Journal of ethnopharmacology最新文献

{"title":"Sanqi qushi formula ameliorates podocyte injury in membranous nephropathy by inhibiting endoplasmic reticulum stress-induced ferroptosis","authors":"Yuan Sun ,&nbsp;Zhuo Cen ,&nbsp;Yumei Li ,&nbsp;Haoxiang Li ,&nbsp;Qiaoru Wu ,&nbsp;Zelong Lin ,&nbsp;Jianzhan Yang ,&nbsp;Bo Liu ,&nbsp;Yunshan Wu ,&nbsp;Kun Bao ,&nbsp;Tingxiu Zhao","doi":"10.1016/j.jep.2025.120453","DOIUrl":"10.1016/j.jep.2025.120453","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Membranous nephropathy (MN) is a primary glomerular disease and a major cause of nephrotic syndrome in adults. According to traditional Chinese medicine (TCM) theory, “dampness” is considered a key pathogenic factor. Sanqi Qushi Formula (SQQS), developed by adding dampness-eliminating herbs to Sanqi Oral Liquid, has been shown to improve remission rates in idiopathic MN, although its pharmacological mechanisms are not yet fully clarified.</div></div><div><h3>Aim of the study</h3><div>This study investigated whether SQQS attenuates podocyte injury in MN by inhibiting endoplasmic reticulum stress (ERS)–induced ferroptosis.</div></div><div><h3>Methods</h3><div>The main components of SQQS were identified and quantified by widely targeted metabolomics. A passive Heymann nephritis (PHN) rat model was established via intravenous injection of anti-Fx1A serum, followed by oral SQQS intervention. Renal function and histopathology were evaluated, and underlying mechanisms were investigated by integrating transcriptomic and proteomic analyses. Structural changes in the endoplasmic reticulum and mitochondria were assessed by transmission electron microscopy. The regulatory effect of SQQS on ERS-induced ferroptosis was further examined using immunohistochemistry, flow cytometry, oxidative stress assays, and related molecular analyses. In vitro, immortalized mouse podocytes MPC-5 were injured with zymosan-activated serum and treated with SQQS-containing serum, the ferroptosis inhibitor Fer-1, the ERS inhibitor 4-PBA, or the ERS activator tunicamycin. The protective effects of SQQS were validated by Western blotting and immunofluorescence.</div></div><div><h3>Results</h3><div>SQQS treatment significantly improved renal function, reduced proteinuria, and alleviated glomerular injury in PHN rats. Histopathological and ultrastructural analyses revealed that SQQS reduced glomerular IgG deposition, basement membrane thickening, fibrosis, and podocyte injury. SQQS dose-dependently restored the expression of key podocyte structural proteins (Nephrin, Synaptopodin, Podocin, α-actinin-4, WT-1) and decreased Desmin levels. Integrated transcriptomic and proteomic analyses identified ERS and ferroptosis as central pathways regulated by SQQS. SQQS suppressed ERS markers (GRP78, p-PERK, p-eIF2α, ATF4, CHOP) and pro-ferroptotic proteins (ACSL4, CHAC1), upregulated antioxidant proteins (GPX4, xCT), reduced iron deposition, and attenuated oxidative stress. In vitro, SQQS-containing serum protected MPC-5 podocytes from ZAS-induced ferroptosis by inhibiting ERS, restoring podocyte marker expression, and enhancing antioxidant defenses.</div></div><div><h3>Conclusion</h3><div>SQQS ameliorates MN by inhibiting the ERS-ferroptosis axis, providing experimental and theoretical support for the application of TCM in the treatment of MN.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120453"},"PeriodicalIF":5.4,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903970","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":"Multi-omics combining bioinformatic network with kidney-entry constituents revealed the bioactive components and potential mechanisms of Zhijun Tangshen decoction against diabetic nephropathy","authors":"Qingheng Tong ,&nbsp;Xinye Zhu ,&nbsp;Jin Liu ,&nbsp;Shuaitao Zhu ,&nbsp;Shuangshuang Wang ,&nbsp;Guanxiong Shang ,&nbsp;Xiaoqi Zhou ,&nbsp;Jiu Yin ,&nbsp;Fangfang Zhang ,&nbsp;Cuiping Zhang ,&nbsp;Fang Yuan ,&nbsp;Suqin Wang ,&nbsp;Weifeng Yao","doi":"10.1016/j.jep.2025.120436","DOIUrl":"10.1016/j.jep.2025.120436","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Diabetic nephropathy (DN) is a common and severe complication of diabetes which could ultimately progress to end-stage renal disease. Zhijun Tangshen Decoction (ZJTSD), a traditional Chinese herbal formula, has shown clinically beneficial effects in the treatment of DN. However, the mechanisms of ZJTSD against DN remain unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;This study was aimed to evaluate the anti-DN effect of ZJTSD in rats and further investigate its potential mechanisms against DN.