Journal of ethnopharmacology最新文献

{"title":"Wenyang Xiaozheng Decoction attenuates renal fibrosis and suppresses pyroptosis-associated signaling: insights from integrated transcriptomics and serum pharmacochemistry.","authors":"You Wu, Yixiao Han, Jiahui Wang, Lijing Du, Younes Zaid, Zhengchun Wang, Xiaomeng Lin, Xudong Cai, Xin Peng","doi":"10.1016/j.jep.2026.122533","DOIUrl":"10.1016/j.jep.2026.122533","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Wenyang Xiaozheng Decoction (WXD) is traditionally prescribed for chronic kidney disease based on the principle of warming yang and resolving blood stasis. However, whether its anti-fibrotic effects involve inflammation-associated pyroptosis remains unclear.</p><p><strong>Aim of the study: </strong>To evaluate the effects of WXD on renal fibrosis and associated changes in NF-κB- and pyroptosis-related signaling.</p><p><strong>Materials and methods: </strong>Thirty-six male C57BL/6 mice were allocated to six groups and subjected to sham surgery or unilateral ureteral obstruction (UUO) with or without valsartan or graded doses of WXD. The effects of WXD were further evaluated in TGF-β1/TNF-α-stimulated HK-2 cells. Kidney transcriptomics was integrated with serum pharmacochemistry-based network pharmacology restricted to blood-absorbed constituents. Pharmacological perturbations using necrosulfonamide (NSA) and lipopolysaccharide (LPS) were performed in HK-2 cells.</p><p><strong>Results: </strong>High-dose WXD reduced serum BUN, renal fibrotic area, and GSDMD-N expression by 24.7%, 27.6%, and 29.1%, respectively, compared with UUO mice (all P < 0.05). Transcriptomic analysis showed that WXD reversed UUO-induced activation of NF-κB, TNF, and NOD-like receptor signaling. Integration with serum pharmacochemistry identified 36 blood-absorbed constituents and yielded inflammation-related target and pathway profiles consistent with the transcriptomic findings. WXD reduced the abundance of phosphorylated p65, cleaved caspase-1, and GSDMD-N in vivo and in vitro. NSA partially reproduced, whereas LPS partially counteracted, the protective effects of WXD.</p><p><strong>Conclusions: </strong>WXD attenuates renal fibrosis in association with reduced NF-κB- and pyroptosis-associated signaling. Integrating transcriptomics with network pharmacology based on blood-absorbed constituents provides a biologically relevant strategy for investigating multi-component traditional Chinese medicine formulas.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"122533"},"PeriodicalIF":6.8,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207173","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":"Zuogui Wan preserves Leydig cell steroidogenesis via G6PD/NADPH/GSH-dependent ferroptosis inhibition in D-galactose-induced hypogonadism.","authors":"Ruonan Li, Shenghan Xu, Yuhao Liu, Shuo Sun, Han Wu, Zhitao Wei, Yong Yang","doi":"10.1016/j.jep.2026.122507","DOIUrl":"10.1016/j.jep.2026.122507","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Zuogui Wan (ZGW), a classical formula for aging-related disorders, may delay reproductive decline, but its effects on late-onset hypogonadism (LOH) remain unclear.</p><p><strong>Aim of the study: </strong>To investigate the effects and underlying mechanisms of ZGW in LOH using rat and cellular models by integrating serum pharmacochemistry, network pharmacology, and transcriptomic analyses.</p><p><strong>Materials and methods: </strong>A D-galactose-induced accelerated aging rat model was established to evaluate the ameliorative effects of ZGW. Blood-absorbed constituents were identified by UHPLC-MS/MS, and candidate pathways and targets were screened by integrating network pharmacology, testicular transcriptomics, molecular docking, and molecular dynamics simulations. Mechanistic validation was performed in rat testicular tissues and TM3 Leydig cells, and the functional role of G6PD was further evaluated using G6PDi-1-mediated pharmacological inhibition and G6pdx knockdown/overexpression rescue experiments.