
Aconitum species have been used as traditional medicines in Asian countries for millennia, and contain well-characterized bioactive diterpenoid alkaloids. In contrast, American Aconitum species have been less studied, despite their close phylogenetical relationship to the important Asian medicinal species. This study aims to investigate the chemistry and bioactivity of American Aconitum, since they also produce diterpenoid alkaloids that possess toxicity. The chemical profiles of three American Aconitum species, A. delphiniifolium, A. columbianum, and A. uncinatum, and their four individual plant parts (roots, stems, leaves, and flowers) were studied using UPLC-qTof-MSe technique, and compared to Asian and European species. Multivariate including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze the chemical profiles. PCA suggests that American Aconitum is more chemically similar to Asian than European species. Using OPLS-DA, 29 unique marker compounds were found in American Aconitum, but not in the Asian or European species, we studied. Nineteen marker compounds were tentatively identified using Progenesis Qi and reference standards, including proved analgesic compounds such as talatisamine and 14-benzoyltalatisamine as well as other bioactive compounds. The results suggest that American Aconitum is a potential source for lead drugs. The cardiotoxicity of American Aconitum root extracts (200 μg/mL) was assessed using a zebrafish embryo model, and compared to the most widely used Asian species, A. carmichaelii. Aconitum delphiniifolium did not show any cardiotoxicity in this zebrafish model, as compared to A. carmichaelii and the control compound, aconitine. However, A. columbianum and A. uncinatum induced some morphological heart differences but not as profoundly as A. carmichaelii.
Abstract:Carex kobomugi is a dioecious perennial sedge native to coastal sand dunes in temperate northeastern Asia. While previous phytochemical investigations of this species have focused exclusively on its roots and rhizomes, this study represents the first report on the chemical constituents of its flowers. From the methanolic extract of the staminate flowers, two new styrylchromones, kobochromones B (1: ) and C (2: ), and a new suberin derivative, kobosuberin (5: ), were isolated. Their structures were elucidated by spectroscopic analysis (1D/2D NMR and HRESIMS). Their cytotoxic activity was assessed against four human cancer cell lines (HCT15, MCF7, 22Rv1, and PANC1), and the normal human hepatic stellate cell line LX-2 was used as a reference normal cell line. The study revealed a unique chemical profile of the staminate flowers, contributing to the understanding of the specialized metabolites in this dioecious species.
Abstract:Allergic rhinitis is a prevalent chronic inflammatory disorder of the nasal mucosa, imposing substantial medical and socioeconomic burdens. Thus, there is an urgent need to develop novel agents capable of both symptom relief and immune modulation. This study elucidates the mechanism by which tetrandrine alleviates allergic rhinitis through REV-ERBα activation and cholinergic pathway suppression. In ovalbumin-induced allergic rhinitis mice, intranasal tetrandrine significantly reduced sneezing frequency and nasal scratching versus controls, while decreasing serum histamine and substance P levels. Mechanistically, tetrandrine dose-dependently upregulated the mRNA and protein expression of REV-ERBα in nasal mucosa, enhancing its transcriptional repression in Gal4 reporter assays. Genetic ablation of Rev-erbα abolished tetrandrine's efficacy, exacerbating allergic rhinitis symptoms and inflammatory mediators. Crucially, tetrandrine suppressed choline acetyltransferase expression in nasal mucosa, reducing the level of acetylcholine; this effect was diminished by α-NETA (choline acetyltransferase inhibitor) pretreatment. This confirmed the essential role of REV-ERBα-dependent suppression of choline acetyltransferase-mediated acetylcholine synthesis in tetrandrine's therapeutic effect on allergic rhinitis. These findings establish tetrandrine as a novel agent targeting the circadian clock pathway and the circadian-allergy crosstalk, providing a new therapeutic strategy for allergic rhinitis.
Origanum calcaratum is an endemic Greek species found in Cyclades, the Eastern Aegean Sea, and Northeastern Crete. The aim of this study was the thorough phytochemical analysis of O. calcaratum extracts and the in vitro assessment against cellular senescence. Overall, 27 constituents were identified in methanolic and hydromethanolic extracts by LC-MS and isolation techniques, predominantly phenolic compounds. Both extracts and rosmarinic acid showed noncytotoxicity to healthy cells. In Li-Fraumeni cells, they exhibited concentration-dependent senolytic activity, with rosmarinic acid and the hydromethanolic extract showing significant effects at low concentrations, while the methanolic extract was active only at higher concentrations. These findings highlight the selective senolytic potential of O. calcaratum, particularly the hydromethanolic extract and rosmarinic acid, supporting further investigation as antisenescence agents.
