outlets that disproportionately host and shape the field’s most visible work. In the VOSviewer bibliographic coupling map, colors indicate algorithm-detected clusters of journals with stronger coupling relationships and are used only to differentiate communities rather than to imply ranking. Accordingly, cluster structure should be interpreted as a relational pattern in the corpus, whereas node prominence and overlay metrics (when used) reflect the configured network weights and selected overlay variable.

In the bibliographic coupling network (Figure 4a) and Bradford-style ranking (Figure 4b), the Journal of Ethnopharmacology appears as the main hub and the highest-volume outlet (n = 9), consistent with its central role in ethnopharmacological framing and bioactivity-driven medicinal plant research. The recent-impact visualization (Figure 4c) indicates that outlets such as Industrial Crops and Products complement this hub by emphasizing industrial and application-oriented dimensions of plant-derived phytochemicals. Citation frequency patterns (Figure 4d) highlight the stable influence of chemistry and phytochemistry-centered journals such as Phytochemistry, Food Chemistry, and Phytotherapy Research, underscoring that chemical characterization and activity interpretation remain the dominant visibility pathways in this corpus. In line with Bradford’s Law, the journal distribution indicates that a small core of sources concentrates a large share of outputs, including several Brazilian journals, reinforcing Brazil’s structural prominence in the publication landscape.

Country-level analysis (Figure 5) confirms Brazil’s leadership in both productivity and citation accumulation. Importantly, the “documents” shown in Bibliometrix represent affiliation-based country occurrences under a full-counting approach; therefore, the country counts can exceed the corpus size (n = 183) because a single article may be attributed to multiple countries and affiliations. Under this scheme, Brazil accounts for 350 occurrences and 2002 citations, followed by Nigeria (75 occurrences; 494 citations) and the USA (23 occurrences; 48 citations). Figure 5c further distinguishes single-country publications (SCP) from multiple-country publications (MCPs), revealing that Brazil’s output is predominantly SCP (>90%), indicating strong domestic research capacity but comparatively limited international co-authorship. Several other countries (e.g., Colombia, Belgium, Cuba, South Africa, and Armenia) also show SCP-dominant profiles, suggesting that cross-border collaboration remains structurally constrained in parts of this field.

Notably, citation impact does not scale proportionally with country occurrence counts. Colombia and Belgium rank among the most cited countries and contribute influential work focused on secondary metabolite characterization in Lippia origanoides and early experimental studies on Spondia mombin, respectively [25,26,28,44,45,46]. Cuba’s contributions emphasize volatile compound characterization, ethnobotanical approaches, and drying-related studies of Justicia pectoralis [47,48,49]. Taken together, these patterns indicate a field with strong regional expertise and clear leadership but uneven international integration. Strengthening MCP-based collaboration is therefore relevant not only to increase visibility but also to improve methodological diversity, comparability, and evidence robustness. In parallel, collaboration agendas can be aligned with sustainability-oriented goals and ethical bioprospecting principles, supporting SDG-linked outcomes in health, responsible production, and climate action [22,50].

3.4.2. Keywords

The keyword co-occurrence networks generated in VOSviewer (Figure 6) provide a structured view of how this corpus organizes its central research problems and experimental approaches. In Figure 6a, keywords cluster around the most recurrent species and endpoints—particularly Spondias mombin, Lippia origanoides, “antioxidant activity”, “antimicrobial activity”, and “in vitro”—indicating that the field is predominantly organized around bioactivity-driven research anchored in species-specific evidence streams.

The overlay visualizations (Figure 6b,c) complement the network structure by showing how topic prominence (average publication year) and citation accumulation vary over time, enabling interpretation that goes beyond description toward the dynamics of influence and consolidation in the field [24].

The trend topic analysis from Bibliometrix (Figure 6d) reinforces this interpretation by showing how keyword frequency changes across years and how the corpus gradually consolidates around pharmacological endpoints and chemical profiling. Clusters 2–4 in Figure 6a are tightly interrelated, particularly for Spondias mombin, where studies repeatedly combine antioxidant (including phenolic acids such as chlorogenic and ellagic acid), antimicrobial, and antiviral themes [8,25,32,33]. The sustained growth of “antioxidant activity”, especially from 2008 to 2021 (Figure 6c,d), indicates not only a persistent research direction but also the expansion of phenolic-centered narratives across health- and food-oriented applications.

Across the network, “antimicrobial activity” co-occurs strongly with broad descriptors such as “plants” and “medicinal plants” (Figure 6a), reflecting a stable applied axis focused on plant-derived antimicrobials. This prominence is scientifically and socially meaningful, given the global relevance of antimicrobial resistance as a driver of research visibility, funding priorities, and therapeutic interest [51]. In this context, the keyword structure supports an interpretation of the field as predominantly oriented toward screening-based evidence generation, with repeated convergence on antimicrobial and antioxidant endpoints across multiple species and extract types.

Figure 6b,d also suggest a progressive emphasis on identifying secondary metabolites in plant extracts, underscoring a key translational requirement: linking traditional uses to defined chemical markers and reproducible pharmacological outcomes. The trend toward chemical profiling and pharmacological validation further highlights the importance of clarifying toxicological boundaries and developing clinically relevant guidance when claims move beyond preclinical screening [52,53,54,55,56]. In parallel, the network shows frequent associations among “plants”, “antioxidant activity”, “antimicrobial activity”, and related antibacterial/antifungal terms (Figure 6a), consistent with the growing interest in herbal medicines and natural agents across pharmacology and nutrition [57,58].

The original network also includes terms related to traditional medicine. Rather than interpreting their relative isolation as a shift toward telemedicine or personalized therapies, the keyword structure is more parsimoniously explained as a methodological transition within the medicinal-plant domain itself: from ethnomedical description toward chemically characterized, endpoint-driven experimental designs. This transition does not imply reduced interdisciplinary potential; instead, it indicates that integration increasingly occurs through standardized chemistry and bioactivity evidence rather than through descriptive ethnomedical clustering.

Species-centered patterns in Figure 6a align with the broader synthesis of evidence. Spondias mombin and Lippia origanoides appear among the most recurrent species keywords and are consistently linked to “antioxidant activity” and “antimicrobial activity”. The overlay by average publication year suggests that “antimicrobial activity” reached stronger prominence earlier (approximately 2013–2016), whereas “antioxidant activity” intensified later (approximately 2018–2020) (Figure 6b). As expected, the citation overlay (Figure 6c) indicates that older, foundational themes tend to accumulate higher citation averages over time.

A high-citation substructure is visible in the purple cluster of Figure 6a, which aligns with the higher citation intensity in Figure 6c. This cluster is concentrated on keywords related to essential oils, Lippia origanoides, antibacterial/antifungal activity, and the dominant volatiles thymol and carvacrol [59,60,61,62]. Thymol has been repeatedly studied for its antifungal effects, including in combination with fluconazole against resistant Candida tropicalis [60]. At the same time, carvacrol shows antifungal activity against C. albicans and plant-pathogenic fungi such as Botrytis cinerea and Aspergillus spp. [61,62]. Both compounds also present notable antibacterial effects and, in several studies, synergy with antibiotics against multidrug-resistant bacteria [63,64,65,66]. Taken together, this cluster-level pattern explains why field visibility is anchored to a relatively narrow set of transferable compounds and assay families: thymol and carvacrol function as recurring “reference actives” across pathogens and application contexts, reinforcing thematic consolidation.

Overall, the keyword analysis indicates a field increasingly centered on plant-derived metabolites and bioactivity endpoints—particularly antimicrobial and antioxidant themes—while simultaneously revealing an evidence gap typical of screening-dominated corpora. Keywords that would signal later-stage translation (standardization, dose–response framing, long-term safety, or clinical trial terminology) are less central than activity-oriented terms. Consequently, the keyword structure supports the manuscript’s broader conclusion that future progress depends less on expanding the volume of screening studies and more on strengthening standardized chemical reporting, comparability across chemotypes and regions, safety-oriented programs, and clinically meaningful validation pathways, especially in areas motivated by antimicrobial resistance [51,52,53,54,55,56].

3.5. Integrating Chemistry, Preclinical Signals, Clinical Evidence, and Safety

Taken together, Table 2 and Figure 7 tell a fairly straightforward story. When the chemistry is well described, and the material can be tracked using clear markers, preclinical findings tend to line up across studies. The hard part is turning that consistency into human evidence supported by product standardization and a safety file that is fit for therapeutic use. In our set of five species, that bridge is most visible for Amburana cearensis and Justicia pectoralis, both of which already have controlled trials in respiratory contexts [55,67,68]. For Lippia origanoides, Libidibia ferrea, and Spondias mombin, the chemical and functional groundwork is substantial, but key steps that usually precede or accompany clinical translation are still missing.

