Journal of ethnopharmacology最新文献

{"title":"Aframomum alboviolaceum (Ridl.) K.Schum. leaf essential oil protects against Benzo(a)pyrene induced prostate cancer in Wistar rats","authors":"Chiara Nange Adjoffoin , Sefirin Djiogue , Emmanuella Regine Mayemi , Florette Motoum Tedjo , Berlise Yengwa Bakam , Benderline Christine Nana , Rosette Megnekou , Stéphane Zingue , Dieudonné Njamen","doi":"10.1016/j.jep.2025.120691","DOIUrl":"10.1016/j.jep.2025.120691","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Regardless of recent research on cancer treatment, the incidence and mortality are still increasing. PCa is the most diagnosed cancer and the second leading cause of death in men worldwide. <em>Aframomum alboviolaceum</em> (Ridl.) K. Schum. is traditionally used in Cameroon to treat various illnesses including inflammatory diseases and cancer. Previous experiments <em>in vitro</em> have indicated that the crude extract possesses cytotoxic properties against multifactorial drug-resistant cancer cell lines. Furthermore, the plant is rich in diterpeniods, which are potential candidates in cancer treatment. However, there is no scientific investigation on the preventive effects of its leaf essential oil against prostate cancer in Wistar rats.</div></div><div><h3>Aim of the study</h3><div>To investigate the preventive effects of <em>A. alboviolaceum</em> leaf essential oil against benzo(a)pyrene -induced PCa in Wistar rats.</div></div><div><h3>Material and methods</h3><div>49 male rats were used in this experiment and PCa was induced in 35 rats by successive administration of bicalutamide(oral), testosterone(subcutaneous) and benzo(a)pyrene(intraprostatic), except those in the sham operated and pharmacological group. The rats were distributed into the normal (SHAM) and negative (BENZO) control groups which received 0.1 % tween 80, positive control group (CASO) was treated with casodex. Three therapeutic groups were treated with <em>A. alboviolaceum</em> leaf essential oil at doses of 10, 100 and 200 mg/kg BW. To evaluate the toxicity of the oil, a pharmacological group treated exclusively with <em>A. alboviolaceum</em> leaf essential oil without carcinogen at a dose of 200 mg/kg BW was added. Animals were treated for 210days, after which tumor incidence, tumor burden and volume, Serum PSA’ level, antioxidant and inflammatory status, liver and kidney biomarkers and histopathology were assessed. The acute toxicity of the oil was assessed using the classical oral toxicity test for 14 days.</div></div><div><h3>Results</h3><div>After 210 days of treatment, six out of seven animals in the negative control group (treated with B(a)P) developed tumors, corresponding to a tumor incidence of 87 %. Similarly, a significant increase in the concentrations of pro-oxidants (MDA and nitrites) and pro-inflammatory cytokines (IL-6, TNF-α, VEGF and TGF-β1) was observed compared to the normal control group. <em>A. Alboviolaceum</em>, just like Casodex, prevented B(a)P-induced tumorigenesis by significantly reducing tumor incidence to 14 % at a dose of 200 mg/kg. Similarly, it was observed that this essential oil led a significant decrease in the levels of pro-oxidants and pro-inflammatory cytokines associated with an increase in the concentrations of antioxidants (SOD, Catalase and GSH) and anti-inflammatory (IL-10 and GM-CSF) cytokines. No major signs of toxicity were observed throughout the experiment. No significant vari","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120691"},"PeriodicalIF":5.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coptidis Rhizome alleviates dexamethasone- and fructose-induced metabolic disorder in rats as an inducer of HO-1 agonist via erythrocyte metabolism.","authors":"Xiaolin Xie, Haikang Fu, Zhixuan Ai, Ziwei Huang, Wenwen Tan, Qingfeng Xie, Yuhong Liu, Yucui Li, Jiannan Chen, Xiaobo Yang, Ziren Su, Zhengquan Lai, Jianhui Xie","doi":"10.1016/j.jep.2025.120713","DOIUrl":"https://doi.org/10.1016/j.jep.2025.120713","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Coptidis Rhizome (CR), a cornerstone medicinal herb, is routinely used to treat metabolic diseases for centuries in China. However, the potential mechanism has not been completely elucidated. Preceding investigation has reported that berberine in CR can bind to hemoglobin (Hb) and utilize erythrocyte-Hb self-assembly drug delivery system to significantly upregulate HO-1 expression.