Journal of ethnopharmacology最新文献

{"title":"Exploring the mechanisms of Hu-gu-xiao-ji formula and its components for treatment on non-small cell lung cancer using UPLC-QTOF-MS/MS, network pharmacology, and experiments.","authors":"Jiao Wang, Xiaoqiang Wang, Yanan Li, Qiong Huang, Zunjiang Li, Yunyi Zhao, Canbin Zhang, Lina Ding, Rui Zhou, Zhenzhen Xiao, Yaya Yu, Yanjuan Zhu, Haibo Zhang","doi":"10.1016/j.jep.2025.120637","DOIUrl":"10.1016/j.jep.2025.120637","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Non-small cell lung cancer (NSCLC) represents the leading cause of cancer-related morbidity and mortality worldwide, where effective and safe therapeutic options for advanced stages remain limited. The Hu-gu-xiao-ji (HGXJ) formula, derived from traditional formulations including Si-jun-zi decoction and Bu-gu pill, has demonstrated efficacy in alleviating bone pain in metastatic NSCLC. Nevertheless, its active components and underlying mechanisms against primary NSCLC are not fully elucidated.</p><p><strong>Aim of the study: </strong>To explore the therapeutic effects, chemical compositions, and molecular mechanisms of HGXJ formula against NSCLC through integrated in vitro and in vivo approaches.</p><p><strong>Materials and methods: </strong>The antitumor efficacy of HGXJ formula was assessed using subcutaneous xenograft models and NSCLC cell lines. Serum-absorbed bioactive compounds were identified by ultra-high performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). Potential targets and signaling pathways were predicted through integrated network pharmacology, bioinformatics analysis, and molecular biology experiments. Molecular docking, cellular assays and in vivo validation were subsequently employed to verify antitumor effects and compound-target interactions.</p><p><strong>Results: </strong>HGXJ formula exhibited significant in vivo and in vitro antitumor activity by promoting apoptosis and inhibiting proliferation. UPLC-QTOF-MS/MS analysis identified 30 blood-entry constituents. Subsequent investigations revealed that HGXJ formula disrupted the kelch-like ECH-associated protein 1 (KEAP1) -nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant pathway, triggering reactive oxygen species (ROS) accumulation and consequent cell death. Three bioactive compounds, isobavachin, bavachalcone, and 18β-glycyrrhetinic acid were screened out and validated to induce ROS-mediated cytotoxicity and target antioxidant pathway. In vivo studies further substantiated the antitumor activity of 18β-glycyrrhetinic acid and its targeting of KEAP1/NRF2 proteins.</p><p><strong>Conclusion: </strong>HGXJ formula and its blood-entry bioactive compounds exerted antitumor effects on NSCLC via suppressing the KEAP1-NRF2 antioxidant axis and inducing ROS-dependent cell death. These findings provide robust evidence supporting the scientific basis for the application of HGXJ formula in advanced NSCLC treatment.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120637"},"PeriodicalIF":5.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137722","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":"Comparative studies on the components and anti-ulcerative colitis effects of raw and carbonized Linderae Radix","authors":"Xunjie Zheng ,&nbsp;Ke Li ,&nbsp;Jiangning Hu ,&nbsp;Ziyi Zhang ,&nbsp;Jialin Pan ,&nbsp;Aixiao Xia ,&nbsp;Zhiwei Ge ,&nbsp;Junwei Wang ,&nbsp;Zhaohuan Lou","doi":"10.1016/j.jep.2025.120629","DOIUrl":"10.1016/j.jep.2025.120629","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Linderae Radix</em> (LR) is a traditional Chinese medicine widely used in the clinical treatment of ulcerative colitis (UC). Carbonized <em>Linderae Radix</em> (CLR) is produced by stir-frying of LR. However, the effects of carbonization on its chemical composition and therapeutic efficacy in UC remain unclear.</div></div><div><h3>Aim of the study</h3><div>To compare the chemical composition and therapeutic effects of LR and CLR in dextran sulfate sodium (DSS)-induced UC.</div></div><div><h3>Materials and methods</h3><div>The chemical profiles of LR and CLR were analyzed by UPLC-Triple-TOF/MS. A 2.5 % DSS-induced UC mouse model was used to assess treatment efficacy. Disease indicators such as DAI scores, colon length, and spleen index were evaluated. Histopathology, AB-PAS staining, immunohistochemistry, and immunofluorescence were employed to assess epithelial integrity, mucus barrier, proliferation, and intestinal stem cells (ISCs). Network pharmacology was performed to explore underlying mechanisms. The above results were verified using molecular docking.