Skip to Content
MDPIMDPI
IJMSInternational Journal of Molecular Sciences
PDF
  • Review
  • Open Access

9 January 2026

The Role of Astaxanthin as an Antioxidant and Anti-Inflammatory Agent in Human Health: A Systematic Review

,
,
,
,
,
,
,
,
…
1
Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy
2
Department of Biomedical, Surgical and Dental Sciences, Milan University, 20122 Milan, Italy
3
Department of Experimental Medicine, University of Salento, 73100 Lecce, Italy
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci.2026, 27(2), 700;https://doi.org/10.3390/ijms27020700
This article belongs to the Topic Natural Bioactive Compounds as a Promising Approach to Mitigating Oxidative Stress
Version Notes
Order Reprints

Abstract

This systematic review aimed to summarize the effects of astaxanthin (ASX) supplementation on oxidative stress, inflammation, and metabolic regulation in human studies. A systematic search was conducted in Scopus, Web of Science (WOS), and PubMed for articles published between 2020 and 2025. Fifteen studies involving human participants were included, while in vitro and animal studies were excluded. ASX consistently reduced pro-inflammatory cytokines (IL-6, TNF-α, TGF-β1) and oxidative stress indices while increasing antioxidant capacity (SOD, TAC). Combined ASX and exercise interventions improved body composition, lipid profiles, insulin sensitivity, and immune recovery. In women with Polycystic Ovary Syndrome (PCOS) or endometriosis, ASX downregulated endoplasmic reticulum stress–related apoptotic pathways and improved oocyte and embryo quality. Cardiometabolic and respiratory outcomes showed improved endothelial function and reduced disease severity. Astaxanthin demonstrates broad antioxidant and anti-inflammatory properties, supporting its role as a promising adjunctive therapy for metabolic, reproductive, and cardiovascular health. Further well-designed clinical trials are needed to confirm optimal dosing and mechanisms of action.

1. Introduction

1.1. Carotenoids and Natural Therapies

Carotenoids represent a family of naturally occurring pigments synthesized by plants, algae, bacteria and fungi [1,2,3,4,5]. These compounds are gaining increasing attention in the field of preventive and integrative medicine because they are accessible via diet or supplementation and often exhibit favorable safety profiles. Among these, astaxanthin is distinguished by a unique chemical structure, a keto-carotenoid (xanthophyll) bearing hydroxyl and keto functional groups at each end of its polyene chain, which confers exceptional antioxidative efficacy [6,7,8]. Its natural occurrence in microalgae (such as Haematococcus pluvialis), krill, shrimp and salmon underscores its marine origin and highlights the concept of leveraging “marine-derived natural products” in human health [9,10]. In the broader context of natural medicine, there is a growing trend toward identifying bioactive compounds that are as close as possible to their dietary or naturally derived forms rather than entirely synthetic molecules [11,12,13,14]. This reflects a philosophy of supporting physiological homeostasis via compounds that complement endogenous defense systems, rather than overriding them with high-dose pharmaceuticals [15,16,17,18,19]. Astaxanthin (ASX), by virtue of its structural similarity to other xanthophylls and its presence in the food chain, fits this paradigm of a “natural intervention” or nutraceutical [20,21,22] that might bridge the gap between lifestyle intervention (diet, exercise) and pharmacologic treatment (Figure 1).
Figure 1. Schematic representation of the natural origin of astaxanthin and its systemic health effects. On the left, the microalga Haematococcus pluvialis is shown as the main natural source of astaxanthin, which is transferred along the aquatic food chain. On the right, an illustrative model of a functionalized nanoparticle is presented: astaxanthin is depicted both as molecules distributed within the nanoparticle matrix and as an astaxanthin-rich core, responsible for scavenging reactive oxygen species (ROS). The antioxidant activity of astaxanthin is associated with benefits for cardiovascular health, neuroprotection, and oral health, highlighting its potential nutraceutical and therapeutic applications.

1.2. Astaxanthin: Oxidative Stress, Inflammation and the Need for Complementary Natural Strategies

Oxidative stress occurs when the generation of reactive oxygen species (ROS) outpaces the body’s antioxidant defenses, leading to lipid peroxidation [23,24,25], protein and DNA damage, mitochondrial dysfunction, and the triggering of pro-inflammatory pathways [26,27,28,29]. Chronic inflammation, in turn, is intertwined with oxidative stress and contributes to the pathogenesis and progression of a wide spectrum of diseases, cardiovascular diseases, metabolic syndrome, neurodegenerative disorders, ocular ailments, and even oral/odontologic conditions such as periodontitis [30,31,32,33]. The integration of natural compounds with antioxidative and anti-inflammatory capacities therefore emerges as a logical strategy to complement standard care and lifestyle modification, particularly in preventive medicine and in fields such as dentistry, where less invasive adjunctive therapeutic options are desirable [34,35,36]. ASX’s molecular configuration allows it to traverse cellular membranes and potentially accumulate in lipid-rich tissues, thereby conferring protective effects at the cellular and sub-cellular level. It has been shown to modulate redox-sensitive transcription factors such as Nrf2 (nuclear factor erythroid 2-related factor 2) and NF-κB (nuclear factor kappa B) [37,38,39], thereby simultaneously enhancing endogenous antioxidant defenses and suppressing pro-inflammatory signaling [40,41,42]. Importantly, the concept of a “natural medicine” in this context underscores not only the origin of the compound, but also its compatibility with physiological processes and minimal side-effect profile, which is particularly relevant in general medicine and dental practice where long-term safety is paramount [43,44,45].
Hormesis is a key conceptual framework for understanding the biological activity of astaxanthin, often referred to as a “hormetic nutrient” [46,47]. Rather than acting solely as a direct antioxidant, astaxanthin exerts its protective effects through mild adaptive stress that activates endogenous defense pathways [48]. In particular, astaxanthin stimulates the Nrf2 signaling cascade, leading to the upregulation of cytoprotective and antioxidant enzymes, while concurrently inhibiting the NF-κB pathway, a central regulator of pro-inflammatory gene expression [49,50]. This dual modulation enables cells to enhance resilience against oxidative and inflammatory insults, promoting homeostatic adaptation rather than simple radical scavenging [51]. Through this hormetic mechanism, astaxanthin supports cellular protection and functional recovery in stress-related disorders, highlighting its role as a biologically active nutrient that strengthens the body’s intrinsic defense systems [52].

1.3. Mechanisms of Action: Antioxidant, Anti-Inflammatory and Tissue-Protective Effects

ASX’s antioxidative mechanisms are multifaceted. It directly scavenges free radicals, such as superoxide anions, hydroxyl radicals, singlet oxygen, and interrupts lipid peroxidation chains due to its conjugated double bond structure [53,54,55,56]. Moreover, ASX has been shown to activate the Nrf2 pathway, promoting the expression of endogenous antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione-peroxidase (GPx) [57,58,59,60]. On the anti-inflammatory side, ASX inhibits the nuclear translocation of NF-κB, decreases expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and interferes with MAPK signaling (p38, JNK, ERK). Interestingly, recent data indicate a direct binding interaction between ASX and IL-6, thereby disrupting the feedback loop of inflammatory amplification [61,62]. Furthermore, ASX protects mitochondrial integrity by reducing mitochondrial ROS, preserving mitochondrial membrane potential, and limiting opening of the mitochondrial permeability transition pore, thus safeguarding cellular energy metabolism and apoptotic resistance [63,64,65,66,67,68]. Collectively, these mechanisms support a paradigm in which ASX functions not simply as a passive antioxidant, but as an “active natural medicine” that modulates cellular signaling networks [69], strengthens endogenous defenses, and attenuates the pro-oxidative/inflammatory cycle [70,71,72,73].

1.4. Challenges, Gaps and the Natural Medicine Perspective

Despite these promising attributes, there remain important challenges in adopting ASX as a standard natural-medicine adjunct [74,75,76,77,78]. One major limitation is heterogeneity in supplementation regimens, differences in dose, formulation (esterified vs. non-esterified) [79,80], duration of intervention and study populations [81,82,83,84,85]. This heterogeneity complicates comparison across trials and limits firm conclusions regarding optimal dosing [86,87,88,89,90]. Additionally, bioavailability remains a barrier: ASX’s lipophilicity means that its absorption depends on dietary fat, matrix formulation and individual variability [91,92,93,94,95]. Moreover, long-term outcome data remains scarce. From the natural medicine standpoint, it is also critical to emphasize that supplementation should not replace foundational interventions, such as proper nutrition, exercise, oral hygiene and risk factor control [96,97,98], but rather complement them [99,100,101]. Looking ahead, future research should address dose-response relationships, long-term safety and efficacy, synergistic interactions with other nutrients or therapies. Investigations into whether ASX supplementation can reduce reliance on anti-inflammatory or antioxidant pharmaceuticals [102,103,104,105], and whether it can shift the paradigm toward more natural-based adjunctive therapies, is of particular interest [106,107,108,109,110].

1.5. The Role of Astaxanthin in Preventive and Adjunctive Natural Medicine

The concept of “natural medicine” emphasizes interventions derived from natural sources, with minimal processing, and with mechanisms of action that harmonize with physiological pathways [111,112,113]. ASX exemplifies this concept: derived from algae, crustaceans or fish, it integrates into cellular membranes, modulates endogenous defense systems and exerts protective effects without the toxicity profile commonly associated with synthetic drugs [114,115]. In an era where patients increasingly seek “natural” or “integrative” options [116,117,118], ASX stands out as a scientifically grounded nutraceutical that bridges the gap between diet and therapeutic intervention [119,120]. In preventive medicine, it may serve as a daily adjunct in populations at increased oxidative/inflammatory risk (e.g., ageing individuals, smokers, those with metabolic dysregulation) [121,122,123,124,125]. Through its dual antioxidant and anti-inflammatory actions, ASX may also promote tissue resilience (e.g., vascular endothelium, gingival epithelium, ocular surface) [126,127], enhance recovery (e.g., post-exercise, post-surgery) and support long-term functional preservation (e.g., cognitive, musculoskeletal and dental) [128,129,130,131]. Moreover, since it is relatively safe and well-tolerated, its inclusion as part of an integrative care model is feasible [132,133,134,135,136]. That said, the adoption of any natural medicine requires rigorous evidence, standardized formulations, patient education and appropriate integration into multidisciplinary care pathways [137,138].

1.6. Aim of the Study

Therefore, the aim of this systematic review is to provide a comprehensive and critical appraisal of the current human clinical evidence on ASX as an antioxidant and anti-inflammatory agent in human health. Specifically, we will examine the effects of ASX supplementation on oxidative stress biomarkers, inflammatory mediators, metabolic and cardiovascular endpoints, immune function, ocular and oral health outcomes, and safety/tolerability. Additionally, we will highlight the implications of these findings for natural medicine practice in general medical and identify gaps in knowledge that must be addressed to support its wider incorporation into integrative care.

2. Materials and Methods

2.1. Protocol and Registration

The current systematic review was conducted following the PRISMA guidelines (Preferred Reporting Items for SR and Meta-Analyses) and International Prospective Register of SR Registry procedures (PROSPERO: 1232406)

2.2. Search Process

The following databases were combed from January 2020 to July 2025, to search for articles published over the last 5 years: PubMed, Web of Science (WoS), and Scopus. The search strategy was developed by combining terms relevant to the study’s purpose. In the advanced search strings used in the databases (detailed search terms are given in Appendix A), the following keywords were applied using Boolean operators to combine terms pertinent to this study’s purpose (Table 1).
Table 1. Indicators for database searches.

2.3. Inclusion and Exclusion Criteria

The reviewers worked in groups to assess all relevant studies that evaluated studies considering eligible if they met the following criteria:
  • Open-access and written in English;
  • Published within the last five years;
  • Full-text articles available for review;
  • Designed as randomized controlled trials (RCTs);
  • Conducted on human participants;
  • Included adults aged 19 years and older;
  • Investigated patients with pathological or clinical conditions relevant to the research topic.
Studies that fulfilled at least one of the following criteria were excluded:
Studies were excluded if they met one or more of the following conditions:
  • Preprints or unpublished manuscripts;
  • Systematic reviews, meta-analyses, case reports, or case series;
  • Letters to the editor, conference abstracts, or commentaries;
  • Studies involving animal models;
  • In vitro or laboratory-based experiments.

