Journal of ethnopharmacology最新文献

{"title":"Gynostemma pentaphyllum polysaccharides alleviate ulcerative colitis in mice via the Nrf2/ROS/NLRP3 axis and modulation of the gut microbiota.","authors":"Min Qiu, Qincheng Yi, Meng Luo, Siwei Duan, Ziyi Zhang, Xiaoqin Wu, Tingting Chen, Chenlu Ma, Tianqi Cui, Bin Zhang, YunHai Zhang, Jun Li, Shaoju Guo, Yong Gao, Dong Zhang","doi":"10.1016/j.jep.2026.121373","DOIUrl":"10.1016/j.jep.2026.121373","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Gynostemma pentaphyllum, a traditional Chinese medicine with a history of use dating back over 500 years, was described for treating conditions such as heat-clearing and detoxification. Contemporary pharmacopoeias confirm its therapeutic value, including anti-inflammatory, immunomodulatory, and antioxidant effects. Gynostemma pentaphyllum polysaccharides (GPP) are its primary bioactive macromolecules, however, its underlying pharmacological mechanisms in ulcerative colitis (UC) remain unclear.</p><p><strong>Aim of the study: </strong>This study aimed to elucidate the protective role and mechanisms of GPP in UC.</p><p><strong>Materials and methods: </strong>The comprehensive structural characterization of GPP was achieved through integrated chromatography coupled with NMR, FT-IR, and SEM analyses. The efficacy and mechanisms of GPP were investigated in a DSS-induced UC mouse model and an LPS-stimulated Caco-2 cell inflammatory model, employing transcriptomic analysis, GeneCards Human Gene Database, 16S rRNA sequencing, and validation in Nrf2^-/- mice.</p><p><strong>Results: </strong>GPP alleviated UC symptoms by suppressing inflammation, reducing oxidative stress, and improving gut barrier dysfunction. RNAseq and GeneCards identified Nrf2 as a key target, with GPP exerting anti-inflammatory and antioxidant effects via the Nrf2/HO-1 pathway; this efficacy was attenuated in Nrf2^-/- mice. Furthermore, 16S rRNA sequencing revealed that GPP modulated the gut microbiota, increasing the abundance of Firmicutes while decreasing Proteobacteria, thereby helping to re-establish microbial homeostasis.</p><p><strong>Conclusions: </strong>Collectively, our findings demonstrate that GPP alleviates UC symptoms by activating the Nrf2/HO-1 pathway, reducing ROS levels, subsequently inhibiting NLRP3 inflammasome activation, mitigating oxidative stress, and improving intestinal barrier dysfunction. These findings identify GPP as a promising macromolecule with translational potential for UC.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"121373"},"PeriodicalIF":5.4,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197714","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":"Polygonatum Sibiricum polysaccharide ameliorates Alzheimer's disease by alleviating cuproptosis and activating the PI3K/AKT signaling pathway","authors":"Shuping Wang ,&nbsp;Yuyan Guo ,&nbsp;Siyi Wang ,&nbsp;Yuxuan Wang ,&nbsp;Shuaiyu Huo ,&nbsp;Mengmeng Li ,&nbsp;Qingshan Chen ,&nbsp;Lili Zhang ,&nbsp;Haixue Kuang ,&nbsp;Juan Pan ,&nbsp;Yan Liu","doi":"10.1016/j.jep.2026.121359","DOIUrl":"10.1016/j.jep.2026.121359","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Defined by the selective loss of central nervous system neurons, a progressive neurodegenerative disorder is what Alzheimer's disease (AD) constitutes. It is recognized as the leading cause of dementia globally. <em>Polygonatum sibiricum</em>, also known as “tiger ginger” and “chicken-head ginseng”, was hailed as a “treasure herb” by the ancient Chinese pharmacologist Li Shizhen. As a traditional Chinese medicine, its primary active component, <em>Polygonatum sibiricum</em> polysaccharide (PSP), has demonstrated well-defined neuroprotective effects.</div></div><div><h3>Aim of the study</h3><div>The core objective of the present research was to dissect the molecular mechanisms that underlie the therapeutic actions of PSP in AD.</div></div><div><h3>Materials and methods</h3><div>PSP was purified through water extraction, alcohol precipitation, decolorization, Sevag method deproteinization, and dialysis. The purified polysaccharide was characterized by ultraviolet and infrared spectroscopy. Spatial learning was evaluated as examined by performance in the Morris water maze. To investigate the pathological processes involved in PSP's effects, a range of techniques were employed, including Nissl staining, biochemical assays, immunohistochemistry, transmission electron microscopy, immunofluorescence, and western blotting. The interaction between PSP and the DLAT protein was examined using the CETSA.</div></div><div><h3>Results</h3><div>Experimental findings indicated that administration of PSP mitigated cognitive impairments in mice with AD and attenuated the loss of neuronal cells. Furthermore, PSP ameliorated mitochondrial damage, modulated cuproptosis-related proteins, and activated the phosphorylation of PI3K and AKT.</div></div><div><h3>Conclusion</h3><div>The present study demonstrates that PSP improves cognitive impairments in 3 × Tg-AD mice by targeting DLAT and subsequently activating the PI3K/AKT pathway. The findings from in vitro cellular models align with those observed in vivo studies. Consequently, PSP emerges as a promising agent endowed with therapeutic potential for AD treatment.