Journal of ethnopharmacology最新文献

{"title":"A novel cholesterol-reducing mechanism of polygonati rhizoma: Dual action via Bacteroides-mediated cholesterol sulfonation and feedback inhibition of ACAT2 by sulfated metabolite","authors":"Xinhong Wang , Manru Chen , Yu Su , Xia Zhang , Jingzhi Chen , Ziwei Huang , Jianhui Xie , Qingfeng Xie , Lianfang He , Lingye Su , Ziren Su , Hongfeng Wang , Yucui Li","doi":"10.1016/j.jep.2025.120619","DOIUrl":"10.1016/j.jep.2025.120619","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Polygonati Rhizoma (PR) has the function of “invigorating spleen and tonifying kidney”, and is historically applied as a homology of medicine and food to prevent and treat dyslipidemia in China. However, there is limited experimental evidence to support this application, and the underlying mechanism has not been fully deciphered.</div></div><div><h3>Aim of the study</h3><div>To analyze the composition and illuminate the cholesterol-lowering potential and molecular mechanism of PR's aqueous extract (PRE) in high-fat emulsion (HFE)-induced hypercholesterolemia mouse model.</div></div><div><h3>Materials and methods</h3><div>Ion chromatograph was employed to determine the monosaccharide composition of PRE. HFE-induced Kunming mouse model was constructed to evaluate the anti-hypercholesterolemia effect of PRE. Metagenomic sequences and liquid chromatography-mass spectrometry (LC-MS) analysis were performed to elucidate the mechanism through which PR regulated cholesterol metabolism. Antibiotic cocktail (ABX) intervention and fecal microbiota transplantation (FMT) were used to validate whether PRE regulated cholesterol metabolism through the intestinal microbiota. The cholesterol-reducing effect of cholesterol sulfate (CS) was explored in poloxamer 407 (P407)-induced mouse model of dyslipidemia. Molecular docking and molecular dynamics (MD) simulation were also employed to elucidate the underlying mechanisms. Furthermore, a combination of qRT-PCR, Western blot, and surface plasmon resonance (SPR) were employed to delineate its mechanism.</div></div><div><h3>Results</h3><div>Our study indicated that the polysaccharides of PRE were mainly composed of fructose (92.33 %) and glucose (5.25 %). PRE treatment effectively blocked body weight gain, significantly decreased serum and hepatic levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C) level. Additionally, PRE ameliorated hepatic lipid accumulation in mice with HFE-elicited hypercholesterolemia. Notably, metagenomic sequencing and LC-MS analysis indicated that PRE markedly increased the abundance of intestinal genera <em>Bacteroides</em> and significantly elevated the fecal CS concentration in HFE mice. Genome-based functional analysis further indicated that cofactors of sulfonation (ATP sulfurylase CysD and CysN, BT0414-BT0415) were significantly upregulated after treatment with PRE. The cholesterol-lowering effect of PRE was largely contingent upon microbial conversion of cholesterol-to-CS mediated by <em>Bacteroides</em>, as validated by antibiotics-induced intestinal microbiota depletion in pseudo-germ-free model and restoration of gut microbiota through FMT. <em>In vitro</em> study also showed that PRE promoted the growth of <em>Bacteroides thetaiotaomicron</em>. Furthermore, CS markedly alleviated serum, hepatic, bile, and fecal levels of TG, T","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120619"},"PeriodicalIF":5.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091894","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":"Magnoliae Officinalis Cortex volatile oil alleviated asthma via dual cAMP-mediated pathways: Anti-Inflammation and Bronchodilation","authors":"Kedi Li ,&nbsp;Zhangjing Cao ,&nbsp;Jiayao Sun ,&nbsp;Ruizhi Liu ,&nbsp;Xinya Wen ,&nbsp;Fei Tang ,&nbsp;Lin Liu ,&nbsp;Fu Peng ,&nbsp;Cheng Peng ,&nbsp;Hui Ao","doi":"10.1016/j.jep.2025.120622","DOIUrl":"10.1016/j.jep.2025.120622","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Magnoliae Officinalis Cortex, a commonly used Chinese medicinal herb, has a long history in traditional East Asian medicine and is widely employed in the treatment of gastrointestinal disorders, asthma, depression, and other ailments. However, the potential of volatile oil derived from the bark of Magnolia officinalis Cortex (MVO) in asthma treatment remains to be determined.