</p><p><strong>Results: </strong>ZGW ameliorated D-galactose-induced reproductive endocrine dysfunction and testicular aging-related injury in rats and attenuated injury in TM3 Leydig cells. Based on the identification of 36 blood-absorbed constituents, integrated analyses prioritized G6PD and suggested that it may be involved in redox regulation and ferroptosis-related mechanisms. In vivo and in vitro experiments showed that ZGW restored G6PD-related NADPH/GSH redox homeostasis, strengthened GPX4-dependent defense against lipid peroxidation, attenuated ferroptosis-related injury, and preserved mitochondrial function and StAR/CYP11A1-associated steroidogenesis. Both G6PDi-1 and G6pdx knockdown partially attenuated the effects of ZGW, whereas G6pdx rescue partially restored these changes.</p><p><strong>Conclusions: </strong>ZGW may alleviate D-gal-induced LOH-like dysfunction by restoring G6PD-related NADPH/GSH homeostasis and GPX4-dependent lipid-peroxide defense. These effects may limit ferroptosis-related injury and preserve the mitochondrial conditions required for StAR/CYP11A1-associated steroidogenesis.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"122507"},"PeriodicalIF":6.8,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207186","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":"Systematic multi-model toxicological evaluation and phytochemical signatures of Carthamus tinctorius L., Scabiosa comosa, and their mixture: Acute and 28-day oral toxicity studies.","authors":"Wei Lv, Chenlu Zhang, Ming Xue, Yuehong Ma","doi":"10.1016/j.jep.2026.122515","DOIUrl":"10.1016/j.jep.2026.122515","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Carthamus tinctorius L. and Scabiosa comosa Fisch. ex Roem. & Schult. are traditional medicinal plants used within the Traditional Chinese Medicine (TCM) and Traditional Mongolian Medicine (TMM) systems in China. Historically, the dried florets of C. tinctorius are administered as an aqueous decoction, typically at 3-10 g/day, and are prescribed to invigorate blood circulation and resolve blood stasis, whereas the capitula of S. comosa are prepared as a decoction or powder, typically at 6-9 g/day, and are utilized to clear heat and detoxify, with traditional indications for liver and pulmonary febrile diseases. However, comprehensive evaluations of their antioxidant properties and toxicological characteristics, particularly regarding their individual and combined applications, remain limited.</p><p><strong>Aim of the study: </strong>This study aimed to systematically characterize the phytochemical composition, antioxidant capacity, and safety profiles of C. tinctorius, S. comosa, and their combination using multiple extraction strategies and complementary biological models.</p><p><strong>Materials and methods: </strong>Water extracts, ethanol extracts, and sequential water-ethanol extracts were prepared and analyzed by LC-MS/MS and total flavonoid content determination. Their antioxidant capacities were evaluated using complementary in vitro assays. The toxicological profiles were investigated using BRL-3A rat hepatocytes, zebrafish embryo toxicity assays, acute oral toxicity studies in mice, and a 28-day repeated-dose oral toxicity study in Wistar rats.</p><p><strong>Results: </strong>LC-MS/MS profiling revealed diverse chemical constituents, including phenolic acids, flavonoids, coumarins, and iridoids. Notably, C. tinctorius exhibited the highest total flavonoid content (TFC), and sequential extraction significantly increased TFC compared to single-solvent extractions. In the antioxidant evaluations, S. comosa demonstrated the most potent antioxidant capacity with the lowest EC₅₀ values. Toxicity varied by concentration and extract type, with water extracts displaying the lowest toxicity. While high concentrations induced developmental abnormalities (e.g., mortality, oedema) in zebrafish, rodent models demonstrated high safety. Acute (5000 mg/kg) and 28-day repeated administrations caused no mortality or severe histopathological lesions, yielding only minor body weight and biochemical fluctuations.</p><p><strong>Conclusions: </strong>The present study provides a systematic chemical and toxicological evaluation of C. tinctorius, S. comosa, and their combination. These extracts exhibited antioxidant potential and favorable safety profiles in multiple experimental models, providing important evidence for their further development as medicinal or functional food-related products.