</div></div><div><h3>Results</h3><div>Carbonization significantly altered LR's chemical profile, with the loss of bioactive compounds such as Linderalactone and Norisoboldine, and the emergence of new constituents like Ethyl caffeate. Both LR and CLR improved UC symptoms, preserved tight junctions, protected ISCs, and promoted epithelial proliferation. LR more effectively reduced histological damage and maintained crypt structure and goblet cells. CLR showed superior effects on mucus barrier restoration by upregulating MUC2 expression. Network analysis revealed that CLR targets were mainly enriched in inflammation- and apoptosis-related pathways (MAPK, PI3K-Akt, IL-17), while LR was enriched in regenerative and stemness-related pathways (Wnt, Notch, and JAK-STAT).</div></div><div><h3>Conclusion</h3><div>Carbonization alters the chemical composition and therapeutic focus of LR. LR primarily enhances mucosal regeneration and ISCs activity, while CLR improves the mucus barrier and modulates inflammatory responses.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120629"},"PeriodicalIF":5.4,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131057","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":"Tetrahydroxy stilbene glucoside promotes hair regeneration by inducing Th22 cell differentiation","authors":"Lingjie Zhang ,&nbsp;Nana Tao ,&nbsp;Yuchi Chen ,&nbsp;Jie Xu ,&nbsp;Zhiwei Chen ,&nbsp;Guangji Zhang ,&nbsp;Jianli Gao","doi":"10.1016/j.jep.2025.120627","DOIUrl":"10.1016/j.jep.2025.120627","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Hair plays an important roles in both local protection and information transmission. But as a widespread problem, the existing therapies of hair loss are limited. 2,3,5,4′-Tetrahydroxystilbene-2-<em>O-β</em>-D-Glucoside (Tetrahydroxy stilbene glucoside, TSG) is the main active compound of a hair promoting herb, <em>Polygonum multiflorum</em> Thunb., that has been used in China for over 1000 years. However, its role and mechanism of action remain unclear.</div></div><div><h3>Aim of the study</h3><div>To investigate the promoting effect of TSG on hair growth and elucidate the mechanism by which TSG affects hair regeneration via Th22.</div></div><div><h3>Materials and methods</h3><div>Mouse skin explants and 3D <em>ex vivo</em> culture systems were employed to screen substances of <em>P. multiflorum</em> for promoting hair growth. The hair regeneration effect of TSG was explored via mice model by subcutaneous injection. The changes of biological dynamics, hair regeneration, histomorphology of skin, and morphology of hair follicle were observed. T cell subsets in peripheral blood was analyzed by Flow cytometry. Network pharmacology was used to predict the mechanism of TSG, immunohistochemistry and immunofluorescence staining were used to analyzed the distribution of T cell subsets around hair follicles. IL-22BP was used to verify the role of Th22 cells in TSG regulating hair regeneration in mice.</div></div><div><h3>Results</h3><div><em>Ex vivo</em> organ experiments showed that compared with emodin and catechol, TSG could effectively promote the process of hair follicle transition from telogen to anagen, and make them rapidly proliferate and differentiate into hair matrix. TSG accelerated the hair growth in mice, increased the number of hair follicles and the proportion of CD4⁺ T cells in peripheral blood, unregulated the expression of CCR10 (Th22 marker) in the hair root sheath of hair follicle. Network pharmacology suggested TSG treatment was associated with T cell differentiation related signaling pathways, it could facilitated the differentiation and development of T cells around hair follicles, driving their transition to the Th22 subtype. IL-22BP confirmed that IL-22 secreted by activated Th22 cells is the key factor mediating hair regeneration promoted by TSG, which indirectly verifies that Th22 cells are the effector cells responsible for TSG-induced hair regeneration.</div></div><div><h3>Conclusions</h3><div>TSG accelerates the growth of mice hair follicles and promoting the regeneration of hair follicles by regulating the distribution and immune homeostasis of T cell subsets around hair follicles and promoting the differentiation and development of Th22 cells.