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The streptozotocin (STZ)-induced DN model was established in SD rats. The protective effect of ZJTSD on the DN rats was assessed by biochemical markers, inflammatory cytokines, renal measurements, and histopathological analysis. The migrant components of ZJTSD in the rat kidneys, including both prototype compounds and metabolites, were identified utilizing UPLC-Q-TOF-MS. Besides, renal metabolomics was conducted to identify potential biomarkers and metabolic pathways, while transcriptomics of kidneys was used to uncover related signaling pathways. Network pharmacology analysis based on prototype compounds and metabolites of ZJTSD found in the kidneys was used to predict the action biological network. Finally, a comprehensive strategy involving metabolomics, transcriptomics, and network pharmacology was integrated to elucidate the underlying mechanisms of ZJTSD, and the key proteins involved in the mechanisms were validated by Western blotting assay.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The results of biochemical indexes and ELISA showed that ZJTSD could significantly improve blood glucose levels and renal function, inhibiting the inflammatory response and renal fibrosis in model rats. The pathological results suggested that ZJTSD could alleviate histological changes, renal injury, and interstitial fibrosis in DN rat kidney tissue. Renal metabolome indicated that amino acid metabolism and nucleotide metabolism may represent the primary pathways affected by ZJTSD treatment. Transcriptomic analysis was applied to identify differentially expressed genes among the control, model, and ZJTSD-H groups, resulting in the identification of 93 differentially expressed genes from the intersection of these groups. The functional enrichment analysis suggested that DEGs were mainly involved in biological processes, including cellular metabolism, immune regulation, and oxidative stress response. A total of 191 compounds were identified in the kidney, comprising 54 prototype compounds and 137 metabolites, with flavonoids identified as the predominant active constituents. Network pharmacology analysis indicated that ZJTSD targets key proteins, including EGFR, STAT3, HSP90AA1, AKT1, and SRC. Comprehensive integrative analysis revealed that there were nine pathways related to DN, including PI3K-Akt signaling pathway, Phospholipase D signaling pathway, Natural killer cell mediated cytot","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120436"},"PeriodicalIF":5.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880263","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":"Pharmacologically active constituents of Buyang Huanwu Decoction against cerebral ischemia–reperfusion injury and verification of its effects on oxidative stress, energy metabolism, and inflammation","authors":"Yuan Chen ,&nbsp;Zhongji Hu ,&nbsp;Yanling Li ,&nbsp;Xiao Lan ,&nbsp;Yang Bai ,&nbsp;Hongping Long ,&nbsp;Changqing Deng ,&nbsp;Long Zou","doi":"10.1016/j.jep.2025.120405","DOIUrl":"10.1016/j.jep.2025.120405","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Buyang Huanwu Decoction (BYHWD) is traditionally prescribed for Qi-deficiency and blood-stasis stroke in TCM, yet its key pharmacologically active constituents and mechanistic basis remain to be fully elucidated.&lt;/div&gt;&lt;div&gt;Aim of the study:To investigate the key pharmacologically active constituents of BYHWD against Qi-deficiency and blood-stasis type cerebral ischemia-reperfusion injury (QDBS + CI/R), and to clarify their roles in counteracting oxidative stress, suppressing inflammation, and improving energy metabolism.