Abstract:Achillea filipendulina, a polyphenol-rich species, was used to establish in vitro shoot cultures and to compare their phytochemical and biological properties with those of field-grown material. In vitro shoots cultivated on agar medium (AFiv) and in Plantform bioreactors (AFB) were extracted with ethanol, 50% ethanol, or water and evaluated alongside extracts from field-grown plants (AFH). HPLC-ESI-QTOF-MS/MS profiling revealed 37 phenolic constituents. At the same time, quantitative analysis by LC-MS confirmed that chlorogenic acid was the major compound, reaching the highest concentrations in AFH and AFB ethanol-based extracts. In contrast, AFiv samples contained lower but consistently detectable levels. Similarly, p-hydroxybenzoic acid, quercetin, and rutin were quantified above LOQ in nearly all samples, with their highest amounts in AFH EtOH and 50% EtOH extracts and the lowest levels in AFiv H2O extracts, demonstrating clear solvent- and biomass-dependent variation. Abstract:AFH extracts showed the strongest antioxidant activity (IC50 50% EtOH=30.1; TPC = 1.32 mg GAE/g DW), while AFiv and AFB displayed lower TPC (0.36 - 0.38 and 0.19 - 0.30 mg GAE/g DW) and weaker activity (IC50 = 254 µg/mL and ≥ 1000 µg/mL). In tyrosinase assays, AFiv extracts were the most potent, inhibiting murine tyrosinase by 56.8 - 62.8% and human tyrosinase by 17.6 - 29.9%, comparable to kojic acid, whereas AFH and AFB demonstrated weaker or selective inhibition. Abstract:Cytotoxicity testing showed that AFH extracts reduced HaCaT viability by 25 - 38%, while AFiv and AFB were non-cytotoxic and exhibited reduced or no cytotoxicity toward melanoma cells. Moreover, technological validation of the most potent AFiv 50EtOH extract within model O/W and W/O emulsions demonstrated exceptional 30-day physicochemical stability and compatibility.
Abstract:Elaeocarpus ganitrus, popularly known as Rudraksha, is of immense holistic importance in traditional Indian culture with spiritual and medicinal benefits. The present study aims to characterize and explore the cytotoxic and tumor inhibitory potential of hydroalcoholic extract of Rudraksha beads in preclinical models. Hydroalcoholic extract was prepared from powdered Rudraksha beads and was characterized through qualitative and quantitative phytochemical analysis, FT-IR, and LC-MS/MS analysis. In vitro cytotoxic activity of Rudraksha bead extract was evaluated in PC3, U87MG, A549, HCT116, FaDu, MCF-7, and LLC1 cell lines by MTT assay. Apoptotic activity was assessed by Western blot analysis of Bax, Caspase-3, and Cleaved Caspase-3 proteins in the HCT116 cell line. In vivo antitumor efficacy was evaluated in the LLC1 allograft and HCT116 xenograft mouse model. Hydroalcoholic extract of Rudraksha bead showed abundance of polyphenolic compounds and their subtypes like phenols, flavonoids, and anthocyanins in different analytical techniques. Treatment with hydroalcoholic extract elicited a dose-dependent decrease in cell viability in all the tested cell lines, with the best response in HCT116 (CC50 = 47.22, 95% confidence interval (CI): 42.75 - 49.06 µg/mL), with upregulated expression of pro-apoptotic markers, Caspase-3 (1.53-fold), Cleaved Caspase-3 (1.47-fold), and Bax (6.4-fold). Treatment with 500 mg/kg of Rudraksha extract in the LLC1 tumor allograft model (QD × 9 days) and HCT116 xenograft model (QD × 21 days) demonstrated significantly reduced tumor volume in comparison to the vehicle control. Hydroalcoholic extract of Rudraksha demonstrated a promising tumor inhibition response in preclinical settings, therefore making it a potential therapeutic candidate for cancer treatment.