2.4. PICO Question

The PICO format is a framework used in qualitative research to structure clinical research questions. In this study, the PICO addressed the following question: “What are the mechanistic and biological effects of orally administered ASX in adults, compared with placebo or no treatment, on markers of oxidative stress, inflammation, and metabolic function? “
Population (P): Adults (≥19 years), both males and females, either healthy or diagnosed with chronic metabolic or inflammatory conditions (e.g., type 2 diabetes, polycystic ovary syndrome, obesity, cardiovascular diseases, arthritis, or ocular disorders).
Intervention (I): Oral administration of ASX, either natural or synthetic, is delivered as capsules, oils, or other lipid-based formulations.
Comparison (C): Placebo, no treatment, or standard care (e.g., dietary interventions, physical activity, or non-carotenoid supplementation).
Outcome (O): Changes in plasma or tissue biomarkers and improvements in physiological function related to oxidative stress, inflammation, and metabolism.

2.5. Data Processing

Five independent reviewers (L.C., I.T., L.F., M.L. and F.I.) assessed the methodological quality and risk of bias of the included studies using the Cochrane Risk of Bias 2 (RoB 2) tool. The tool evaluates five key domains such as selection, measurement validity, confounding, and data analysis. Discrepancies in scoring were resolved through discussion and consensus, with support from additional reviewers (G.M., A.D.I., A.P., G.Mn., A.M.I., and G.D.) when needed. The reviewers screened all retrieved records based on predefined inclusion and exclusion criteria. After screening, a total of 805 articles were imported into Zotero (version 6.0.36) for organization and full-text analysis.

3. Results

3.1. Selected Studies and Their Characteristics

The systematic search process, conducted according to PRISMA guidelines (Figure 2), identified a total of 805 records from three major databases: PubMed (n = 613), Scopus (n = 74), and Web of Science (n = 59). After the removal of 200 duplicates, 605 articles were screened by title and abstract. Following the application of the predefined inclusion and exclusion criteria, 247 full-text articles were assessed for eligibility. Of these, 230 were excluded for the following reasons: systematic reviews or meta-analyses (n = 75), in vitro studies (n = 136), animal studies (n = 1), participants under 19 years of age (n = 3), case reports (n = 12), and off-topic articles (n = 5). Ultimately, 15 randomized controlled trials (RCTs) met all inclusion criteria and were included in the final synthesis (Table 2).
Figure 2. PRISMA flow diagram illustrates the study selection process, including the number of records identified, screened, assessed for eligibility, and included in the final systematic review.
Table 2. Summary of the studies selected and included in the systematic review, indicating authors, publication year, study design, sample characteristics, interventions, and main outcomes.

3.2. Quality and Risk of Bias Assessment for the Included Articles

The methodological quality and risk of bias of the fifteen included randomized controlled trials were assessed using the Cochrane Risk of Bias 2 (RoB 2) tool (Table 3). This tool is specifically designed to evaluate potential bias in randomized clinical trials. Each study was independently reviewed by four reviewers (L.C., I.T., L.F., and M.L.), and any discrepancies in the assessments were resolved through discussion and consensus, with additional researchers (Giuseppina Malcangi., F.I., Grazia Marinelli., A.P; A.D.I., and A.M.I.) involved when necessary to ensure consistency and accuracy.
Table 3. A tabular summary of the risk of bias assessment for 15 studies, evaluated across the five domains of RoB 2 (Risk of Bias 2).
The RoB 2 tool evaluates five key domains: (1) bias arising from the randomization process, (2) bias due to deviations from intended interventions, (3) bias due to missing outcome data, (4) bias in the measurement of the outcome, and (5) bias in the selection of the reported result. Each domain was judged as “low risk,” “some concerns,” or “high risk,” leading to an overall judgment of the study’s risk of bias.
The results of the assessment showed that most of the included studies presented a low risk of bias across all domains of the Cochrane RoB 2 tool. This finding can be attributed to the adoption of rigorous experimental designs, predominantly randomized, double- or triple-blind trials, with pre-registered study protocols, clearly described randomization procedures, and minimal loss of participants during follow-up. Only one study [149] showed some concerns in the domains related to the randomization process and deviations from intended interventions, as it lacked a control group and employed a quasi-experimental design (Figure 2).
Overall, the global risk of bias (Overall) was judged to be low for the vast majority of the included trials, indicating a high methodological quality and reliability of the available evidence. A detailed summary of the item-by-item assessment for each trial is presented in Table 3, providing a comprehensive overview of the methodological rigor and potential sources of bias across the included studies. This evaluation ensures a reliable interpretation of the evidence regarding the effects of ASX supplementation in human clinical trials (Table 3).

4. Discussion

4.1. Obesity and Lipid Metabolism: A Complex Picture of Synergies and Specific Contexts

The impact of ASX supplementation on obesity and lipid metabolism is emerging as an extremely promising area of research, although the results show nuances that depend on the clinical context, the study population, and the combination with other interventions. The most robust evidence comes from studies combining ASX with physical exercise in obese subjects. Research by Saeidi et al. (2023) demonstrated that the combination of high-intensity functional training (HIFT) with 12 weeks of supplementation produced significantly greater benefits compared to the individual interventions [152]. Specifically, a marked reduction in anthropometric indices (body weight, BMI, fat percentage), an improvement in the complete lipid profile (increased HDL-C, reduced LDL-C, total cholesterol, and triglycerides), and metabolic markers (glucose, insulin, HOMA-IR) was observed. In parallel, studies by Supriya et al. (2023) and Moqaddam et al. (2024), both conducted on obese men undergoing 12 weeks of CrossFit training, further investigated the effect on adipo-myokines—the signaling molecules that orchestrate communication between adipose and muscle tissue [139,153]. Supriya et al. (2023) reported that the combination of CrossFit and ASX increased the levels of beneficial adipokines such as adiponectin and omentin-1, while reducing those associated with metabolic dysfunctions, including leptin, visfatin, vaspin, and SEMA3C [153]. This confirms the hypothesis of a synergistic action, where physical exercise stimulates the release of myokines and induces a negative energy balance, while ASX, through its antioxidant and anti-inflammatory properties (such as activating the PPARγ pathway and inhibiting NF-κB), improves insulin sensitivity and lipid metabolism [146]. Delving deeper, Moqaddam et al. (2024) documented how the combined intervention beneficially and divergently modulates the adipo-myokine profile: an increase in anabolic and protective molecules like decorin (DCN) and follistatin (FST) was recorded, along with a concurrent decrease in catabolic and pro-fibrotic factors belonging to the TGF-β superfamily, namely activin A, myostatin (MST), and TGF-β1 [139]. These findings suggest that ASX not only supports weight loss and lipid improvement but also acts at the molecular level to rebalance the hormonal environment, promoting muscle health and counteracting the chronic inflammatory processes typical of obesity.
This positive effect on the lipid profile is corroborated by studies in other populations with metabolic disorders. In the study by Ciaraldi et al. (2023) on individuals with prediabetes and dyslipidemia, ASX induced a statistically significant reduction in total cholesterol and LDL cholesterol, accompanied by an increase in HDL cholesterol [143]. This study reinforces the idea that ASX is particularly effective in subjects with an already compromised lipid profile. Similarly, the study by Jabarpour et al. (2024) on women with polycystic ovary syndrome (PCOS), a condition often associated with dyslipidemia, found a significant reduction in LDL cholesterol and an increase in HDL after eight weeks of supplementation with 12 mg/day [145]. However, the picture is not universally homogeneous. The study by Heidari et al. (2023) on patients with coronary artery disease (CAD) found no statistically significant effect on the lipid profile when comparing the ASX group to the placebo group [148]. The authors, however, provide a crucial explanation: most participants were already on statin therapy, highly potent drugs that had likely already optimized their lipid parameters. It is interesting to note that, when analyzing only the ASX-treated group, a significant reduction in total and LDL cholesterol was observed, suggesting a potential additive effect or a benefit in the absence of other therapies. This hypothesis is further supported by the results of Gonzalez et al. (2024) who found no significant differences in the lipid profiles of healthy, trained firefighters after four weeks of supplementation [141]. In this case, it is likely that the participants already had optimal lipid values at rest, leaving little room for improvement. Finally, the study by Moqaddam et al. (2024) although a research protocol for patients with heart failure, cites previous literature confirming ASX’s ability to increase HDL and decrease triglycerides, positioning it as a supplement of great interest for future cardiovascular applications [139]. In summary, ASX demonstrates robust efficacy in improving the lipid profile and metabolic parameters related to obesity, especially in populations with pre-existing metabolic dysfunctions and when combined with physical exercise. The effect appears less evident in healthy individuals or in patients already undergoing lipid-lowering drug therapies, indicating that its primary role may be as an adjuvant and preventive agent.

4.2. Diabetes and Glycemic Control: Molecular Mechanisms and Clinical Perspectives

The application of ASX in the context of diabetes and prediabetes reveals significant therapeutic potential, acting through complex cellular mechanisms that go beyond simple glycemic control (Figure 3). The most emblematic study in this field is that of Sharifi-Rigi et al. (2023),which examined the effects of a 10 mg/day supplementation for 12 weeks in patients with type 2 diabetes (T2D) [140]. The results were clinically relevant, showing a significant decrease in both fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c), two fundamental parameters for diabetes management. The most innovative aspect of this study lies in the analysis of the underlying molecular mechanisms. The researchers observed that ASX positively modulates the process of autophagy, a cellular “cleanup” mechanism that is often dysregulated in diabetes. Specifically, supplementation reduced the expression of the mTOR gene, a known inhibitor of autophagy, and simultaneously increased the expression of genes and proteins essential for activating the autophagic process, such as beclin-1, LC3B, Atg-5, and Atg-7. The authors hypothesize that this effect is mediated by ASX’s ability to activate AMPK protein kinase, a cellular energy sensor that inhibits mTOR and promotes autophagy. In parallel, the study confirmed the carotenoid’s potent anti-inflammatory properties, documenting a significant reduction in serum levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. This effect is attributed to ASX’s ability to suppress the NF-κB inflammatory pathway, partly by activating the Nrf2 antioxidant pathway. In effect, ASX appears to break the vicious cycle in which chronic inflammation inhibits autophagy, leading to an overall improvement in the metabolic and inflammatory state of the diabetic patient.
Figure 3. The figure provides a schematic overview of the main mechanisms and clinical effects of astaxanthin (ASX). At the center, ASX is depicted as the key bioactive compound with antioxidant and anti-inflammatory actions. On the left, its antioxidant effects are illustrated by reducing reactive oxygen species (ROS) and enhancing endogenous antioxidant defenses, such as superoxide dismutase (SOD) and total antioxidant capacity (TAC). On the right, the anti-inflammatory effects are shown by downregulating inflammatory cytokines (e.g., CRP, IL-6, TNF-α) and modulating redox- and inflammation-related signaling pathways. These molecular mechanisms are linked to beneficial clinical outcomes in metabolic, reproductive, cardiovascular, and immune health, summarized in the lower panel.
However, when examining the stage preceding overt diabetes, namely prediabetes, the results appear more nuanced, as highlighted by the study of Ciaraldi et al. (2023) on individuals with prediabetes and dyslipidemia [143]. In this research, the primary endpoint—improvement in whole-body insulin sensitivity measured with the gold-standard euglycemic-hyperinsulinemic clamp technique—did not reach statistical significance. This result, while disappointing at first glance, does not invalidate ASX’s potential but suggests that its effects on insulin action may be more subtle or tissue-specific. Indeed, the same study noted positive trends: a tendency towards a reduction in the HOMA-IR index (a marker of insulin resistance) and an improvement in insulin sensitivity specifically at the hepatic level were observed. The liver could therefore be a primary target organ for ASX’s action, an aspect that warrants further investigation. Other studies also indirectly support a beneficial effect on glucose metabolism. In the study by Jabarpour et al. (2024) on women with PCOS, a condition characterized by strong insulin resistance, eight weeks of supplementation led to a significant reduction in fasting glucose and insulin, as well as the HOMA-IR index [145,146]. Similarly, the research by Saeidi et al. (2023) on obese men showed how the combination of physical exercise and ASX improved glucose, insulin, and HOMA-IR parameters more markedly than exercise alone [152]. Comparing these studies, it can be hypothesized that ASX’s effectiveness on glycemic control and insulin sensitivity is dose-dependent, duration-dependent, and, above all, context-dependent. In patients with diagnosed type 2 diabetes, where inflammation and autophagic dysfunction are pronounced, ASX seems to exert a robust and measurable therapeutic effect [140]. In earlier stages, such as prediabetes, the benefits may be less evident at a systemic level but still present in specific organs like the liver. Finally, in conditions of secondary insulin resistance, as in obesity or PCOS, ASX is confirmed as a valid adjuvant, especially when integrated into a multifactorial approach that includes physical activity [143].