</p><p><strong>Aim of the study: </strong>This study was designed in a pioneering endeavor to explore the therapeutic potential and underlying mechanism of CR in dexamethasone- and fructose-induced glycolipid metabolism disorders (GLD) rat models.</p><p><strong>Material and methods: </strong>The major elements of CR were identified by high performance liquid chromatograph (HPLC). Dexamethasone- and fructose-induced rat GLD model was constructed. Glucolipid metabolism, oxidative status, and insulin sensitivity were investigated. Histopathological, transcriptomic, in silico simulations, immunofluorescence, immunohistochemistry, and Western blotting analyses were performed to gain further mechanism insight.</p><p><strong>Results: </strong>HPLC analysis revealed that berberine, palmatine, coptisine, epiberberine, and jatrorrhizine were detected in CR, with berberine as the most abundant. Administration of CR favorably regulated the organ indexes, and significantly improved glucose metabolism by decreasing the FBG and GSP levels along with improved OGTT. CR promoted insulin sensitivity by suppressing the increased levels of FINS, HOMA-IR and ISI, and concomitantly improving ITT. Furthermore, CR normalized lipid metabolism by decreasing the elevated TG, TC and LDL-C levels. Additionally, CR effectively ameliorated histopathological deterioration in pancreatic and hepatic tissues and reduced serum ALT and AST activities. CR also ameliorated oxidative stress by remarkably lowering hepatic ROS fluorescence intensity and serum MDA content, whereas enhancing SOD and CAT enzymatic activity, and T-AOC level. Hepatic transcriptomics analysis revealed the oxidative stress-related gene HMOX1 encoding HO-1 and AMPK pathway critically involved in the therapeutic effect of CR. Furthermore, CR was found to significantly up-regulate the protein expression levels of HO-1, NQO1 and p-AMPK. On the other hand, in silico simulations indicated that strong van der Waals forces interaction between these alkaloids and HO-1. Notably, CR exhibited potent HO-1 agonistic activity comparable to the HO-1 inducer hemin, as manifested by enhanced HMOX1 mRNA level, HO-1 expression level, cytoplasmic HO-1 fluorescence intensity, carbon monoxide production, and reduced heme level, which were the markers of erythrocyte metabolism. Administration of CR or hemin significantly improved fasting glycemia, blood fat, insulin sensitivity, and antioxidant capacity. Nevertheless, these effects were observably reversed by the HO-1 inhibitor zinc protoporphyrin (ZnPP).</","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120713"},"PeriodicalIF":5.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing the potential of medicinal plants in the malaria fighting: In vitro and in vivo antiplasmodial activities of Feretia apodanthera Delille (Rubiaceae).","authors":"Saamou Isaac Boni, Domonbabele François de Sales Hien, Kouliga Benjamin Koama, Mariam Youba, Virginie Vaissayre, Zachari Kabre, Stephane Dussert, Abdoulaye Diabate, Thierry Lefevre, Rakiswende Serge Yerbanga, Mohamed Haddad, Nâg-Tero Roland Meda","doi":"10.1016/j.jep.2025.120729","DOIUrl":"10.1016/j.jep.2025.120729","url":null,"abstract":"<p><strong>Ethnopharmacological relevanc: </strong>Feretia apodanthera is traditionally valued for its antibacterial, antiparasitic, and antiviral properties. With Plasmodium resistance to antimalarial drugs increasing, the need for alternative therapies has become urgent. Medicinal plants like F. apodanthera offer promising candidates for new treatments.</p><p><strong>Aim of the study: </strong>This study investigates the antiplasmodial potential of F. apodanthera to support local malaria control strategies.</p><p><strong>Material and methods: </strong>The antiplasmodial activity of F. apodanthera leaf, stem bark and root extracts were assessed in vitro using the SYBR Green assay and in vivo with Plasmodium berghei NMRI-infected mice through suppressive, curative, and prophylactic approaches. Toxicity was evaluated in mice and red blood cells, while phytochemical composition was analysed using UHPLC-HRMS and GC-MS.