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"122515"},"PeriodicalIF":6.8,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207199","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":"Total Ginsenosides from Panax ginseng Improve Exercise Tolerance in Rats with Spleen Qi Deficiency-like Features: Integrated Metabolomics of Serum and Hepatic Mitochondria-enriched Fractions.","authors":"Hui Li, Wantong Zhao, Xiaotong Fu, Meng Ge, Jielin Wang, Wei Wu","doi":"10.1016/j.jep.2026.122521","DOIUrl":"https://doi.org/10.1016/j.jep.2026.122521","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Panax ginseng C.A.Mey. has traditionally been used to replenish Qi and strengthen the spleen, including for poor appetite and weakness associated with spleen deficiency. Ginsenosides are major constituents, but their metabolic effects under spleen Qi deficiency-like conditions remain to be clarified.</p><p><strong>Aim of the study: </strong>To evaluate whether total ginsenosides (TGS) improve spleen Qi deficiency-like features in rats and characterize systemic and hepatic metabolic changes.</p><p><strong>Materials and methods: </strong>A rat model was established using 50% food restriction combined with repeated weight-loaded swimming, and TGS (75, 150, or 300 mg·kg^-1) was administered for 21 days. Body weight, grip strength, swimming endurance, biochemical indices, and mitochondrial ultrastructure were evaluated. Untargeted metabolomic analyses of serum and hepatic mitochondria-enriched fractions were performed in the control (CON), model (MOD), and high-dose TGS (TGS-H) groups, and hepatic SIRT1 and PGC-1α protein expression was measured. Lipid accumulation, mitochondrial membrane potential, and SIRT1 and PGC-1α expression were also examined in oleic acid-treated HepG2 cells.</p><p><strong>Results: </strong>TGS, particularly at 300 mg·kg^-1, attenuated the suppression of body-weight gain and improved grip strength and swimming endurance. These functional improvements were accompanied by increased ATP content and ATPase activities and attenuation of mitochondrial ultrastructural abnormalities. After TGS-H treatment, serum levels of several amino acids increased, and lipid profiles shifted toward the control pattern. In hepatic mitochondria-enriched fractions, accumulation of selected fatty acids decreased, and levels of selected organic acids increased. TGS increased hepatic PGC-1α protein expression at all three doses, whereas SIRT1 expression increased significantly only at the high dose. In oleic acid-treated HepG2 cells, increased expression of both proteins was accompanied by reduced lipid accumulation and partial recovery of mitochondrial membrane potential.</p><p><strong>Conclusions: </strong>In rats with spleen Qi deficiency-like features induced by limited nutritional supply and repeated physical exertion, TGS attenuated the suppression of body-weight gain and improved exercise tolerance, accompanied by changes in energy-related indices. These findings provide experimental support for the traditional use of ginseng to replenish Qi and strengthen the spleen in relation to symptoms of weakness.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"122521"},"PeriodicalIF":6.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207201","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":"Aquilaria leaves (Thymelaeaceae): A comprehensive review of ethnobotany, traditional applications, phytochemistry, pharmacological activities, toxicity and quality evaluation.","authors":"Yuanyuan Yu, Almaz Borjigidai, Yuxia Zhang, Miao Yu, Huiqin Chen, Shengzhuo Huang, Tian Liang, Zesheng Li, Honglei Jin, Yijun Chen, Wenli Mei, Haofu Dai","doi":"10.1016/j.jep.2026.122510","DOIUrl":"10.1016/j.jep.2026.122510","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Aquilaria species are well known for agarwood, while their leaves are also used in regional folk medicine and consumed as herbal teas in southern China and Southeast Asia, mainly for inflammatory conditions, infections, and stress-related symptoms.</p><p><strong>Aims of the review: </strong>This review summarizes the ethnobotany, taxonomy, traditional applications, phytochemistry, pharmacology, toxicity and quality evaluation of Aquilaria leaves, and identifies gaps that warrant further investigation.