4.3. Gynecological Use: Support for Fertility Through the Modulation of Cellular Stress

The field of gynecology and reproductive medicine represents one of the most innovative areas for the application of ASX, where its antioxidant and anti-inflammatory properties translate into tangible clinical benefits for complex conditions like polycystic ovary syndrome (PCOS) and endometriosis. Both pathologies are characterized by a pro-inflammatory environment and high oxidative stress, factors that compromise oocyte quality and fertility. Studies conducted by the group of Jabarpour et al. (2023, 2024) offer a comprehensive view of ASX’s mechanisms of action in women with PCOS [144,145]. In their 2024 study, they demonstrated that supplementation with 12 mg/day for eight weeks in infertile women with PCOS significantly improves systemic metabolic parameters, with a reduction in fasting glucose and insulin, the HOMA-IR index, and LDL cholesterol, along with an increase in HDL. These metabolic effects are in themselves important for ovarian function, but the same group’s 2023 research unveiled an even deeper mechanism of action at the cellular level. This study revealed that a 60-day treatment with ASX modulates endoplasmic reticulum stress (ER stress) in granulosa cells, a key pathogenetic factor in PCOS. Specifically, ASX reduced the expression of major ER stress markers, such as GRP78 and CHOP, and the mediator XBP1. Analysis of the follicular fluid confirmed its antioxidant action, showing a significant increase in total antioxidant capacity (TAC). The clinical relevance of this molecular modulation was extraordinary: while not increasing the total number of retrieved oocytes, the ASX-treated group showed a significantly higher percentage of mature (MII) oocytes, high-quality oocytes, and consequently, high-quality embryos. This suggests that ASX does not act on quantity but drastically improves the quality of the follicular microenvironment, breaking the vicious cycle between oxidative stress and ER stress and creating more favorable conditions for the development of healthy gametes.
This potential also extends to another debilitating gynecological condition, endometriosis. The study by Rostami and colleagues (2023), a randomized, triple-blind clinical trial, evaluated the effect of ASX supplementation in women with endometriosis undergoing assisted reproductive technology (ART) procedures [150]. Consistent with the results observed in PCOS, the supplementation proved effective in mitigating both oxidative stress and markers of systemic inflammation, which are pillars of endometriosis pathogenesis. Most importantly, this biochemical improvement translated into a direct and positive clinical impact on reproductive outcomes. The ASX-treated group showed a significant improvement in ART-related outcomes compared to the placebo group, suggesting that a less inflamed and oxidized environment favors higher fertilization rates, embryo quality, and pregnancy rates. Comparing the studies on PCOS and endometriosis, a common and fundamental mechanism of action emerges: ASX acts as a powerful “normalizing” agent for the pelvic and follicular microenvironment. In both conditions, characterized by excessive inflammation and free radical production, ASX neutralizes these deleterious factors. In PCOS, this translates into better metabolic function and reduced cellular stress, allowing for the maturation of higher-quality oocytes. In endometriosis, the reduction of inflammation and oxidative stress improves the overall environment for implantation and embryonic development. Both scenarios highlight how ASX is not merely a generic antioxidant but a targeted modulator that intervenes in the key pathogenetic processes of female subfertility, representing a promising and safe adjuvant strategy to improve the success rates of ART procedures in these challenging patient populations.

4.4. Other Studies: From Physical Exertion Response to the Management of Systemic and Local Inflammation

Beyond its applications in the metabolic and gynecological fields, ASX demonstrates remarkable versatility in a wide range of clinical and physiological contexts, primarily due to its exceptional anti-inflammatory and antioxidant properties. An area of great interest is its ability to modulate the body’s response to intense physical exercise. The study by Gonzalez et al. (2024) on professional firefighters showed that while supplementation with 12 mg/day for four weeks did not improve overall physical performance, it significantly attenuated the inflammatory response and acute physiological stress induced by exertion [141]. Specifically, lower levels of pro-inflammatory cytokines (IL-1β, IL-2, TNF-α) and the stress hormone cortisol were recorded after exercise. This suggests that ASX helps the body better manage the biochemical stress of intense activity. This connects perfectly with the study by Nieman e al. (2023), which investigated the effect of ASX on the “open window” of immunosuppression that follows strenuous exercise [151]. The results indicated that supplementation helps maintain more stable levels of certain plasma proteins crucial for immune function, which normally decrease due to oxidative stress. Read together, these two studies paint a consistent picture: ASX may not be a direct ergogenic aid (i.e., it doesn’t increase strength or endurance), but it acts as a protective agent that supports recovery by reducing inflammation and counteracting post-exercise immune suppression—a valuable benefit for athletes and workers subjected to extreme physical exertion.
This potent anti-inflammatory action has also proven effective in acute pathological contexts. The pioneering study by Youssef et al. (2025) evaluated ASX as an add-on therapy in community-acquired pneumonia (CAP) [147]. The results were remarkable: treated patients showed a substantial decrease in major systemic inflammation markers, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). This biochemical improvement translated into a tangible clinical benefit, with a significant improvement in SOFA and APACHE II severity scores. This study is crucial because it transfers the anti-inflammatory effect, already observed in contexts of physiological stress (Gonzalez et al., 2024) and chronic diseases to an acute infectious disease, suggesting that ASX’s ability to inhibit pathways like NF-κB can be a valuable support to standard therapies for controlling the “cytokine storm” that characterizes many severe infections [141]. ASX also demonstrates the ability to act at a local level. The study by Tian et al. (2021) on dry eye syndrome revealed that oral intake of 12 mg/day for one month significantly improved subjective symptoms (OSDI index), tear film stability (NIBUT and FBUT), and corneal epithelial integrity [149]. Interestingly, it did not increase the quantity of tears produced but improved their quality. This indicates a targeted action to reduce oxidative stress and inflammation on the ocular surface, promoting the proper functioning of the Meibomian glands and tissue repair. Finally, research continues to explore new frontiers, as highlighted by the study protocol of Mohammadi et al. (2024), which aims to evaluate the impact of ASX on patients with heart failure for the first time [142]. This study, despite its inherent limitations such as the presence of concomitant therapies, underscores the growing scientific interest in this carotenoid as a potential cardioprotective agent. In conclusion, this collection of “other studies” confirms that ASX is a pleiotropic compound whose efficacy extends from supporting athletic recovery and managing acute systemic inflammation like pneumonia, to treating localized disorders such as dry eye syndrome, paving the way for future and promising clinical applications in severe chronic diseases.

5. Conclusions

ASX emerges as a natural compound of considerable clinical interest due to its ability to synergistically modulate key processes related to oxidative stress, inflammation, and cellular metabolism. Available evidence shows that this carotenoid does not act merely as a simple free radical scavenger but exerts deeper regulatory effects on major molecular pathways, activating protective signaling such as Nrf2 and AMPK while inhibiting pro-inflammatory cascades like NF-κB and mTOR. These mechanisms translate into tangible systemic benefits, including improvements in glucose and lipid metabolism, insulin sensitivity, endothelial function, and overall antioxidant capacity of tissues.
ASX shows effectiveness in conditions characterized by heightened inflammation and metabolic dysfunction—such as type 2 diabetes, metabolic syndrome, obesity, PCOS, and endometriosis—where it helps restore a more balanced cellular microenvironment, enhancing oocyte quality, reproductive outcomes, and various clinical parameters. In contexts of intense physical stress, such as high-intensity athletic activity or physically demanding professions, ASX also proves valuable by reducing post-exercise inflammatory responses and supporting immune function. Moreover, its protective actions extend to acute conditions like pneumonia and to specific anatomical sites such as the ocular surface, where it helps promote tissue repair and maintain tear film stability.
Overall, ASX stands out for its favorable safety profile, biological compatibility, and ability to integrate with conventional therapeutic approaches, making it a valuable support in preserving systemic and reproductive health. Through its multi-target activity and broad applicability, it represents a promising option within integrative medicine, with significant potential to improve clinical outcomes, promote overall well-being, and strengthen physiological resilience across a wide range of conditions.

6. Future Limitations

Despite the encouraging findings, several limitations must be addressed to strengthen the clinical application of ASX. The considerable heterogeneity among existing studies—particularly in dosage, duration of supplementation, formulation type (esterified vs. non-esterified), and characteristics of the study populations—makes it difficult to establish standardized therapeutic protocols. Additionally, current evidence does not sufficiently clarify the compound’s real bioavailability or the individual factors that influence its absorption and metabolic utilization. Long-term data are also lacking, especially regarding safety, cumulative effects, and the impact on sustained clinical outcomes. Other fields, such as dentistry and advanced cardiovascular disease, remain underexplored, limiting the understanding of its broader therapeutic potential. Furthermore, interactions between ASX and commonly used pharmacological treatments are still poorly investigated. For these reasons, there is a clear need for larger, rigorously controlled clinical trials aimed at defining optimal dosages, mechanisms of action, and real-world benefits across more diverse and representative patient populations.

Author Contributions

Conceptualization, M.L., A.M.I., L.C., I.T., F.I., A.D.I., G.M. (Giuseppina Malcangi), and G.M. (Grazia Marinelli); methodology, G.D., A.M.I., M.L., F.I., L.C., and I.T.; software, L.F., F.I., G.D., G.M. (Giuseppina Malcangi), L.C., M.L., A.M.I., and G.D.; validation, G.M. (Grazia Marinelli), M.L., G.D., A.D.I., A.M.I., F.I., and L.C.; formal analysis, A.P., L.C., I.T., A.M.I., G.M. (Giuseppina Malcangi), L.F., A.D.I., and G.D.; resources, M.L., G.D., A.M.I., F.I., and L.C.; data curation, L.C., G.D., M.L., A.M.I., L.F., I.T., F.I., and G.D.; writing—original draft preparation, M.L., A.P., G.M. (Grazia Marinelli), A.M.I., G.D., L.C., and F.I.; writing—review and editing, I.T., L.F., L.C., A.M.I., F.I., A.D.I., and G.D.; visualization, M.L., G.D., A.D.I., A.M.I., F.I., and L.C.; supervision, G.M. (Giuseppina Malcangi), M.L., L.C., L.F., A.M.I., F.I., and G.D.; project administration, G.D., M.L., A.D.I., A.M.I., F.I., G.M. (Grazia Marinelli), and L.C. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Data Availability Statement

The data are contained within the article.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
AMPKAMP-Activated Protein Kinase
APACHEAcute Physiology and Chronic Health Evaluation
ARTAssisted Reproductive Technology
ASXAstaxanthin
BMIBody Mass Index
CADComputer-Aided Diagnosis
CHOPC/EBP Homologous Protein
CRPC-Reactive Protein
DNADeoxyribonucleic Acid
EREndoplasmic Reticulum
HDL-CHigh-Density Lipoprotein Cholesterol
IL-2Interleukin-2
IL-6Interleukin-6
LDL-CLow-Density Lipoprotein Cholesterol
MDAMalondialdehyde
NF-κBNuclear Factor kappa-light-chain-enhancer of activated B cells
Nrf2Nuclear Factor Erythroid 2-Related Factor 2
PCOSPolycystic Ovary Syndrome
ROSReactive Oxygen Species
SODSuperoxide Dismutase
SOFASequential Organ Failure Assessment
TACTotal Antioxidant Capacity
TGF-βTransforming Growth Factor-beta
TNF-αTumor Necrosis Factor-alpha
XBP1X-Box Binding Protein-1

Appendix A

Appendix A.1. PubMed Query String

(astaxanthin OR astaxantin OR “Haematococcus pluvialis”) OR (“oral administration” OR “oral supplement*” OR “dietary supplementation”) AND (“oxidative stress” OR “reactive oxygen species” OR inflammation OR inflammatory OR “anti-inflammatory” OR metabolism OR metabolic OR “metabolic syndrome” OR glucose OR lipid);

Appendix A.2. Scopus Query String

TITLE-ABS-KEY (astaxanthin OR astaxantin OR “Haematococcus pluvialis”) AND TITLE-ABS-KEY (“oral administration” OR “oral supplement*” OR “dietary supplementation”) AND TITLE-ABS-KEY (“oxidative stress” OR “reactive oxygen species” OR inflammation OR inflammatory OR “anti-inflammatory” OR metabolism OR metabolic OR “metabolic syndrome” OR glucose OR lipid);

Appendix A.3. Web of Science Query String

TS = (astaxanthin OR astaxantin OR “Haematococcus pluvialis”) AND TS = (“oral administration” OR “oral supplement*” OR “dietary supplementation”) AND TS = (“oxidative stress” OR “reactive oxygen species” OR inflammation OR inflammatory OR “anti-inflammatory” OR metabolism OR metabolic OR “metabolic syndrome” OR glucose OR lipid).

