Drugs and Drug Candidates

The 33^rd Annual Conference of the Group for the Promotion of Pharmaceutical Chemistry in Academia (GP₂A), held in Nantes from 11 to 13 June 2025, marked a significant expansion of the organization’s scope and collaborative efforts. Building on the success of the previous meeting in Coimbra, the 2025 edition brought together 168 participants and featured a comprehensive scientific programme comprising 102 abstracts. A key highlight of this year’s conference was the collaboration with COST Action OneHealthdrugs and the Paul Ehrlich (PE) Euro-PhD Network, fostering interdisciplinary exchange and identifying future research synergies. The event included 1 computational workshop and 8 keynote lectures by international experts, alongside a strong emphasis on early-career researchers, with 25 oral presentations and 25 flash poster communications. In addition, 77 posters were presented across three dedicated sessions. All the presentations were eligible for 18 conference awards. Staying true to the GP₂A and PE mission, the conference provided a dynamic platform for young scientists to engage with established researchers. Full article

Background. Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used treatments for mild to moderate pain and fever in pediatric patients. Notwithstanding, greater caution and awareness of their distinct safety profiles is warranted, especially in children with comorbidities. Expert opinion. Herein, expert opinion is presented on the use of these drugs in this setting. Paracetamol is suggested as first-line treatment for managing fever in pediatric patients. For pain, paracetamol is suggested for acute mild-to-moderate pain, whereas NSAIDs are preferred for pain associated with inflammatory conditions. A fixed-dose combination of paracetamol and ibuprofen may be considered for moderate pain, which allows effective analgesia while potentially reducing the risk of adverse events associated with monotherapy. Based on opinion and clinical experience, suggestions were made for pediatric patients considering a large variety of comorbidities. For example, in patients with infection/influenza, the panel concluded that paracetamol should be preferred over NSAIDs. In pediatric patients with inflammatory bowel disease, it was suggested to avoid long-term or high-dose NSAID treatment, particularly in those with active disease. In the presence of skin and soft tissue infections, it was suggested to limit the use of NSAIDs and prioritize paracetamol as first-line therapy. It was also recommended to exercise caution when using NSAIDs in pediatric patients with diabetes. Lastly, shared therapeutic flowcharts were developed that facilitate the patient journey of pediatric patients with comorbidity and fever or pain, which may help promote therapeutic appropriateness and reduce the risk of adverse events, providing practical guidance for general practitioners and pediatricians. Full article

Hypertension is a major global health concern affecting over one billion people worldwide and is a leading risk factor for cardiovascular diseases, stroke, and kidney failure. Plant-derived bioactive compounds provide promising natural strategies for hypertension management by improving endothelial function, promoting vasorelaxation and diuresis, reducing oxidative stress, and modulating key molecular pathways. This review focuses on some important traditional medicinal plants from Northeast India with potential antihypertensive activity, summarizing their phytochemical constituents, pharmacological evidence, and proposed mechanisms of action. Northeast India lies within the Eastern Himalayas and Indo-Burma biodiversity hotspots and is recognized for its rich plant diversity. We conducted a systematic literature search using PubMed, Google Scholar, ScienceDirect, and Scopus following PRISMA guidelines. We further evaluated identified compounds for ADMET using open-source computational tools. Ten medicinal plants: Clerodendrum colebrookeanum, Moringa oleifera, Garcinia dulcis, Centella asiatica, Terminalia bellirica, Hibiscus sabdariffa, Citrus limon, Passiflora edulis, Garcinia cowa, and Solanum torvum yielded 22 bioactive compounds with notable antihypertensive activity. These compounds exhibited antioxidant, anti-inflammatory, and vasorelaxant effects via nitric oxide synthase activation, MAPK/NF-κB inhibition, ACE inhibition, calcium channel modulation, and reactive oxygen species scavenging. ADMET profiling indicated favorable pharmacokinetics, with vitexin, isovitexin, isoquercetin, and nobiletin showing low predicted toxicity and high stability. Full article