</p><p><strong>Results: </strong>F. apodanthera extracts were non-toxic (LD₅₀ > 5000 mg/kg) and exhibited strong in vitro trophozoitocidal activity (IC₅₀: 0.140 ± 0.015-0.620 ± 0.014 μg/mL) with minimal haemolysis (<1 %). In vivo, parasitaemia reduction was tissue-and dose-dependent, with leaf showing the highest chemosuppressive efficacy across suppressive (32.33 ± 9.42 % at 125 mg/kg, 68.01 ± 9.73 % at 250 mg/kg, and 76.31 ± 8.77 % at 500 mg/kg), curative (68.41 ± 12.41 % at Day 5 and 63.41 ± 12.28 % at Day 7), and prophylactic (63.60 ± 8.78 % at Day 5 and 57.10 ± 13.20 % at Day 7) tests. Root and stem bark extracts had moderate chemosuppressive efficacy across the three tests. UHPLC-HRMS analysis revealed a diverse range of bioactive compounds in leaf, stem bark and root extracts, including terpenoids, polyphenols, flavonoids, tannins, carbohydrates, iridoids, and alkaloids, and GC/MS analysis found alkaloids only in leaf and root extracts. The compounds identified may contribute to their antiplasmodial activity. Notably, polyphenols and alkaloids compounds were more abundant in leaf, which may explain their higher antiplasmodial activity.</p><p><strong>Conclusion: </strong>Overall, all three organs of F. apodanthera exhibited antiplasmodial activity both in vitro and in vivo while remaining non-toxic. The leaf demonstrated superior chemosuppressive and schizonticidal activity, along with strong trophozoitocidal effects, whereas the root and stem bark excelled in trophozoitocidal activity. These findings support the traditional use of F. apodanthera in malaria treatment and highlight its potential for developing antimalarial phytomedicines.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120729"},"PeriodicalIF":5.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ganoderma lucidum polysaccharides alleviate non-alcoholic fatty liver disease by modulating gut microbiota against TLR4/NF-κB/MAPK pathway and activating AMPK pathway","authors":"Huajie Zhao,&nbsp;Yun Li,&nbsp;Ningning Liu,&nbsp;Ping Chen,&nbsp;Xiaojie Yu,&nbsp;Guofang Li,&nbsp;Baoguo Deng,&nbsp;Duan Li,&nbsp;Fan Yang,&nbsp;Ge Wang","doi":"10.1016/j.jep.2025.120723","DOIUrl":"10.1016/j.jep.2025.120723","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Ganoderma lucidum</em> (Leyss. ex Fr.) Karst has been a revered traditional Chinese medicinal herb, widely used in folk medicine to treat various metabolic diseases due to its remarkable bioactivities. Among its active components, <em>G. lucidum</em> polysaccharides are particularly recognized as one of the main contributors to its therapeutic effects. However, the therapeutic efficacy of <em>G. lucidum</em> polysaccharides against non-alcoholic fatty liver disease (NAFLD) and its underlying mechanisms remain to be elucidated.</div></div><div><h3>Aims of the study</h3><div>This study aimed to assess the therapeutic efficacy of a novel polysaccharide (EPGLa) derived from <em>G. lucidum</em> in the treatment of NAFLD and to elucidate its underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>The chemical characterization of the isolated and purified EPGLa was conducted using monosaccharide composition analysis, Fourier-transform infrared (FT-IR) spectroscopy, molecular weight determination, methylation analysis, and 1D/2D nuclear magnetic resonance (NMR) spectroscopy. Following the establishment of a NAFLD mouse model, the therapeutic effect of EPGLa on NAFLD was assessed, and its underlying mechanism was clarified.</div></div><div><h3>Results</h3><div>The backbone of EPGLa consists of the following glycosidic linkages: →6)-β-D-Glc<em>p</em>-(1→, →3)-β-D-Glc<em>p</em>-(1→, →4,6)-α-D-Glc<em>p</em>-(1→, →3,6)-β-D-Man<em>p</em>-(1→, →2)-α-D-Man<em>p</em>-(1→, and →4)-β-D-Gal<em>p</em>-(1 → . Its branches are composed of β-D-Glc<em>p</em>-(1→, β-D-Glc<em>p</em>-(1 → 3)-β-D-Glc<em>p</em>-(1→, and α-L-Fuc<em>p</em>-(1 → . <em>In vivo</em> results demonstrated that EPGLa effectively alleviated NAFLD by promoting the growth of beneficial gut bacteria to repair the intestinal barrier against Lipopolysaccharides (LPS)/toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (MAPK) pathways, and simultaneously enhancing short-chain fatty acid (SCFA) production to activate the AMP-activated protein kinase (AMPK) pathway. To further validate these findings, we employed fecal microbiota transplantation (FMT), which confirmed the role of EPGLa in modulating gut microbiota against NAFLD.