References

  1. Abebe, W. An Overview of Herbal Supplement Utilization with Particular Emphasis on Possible Interactions with Dental Drugs and Oral Manifestations. J. Dent. Hyg. 2003, 77, 37–46. [Google Scholar]
  2. Lotto, M.; Zakir Hussain, I.; Kaur, J.; Butt, Z.A.; Cruvinel, T.; Morita, P.P. Analysis of Fluoride-Free Content on Twitter: Topic Modeling Study. J. Med. Internet Res. 2023, 25, e44586. [Google Scholar] [CrossRef] [PubMed]
  3. Rafey, A.; Amin, A.; Kamran, M.; Haroon, U.; Farooq, K.; Foubert, K.; Pieters, L. Analysis of Plant Origin Antibiotics against Oral Bacterial Infections Using In Vitro and In Silico Techniques and Characterization of Active Constituents. Antibiotics 2021, 10, 1504. [Google Scholar] [CrossRef] [PubMed]
  4. Inchingolo, A.D.; Dipalma, G.; Inchingolo, A.M.; Malcangi, G.; Santacroce, L.; D’Oria, M.T.; Isacco, C.G.; Bordea, I.R.; Candrea, S.; Scarano, A.; et al. The 15-Months Clinical Experience of SARS-CoV-2: A Literature Review of Therapies and Adjuvants. Antioxidants 2021, 10, 881. [Google Scholar] [CrossRef] [PubMed]
  5. Inchingolo, F.; Tatullo, M.; Abenavoli, F.M.; Marrelli, M.; Inchingolo, A.D.; Corelli, R.; Inchingolo, A.M.; Dipalma, G. Upper Eyelid Reconstruction: A Short Report of an Eyelid Defect Following a Thermal Burn. Head. Face Med. 2009, 5, 26. [Google Scholar] [CrossRef]
  6. Ihn, H.J.; Kim, T.H.; Kim, K.; Kim, G.-Y.; Jeon, Y.-J.; Choi, Y.H.; Bae, J.-S.; Kim, J.-E.; Park, E.K. 2-O-Digalloyl-1,3,4,6-Tetra-O-Galloyl-β-D-Glucose Isolated from Galla Rhois Suppresses Osteoclast Differentiation and Function by Inhibiting NF-κB Signaling. BMB Rep. 2019, 52, 409–414. [Google Scholar] [CrossRef]
  7. Chin, Y.-T.; Hsieh, M.-T.; Lin, C.-Y.; Kuo, P.-J.; Yang, Y.-C.S.H.; Shih, Y.-J.; Lai, H.-Y.; Cheng, G.-Y.; Tang, H.-Y.; Lee, C.-C.; et al. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-Glucoside Isolated from Polygoni Multiflori Ameliorates the Development of Periodontitis. Mediators Inflamm. 2016, 2016, 6953459. [Google Scholar] [CrossRef]
  8. Wang, T.-H.; Chou, L.-F.; Chen, C.-C.; Yeh, C.-T.; Liu, Y.-T.; Chu, Y.-D.; Lin, H.-W.; Chen, K.-Y.; Yu, C.-C.; Chen, C.-Y. 4′-Hydroxywogonin Inhibits Oral Squamous Cell Carcinoma Progression by Targeting Gas6/Axl Signaling Axis. J. Dent. Sci. 2025, 20, 1639–1647. [Google Scholar] [CrossRef]
  9. Uctasli, M.B.; Garoushi, S.; Uctasli, M.; Vallittu, P.K.; Lassila, L. A Comparative Assessment of Color Stability among Various Commercial Resin Composites. BMC Oral Health 2023, 23, 789. [Google Scholar] [CrossRef]
  10. Gopikrishnan, S.; Melath, A.; Ajith, V.V.; Mathews, N.B. A Comparative Study of Bio Degradation of Various Orthodontic Arch Wires: An In Vitro Study. J. Int. Oral Health 2015, 7, 12–17. [Google Scholar]
  11. Prasad, M.; Jayaraman, S.; Eladl, M.A.; El-Sherbiny, M.; Abdelrahman, M.A.E.; Veeraraghavan, V.P.; Vengadassalapathy, S.; Umapathy, V.R.; Jaffer Hussain, S.F.; Krishnamoorthy, K.; et al. A Comprehensive Review on Therapeutic Perspectives of Phytosterols in Insulin Resistance: A Mechanistic Approach. Molecules 2022, 27, 1595. [Google Scholar] [CrossRef] [PubMed]
  12. Ullah, A.; Ul Haq, M.; Iqbal, M.; Irfan, M.; Khan, S.; Muhammad, R.; Ullah, A.; Khurram, M.; Alharbi, M.; Alasmari, A.F.; et al. A Computational Quest for Identifying Potential Vaccine Candidates against Moraxella Lacunata: A Multi-Pronged Approach. J. Biomol. Struct. Dyn. 2024, 42, 2976–2989. [Google Scholar] [CrossRef]
  13. Yano, J.; Lilly, E.A.; Noverr, M.C.; Fidel, P.L. A Contemporary Warming/Restraining Device for Efficient Tail Vein Injections in a Murine Fungal Sepsis Model. J. Vis. Exp. (JoVE) 2020, 165, e61961. [Google Scholar]
  14. Abidi, A.H.; Alghamdi, S.S.; Derefinko, K. A Critical Review of Cannabis in Medicine and Dentistry: A Look Back and the Path Forward. Clin. Exp. Dent. Res. 2022, 8, 613–631. [Google Scholar] [CrossRef] [PubMed]
  15. Atsumi, T.; Tonosaki, K.; Fujisawa, S. Salivary Free Radical-Scavenging Activity Is Affected by Physical and Mental Activities. Oral. Dis. 2008, 14, 490–496. [Google Scholar] [CrossRef] [PubMed]
  16. Abdul-Wahab, H.Y.; Salah, R.; Abdulbaqi, H.R. Salivary Levels of Catalase, Total Antioxidant Capacity and Interleukin-1β and Oral Health-Related Quality of Life after Matcha and Green Tea Consumption for Patients with Gingivitis: A Randomized Clinical Trial. Int. J. Dent. Hyg. 2025, 23, 114–123. [Google Scholar] [CrossRef]
  17. Tenovuo, J.; Lumikari, M.; Soukka, T. Salivary Lysozyme, Lactoferrin and Peroxidases: Antibacterial Effects on Cariogenic Bacteria and Clinical Applications in Preventive Dentistry. Proc. Finn. Dent. Soc. 1991, 87, 197–208. [Google Scholar]
  18. Levrini, L.; Nosotti, M.G.; Saran, S.; Deppieri, A.; Carganico, A. Salivary pH after Taking Coffee with and without Sugar. Minerva Dent. Oral Sci. 2025, 74, 172–176. [Google Scholar] [CrossRef]
  19. Guo, Y.; Li, Y.; Xue, L.; Severino, R.P.; Gao, S.; Niu, J.; Qin, L.-P.; Zhang, D.; Brömme, D. Salvia miltiorrhiza: An Ancient Chinese Herbal Medicine as a Source for Anti-Osteoporotic Drugs. J. Ethnopharmacol. 2014, 155, 1401–1416. [Google Scholar] [CrossRef]
  20. Apolinario, R.S.; Mdgam, C.; Gonçalves, H.R.M.; Martins, I.C.F.; De Paula, R.M.; Granato, A.P.A.; Polonini, H.C.; Brandão, M.A.F.; Ferreira, A.D.O.; Raposo, N.R.B. Compounded Orodispersible Films with Natural Ingredients for Halitosis: A Clinical Experience. Int. J. Pharm. Compd. 2018, 22, 512–515. [Google Scholar]
  21. Karygianni, L.; Cecere, M.; Argyropoulou, A.; Hellwig, E.; Skaltsounis, A.L.; Wittmer, A.; Tchorz, J.P.; Al-Ahmad, A. Compounds from Olea europaea and Pistacia lentiscus Inhibit Oral Microbial Growth. BMC Complement. Altern. Med. 2019, 19, 51. [Google Scholar] [CrossRef] [PubMed]
  22. Antoniadou, M.; Rozos, G.; Vaou, N.; Zaralis, K.; Ersanli, C.; Alexopoulos, A.; Dadamogia, A.; Varzakas, T.; Tzora, A.; Voidarou, C.C. Comprehensive Bio-Screening of Phytochemistry and Biological Capacity of Oregano (Origanum vulgare) and Salvia triloba Extracts against Oral Cariogenic and Food-Origin Pathogenic Bacteria. Biomolecules 2024, 14, 619. [Google Scholar] [CrossRef] [PubMed]
  23. Zulhendri, F.; Felitti, R.; Fearnley, J.; Ravalia, M. The Use of Propolis in Dentistry, Oral Health, and Medicine: A Review. J. Oral Biosci. 2021, 63, 23–34. [Google Scholar] [CrossRef]
  24. Blaudez, F.; Ivanovski, S.; Fournier, B.; Vaquette, C. The Utilisation of Resolvins in Medicine and Tissue Engineering. Acta Biomater. 2022, 140, 116–135. [Google Scholar] [CrossRef] [PubMed]
  25. Zou, Y.; Huang, D.; Jiang, Q.; Guo, Y.; Chen, C. The Vaccine Efficacy Against the SARS-CoV-2 Omicron: A Systemic Review and Meta-Analysis. Front. Public Health 2022, 10, 940956. [Google Scholar] [CrossRef]
  26. Rosen, E.; Venezia, N.B.; Azizi, H.; Kamburoglu, K.; Meirowitz, A.; Ziv-Baran, T.; Tsesis, I. A Comparison of Cone-Beam Computed Tomography with Periapical Radiography in the Detection of Separated Instruments Retained in the Apical Third of Root Canal-Filled Teeth. J. Endod. 2016, 42, 1035–1039. [Google Scholar] [CrossRef]
  27. Snarska, J.; Jakimiuk, K.; Strawa, J.W.; Tomczyk, T.M.; Tomczykowa, M.; Piwowarski, J.P.; Tomczyk, M. A Comprehensive Review of Pedunculagin: Sources, Chemistry, Biological and Pharmacological Insights. Int. J. Mol. Sci. 2024, 25, 11511. [Google Scholar] [CrossRef]
  28. De-Deus, G.; Belladonna, F.G.; Carestiato, M.H.; da Silva Oliveira, D.; Carvalhal, J.C.A.; Simões-Carvalho, M.; Silva, E.J.N.L.; Souza, E.M.; Versiani, M.A. Extrusion Degree of a New Low-Viscosity, Injectable, Light-Cured Endodontic Filling Material: An in-Situ Study in a Cadaveric Close-to-Mouth Experimental Model. Clin. Oral Investig. 2025, 29, 254. [Google Scholar] [CrossRef]
  29. Inchingolo, F.; Inchingolo, A.M.; Ferrante, L.; de Ruvo, E.; Di Noia, A.; Palermo, A.; Inchingolo, A.D.; Dipalma, G. Pharmacological Sedation in Paediatric Dentistry. Eur. J. Paediatr. Dent. 2024, 25, 230–237. [Google Scholar] [CrossRef]
  30. Iwanaga, J.; Fukuoka, H.; Fukuoka, N.; Yutori, H.; Ibaragi, S.; Tubbs, R.S. A Narrative Review and Clinical Anatomy of Herpes Zoster Infection Following COVID-19 Vaccination. Clin. Anat. 2022, 35, 45–51. [Google Scholar] [CrossRef]
  31. Flynn, P.M.; Stull, C.; Jain, V.M.; Evans, M.D. A National Cross-Sectional Study of Dentists’ Vaccine Hesitancy and Intention to Provide HPV Vaccines Following Emergency COVID-19 Vaccination Authorization. Vaccine 2025, 53, 127035. [Google Scholar] [CrossRef] [PubMed]
  32. Haldar, R.; Halder, P.; Koley, H.; Miyoshi, S.-I.; Das, S. A Newly Developed Oral Infection Mouse Model of Shigellosis for Immunogenicity and Protective Efficacy Studies of a Candidate Vaccine. Infect. Immun. 2025, 93, e0034624. [Google Scholar] [CrossRef] [PubMed]