Backgrounds: Astragalus membranaceus (AM), a traditional Chinese medicinal herb, has garnered interest for its potential in anticancer therapy. Preclinical evidence suggests that AM inhibits tumor growth and could mitigate the adverse effects associated with conventional treatments. However, a comprehensive review of its efficacy across various cancer types is lacking. Objectives: This systematic review evaluates the preclinical evidence for the antitumor efficacy of AM and its active components to inform future clinical translation. Methods: A systematic literature search was conducted in PubMed, EMBASE, and Web of Science from their earliest records to February 2026 to identify relevant studies. Studies reporting on the antitumor effects of AM or its constituents in murine models were included. Results: Seventy-six studies met the inclusion criteria. The most frequently investigated compounds were formononetin (21 studies), Astragaloside IV (20 studies), and Astragalus polysaccharide (16 studies). The evidence indicates that these compounds, both as monotherapies and in combination with standard chemotherapy, can inhibit tumor growth and potentiate antitumor efficacy. Conclusions: AM and its bioactive constituents exhibit promising anticancer effects against solid tumors, including breast, lung, hepatocellular, and colorectal carcinomas in preclinical models. Clinical investigation is warranted to confirm the utility of AM for cancer therapy. Full article

Background: Geraniol is an acyclic monoterpene widely distributed in the essential oils of aromatic species such as Cymbopogon citratus, Pelargonium graveolens, and Rosa damascena, It is known for its antioxidant, anti-inflammatory, neuroprotective, and antitumor activities. Methods: This study aimed to investigate, through network pharmacology and computational ADMET modeling, the molecular mechanisms and pharmacological potential of geraniol, integrating drug-likeness parameters, toxicity prediction, and multitarget interactions. Results: A total of 25 core targets were identified, mainly involved in inflammation, oxidative stress, apoptosis, and transcriptional regulation. Geraniol exhibited a favorable drug-likeness profile, high predicted intestinal absorption, and low systemic toxicity, supporting its pharmaceutical applicability. Mechanistically, it modulates the Nrf2/HO-1 ↔ NF-κB axis, reducing reactive oxygen species, pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and apoptotic markers (caspases, Bax), while enhancing antioxidant enzymes (SOD, CAT, GPx) and antiapoptotic proteins (Bcl-2). Conclusions: These findings confirm its multitarget and pleiotropic nature, highlighting its potential as a therapeutic candidate for inflammatory, metabolic, and neurodegenerative disorders. Furthermore, this study provides a robust mechanistic rationale for future in vitro and in vivo validation, as well as for the design of nanostructured formulations to improve geraniol’s bioavailability and therapeutic safety. Full article

Carbapenem-resistant Acinetobacter baumannii (CRAB) is classified by the World Health Organization among the critical-priority pathogens, reflecting high mortality, near-ubiquitous nosocomial spread, and a depleted therapeutic pipeline. No antibiotic chemical class with a genuinely novel target and activity against A. baumannii reached patients for more than fifty years, and current options—sulbactam–durlobactam, cefiderocol, polymyxins, high-dose ampicillin–sulbactam and tetracyclines—are constrained by toxicity, inconsistent efficacy, or emerging resistance. Against this background, zosurabalpin (RG6006), the first member of the tethered macrocyclic peptide (MCP) class, represents a potentially important conceptual advance. Identified through whole-cell phenotypic screening of nearly 45,000 macrocyclic peptides and optimized into a zwitterionic clinical candidate, zosurabalpin inhibits the LptB₂FGC complex, the inner-membrane ATP-binding-cassette transporter that initiates lipopolysaccharide (LPS) export. By trapping LPS within the transporter, the drug causes lethal accumulation of the molecule at the inner membrane. This mechanism is structurally distinct from that of every clinically used antibiotic and, in preclinical studies, is not affected by the major currently recognized CRAB resistance mechanisms. Zosurabalpin shows potent, narrow-spectrum activity essentially restricted to the Acinetobacter baumannii–calcoaceticus complex, retaining activity in vitro against isolates resistant to cefiderocol and last-line agents; its clinical efficacy in patients, however, remains to be established. Here we review the discovery, structural mechanism, microbiological spectrum, and clinical development of zosurabalpin, and we situate it within a broader revival of pathogen-specific (narrow-spectrum) antibiotic development, discussing the diagnostic, stewardship, and economic implications of this paradigm. Full article