</div></div><div><h3>Aim of the study</h3><div>This study aimed to explore the therapeutic effect of MVO on asthma and to explore its pathway and molecular mechanism under cAMP signal background.</div></div><div><h3>Methods</h3><div>This study combined GC-MS with in vivo and in vitro experiments to elucidate the anti-asthmatic mechanism of MVO. An OVA-induced asthma model was established to evaluate the therapeutic effect of MVO via pulmonary function tests, H&amp;E, BALF inflammatory cell counting, and ELISA. Fluo-4 AM, immunofluorescence and WB were further used to explore the underlying mechanism. In vitro, isolated tracheal rings were used as the object, and contraction models were constructed with KCl and acetylc holine to observe the relaxatory effect of MVO. Nifedipine (an L-type calcium channel blocker) and Pyr3 (a TRPC3 channel inhibitor) were used to intervene in the calcium signaling pathway, and the involvement of the cAMP pathway was analyzed by detecting cAMP level.</div></div><div><h3>Results</h3><div>GC-MS analysis identified high concentrations of α-eudesmol, β-eudesmol, γ-eudesmol, and <em>o</em>-cymene in MVO. In vivo experiments showed that MVO reduced OVA-induced inflammatory cell infiltration and mucus secretion, improved pulmonary function, decreased Th2-type cytokines in BALF and serum IgE level, up-regulated the level of cAMP and the expressions of p-PKA/p-CREB in lung tissues, and inhibited NF-κB activation, reducing Ca²⁺ level and membrane localization in lung tissues. In vitro experiments showed that MVO could relax tracheal smooth muscle contractions induced by KCl and ACh in a dose-dependent manner. Application of nifedipine and Pyr3 confirmed that MVO exerted its relaxant effect by blocking L-VDCC and NSCC/TRPC channels.</div></div><div><h3>Conclusion</h3><div>MVO attenuated airway hyperresponsiveness by modulating the cAMP/PKA/CREB pathway, which subsequently suppressed NF-κB-driven inflammatory responses, while concurrently restoring cAMP/Ca²⁺ homeostasis. Significantly, our study demonstrated a novel dual-action therapeutic strategy targeting cAMP for asthma, bridging bronchodilatory and anti-inflammatory effects.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120622"},"PeriodicalIF":5.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091869","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":"Optimised formula of Fufang Biejia Ruangan tablets alleviates renal fibrosis by suppressing matrix-stiffness–induced fibroblast activation via inhibition of integrin αVβ1 binding","authors":"Yuanrong Wang ,&nbsp;Lan Zhang ,&nbsp;Bing Xu ,&nbsp;Kai Wang ,&nbsp;Tong Zhang ,&nbsp;Zijie Zhang ,&nbsp;Shuangshuang He ,&nbsp;Fang Zhang ,&nbsp;Xiting Wang ,&nbsp;Yu Li","doi":"10.1016/j.jep.2025.120614","DOIUrl":"10.1016/j.jep.2025.120614","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Fufang Biejia Ruangan Tablets (FFBJ), a traditional Chinese medicine, has long been used in the management of fibrosis, demonstrating notable efficacy and safety. However, the bioactive components of FFBJ and their mechanisms of action remain poorly understood.</div></div><div><h3>Aim of the study</h3><div>To identify the core bioactive components of FFBJ and elucidate their mechanisms of action against renal fibrosis.