  33. Accardo, C.; Himel, V.T.; Lallier, T.E. A Novel GuttaFlow Sealer Supports Cell Survival and Attachment. J. Endod. 2014, 40, 231–234. [Google Scholar] [CrossRef] [PubMed]
  34. De Rossi, S.S.; Thoppay, J.; Dickinson, D.P.; Looney, S.; Stuart, M.; Ogbureke, K.U.E.; Hsu, S. A Phase II Clinical Trial of a Natural Formulation Containing Tea Catechins for Xerostomia. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2014, 118, 447–454.e3. [Google Scholar] [CrossRef]
  35. Awadalla, H.I.; Ragab, M.H.; Bassuoni, M.W.; Fayed, M.T.; Abbas, M.O. A Pilot Study of the Role of Green Tea Use on Oral Health. Int. J. Dent. Hyg. 2011, 9, 110–116. [Google Scholar] [CrossRef]
  36. Schmierer, K.; Wiendl, H.; Oreja-Guevara, C.; Centonze, D.; Chudecka, A.; Roy, S.; Boschert, U. A Plain Language Summary of the Impact of Vaccines against Flu and Chickenpox in People with Multiple Sclerosis Treated with Cladribine Tablets. Neurodegener. Dis. Manag. 2023, 13, 15–21. [Google Scholar] [CrossRef]
  37. Inchingolo, A.M.; Malcangi, G.; Inchingolo, A.D.; Mancini, A.; Palmieri, G.; Di Pede, C.; Piras, F.; Inchingolo, F.; Dipalma, G.; Patano, A. Potential of Graphene-Functionalized Titanium Surfaces for Dental Implantology: Systematic Review. Coatings 2023, 13, 725. [Google Scholar] [CrossRef]
  38. The Most Suitable System to Grind the Whole Tooth to Use It as Graft Material. Available online: https://www.explorationpub.com/Journals/em/Article/1001202 (accessed on 28 November 2025).
  39. Salles, M.M.; Badaró, M.M.; de Arruda, C.N.F.; Leite, V.M.F.; da Silva, C.H.L.; Watanabe, E.; de Cássia Oliveira, V.; de Freitas Oliveira Paranhos, H. Antimicrobial Activity of Complete Denture Cleanser Solutions Based on Sodium Hypochlorite and Ricinus Communis—A Randomized Clinical Study. J. Appl. Oral Sci. 2015, 23, 637–642. [Google Scholar] [CrossRef]
  40. Arumugam, B.; Subramaniam, A.; Alagaraj, P. A Review on Impact of Medicinal Plants on the Treatment of Oral and Dental Diseases. Cardiovasc. Hematol. Agents Med. Chem. 2020, 18, 79–93. [Google Scholar] [CrossRef]
  41. Kapourani, A.; Kontogiannopoulos, K.N.; Manioudaki, A.-E.; Poulopoulos, A.K.; Tsalikis, L.; Assimopoulou, A.N.; Barmpalexis, P. A Review on Xerostomia and Its Various Management Strategies: The Role of Advanced Polymeric Materials in the Treatment Approaches. Polymers 2022, 14, 850. [Google Scholar] [CrossRef]
  42. Zhang, P.; Chen, S.G.; Wang, J.T.; Wang, J.D.; Chen, Z.H.; Lin, H.S. A Study on the Impact of Gargling with Compound Scutellaria baicalensis Georgi on Oral Health and Microflora Changes in Fixed Orthodontic Patients: An Experimental Study. Medicine 2024, 103, e39397. [Google Scholar] [CrossRef]
  43. Aizenbud, D.; Peled, M.; Figueroa, A.A. A Combined Orthodontic and Surgical Approach in Osteogenesis Imperfecta and Severe Class III Malocclusion: Case Report. J. Oral Maxillofac. Surg. 2008, 66, 1045–1053. [Google Scholar] [CrossRef] [PubMed]
  44. Ballini, A.; Cantore, S.; Scacco, S.; Perillo, L.; Scarano, A.; Aityan, S.K.; Contaldo, M.; Cd Nguyen, K.; Santacroce, L.; Syed, J.; et al. A Comparative Study on Different Stemness Gene Expression between Dental Pulp Stem Cells vs. Dental Bud Stem Cells. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 1626–1633. [Google Scholar] [CrossRef] [PubMed]
  45. Bianchi, F.P.; Stefanizzi, P.; Migliore, G.; Melpignano, L.; Daleno, A.; Vimercati, L.; Marra, M.; Working Group, C.R.; Tafuri, S. A COVID-19 Nosocomial Cluster in a University Hospital in Southern Italy: A Social Network Analysis. Ann. Ig. 2023, 35, 39–48. [Google Scholar] [CrossRef] [PubMed]
  46. Shin, J.; Saini, R.K.; Oh, J.-W. Low Dose Astaxanthin Treatments Trigger the Hormesis of Human Astroglioma Cells by Up-Regulating the Cyclin-Dependent Kinase and Down-Regulated the Tumor Suppressor Protein P53. Biomedicines 2020, 8, 434. [Google Scholar] [CrossRef]
  47. D’Amico, R.; Trovato Salinaro, A.; Cordaro, M.; Fusco, R.; Impellizzeri, D.; Interdonato, L.; Scuto, M.; Ontario, M.L.; Crea, R.; Siracusa, R.; et al. Hidrox® and Chronic Cystitis: Biochemical Evaluation of Inflammation, Oxidative Stress, and Pain. Antioxidants 2021, 10, 1046, Correction in Antioxidants 2025, 14, 1106. https://doi.org/10.3390/antiox14091106. [Google Scholar] [CrossRef]
  48. Scuto, M.; Rampulla, F.; Reali, G.M.; Spanò, S.M.; Trovato Salinaro, A.; Calabrese, V. Hormetic Nutrition and Redox Regulation in Gut-Brain Axis Disorders. Antioxidants 2024, 13, 484. [Google Scholar] [CrossRef]
  49. Scuto, M.; Majzúnová, M.; Torcitto, G.; Antonuzzo, S.; Rampulla, F.; Di Fatta, E.; Trovato Salinaro, A. Functional Food Nutrients, Redox Resilience Signaling and Neurosteroids for Brain Health. Int. J. Mol. Sci. 2024, 25, 12155. [Google Scholar] [CrossRef]
  50. D’Amico, R.; Cordaro, M.; Siracusa, R.; Impellizzeri, D.; Trovato Salinaro, A.; Scuto, M.; Ontario, M.L.; Crea, R.; Cuzzocrea, S.; Di Paola, R.; et al. Wnt/β-Catenin Pathway in Experimental Model of Fibromyalgia: Role of Hidrox®. Biomedicines 2021, 9, 1683. [Google Scholar] [CrossRef]
  51. Scuto, M.C.; Anfuso, C.D.; Lombardo, C.; Di Fatta, E.; Ferri, R.; Musso, N.; Zerbo, G.; Terrana, M.; Majzúnová, M.; Lupo, G.; et al. Neuronutrition and Nrf2 Brain Resilience Signaling: Epigenomics and Metabolomics for Personalized Medicine in Nervous System Disorders from Bench to Clinic. Int. J. Mol. Sci. 2025, 26, 9391. [Google Scholar] [CrossRef]
  52. Cordaro, M.; Scuto, M.; Siracusa, R.; D’amico, R.; Filippo Peritore, A.; Gugliandolo, E.; Fusco, R.; Crupi, R.; Impellizzeri, D.; Pozzebon, M.; et al. Effect of N-Palmitoylethanolamine-Oxazoline on Comorbid Neuropsychiatric Disturbance Associated with Inflammatory Bowel Disease. FASEB J. 2020, 34, 4085–4106, Erratum in FASEB J. 2024, 38, e23503. https://doi.org/10.1096/fj.202400297. [Google Scholar] [CrossRef] [PubMed]
  53. Amanpour, S.; Akbari Javar, M.; Sarhadinejad, Z.; Doustmohammadi, M.; Moghadari, M.; Sarhadynejad, Z. A Systematic Review of Medicinal Plants and Herbal Products’ Effectiveness in Oral Health and Dental Cure with Health Promotion Approach. J. Educ. Health Promot. 2023, 12, 306. [Google Scholar] [CrossRef] [PubMed]
  54. Gartika, M.; Pramesti, H.T.; Kurnia, D.; Satari, M.H. A Terpenoid Isolated from Sarang Semut (Myrmecodia Pendans) Bulb and Its Potential for the Inhibition and Eradication of Streptococcus Mutans Biofilm. BMC Complement. Altern. Med. 2018, 18, 151. [Google Scholar] [CrossRef] [PubMed]
  55. Liu, J.; Willems, H.M.E.; Sansevere, E.A.; Allert, S.; Barker, K.S.; Lowes, D.J.; Dixson, A.C.; Xu, Z.; Miao, J.; DeJarnette, C.; et al. A Variant ECE1 Allele Contributes to Reduced Pathogenicity of Candida albicans during Vulvovaginal Candidiasis. PLoS Pathog. 2021, 17, e1009884. [Google Scholar] [CrossRef]
  56. Kawano, Y.; Tanaka, M.; Fujishima, M.; Okumura, E.; Takekoshi, H.; Takada, K.; Uehara, O.; Abiko, Y.; Takeda, H. Acanthopanax Senticosus Harms Extract Causes G0/G1 Cell Cycle Arrest and Autophagy via Inhibition of Rubicon in Human Liver Cancer Cells. Oncol. Rep. 2021, 45, 1193–1201. [Google Scholar] [CrossRef]
  57. Chanapairin, B.; Kulvitit, S.; Sathorn, C. Post Retention Strength of Apical and Conventional Coating Obturation Methods Using Bioceramic Sealer: A Laboratory Investigation. BMC Oral Health 2024, 24, 3. [Google Scholar] [CrossRef]
  58. Khabiri, M.; Kamgar, S.; Iranmanesh, P.; Khademi, A.; Torabinejad, M. Postoperative Pain of Single-Visit Endodontic Treatment with Gutta-Percha versus MTA Filling: A Randomized Superiority Trial. BMC Oral Health 2023, 23, 1026. [Google Scholar] [CrossRef]
  59. Veloso, D.J.; Abrão, F.; Martins, C.H.G.; Bronzato, J.D.; Gomes, B.P.F.A.; Higino, J.S.; Sampaio, F.C. Potential Antibacterial and Anti-Halitosis Activity of Medicinal Plants against Oral Bacteria. Arch. Oral Biol. 2020, 110, 104585. [Google Scholar] [CrossRef]
  60. Nilsson, B.; Back, V.; Wei, R.; Plane, F.; Jurasz, P.; Bungard, T.J. Potential Antimigraine Effects of Warfarin: An Exploration of Biological Mechanism with Survey of Patients. TH Open 2019, 3, e180–e189. [Google Scholar] [CrossRef]
  61. Inchingolo, A.D.; Inchingolo, A.M.; Malcangi, G.; Avantario, P.; Azzollini, D.; Buongiorno, S.; Viapiano, F.; Campanelli, M.; Ciocia, A.M.; De Leonardis, N.; et al. Effects of Resveratrol, Curcumin and Quercetin Supplementation on Bone Metabolism-A Systematic Review. Nutrients 2022, 14, 3519. [Google Scholar] [CrossRef]
  62. Inchingolo, A.D.; Pezzolla, C.; Patano, A.; Ceci, S.; Ciocia, A.M.; Marinelli, G.; Malcangi, G.; Montenegro, V.; Cardarelli, F.; Piras, F.; et al. Experimental Analysis of the Use of Cranial Electromyography in Athletes and Clinical Implications. Int. J. Environ. Res. Public Health 2022, 19, 7975. [Google Scholar] [CrossRef] [PubMed]
  63. Kurnia, D.; Lestari, S.; Mayanti, T.; Gartika, M.; Nurdin, D. Anti-Infection of Oral Microorganisms from Herbal Medicine of Piper Crocatum Ruiz & Pav. Drug Des. Devel Ther. 2024, 18, 2531–2553. [Google Scholar] [CrossRef] [PubMed]