Drug recall is a critical regulatory mechanism implemented to protect public health by removing defective, unsafe, or non-compliant pharmaceutical products from the market. Despite stringent regulatory approval processes, issues related to manufacturing defects, contamination, labeling errors, stability failures, and post-marketing safety concerns may lead to drug recalls. Regulatory authorities across the world, including the Central Drugs Standard Control Organization (CDSCO), the United States Food and Drug Administration (US FDA), the European Medicines Agency (EMA), and other national agencies, have developed structured recall guidelines and rapid alert systems to ensure timely withdrawal of defective products. Drug recalls are typically classified based on the level of health risk and may be executed at different levels of the distribution chain, including wholesale, retail, and consumer levels. Effective recall management involves risk assessment, recall communication, product traceability, documentation, and recall effectiveness checks. Pharmacovigilance systems also play an important role in identifying adverse drug reactions and quality defects that may lead to product recalls. This review article provides a comprehensive overview of drug recall systems, including causes of recalls, regulatory frameworks in India and other countries, recall classification, recall procedures, rapid alert systems, and global recall trends. The article also discusses challenges in recall implementation and provides recommendations to strengthen drug recall systems and regulatory coordination worldwide. The review additionally summarizes major official sources of recall information, including recall alerts, safety communications, and regulatory databases maintained by the Food and Drug Administration (FDA), EMA, CDSCO, Medicines and Healthcare products Regulatory Agency (MHRA), and World Health Organization (WHO), and provides a comparative global perspective on contemporary pharmaceutical recall practices. Full article

One of the most pressing challenges facing healthcare today is the rise of biofilm infections and antibiotic-resistant bacteria, which demand entirely new therapeutic strategies beyond conventional antibiotic reliance. A biofilm is a structured community of microorganisms encased in a self-produced extracellular polymeric substance (EPS) matrix, which confers resistance to host immune defenses and antimicrobial agents. Accumulating evidence demonstrates that plant-derived secondary metabolites—including flavonoids, phenolic acids, tannins, terpenoids, and alkaloids—exert potent antibacterial and antibiofilm activities through diverse mechanisms of action. These natural compounds inhibit biofilm formation by disrupting bacterial adhesion, suppressing quorum sensing, degrading the EPS matrix, and impairing bacterial motility. Beyond independent bioactivity, phytochemicals demonstrate significant synergistic potential when combined with conventional antibiotics, revitalizing antimicrobial efficacy against drug-resistant pathogens. Nanoformulation and biogenic carrier technologies further enhance the bioavailability and therapeutic potency of these compounds. Despite these advances, critical challenges persist, including poor bioavailability, physicochemical instability, dose-dependent toxicity, and the risk of resistance development. This review presents a critical and integrative analysis of the pharmacological mechanisms of plant secondary metabolites, with particular emphasis on their role in combating biofilm-associated infections and antibiotic resistance, and discusses translational opportunities including structure–activity relationship (SAR)-guided optimization, high-throughput screening platforms, and advanced drug delivery systems. Collectively, plant secondary metabolites represent a scientifically compelling and clinically relevant pipeline for the development of next-generation antimicrobial and antibiofilm therapeutics. Full article

Background: Microbiome-oriented therapies, including fecal microbiota transplantation (FMT), phage therapy, and live biotherapeutic products (LBPs), represent a promising direction in modern biomedicine for addressing antimicrobial resistance (AMR), recurrent Clostridioides difficile infection (rCDI), and dysbiosis-associated conditions. Despite encouraging clinical outcomes, their integration into routine clinical practice remains limited due to regulatory heterogeneity and unresolved ethical challenges. Objective: This review aims to analyze international regulatory approaches to microbiome-based therapies and to identify key bioethical issues associated with their clinical application. Main content: The paper summarizes current scientific evidence and regulatory frameworks governing microbiome therapies in the United States, the European Union, Ukraine, and selected Asia-Pacific countries. Particular attention is given to differences in classification, approval pathways, and safety requirements. The review also examines major ethical concerns, including informed consent, donor screening, biosafety, data protection, and equitable access to innovative treatments. Conclusions: The analysis demonstrates that microbiome therapies have significant potential for improving clinical outcomes and supporting antimicrobial stewardship. However, their broader implementation requires the harmonization of regulatory frameworks, strengthening of biosafety standards, and development of clear ethical guidelines. International cooperation and accumulation of clinical evidence are essential for the safe and effective integration of microbiome-based interventions into healthcare systems. Full article