</p><p><strong>Materials and methods: </strong>Relevant literature was collected from Web of Science, ScienceDirect, Google Scholar, PubMed, CNKI, and Wan Fang Data, including journal articles, books, and dissertations. Flora of China and Plants of the World Online were consulted to verify species distribution and accepted botanical names. Chemical structures were drawn using ChemDraw 22.0.0.</p><p><strong>Results: </strong>A total of 185 compounds have been recorded from Aquilaria leaves. Phytochemical and pharmacological studies mainly involve three species, A. sinensis, A. crassna, and A. malaccensis. The major compound classes include flavonoids, terpenoids, benzophenones, organic acids, xanthones, and 2-(2-phenylethyl)chromones, with flavonoids (39) and terpenoids (43) predominating. Pharmacological studies have largely focused on crude extracts, with relatively few investigations of isolated compounds, and have demonstrated anti-inflammatory, antioxidant, antibacterial, antidiabetic, laxative, and neuroprotective activities. Available toxicological studies generally indicate low acute toxicity within the tested dose ranges, although evidence on long-term safety remains limited. Quality evaluation has mainly relied on chromatographic profiling and multi-component determination, while standardized quality criteria remain to be established.</p><p><strong>Conclusions: </strong>This review highlights Aquilaria leaves as a renewable and underexplored medicinal resource by integrating evidence from traditional applications, phytochemistry, pharmacology, toxicity, and quality evaluation. However, current evidence is still limited by crude-extract-based studies, insufficient active-constituent characterization, and limited long-term safety and clinical data. Further research is needed to identify the active constituents, elucidate their underlying mechanisms, and establish standardized quality control and safety evaluation systems for the safe and effective use of Aquilaria leaves.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"122510"},"PeriodicalIF":6.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207167","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":"Spermacoce stachydea DC. (Rubiaceae), a Traditionally Used Antimalarial Plant: Phytochemical Profiling, Antioxidant and Antiplasmodial Activities, Host-Protective Effects, and Preclinical Safety Assessment.","authors":"Saamou Isaac Boni, Kouliga Benjamin Koama, Domonbabele François de Sales Hien, Mariam Youba, Manon Vitou, Virginie Vaissayre, Zachari Kabre, Stephane Dussert, Sylvie Morel, Françoise Fons, Rakiswende Serge Yerbanga, Thierry Lefevre, Mohamed Haddad, Abdoulaye Diabate, Nâg-Tero Roland Meda","doi":"10.1016/j.jep.2026.122518","DOIUrl":"https://doi.org/10.1016/j.jep.2026.122518","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Ethnopharmacological relevance: &lt;/strong&gt;Spermacoce stachydea (Rubiaceae) is traditionally used for malaria treatment across West Africa, yet its phytochemical composition, antioxidant properties, antiplasmodial activity, and safety profile remain insufficiently characterised. This study aimed to provide a comprehensive preclinical characterisation for its ethnomedicinal use in malaria management.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The whole-plant methanolic extract was profiled by ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and gas chromatography-mass spectrometry (GC-MS). Total phenolic (TPC), flavonoid (TFC), and condensed tannin (CTC) contents were quantified, and antioxidant capacity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC) assays. Antiplasmodial activity was evaluated in vitro against Plasmodium falciparum 3D7 using a growth inhibition assay and in vivo in Plasmodium berghei ANKA-mice using a four-day suppressive test at 125, 250, and 500 mg/kg b.wt., and curative and prophylactic models at 250 mg/kg b.wt. Host-protective effects defined as the capacity of the extract to attenuate malaria-induced physiological disturbances including anaemia, organ enlargement, and hepatic and renal dysfunction were evaluated at 250 mg/kg b.wt. through restorative