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A QDBS + CI/R rat model was used to assess BYHWD's therapeutic effects via neurological and syndrome scoring, histology (HE, Nissl), and biochemical markers (T-AOC, IL-1β, IL-6, ATP, ADP). Blood-absorbed compounds were identified by UPLC-QTOF-MS/MS and correlated with efficacy using spectrum-effect analyses (GRA-EWM, PLSR). Key anti-CI/R constituents were screened and their targets explored through network pharmacology, molecular docking, and MD simulations. Effects on energy metabolism, oxidative stress, and inflammation were validated in HT22 cells under OGD/R conditions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;BYHWD alleviated neurological deficits and histopathological damage in CI/R rats, improved energy metabolism, reduced oxidative stress, and suppressed inflammation. UPLC-QTOF-MS/MS identified 24 and 26 blood-absorbed constituents in BYHWD-L and BYHWD-H, respectively. Spectrum–effect analysis linked Sucrose, Lactiflorin, Albiflorin, and others to anti-CI/R effects. Paeonol, Asperulosidic acid, and Calycosin-7-O-beta-D-glucoside, among others, showed antioxidative activity; Hydroxysafflor yellow A, Albiflorin, and Paeoniflorin, among others, exhibited anti-inflammatory potential; Ononin, Lactiflorin, and Paeonol, among others, contributed to energy metabolism. Network pharmacology, docking, and MD simulations suggested strong binding of key compounds to targets related to oxidative stress, inflammation, and energy metabolism. &lt;em&gt;In vitro&lt;/em&gt; validation in OGD/R-induced HT22 cells showed that Paeonol, Z-Ligustilide, Paeoniflorin, and Albiflorin enhanced T-AOC, GSH-Px, and SOD, and decreased MDA and 4-HNE. Paeonol, Amygdalin, Calycosin-7-O-beta-D-glucoside, and Albiflorin increased ATP and ADP, reduced ECAR, and raised OCR. All six compounds significantly suppressed IL-1β and IL-6, confirming anti-inflammatory activity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;BYHWD protects against CI/R injury via coordinated antioxidative, anti-inflammatory, and energy metabolism-enhancing mechanisms. Major antioxidative constituents include Albiflorin, Paeoniflorin, Paeonol, and Z-Ligustilide, among others. Calycosin-7-O-beta-D-glucoside, Paeoniflorin, Albiflorin, Amygdalin, Z-Ligustilide, and Paeonol, among others, contribute to anti-inflammatory effects. Albiflorin, Paeonol, Amygdalin, and Calycosin-7-O-beta-D-glucoside, among others, are key to improvin","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120405"},"PeriodicalIF":5.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892003","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":"Chebulinic acid shields Villin 1 from covalent attack to mitigate Euphorbia fischeriana enterotoxicity: A basis for safer anti-ascites therapy","authors":"Hang Wang ,&nbsp;Jie Cao ,&nbsp;Sheng Li ,&nbsp;Ruolan Yang ,&nbsp;Qinman He ,&nbsp;Shengjie Hua ,&nbsp;Yuqi Pan ,&nbsp;Zeyu Jiang ,&nbsp;Xin Li ,&nbsp;Ronglu Yu ,&nbsp;Laga Litong ,&nbsp;Hongli Yu ,&nbsp;Bingbing Liu ,&nbsp;Hao Wu ,&nbsp;Xinzhi Wang","doi":"10.1016/j.jep.2025.120435","DOIUrl":"10.1016/j.jep.2025.120435","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Euphorbia f<em>ischeriana</em> (EF), an herb used in ethnomedicine for cancerous ascites, particularly in Inner Mongolian practices, is limited by severe enterotoxicity. Traditionally, co-decoction with <em>Terminalia chebula</em> (TC) mitigates this toxicity, but the underlying mechanism is unknown, hindering its rational clinical development.</div></div><div><h3>Aim of the study</h3><div>To elucidate the molecular mechanism by which TC detoxifies EF, providing a scientific basis for developing safer EF-based therapies against malignant ascites.</div></div><div><h3>Materials and methods</h3><div>The study employed intestinal organoid models, chemical biology, proteomics, and genetic engineering (Villin 1 knockout/mutagenesis). Enterotoxic EF constituents and protective TC compounds were identified, and their interactions with the cellular target Villin 1 were analyzed <em>in vitro</em> and validated <em>in vivo</em>, assessing effects on F-actin networks and intestinal barrier integrity.