</div></div><div><h3>Conclusion</h3><div>Our study provides compelling evidence that EPGLa holds promise as a potential therapeutic agent for the intervention of NAFLD, and our findings also offer novel insights into the therapeutic targets of other bioactive polysaccharides.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120723"},"PeriodicalIF":5.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory activity of 7-methoxycoumarin isolated from Ayapana triplinervis Vahl (Compositae) via inhibition of inflammatory mediators - In-vivo, in-vitro and in-silico studies.","authors":"Binoy Varghese Cheriyan, Jaikumar Shanmugasundaram, Vijaykumar Sayeli, Jagan Nadipelly, Lally Hanna Luke, Shanmugam Anandakumar","doi":"10.1016/j.jep.2025.120722","DOIUrl":"https://doi.org/10.1016/j.jep.2025.120722","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Ayapana triplinervis is a medicinal plant traditionally used in South India for treating wounds and insect bites. Fresh bruised leaves are applied on affected parts. Its widespread use in wound healing inspired this study, which investigates the anti-inflammatory potential of its major bioactive compound, 7-methoxycoumarin. Since inflammation is a key component of the wound healing process, it is hypothesized that the compound's anti-inflammatory effect may underlie its traditional therapeutic efficacy.</p><p><strong>Aim of the study: </strong>To evaluate the anti-inflammatory activity of 7-methoxycoumarin isolated from the leaves of Ayapana triplinervis and to elucidate its underlying mechanisms using in vivo, in vitro and in silico approaches.</p><p><strong>Material and methods: </strong>The in vivo anti-inflammatory effect of 7-methoxycoumarin (3.5 and 7 mg/kg) was assessed in rats using the carrageenan-induced paw edema model, with indomethacin as the reference drug. In vitro assays were conducted to determine inhibition of COX-2, IL-1β and TNF-α. Molecular docking studies were carried out using Patch Dock to validate the inhibitory effect on the above inflammatory mediators.</p><p><strong>Results: </strong>7-Methoxycoumarin significantly reduced paw edema in a dose- and time-dependent manner (p < 0.001), showing 49.78% inhibition compared to 57.93% by indomethacin. It inhibited COX-2 with an IC₅₀ of 17.26 μM (vs. 4.89 μM for celecoxib) and IL-1β and TNF-α with IC₅₀ values of 110.96 μM and 34.32 μM, respectively (vs. 96.10 μM and 29.20 μM for dexamethasone). Docking studies revealed good binding affinities at COX-2 (-184.30 kcal/mol), IL-1β (-158.45 kcal/mol) and TNF-α (-193.83 kcal/mol) receptors.</p><p><strong>Conclusion: </strong>The present study demonstrated the anti-inflammatory potential of 7-methoxycoumarin and provide pharmacological support for the traditional use of Ayapana triplinervis in wound healing.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120722"},"PeriodicalIF":5.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the effectiveness of Vernonia cinerea for the treatment of smoking cessation: a systematic review and meta-analysis.","authors":"Omar De Santi, Cecilia Andrea Di Niro, Suthat Rungruanghiranya, Vanina Greco","doi":"10.1016/j.jep.2025.120690","DOIUrl":"https://doi.org/10.1016/j.jep.2025.120690","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Vernonia cinerea (VC) has been traditionally used in various cultures for its medicinal properties, including its potential role in smoking cessation. Understanding its efficacy and safety can provide valuable insights for public health strategies in tobacco control.</p><p><strong>Materials and methods: </strong>A systematic review was conducted following PRISMA guidelines to evaluate the efficacy and safety of VC for smoking cessation. We identified randomized controlled trials (RCTs) that compared VC with placebo, alongside behavioral therapy and approved pharmacotherapy for smoking cessation, across health centers. Participants included smokers of any age or gender.