</div></div><div><h3>Materials and methods</h3><div>The constituents of FFBJ were characterised using high-performance liquid chromatography–High-resolution mass spectrometry (HPLC-HRMS). A multi-tiered strategy integrating pharmacokinetic evaluation, ADMET predictions, molecular docking, and efficacy assessments (MTT/Sirius-Red assays) identified five core bioactive compounds. The synergistic ratios of these compounds were optimised using the Box–Behnken design. <em>In vitro</em>, TGF-β1–stimulated NRK49F cells were treated with FFBJ-COF, a compound composed optimised formula from FFBJ, at low (half-medium dose), medium (30 μM taxifolin, 7.732 μM turtle-shell heptapeptide [OC1], 13.623 μM quercetin, 13 μM curcumenol, and 3.3 μM hederagenin), or high (double-medium dose) concentrations. <em>In vivo</em>, mice with unilateral ureteral obstruction (UUO) were treated with FFBJ-COF via gavage at low (half-medium dose), medium (64.85 mg/kg/d taxifolin, 30.30 mg/kg/d turtle-shell heptapeptide [OC1], 29.25 mg/kg/d quercetin, 21.83 mg/kg/d curcumenol, and 10.07 mg/kg/d hederagenin), or high (1.5-fold medium dose) levels. Polyacrylamide hydrogels (1–20 kPa) were employed to mimic fibrotic-matrix stiffness. Co-immunoprecipitation and western blotting were used to investigate the regulation of integrin αVβ1 binding and the downstream FAK/RhoA/MRTF-A signalling.</div></div><div><h3>Results</h3><div>HPLC-HRMS analysis revealed 76 components. FFBJ-COF, comprising curcumenol, hederagenin, taxifolin, quercetin, and OC1, was formulated based on efficacy screening and ratio optimization. FFBJ-COF treatment attenuated renal injury and fibrosis by reducing fibroblast activation and extracellular matrix (ECM) deposition in both <em>in vivo</em> and <em>in vitro</em> model. Mechanistic studies showed that ECM stiffness activated fibroblasts, which was inhibited by FFBJ-COF. Co-immunoprecipitation demonstrated that matrix stiffness enhanced the binding of integrin αVβ1, <strong>whereas</strong> FFBJ-COF suppressed this interaction and inhibited the downstream FAK/RhoA/MRTF-A signalling pathway.</div></div><div><h3>Conclusion</h3><div>FFBJ-COF was identified as the core bioactive fraction of FFBJ. FFBJ-COF exerts anti-fibrotic effects by inhibiting integrin αVβ1 binding, thereby suppressing the FAK/RhoA/MRTF-A signalling and disrupting the positive feedback loop between ECM stiffness and fibrosis. These findings highlight the potential of FFBJ as a novel therapeutic agent for renal fibrosis.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120614"},"PeriodicalIF":5.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086158","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":"Yu-Ping-Feng nasal drops relieve allergic rhinitis via TRPV1/Ca2+/NFAT pathway","authors":"Yucheng Hu ,&nbsp;Linyou Fu ,&nbsp;Qiuyi Ren ,&nbsp;Fu Wang ,&nbsp;Hongping Luo ,&nbsp;Junjie Li ,&nbsp;Xiaobo Wang ,&nbsp;Li Tian","doi":"10.1016/j.jep.2025.120618","DOIUrl":"10.1016/j.jep.2025.120618","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Allergic rhinitis (AR) is a chronic inflammatory disorder of the nasal mucosa mediated by immunoglobulin E (IgE). Yu-Ping-Feng nasal drops (YPFND), a compound derived from traditional Chinese medicine, is extensively utilized in the management of respiratory ailments, including AR. Nonetheless, the precise biological pathways through which YPFND influences AR are yet to be fully elucidated.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;We aim to investigate the bioactivity of YPFND against AR and its therapeutic potential molecular mechanism.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted a 14-day randomized controlled trial involving 60 AR patients assigned to control group (10 % YPFND solution, Con group), mometasone furoate group (MFN group), and YPFND group, with nasal symptom outcomes assessed post-treatment. In parallel, an ovalbumin (OVA)- developed AR rat model was established to investigate the effect of YPFND on nasal mucosal inflammation. Nasal tissues and serum were analyzed by ELISA, Western blot, quantitative PCR (qPCR), histology, immunofluorescence and flow cytometry. Chemical constituents of YPFND were identified via LC-MS/MS. Serum proteomics in control and OVA-induced AR rats was analyzed by nano-HPLC–MS/MS with DIA-NN identification and MaxLFQ quantification. Molecular docking and molecular dynamics (MD) simulations were performed to predict the binding affinity of active compounds to the transient receptor potential vanilloid 1 (TRPV1) protein. &lt;em&gt;In vitro&lt;/em&gt;, human nasal epithelial cells (HNEpC) were stimulated with interleukin-17 A (IL-17 A) to induce inflammation. The effects of YPFND on TRPV1-mediated Ca&lt;sup&gt;2+&lt;/sup&gt; influx and nuclear factor of activated T cells (NFAT) activation were assessed, and TRPV1 specificity was confirmed using the antagonist SB-366791.