</div></div><div><h3>Results</h3><div>The EF diterpenoid Euphorin G was identified as the enterotoxin, covalently modifying Cys624 in the actin-regulatory protein Villin 1, leading to F-actin disassembly and intestinal barrier failure. Chebulinic acid from TC prevented this by non-covalently binding to Villin 1, shielding Cys624 from Euphorin G and allosterically enhancing Villin 1's F-actin binding affinity. This dual protective mechanism occurred without reducing Euphorin G levels.</div></div><div><h3>Conclusions</h3><div>This study reveals that Chebulinic acid from TC detoxifies EF by protecting and potentiating the host protein Villin 1 against Euphorin G. This molecular insight validates a traditional ethnopharmaceutical practice, enabling the rational development of safer EF-based therapies for refractory cancerous ascites by preserving therapeutic efficacy while mitigating toxicity.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120435"},"PeriodicalIF":5.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888788","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":"Corydalis rhizoma attenuates primary dysmenorrhea in rats by inhibiting the FAK/PI3K-AKT/NF-κB signaling pathway","authors":"Jie Zhang ,&nbsp;Ming Dang ,&nbsp;Yanan Wu ,&nbsp;Andong Dong ,&nbsp;Hongwei Wang ,&nbsp;Duo Li ,&nbsp;Qiao Zhang ,&nbsp;Xiaofei Zhang ,&nbsp;Mengmeng Zhang ,&nbsp;Chongbo Zhao ,&nbsp;Jing Sun","doi":"10.1016/j.jep.2025.120420","DOIUrl":"10.1016/j.jep.2025.120420","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Primary dysmenorrhea (PD) is a prevalent condition affecting women globally. Corydalis rhizoma (known as Yanhusuo in Chinese, YHS) is commonly used to treat PD. However, the mechanisms by which raw-YHS (YHS-R) and vinegar-processed YHS (YHS-V) exert the therapeutic effects on PD remain unclear.</div><div><em>Aim of the study</em>: To investigate the potential mechanisms of YHS-R and YHS-V in alleviating PD.</div></div><div><h3>Materials and methods</h3><div>UPLC-Q-TOF/MS technology was utilized to identify and quantify the components present in both YHS-R and YHS-V, as well as in the blood. The targets of these blood-absorbed components, in relation to PD, were subjected to KEGG enrichment analysis. A rat model of PD was established using estradiol benzoate and oxytocin. The therapeutic effects of YHS-R and YHS-V on PD were evaluated through the torsion response, uterine and ovarian indices, levels of PGE₂ and PGF_2α, and histopathological examination of the uterus and ovaries. Furthermore, the regulatory mechanisms of YHS-R and YHS-V on PD were investigated through RNA sequencing (RNA-seq), Western blotting, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and non-targeted metabolomics.</div></div><div><h3>Results</h3><div>Both YHS-R and YHS-V significantly alleviated PD, as demonstrated by reduced writhing scores, improved uterine and ovarian indices, and decreased pathological damage to the uterus and ovaries. Additionally, they lowered the PGF_2α/PGE₂ ratio and inflammatory factor levels in the uterus and ovaries, with YHS-V showing a superior effect. Network pharmacology and RNA-seq analysis indicated that the PI3K-AKT and NF-κB pathways were involved in the PD-alleviating effects of YHS-R and YHS-V. Moreover, the glycerophospholipid and amino acid metabolism pathways were identified as significant metabolic pathways, the key metabolites PE and PG are closely correlated with the expression of the ITGB3, IL-24, and Thbs4 genes. Western blotting and RT-qPCR assays revealed that both YHS-R and YHS-V reduced the expression of FAK, PI3K, AKT, P65, and COX-2 in the uterus.</div></div><div><h3>Conclusion</h3><div>Collectively, both YHS-V and YHS-R alleviate PD through mechanisms involving suppression of inflammatory factor release, mitigation of uterine histopathological damage, and regulation of the FAK/PI3K-AKT/NF-κB signaling pathway and glycerophospholipid metabolism pathway. This study is the first to investigate the therapeutic effects of YHS-R and YHS-V in PD and elucidate the underlying mechanism, providing novel evidence supporting YHS application.