  64. Alexandre, J.T.M.; Sousa, L.H.T.; Lisboa, M.R.P.; Furlaneto, F.A.C.; do Val, D.R.; Marques, M.; Vasconcelos, H.C.; de Melo, I.M.; Leitão, R.; Castro Brito, G.A.; et al. Anti-Inflammatory and Antiresorptive Effects of Calendula Officinalis on Inflammatory Bone Loss in Rats. Clin. Oral Investig. 2018, 22, 2175–2185. [Google Scholar] [CrossRef] [PubMed]
  65. Niazi, F.H.; Kamran, M.A.; Naseem, M.; AlShahrani, I.; Fraz, T.R.; Hosein, M. Anti-Plaque Efficacy of Herbal Mouthwashes Compared to Synthetic Mouthwashes in Patients Undergoing Orthodontic Treatment: A Randomised Controlled Trial. Oral. Health Prev. Dent. 2018, 16, 409–416. [Google Scholar] [CrossRef]
  66. Oh, J.-H.; Mo, S.; Ngoc, L.T.N.; Lee, J.; Kim, M.-Y.; Park, H.-S.; Kim, J.-H.; Ha, Y.-J.; Sung, L.; Lee, Y.-C.; et al. Anti-Streptococcus Mutans and Anti-Inflammatory Effects of Ginsenoside Compound K and Enzyme-Treated Red Ginseng Extract (BTEX-K). J. Oral Biosci. 2024, 66, 19–27. [Google Scholar] [CrossRef]
  67. Ocheng, F.; Bwanga, F.; Joloba, M.; Borg-Karlson, A.-K.; Gustafsson, A.; Obua, C. Antibacterial Activities of Extracts from Ugandan Medicinal Plants Used for Oral Care. J. Ethnopharmacol. 2014, 155, 852–855. [Google Scholar] [CrossRef]
  68. Saccomanno, S.; Saran, S.; Petricca, M.T.; Caramaschi, E.; Ferrante, L.; Inchingolo, F.; Inchingolo, A.M.; Palermo, A.; Dipalma, G.; Inchingolo, A.D. Does Orthodontic Postgraduate Education Influence the Choice of Orthodontic Treatment? Front. Dent. Med. 2025, 6, 1665422. [Google Scholar] [CrossRef]
  69. Mazur, M.; Duś-Ilnicka, I.; Jedliński, M.; Ndokaj, A.; Janiszewska-Olszowska, J.; Ardan, R.; Radwan-Oczko, M.; Guerra, F.; Luzzi, V.; Vozza, I.; et al. Facial and Oral Manifestations Following COVID-19 Vaccination: A Survey-Based Study and a First Perspective. Int. J. Environ. Res. Public Health 2021, 18, 4965. [Google Scholar] [CrossRef]
  70. Sakagami, H.; Kishino, K.; Kobayashi, M.; Hashimoto, K.; Iida, S.; Shimetani, A.; Nakamura, Y.; Takahashi, K.; Ikarashi, T.; Fukamachi, H.; et al. Selective Antibacterial and Apoptosis-Modulating Activities of Mastic. In Vivo 2009, 23, 215–223. [Google Scholar]
  71. Baker, D.; MacDougall, A.; Kang, A.S.; Schmierer, K.; Giovannoni, G.; Dobson, R. Seroconversion Following COVID-19 Vaccination: Can We Optimize Protective Response in CD20-Treated Individuals? Clin. Exp. Immunol. 2022, 207, 263–271. [Google Scholar] [CrossRef]
  72. Arias-Moliz, M.-T.; Rojas, L.; Liébana-Cabanillas, F.; Bernal, C.; Castillo, F.; Rodríguez-Archilla, A.; Castillo, A.; Liébana, J. Serologic Control against Hepatitis B Virus among Dental Students of the University of Granada, Spain. Med. Oral Patol. Oral Cir. Bucal 2015, 20, e566–e571. [Google Scholar] [CrossRef]
  73. Edris, A.; Nour, M.O.; Zedan, O.O.; Mansour, A.E.; Ghandour, A.A.; Omran, T. Seroprevalence and Risk Factors for Hepatitis B and C Virus Infection in Damietta Governorate, Egypt. East. Mediterr. Health J. 2014, 20, 605–613. [Google Scholar] [CrossRef] [PubMed]
  74. Tallarico, M.; Ortensi, L.; Martinolli, M.; Casucci, A.; Ferrari, E.; Malaguti, G.; Montanari, M.; Scrascia, R.; Vaccaro, G.; Venezia, P.; et al. Multicenter Retrospective Analysis of Implant Overdentures Delivered with Different Design and Attachment Systems: Results Between One and 17 Years of Follow-Up. Dent. J. 2018, 6, 71. [Google Scholar] [CrossRef] [PubMed]
  75. Alves, M.D.; Tateyama, M.A.; Pavan, N.; Queiroz, A.F.; Nunes, M.; Endo, M.S. Multidisciplinary Approach to Complicated Crown-Root Fracture Treatment: A Case Report. Oper. Dent. 2021, 46, 484–490. [Google Scholar] [CrossRef] [PubMed]
  76. Nakao, R.; Takatsuka, A.; Mandokoro, K.; Narisawa, N.; Ikeda, T.; Takai, H.; Ogata, Y. Multimodal Inhibitory Effect of Matcha on Porphyromonas Gingivalis. Microbiol. Spectr. 2024, 12, e0342623. [Google Scholar] [CrossRef]
  77. Guan, Y.; Xu, J.; Qiu, J.; Cai, H.; Xia, W.; Ye, Z.; Sang, T. Multiparametric Performance Comparison of Dental Composites for Clear Aligner Attachments. BMC Oral Health 2025, 25, 1206. [Google Scholar] [CrossRef]
  78. Dipalma, G.; Inchingolo, A.D.; Calò, F.; Lagioia, R.; Bassi, P.; de Ruvo, E.; Inchingolo, F.; Palermo, A.; Marinelli, G.; Inchingolo, A.M. Eighty-Four-Month Clinical Outcomes of Autologous Dentin Graft Using Tooth Transformer® and Concentrated Growth Factors in Maxillary Atrophy: A Retrospective Study of 31 Patients. J. Funct. Biomater. 2025, 16, 357. [Google Scholar] [CrossRef]
  79. Israelson, L. The Role of Natural Products in Oral Health Care. J. Clin. Dent. 1988, 1, A4–A5. [Google Scholar]
  80. Budala, D.G.; Martu, M.-A.; Maftei, G.-A.; Diaconu-Popa, D.A.; Danila, V.; Luchian, I. The Role of Natural Compounds in Optimizing Contemporary Dental Treatment-Current Status and Future Trends. J. Funct. Biomater. 2023, 14, 273. [Google Scholar] [CrossRef]
  81. Aghaloo, T.; Valentini, P.; Yardley, R.; Zadeh, H.H. Application of Biologics in Maxillary Sinus Augmentation Surgery: A Narrative Review. Clin. Implant. Dent. Relat. Res. 2025, 27, e70004. [Google Scholar] [CrossRef]
  82. Baelum, V.; Machiulskiene, V.; Nyvad, B.; Richards, A.; Vaeth, M. Application of Survival Analysis to Carious Lesion Transitions in Intervention Trials. Community Dent. Oral Epidemiol. 2003, 31, 252–260. [Google Scholar] [CrossRef]
  83. Abbasi, A.J.; Mohammadi, F.; Bayat, M.; Gema, S.M.; Ghadirian, H.; Seifi, H.; Bayat, H.; Bahrami, N. Applications of Propolis in Dentistry: A Review. Ethiop. J. Health Sci. 2018, 28, 505–512. [Google Scholar] [CrossRef]
  84. Michelotto, A.L.d.C.; Gasparetto, J.C.; Campos, F.R.; Sydney, G.B.; Pontarolo, R. Applying Liquid Chromatography-Tandem Mass Spectrometry to Assess Endodontic Sealer Microleakage. Braz. Oral Res. 2015, 29, 1–7. [Google Scholar] [CrossRef] [PubMed][Green Version]
  85. Inchingolo, A.M.; Fatone, M.C.; Malcangi, G.; Avantario, P.; Piras, F.; Patano, A.; Di Pede, C.; Netti, A.; Ciocia, A.M.; De Ruvo, E.; et al. Modifiable Risk Factors of Non-Syndromic Orofacial Clefts: A Systematic Review. Children 2022, 9, 1846. [Google Scholar] [CrossRef] [PubMed]
  86. Khemawoot, P.; Hunsakunachai, N.; Anukunwithaya, T.; Bangphumi, K.; Ongpipattanakul, B.; Jiratchariyakul, W.; Soawakontha, R.; Inthachart, T.; Dechatiwongse Na Ayudhya, T.; Koontongkaew, S.; et al. Pharmacokinetics of Compound D, the Major Bioactive Component of Zingiber Cassumunar, in Rats. Planta Med. 2016, 82, 1186–1191. [Google Scholar] [CrossRef] [PubMed]
  87. Riley, P.; Glenny, A.-M.; Hua, F.; Worthington, H.V. Pharmacological Interventions for Preventing Dry Mouth and Salivary Gland Dysfunction Following Radiotherapy. Cochrane Database Syst. Rev. 2017, 7, CD012744. [Google Scholar] [CrossRef]
  88. Sedek, E.M.; Kamoun, E.A.; El-Deeb, N.M.; Abdelkader, S.; Fahmy, A.E.; Nouh, S.R.; Khalil, N.M. Photocrosslinkable Gelatin-Treated Dentin Matrix Hydrogel as a Novel Pulp Capping Agent for Dentin Regeneration: I. Synthesis, Characterizations and Grafting Optimization. BMC Oral Health 2023, 23, 536. [Google Scholar] [CrossRef]
  89. Saitawee, D.; Teerakapong, A.; Morales, N.P.; Jitprasertwong, P.; Hormdee, D. Photodynamic Therapy of Curcuma Longa Extract Stimulated with Blue Light against Aggregatibacter Actinomycetemcomitans. Photodiagn. Photodyn. Ther. 2018, 22, 101–105. [Google Scholar] [CrossRef]
  90. Dipalma, G.; Inchingolo, A.M.; Patano, A.; Palumbo, I.; Guglielmo, M.; Trilli, I.; Netti, A.; Ferrara, I.; Viapiano, F.; Inchingolo, A.D.; et al. Photobiomodulation and Growth Factors in Dentistry: A Systematic Review. Photonics 2023, 10, 1095. [Google Scholar] [CrossRef]
  91. Rapone, B.; Inchingolo, A.D.; Trasarti, S.; Ferrara, E.; Qorri, E.; Mancini, A.; Montemurro, N.; Scarano, A.; Inchingolo, A.M.; Dipalma, G.; et al. Long-Term Outcomes of Implants Placed in Maxillary Sinus Floor Augmentation with Porous Fluorohydroxyapatite (Algipore® FRIOS®) in Comparison with Anorganic Bovine Bone (Bio-Oss®) and Platelet Rich Plasma (PRP): A Retrospective Study. J. Clin. Med. 2022, 11, 2491. [Google Scholar] [CrossRef]
  92. Kandasamy, B.; Kaur, N.; Tomar, G.K.; Bharadwaj, A.; Manual, L.; Chauhan, M. Long-Term Retrospective Study Based on Implant Success Rate in Patients with Risk Factor: 15-Year Follow-Up. J. Contemp. Dent. Pract. 2018, 19, 90–93. [Google Scholar] [CrossRef]
  93. Inchingolo, F.; Tatullo, M.; Abenavoli, F.M.; Marrelli, M.; Inchingolo, A.D.; Palladino, A.; Inchingolo, A.M.; Dipalma, G. Oral Piercing and Oral Diseases: A Short Time Retrospective Study. Int. J. Med. Sci. 2011, 8, 649–652. [Google Scholar] [CrossRef]
  94. Johnson, B.; Toland, B.; Chokshi, R.; Mochalin, V.; Koutzaki, S.; Polyak, B. Magnetically Responsive Paclitaxel-Loaded Biodegradable Nanoparticles for Treatment of Vascular Disease: Preparation, Characterization and in Vitro Evaluation of Anti-Proliferative Potential. Curr. Drug Deliv. 2010, 7, 263–273. [Google Scholar] [CrossRef]