and protective assays encompassing physiological, haematological, biochemical analyses. Safety was assessed following single oral administration at 2000 and 5000 mg/kg b.wt. and repeated oral administration at 20, 200, and 2000 mg/kg b.wt./day in accordance with Organisation for Economic Co-operation and Development (OECD) guidelines 423 and 407, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Phytochemical profiling revealed a diverse array of bioactive metabolites including flavonoids, terpenoids, coumarins, iridoids, alkaloids, and polyphenols. The extract exhibited a flavonoid-dominant phenolic profile (TPC: 33.99 ± 0.07 mg GAE/100 mg; TFC: 7.57 ± 0.03 mg QE/100 mg) and strong DPPH radical-scavenging activity reached 774 ± 3.9 μmol AAE/g, compared with 647 ± 3.5 and 766 ± 2.9 μmol AAE/g for Trolox and quercetin, respectively. In vitro antiplasmodial activity was significant (IC&lt;sub&gt;50&lt;/sub&gt; = 6.30 ± 0.13 μg/mL) with negligible haemolysis (&lt;1%). In vivo, parasitaemia suppression reached 88.10 ± 6 % at 500 mg/kg (suppressive model), with good curative (58.40 ± 14.70%) and moderate prophylactic (35.70 ± 5.60%) activities at 250 mg/kg b.wt.. The extract attenuated malaria-associated physiological disturbances including anaemia, organ enlargement, and hepatic and renal dysfunction while demonstrated hepatoprotective effects. No mortality or consistent treatment-related toxicological alterations were observed after a single oral dose up to 5000 mg/kg b.wt. or repeated adminis","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"122518"},"PeriodicalIF":6.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194638","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":"Corrigendum to \"Predicting the potential mechanism of radix chimonanthi pracecocis in treating osteoarthritis by network pharmacology analysis combined with experimental validation\" [J. Ethnopharmacol. 331, (2024), 118231].","authors":"Xudong Zhang, Dongwen Wu, Lukai Zhang, Hongyan Zhang, Liping Yang, Li Wei, Huimin Mei, Liying Luo, Zong Jiang, Cong Huang","doi":"10.1016/j.jep.2026.122503","DOIUrl":"https://doi.org/10.1016/j.jep.2026.122503","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"122503"},"PeriodicalIF":6.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194651","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":"Discovery of the mechanism of Huangqi Guizhi Wuwu Decoction in the treatment of Diabetic Peripheral Neuropathy with Qi Deficiency and Blood Stasis based on the dynamic metabolic trajectory analysis.","authors":"Jingyu Wen, Li Yan, Yujie Xiang, Xu Wang, Cheng Fang, Shuyi Ru, Xinyue Zhang, Ziyi Liu, Xiuhong Wu","doi":"10.1016/j.jep.2026.122422","DOIUrl":"https://doi.org/10.1016/j.jep.2026.122422","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Huangqi Guizhi Wuwu Decoction (HGWD), a classic Traditional Chinese Medicine formula, has shown clinical efficacy in the treatment of diabetic peripheral neuropathy (DPN) with Qi deficiency and blood stasis syndrome. However, its pharmacodynamic material basis and underlying therapeutic mechanisms remain unclear.</p><p><strong>Purpose: </strong>This study aimed to systematically elucidate the pharmacodynamic material basis and therapeutic mechanisms of HGWD in the treatment of DPN using an integrated Chinmedomics strategy.</p><p><strong>Materials and methods: </strong>A rat model of DPN with Qi deficiency and blood stasis syndrome was established by streptozotocin (STZ) injection combined with dietary intervention and exhaustive swimming. HGWD was administered continuously for 8 weeks to assess its therapeutic effects. In addition to conventional pharmacological assessments, ANOVA-simultaneous component analysis (ASCA) was applied to urinary metabolomics analysis to dynamically track metabolic trajectories and characterize time-dependent changes in disease-related urinary biomarkers. Blood-absorbed components in the HGWD-treated group were characterized using UHPLC-QE-Orbitrap-MS. Correlation analysis was then performed among urinary biomarkers, key pharmacodynamic indicators, and in vivo active components. Molecular docking, molecular dynamics simulations, and in vitro experiments were further conducted to validate the core active components and their corresponding targets.