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120420"},"PeriodicalIF":5.4,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867204","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":"Ethyl gallate isolated from Gypsophila licentiana Hand. -Mazz reduces the risk of liver injury by modulating the RAS pathway","authors":"Qinqin Zhang ,&nbsp;Haoyang Dai ,&nbsp;Chenxi Bu ,&nbsp;Zhining Gao ,&nbsp;Chengbo Hou ,&nbsp;Suiqing Chen","doi":"10.1016/j.jep.2025.120442","DOIUrl":"10.1016/j.jep.2025.120442","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Shanyin Chaihu (<em>Gypsophila licentiana</em> Hand. -Mazz) is a traditional Chinese medicine and possesses a history of use for the treatment of various diseases, including hepatitis. Ethyl gallate (EG), the natural pharmacologically active ingredient of Shanyin Chaihu, exerts obvious pharmacological effects against inflammation. However, the underlying therapeutic mechanisms of EG against ALI remain unknown.</div></div><div><h3>Aim of the study</h3><div>To investigate the role and elucidate the mechanisms of EG in ALI mice underlying by performing an integrated analysis.</div></div><div><h3>Methods</h3><div>EG was isolated and identified from <em>Gypsophila licentiana</em> Hand. -Mazz. The effects and action mechanisms of EG on ALI in mice were assessed using H&amp;E staining, DIA proteomics, western blotting, immunohistochemistry, molecular dynamics, CETSA, and immunofluorescence.</div></div><div><h3>Results</h3><div>The results showed that EG was able to significantly decrease the liver coefficient, reduce the levels of ALT and AST in serum, attenuate the expression levels of ROS, F4/80 and LY6G in liver tissue. EG treatment significantly regulated the alteration of RAS signaling pathway in mice. In addition, EG had a good binding score with RAS. Furthermore, we added RAS agonists (ML-099) to mice and found that the effect of EG on improving liver injury was weakened. The experiment further proved that EG could target RAS.</div></div><div><h3>Conclusion</h3><div>These results suggest that EG has the vigour to alleviate liver injury in mice through RAS signaling. The findings provide a strategy for developing the EG, the compound isolated from Shanyin Chaihu, as a potential therapeutic agent for ALI.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120442"},"PeriodicalIF":5.4,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867205","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":"Gut microbiota modified by Mulberry leaf water extract improves T2DM through browning of WAT/BAT activation mediated by SCFAs-AMPK/SIRT1/PGC-1α signaling pathway","authors":"Yuhang Du ,&nbsp;Changhao He ,&nbsp;Yongcheng An ,&nbsp;Yige Zhao ,&nbsp;Huilin Zhang ,&nbsp;Ziyi Shan ,&nbsp;Yang Yang ,&nbsp;Menglu Wang ,&nbsp;Jiamei Xie ,&nbsp;Yan Huang ,&nbsp;Wanxin Fu ,&nbsp;Yueying Yuan ,&nbsp;Baosheng Zhao","doi":"10.1016/j.jep.2025.120408","DOIUrl":"10.1016/j.jep.2025.120408","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Mulberry leaf (<em>Morus alba</em> L.), traditionally recorded in “Compendium of Materia Medica” for diabetes treatment. Mulberry leaf water extract (MLE) has also been shown in modern studies to improve blood glucose levels while restoring gut microbiota homeostasis and increasing short-chain fatty acids (SCFAs) levels. However, the causal relationship between MLE-promoted SCFAs elevation and improvements in glucose/lipid metabolism as well as the exact mechanism, remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to clarify the causal relationship between MLE-promoted SCFAs elevation and improvements in glucose/lipid metabolism as well as the exact mechanism.