Abstract Infectious diseases caused by viruses, fungi, parasites, and bacteria continue to pose significant challenges to public health globally. In this context, the Ibero-American Program of Science and Technology for Development (CYTED) Network, “Potential Antimicrobial Agents Present in Plant Foods of Regional Interest” (REDALIM-MIC), aims to detect antimicrobial compounds in edible plants from Ibero-American countries and to promote collaborative research on their potential applications in health and nutrition. This report summarizes the main discussions and key outcomes of expert meetings conducted within the REDALIM-MIC Network, underscoring the importance of integrated and interdisciplinary research, with particular emphasis on the potential of edible plants as innovative and sustainable sources of bioactive compounds for the prevention and control of infectious diseases. Key outcomes included the identification of promising plant species and the prioritization of bioactive extracts for further phytochemical characterization and pharmacological evaluation. The potential application of these findings in the development of scientific evidence-based functional claims for foods and novel therapeutics, as well as the importance of strengthening regional collaboration, was also recognized. The REDALIM-MIC Network focuses on detecting antimicrobial compounds in edible plant species, evaluating their immunomodulatory properties, assessing their nutritional and health value, and fostering collaboration among Ibero-American institutions to support innovative, food-based approaches for preventing and managing infectious diseases. During the meetings, key topics such as regulatory frameworks, analytical techniques, quality control, methodologies, and cell-based assays for the evaluation of their antimicrobial activity were discussed. In addition, good agricultural practices and biotechnological tools for sustainable production were addressed.
Abstract:Ginsenoside Rd shows positive effects on T2DM, but its mechanism remains unclear. In this study, we explored its mechanism focusing on inflammation levels in the pancreas and intestine, and provided evidence that this is related to modulation of the GLP-1/MAPK/NF-κB signaling pathway. We recorded and compared changes in metabolic indicators of T2DM, and tested levels of GLP-1 and GLP-1R through immunohistochemistry, Western blotting, and PCR after the mice were euthanized. Additionally, we detected the effects of ginsenoside Rd on inflammatory related molecules such as AMPK, Sirt1, MAPK, and NF-κB by ELISA, transcriptomics, Western blot, and PCR, while also conducting in vitro experiments to investigate the GLP-1 signaling pathway. After treatment with ginsenoside Rd, blood glucose decreased and insulin resistance weakened in db/db mice, and the results showed an increase in the expression of GLP-1 and GLP-1R. Transcriptome analysis revealed differences in inflammatory response-related signaling pathways after treatment, and Western blot results showed increased AMPK phosphorylation and decreased MAPK phosphorylation. Consistent experimental results were also obtained in vitro. In conclusion, our data suggest that ginsenoside Rd may ameliorate T2DM in db/db mice, potentially through the inhibition of inflammatory responses in the intestine and pancreas, an effect that might be mediated by the promotion of GLP-1 secretion.
Abstract:Phytochemical study of Cedrus atlantica aerial parts apolar extract led to the isolation of a new abietane diterpene (1: ), an abietane diterpene reported for the first time as a genuine natural product (2: ), 2 new megastigmane glycosides (3: -4: ), and 9 known compounds (5: -13: ), including 7 abietanes. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRMS experiments. The crude extract was then evaluated through a broad screening against both Gram-positive and Gram-negative bacterial strains, with Staphylococcus epidermidis being the only affected microorganism. In a next step, a selection of pure compounds was also investigated, and the diterpene 15-hydroxydehydroabietic acid (15-HDAA) (11: ) was shown to exhibit detectable antibacterial activity against S. epidermidis. Growth kinetics analysis revealed a clear modulation of bacterial growth at sub-minimum inhibitory concentration (MIC), indicating a measurable physiological impact on the bacterium. This effect, when combined, allows a significant reduction in the effective concentration of ampicillin.