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120627"},"PeriodicalIF":5.4,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120049","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":"SitoshnaPred: Learning phytochemical descriptors to elucidate Ayurvedic herbal potency","authors":"Ashish Panghalia,&nbsp;Vikram Singh","doi":"10.1016/j.jep.2025.120620","DOIUrl":"10.1016/j.jep.2025.120620","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;In Ayurveda, the potency of herbs is traditionally classified into three categories, namely, Sīta (cold), Uṣṇa (hot), and Unuṣṇa (neutral). In this study, a gold standard dataset of 627 herbs with their potency preferences has been developed using the classical literature-based textbooks. With the premise that the herbal potencies must be associated with their phytochemical constituents, a machine learning framework is developed using the molecular descriptors of the phytochemicals. This study will pave the way for characterizing the molecular basis of the traditional wisdom of herbal potencies and for utilizing this knowledge for the future development of artificial intelligence-guided technologies towards predicting the potency and other features of the traditional herbs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;This study aims to examine the cold and hot nature of Ayurvedic herbs by analyzing their constituent phytochemicals and to develop an ensemble learning-based binary classifier.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We developed a standard dataset of 627 herbs that are commonly used in Ayurvedic formulations and are well classified into the Sīta (cold), Uṣṇa (hot), and Unuṣṇa (neutral) categories as per their potency. Since only 7 herbs were associated with Unuṣṇa category, this class of herbs were not used in the further studies. Firstly, a dataset comprising of 13,534 phytochemicals associated with 454 herbs was developed; no associations could be retrieved for remaining herbs. Further, the phytochemicals distribution into the Sīta and Uṣṇa herbs was studied, and 1613 two-dimensional and 213 three-dimensional molecular descriptors were calculated for each phytochemical. By reducing the dimensionality of the dataset corresponding to the 95 % variability, binary and ternary SitoshnaPred classifiers were developed using the LightGBM algorithm. SHAP (SHapley Additive exPlanations) analysis and Loadings analysis were conducted to interpret the models’ predictions and to identify the most influential molecular descriptors contributing to classification performance.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 7193 phytochemicals were identified in the herbs of Sīta group, and 9116 phytochemicals in the herbs of Uṣṇa group. The LightGBM algorithm-based SitoshnaPred models were developed using the top 92 principal components corresponding to 95 % of the total variance. The binary classification model achieved an accuracy of 94.01 % and an AUC of 98.41 %, whereas the ternary classification model attained an accuracy of 79.84 % and an AUC of 98.10 %. SHAP (SHapley Additive exPlanations) analysis, combined with loadings analysis, was used to interpret the models’ predictions and identify the most influential molecular descriptors contributing to classification performance.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Molecular descriptors of the constituent phytochemicals carry strong signals of the he","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120620"},"PeriodicalIF":5.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102888","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 analysis reveals the mechanism of Cistanche deserticola against alcoholic liver disease via bile salt hydrolase and SCD1","authors":"Shuo Yuan,&nbsp;Peng Gao,&nbsp;Jun Lei,&nbsp;Jiaxu Sun,&nbsp;Xinlan Fang,&nbsp;Pengfei Tu,&nbsp;Yingyuan Lu,&nbsp;Yong Jiang","doi":"10.1016/j.jep.2025.120626","DOIUrl":"10.1016/j.jep.2025.120626","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Cistanche deserticola</em> Y. C. Ma, revered as “desert ginseng” in traditional Chinese medicine, has been historically prescribed for treating five strains and seven injuries, and nourishing the five zang organs. While the total glycosides from <em>C. deserticola</em> (GCs) demonstrate hepatoprotective potential against acute alcoholic liver disease (ALD), their efficacy in chronic ALD and mechanism remain unexplored.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the protective effects of GCs against chronic ALD and to elucidate its molecular mechanisms by multi-omics approach.