</div></div><div><h3>Materials and methods</h3><div><em>db/db</em> mice received antibiotic-induced microbiota depletion to generate pseudo-germ-free model, followed by parallel interventions: fecal microbiota transplantation (FMT) from MLE (4 g crude drug/kg)-treated or untreated donors, and direct SCFAs supplementation. Glucose and lipid metabolism in brown adipose tissue (BAT) and inguinal white adipose tissue (IWAT), and hepatic steatosis/inflammation were evaluated through biochemical assays, qRT-PCR and histology. Protein expressions in adipose tissues were assessed by Western blotting and immunohistochemistry. Gut microbiota composition was analyzed by 16S rRNA sequencing and fecal SCFAs levels were detected by targeted metabolomics.</div></div><div><h3>Results</h3><div>Both FMT-MLE and SCFAs treatments demonstrated marked metabolic benefits, including enhanced glucose/lipid homeostasis, improved lipid metabolism, alleviated hepatic steatosis and inflammation, restored microbial balance, and elevated SCFAs concentrations. Mechanistically, mice treated with FMT-MLE and SCFAs showed increased BAT activity and exhibited increased energy expenditure, and browning of WAT. Additionally, FMT-MLE and SCFAs upregulated the protein expression of phosphorylated-AMP-activated protein kinase (p-AMPK), p-AMPK/adenosine monophosphate-activated protein kinase (AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) in BAT and IWAT.</div></div><div><h3>Conclusion</h3><div>MLE-modulated gut microbiota ameliorates T2DM via SCFAs-activated AMPK/SIRT1/PGC-1α signaling , promoting WAT browning and BAT activation.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120408"},"PeriodicalIF":5.4,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873482","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-breast cancer effects of Pterocarpus soyauxii Taub aqueous extract and its compounds by integrating ADMET, network pharmacology, molecular docking, dynamic simulation, CLC-Pred and pdCSM-Cancer/PPI approaches, and in vitro validation","authors":"Owona Pascal Emmanuel ,&nbsp;Mengue Ngadena Yolande Sandrine ,&nbsp;Bilanda Danielle Claude ,&nbsp;Ayissi Mbomo Rigobert-Espoir ,&nbsp;Oluwafemi Adeleke Ojo ,&nbsp;Ella Armand Fils ,&nbsp;Bidingha A Goufani Ronald ,&nbsp;Bindzi Georges Michel ,&nbsp;Dzeufiet Djomeni Paul Désiré ,&nbsp;Tariq Aziz ,&nbsp;Abdulhakeem S. Alamri ,&nbsp;Walaa F. Alsanie ,&nbsp;Majid Alhomrani","doi":"10.1016/j.jep.2025.120407","DOIUrl":"10.1016/j.jep.2025.120407","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Breast cancer is one of the most common reasons women seek treatment at hospitals, and it has an exceptionally high mortality rate. Powder from the heartwood of &lt;em&gt;Pterocarpus soyauxii&lt;/em&gt; Taub (&lt;em&gt;P. soyauxii&lt;/em&gt;) is used in the department of Lékoumou in the Republic of the Congo (Congo-Brazzaville) in Central Africa to treat cancer.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;This exploratory study evaluated the anti-breast cancer effects of &lt;em&gt;Pterocarpus soyauxii&lt;/em&gt; (&lt;em&gt;P. soyauxii&lt;/em&gt;) compounds identified through the LC-MS in our recently published studies and its water extract.&lt;/div&gt;&lt;div&gt;Material and methods: The physicochemical, pharmacokinetic, and toxicological properties of these compounds were predicted via the MolSoft, AI-Druglab, ToxCSM, and SToPToX databases. Network pharmacology was conducted on both target proteins of breast cancer and &lt;em&gt;P. soyauxii&lt;/em&gt; compounds via GeneCards, Metascape, STRING, and Cytoscape. Mapping of the signaling pathways involved in breast cancer and the PI3K/AKT/mTOR pathway was performed, and a KEGG pathway was constructed. A PPI network was established, and proteins with high scores were selected for molecular docking via Biovia and Molegro Virtual Docker software. The cytotoxic and proliferation-inhibitory capacities of breast cancer cell lines, as well as the proteins involved, were predicted using the CLC-Pred, way2drug, and pdCSM databases and &lt;em&gt;in vitro&lt;/em&gt; assay.