To facilitate comparison across the five focal medicinal species, Figure 7 presents a review-specific semi-quantitative evidence-intensity matrix organized into four translational domains: Chemistry, Preclinical, Clinical, and Safety. In this matrix, species were arranged as rows and domains as columns, and each species–domain intersection received an ordinal score from 0 to 3, where 0 indicates the absence of evidence, 1 limited evidence, 2 moderate evidence, and 3 strong evidence. These scores were assigned to summarize the apparent maturity and consistency of the available evidence in each domain, rather than to represent the absolute number of publications [69,70]. Accordingly, the figure should be interpreted as a comparative synthesis tool, and the cumulative values shown in the side summaries represent evidence scores rather than counts of unique studies.

Table 2. Comparative translational profile of five medicinal plants: chemical markers, preclinical evidence, human studies, and safety gaps.

Chemical Constituents (Overview)	Amburana cearensis (Fabaceae)	Justicia pectoralis (Fabaceae)	Libidibia ferrea (Acanthaceae)	Lippia origanoides (Verbenaceae)	Spondias mombin (Anacardiaceae)
Main Extract(s)/Fraction(s) Used Across Studies	Ethanolic/hydroalcoholic extracts; bark/seed fractions.	Syrup/extract preparations used in traditional/clinical context.	Bark extracts; phenolic-rich fractions.	Essential oils (chemotype-dependent).	Leaf/bark/fruit-related preparations across the literature.
Notable Chemical Markers	Phenylpropanoids; coumarins.	Coumarins; phenolics.	Polyphenols; tannins.	Monoterpenes; phenolic monoterpenes.	Flavonoids; phenolic acids; tannins (varies by tissue).
Main Marker(s)/Anchor Compounds Typically Tracked	Coumarin; amburoside A.	Marker quantification is rarely standardized in “finished product” formats.	Phenolic load varies with matrix/extract conditions; needs harmonized assays and marker thresholds.	Strong chemotype/seasonality variability; chemotype declaration is essential.	Tissue-dependent composition; need plant part specification + marker panel.
Notes Relevant To Standardization/Chemotype	Need quantitative marker control (e.g., HPLC) and batch-to-batch marker ranges.	Coumarin; umbelliferone.	Gallic acid; ellagic acid; total phenolics/tannins.	Thymol; carvacrol (chemotypes).	Quercetin/rutin (reported); phenolic acids (reported)
Reference(s)	[56]	[55]	[56,71]	[72,73]	[54,74,75]
Biological Activities and Mechanisms (Preclinical)	Amburana cearensis (Fabaceae)	Justicia pectoralis (Fabaceae)	Libidibia ferrea (Acanthaceae)	Lippia origanoides (Verbenaceae)	Spondias mombin (Anacardiaceae)
Main Preclinical Endpoints Repeatedly Reported	Anti-inflammatory; antioxidant; airway-related endpoints.	Gastroprotection; antitussive/airway-related signals.	Antimicrobial; antioxidant; protective effects (incl. applied contexts).	Antibacterial/antibiofilm; antifungal; anticonvulsant (PTZ).	Antioxidant; anti-inflammatory; metabolic-related endpoints; uterotonic signal.
Strongest Mechanistic “Signals”	Inflammatory pathway modulation; oxidative stress attenuation.	Multiple bioactivity axes are consistent with a coumarin-rich profile.	Polyphenol-driven antimicrobial/antioxidant effects.	Thymol/carvacrol-driven antimicrobial actions; CNS signal in PTZ.	Multi-pathway phenolic effects; reproductive signal needs caution
Typical Models Used	BV-2 microglia; airway-related models (varied).	Rodent GI models; functional assays.	In vitro panels; applied biological assays.	Biofilm assays; Candida models; PTZ seizures.	Rodent metabolic/inflammation models.
Main Warnings	Mechanistic strength does not automatically imply clinical effectiveness.	Requires safety framing when coumarin exposure may repeat.	Needs clarity on extract type, marker load, and dose windows.	Chemotype variability complicates translation; safety/PK gaps persist.	Preclinical breadth ≠ clinical readiness; reproductive caution.
Reproducibility/Standardization Requirements	Link dose ↔ marker content ↔ endpoint is still inconsistently reported.	Marker quantification and exposure ceilings remain underreported.	Cross-study heterogeneity of extracts and phenolic reporting.	Chemotype-declared oil + standardized dosing is essential.	Must specify plant part + marker panel + safety boundaries.
Reference(s)	[4]	[55]	[76,77]	[62,78]	[54,73,75]
Clinical Evidence (Human Studies)	Amburana cearensis (Fabaceae)	Justicia pectoralis (Fabaceae)	Libidibia ferrea (Acanthaceae)	Lippia origanoides (Verbenaceae)	Spondias mombin (Anacardiaceae)
Study Design (n; controls)	Randomized, double-blind, placebo-controlled parallel trial in adults with mild persistent asthma; 3-phase design (pre-, during, post-treatment). ≈40+ participants total (≈20 per arm).	Randomized, placebo-controlled clinical trial in children with acute cough and upper-airway symptoms (≈100+ children, two arms, blinded outcome assessment, 48 h follow-up).	No human clinical study identified.	No human clinical study identified.	No human clinical study identified.
Preparation/Dose	Standardized “cumaru syrup” orally as adjunct (complementary) therapy for 15 days vs. matched placebo.	Syrup from J. pectoralis given orally 3×/day for 48 h vs. placebo syrup.	—	—	—
Primary Outcomes (direction of effect)	Clinically relevant improvement in asthma-related quality of life and respiratory symptoms: ≈61.9% of treated patients reported global improvement vs. ≈9.5% placebo; spirometric indices (FEV1/FVC) improved consistently with subjective relief.	Faster reduction in cough frequency/severity, nasal congestion, and rhinorrhea; better sleep reported by both children and caregivers vs. placebo (p < 0.0001).	—	—	—
Safety/Adverse Events	No serious adverse events over 15 days; tolerability comparable to placebo.	No serious adverse events in the active arm during the 48 h observation window.	—	—	—
Key Limitations	Adjunct only (not monotherapy); mild asthma only; short follow-up. Extract standardization (coumarin/amburoside A levels) is not fully detailed for regulatory translation.	Very short follow-up (2 days); pediatric acute symptom relief only; chemical standardization (coumarin content).	Evidence remains ethnomedical + preclinical (anti-inflammatory, wound healing, antimicrobial, gut protection).	Despite strong antimicrobial and anticonvulsant signals, there are still no published studies on dosage/safety in humans.	Traditional postpartum/gynecological and anti-inflammatory uses are well documented in ethnic medicine, but lack standardized, IRB-approved clinical trials.
Reference(s)	[69]	[70]	—	—	—
Toxicity and Safety	Amburana cearensis (Fabaceae)	Justicia pectoralis (Fabaceae)	Libidibia ferrea (Acanthaceae)	Lippia origanoides (Verbenaceae)	Spondias mombin (Anacardiaceae)
Toxicity Study Type	Acute/subchronic (rodents); narrative human tolerability rather than broadly cytolytic.	Preclinical + short-term clinical context without lethal dosing in tested ranges.	Preclinical toxicity + cytotoxicity screening.	Cytotoxicity flags + variability; preclinical safety gaps.	Preclinical safety + review-level cautions.
Dose Range/Exposure	Extract-dependent; short-term human exposure;	Short-term syrup use.	Extract/phenolic-load dependent.	Chemotype-dependent EO exposure.	Subacute windows in animals.
Safety Signal(s)	Generally acceptable short-term tolerability.	Acute profile acceptable in short windows.	Safety depends on phenolic load and extract type.	Chemotype-driven potency may bring cytotoxicity concerns.	Subacute margins reported; reproductive caution plausible.
Evidence Gaps	Chronic exposure margins; marker ceilings.	Repeated-dose ceiling (coumarins) not established.	Human tolerability/PK; chronic safety.	Human PK/tolerability; standardized safety windows.	Chronic human safety; pregnancy-related contraindications.
Contraindications/Cautions	Monitor for repeated dosing; quantify coumarin markers.	Avoid overclaiming sustained use without monitoring.	Dose window definition before oral human claims.	Prefer topical/adjunct routes first; chemotype declaration.	Explicit pregnancy caution; monitor organ function.
Regulatory/Special Notes	Needs longer follow-up + quantitative marker.	Define exposure ceiling + quantify markers.	Harmonize marker reporting + tolerability studies.	Phase 0-type tolerability + chemotype-controlled oil.	Build PK/tolerability base before efficacy trials.
Reference(s)	[56]	[55]	[56,71]	[73]	[75]

Table 2. Comparative translational profile of five medicinal plants: chemical markers, preclinical evidence, human studies, and safety gaps.