</div></div><div><h3>Materials and methods</h3><div>A chronic ALD mouse model evaluated the therapeutic effects of GCs, with systematic assessment of hepatic pathological features including liver index, liver functions, and oxidative stress, etc. Integrated multi-omics strategies (plasma-targeted metabolomics, bile acid-specific profiling, hepatic transcriptomics) were employed to delineate metabolic reprogramming and identify critical signaling pathways. The BSH inhibitor caffeic acid phenethyl ester (CAPE) was used as a pharmacological tool for the mechanistic investigation of GCs. The molecular mechanism was validated by qRT-PCR, Western blot, and small interfering RNA (siRNA)-mediated gene silencing methods.</div></div><div><h3>Results</h3><div>GCs treatment significantly attenuated ALD pathologies. Plasma-targeted metabolomics and bile acid profiling demonstrated GCs-mediated remodeling of bile acid homeostasis and lipid metabolic networks. Mechanistically, GCs potently inhibited BSH activity, which was validated the pivotal role in ALD pathogenesis by CAPE. Transcriptomic and molecular analyses revealed that GCs subsequently reduced SCD1, and activated AMPK/mTOR signaling, thereby coordinately regulating lipid catabolism, and inflammatory cascades.</div></div><div><h3>Conclusion</h3><div>These findings highlight the protective effects of GCs against chronic ALD through inhibition of BSH activity to dictate bile acid metabolism, thereby alleviating cholestasis, which subsequently regulate SCD1/AMPK/mTOR signaling pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120626"},"PeriodicalIF":5.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102879","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":"Qingguang’An II decoction attenuates retinal ganglion cell pyroptosis in glaucoma via inhibition of the TRPV4/NF-κB signaling pathway","authors":"Yu Huang ,&nbsp;Xin Xia ,&nbsp;DanYang Li ,&nbsp;Yi Lyu ,&nbsp;Pai Zhou ,&nbsp;Hongda Cui ,&nbsp;YaSha Zhou ,&nbsp;YiJing Yang ,&nbsp;QingHua Peng","doi":"10.1016/j.jep.2025.120576","DOIUrl":"10.1016/j.jep.2025.120576","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Glaucomatous optic neuropathy (GON), characterized by the progressive degeneration of retinal ganglion cells (RGCs), is the primary pathological basis of irreversible visual impairment in glaucoma. Qingguang’An II decoction (QGAII), a traditional Chinese medicine formula with decades of clinical application, has been shown to promote optic nerve repair and preserve the visual field in patients with GON. Nevertheless, the precise mechanisms underlying the neuroprotective effects of QGAII remain incompletely understood.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the specific molecular mechanisms by which QGAII mitigates RGC pyroptosis through the targeted modulation of the TRPV4/NF-κB signaling pathway.</div></div><div><h3>Materials and methods</h3><div>The neuroprotective effects of QGAII were evaluated both in vivo using a DBA/2J mouse model of chronic ocular hypertension and <em>in vitro</em> using a novel cell model of glaucomatous injury. <em>In vivo</em>, the effect of QGAII intervention was assessed by hematoxylin and eosin (H&amp;E) staining and transmission electron microscopy (TEM). The mechanism of action was further investigated by immunofluorescence, flow cytometry, Western blot (WB), qPCR, and ELISA. <em>In vitro</em>, a novel glaucomatous cell injury model was established by combining continuous hydrostatic pressure (CHP) and oxygen-glucose deprivation (OGD). Liposome transfection was employed to explore the roles of TRPV4, NF-κB, and GSDMD. Subsequently, QGAII was administered to this injury model, and its effects were analyzed using a cell counting kit-8 (CCK-8), flow cytometry, scanning electron microscopy (SEM), immunofluorescence, WB, qPCR, and ELISA to clarify its role in attenuating pyroptosis via the TRPV4/NF-κB signaling pathway.</div></div><div><h3>Results</h3><div><em>In vivo</em>, H&amp;E staining and TEM showed that QGAII exerted a protective effect on RGCs in the retina of DBA/2J mice, and this effect was linked to a reduction in RGC pyroptosis. Further analysis showed that QGAII attenuated RGC pyroptosis in DBA/2J mice, potentially through the TRPV4/NF-κB signaling pathway. <em>In vitro</em>, we first established that the cell injury model, induced by CHP and OGD, exhibited a GSDMD-dependent pyroptotic phenotype. This process was confirmed to be regulated by the TRPV4/NF-κB signaling pathway. Subsequent QGAII intervention reduced the incidence of RGC pyroptosis. This protective effect was mediated by the inhibition of the TRPV4/NF-κB signaling pathway, as confirmed by immunofluorescence, WB, qPCR, and ELISA.