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The results indicated that the compounds of &lt;em&gt;P. soyauxii&lt;/em&gt; exhibited very low toxicity, were soluble in water, and were more than 30 % absorbable by the intestine, with a distribution greater than 2 L/kg and a half-life of less than 41.64 h. Network pharmacology and molecular docking revealed that the compounds interact with MAPK1 and CDK2, with respective energies lower than tamoxifen, at −87.03 mol/kcal and −125.66 mol/kcal for pterostilbene and linoleic acid. The compounds displayed cytotoxic and inhibitory effects on the proliferation of breast cancer cell lines, including MCF7 and MDA-MB-453, with a probability greater than 0.45 and a minimum GI&lt;sub&gt;50&lt;/sub&gt; % of 4, which was weaker compared to tamoxifen. Additionally, the compounds exhibited antiestrogenic activity, with IC&lt;sub&gt;50&lt;/sub&gt; values less than 5 Mole and Ki values greater than 5.50 Mole. Furthermore, the aqueous extract of &lt;em&gt;P. soyauxii&lt;/em&gt; reduced the viability of MDA-MB-468 and MCF-7 cells less than tamoxifen, with IC&lt;sub&gt;50&lt;/sub&gt;s of 78.389 ± 0.0125 μg/mL and 58.389 ± 0.028 μg/mL, respectively.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;These results suggest that &lt;em&gt;P. soyauxii&lt;/em&gt; and its compounds have protective effects against various types of breast cancer by inhibiting the PI3K/AKT/mTOR pathway, which is essential for cell cycle progression and survival of cancer cells. However, &lt;em&gt;in vivo&lt;/em&gt; experimental validation in models remains necessary to confi","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120407"},"PeriodicalIF":5.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862244","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":"Uncaria attenuata and its main corynanthean alkaloid, villocarine A, exert antinociceptive effects in rats via activation of central μ-opioid receptors","authors":"Tan Ai Fein Ching-Ga ,&nbsp;Nelson Jeng-Yeou Chear ,&nbsp;Mohamad Anuar Ahad ,&nbsp;Boon-Keat Khor ,&nbsp;Francisco León ,&nbsp;Abhisheak Sharma ,&nbsp;Maria ABL. Seabra ,&nbsp;Wen-Nee Tan ,&nbsp;Zurina Hassan ,&nbsp;Vikneswaran Murugaiyah ,&nbsp;Christopher R. McCurdy ,&nbsp;Surash Ramanathan","doi":"10.1016/j.jep.2025.120431","DOIUrl":"10.1016/j.jep.2025.120431","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Uncaria</em> plants (Rubiaceae) are traditionally used to treat various CNS disorders, including pain and drug addiction. In Southeast Asia, <em>Uncaria</em> plants are also used as a substitute for kratom (<em>Mitragyna speciosa</em>).</div></div><div><h3>Aim of the study</h3><div>This study was designed to investigate the opioid analgesic activity of <em>Uncaria attenuata</em> (UA) methanol extract, total alkaloid extract, and the main alkaloid – villocarine A.</div></div><div><h3>Materials and methods</h3><div>The antinociceptive activity of UA methanol extract at doses of 250 and 500 mg/kg, as well as the total alkaloid extract at 50 and 100 mg/kg, and villocarine A at 5, 10, and 20 mg/kg, was evaluated orally in healthy male Sprague Dawley rats using a hot plate model. Morphine and mitragynine were used as positive controls. The extracts were also analyzed for their villocarine A content using a validated HPLC-DAD method. The involvement of central opioid receptors in the antinociceptive effects induced by UA extracts and villocarine A was further confirmed through an <em>in vivo</em> naloxone antagonism test and an <em>in vitro</em> radioligand binding assay.</div></div><div><h3>Results</h3><div>The UA methanol extract (500 mg/kg) and alkaloid extract (100 mg/kg) significantly reduced pain sensation in rats (<em>P</em> &lt; 0.05) in the hot-plate model. Villocarine A (20 mg/kg, p.o.) also significantly reduced pain, with an effect comparable to morphine (5 mg/kg, i.p.) and superior to mitragynine (20 mg/kg, p.o.). The antinociceptive effects of UA alkaloid extract and villocarine A were all blocked by naloxone (2 mg/kg, i.p.), a non-selective opioid receptor antagonist. The receptor-radioligand binding assay further demonstrated that both UA alkaloid extract and villocarine A bound to μ-opioid receptors (<em>Ki</em> = 872 ng/mL; 944 nM, respectively). HPLC analysis revealed that the UA methanol and alkaloid extracts contained approximately 3 % and 25 % (<em>w/w</em>) of villocarine A, respectively.