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;LC-MS/MS analysis identified 984 compounds, among which molecular docking revealed nine candidates exhibiting strong binding affinity to TRPV1. Subsequently, MD simulations confirmed the stability of the 5-O-methylvisammioside-TRPV1 complex. Quantitative proteomics quantified 9978 proteins and identified 527 significantly altered proteins (259 upregulated, 268 downregulated) between OVA-induced AR and control rats, enriched in pathways including inflammatory mediator regulation of TRP channels. YPFND significantly alleviated clinical and experimental AR symptoms. In HNEpC, IL-17 A stimulated the expression of TRPV1 and facilitated Ca&lt;sup&gt;2+&lt;/sup&gt; influx. YPFND inhibited the IL-17 A-provoked NFAT expression via the TRPV1/Ca&lt;sup&gt;2+&lt;/sup&gt; signaling pathway. In addition, YPFND ameliorated airway inflammation by inhibiting the TRPV1/NFAT pathway in AR rats and down-regulated the expression of retinoic acid receptor-related orphan receptor gamma t (RORγ-t), further regulating the balance between T helper 17 (Th17) cells and regulatory T (Treg) cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;di","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120618"},"PeriodicalIF":5.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086131","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":"Investigating the effects and mechanisms of Vernonia anthelmintica (L.) willd., seed extracts on melanogenesis and vitiligo treatment based on multi-omics and network pharmacology","authors":"Deng Zang ,&nbsp;Zulipiya Maimaiti ,&nbsp;Nuramina Mamat ,&nbsp;Xiaoling Ma ,&nbsp;Haorong Li ,&nbsp;Xueying Lu ,&nbsp;Ablajan Turak ,&nbsp;Yuqin Luo ,&nbsp;Haji Akber Aisa","doi":"10.1016/j.jep.2025.120528","DOIUrl":"10.1016/j.jep.2025.120528","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Vitiligo is a depigmentation disorder characterized by the loss of functional melanocytes, leading to skin and/or hair depigmentation. <em>Vernonia anthelmintica</em> (L.) Willd seed extracts have been traditionally used to treat pigmentation disorders in Central Asia. However, its pharmacological mechanism for vitiligo is still unknown.</div></div><div><h3>Aims of the study</h3><div>In a previous study, we isolated the Extracts (encoded as CAM-Y7) from the <em>Vernonia anthelmintica</em> (L.) Willd seed. This research aims to understand the molecular basis of hyperpigmentation triggered by CAM-Y7.</div></div><div><h3>Materials and methods</h3><div>At first, we employed HPLC-MS to examine and measure the components in the CAM-Y7. The possible CAM-Y7–Vitiligo common targets were analyzed by network pharmacology. We explored the effects of CAM-Y7 on melanin production in melanocytes and vitiligo models induced by hydroquinone in mice and hydrogen peroxide in guinea pigs. Tissue-based metabolomics and proteomics were utilized to find varying metabolites and proteins in vitiligo mice. Through confirmatory experiments, potential therapeutic targets and molecular mechanisms were discovered.