</div></div><div><h3>Conclusion</h3><div>QGAII suppresses RGC pyroptosis through the targeted modulation of the TRPV4/NF-κB signaling pathway, providing effective optic neuroprotection for the therapeutic management of GON.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120576"},"PeriodicalIF":5.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102841","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":"Elucidation of the potential molecular mechanisms of Buyang Huanwu Decoction in delaying cardiac aging: Based on network pharmacology, bioinformatics, and in vivo/in vitro experimental validation","authors":"Xiaodong Duan ,&nbsp;Yongan Deng ,&nbsp;Minghao Feng ,&nbsp;Chengkai Chen ,&nbsp;Simin Yang ,&nbsp;Shuting Zeng ,&nbsp;Xiaodie Chen ,&nbsp;Nan Xiao ,&nbsp;Xiangyu Chen ,&nbsp;Jianhua Li ,&nbsp;Yixuan Huang ,&nbsp;Yutong Yang ,&nbsp;Min Yu ,&nbsp;Guangwei Wang ,&nbsp;Wenrong Yu ,&nbsp;Li Zhang ,&nbsp;Yi Wang ,&nbsp;Zunpeng Shu","doi":"10.1016/j.jep.2025.120624","DOIUrl":"10.1016/j.jep.2025.120624","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Cardiac aging is closely associated with the occurrence and progression of various cardiovascular diseases (CVD). Buyang Huanwu Decoction (BYHWD), a classical traditional Chinese medicine formula, is widely used clinically for cerebrovascular and cardiovascular diseases. However, its role in delaying cardiac aging and the underlying molecular mechanisms remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the role of BYHWD in cardiac aging and explore its potential molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>D-galactose (D-gal) was used to establish <em>in vivo</em> and <em>in vitro</em> aging models, with BYHWD administered as an intervention. Histopathological examination and biochemical assays assessed cardiac tissue damage, and Western blot detected aging-related markers. Untargeted metabolomics and network pharmacology identified potential targets and pathways. Finally, molecular biology methods such as RT-qPCR, Immunohistochemistry, and Western blot were used to validate the expression levels of genes and proteins in key pathways.</div></div><div><h3>Results</h3><div>BYHWD effectively alleviated cardiac pathological injury, significantly inhibited the mRNA levels of pro-inflammatory factors <em>Il-1β</em>, <em>Il-6</em>, and <em>Tnf-α</em> in cardiac tissues, and downregulated the expression of senescence-related proteins p16, p21, and p53. Untargeted metabolomics analysis revealed that BYHWD might restore metabolic disorders in the hearts of aging rats by regulating energy and amino acid metabolism pathways. Network pharmacology analysis demonstrated that BYHWD might delay cardiac aging by modulating immune and inflammatory responses, with the CaM/CaMKII/MAPK pathway being significantly enriched in its mechanism of action. RT-qPCR, Immunohistochemistry, and Western blot further confirmed that BYHWD exerted its anti-aging effects on the heart by inhibiting the CaM/CaMKII/MAPK pathway.</div></div><div><h3>Conclusion</h3><div>BYHWD was found to effectively delay D-gal-induced aging in both rat hearts and cardiomyocytes. Mechanistically, BYHWD modulated energy and amino acid metabolic pathways while inhibiting the CaM/CaMKII/MAPK axis to exert anti-inflammatory effects. Overall, this study provides novel insights into the mechanisms through which BYHWD delays cardiac aging.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120624"},"PeriodicalIF":5.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091828","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":"Exploring the neuroprotective mechanism of the Mongolian medicine ZSP against acute ischemic stroke from TRPV1/NMDAR-mediated excitotoxicity","authors":"Rui-Kun Wang ,&nbsp;Ming-Yang Cai ,&nbsp;Xue Yu ,&nbsp;Zhen-Hong Liu ,&nbsp;Hanqiong Hu ,&nbsp;Limuge Che ,&nbsp;Xiaoxuan Li ,&nbsp;Bagen Hurile ,&nbsp;Qiqige Wulan ,&nbsp;Jisiguleng Wu ,&nbsp;Jing Li ,&nbsp;Zhen Yang ,&nbsp;Hai-Ying Tong","doi":"10.1016/j.jep.2025.120625","DOIUrl":"10.1016/j.jep.2025.120625","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Zhachong Thirteen Flavored Pill, a classical preparation of Mongolian medicine, is a commonly used formula in Mongolian medicine for the treatment of ischemic stroke, and it has good clinical efficacy in both the acute and postictal phases of AIS. However, the mechanism of its treatment of AIS is still unclear.