Abstract:The growing urgency to reduce antimicrobial and antiparasitic use in livestock has renewed scientific interest in medicinal plants as sustainable components of veterinary healthcare. However, the absence of a dedicated regulatory framework for herbal veterinary medicinal products (HVMPs) in the European Union continues to hinder their wider application. Abstract:The need for a science-based, multi-criteria framework to identify medicinal plant species as sources of active substances of herbal origin, with the highest potential for future inclusion in a dedicated EU registration pathway for HVMPs, resulted in the establishment of a multidisciplinary expert panel. The panel evaluated over 100 medicinal plant species with documented veterinary application, using a structured scoring system integrating regulatory, pharmacopoeial, toxicological, and sustainability sources. These included regulations and documents related to veterinary, pharmaceutical, food, and feed data, as well as considerations for conservation. Weighted scores reflecting all these aspects were applied to rank the species. Abstract:The assessment resulted in the creation of List A, which contains the most promising candidates for future HVMPs, and List B, which compiles plant species whose simplified registration is currently not considered a priority or is not advisable based on the available data. Eighty-three species received positive overall scores. These medicinal plants demonstrate strong regulatory recognition, pharmacopoeial inclusion, and well-documented safety profiles, highlighting their suitability for evidence-based veterinary use. Abstract:The proposed framework offers a clear, reproducible method for prioritizing botanical species for regulatory consideration as HVMPs. It supports EU initiatives to enhance sustainable animal health, antimicrobial stewardship, and innovation in veterinary phytotherapy.
Abstract:Glechoma hederacea (ground ivy) is an aromatic perennial plant extensively utilized in traditional medicine. Its therapeutic properties have been recorded in Europe since antiquity. Traditionally, it is still used to treat gastrointestinal disorders, liver/bile diseases, respiratory ailments, and skin disorders. This review presents, for the first time, an in-depth examination of ethnopharmacology, phytochemistry, botany, safety of use, biological activity, and non-medical aspects associated with ground ivy. The data were extracted through detailed probing of key databases, including PubMed, Web of Science, Scopus, and SciFinder. In addition, books, papers from conference proceedings, and websites were used. This study reveals that compounds belonging to various classes, including phenolic acids, flavonoids, lignans, alkaloids, and terpenoids, have been identified. Crude extracts, fractions, and some individual compounds have shown various pharmacological activities, including hepatoprotective, anti-inflammatory, antioxidant, anticancer, and melanogenesis-modulating effects. Apart from its value in phytotherapy, G. hederacea also shows potential as a natural pesticide and stabilizing agent in the food industry. The traditional medicinal uses of the ground ivy, combined with modern scientific research, underscore its pharmacological potential. However, future studies should incorporate relevant animal experiments and clinical studies to provide a more comprehensive assessment of the efficacy and bioavailability. Although there is a rich literature on secondary metabolites detected in G. hederacea, it seems right to fill in which compounds are determinants of a given activity. Finally, research on using G. hederacea as a natural pesticide, which could lead to its implementation, warrants further investigation.
Abstract:Mitragyna speciosa (kratom) is a psychoactive plant native to Southeastern Asia, belonging to the Rubiaceae family. Traditionally, its fresh leaves have been consumed in the region for centuries due to their therapeutic properties, including pain relief. The leaves contain a variety of phytochemicals with the alkaloids being the most biologically significant constituents. In the present study-the first investigation exploring sustainable extraction methods for kratom-47 natural deep eutectic solvent (NaDES) systems were screened. The most effective system demonstrated significantly higher extraction efficiency compared to commonly used organic solvents. The food-grade system, lactic acid : glucose was subsequently selected for optimization using a one-factor-at-a-time approach, and the optimal conditions were a molar ratio of 4 : 1 and a water content of 20%. Further optimization using a Box-Behnken design and response surface methodology identified the optimal extraction conditions as a solid-to-liquid ratio of 30 mg/mL, a temperature of 70 °C and an ultrasound treatment time of 12 min. Finally, three recovery methods were evaluated: solid phase extraction (including strong cation exchange and reversed-phase types), macroporous resins (six types), and acid-base extraction. The highest recovery yields were obtained with strong cation exchange solid phase extraction (95%) followed by the macroporous resins XAD 18 and XAD 1600 N (85%).
Abstract:Cultivated lichen mycobionts represent a valuable resource for obtaining unique natural compounds. Mycobionts of Astrothelium straminicolor and Nigrovothelium inspersotropicum, collected in Vietnam, were isolated, cultivated, and subjected to chemical investigation. Consequently, three new compounds, straminones A - B (A1: and A2: ) and chlorosemivioxanthin (N1: ), along with five known compounds, 3S,4R-(+)-4-hydroxymellein (A3: ), 6-methoxymellein (A4: ), vioxanthin (N2: ), pigmentosin A (N3: ), and semivioxanthin (N4: ), were isolated and structurally elucidated. Straminones A and B represent the first examples of 3-methylhexahydrocyclopenta[c]pyran-1(3H)-one skeletons found in nature. The relative configuration of A1: was confirmed by DFT calculation. Compounds A3: and N4: demonstrated weak alpha-glucosidase inhibitory activity, with IC50 values of 314 and 366 µM, respectively. The other compounds showed no inhibition in the tested assay. Notably, compounds N1: -N3: showed significant inhibitory effects on NO production, with IC50 values ranging from 14 to 25 µM, compared with the positive control L-NMMA (IC50 = 49 µM). Further molecular docking clarified the inhibitory mechanism of the active compounds.