</p><p><strong>Results: </strong>Thirteen RCTs from Thailand were included in the review. Ten trials compared VC to placebo, involving 1,878 patients (943 receiving VC), with a risk ratio (RR) of 1.51 (95% CI 1.16 to 1.97; low-quality evidence). However, longer follow-up studies (≥24 weeks) indicated no significant association (RR 0.98, 95% CI = 0.68 to 1.41; low-quality evidence). There was no clear benefit of VC compared to nicotine replacement therapy or nortriptyline. Non-serious adverse effects included mild and transient symptoms such as tongue numbness, nausea, vomiting, drowsiness, and dizziness.</p><p><strong>Conclusion: </strong>VC appears to be a promising aid for smoking cessation particularly effective in trials with follow-ups under 12 weeks. VC demonstrated a benign safety profile, with no serious safety concerns reported. Further research outside Thailand is essential to fully assess its efficacy and applicability.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120690"},"PeriodicalIF":5.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wu-Wei-Zi decoction reshapes the tumor immune microenvironment by targeting the IL-6/CD73 axis in myeloid-derived suppressor cells to inhibit non-small cell lung cancer.","authors":"Ming-Xi Liu, Lin Su, Xiao-Wen Zhu, Yang-Zhuangzhuang Zhu, Xiao Chen, Xiao-Yu Wang, Xue-Wei Yan, Xiao-Wen Wu, Fei Zhang, Chun-Pu Zou, Zi-Hang Xu","doi":"10.1016/j.jep.2025.120727","DOIUrl":"https://doi.org/10.1016/j.jep.2025.120727","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Wu-Wei-Zi decoction (WWZ) is a clinically utilized classical herbal formula for non-small cell lung cancer (NSCLC). Nevertheless, the underlying mechanism of WWZ-treated lung cancer that is still unknown requires further investigation.</p><p><strong>Aim of the study: </strong>This study investigates how WWZ reprograms tumor immune micro-environment (TIME) by regulating myeloid-derived suppressor cells (MDSCs).</p><p><strong>Methods: </strong>Orthotopic NSCLC models were established in immunocompetent and immunodeficient mice to evaluate WWZ efficacy. MDSCs dynamics (frequency, apoptosis, immunosuppressive function) and CD8⁺ T cells infiltration were assessed by flow cytometry. Target specificity was validated by depleting MDSCs with anti-Gr-1 antibodies. The key pathways were identified via network pharmacology, molecular docking and RNA-sequencing, validated through immunofluorescence co-localization in human NSCLC tissues, bioinformatic analysis, and CD73-knockdown in the immortalized MDSCs (MSC-2).</p><p><strong>Results: </strong>WWZ significantly prolonged survival by decreasing MDSCs infiltration and immunosuppressive function to restore the CD8⁺ T cells cytotoxicity. MDSCs depletion abrogated WWZ's therapeutic effects, confirming their pivotal role. Mechanistically, we reveal for the first time that IL-6 modulates MDSCs immunosuppression via CD73 activation in NSCLC. WWZ suppressed the IL-6/CD73 axis in MDSCs, decreasing CD73⁺ MDSCs and downregulating immunosuppressive markers iNOS/Arg1, thereby reversing TIME suppression.</p><p><strong>Conclusions: </strong>WWZ modulates immunosuppressive activity by inhibiting the IL-6/CD73 axis in MDSCs in the TIME, thereby delaying tumor progression in NSCLC. This study provides the first mechanistic evidence supporting WWZ's clinical utility as a TCM immunomodulatory agent for NSCLC.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120727"},"PeriodicalIF":5.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TCM compatibility-driven mechanism of Shenshuaining (SSN) capsules against renal fibrosis: Integrated metabolomic and network analyses","authors":"Yun Tsai ,&nbsp;Hao Yang ,&nbsp;Zhenqi Yao ,&nbsp;Yue Tu ,&nbsp;Mengmeng Cai ,&nbsp;Xianrui Song","doi":"10.1016/j.jep.2025.120712","DOIUrl":"10.1016/j.jep.2025.120712","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Shenshuaining (SSN), a formula documented in the <em>Chinese Pharmacopoeia</em> (2020), is used to treat chronic kidney disease (CKD) based on the TCM “Qi deficiency with turbid stasis” theory. Its composition of ten herbs follows the “Monarch, Minister, Assistant, and Guide” principle: Monarch drugs strengthen Qi and eliminate turbidity; Minister drugs resolve dampness and clear heat; Assistant drugs activate blood circulation; and the Guide drug harmonizes the formula.