</div></div><div><h3>Results</h3><div>Twenty compounds were identified in CAM-Y7, including caffeoylquinic acids, sesquiterpenoids, and flavonoids. Network pharmacology indicated that CAM-Y7 acts on vitiligo through melanogenesis, MITF-M-regulated melanocyte development, and Tyrosine metabolism. Oral administration of CAM-Y7 progressively darkened the dorsal skin and hair of C57BL/6 mice and guinea pigs. Both Lillie staining and hematoxylin-eosin staining further demonstrated that CAM-Y7 induced melanogenesis in the epidermis and hair follicles of the animals. Multi-omics studies have shown that the Tyrosinase and MAPK pathways are important in CAM-Y7 treatment for vitiligo. Confirmatory experiments also indicated that CAM-Y7 promotes melanogenesis by upregulating MITF-induced Tyrosinase expression via the P38/MAPK-MAPKAPK2 signaling axis in melanocytes. Finally, molecular docking and SPR techniques suggested that Vernodalin is a potentially active compound in CAM-Y7.</div></div><div><h3>Conclusion</h3><div>The regulation of melanogenesis by <em>Vernonia anthelmintica</em> (L.) Willd seed extracts might be facilitated through the activation of the P38/MAPK-MAPKAPK2 signaling axis, with Tyrosinase playing a crucial role in the melanogenesis induced by CAM-Y7.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120528"},"PeriodicalIF":5.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086146","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":"Cornuside ameliorates LPS induced cognitive dysfunction and microglial NLRP3 inflammasome activation by enhancing Sirt1-mediated autophagy","authors":"Wenwen Lian ,&nbsp;Xiaotang Yuan ,&nbsp;Fulin Zhou ,&nbsp;Zhuohang Tong ,&nbsp;Yungchi Cheng ,&nbsp;Weiku Zhang ,&nbsp;Jun He ,&nbsp;Jiekun Xu","doi":"10.1016/j.jep.2025.120615","DOIUrl":"10.1016/j.jep.2025.120615","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Corni fructus</em> are the fruits of <em>Cornus officinalis</em> Sieb. et Zucc. and is widely used in traditional Chinese Medicine for the treatment of dementia. Cornuside, derived from <em>Corni fructus</em>, has been shown to be effective in improving cognition of AD mouse.</div></div><div><h3>Aim</h3><div>In the present study, we investigated the effect of cornuside on cognitive dysfunction and microglial NLRP3 inflammasome activation, as well as explored the underlying mechanism with respect to Sirt1 and autophagy.</div></div><div><h3>Methods</h3><div>AD mice were established and then treated with cornuside (3, 10, and 30 mg/kg) for 2 weeks. A series of behavioral tests were performed to assess cognition, including the Morris water maze, Y maze, nest building, step-down and step-through tests. Nissl staining was used to evaluate neuronal structural damage. LPS-stimulated BV2 cells were used for <em>in vitro</em> experiments. The anti-inflammatory effects of cornuside on cytokines and NLRP3 inflammasome activation were assessed using ELISA, RT-PCR, immunohistochemistry, western blotting, and immunofluorescence assays. To further elucidate the relationship between Sirt1, autophagy, and NLRP3 inflammasome activation, EX527 and 3-MA were used to inhibit Sirt1 and block autophagy flux <em>in vitro</em>, respectively.</div></div><div><h3>Results</h3><div>Cornuside significantly improved various behavioral performance and inhibited NLRP3 inflammasome activation in LPS-induced mice, as evidenced by decreased levels of NLRP3, ASC, pro-caspase1, caspase1, pro-IL-1β, IL-1β, GSDMD, GSDMD-NT and IL-18. Similar inhibitory effects of cornuside on NLRP3 inflammasome activation was also detected in LPS stimulated BV2 cells. The involvement of Sirt1 and autophagy were further explored <em>in-vivo</em> and <em>in-vitro</em>, revealing that cornuside increased the expression of Sirt1 and enhanced autophagy, with decreased SQSTM1/p62 and increased LC3BII. However, the inhibitory effect of cornuside on NLRP3 inflammasome activation was abrogated by 3-MA, and the effects of cornuside on promoting autophagy and inhibiting NLRP3 inflammasome activation was abolished by EX527.</div></div><div><h3>Conclusion</h3><div>Cornuside exerts therapeutic effects on LPS induced AD mice by inhibiting microglial activation and NLRP3 inflammasome overactivation. And Sirt1 mediated autophagy activation is a vital mechanism by which cornuside degrades NLRP3 inflammasome, thereby alleviating neuroinflammation and improving cognitive function.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120615"},"PeriodicalIF":5.