Abstract:Hydroxychloroquine (HCQ), a commonly used drug for Sjögren's syndrome (SS), is ineffective, highlighting the need for better treatments for salivary gland damage in SS. The study evaluated the effects of Polygonatum sibiricum (HJ) on SS using non-obese diabetic (NOD) mice treated with HJ, HCQ, or both for six weeks. Body weight, saliva levels, and submandibular gland histology were assessed. Various techniques were used to analyze apoptosis and oxidative stress. Network pharmacology identified therapeutic targets, and lentivirus technology was used to suppress CHRM3 gene expression to understand HJ's mechanisms against SS. HJ treatment significantly mitigates salivary gland damage, resulting in increased body weight, reduced water intake, and improved saliva flow rates. Histological evaluations revealed HJ reduced lymphocytic infiltration, restored glandular architecture, and alleviated oxidative stress. In addition, the study has the following key mechanistic finding: HJ upregulated the expression of the target proteins CHRM3 and AQP5 in submandibular glands. Additionally, HJ can significantly enhance the expression of CHRM3 and AQP5 in human salivary gland (HSG) cells after silencing CHRM3. This study revealed that HJ may act as a novel SS treatment by activating the CHRM3/AQP5 axis, promoting water channel transport, alleviating salivary gland damage, and enhancing saliva secretion. Moreover, the combination of HJ and HCQ could significantly improve the therapeutic benefit. These findings provide a new therapeutic strategy for SS.
Abstract:The scientific literature is increasingly challenged by miscitation, publication bias, and the uncritical perpetuation of false information. One such case concerns the purported presence of caffeine in damiana, a botanical ingredient marketed for "sexual well-being". While consumer perception and regulatory implications make caffeine content highly relevant, a systematic review of the literature indicates that claims of caffeine in damiana (Turnera diffusa) largely stem from erroneous or circular referencing, including citations of studies where caffeine was never reported. To address this discrepancy experimentally, we conducted NMR analyses on authenticated aerial and seed material of T. diffusa and seeds of T. ulmifolia. No caffeine was detected, with a detection limit of < 4 nM, corresponding to < 4 µg caffeine per daily serving of damiana. These findings confirm that damiana is effectively caffeine-free. Beyond correcting a specific phytochemical misconception, this study highlights how flawed referencing practices can perpetuate modern "scientific myths", emphasizing the need for more rigorous citation ethics and the value of experimental data. Addressing such errors is critical not only for scientific accuracy but also for consumer trust and evidence-based regulatory decision-making.
Abstract:Borassus aethiopum, a widely used West African palm, is a staple food source and a traditional medicinal plant with emerging relevance to immunometabolic pharmacology. This narrative review integrates ethnobotanical, phytochemical and pharmacological evidence, with particular emphasis on oxidative stress, cytokine signalling and low-grade inflammation. Available non-clinical and limited human data indicate that preparations derived from inflorescences, fruit pulp and kernels may exert antioxidant, anti-inflammatory and cardiometabolic effects, although the evidence base remains heterogeneous. Major constituents, including polyphenols, terpenoids, sterols, saponins and lipid fractions, are discussed in relation to redox-sensitive and inflammation-related pathways, particularly nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2), as well as cytokine networks implicated in metabolic and cardiovascular disorders. In rodent models, B. aethiopum preparations have been associated with reductions in oedema, nociception, pyrexia, hyperglycaemia and dyslipidaemia, often alongside lower C-Reactive protein and oxidative stress markers. Preliminary human studies using B. aethiopum-enriched bread in individuals at cardiometabolic risk have reported improvements in blood pressure (BP) and lipid profile, suggesting a possible effect on low-grade inflammatory status. Overall, the available evidence supports a multi-target framework in which B. aethiopum may influence cytokine-related and redox-regulated processes, while highlighting substantial limitations, including variable extraction methods, incomplete phytochemical characterisation, sparse cytokine measurements and small clinical samples. Future work should prioritise standardised chemo-fingerprinting, multiplex cytokine profiling, metabolomic integration and pragmatic dietary or extract-based interventions in at-risk populations. B. aethiopum may therefore serve as a useful model for a structured pharmacological evaluation of plant-derived foods within an immunometabolic context.