</p><p><strong>Results: </strong>HGWD significantly improved neurological function and alleviated pathological damage in the DPN rat model. Urinary metabolomics analysis identified 28 disease-related urinary biomarkers that were markedly modulated by HGWD treatment. Under conditions of confirmed therapeutic efficacy, 98 blood-absorbed components, including 63 prototype compounds and 35 metabolites, were identified. Integrated correlation analysis and network pharmacology revealed eight key pharmacodynamic components and three core targets closely associated with the therapeutic effects of HGWD. Among these components, astragaloside II, paeoniflorin, and quercetin were identified as major bioactive compounds, which may exert therapeutic effects by regulating the protein expression of P-gp, PTP1B, and MMP2.</p><p><strong>Conclusion: </strong>This study systematically clarified the pharmacodynamic material basis and therapeutic mechanisms of HGWD in the treatment of DPN using an integrated Chinmedomics approach. The integrated analysis identified 17 urinary biomarkers, 8 core components, and 3 core targets, namely ABCB1, MMP2, and PTPN1, which were further supported by molecular simulations and in vitro validation These findings provide a comprehensive strategy for deciphering the mechanisms of Traditional Chinese Medicine formulas and support the potential application of HGWD in DPN treatment.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"122422"},"PeriodicalIF":6.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182357","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":"Protective effects and possible mechanisms of Salvia miltiorrhiza-derived interventions in animal models of osteoarthritis: a preclinical systematic review and meta-analysis.","authors":"Dongping Wan, Danyuan Wang, Yu Cui, Tao Chen, Chengcheng Zhang, Yuhang Liu, Ming Li, Zhong Li, Taotao Ren, Bing Du","doi":"10.1016/j.jep.2026.122511","DOIUrl":"https://doi.org/10.1016/j.jep.2026.122511","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Ethnopharmacological relevance: &lt;/strong&gt;Salvia miltiorrhiza Bunge, commonly known as Danshen, is a traditional Chinese medicinal herb historically used for blood stasis- and pain-related disorders. Its extracts and bioactive constituents have shown anti-inflammatory, antioxidant, anti-apoptotic, and tissue-protective effects, suggesting potential value for osteoarthritis (OA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim of the study: &lt;/strong&gt;This systematic review and meta-analysis evaluated the protective effects and possible mechanisms of Salvia miltiorrhiza-derived interventions in animal models of OA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;PubMed, EMBASE, Web of Science, Scopus, CNKI, and Wanfang were searched from inception to March 2026. Controlled in vivo animal studies assessing Salvia miltiorrhiza-derived interventions or related constituents in OA models were included. Primary outcomes were histological cartilage damage scores, including OARSI and Mankin scores. Secondary outcomes included inflammatory cytokines, cartilage matrix metabolism markers, apoptosis-related indicators, and oxidative stress markers. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Twenty-two studies involving 456 animals were included. Salvia miltiorrhiza-derived interventions significantly attenuated histological cartilage damage, as reflected by lower OARSI scores (SMD = -4.20, 95% CI -5.31 to -3.09; I&lt;sup&gt;2&lt;/sup&gt; = 69.26%) and Mankin scores (SMD = -6.50, 95% CI -8.50 to -4.50; I&lt;sup&gt;2&lt;/sup&gt; = 85.61%). Model type showed a significant subgroup difference for OARSI score, and intervention category showed a significant subgroup difference for Mankin score, suggesting possible sources of heterogeneity. Significant reductions were observed in serum IL-1β, serum IL-6, cartilage/chondrocyte IL-6, and serum TNF-α, whereas the reduction in cartilage TNF-α did not reach statistical significance. Salvia miltiorrhiza-derived interventions also increased Aggrecan and Collagen II expression and modulated MMP-13 expression, supporting an improvement in cartilage matrix homeostasis. Apoptosis-related analyses showed increased Bcl-2 expression and reduced caspase-3 expression and TUNEL-positive apoptotic cells, whereas the reduction in Bax expression was not statistically significant. Cartilage MDA levels were also significantly reduced. Leave-one-out sensitivity analysis indicated that the pooled OARSI result was robust. Although funnel plot asymmetry was observed, trim-and-fill analysis did not alter the direction of the pooled effect.