Background/Objectives: Course-based Undergraduate Research Experiences (CUREs) represent a form of student crowdsourcing in which individuals perform authentic discovery-based research in a class setting with interest to outside stakeholders. Here, the renowned Tiny Earth (TE) CURE is being utilized to teach microbiology and perform natural product discovery research by students in the course. Methods: In our TE CURE, students collect soil samples from their hometown and characterize bacteria that can inhibit plant and animal pathogens. This unique growing collection of isolates from across Ohio has provided opportunities to facilitate drug discovery and establish biotechnology collaborations. Results: In this study, we describe two outcomes using our environmental strain collection that initiated biotechnology collaborations and identified bacterial candidates for drug discovery. Results from one project led to a partnership with an aquaculture company. A novel biosynthetic gene cluster involved in antagonistic activity was identified, whose product inhibits Aeromonas pathogens, which cause disease in freshwater fish. The other project involves a collaboration with a global commercial cleaning and equipment company to identify lipase activity among Bacillus strains for its potential use in bioremediation. Conclusions: The unique strain collection generated by students in the CURE led to collaboration with biotechnology companies, which contributed to natural product discovery of an antimicrobial product and active enzymatic activity, all of which benefit education and scientific discovery. Full article

Obesity is a growing public health concern linked to poor dietary habits, physical inactivity, and metabolic disturbances, which can be evaluated using complementary laboratory tests. Among pharmacological interventions, semaglutide, a GLP-1 receptor agonist, has shown promise by acting on the central nervous system to reduce appetite and stimulate insulin secretion, thereby improving the lipid profile and reducing inflammation biomarkers. This review focused on changes in lipid parameters and C-reactive protein (CRP) levels in overweight or obese individuals treated with semaglutide, based on phase 3 studies from the STEP program (“Semaglutide Treatment Effect in People with Obesity”). The STEP clinical trial program was conducted across 36 countries, reflecting a broad and diverse geographic representation. Key findings include significant reductions between placebo vs. semaglutide in body weight (−1.3 vs. −13.0 Kg), body mass index (−0.69 vs. −4.72 kg/m²), and waist circumference (−2.79 × −11.81 cm). Additionally, there were notable decreases in triglycerides (−0.67 vs. −20.89%), VLDL-C (−0.99 vs. 20.82%), and CRP levels (−15.45 vs. −55.55%). These changes reflect improvements in both inflammatory and metabolic markers. The observed benefits suggest that semaglutide may contribute to reducing comorbidities associated with metabolic syndrome and to the prevention of cardiovascular disease. Current evidence also supports its potential role in individualized treatment strategies based on patients’ clinical and biochemical profiles. However, despite these promising findings, further long-term studies are required to confirm the efficacy and safety of semaglutide across diverse populations. Full article

Background/Objectives: Upper respiratory tract infections (URTIs), including common cold and influenza, remain a major global health burden, and their symptomatic management often includes the use of herbal medicines alongside conventional therapies. The aim of this study was to evaluate the real-world use of herbal medicines as drug candidates in the management of URTIs in Estonia, with a focus on differences between pharmacy customers and pharmacy professionals. Methods: A cross-sectional survey was conducted among 905 participants, including 400 pharmacy customers and 505 pharmacy professionals (pharmacists and pharmacy assistants). Standardized questionnaires were used to assess the frequency of use, perceived effectiveness, and safety considerations of commonly used herbal substances and home remedies in adults and children. Results: Herbal medicines and home remedies were widely used, reported by 68% (95% CI: 63.4–72.6%) of pharmacy customers and 71% (95% CI: 67.0–75.0%) of pharmacy professionals. The most commonly used herbal substances included lemon (79%), ginger (57%), garlic (56%), raspberry (55%), and chamomile (50%). While most respondents perceived these remedies as effective for symptom relief, notable discrepancies were observed between customer and professional assessments of efficacy. The use of several herbal substances in children did not consistently align with European Medicines Agency recommendations, highlighting potential safety concerns. The findings demonstrate that widely used herbal substances represent real-world candidates for supportive URTI management; however, their perceived effectiveness and patterns of use are not always supported by regulatory guidance or clinical evidence. These results underscore the need for further pharmacological and clinical studies, as well as improved evidence-based communication between healthcare professionals and patients. Conclusions: The results allow the identification and prioritization of herbal substances as real-world drug candidates for further pharmacological and clinical development. Full article