Chemical Constituents (Overview)	Amburana cearensis (Fabaceae)	Justicia pectoralis (Fabaceae)	Libidibia ferrea (Acanthaceae)	Lippia origanoides (Verbenaceae)	Spondias mombin (Anacardiaceae)
Main Extract(s)/Fraction(s) Used Across Studies	Ethanolic/hydroalcoholic extracts; bark/seed fractions.	Syrup/extract preparations used in traditional/clinical context.	Bark extracts; phenolic-rich fractions.	Essential oils (chemotype-dependent).	Leaf/bark/fruit-related preparations across the literature.
Notable Chemical Markers	Phenylpropanoids; coumarins.	Coumarins; phenolics.	Polyphenols; tannins.	Monoterpenes; phenolic monoterpenes.	Flavonoids; phenolic acids; tannins (varies by tissue).
Main Marker(s)/Anchor Compounds Typically Tracked	Coumarin; amburoside A.	Marker quantification is rarely standardized in “finished product” formats.	Phenolic load varies with matrix/extract conditions; needs harmonized assays and marker thresholds.	Strong chemotype/seasonality variability; chemotype declaration is essential.	Tissue-dependent composition; need plant part specification + marker panel.
Notes Relevant To Standardization/Chemotype	Need quantitative marker control (e.g., HPLC) and batch-to-batch marker ranges.	Coumarin; umbelliferone.	Gallic acid; ellagic acid; total phenolics/tannins.	Thymol; carvacrol (chemotypes).	Quercetin/rutin (reported); phenolic acids (reported)
Reference(s)	[56]	[55]	[56,71]	[72,73]	[54,74,75]
Biological Activities and Mechanisms (Preclinical)	Amburana cearensis (Fabaceae)	Justicia pectoralis (Fabaceae)	Libidibia ferrea (Acanthaceae)	Lippia origanoides (Verbenaceae)	Spondias mombin (Anacardiaceae)
Main Preclinical Endpoints Repeatedly Reported	Anti-inflammatory; antioxidant; airway-related endpoints.	Gastroprotection; antitussive/airway-related signals.	Antimicrobial; antioxidant; protective effects (incl. applied contexts).	Antibacterial/antibiofilm; antifungal; anticonvulsant (PTZ).	Antioxidant; anti-inflammatory; metabolic-related endpoints; uterotonic signal.
Strongest Mechanistic “Signals”	Inflammatory pathway modulation; oxidative stress attenuation.	Multiple bioactivity axes are consistent with a coumarin-rich profile.	Polyphenol-driven antimicrobial/antioxidant effects.	Thymol/carvacrol-driven antimicrobial actions; CNS signal in PTZ.	Multi-pathway phenolic effects; reproductive signal needs caution
Typical Models Used	BV-2 microglia; airway-related models (varied).	Rodent GI models; functional assays.	In vitro panels; applied biological assays.	Biofilm assays; Candida models; PTZ seizures.	Rodent metabolic/inflammation models.
Main Warnings	Mechanistic strength does not automatically imply clinical effectiveness.	Requires safety framing when coumarin exposure may repeat.	Needs clarity on extract type, marker load, and dose windows.	Chemotype variability complicates translation; safety/PK gaps persist.	Preclinical breadth ≠ clinical readiness; reproductive caution.
Reproducibility/Standardization Requirements	Link dose ↔ marker content ↔ endpoint is still inconsistently reported.	Marker quantification and exposure ceilings remain underreported.	Cross-study heterogeneity of extracts and phenolic reporting.	Chemotype-declared oil + standardized dosing is essential.	Must specify plant part + marker panel + safety boundaries.
Reference(s)	[4]	[55]	[76,77]	[62,78]	[54,73,75]
Clinical Evidence (Human Studies)	Amburana cearensis (Fabaceae)	Justicia pectoralis (Fabaceae)	Libidibia ferrea (Acanthaceae)	Lippia origanoides (Verbenaceae)	Spondias mombin (Anacardiaceae)
Study Design (n; controls)	Randomized, double-blind, placebo-controlled parallel trial in adults with mild persistent asthma; 3-phase design (pre-, during, post-treatment). ≈40+ participants total (≈20 per arm).	Randomized, placebo-controlled clinical trial in children with acute cough and upper-airway symptoms (≈100+ children, two arms, blinded outcome assessment, 48 h follow-up).	No human clinical study identified.	No human clinical study identified.	No human clinical study identified.
Preparation/Dose	Standardized “cumaru syrup” orally as adjunct (complementary) therapy for 15 days vs. matched placebo.	Syrup from J. pectoralis given orally 3×/day for 48 h vs. placebo syrup.	—	—	—
Primary Outcomes (direction of effect)	Clinically relevant improvement in asthma-related quality of life and respiratory symptoms: ≈61.9% of treated patients reported global improvement vs. ≈9.5% placebo; spirometric indices (FEV1/FVC) improved consistently with subjective relief.	Faster reduction in cough frequency/severity, nasal congestion, and rhinorrhea; better sleep reported by both children and caregivers vs. placebo (p < 0.0001).	—	—	—
Safety/Adverse Events	No serious adverse events over 15 days; tolerability comparable to placebo.	No serious adverse events in the active arm during the 48 h observation window.	—	—	—
Key Limitations	Adjunct only (not monotherapy); mild asthma only; short follow-up. Extract standardization (coumarin/amburoside A levels) is not fully detailed for regulatory translation.	Very short follow-up (2 days); pediatric acute symptom relief only; chemical standardization (coumarin content).	Evidence remains ethnomedical + preclinical (anti-inflammatory, wound healing, antimicrobial, gut protection).	Despite strong antimicrobial and anticonvulsant signals, there are still no published studies on dosage/safety in humans.	Traditional postpartum/gynecological and anti-inflammatory uses are well documented in ethnic medicine, but lack standardized, IRB-approved clinical trials.
Reference(s)	[69]	[70]	—	—	—
Toxicity and Safety	Amburana cearensis (Fabaceae)	Justicia pectoralis (Fabaceae)	Libidibia ferrea (Acanthaceae)	Lippia origanoides (Verbenaceae)	Spondias mombin (Anacardiaceae)
Toxicity Study Type	Acute/subchronic (rodents); narrative human tolerability rather than broadly cytolytic.	Preclinical + short-term clinical context without lethal dosing in tested ranges.	Preclinical toxicity + cytotoxicity screening.	Cytotoxicity flags + variability; preclinical safety gaps.	Preclinical safety + review-level cautions.
Dose Range/Exposure	Extract-dependent; short-term human exposure;	Short-term syrup use.	Extract/phenolic-load dependent.	Chemotype-dependent EO exposure.	Subacute windows in animals.
Safety Signal(s)	Generally acceptable short-term tolerability.	Acute profile acceptable in short windows.	Safety depends on phenolic load and extract type.	Chemotype-driven potency may bring cytotoxicity concerns.	Subacute margins reported; reproductive caution plausible.
Evidence Gaps	Chronic exposure margins; marker ceilings.	Repeated-dose ceiling (coumarins) not established.	Human tolerability/PK; chronic safety.	Human PK/tolerability; standardized safety windows.	Chronic human safety; pregnancy-related contraindications.
Contraindications/Cautions	Monitor for repeated dosing; quantify coumarin markers.	Avoid overclaiming sustained use without monitoring.	Dose window definition before oral human claims.	Prefer topical/adjunct routes first; chemotype declaration.	Explicit pregnancy caution; monitor organ function.
Regulatory/Special Notes	Needs longer follow-up + quantitative marker.	Define exposure ceiling + quantify markers.	Harmonize marker reporting + tolerability studies.	Phase 0-type tolerability + chemotype-controlled oil.	Build PK/tolerability base before efficacy trials.
Reference(s)	[56]	[55]	[56,71]	[73]	[75]

For Amburana cearensis, the translational pathway is comparatively mature. The markers most often discussed for this species, especially coumarin and amburoside A, support an anti-inflammatory and antioxidant rationale that also appears in mechanistic work, including neuroinflammation models, and there is a short-term clinical signal in mild asthma when used as an adjuvant [4,67]. A reasonable next step, based on the current evidence, would be “more studies” in the generic sense. What the field needs is tighter standardization in the actual product, quantitative marker ranges, batch-to-batch control, and follow-up that is long enough to capture the durability of benefit and adverse events under repeated use. That is how dose, exposure, mechanism, and clinical outcome can be connected in a way that supports real-world therapeutic positioning.

For Justicia pectoralis, the pattern is similar, although the evidence base is smaller and largely short-term. The repeated appearance of coumarin and umbelliferone is consistent with the respiratory-related preclinical signals and with symptom relief reported in a pediatric setting over a short duration [55,68]. If this species is to move forward credibly, the most practical priorities are straightforward. The finished formulation, such as a syrup, needs marker-based standardization with an explicit range, and the clinical work needs a clearer safety framework for repeated exposure, including simple monitoring that matches the intended use context. The bottleneck here is not the absence of biological activity; it is the lack of a standardized, safety-aware clinical package that would allow claims to be made responsibly.

For Lippia origanoides, the preclinical signal is strong, but translation is constrained by a structural issue that shows up repeatedly in the literature. Chemotype variability, especially thymol-rich versus carvacrol-rich profiles, can shift potency and reproducibility if the plant material is not tightly controlled [73]. At the same time, the dataset includes specific findings that help define a cautious and realistic pathway. There is evidence that the essential oil, or thymol, can act in combination with fluconazole in a way that damages cells and reverses an azole-resistant phenotype in Candida tropicalis [60], and there is anticonvulsant activity in a PTZ-induced seizure model in rodents [78]. The practical implication is that clinical translation would likely benefit from a sequenced approach. Chemotype must be declared, key markers need to be tracked, tolerability windows should be defined first, and early human-facing work should prioritize lower-risk applications, for example, topical use or adjunct strategies, with clear endpoints and safety monitoring.