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Current preclinical evidence suggests that Salvia miltiorrhiza-derived interventions may attenuate cartilage structural damage in animal models of OA, with possible involvement of inflammatory responses, extracellular matrix metabolism, chondrocyte apoptosis, and oxidative stress. However, these findings should be interpreted cautiously beca","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"122511"},"PeriodicalIF":6.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182347","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":"Agriophyllum squarrosum oligosaccharides ameliorate inflammation and lipid accumulation in T2DM-induced MASLD via miR-155-regulated PPARγ signaling pathways.","authors":"Shuyin Bao, Meijun Lin, Xuan Wang, Qiong Wu, Junguo Yin, Ruibo Wu, Yiping Che, Qianqian Ma, Xiuzhi Wang, Wuliji Ao","doi":"10.1016/j.jep.2026.122462","DOIUrl":"https://doi.org/10.1016/j.jep.2026.122462","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Agriophyllum squarrosum (L.) Moq., is a traditional medicinal herb first recorded in the \"Four Medical Tantras\" during the 8th century AD. It is commonly employed in Mongolian medicine for various therapeutic diseases, including the dispelling epidemics, heat clearance, detoxification, and diuresis. This herb is known to inhibit \"He Yi,\" regulate \"Ba Da Gan,\" and is utilized in the treatment of \"Xi He Ri Xi Jing Bing\" which corresponds to modern diabetes and xiaoke in traditional Chinese medicine. Agriophyllum squarrosum oligosaccharides (AOS) are recognized as major bioactive constituents, however, the molecular mechanisms underlying their therapeutic effects on type 2 diabetes mellitus (T2DM)-related metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear.</p><p><strong>Aim of the study: </strong>This study investigates the therapeutic effects of AOS in T2DM-MASLD and explores the underlying mechanisms involving miR-155-mediated signaling pathways.</p><p><strong>Materials and methods: </strong>In vivo, db/db mice were treated with AOS, and hepatic lipid accumulation and insulin resistance were evaluated using biochemical and histological analyses. Hepatic expression of miR-155 and associated signaling proteins was observed by qRT-PCR, Western blotting, and immunohistochemistry. Exosomes derived from ATMs of db/db mice were co-cultured with AML-12 hepatocytes to investigate the role of exosomal miR-155 in MASLD progression. In vitro, inflammatory cytokine production and miR-155 expression were quantified using ELISA and qRT-PCR, while exosomal miR-155 secretion was evaluated in glucolipid-induced cellular injury models.</p><p><strong>Results: </strong>AOS treatment reduced hepatic steatosis and improved insulin resistance in db/db mice. AOS was associated with decreased hepatic miR-155 expression. Exosomal miR-155 derived from ATMs aggravated hepatocyte injury in the co-culture system, accompanied by increased expression of SREBP1c, NLRP3, and NF-κB p65. In vitro, AOS inhibited exosomal miR-155 secretion and downregulated the expression of SREBP1c, P2X7R, NF-κB p65, and inhibitor of IκBα, thus attenuating glucolipid metabolism-associated inflammatory responses and lipid dysregulation.</p><p><strong>Conclusion: </strong>AOS ameliorates inflammation, hepatic lipid accumulation, and insulin resistance in T2DM-associated MASLD, possibly via suppression of miR-155 and modulation of downstream inflammatory and lipogenic signaling pathways. These results identify AOS as a promising therapeutic candidate for treating T2DM-associated MASLD.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"122462"},"PeriodicalIF":6.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182362","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}