</div></div><div><h3>Aim of the study</h3><div>This study aims to elucidate the pharmacological mechanisms of SSN and its functional groups based on TCM compatibility principles, using integrated metabolomics and network pharmacology.</div></div><div><h3>Materials and methods</h3><div>A Unilateral Ureteral Obstruction (UUO)-induced renal fibrosis rat model was used to evaluate SSN and the components of its four functional groups. Renal pathology as well as fibrosis, inflammation, and oxidative stress biomarkers were analyzed, and HPLC-MS was used to identify SSN's components, while network pharmacology predicted targets. Metabolomics revealed differential metabolites, and compound–target–metabolite networks were constructed, while molecular docking was used to assess interactions between key compounds and targets, supported by biochemical validation of functional group mechanisms. The protective effects and mechanisms of SSN and its functional groups were further validated in TGF-β-induced HK-2 cells.</div></div><div><h3>Results</h3><div>SSN significantly attenuated renal fibrosis, inflammation, and oxidative stress, as confirmed by histopathology and biomarker assays. Metabolomics revealed that the functional groups of SSN, Monarch, Minister, Assistant, and Guide, showed sequentially reduced regulatory effects on differentially metabolites in both serum and renal tissues, enriched pathways were primarily associated with lipid-related metabolism. Integrated analysis of renal fibrosis related targets associated with 63 compounds and 50 differential metabolites revealed that CA2, NOS3, and PLA2G2A serve as specific targets for the Monarch, Minister, and Guide groups respectively, while PPARG was identified as a common target regulated by the Monarch, Minister, and Assistant group to collaboratively suppressed lipid accumulation. Each functional group inhibited fibrosis via its respective targets, illustrating integrated synergistic actions and target-specific anti-fibrotic mechanisms.</div></div><div><h3>Conclusions</h3><div>The functional groups of SSN ameliorated renal fibrosis through their respective targets, while also synergistically modulating lipid-related metabolism to attenuate fibrosis. This integrated multi-target mechanism systematically validates the TCM compatibility principle and provide a scientific rationale for the composition of SSN.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120712"},"PeriodicalIF":5.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jiawei Qingxin Zishen Decoction mitigates granulosa cell apoptosis and enhances ovarian reserve through Netrin/UNC5B signaling pathway.","authors":"Tao Shen, Qian Yu, Jing Zhang, Jing Wang, Jing Wang, Tao Zhou, Jiajia Wang, Xia Zhao","doi":"10.1016/j.jep.2025.120686","DOIUrl":"https://doi.org/10.1016/j.jep.2025.120686","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Diminished ovarian reserve (DOR) is a leading cause of female infertility, characterized by a decline in ovarian function and follicular pool. Jiawei Qingxin Zishen Decoction (JWQZD) is a modernized formulation rooted in the classical theory of 'Heart-Kidney Interaction' from Fu Qingzhu's Gynecology. It is derived from the empirical formula Qingxin Zishen Decoction (QZD), which was traditionally used for perimenopausal syndrome. JWQZD has been specifically optimized to tonify the kidney, clear heart fire, and regulate the heart-kidney-uterus axis, thereby addressing the modern clinical need for treating infertility associated with DOR. It has been clinically used to improve ovarian function and menstrual regularity in women with DOR-related infertility. However, the precise mechanisms through which JWQZD exerts its therapeutic effects remain incompletely elucidated.</p><p><strong>Aim of the study: </strong>To reveal the mechanism by which JWQZD mitigates granulosa cell apoptosis through the Netrin/UNC5B signaling pathway and thereby alleviates DOR.