The therapeutic landscape for heart failure (HF), particularly in patients with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF), has historically been characterized by limited effective disease-modifying options. The recent approval of nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), specifically finerenone, represents a major paradigm shift. This review synthesizes contemporary evidence, including the landmark FINEARTS-HF trial, which demonstrated significant reductions in cardiovascular death and heart failure hospitalizations in patients with left ventricular ejection fraction (LVEF) ≥ 40%. These findings contrast with the neutral overall results and subgroup limitations observed with steroidal MRAs such as spironolactone in the TOPCAT trial. Mechanistic distinctions, cardiorenal benefits, and emerging metabolic effects of finerenone are explored alongside its complementary role with sodium–glucose cotransporter-2 (SGLT2) inhibitors. Practical considerations for implementation, including patient selection, dosing, monitoring, and combination therapy strategies, are discussed. Overall, nsMRAs establish a new foundation for the management of HFmrEF and HFpEF and represent a critical advancement in contemporary heart failure therapeutics. Full article

Background/Objectives: Achillea millefolium is a well-known plant used in traditional medicine for the treatment of inflammation, gastrointestinal disorders, respiratory diseases, hypertension, and diabetes, among others. These effects are attributed to the metabolite content of flavonoids and terpenes such as achillin (1) and leucodin (2). Thus, the current investigation aims to standardize the extracts from A. millefollium based on the presence of 1 and 2 and relate them to their relaxant effect in ex vivo assays. Methods: A validated High-Performance Liquid Chromatography (HPLC) method was used to determine the concentration of the main compounds, employing standard molecules previously isolated from the same species and characterized by nuclear magnetic resonance (NMR) and X-ray diffraction. Also, the relaxant effects of both compounds and their combinations were assayed on aortic and tracheal rat rings in an organ bath. Results: Compounds (1) and (2) are the main compounds in hexane, dichloromethane, and hydroalcoholic extracts, present in different proportions. The relaxant effects in ex vivo models of the aorta and trachea showed that the sesquiterpene lactones achillin (1) [Trachea, maximum effect (Emax): 67.67 ± 5.01%, medium effective concentration (EC50): 304.44 ± 2.61 µM; Aorta: Emax: 63.94 ± 6.28%, EC50: 225.73 ± 4.49 µM)] and leucodin (2) (Trachea: Emax: 76.71 ± 4.73%, EC50: 266.40 ± 2.05 µM; Aorta, Emax: 72.96 ± 1.73%, EC50: 163.29 ± 2.99 µM) are responsible for the relaxant effects shown by the extracts. The observed effect is proportional to the concentration of these molecules, with hexane extracts being more active. Additionally, we demonstrate the safety of molecules 1 and 2 through toxicological studies recommended by the OECD. Conclusions: The isolated compounds achillin and leucodin are the primary constituents in the flowers of A. millefolium, with higher concentrations found in hexane extracts, particularly of achillin, which shows a correlation of 2.33 with respect to leucodin. This correlation is closely related to their relaxant effect, as these compounds are the main contributors to the relaxant response in the trachea and aorta, being more effective when used together. Full article

Background/Objectives: A matrix system for topical application was developed for a hydrophobic drug model, benzoyl peroxide (BPO), by turning it into its amorphous state to increase its bioavailability. BPO is commonly used to treat acne vulgaris; however, the commercially available products possess several drawbacks including poor absorption due to large crystal size and thus reduced efficacy and skin irritation. Methods: Several polymeric films containing amorphous BPO were successfully prepared for the first time from polymer + plasticizer colloidal dispersions and characterized. Results: The loaded BPO maintained its amorphous state even after 24 months of storage at 5 °C, and drug release could be modulated by adjusting the film compositions. The prepared films were obtained by solvent evaporation, and residual acetone remained below the level of quantification of the analytical method. In addition, the films were thin, flexible, transparent, bioadhesive, and able to remain on the skin for a clinically relevant period. Microscopic imaging confirmed a homogeneous and continuous morphology. Conclusions: The developed formulations may represent promising alternatives for the treatment of acne vulgaris. Full article