</div><div>Aim of the study: This study aims to elucidate the molecular mechanism by which Zhachong Thirteen Flavored Pill alleviates cerebral ischemia-reperfusion (MCAO/R) injury through targeted regulation of TRPV1 channels and their downstream signaling pathways, and to validate its neuroprotective effects.</div></div><div><h3>Methods</h3><div>At the cellular level, whole-cell patch-clamp was used to demonstrate the effect of Zhachong Thirteen Flavored Pill on the electrophysiology of TRPV1; the potential targets of Zhachong Thirteen Flavored Pill for the treatment of AIS were found through the use of network pharmacology, as well as the correlation between the core targets and TRPV1; MCAO/R model rats were replicated using the wire bolus method and divided into the sham-operation group, the model group, the edaravone group, as well as the equivalent dose and high dose of Zhachong Thirteen Flavored Pill groups. The effects of this formula on the volume of cerebral infarction in the MCAO/R model rats were evaluated by the mNSS scores, the grip traction test, and the TTC staining.</div></div><div><h3>Results</h3><div>Zhachong Thirteen Flavored Pill can target TRPV1, activate TRPV1 on TRPV1-HEK293 cells, and generate transmembrane currents; the core target is closely related to TRPV1; the binding energies of TRPV1 and NMDAR with CMGS, GCC, and LKL of AIS are all less than -7 kJ/mol; it can also lead to a increase in body weight of the MCAO/R model rat compared with that of the pre-modeling period, with no neurological deficits and normal muscle strength of the upper limbs. It reduced the infarct volume of rat brain tissue, upregulated the expression of NF-200 and NeuN, and downregulated the protein expression of Bax/Bcl-2, cytochrome C, and Cleaved-Caspase-3. The mRNA expression and protein expression of TRPV1, NMDAR1, NMDAR2B, pNMDAR2B, nNOS, CaMKII, and pCaMKⅡ were all downregulated compared with the model group.</div></div><div><h3>Conclusion</h3><div>By inhibiting TRPV1, regulating NMDAR/PSD-95/nNOS, down-regulating the expression of nNOS, Zhachong Thirteen Flavored Pill can attenuate neuronal apoptosis caused by excitotoxicity to alleviate neuronal damage, reduce the volume of cerebral infarction, improve neurological deficits and physical dysfunction, and exert neuroprotective effects.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120625"},"PeriodicalIF":5.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091821","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":"The discovery of the material basis and mechanism of gypsum as an antipyretic based on the theory of the diverse applications of raw and processed products","authors":"Taotao Wang,&nbsp;Delin Yang,&nbsp;Rong Gao,&nbsp;Yuanyuan Wen,&nbsp;Zhihui Liu,&nbsp;Jianxiu Zhai,&nbsp;Sikai Li,&nbsp;Na Han,&nbsp;Jun Yin","doi":"10.1016/j.jep.2025.120623","DOIUrl":"10.1016/j.jep.2025.120623","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Gypsum (CaSO₄·2H₂O), recognized as a classical mineral medicine in traditional Chinese medicine (TCM), has been traditionally used to treat fever. However, the specific bioactive constituents and the underlying molecular mechanisms of its action have yet to be fully elucidated.</div></div><div><h3>Aim of the study</h3><div>To address this knowledge gap, we systematically elucidated the antipyretic material basis and underlying mechanisms of gypsum through integrating the analysis of metal profile, gut microbiota profiling, and serum metabolomics.</div></div><div><h3>Materials and methods</h3><div>Metal chemical profiling was firstly used to elucidate the antipyretic composition by comparing the serum composition of gypsum and calcined gypsum. Subsequently, this research investigated the differential antipyretic effects of gypsum, calcined gypsum and key elements in a lipopolysaccharide (LPS)-induced fever model in rats by monitoring changes in body temperature and inflammatory cytokines. Furthermore, the underlying mechanism was explored through western blotting (WB), quantitative real-time PCR (qPCR), and gut microbiota in conjunction with metabolomics.