</p><p><strong>Materials and methods: </strong>Components of JWQZD were analyzed using UPLC-Q-Exactive Plus tandem mass spectrometry. Network pharmacology identified core targets and pathways via HERB, DisGeNET, and the HPA databases. For in vivo validation, a cyclophosphamide-induced DOR rat model was used (n=6 per group). Groups included control, model, JWQZD-low (16 g/kg), and JWQZD-high (32 g/kg). Hormone levels (AMH, E2, FSH, LH), apoptosis (TUNEL, Bcl-2, Bax, and cleaved caspase-3), and pathway proteins (Netrin/UNC5B, PI3K/AKT/mTOR) were assessed.</p><p><strong>Results: </strong>Chemical analysis identified 316 components in JWQZD, with network pharmacology revealing 10 core targets (including TP53) and significant enrichment of the Netrin/UNC5B pathway. In vivo studies demonstrated that JWQZD treatment exerted significant therapeutic effects: serum AMH levels increased from 2.35 ± 1.00 to 7.12 ± 2.28 ng/mL (P<0.01) and E2 levels rose from 40.44 ± 7.06 to 85.83 ± 18.28 pg/mL (P<0.01), while simultaneously decreasing FSH (50.74 ± 6.12 to 19.00 ± 5.36 mIU/mL, P<0.01) and LH levels (33.07 ± 4.86 to 13.89 ± 4.44 mIU/mL, P<0.01). JWQZD treatment reduced granulosa cell apoptosis by approximately 40% (P<0.01) and elevated the Bcl-2/Bax ratio 2.1-fold (P<0.001). Mechanistically, JWQZD activated Netrin/UNC5B signaling, leading to a 65% reduction in p53 expression (P<0.001) and a 3.2-fold increase in AKT phosphorylation (P<0.001), indicating potent stimulation of the PI3K/AKT/mTOR pathway.</p><p><strong>Conclusion: </strong>This pioneering study established that JWQZD mitigates granulosa cell apoptosis and enhances ovarian reserve by activating the Netrin/UNC5B signaling pathway, offering a solid pharmacological foundation for the practical use of JWQZD in clinical settings.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120686"},"PeriodicalIF":5.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-targeted metabolomic profiling of Cistus species and association with anticholinesterase efficacy for Alzheimer's disease: In vitro and in silico evaluation.","authors":"Çiğdem Kahraman, Ekrem Murat Gönülalan, Engin Koçak, Fatma Şen Gökmen, Miyase Gözde Gündüz, Emirhan Nemutlu, I İrem Tatlı Çankaya","doi":"10.1016/j.jep.2025.120692","DOIUrl":"https://doi.org/10.1016/j.jep.2025.120692","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Alzheimer's disease (AD) is characterized by decreased glucose utilization, and insulin therapy has been associated with improved memory. Therefore, AD is suggested to be classified as \"Type 3 diabetes\". Cistus L. species are traditionally used to treat diabetes, which is highly associated with AD, and the potential of this genus for treating AD has not been sufficiently investigated.</p><p><strong>Aim: </strong>This study focused on the untargeted metabolomic profiling of methanolic extracts from five Cistus species to investigate the correlation between the metabolites and bioactivity.</p><p><strong>Materials and methods: </strong>Gas chromatography-mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were employed for metabolomics analysis. The inhibitory activity of the extracts on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), as well as their antioxidant capacity, were assessed. Additionally, molecular modeling techniques were utilized to corroborate the correlation between the metabolites and their cholinesterase inhibitory potency.</p><p><strong>Results: </strong>The plant extracts demonstrated inhibitory effects on BChE with IC₅₀ values ranging from 1.80 to 9.83 μg/mL, which were notably lower than those observed for AChE. Correlation analysis revealed that chlorogenic acid demonstrated strong correlations with AChE inhibitory activity, while sinapyl alcohol was closely associated with BChE inhibitory activity. Additionally, molecular modeling studies supported the inhibitory potential of these metabolites.</p><p><strong>Conclusion: </strong>This study highlights the substantial cholinesterase inhibitory capabilities of Cistus species, with C. creticus demonstrating particularly strong activity against both AChE and BChE. The results indicate that extracts from these species could be valuable natural sources of active metabolites with potent cholinesterase inhibitory effects, presenting promising new options for AD therapy.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120692"},"PeriodicalIF":5.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}