Abstract:Previous studies have highlighted the effects of lemongrass essential oil (Cymbopogon citratus) on the cardiovascular system, particularly its hypotensive and vasodilatory properties. Given the heart's crucial role in blood pressure regulation, this study aimed to investigate the impact of lemongrass essential oil (EOCC) on cardiac excitation-contraction coupling and voltage-gated ion channel currents. Chemical analysis of EOCC, conducted through gas chromatography-mass spectrometry, identified geranial (39.9%) and neral (27.4%) as the primary components. The effect of EOCC on cardiac contractility was assessed using isolated guinea pig atria. The results showed that EOCC decreased both the contraction amplitude and the frequency of spontaneous atrial contraction in a concentration-dependent manner (IC50 values of 106.8 µg/mL, 95% CI=78.9 to 133 µg/mL and 258.4 µg/mL, 95% CI=202.7 to 443.2 µg/mL n = 5 - 8, respectively). Notably, EOCC exhibited arrhythmogenic activity, since it induced spontaneous contractions in isolated atrial preparations. Additionally, in an arrhythmia model induced by ouabain, EOCC significantly reduced the time to arrhythmia onset by 67.8% (n = 4). To further explore the mechanisms of the essential oil in atrial excitability, we employed the patch-clamp technique on isolated ventricular cardiomyocytes to examine EOCC's effects on the L-type calcium current (ICa-L). The human embryonic kidney cell line (HEK293) transiently expressing human NaV 1.5 was used to study the effects on cardiac sodium currents (INa). EOCC reduced the peak amplitude of both INa and ICa-L in a concentration- and voltage-dependent manner, with IC50 values of 299.7 µg/mL (95% CI=241.5 to 358 µg/mL, n = 6 - 7) for INa and 132.8 µg/mL (95% CI=71 to 173.8, n = 9) for ICa-L. In conclusion, the negative inotropic of EOCC may significantly contribute to its hypotensive effects. However, the association of relatively low concentrations of EOCC with cardiac arrhythmias raises concerns about its medicinal use.
Abstract:Herbal medicinal products (HMPs) are widely used in European paediatric practice, but formal authorisations for their use in children remain limited. Following the 2024 workshop in Krakow, the Foundation Plants for Health (FPfH) organised a further workshop in Naples on 31 August 2025 as part of the 73rd International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA) to present updates of recent activities in the field of real-world data (RWD) and real-world evidence (RWE) for rationalising the usage of herbal medicines in children. Speakers presented concrete new data sources - private health insurance claims, patient reported outcome cohorts, and a social-media-based user survey - as well as modern methods in epidemiology. The workshop concluded that decision-relevant paediatric data on the use of HMPs can be generated efficiently by establishing new RWD data sources. For the subsequent next steps, it is necessary to engage with regulators to open usage of these data pools in regulatory practice.
The Japanese pearl tree (Styphnolobium japonicum), an ornamental species native to East Asia, has long been valued in traditional Chinese medicine and is now gaining renewed attention for its multifaceted pharmacological potential. This review synthesizes the current knowledge of its bioactive compounds, particularly flavonoids such as genistein, rutoside, quercetin, and sophoricoside, and their broad-spectrum biological activities, including antioxidant, anti-inflammatory, antimicrobial, neuroprotective, and wound-healing effects. These phytochemicals contribute to protective mechanisms against oxidative stress, skin photoaging, osteoporosis, cardiovascular dysfunction, and metabolic disorders such as diabetes and obesity. Emerging evidence also supports their role in managing neurodegenerative and inflammatory diseases, alopecia, and postmenopausal symptoms. Despite its promise, the clinical translation of S. japonicum remains limited by gaps in safety, pharmacokinetic characterization, and standardized extraction protocols. Looking ahead, integrative approaches combining phytochemistry, pharmacogenomics, and advanced biotechnology are expected to unlock its full therapeutic potential. By bridging traditional use with precision medicine and sustainable bioprocessing, S. japonicum stands as a prospective source of next-generation plant-based therapeutics for modern healthcare.