Background/Objectives: Oral cancer remains a major global health challenge, with persistent limitations in treatment efficacy and significant therapy-related morbidity. Probiotics, owing to their immunomodulatory, anti-inflammatory, and microbiota-regulating properties, have emerged as potential therapeutic and adjuvant agents. This scoping review aimed to systematically map and critically appraise preclinical and clinical evidence regarding the therapeutic and supportive effects of probiotics in oral cancer. Methods: A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar without temporal restrictions, including studies published up to February 2026. Eligible studies comprised in vitro, in vivo, and clinical investigations evaluating the effects of live or non-viable probiotic interventions on oral cancer biology and related clinical outcomes. Results: Twenty-one studies were included: 13 in vitro, 3 in vivo, and 6 clinical studies. Preclinical evidence indicates that strains such as Lactiplantibacillus plantarum, Lactobacillus acidophilus, and Lacticaseibacillus paracasei exert selective antiproliferative effects (up to 85% inhibition) via apoptosis induction, modulation of PTEN/MAPK and NF-κB signaling, and reduction in pro-inflammatory mediators. In vivo models demonstrated tumor growth suppression and improved survival without significant toxicity. Clinically, probiotics reduced treatment-induced oral mucositis, improved salivary function, and enhanced microbiota stability and patient-reported outcomes. However, evidence on direct oncological endpoints remains limited. Conclusions: Probiotics demonstrate biologically plausible, strain-specific antitumor and supportive effects, with the strongest evidence supporting their role as adjunctive agents, particularly in managing treatment-related complications. Further well-designed in vivo and clinical studies are required to define optimal strains, dosing strategies, and integration with standard oncologic treatments. Full article

Background/Objectives: Multidrug-resistant (MDR) Enterobacter spp. are critical pathogens within the ESKAPE group, frequently exhibiting resistance to carbapenems. Antimicrobial photodynamic therapy (aPDT) represents a promising non-antibiotic strategy to circumvent these resistance mechanisms. This scoping review aims to map the current evidence regarding the efficacy of aPDT in inactivating Enterobacter spp., identifying the most effective photosensitizers (PS), light parameters, and existing research gaps. Methods: A systematic search was performed across PubMed, Scopus, and Google Scholar (2013–2025) following PRISMA-ScR guidelines and registered on OSF. Studies were included if they evaluated aPDT against Enterobacter spp. (in vitro or in vivo) and provided quantitative data on microbial reduction. Data was extracted using a standardized charting form covering bacterial strains, PS type, light source, and viability reduction. The results from the eligible sources of evidence were synthesized narratively to address the review objectives. Results: Despite the clinical priority of Enterobacter, only seven studies met the eligibility criteria. Methylene Blue remains the most frequently studied PS, achieving reductions of 3–8 log₁₀. Emerging evidence highlights the synergistic efficacy of monocationic chlorins and graphene-based nanomaterials in enhancing the bactericidal effect of light-based treatments. Notably, aPDT demonstrated the ability to inactivate carbapenemases, the bacterial enzymes responsible for carbapenem resistance. However, only two studies evaluated in vivo applications, primarily within dental settings. Conclusions: aPDT is a promising method against MDR Enterobacter spp. and bypasses traditional resistance mechanisms. However, the limited number of studies indicates a significant knowledge gap. Future research should focus on standardized in vivo protocols and the synergy between aPDT and conventional antibiotics to support clinical translation. Full article

Background: Diabetes mellitus is a metabolic disturbance characterized by chronic hyperglycemia, which stems from defective secretion and/or action of insulin. D-Limonene has been studied for the confirmation of its antidiabetic and antioxidant effects. This paper aims to investigate the antidiabetic and antioxidants effects of D-Limonene in an experimental model of DM1. Methods: Female Wistar rats (180–250g) received streptozotocin (STZ, 45 mg/kg) intraperitoneally. Animals with capillary glycemia ≥ 250 mg/dL were considered diabetic. D-Limonene at oral doses of 12.5 mg/kg, 25 mg/kg and 50 mg/kg was administered during 28-day treatment. Water and food intake, weight gain and capillary glycemia were evaluated. At the end of the treatment, the following biochemical parameters were assessed: serum glucose, HbA1c, urea, creatinine, AST, ALT, GGT, ALP and albumin. The oxidative stress markers were determined in plasma, erythrocytes, and aortic homogenates: malondialdehyde, nitrite, myeloperoxidase, superoxide dismutase and catalase. Results: D-Limonene (25 and 50 mg/kg) significantly reduced serum glucose, HbA1c, AST, ALT, GGT and ALP when compared to DC, as well as plasma MDA and nitrite concentrations. Interestingly, D-Limonene (25 and 50 mg/kg) decreased both plasma and aortic myeloperoxidase activities, as well as increased both erythrocytic and aortic catalase activities. Conclusions: These findings, besides a marked D-Limonene-induced hypoglycemic effect, pave the way for further studies comprising a multi-target treatment by providing benefits on hepatic and vascular complications related to the diabetic condition. Full article