  95. Dipalma, G.; Inchingolo, A.M.; Malcangi, G.; Ferrara, I.; Viapiano, F.; Netti, A.; Patano, A.; Isacco, C.G.; Inchingolo, A.D.; Inchingolo, F. Sixty-Month Follow Up of Clinical MRONJ Cases Treated with CGF and Piezosurgery. Bioengineering 2023, 10, 863. [Google Scholar] [CrossRef] [PubMed]
  96. Asmussen, E.; Peutzfeldt, A. Substitutes for Methylene Chloride as Dental Softening Agent. Eur. J. Oral Sci. 2000, 108, 335–340. [Google Scholar] [CrossRef] [PubMed]
  97. Inchingolo, A.M.; Ceci, S.; Coloccia, G.; Azzollini, D.; Malcangi, G.; Mancini, A.; Inchingolo, F.; Trerotoli, P.; Dipalma, G.; Patano, A. Predictability and Effectiveness of Nuvola® Aligners in Dentoalveolar Transverse Changes: A Retrospective Study. Biomedicines 2023, 11, 1366. [Google Scholar] [CrossRef]
  98. Minetti, E.; Palermo, A.; Malcangi, G.; Inchingolo, A.D.; Mancini, A.; Dipalma, G.; Inchingolo, F.; Patano, A.; Inchingolo, A.M. Dentin, Dentin Graft, and Bone Graft: Microscopic and Spectroscopic Analysis. J. Funct. Biomater. 2023, 14, 272. [Google Scholar] [CrossRef]
  99. Inchingolo, A.M.; Patano, A.; De Santis, M.; Del Vecchio, G.; Ferrante, L.; Morolla, R.; Pezzolla, C.; Sardano, R.; Dongiovanni, L.; Inchingolo, F.; et al. Comparison of Different Types of Palatal Expanders: Scoping Review. Children 2023, 10, 1258. [Google Scholar] [CrossRef] [PubMed]
  100. Jacobsen, P.L.; Cohan, R.P. Alternative Dental Products. J. Calif. Dent. Assoc. 1998, 26, 191–198. [Google Scholar] [CrossRef]
  101. Hwang, S.-Y.; Chae, J.-I.; Kwak, A.-W.; Lee, M.-H.; Shim, J.-H. Alternative Options for Skin Cancer Therapy via Regulation of AKT and Related Signaling Pathways. Int. J. Mol. Sci. 2020, 21, 6869. [Google Scholar] [CrossRef]
  102. Saleh, W.; Alharbi, H.; Cha, S. Increased Prevalence of Erythema Multiforme in Patients with COVID-19 Infection or Vaccination. Sci. Rep. 2024, 14, 2801. [Google Scholar] [CrossRef] [PubMed]
  103. Wong, A.W.-Y.; Zhang, S.; Li, S.K.-Y.; Zhu, X.; Zhang, C.; Chu, C.-H. Incidence of Post-Obturation Pain after Single-Visit versus Multiple-Visit Non-Surgical Endodontic Treatments. BMC Oral Health 2015, 15, 96. [Google Scholar] [CrossRef] [PubMed]
  104. Charitos, I.A.; Inchingolo, A.M.; Ferrante, L.; Inchingolo, F.; Inchingolo, A.D.; Castellaneta, F.; Cotoia, A.; Palermo, A.; Scacco, S.; Dipalma, G. The Gut Microbiota’s Role in Neurological, Psychiatric, and Neurodevelopmental Disorders. Nutrients 2024, 16, 4404. [Google Scholar] [CrossRef] [PubMed]
  105. Rattanpornsompong, K.; Rattanaprukskul, K.; Prachanukoon, S.; Sriwangyang, K.; Rinkrathok, M.; Tagami, J.; Porntaveetus, T. Influence of Alloplastic Materials, Biologics, and Their Combinations, along with Defect Characteristics, on Short-Term Intrabony Defect Surgical Treatment Outcomes: A Systematic Review and Network Meta-Analysis. BMC Oral Health 2025, 25, 413. [Google Scholar] [CrossRef]
  106. Dabdoub, S.M.; Greenlee, A.; Abboud, G.; Brengartner, L.; Zuiker, E.; Gorr, M.W.; Wold, L.E.; Kumar, P.S.; Cray, J. Acute Exposure to Electronic Cigarette Components Alters mRNA Expression of Pre-Osteoblasts. FASEB J. 2024, 38, e70017. [Google Scholar] [CrossRef]
  107. Tomita, J.; Mochizuki, S.; Fujimoto, S.; Kashihara, N.; Akasaka, T.; Tanimoto, M.; Yoshida, K. Acute Improvement of Endothelial Functions after Oral Ingestion of Isohumulones, Bitter Components of Beer. Biochem. Biophys. Res. Commun. 2017, 484, 740–745. [Google Scholar] [CrossRef]
  108. Periyasamy, S.; Krishnappa, P.; Renuka, P. Adherence to Components of Health Promoting Schools in Schools of Bengaluru, India. Health Promot. Int. 2019, 34, 1167–1178, Correction in Health Promot. Int. 2020, 35, 174. https://doi.org/10.1093/heapro/day115. [Google Scholar] [CrossRef]
  109. Palmer, R.M.; Matthews, J.P.; Wilson, R.F. Adjunctive Systemic and Locally Delivered Metronidazole in the Treatment of Periodontitis: A Controlled Clinical Study. Br. Dent. J. 1998, 184, 548–552. [Google Scholar] [CrossRef]
  110. Di Lorenzo, L.; Inchingolo, F.; Pipoli, A.; Cassano, F.; Maggiore, M.E.; Inchingolo, A.M.; Ceci, S.; Patano, A.; Malcangi, G.; Mancini, A.; et al. Mixed-Dust Pneumoconiosis in a Dental Technician: A Multidisciplinary Diagnosis Case Report. BMC Pulm. Med. 2022, 22, 161. [Google Scholar] [CrossRef]
  111. de Menezes, R.F.; de Araújo, N.C.; Santa Rosa, J.M.C.; Carneiro, V.S.M.; Santos Neto, A.P.D.; Costa, V.; Moreno, L.M.; Miranda, J.M.; de Albuquerque, D.S.; Albuquerque, M.; et al. Detection of Vertical Root Fractures in Endodontically Treated Teeth in the Absence and in the Presence of Metal Post by Cone-Beam Computed Tomography. BMC Oral Health 2016, 16, 48. [Google Scholar] [CrossRef]
  112. Montero, J.; Leiva, L.A.; Martín-Quintero, I.; Rosel, E.; Barrios-Rodriguez, R. Determinants of Masticatory Performance Assessed by Mixing Ability Tests. J. Prosthet. Dent. 2022, 128, 382–389. [Google Scholar] [CrossRef] [PubMed]
  113. Silva, T.M.; Bolzan, T.C.A.; Zanini, M.S.; Alencar, T.; Rodrigues, W.D.; Bastos, K.A.; Severi, J.A.; Resende, J.A.; Villanova, J.C.O. Development and Evaluation of a Novel Oral Mucoadhesive Ointment Containing Pomegranate Peel Extract as an Adjuvant for Oral Hygiene of Dogs. J. Vet. Dent. 2020, 37, 133–140. [Google Scholar] [CrossRef] [PubMed]
  114. Uddin, T.M.; Chakraborty, A.J.; Khusro, A.; Zidan, B.R.M.; Mitra, S.; Emran, T.B.; Dhama, K.; Ripon, M.K.H.; Gajdács, M.; Sahibzada, M.U.K.; et al. Antibiotic Resistance in Microbes: History, Mechanisms, Therapeutic Strategies and Future Prospects. J. Infect. Public Health 2021, 14, 1750–1766. [Google Scholar] [CrossRef]
  115. Liu, C.; Wang, L.; Zhu, R.; Liu, H.; Ma, R.; Chen, B.; Li, L.; Guo, Y.; Jia, Q.; Shi, S.; et al. Rehmanniae Radix Preparata Suppresses Bone Loss and Increases Bone Strength through Interfering with Canonical Wnt/β-Catenin Signaling Pathway in OVX Rats. Osteoporos. Int. 2019, 30, 491–505, Erratum in Osteoporos. Int. 2019, 30, 1537–1540. https://doi.org/10.1007/s00198-019-05028-0. [Google Scholar] [CrossRef]
  116. Ferati, K.; Bexheti-Ferati, A.; Palermo, A.; Pezzolla, C.; Trilli, I.; Sardano, R.; Latini, G.; Inchingolo, A.D.; Inchingolo, A.M.; Malcangi, G.; et al. Diagnosis and Orthodontic Treatment of Obstructive Sleep Apnea Syndrome Children-A Systematic Review. Diagnostics 2024, 14, 289. [Google Scholar] [CrossRef] [PubMed]
  117. Nuno-Gonzalez, A.; Martin-Carrillo, P.; Magaletsky, K.; Martin Rios, M.D.; Herranz Mañas, C.; Artigas Almazan, J.; García Casasola, G.; Perez Castro, E.; Gallego Arenas, A.; Mayor Ibarguren, A.; et al. Prevalence of Mucocutaneous Manifestations in 666 Patients with COVID-19 in a Field Hospital in Spain: Oral and Palmoplantar Findings. Br. J. Dermatol. 2021, 184, 184–185. [Google Scholar] [CrossRef]
  118. Nunn, M.E.; Fan, J.; Su, X.; Levine, R.A.; Lee, H.-J.; McGuire, M.K. Development of Prognostic Indicators Using Classification and Regression Trees for Survival. Periodontology 2000, 58, 134–142. [Google Scholar] [CrossRef]
  119. Inchingolo, A.M.; Inchingolo, A.D.; Latini, G.; Garofoli, G.; Sardano, R.; De Leonardis, N.; Dongiovanni, L.; Minetti, E.; Palermo, A.; Dipalma, G.; et al. Caries Prevention and Treatment in Early Childhood: Comparing Strategies. A Systematic Review. Eur. Rev. Med. Pharmacol. Sci. 2023, 27, 11082–11092. [Google Scholar] [CrossRef]
  120. Inchingolo, F.; Tatullo, M.; Marrelli, M.; Inchingolo, A.M.; Tarullo, A.; Inchingolo, A.D.; Dipalma, G.; Podo Brunetti, S.; Tarullo, A.; Cagiano, R. Combined Occlusal and Pharmacological Therapy in the Treatment of Temporo-Mandibular Disorders. Eur. Rev. Med. Pharmacol. Sci. 2011, 15, 1296–1300. [Google Scholar]
  121. Chai, S.J.; Fong, S.C.Y.; Gan, C.P.; Pua, K.C.; Lim, P.V.H.; Lau, S.H.; Zain, R.B.; Abraham, T.; Ismail, S.M.; Abdul Rahman, Z.A.; et al. In Vitro Evaluation of Dual-Antigenic PV1 Peptide Vaccine in Head and Neck Cancer Patients. Hum. Vaccin. Immunother. 2019, 15, 167–178. [Google Scholar] [CrossRef]
  122. Abdelnaby, P.; Ibrahim, M.; ElBackly, R. In Vitro Evaluation of Filling Material Removal and Apical Debris Extrusion after Retreatment Using Reciproc Blue, Hyflex EDM and ProTaper Retreatment Files. BMC Oral Health 2023, 23, 902. [Google Scholar] [CrossRef]
  123. Polat Sagsoz, N.; Orhan, F.; Baris, O.; Sagsoz, O. In Vitro Evaluation of Plant Antimicrobials Against Candida Albicans Biofilm on Denture Base Materials: A Comparison with Chemical Denture Cleansers. Polymers 2025, 17, 2869. [Google Scholar] [CrossRef] [PubMed]
  124. Laghios, C.D.; Cutler, C.W.; Gutmann, J.L. In Vitro Evidence That Lipopolysaccharide of an Oral Pathogen Leaks from Root-End Filled Teeth. Int. Endod. J. 2000, 33, 333–339. [Google Scholar] [CrossRef] [PubMed]