For Libidibia ferrea, the tables highlight a dense phenolic and tannin-based chemistry that supports repeated antimicrobial and protective signals, including applied contexts, yet the absence of controlled human trials remains the main translational gap [71,76,77]. Importantly, that gap does not negate the potential. It simply sets the order of operations. An incremental route appears to be the most defensible based on the current evidence. It starts with standardization of the extract and its phenolic load, then moves into safety margin definition for the intended extract type, and only then proceeds to conservative human designs that fit the risk profile. If oral use is envisioned, the need for tolerability and safety margins becomes even more immediate because tannin-rich materials can vary substantially by season, habitat, and extraction choices.

For Spondias mombin, the volume of research is not the problem. The issue is that the breadth of preclinical effects, including antioxidant and metabolic signals, still needs to be organized around plant part specificity, marker panels, and a safety-oriented clinical pathway, particularly because reproductive-relevant signals justify caution [74,75]. More papers do not necessarily mean higher translational readiness. Readiness comes from a controlled material, a credible safety base, and a clinical plan that starts where risk is manageable. If a metabolic indication is prioritized, a sensible early step would be adult-only studies with explicit exclusion of pregnancy and routine liver and kidney monitoring aligned with the expected exposure.

Figure 7 helps make these gaps visible at a glance by summarizing how evidence is distributed by species and by domain. The marginal totals point to a general gradient, with preclinical evidence dominating, and safety documentation lagging. In other words, the literature often progresses far enough to show activity in models, but stops before building the safety and tolerability foundations that regulators and clinicians require for translation. One point matters for interpretation. In the heatmap, “Clinical” is used broadly for clinical-oriented research, whereas Table 2 (clinical evidence) only captures controlled human trials; so, differences between heatmap counts and Table 2 entries are expected.

Based on the cross-species evidence domain synthesis (Table 2) and the integrated translational reading presented in this section, Amburana cearensis and Justicia pectoralis currently show the most advanced translational signals, as they include at least some controlled human evidence and clearer safety-oriented framing. In contrast, Libidibia ferrea and Spondias mombin remain largely anchored in chemistry- and preclinical-dominant evidence, with limited clinical validation and uneven safety/PK reporting. Lippia origanoides occupies an intermediate position: it is influential in antimicrobial/antioxidant screening and essential oil research, but translation remains constrained by chemotype variability and the limited integration of standardized extract specifications, pharmacokinetics, and longer-term safety evidence.

Overall, the comparative reading suggests three practical actions that can advance the field by directly addressing the main translational bottlenecks. First, standardize the tested material using chemical markers and declare chemotype when relevant. Second, strengthen the safety and tolerability base, including basic pharmacokinetic or exposure-relevant evidence where it is missing. Third, conduct targeted clinical studies aligned with the most plausible indications and routes, using validated endpoints and follow-up long enough to capture both benefit and adverse effects. This sequence, standardize, document safety, then test rigorously, provides the most direct path from promising pharmacology to clinically usable evidence.

In practice, this translational gap persists largely because many studies still lack consistent extract standardization, pharmacokinetic (PK) characterization, and systematically reported toxicological evidence to support dose setting and clinically defensible use.

3.6. Phytochemical Profile

The exploration of plant-derived secondary metabolites remains a cornerstone in the development of innovative therapeutic strategies. Among the diverse medicinal flora, five species—Lippia origanoides, Spondias mombin, Libidibia ferrea, Justicia pectoralis, and Amburana cearensis—have emerged as promising candidates due to their distinct phytochemical compositions and pharmacological activities. Each species features a major compound responsible for key biological effects, with evidence pointing toward antimicrobial, antiviral, antioxidant, anti-inflammatory, and neuroprotective mechanisms.

Table 3. A summary of key studies on five plant species highlighting their antioxidant, antimicrobial, and related biological activities, retrieved from the Web of Science database.

Reference	Plant Species *	Title and Objective	Main Results	Main Compound	NC **
[5]	Lippia origanoides	Title: Antimicrobial activity of the essential oil from Lippia sidoides, carvacrol and thymol against oral pathogens Objective: To evaluate the composition and antimicrobial activity of the essential oil.	1. Essential oil contains thymol (56.7%) and carvacrol (16.7%) as major antimicrobial components. 2. Exhibited potent inhibition against Streptococcus mutans and Candida albicans (MIC: 0.625–10 mg/mL). 3. Isolated compounds (thymol/carvacrol) were more effective than crude oil, suggesting antagonistic minor components.	THYMOL	274
Brazil
[25]	Spondias mombin	Title: Antiviral ellagitannins from Spondias mombin Objective: To investigate the antiviral effects of ellagitannins isolated from leaves and stems.	1. Geraniin and galloylgeraniin were isolated via bio-guided fractionation. 2. Both compounds demonstrated strong antiviral activity against Coxsackie B2 and HSV-1 (viral titer reduction: 103 at 50 µg/mL). 3. Weak or no antibacterial/fungal activity was observed at standard concentrations.	GERANIIN	89
Belgium
[79]	Libidibia ferrea	Title: Antioxidant and antiulcerogenic activity of the dry extract of pods of Libidibia ferrea Mart. ex Tul. (Fabaceae). Objective: To evaluate the antiulcer and antioxidant properties of the pod extract.	1. Extract contains phenolic acids (gallic, ellagic) with confirmed antioxidant properties. 2. Exhibited gastroprotective and antiulcerogenic effects via mucus stimulation and acid reduction. 3. Showed H. pylori inhibition and SH compound-dependent healing in the chronic ulcer model.	ELLAGIC ACID	29
Brazil
[4]	Amburana cearensis	Title: Antineuroinflammatory effect of Amburana cearensis and its molecules coumarin and amburoside a by inhibiting the MAPK signaling pathway in LPS-activated BV-2 microglial cells Objective: To assess anti-inflammatory effects.	1. Aqueous extract had the highest phenolic content and antioxidant activity (765.3 µM TE/g). 2. Demonstrated strong antimicrobial effect, especially against Staphylococcus aureus (MIC: 0.84 mg/mL). 3. Bacterial cell wall damage was confirmed via electron microscopy; the extract was non-cytotoxic.	COUMARIN	5
Brazil
[3]	Justicia pectoralis	Title: Potential of chambá (Justicia pectoralis Jacq.) leaves extracts as a source of bioactive compounds and natural antimicrobial agent. Objective: To assess biocompounds and antimicrobial potential.	1. The dry extract from A. cearensis and its compounds (coumarin, amburoside A) reduced nitric oxide, TNF-α, and IL-6 without cytotoxicity. 2. Inhibited iNOS expression and MAPK pathway (JNK, ERK1/2) activation in microglial cells. 3. Demonstrated strong antioxidant and anti-inflammatory potential relevant to neurodegenerative disease.	UMBELLIFERONE	4
Brazil

* Species names in the “Plant Species” column follow the current accepted taxonomy, whereas article titles are reported as originally published. ** NC = Number of citations.

presents a comparative synthesis of five key studies, one for each species highlighted in our survey. The variation in citation counts reflects both the chronological maturity of the publications and the growing relevance of recently emerging research in pharmacognosy and natural therapeutics.

Lippia sidoides Cham., a shrub native to the semi-arid region of northeastern Brazil, is traditionally used in folk medicine for respiratory and infectious conditions. Its essential oil is primarily composed of thymol (56.7%) and carvacrol (16.7%), both phenolic monoterpenes with well-documented antimicrobial properties; the study by Botelho et al. [5] demonstrated potent activity of this essential oil against Streptococcus mutans and Candida albicans, pathogens associated with dental caries and oral candidiasis. Thymol’s primary mechanism of action involves membrane disruption, leading to leakage of cytoplasmic contents and bacterial death. Interestingly, the study also observed that isolated thymol and carvacrol were more effective than the crude oil, suggesting that minor components may antagonize the activity of major constituents. This highlights the importance of chemical refinement and structure–activity studies to maximize efficacy. Beyond oral care, thymol has shown potential for integration into bioactive coatings and preservative systems due to its safety profile (GRAS) and stability.

Spondias mombin L., a tree widely distributed across tropical regions of Africa and the Americas, is valued in ethnomedicine for its antimicrobial and wound-healing properties. Corthout et al. [25] were among the first to isolate geraniin and galloylgeraniin—two ellagitannins—from the leaves and stems of this species. Both compounds exhibited significant antiviral activity against Coxsackie B2 and Herpes simplex virus type 1, reducing viral titers at low micromolar concentrations. Geraniin, in particular, interferes with early stages of viral replication and has since been investigated as a scaffold for anti-SARS-CoV-2 therapeutics. Its molecular structure, characterized by multiple galloyl and HHDP (hexahydroxydiphenoyl) groups, allows for extensive hydrogen bonding and redox interactions, which may underpin its broad-spectrum antiviral effects. Despite low antibacterial activity, the antiviral potency of these ellagitannins remains highly relevant, especially in the context of emerging viral threats and the need for novel, natural antivirals.

Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz, commonly referred to as “jucá,” is used extensively in Brazilian traditional medicine for treating gastrointestinal ailments, inflammation, and wounds. The pods contain high levels of ellagic acid and gallic acid—phenolic compounds known for their potent antioxidant activity. Prazeres et al. [79] reported that the dry pod extract of L. ferrea demonstrated gastroprotective and antiulcerogenic effects, attributed to increased mucus secretion and decreased gastric acid production. Notably, the extract also inhibited Helicobacter pylori, a major etiological agent in peptic ulcer disease. The action of ellagic acid appears to be linked to its ability to scavenge reactive oxygen species (ROS) and to modulate inflammatory pathways in gastric tissues. Given its multi-target profile, L. ferrea may serve as a promising botanical therapy for peptic ulcers and oxidative stress-related gastric disorders, offering an alternative to conventional proton pump inhibitors or H₂ blockers.

Amburana cearensis (Allemão) A.C. Sm., an endangered legume native to northeastern Brazil, has long been used for respiratory and inflammatory disorders. The seeds contain amburoside A, a glycosylated coumarin with high pharmacological interest. Araújo et al. [4] demonstrated that amburoside A significantly reduced levels of pro-inflammatory mediators (NO, TNF-α, IL-6) in LPS-stimulated BV-2 microglial cells. These effects were achieved through inhibition of the MAPK signaling pathway, specifically the ERK1/2 and JNK branches. Importantly, the treatment was not cytotoxic, highlighting amburoside A’s safety in neural models. Given the increasing prevalence of neurodegenerative diseases and the lack of curative therapies, amburoside A represents a promising neuroprotective agent capable of modulating neuroinflammatory responses—a key pathological hallmark in Alzheimer’s and Parkinson’s diseases.

Finally, Justicia pectoralis Jacq., locally known as “chambá,” is traditionally used in Brazil and parts of the Caribbean for treating bronchitis, cough, and anxiety. The aqueous extract of its leaves is rich in phenolic compounds, especially umbelliferone, a coumarin derivative. Guimarães et al. [3] reported that umbelliferone-rich extracts displayed strong antimicrobial activity, particularly against Staphylococcus aureus, a Gram-positive bacterium frequently implicated in skin and foodborne infections. Electron microscopy revealed morphological damage to bacterial cell walls, suggesting a bactericidal mechanism. Beyond antimicrobial activity, umbelliferone exhibits antioxidant and anti-inflammatory properties and has been associated with photoprotective and hepatoprotective effects in other studies. Its low cytotoxicity and water solubility further support its potential for use as a natural food preservative or as a topical agent in dermatological formulations.

The selection of plant species in this review—such as Lippia origanoides and Spondias mombin—also reflects a commitment to biodiversity-based innovation. These species are native or well-adapted to tropical and subtropical environments, making them suitable for cultivation under agroecological models with minimal inputs, thus supporting circular bioeconomy principles. Such approaches reduce dependency on synthetic agrochemicals and align with sustainable supply chains, reinforcing the environmental pillars of green pharmacy [36,80].

Altogether, these five plant species exemplify how major phytochemicals define the therapeutic identity of each botanical source. Whether acting through redox modulation, membrane disruption, viral inhibition, or cytokine regulation, these compounds illustrate the diverse mechanisms by which nature-derived molecules may address modern health challenges. Further investigations into structure–activity relationships, pharmacokinetics, and clinical efficacy are necessary to translate these findings into real-world applications. Nonetheless, the data presented reinforces the role of phytochemistry not only as a scientific discipline but as a conduit for sustainable, innovative, and culturally rooted therapeutic development.

3.7. Industrial Applications of Antimicrobial and Antioxidant Compounds from Medicinal Plant Extracts

Medicinal plants have long attracted public and scientific interest due to their pharmacological, cosmetic, and nutritional attributes. Their use has evolved into a widespread and strategic practice, paralleling advances in modern medicine and industrial pharmaceutical development [81]. Ancient civilizations—including Chinese, Greek, Roman, and Muslim societies—recognized the therapeutic and ritualistic value of medicinal and aromatic plants, and over time, these species became integral to the health and cultural practices of ethnic and tribal communities [9,82].

Beyond their historical and cultural significance, medicinal plants have emerged as essential tools in addressing contemporary challenges, especially in food safety and health protection. Food safety remains a major public health concern, with biological (e.g., microbial pathogens), chemical, and physical hazards still prevalent in global food systems despite technological progress [83]. Among these hazards, microbial contamination continues to be a critical concern, contributing to foodborne illnesses such as acute intoxications, central nervous system infections, and even carcinogenic outcomes [84].

From a green chemistry perspective, plant-derived antimicrobials and antioxidants exemplify sustainable design, given their inherent biodegradability, renewable sourcing, and reduced toxicity compared to synthetic analogs. Their use contributes to minimizing environmental hazards in both food and pharmaceutical production chains, as proposed by the 12 guiding principles of green chemistry, especially those relating to safer solvents and renewable feedstocks [21,85].

In addition to the benefits offered by bioactive compounds during production and use, attention must also be given to their post-use impacts. Life cycle assessments (LCAs) of plant-based antimicrobials and antioxidants can provide insights into their environmental fate, including biodegradability, ecotoxicity, and accumulation potential in ecosystems. Ensuring low-impact degradation pathways and minimizing persistent residues are essential to avoid shifting the environmental burden from chemical synthesis to natural compound waste streams [36,86,87].

In this context, plant-derived bioactive compounds, particularly those with antimicrobial properties, are receiving increasing attention as natural alternatives to synthetic preservatives. These compounds have found growing application across the pharmaceutical, cosmetic, and food industries. As shown in Figure 8, various efforts are currently directed at harnessing the antimicrobial potential of medicinal plant extracts to enhance product safety, extend shelf life, and reduce microbial load in formulations. Their mechanisms of action—ranging from disrupting microbial membranes to inhibiting enzymatic systems—are being progressively characterized and optimized for industrial use [88].

Alongside antimicrobial activity, many of these same extracts exhibit potent antioxidant effects, which are increasingly being recognized as equally important in product preservation and health promotion. Oxidative stress, resulting from the accumulation of reactive oxygen species (ROS), contributes significantly to the degradation of biomolecules and the development of chronic diseases. Incorporating antioxidant-rich plant extracts into industrial products not only prolongs shelf life by delaying oxidative spoilage but also provides functional health benefits to consumers. In the food industry, antioxidants prevent lipid peroxidation and maintain the sensory properties of products [89,90]. In cosmetics, they protect formulations from degradation and enhance skin health by counteracting oxidative stress [89,91]. In pharmaceuticals, these compounds help stabilize formulations and support therapeutic efficacy by reducing oxidative degradation of active ingredients [89,92].

Therefore, the dual antimicrobial and antioxidant capacities of medicinal plant extracts represent a valuable intersection between efficacy and safety in natural product applications. This duality positions them as multifunctional agents with cross-industry relevance. As illustrated, their inclusion in pharmaceutical and food formulations offers a promising response to microbial resistance and chemical preservative concerns. Nevertheless, challenges persist in ensuring consistent efficacy, stability under various processing conditions, and regulatory acceptance, especially within food systems. Such limitations may hinder their full-scale adoption. Even so, growing consumer demand for clean-label and natural products continues to drive innovation toward plant-based alternatives [89].

In this light, the integration of medicinal plant extracts with proven antimicrobial and antioxidant activities not only enhances product safety and quality across industries but also contributes to broader goals of public health promotion and sustainable technological development.

3.7.1. Antimicrobial Activity

Antimicrobial substances derived from medicinal plants offer significant potential for form applications across various industries, including food and pharmaceuticals. As public awareness of the potential health risks associated with the use of chemical preservatives in food increases, there is growing interest in alternative, natural antimicrobial compounds. Consumers are enthusiastic about the use of antimicrobial substances from medicinal plant extracts, which can enhance food quality and reduce contamination by spoilage and pathogenic microorganisms [93].

With the rising global population, the food industry faces the dual challenge of increasing production rates and speeding up transportation processes. This has contributed to a greater risk of compromised food safety as a result of microbiological contamination by important foodborne pathogens [94].

Foodborne illnesses not only negatively impact human health, leading to hospitalization and treatment costs, but also cause significant economic losses to the food industry. Microbial contamination is one of the leading foodborne illness outbreaks and contributes to the spoilage of millions of tons of food each year. Bacteria, fungi, and viruses are responsible for over 200 types of foodborne illnesses, including diarrhea and life-threatening diseases such as cancer [95].

Food preservation techniques aim to extend the shelf life of food, as well as to favor the absence of most foodborne pathogenic microorganisms that may be present in food products [88]. However, physical food preservation techniques such as cooling, drying, thermal processing, and chemical preservation, including the use of ammonia, salts, and organic acids, can compromise the nutritional quality and sensory characteristics of the food. Furthermore, the overuse of chemical preservatives has raised concerns about food toxicity, prompting many food manufacturers to reduce or exclude these substances [95].