</div></div><div><h3>Conclusion</h3><div>The UA methanol extract and its alkaloid-enriched extract, and villocarine A exhibited significant opioid analgesic effects in animal and <em>in vitro</em> models. This study supports the potential use of <em>Uncaria</em> species as a pain reliever as well as an alternative to kratom.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120431"},"PeriodicalIF":5.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862248","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":"Ma Xing Shi Gan Decoction alleviates lipopolysaccharide-induced pneumonia by inhibiting NLRP3 inflammasome activation via AMPK/mTOR/ULK1-mediated autophagy","authors":"Chen Su ,&nbsp;Hui Liu ,&nbsp;Lina Liu ,&nbsp;Chen Bai ,&nbsp;Qianqian Li ,&nbsp;Lin Jiang ,&nbsp;Yongkuan Ji ,&nbsp;Futongyu Sun ,&nbsp;Xue Li ,&nbsp;Xiaohong Gu ,&nbsp;Tiegang Liu","doi":"10.1016/j.jep.2025.120418","DOIUrl":"10.1016/j.jep.2025.120418","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Pneumonia represents a common acute respiratory infection that presents a major health concern worldwide. The Ma Xing Shi Gan Decoction (MXSG) is a famous formulation utilized for respiratory ailments for millennia and celebrated for its impressive therapeutic benefits. However, the specific mechanism of MXSG alleviating pneumonia remains unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;This research aimed to investigate the involvement of the NLRP3 inflammasome and autophagy in pneumonia induced by lipopolysaccharide (LPS), and to examine the therapeutic mechanisms associated with MXSG.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;The principal MXSG components were characterized through the application of high-performance liquid chromatography coupled with mass spectrometry. To investigate how MXSG impacts the inflammatory response and autophagy, and NLRP3 inflammasome activation, a rat model of pneumonia was created via LPS inhalation. Additionally, LPS-stimulated J774A.1 macrophages were utilized for in vitro investigations. Furthermore, the processes through which MXSG promotes autophagy and subsequently suppresses excessive NLRP3 inflammasome activation were examined utilizing 3-methyladenine (3-MA, which inhibits autophagy), compound C (CC, an inhibitor of AMPK), and siAMPK (siRNA targeting AMPK). To evaluate the binding affinity of the primary active compounds in MXSG with the essential proteins associated with autophagy, molecular docking studies were conducted.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A comprehensive analysis revealed the identification of 828 active compounds within MXSG. In vivo, MXSG significantly alleviated lung inflammation in rats with pneumonia induced by LPS. The mechanism included improving autophagy and the subsequent inhibition of excessive NLRP3 inflammasome activation via the AMPK/mTOR/ULK1 pathway. Notably, 3-MA and CC greatly reduced the suppressive impact of MXSG on NLRP3 inflammasome activation. Molecular docking revealed that the active compounds of MXSG (amygdalin, licoricesaponin G2, and daidzein) exhibited high binding affinities to autophagy-related proteins (AMPK, mTOR, and ULK1). In vitro, MXSG demonstrated anti-inflammatory properties in LPS-activated J774A.1 macrophages and suppressed excessive NLRP3 inflammasome activation by promoting autophagy. Similarly, silencing AMPK genes notably diminished the suppressive effects of MXSG on NLRP3 inflammasome activation. This confirms that MXSG enhances autophagy and inhibits NLRP3 inflammasome activation is dependent on the AMPK/mTOR/ULK1 pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;MXSG activates the AMPK/mTOR/ULK1 pathway, promoting autophagy and inhibiting excessive NLRP3 inflammasome activation induced by LPS. This subsequently reduces inflammatory cytokine (IL-1β, IL-18) levels, thereby mitigating LPS-triggered lung inflammation. The primary active compounds of MXSG that promote autophagy","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"353 ","pages":"Article 120418"},"PeriodicalIF":5.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862245","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}