  125. Yoon, C.S.; Kim, M.K.; Kim, Y.S.; Lee, S.K. In Vitro Protein Expression Changes in RAW 264.7 Cells and HUVECs Treated with Dialyzed Coffee Extract by Immunoprecipitation High Performance Liquid Chromatography. Sci. Rep. 2018, 8, 13841. [Google Scholar] [CrossRef]
  126. Manton, D.J.; Walker, G.D.; Cai, F.; Cochrane, N.J.; Shen, P.; Reynolds, E.C. Remineralization of Enamel Subsurface Lesions in Situ by the Use of Three Commercially Available Sugar-Free Gums. Int. J. Paediatr. Dent. 2008, 18, 284–290. [Google Scholar] [CrossRef]
  127. Dipalma, G.; Marinelli, G.; Bassi, P.; Lagioia, R.; Calò, F.; Cavino, M.; Inchingolo, F.; Vinjolli, F.; Bordea, I.R.; Minervini, G.; et al. Impact of Functional Therapy on Skeletal Structures and Airways in Patients with Class II Malocclusion: Comparison of Treatment in Prepubertal and Pubertal Phases. Life 2025, 15, 1144. [Google Scholar] [CrossRef] [PubMed]
  128. Hayasaki, H.; Sawami, T.; Saitoh, I.; Iwase, Y.; Nakata, S.; Nakata, M. Length of the Occlusal Glide during Chewing in Children with Primary Dentition. J. Oral Rehabil. 2003, 30, 1138–1141. [Google Scholar] [CrossRef]
  129. Liu, M.; Xiong, S.; Tan, F.; Liu, Y. Less Extrusion Debris during the Retreatment of Curved Canals Using Twisted Files with Higher Rotational Speeds: An Ex Vivo Study. BMC Oral Health 2017, 17, 45. [Google Scholar] [CrossRef][Green Version]
  130. Francis, C.A.; Hector, M.P.; Proctor, G.B. Levels of Pre-Kallikrein in Resting and Stimulated Human Parotid and Submandibular Saliva. Eur. J. Oral Sci. 2001, 109, 365–368. [Google Scholar] [CrossRef]
  131. Saleh, W.; Alharbi, H.; Yue, S.; Fernandes, R.P. Lichen Planus after COVID-19 Infection and Vaccination. Oral. Dis. 2024, 30, 3925–3930. [Google Scholar] [CrossRef]
  132. Lombardo Bedran, T.B.; Palomari Spolidorio, D.; Grenier, D. Green Tea Polyphenol Epigallocatechin-3-Gallate and Cranberry Proanthocyanidins Act in Synergy with Cathelicidin (LL-37) to Reduce the LPS-Induced Inflammatory Response in a Three-Dimensional Co-Culture Model of Gingival Epithelial Cells and Fibroblasts. Arch. Oral Biol. 2015, 60, 845–853. [Google Scholar] [CrossRef]
  133. Lagha, A.B.; Groeger, S.; Meyle, J.; Grenier, D. Green Tea Polyphenols Enhance Gingival Keratinocyte Integrity and Protect against Invasion by Porphyromonas Gingivalis. Pathog. Dis. 2018, 76, fty030. [Google Scholar] [CrossRef] [PubMed]
  134. Gaur, S.; Agnihotri, R. Green Tea: A Novel Functional Food for the Oral Health of Older Adults. Geriatr. Gerontol. Int. 2014, 14, 238–250. [Google Scholar] [CrossRef] [PubMed]
  135. Giannobile, W.V.; Somerman, M.J. Growth and Amelogenin-like Factors in Periodontal Wound Healing. A Systematic Review. Ann. Periodontol. 2003, 8, 193–204. [Google Scholar] [CrossRef] [PubMed]
  136. Klionsky, D.J.; Abdel-Aziz, A.K.; Abdelfatah, S.; Abdellatif, M.; Abdoli, A.; Abel, S.; Abeliovich, H.; Abildgaard, M.H.; Abudu, Y.P.; Acevedo-Arozena, A.; et al. Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy (4th Edition)1. Autophagy 2021, 17, 1–382. [Google Scholar] [CrossRef]
  137. Triggiano, F.; Veschetti, E.; Veneri, F.; Montagna, M.T.; De Giglio, O. Best Practices for Disinfection in Dental Settings: Insights from Italian and European Regulations. Ann. Ig. 2025, 37, 292–301. [Google Scholar] [CrossRef]
  138. Minetti, E.; Dipalma, G.; Palermo, A.; Patano, A.; Inchingolo, A.D.; Inchingolo, A.M.; Inchingolo, F. Biomolecular Mechanisms and Case Series Study of Socket Preservation with Tooth Grafts. J. Clin. Med. 2023, 12, 5611. [Google Scholar] [CrossRef]
  139. Moqaddam, M.A.; Nemati, M.; Dara, M.M.; Hoteit, M.; Sadek, Z.; Ramezani, A.; Rand, M.K.; Abbassi-Daloii, A.; Pashaei, Z.; Almaqhawi, A.; et al. Exploring the Impact of Astaxanthin Supplementation in Conjunction with a 12-Week CrossFit Training Regimen on Selected Adipo-Myokines Levels in Obese Males. Nutrients 2024, 16, 2857. [Google Scholar] [CrossRef]
  140. Sharifi-Rigi, A.; Zal, F.; Aarabi, M.-H.; Rad, N.R.; Naghibalhossaini, F.; Shafiee, S.M.; Aminorroaya, A. The Effects of Astaxanthin on AMPK/Autophagy Axis and Inflammation in Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Trial. Gene Rep. 2023, 33, 101844. [Google Scholar] [CrossRef]
  141. Gonzalez, D.E.; Dickerson, B.L.; Johnson, S.E.; Woodruff, K.E.; Leonard, M.; Yoo, C.; Ko, J.; Xing, D.; Martinez, V.; Kendra, J.; et al. Impact of Astaxanthin Supplementation on Markers of Cardiometabolic Health and Tactical Performance among Firefighters. J. Int. Soc. Sports Nutr. 2024, 21, 2427751. [Google Scholar] [CrossRef]
  142. Mohammadi, S.G.; Feizi, A.; Bagherniya, M.; Shafie, D.; Ahmadi, A.R.; Kafeshani, M. The Effect of Astaxanthin Supplementation on Inflammatory Markers, Oxidative Stress Indices, Lipid Profile, Uric Acid Level, Blood Pressure, Endothelial Function, Quality of Life, and Disease Symptoms in Heart Failure Subjects. Trials 2024, 25, 518. [Google Scholar] [CrossRef]
  143. Ciaraldi, T.P.; Boeder, S.C.; Mudaliar, S.R.; Giovannetti, E.R.; Henry, R.R.; Pettus, J.H. Astaxanthin, a Natural Antioxidant, Lowers Cholesterol and Markers of Cardiovascular Risk in Individuals with Prediabetes and Dyslipidaemia. Diabetes Obes. Metab. 2023, 25, 1985–1994. [Google Scholar] [CrossRef] [PubMed]
  144. Jabarpour, M.; Aleyasin, A.; Nashtaei, M.S.; Lotfi, S.; Amidi, F. Astaxanthin Treatment Ameliorates ER Stress in Polycystic Ovary Syndrome Patients: A Randomized Clinical Trial. Sci. Rep. 2023, 13, 3376. [Google Scholar] [CrossRef]
  145. Jabarpour, M.; Amidi, F.; Aleyasin, A.; Nashtaei, M.S.; Marghmaleki, M.S. Randomized Clinical Trial of Astaxanthin Supplement on Serum Inflammatory Markers and ER Stress-Apoptosis Gene Expression in PBMCs of Women with PCOS. J. Cell Mol. Med. 2024, 28, e18464. [Google Scholar] [CrossRef] [PubMed]
  146. Jabarpour, M.; Aleyasin, A.; Shabani Nashtaei, M.; Amidi, F. Astaxanthin Supplementation Impact on Insulin Resistance, Lipid Profile, Blood Pressure, and Oxidative Stress in Polycystic Ovary Syndrome Patients: A Triple-Blind Randomized Clinical Trial. Phytother. Res. 2024, 38, 321–330. [Google Scholar] [CrossRef] [PubMed]
  147. Youssef, F.M.; Ateyya, H.; Hanna Samy, A.E.; Elmokadem, E.M. The Anti-Inflammatory and Antioxidant Effects of Astaxanthin as an Adjunctive Therapy in Community-Acquired Pneumonia: A Randomized Controlled Trial. Front. Pharmacol. 2025, 16, 1621308. [Google Scholar] [CrossRef]
  148. Heidari, M.; Chaboksafar, M.; Alizadeh, M.; Sohrabi, B.; Kheirouri, S. Effects of Astaxanthin Supplementation on Selected Metabolic Parameters, Anthropometric Indices, Sirtuin1 and TNF-α Levels in Patients with Coronary Artery Disease: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Front. Nutr. 2023, 10, 1104169. [Google Scholar] [CrossRef]
  149. Tian, L.; Wen, Y.; Li, S.; Zhang, P.; Wang, Y.; Wang, J.; Cao, K.; Du, L.; Wang, N.; Jie, Y. Benefits and Safety of Astaxanthin in the Treatment of Mild-To-Moderate Dry Eye Disease. Front. Nutr. 2021, 8, 796951. [Google Scholar] [CrossRef]
  150. Rostami, S.; Alyasin, A.; Saedi, M.; Nekoonam, S.; Khodarahmian, M.; Moeini, A.; Amidi, F. Astaxanthin Ameliorates Inflammation, Oxidative Stress, and Reproductive Outcomes in Endometriosis Patients Undergoing Assisted Reproduction: A Randomized, Triple-Blind Placebo-Controlled Clinical Trial. Front. Endocrinol. 2023, 14, 1144323. [Google Scholar] [CrossRef]
  151. Nieman, D.C.; Woo, J.; Sakaguchi, C.A.; Omar, A.M.; Tang, Y.; Davis, K.; Pecorelli, A.; Valacchi, G.; Zhang, Q. Astaxanthin Supplementation Counters Exercise-Induced Decreases in Immune-Related Plasma Proteins. Front. Nutr. 2023, 10, 1143385. [Google Scholar] [CrossRef]
  152. Saeidi, A.; Nouri-Habashi, A.; Razi, O.; Ataeinosrat, A.; Rahmani, H.; Mollabashi, S.S.; Bagherzadeh-Rahmani, B.; Aghdam, S.M.; Khalajzadeh, L.; Al Kiyumi, M.H.; et al. Astaxanthin Supplemented with High-Intensity Functional Training Decreases Adipokines Levels and Cardiovascular Risk Factors in Men with Obesity. Nutrients 2023, 15, 286. [Google Scholar] [CrossRef]
  153. Supriya, R.; Shishvan, S.R.; Kefayati, M.; Abednatanzi, H.; Razi, O.; Bagheri, R.; Escobar, K.A.; Pashaei, Z.; Saeidi, A.; Shahrbanian, S.; et al. Astaxanthin Supplementation Augments the Benefits of CrossFit Workouts on Semaphorin 3C and Other Adipokines in Males with Obesity. Nutrients 2023, 15, 4803. [Google Scholar] [CrossRef] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Article Metrics

Citations

Article Access Statistics

Journal Statistics
Multiple requests from the same IP address are counted as one view.
NLRP3 Inflammasome and Polycystic Ovary Syndrome (PCOS): A Novel Profile in Adipose Tissue
Previous
Sea Buckthorn, Aronia, and Black Currant Pruning Waste Biomass as a Source of Multifunctional Skin-Protecting Cosmetic and Pharmaceutical Cream Ingredients
Next