As a result, there has been a growing interest in the use of natural preservatives to reduce spoilage and prevent the growth of important foodborne pathogens. Compounds with antimicrobial and pharmacological properties, such as organic acids (lactic, citric, acetic), phenols (phenolic acid, tannins, and polyphenols), essential oils, alkaloids, terpenoids, flavonoids, and peptides, are commonly recovered from plant materials to address this challenge [96,97].

The antimicrobial mechanisms of these substances, particularly in the form of plant extracts, are influenced by their structural arrangement. Research into the mechanism of herbal antimicrobial substances is progressing rapidly, and their inhibitory effect on pathogens can be attributed to several pathways (Figure 9). These pathways include (1) disruption of cell wall and cell membrane integrity and alteration of cell membrane permeability and fluidity, causing leakage of cell contents [98]; (2) interruption of protein synthesis and inhibition of enzyme activity, affecting the physiological activity of pathogenic microorganisms [99]; (3) action on replication, transcription, synthesis, and expression of nucleic acids, causing impairment of gene expression and inhibition of growth and reproduction of pathogens [100]; and (4) inhibition of the pathogen’s metabolism targeting the tricarboxylic acid (TCA) cycle, blocking the synthesis of adenosine triphosphate (ATP) and producing reactive oxygen species (ROS) [101].

Despite their potential, antimicrobial plant extracts have challenges such as variability in composition, extraction techniques, and regulatory approval. Even though research continues, it keeps finding their inclusion to be efficacious in food safety. Certainly, such plant-derived compounds would be an important means of meeting the ever-increasing consumer demand for natural alternatives by reducing reliance on synthetic preservatives, thereby providing a solution for the food industry’s sustainable application.

3.7.2. Antioxidant Activity

Antioxidant, antimicrobial, antiulcerogenic, anti-inflammatory, and antidiabetic activity are some of the beneficial effects associated with the plant extracts from the evaluated field, as illustrated in Figure 10 [3,4,79,102,103,104]. Among these, antioxidant activity has gained greater prominence in recent research, as previously highlighted (Section 3.4.2, Figure 6).

Reactive oxygen species (ROS) are chemically active substances with a tendency to oxidize and generate an excess of free radicals within the body’s tissues, favoring the degradation of low-density lipoproteins and ultimately exacerbating bodily deterioration. Antioxidants, which are bioactive molecules found in plants, effectively neutralize ROS, thus mitigating oxidative stress. These bioactive compounds, including flavonoids, tannins, saponins, terpenes, alkaloids, and ascorbic acid, have therapeutic potential due to their ability to combat oxidative damage [105].

Oxidative stress occurs when the body is unable to neutralize ROS with its natural antioxidants, leading to cellular damage. This imbalance can affect critical biomolecules, such as proteins, lipids, and DNA, contributing to the development of diseases such as cancer, cardiovascular disease, neurodegenerative disorders, and diabetes [106,107]. By neutralizing free radicals, antioxidants help protect cells from the harmful effects of oxidative stress, thereby promoting health and reducing the risk of these diseases [108,109,110].

Various factors, including metabolic processes, catalytic enzymes, exposure to UV radiation, stress, infections, and pollution, can trigger the formation of free radicals [111,112]. Consequently, the consumption of antioxidants found in foods such as fruits and vegetables, or natural products containing bioactive molecules, has been recommended as a strategy to reduce oxidative damage and prevent related diseases like diabetes and cardiovascular issues [113].

In this scenario, aromatic and medicinal plants have become valuable sources of natural antioxidants in recent decades. These plants, which contain various secondary metabolites such as flavonoids, phenolic compounds, alkaloids, and terpenoids, are not only essential for plant defense but also offer health benefits to humans, including antioxidant and antimicrobial properties [114,115,116]. These compounds play vital roles in plant survival, and their presence in different parts of the plant, such as fruits, leaves, stems, and tubers, contributes to the plant’s ability to combat environmental stressors.

In the food industry, plant extracts from aromatic and medicinal plants are increasingly used to enhance flavor and extend shelf life, replacing synthetic antioxidants and protecting against microbial contamination, as well as improving the sensory characteristics of foods [117,118]. Phenolic compounds and essential oils, in particular, have garnered interest as alternative sources for food preservation [119].

Essential oils (EOs) are volatile, odorous compounds naturally present in plants used as seasonings and spices. These compounds support important biological functions such as the survival of plants in the face of defense mechanisms, which include protection against excess ultraviolet, microorganisms, insects, and animals [120]. EOs primarily consist of terpenes, terpenoids, and various aliphatic and aromatic compounds (such as aldehydes and phenols), all of which contribute to their antioxidant and antimicrobial activities [121]. For example, phenolic compounds found in the leaves of Kulim (Scorocarpus borneensis) have shown bacteriostatic effects [122,123,124].

These bioactive compounds also serve as preservatives in food products, prolonging the shelf life of food products while benefiting consumer health [122,125]. Polyphenols present in essential oils are also being explored for their potential in the food industry. For instance, polyphenol-based films can be used to protect fruits, preserving their ripeness and organoleptic properties [126]. Additionally, phenolic compounds such as ellagic acid, catechin, and quercetin, found in red grapes, are known to inhibit the growth of Cronobacter sakazakii in baby food. Olive oil, which is rich in polyphenolic compounds like hydroxytyrosol, oleuropein, and tyrosol, has demonstrated antimicrobial activity against pathogens such as S. aureus, Salmonella sp., and Moraxella catarrhallis [121].

The antioxidant properties of medicinal plant extracts offer great potential for preventing oxidative stress-related diseases. However, using these compounds in food preservation comes with challenges. Variations in bioactive content can affect consistency, and incorporating them might alter flavor, texture, or shelf life. Despite these hurdles, the growing demand for natural preservatives creates opportunities for the food industry to explore sustainable, plant-based alternatives to synthetic antioxidants.

3.8. Challenges and Future Perspectives

Future strategies in medicinal plant research should prioritize eco-innovation by integrating life cycle assessments and green metrics into extraction, purification, and formulation protocols. Approaches such as supercritical CO₂ extraction and microwave-assisted methods have demonstrated lower environmental footprints compared to conventional solvent-based techniques [85]. Incorporating greener processing routes can strengthen the sustainability profile of plant-based bioactives and improve alignment with climate-resilient development frameworks.

Despite significant advances in mapping biological activities and identifying major phytochemicals, important challenges still limit translation to therapeutic and industrial settings. A central constraint is the complexity and variability of phytochemical profiles, which often comprise multiple compounds with distinct or overlapping mechanisms of action. Accordingly, evidence packages that support translation require not only bioactivity reports, but also marker-based chemical standardization, explicit reporting of plant part and origin, clearer dose–exposure logic, and more systematic integration of safety endpoints. In parallel, the scientometric patterns observed in this review indicate strong leadership but uneven international integration: Brazil leads output, while the predominance of single-country publications (Figure 5c) suggests limited multicenter validation and reduced opportunities for inter-laboratory harmonization. Expanding international partnerships would therefore be relevant not only to increase visibility but also to improve methodological diversity, evidence comparability, and knowledge transfer while supporting sustainability-oriented agendas aligned with SDGs and ethical bioprospecting principles [22,50].

A methodological limitation of the present review is the use of a single indexed database. Although this choice favored metadata consistency and reproducibility in the scientometric workflow, it may have reduced the retrieval of studies indexed exclusively in other sources and may therefore underrepresent part of the regional or non-overlapping literature. Even so, the WOS-based corpus was considered adequate for identifying major publication trends, collaboration patterns, and evidence gaps within a standardized analytical framework. This choice may bias estimates of productivity, collaboration, and citation concentration toward journals and regions more comprehensively indexed by WOS, potentially underrepresenting locally relevant or regionally indexed research. Therefore, country- and author-level rankings and some network structures should be interpreted as WOS-based patterns rather than as exhaustive representations of the overall literature landscape.

Regarding global health challenges, particularly antimicrobial resistance, plant-derived antimicrobials remain a practical driver of research relevance. Future progress in this area will depend on moving beyond screening toward standardized evaluation frameworks, including reproducible chemistry, formulation feasibility, and safety boundaries. Similarly, in the food industry, antioxidant-rich extracts remain promising for shelf life and safety applications, but require robust chemical markers and performance validation in realistic matrices. The integration of bioinformatics, high-throughput screening, and omics approaches can accelerate hypothesis prioritization; however, their translational value depends on confirmatory assays and coherent study designs connecting chemical composition to biologically meaningful and safety-relevant endpoints [52,53,54,55,56]. A holistic approach also supports interpreting phenolic compounds not only as isolated actives but also as components of broader functional frameworks for health and well-being [57,58].

Table 4. Recent original research articles published in 2025 in the evaluated field, retrieved from the Web of Science^® database.