</div></div><div><h3>Results</h3><div>The results reveal that Mg, Ca, Zn, and Mo were the strong candidates for active substances of gypsum. Furthermore, the research proved that gypsum and key elements (Mg, Ca, Zn, Mo) exhibits a notable antipyretic effect, while calcined gypsum does not. WB and qPCR analyses revealed a reduction in the expression of cyclooxygenase-2 (COX-2) in hypothalamic tissue in the gypsum-exposed group. Metabolomics profiling of serum suggests that the antipyretic effect of gypsum may involve primary bile acid biosynthesis. Association analysis involving gut microbiota indicated that gypsum may lead to the downregulation of five significant metabolites, including 15-Hydroxy-5,8,11,13-Eicosatetraenoic Acid, PC(16:1 (9Z)/0:0), PC(22:6 (4Z,7Z,10Z,13Z,16Z,19Z)/0:0) and PC(P-18:0/PGJ2), by downregulating <em>Bacteroides</em>, <em>Ruminococcaceae</em> and <em>Roseburia</em> to inhibit fever. Experiments involving fecal microbiota transplantation provide additional evidence for the involvement of gut bacteria in facilitating the antipyretic effects associated with gypsum.</div></div><div><h3>Conclusions</h3><div>This study pioneers in identifying the key elements (Mg, Ca, Zn, Mo) as the core antipyretic component of gypsum while establishing a multidimensional “mineral composition-gut microbiota-host metabolism” interaction network. Our findings provide mechanistic insights for optimizing quality standards of mineral-based TCM formulations.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120623"},"PeriodicalIF":5.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091896","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":"Reinwardtia indica Dumort. protects against ponatinib-induced cerebral ischemia in adult zebrafish via attenuation of oxidative stress, neuroinflammation, mitochondrial dysfunction, and neurotransmitter dysregulation: A multi-target therapeutic strategy","authors":"Karan Wadhwa,&nbsp;Payal Chauhan,&nbsp;Govind Singh","doi":"10.1016/j.jep.2025.120621","DOIUrl":"10.1016/j.jep.2025.120621","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Reinwardtia indica</em> Dumort. holds substantial importance in traditional medicine systems across Asian countries, particularly in India, Nepal, and China. The plant has been utilized in folk medicine for treating a wide range of ailments, treating neurological disorders, particularly paralysis; managing wound care and various skin conditions; providing pain relief for headaches and backaches; and aiding in gastrointestinal issues such as indigestion.</div></div><div><h3>Aim of the study</h3><div>This study investigated the potential neuroprotective effects of <em>R. indica</em>, a medicinal plant well recognized for its numerous ethnopharmacological uses, against cerebral ischemia-induced brain damage in adult zebrafish.</div></div><div><h3>Material and methods</h3><div>Zebrafish were subjected to a ponatinib-induced ischemic insult for 24 h and afterwards treated with the hydroalcoholic leaf extract of <em>R. indica</em> for 7 consecutive days. After treatment, zebrafish were evaluated for diverse biochemical parameters, including oxidative stress, neuroinflammatory markers, mitochondrial complexes, and neurotransmitter profiles, along with survival rate and brain damage analysis. Furthermore, several behavioural parameters, such as novel tank test, light and dark maze, and open field test, were also analysed to assess locomotive and cognitive impairments.</div></div><div><h3>Results</h3><div>The results demonstrated that <em>R. indica</em> post-treatment significantly attenuated oxidative stress, as evidenced by reduced levels of lipid peroxidation and increased antioxidant enzyme activity of SOD and catalase. Additionally, the extract restored mitochondrial function, as indicated by increased levels of mitochondrial complexes. Furthermore, <em>R. indica</em> treatment reduced neuroinflammation, characterized by decreased levels of inflammatory cytokines, i.e. TNF-α and IL-1β. Furthermore, <em>R. indica</em> effectively restored and normalized the level of key neurotransmitters such as glutamate, GABA, acetylcholine, serotonin, dopamine and noradrenaline, along with improvement in locomotion ability and reduced depressive-like behaviours as evident by various behavioural outcomes.</div></div><div><h3>Conclusion</h3><div>These findings suggest that <em>R. indica</em> may be a promising therapeutic candidate for mitigating the detrimental effects of cerebral ischemia by targeting behavioural alterations, oxidative stress, mitochondrial dysfunction, and neuroinflammation. However, further research is warranted to explore the potential clinical applications of <em>R. indica</em> in the treatment of stroke and other ischemic brain injuries.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120621"},"PeriodicalIF":5.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091874","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}