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080929","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":"Clarification of the Yin-Jing medicinal property characteristic of Ligusticum chuanxiong Hort. via potentiating therapeutic effect, guidance and targetability","authors":"Shu-Cheng Zhang ,&nbsp;Hong-Xiang Jiang ,&nbsp;Xin Yu ,&nbsp;Xiang-Wen Kong ,&nbsp;Jun-Hong Chai ,&nbsp;Jun Liang ,&nbsp;Hai-Xue Kuang ,&nbsp;Yong-Gang Xia","doi":"10.1016/j.jep.2025.120616","DOIUrl":"10.1016/j.jep.2025.120616","url":null,"abstract":"<div><h3>Ethnic pharmacological relevance</h3><div><em>Ligusticum chuanxiong</em> Hort. (LC) is a Yin-Jing medicine in Buyang Huanwu decoction (BYHWD), carries the function of a “guiding the drug upward” to strengthen the treatment outcomes of BYHWD. However, how LC guides other drugs to target organs remains unclear, and no studies have clarified the material basis of LC's Yin-Jing medicinal properties (YJMP).</div></div><div><h3>Aim of the study</h3><div>The primary objective of this investigation is to clarify the material basis of LC's YJMP via molecular biology methods and explore its related potential mechanisms.</div></div><div><h3>Materials and methods</h3><div>This investigation developed a rat-based model of cerebral ischemia-reperfusion injury (CIRI). Based on the systematic characterization of the chemical composition of BYHWD, the optimal effective dose of BYHWD was screened out, and the therapeutic effect differences between BYHWD and [BYHWD-LC] were compared. Meanwhile, the potentiating therapeutic effects (PTE), guidance and targetability assays were employed to assess “Yin-Jing” functions by coupled with hydroxysafflor yellow A (HYA) using molecular biology techniques, etc.</div></div><div><h3>Results</h3><div>The optimum efficacious dosage of BYHWD is twice the dose, and the LC can potentiate the therapeutic effect of [BYHWD-LC]. The findings from the PTE experiments demonstrated that fragments A-C (Fr.A, Fr.B and Fr.C) could potentiate the therapeutic effect of [BYHWD-LC] in <em>vivo</em>, while Fr.A and Fr.C could enhance the therapeutic effect of HYA in <em>vitro</em>. The results of the guidance tests indicated that Fr.C enhanced the permeability of HYA in PC12 cells. Proteomic revealed that there are differentially expressed proteins related to endoplasmic reticulum (ER)-Golgi and synaptic vesicle cycling between BYHWD and [BYHWD-LC]. Targetability experiments further confirmed that Fr.C increased the permeability of HYA and activated the ER-Golgi, and identified the Endophilin-A1 protein (related to synaptic vesicle cycling) as the core affinity target mediating the brain targetability of Fr.C.</div></div><div><h3>Conclusions</h3><div>In this study, within the evaluation system based on PTE, guidance and targetability, Fr.C was first identified as the material basis underlying LC's YJMP, and clarified that the potential mechanism may be related to the activation of the ER-Golgi transport system and the promotion of synaptic vesicle cycling.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120616"},"PeriodicalIF":5.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080876","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":"Prevalence and use patterns of kava (Piper methysticum) in a US nationally representative sample","authors":"Jessica Mamallapalli ,&nbsp;Allison Henderson ,&nbsp;Erin Berthold ,&nbsp;Saunjoo L. Yoon ,&nbsp;Diane Ray ,&nbsp;Matthew Lowe ,&nbsp;Oliver Grundmann","doi":"10.1016/j.jep.2025.120617","DOIUrl":"10.1016/j.jep.2025.120617","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Piper methysticum</em> G. Forst., commonly known as kava, has a long ethnopharmacological history among Pacific Islanders. In recent years, its use in the US has grown as we understand more about its active constituents, kavalactones, which have demonstrated anxiolytic effects in clinical trials. Extracts of this plant have been marketed in many dosage forms including beverages and tea bags.