Reference—Country	Title—Objective	Methodology	Main Results
[127]	Title: Protective effect of Spondias mombin leaf extracts against aluminum chloride-induced brain oxidative stress, inflammation and apoptosis in rats Objective: To evaluate whether Spondias mombin leaf extracts can protect against aluminum chloride-induced neurotoxicity.	1. Male Wistar rats received AlCl3 (100 mg/kg) to induce neurotoxicity. 2. Treatment: Spondias mombin leaf extract (SME) or fraction (SMF) at 100–200 mg/kg. 3. Brain endpoints: oxidative stress, inflammation, and apoptosis markers (biochemical/molecular). 4. Phytochemical profiling (kaempferol-rich) plus hippocampal histology/neuronal integrity assessment.	1. AlCl3 increased oxidative stress, inflammatory mediators, and apoptotic signaling in the brain 2. SME/SMF reduced TNF-α, NO, and other pro-inflammatory/oxidative biomarkers. 3. Apoptosis markers (caspase-3, Bax) were attenuated, and hippocampal architecture was preserved. 4. Kaempferol and related polyphenols were proposed as key contributors to neuroprotection.
Nigeria
[128]	Title: Synergistic potency and GC-MS analysis of Persea americana extracts against Aedes aegypti Objective: To assess insecticidal activity and chemical composition of Persea americana pulp and seed extracts against Aedes aegypti.	1. Prepared methanol, ethanol, hexane, and acetone leaf extracts of Persea americana. 2. Larvicidal bioassay on 4th-instar Aedes aegypti larvae (24 h) with LC50 estimation. 3. Evaluated synergistic mixtures between selected extracts. 4. Phytochemical screening and GC–MS used to characterize likely active constituents.	1. All extracts showed significant larvicidal activity against A. aegypti after 24 h. 2. LC50 values: ethanol 14.606 ppm; methanol 22.548 ppm; hexane 146.157 ppm. 3. Synergistic mixtures improved activity (e.g., ethanol + methanol LC50 15.181 ppm). 4. GC–MS indicated fatty acids/esters and other compounds consistent with larvicidal action.
Nigeria
[129]	Title: Hydroethanolic extract of Spondias mombin L. leaves attenuates alveolar bone loss and inflammation in a model of periodontitis induced in male Wistar rats. Objective: To test whether a hydroethanolic Spondias mombin leaf extract reduces tissue destruction and inflammation in experimental periodontitis.	1. Ligature-induced periodontitis in 63 male Wistar rats (five experimental groups). 2. Oral gavage of Spondias mombin leaf extract at 50, 100, or 200 mg/kg for 10 days. 3. Micro-CT and histology to quantify alveolar bone loss and tissue inflammation. 4. Cytokines/RT-qPCR in the gingiva plus blood biochemistry to assess systemic safety.	1. Extract reduced linear alveolar bone loss at 100 and 200 mg/kg (micro-CT). 2. Trabecular separation improved at 200 mg/kg, with better histological scores. 3. Pro-inflammatory cytokine expression decreased at 50 and 100 mg/kg (tissue assays). 4. Blood biochemical markers were unchanged, supporting short-term tolerability.
Brazil
[130]	Title: Searching for Hypoglycemic Compounds from Brazilian Medicinal Plants Through UPLC-HRMS and Molecular Docking. Objective: To identify candidate hypoglycemic compounds and mechanistic targets from Brazilian medicinal plants in the context of diabetes management.	1. Aqueous extracts from five Brazilian medicinal plants were prepared and screened. 2. In vitro inhibition assays for α-glucosidase and invertase (enzyme-based testing). 3. UPLC–HRMS chemical profiling plus molecular docking and ADME in silico prediction. 4. Acute toxicity screening in zebrafish to support a first-pass safety assessment.	1. L. origanoides, A. cearensis, and J. pectoralis showed the strongest enzyme inhibition. 2. Isoquercitrin confirmed as a potent α-glucosidase inhibitor (IC50 = 0.09 mg/mL). 3. Docking highlighted hyperoside/eudesmic acid/isoquercitrin as major inhibitors per species. 4. Zebrafish assays suggested low toxicity (Lippia/Amburana) and moderate levels (Justicia).
Brazil
[131]	Title: Underexploited fruits from the Brazilian Cerrado: Biodiversity, phenolic composition and biological activities. Objective: To synthesize evidence on biodiversity, phenolic composition, and bioactivities of underexploited fruits from the Brazilian Cerrado.	1. Structured literature synthesis covering 40 native fruits from the Brazilian Cerrado. 2. Compiled phenolic profiles by plant part (pulp, peel, seeds) and extraction approaches. 3. Summarized antioxidant tests (e.g., DPPH, ORAC, FRAP) and reported bioactivities. 4. Assessed environmental drivers of phytochemistry and implications for sustainable use.	1. Across 40 fruits, phenolic composition varied markedly by tissue (pulp, peel, seeds). 2. Gallic acid, quercetin, catechin, and related phenolics were recurrent across species. 3. Strong antioxidant capacity was repeatedly reported (DPPH, ORAC, and FRAP outcomes). 4. Environmental factors and processing were highlighted as key drivers of bioactive yield.
Brazil
[132]	Title: Low-Cost Electronic Nose for Identification of Wood Species in Which Brazilian Sugar Cane Spirit Was Aged. Objective: To evaluate whether an electronic nose can discriminate Amburana cearensis extracts and relate sensor responses to chemical differences.	1. Developed a low-cost electronic nose (four conductive polymer gas sensors). 2. Analyzed spirits aged in different woods, including Amburana cearensis. 3. Applied PCA and leave-one-out validation for pattern recognition/classification. 4. Assessed performance for rapid wood identification in beverage quality control.	1. The electronic nose enabled rapid discrimination among woods used for aging spirits. 2. PCA separated samples by wood type, including Amburana cearensis, with clear clustering. 3. Leave-one-out validation achieved perfect classification for the tested set. 4. Approach supports authentication and process standardization in beverage production.
Brazil
[133]	Title: Antitumor and Cytogenotoxic Activities of Libidibia ferrea Hydroalcoholic Extracts in Murine Breast Carcinoma. Objective: To evaluate the antitumor activity of Libidibia ferrea extracts while screening for cytogenotoxicity signals relevant to safety.	1. Prepared hydroalcoholic leaf (HAFL) and fruit (HAFR) extracts of Libidibia ferrea. 2. Chemical profiling focused on phenolic constituents (gallic/ellagic acids). 3. In vitro testing in MDA-MB-231 cells for cytotoxicity and DNA damage. 4. In vivo 4T1 model with oral dosing (0.3 and 3.0 g/kg) and body/liver weight monitoring.	1. Fruit extract (HAFR) had ~3× higher total phenolics than leaf extract (HAFL). 2. HAFR induced DNA damage and cell death in MDA-MB-231 breast cancer cells. 3. In vivo, HAFR reduced 4T1 tumor growth by 94% at 0.3 and 3.0 g/kg. 4. No changes in body or liver weight were observed, suggesting tolerability at the tested doses.
Brazil
[134]	Title: Evaluation of the stability and antimicrobial activity of emulsions loaded with thymol for the post-harvest sanitization of lettuce (Lactuca sativa L.). Objective: To evaluate the stability and antimicrobial performance of thymol-loaded emulsions designed for post-harvest lettuce sanitization.	1. Prepared thymol emulsions by primary emulsification and high-energy shear methods. 2. Measured droplet size, zeta potential, and PDI to select the most stable systems. 3. Determined MIC and applied emulsions to lettuce for sanitization challenges. 4. Quantified pathogen reduction and recorded sensory/quality changes after 15 min.	1. High-energy shear produced the most stable emulsions (145–193 nm; favorable PDI/zeta). 2. Lowest MIC was 1 mg/mL (SRS-thymol) and 2 mg/mL (L. sidoides EO) emulsions. 3. Application achieved up to ~3 log reductions against key pathogens on lettuce. 4. At 2× MIC, treatments affected leaf texture and color, indicating a usability trade-off.
Brazil
[135]	Title: Chemical Characterization, Antioxidant, and Anticholinesterase Activities of Libidibia ferrea (Mart. Ex Tul.) LP Queiroz and In Silico Studies with the Acetylcholinesterase Enzyme. Objective: To characterize antioxidant and anticholinesterase activities of Libidibia ferrea fruit and stem bark extracts and explore potential molecular interactions.	1. Obtained L. ferrea extracts (leaves/bark; hydroethanolic) and fractions plus flower essential oil. 2. Antioxidant assays (DPPH/ABTS) and AChE inhibition via the Ellman method. 3. HPLC characterization of key phenolics; GC–MS for essential oil constituents. 4. Molecular docking to evaluate the binding of major compounds to the AChE active site.	1. EOLF and MFLF showed high tannin levels and strong antioxidant/AChE inhibition. 2. HPLC confirmed phenolic-rich profiles including chlorogenic acid, catechin, rutin, and ellagic acid. 3. Docking suggested (Z)-9-tetradecenyl acetate interacts at the AChE site of galantamine. 4. Findings support L. ferrea as a candidate source of AChE-active phytochemicals.
Brazil
[136]	Title: Antioxidant potential and phytochemical constituents of a synergy-based combined extract of Spondias mombin L., Spilanthes filicaulis (Schumach. & Thonn.) C.D. Adams and Piper guineense Thonn. Objective: To examine whether combining Spondias mombin with Spilanthes filicaulis and Piper guineense enhances antioxidant performance and antioxidant synergy indices.	1. Prepared two combined extracts (H1/H2) from S. mombin, S. filicaulis, and P. guineense. 2. Assessed antioxidant capacity by DPPH (IC50) and FRAP reducing power. 3. Measured total phenolic and flavonoid contents for both mixtures. 4. GC–MS profiling to compare phytochemical composition of H1 vs. H2.	1. H1 outperformed H2 in DPPH scavenging (IC50 72.87 ± 0.63 µg/mL vs. 150.2 ± 1.08). 2. FRAP reducing power and total phenolic/flavonoid contents were higher for H1. 3. GC–MS detected 28 compounds in H1 and 17 in H2, indicating compositional differences. 4. Combined extracts, especially H1, were highlighted as promising antioxidant candidates.
Nigeria
[137]	Title: Antimalarial potentials, toxicological impacts, and gas chromatography-mass spectrometric analysis of ethanol extract of Spondias mombin Linn. Objective: To evaluate the antiplasmodial activity of Spondias mombin extract in vivo and explore impacts on hematological and antioxidant markers.	1. P. berghei-infected mice treated with graded doses of S. mombin ethanol extract. 2. Measured hematology and oxidative stress markers (CAT/GPX/SOD; MDA). 3. Evaluated liver/kidney function and serum electrolytes for toxicity signals. 4. GC–MS profiling identified 65 bioactive components associated with the extract.	1. Extract significantly inhibited parasite growth and improved several hematological indices. 2. CAT activity increased (100 mg/kg), and MDA decreased (200 mg/kg); SOD was unchanged. 3. Some renal/electrolyte stress signals appeared at higher doses (urea/creatinine; Na/K). 4. GC–MS identified 65 constituents; authors propose adjunct potential pending bioactive isolation.
Nigeria
[138]	Title: Antiplasmodial Potentials, Phytocompounds, and the Possible Toxic Effects of Administration of Ethylacetate Extract of Spondias mombin Linn. Objective: To investigate antiplasmodial activity, phytocompounds, and proposed mechanisms after administration of an ethyl acetate Spondias mombin extract.	1. Plasmodium berghei infection model with treatment using ethyl acetate S. mombin extract. 2. Assessed parasite growth suppression versus the standard antimalarial drug. 3. Measured hematology, antioxidant markers (SOD/GPX/MDA), liver enzymes, and electrolytes. 4. GC–MS profiling identified 78 bioactive components in the extract.	1. Extract markedly reduced parasite growth and improved RBC/platelet counts in infected mice. 2. Antioxidant profile improved (higher SOD/GPX; lower MDA), consistent with redox modulation. 3. Liver enzymes showed mixed changes, including ALT elevation at the highest dose. 4. Electrolytes remained stable, and GC–MS identified 78 constituents; further mechanistic work is needed.
Nigeria
[139]	Title: Phytochemical Composition and Evaluation of Acute Toxicity, Antioxidant, and Antibacterial Activities of Spondias mombin L. and Myracrodruon urundeuva Allemao Ethanolic Extracts Against Vibrio parahaemolyticus. Objective: To define the phytochemical profile of Justicia pectoralis and evaluate acute and subacute toxicity to support evidence-based safety assessment.	1. Ethanolic extracts of Spondias mombin and Myracrodruon urundeuva analyzed by UPLC–MS. 2. Antibacterial testing against Vibrio parahaemolyticus with MIC and bactericidal evaluation. 3. Antioxidant assessment by DPPH and related ROS/RNS protection rationale. 4. Acute toxicity screening using Artemia salina nauplii (LC50 assessment).	1. M. urundeuva contained tannins/flavonoids; S. mombin extracts showed mainly procyanidins. 2. Both extracts showed moderate antibacterial activity; M. urundeuva MIC reached 0.625 mg/mL. 3. S. mombin demonstrated bactericidal activity reported as surpassing ampicillin. 4. Low acute toxicity (LC50 > 1000 µg/mL) supported potential use in aquaculture pathogen control.
Brazil