</div></div><div><h3>Aim of the study</h3><div>Identify the conceptualization and patterns of use for kava products in the US and past-year prevalence via a survey study.</div></div><div><h3>Materials and methods</h3><div>Non-probabilistic sampling through a third-party marketing company was conducted, inviting persons who previously opted to participate in surveys. Participants reported use patterns including frequency, quantity, length of time used, and co-use with other products across several indications, along with product types, perceived effects, and Kava product purchasing patterns.</div></div><div><h3>Results</h3><div>The final sample included 2000 respondents, half identified as kava users. Past-year prevalence of kava use was 10.7 %. Over 50 % of kava users indicated co-use with alternative products. Prescription medicines were co-used for the largest number of indications. The largest proportion of users purchased kava in kava bars (33.7 %) and consumed it at home (59.4 %). The most reported perceived effects were happy, relaxed, and friendly. Kava was most commonly (88.1 %) rated as effective for relaxation and stress relief, while drowsiness (15.4 %) and sweating (15.0 %) were the most frequently reported unwanted effects.</div></div><div><h3>Conclusions</h3><div>Survey results provide additional insights into kava use patterns in the general population and conceptualization of kava in the context of health and well-being.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120617"},"PeriodicalIF":5.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080959","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":"Mechanistic insights into myricetin-regulated autophagy via the PI3K/Akt and PINK1/Parkin pathway in diabetic kidney disease treatment","authors":"Xin Liu ,&nbsp;Pu-yu Wang ,&nbsp;Si-qi Tang ,&nbsp;Mei-ling Zhang ,&nbsp;Xiao-feng Fan ,&nbsp;Shu-qing Sun ,&nbsp;Yue Guo ,&nbsp;Jin-xia Wu ,&nbsp;Zhi-heng Su ,&nbsp;Hua Zheng","doi":"10.1016/j.jep.2025.120613","DOIUrl":"10.1016/j.jep.2025.120613","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Rubus suavissimus</em> S.Lee (RS), a traditional ethnomedicine Guangxi, China, has long been used to manage diabetes and its complications. Existing studies have demonstrated the antidiabetic activity of RS and its complications, but the pharmacological material basis and molecular mechanism of its efficacy have not been clarified.</div></div><div><h3>Aim of the study</h3><div>This study aimed to elucidate the active constituents and specific molecular mechanisms underlying the therapeutic effects of RS in diabetic kidney disease (DKD).</div></div><div><h3>Materials and methods</h3><div>Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to identify major active components within RS polyphenol extracts. Core signaling pathways and key active components were screened using network pharmacology analysis and enrichment methods. Subsequently, an <em>in vitro</em> MPC-5 podocyte cell model was established under high-glucose and high-lipid conditions. Data-independent acquisition (DIA) mass spectrometry was used to analyze differentially expressed proteins in the cellular secretome. Mitochondrial ultrastructure was assessed using transmission electron microscopy (TEM). Key protein expression changes were validated by Western blotting.</div></div><div><h3>Results</h3><div>Network pharmacology screening identified myricetin (Myr) as the compound exhibiting the highest binding affinity to PIK3R1, suggesting its role as a key active component in the anti-DKD effects of RS polyphenols. <em>In vitro</em>, high-glucose and high-lipid exposed MPC-5 cells exhibited pronounced mitochondrial swelling and cristae disruption. Myr treatment significantly preserved mitochondrial morphology and induced the formation of double-membrane autophagic vesicles encapsulating damaged mitochondria, indicative of activated mitophagy. Proteomic analysis corroborated these findings. This study demonstrates for the first time that Myr, a principal active component of RS polyphenols, exerts its therapeutic potential in DKD by inhibiting PIK3R1. This inhibition promotes XBP1 expression, indirectly activating both the PI3K/Akt and PINK1/Parkin pathways, ultimately enhancing autophagic flux.</div></div><div><h3>Conclusions</h3><div>Myr effectively activated autophagy and mitophagy by targeting the PI3K/Akt and PINK1/Parkin signaling pathways, facilitating the removal of dysfunctional mitochondria and mitigating cellular damage in DKD models. These findings provide a mechanistic foundation for the use of RS-derived polyphenols in chronic kidney disease management and highlight Myr's potential as a natural therapeutic agent for DKD.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120613"},"PeriodicalIF":5.4,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075418","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":"Shilajit extract (ZhaXun) protects against acetaminophen-induced liver injury via modulation of the NF-κB/AKT/Caspase-3 axis","authors":"Shi-qi He ,&nbsp;Si-yan Yang ,&nbsp;Yuan Li ,&nbsp;Rong Ding ,&nbsp;Jie-lin Zhang ,&nbsp;Shi-hong Zhong ,&nbsp;Rui Gu","doi":"10.1016/j.jep.2025.120612","DOIUrl":"10.1016/j.jep.2025.120612","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Shilajit, a natural product utilized in traditional Tibetan medicine and known in China as ZhaXun (ZX), has been historically used for treating liver disorders. Recent studies have indicated that bioactive components in ZX, such as humic acid, fulvic acid, and isorhamnetin, exhibit anti-inflammatory, antioxidant, and immunomodulatory activities. These properties suggest its potential therapeutic relevance in alleviating acetaminophen (APAP)-induced acute liver injury (ALI).</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the hepatoprotective effects of ZX against APAP-induced ALI.</div></div><div><h3>Materials and methods</h3><div>The potential targets of ZX for ALI treatment were screened and then used to construct the protein-protein interaction (PPI) network. Core targets were identified using Cytoscape software, followed by GO and KEGG analyses. The effects of ZX on APAP-stimulated HepG2 cells and mice were determined by evaluating oxidative stress, inflammation and apoptosis. The potential mechanisms of ZX against ALI were verified by immunohistochemistry (IHC), immunofluorescence (IF), Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and Western blotting (WB) methods.</div></div><div><h3>Results</h3><div>Pretreatment with ZX at doses of 0.4, 0.8, 1.6 g/kg (administration by gavage) effectively attenuated APAP-induced liver injury (300 mg/kg), as confirmed by a decrease in plasma ALT and AST levels (75.0 % and 69.8 %, respectively). Network pharmacology analysis predicted ZX exerts a comprehensive protective effect against APAP-induced ALI by regulating oxidative stress, inflammatory response and apoptotic pathways. The results suggested that ZX not only ameliorated APAP-induced liver oxidative damage by regulating oxidative stress markers (SOD, MDA, CAT, GSH), but also diminished liver inflammation by inhibiting the levels of related inflammatory factors (TNF-α, IL-6, IL-1β). In addition, hepatocyte apoptosis was quantified by TUNEL staining. Finally, WB and RT-qPCR results further verified that ZX attenuated APAP-induced liver inflammation through PI3K/AKT and TLR4/NF-κB pathways. ZX inhibited hepatocyte apoptosis by balancing Bax/Bcl-2 expression and reducing Caspase-3 activation.</div></div><div><h3>Conclusion</h3><div>ZX alleviates APAP-induced ALI by attenuating inflammatory response and hepatocyte apoptosis. Both in vivo and in vitro experiments have demonstrated that ZX alleviates APAP-induced ALI through NF-κB/AKT/Caspase-3 pathways.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"355 ","pages":"Article 120612"},"PeriodicalIF":5.4,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075423","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}