consolidates thirteen original studies published in 2025 and provides a practical snapshot of emerging methodological priorities. The distribution of countries in this subset is consistent with the broader country patterns (Figure 5): most 2025 outputs originate from Brazil and Nigeria, reinforcing the leadership of these two countries in the field. Across these studies, in vivo models remain central for establishing mechanistic plausibility and therapeutic relevance.

This is illustrated by neuroprotection in an aluminum chloride model using Spondias mombin leaf extracts [127], reduced inflammatory burden and alveolar bone loss in experimental periodontitis treated with a hydroethanolic S. mombin extract [129], and antiplasmodial efficacy against Plasmodium berghei alongside improvements in hematological and oxidative stress markers [137,138]. Oncology-oriented testing further reflects the breadth of applications being explored, as Libidibia ferrea extracts were assessed for antitumor potential together with cytogenotoxicity screening, which is essential for balancing efficacy claims with safety constraints [133]. The acute and subacute toxicity evaluation of Justicia pectoralis provides an additional example of coupling phytochemical profiling with safety endpoints to support dose setting and more defensible longer-term design choices [134].

Several 2025 studies also highlight the importance of moving beyond single-plant, single-assay approaches by adopting tools that improve comparability and quality control. Synergy-driven combinations involving Spondias mombin, Spilanthes filicaulis, and Piper guineense suggest that rational blends can enhance antioxidant responses, while simultaneously increasing the requirement for marker-based standardization and batch-to-batch control [136]. Methodological innovation contributes directly to standardization: the electronic nose approach applied to Amburana cearensis extracts illustrates a practical path for rapid discrimination and quality screening when full chromatographic workflows are not feasible [132]. Computational screening also appears as a pragmatic strategy to prioritize hypotheses before resource-intensive validation, as shown by in silico-driven studies aimed at identifying hypoglycemic candidates from Brazilian medicinal plants and assessing anticholinesterase potential in Libidibia ferrea extracts—while still requiring confirmatory assays and pharmacokinetic follow-up [130,135].

From an application perspective, antimicrobial and food safety themes remain prominent. Thymol-loaded emulsions designed for post-harvest lettuce sanitization show how antimicrobial performance can be paired with technological feasibility in food systems, supporting plant-based preservatives that remain active over time [134]. Extracts and formulations were also evaluated against clinically and industrially relevant targets, including Vibrio parahaemolyticus, reinforcing phytochemicals as candidates for complementary antimicrobial strategies [134]. Beyond microbes, Persea americana extract activity against Aedes aegypti expands the translational landscape toward vector control, where plant-derived actives may complement integrated pest management approaches [128]. Finally, syntheses of underexploited Cerrado fruits emphasize that Brazil’s biodiversity remains a major reservoir for bioactive discovery, while also highlighting persistent challenges in extraction heterogeneity, outcome reporting, and cross-study comparability [131]. Taken together, the 2025 studies summarized in Table 4 support a pragmatic agenda that links greener processing, stronger standardization, deeper in vivo validation, and safety-centered programs, supported by quality control tools that can accelerate translation without compromising rigor.

4. Conclusions

This scientometric review, based on a transparent and reproducible workflow, shows that research on five South/Central American medicinal plants is active, regionally concentrated, and increasingly organized around antimicrobial and antioxidant applications. Brazil remains the central scientific actor in terms of productivity, institutional presence, and citation impact, while journals such as the Journal of Ethnopharmacology and Industrial Crops and Products function as major publication hubs linking pharmacological and application-oriented research.

At the same time, the integrated synthesis of chemistry, preclinical evidence, human studies, and safety shows that the field is not advancing uniformly across translational stages. Across most species, preclinical evidence substantially exceeds controlled human validation and systematic safety reporting, which creates a clear bottleneck between biological promise and practical applicability. The current literature, therefore, supports cautious optimism rather than direct translational confidence.

Three take-home messages emerge from this review. First, evidence imbalance remains a central issue: chemistry and preclinical bioactivity are well represented, but controlled clinical and safety evidence are still limited for most species. Second, standardization is a major bottleneck: future progress depends on better marker-based characterization, chemotype declaration when relevant, and improved comparability across extracts, plant parts, and study designs. Third, translation will require stronger integration between regional expertise, multicenter collaboration, and safety-oriented validation, particularly if these plants are to support pharmaceutical, food, or phytotherapeutic applications in regulated settings.

Overall, this review provides a comparative roadmap for future research by showing that the next phase of the field should not be defined only by continued screening of promising plants, but by the production of more reproducible, clinically interpretable, and safety-aware evidence. In this sense, the value of medicinal plant research lies not only in identifying bioactive compounds, but in building an evidence structure capable of supporting responsible and sustainable translation.