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121359"},"PeriodicalIF":5.4,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146191864","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":"Lithocarpus litseifolius leaf extract alleviate hyperuricemia-induced renal injury by regulating uric acid metabolism and inhibiting the AKT/S6K pathway","authors":"Wenbo Yang ,&nbsp;Rui Gui ,&nbsp;Yiheng Liu ,&nbsp;Hui Zou ,&nbsp;Ling Xiao ,&nbsp;Guiming Deng ,&nbsp;Zuyou Wan ,&nbsp;Xia Yu ,&nbsp;Xing Feng ,&nbsp;Hongping Long ,&nbsp;Yikun Wang ,&nbsp;Dandan Li ,&nbsp;Xiaoai He ,&nbsp;Kangping Xu","doi":"10.1016/j.jep.2026.121362","DOIUrl":"10.1016/j.jep.2026.121362","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Lithocarpus litseifolius</em> (Hance) Chun is a tall evergreen tree belonging to the genus <em>Lithocarpus</em> in the family <em>Fagaceae</em>. According to the <em>Chinese Materia Medica</em>, its roots, stems, leaves, and fruits can all be used medicinally. Documented functions include clearing heat, detoxification, dispelling wind, lowering blood pressure, promoting blood circulation to alleviate pain, tonifying the liver and kidney, harmonizing the stomach, and directing rebellious <em>qi</em> downward.</div></div><div><h3>Aim of the study</h3><div>This study aimed to elucidate the active constituents and mechanisms of action underlying the hypouricemic and renoprotective effects of <em>L. litseifolius</em>.</div></div><div><h3>Materials and methods</h3><div>The chemical constituents of <em>L. litseifolius</em> extract (LLE) were identified by UPLC-Q-TOF-MS/MS. The hypouricemic effect of LLE was first confirmed in a hyperuricemia (HUA) mouse model induced by potassium oxonate and yeast extract. Mechanistic studies were then conducted using renal untargeted metabolomics and Western blot analysis. To identify the key active component, we employed a multi-method approach: identifying blood-absorbed constituents in rats, performing <em>in vitro</em> XOD inhibition and HK-2 cell UA reabsorption assays, and finally verifying efficacy in the HUA mouse model.</div></div><div><h3>Results</h3><div>A total of 42 compounds were identified from the LLE, predominantly flavonoids, of which 10 were identified as prototype blood-absorbed components. <em>In vivo</em> and <em>in vitro</em> experiments results demonstrated that the LLE and its major active component, trilobatin (TR), dose-dependently reduced serum levels of UA, creatinine, and blood urea nitrogen in HUA mice. These effects were accompanied by downregulating URAT1 and upregulating OAT1 expression in kidney, as well as inhibiting both the activity and expression of XOD in liver. Untargeted metabolomics and Western blot analysis confirmed that the LLE and TR effectively inhibited the expression of p-AKT and p-S6K. <em>In vitro</em> assays revealed that TR not only exhibited XOD inhibitory activity but also suppressed UA uptake in HK-2 cells. Furthermore, results from both cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) assay experiments indicated that TR shows direct interaction potential with URAT1.</div></div><div><h3>Conclusion</h3><div>LLE and its active component TR reduced serum UA in HUA mice through a dual mechanism: decreasing hepatic UA production (inhibiting XOD) and promoting renal UA excretion (downregulating URAT1 and upregulating OAT1). Simultaneously, they ameliorated renal injury, which was associated with the suppression of AKT/S6K signaling pathway overexpression.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121362"},"PeriodicalIF":5.4,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192078","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 “homotherapy for heteropathy” mechanism of Danggui Shaoyao San in Alzheimer's disease and polycystic ovary syndrome via MAPK signaling pathway and metabolomics","authors":"Xin Fu ,&nbsp;Zhikun Zang ,&nbsp;Rong Ji ,&nbsp;Yang Yu ,&nbsp;Songquan Wu ,&nbsp;Zhibin Wang","doi":"10.1016/j.jep.2026.121360","DOIUrl":"10.1016/j.jep.2026.121360","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Danggui Shaoyao San (DSS), a classic TCM formula traditionally for gynecological diseases, shows promising efficacy in Alzheimer's disease (AD) per recent studies. It regulates metabolic disorders, which is a key feature of AD and polycystic ovary syndrome (PCOS), yet the mechanism of its \"homotherapy for heteropathy\" across these diseases remains unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to verify the therapeutic effects of DSS on both AD and PCOS, and explore its underlying mechanisms involving metabolic regulation, gut microbiota modulation, and the MAPK signaling pathway.</div></div><div><h3>Materials and methods</h3><div>Materials and methods: AD models were established by Aβ_25-35 hippocampal injection, and PCOS models by testosterone propionate combined with high-fat diet. These models were validated via behavior tests and histopathology. Network pharmacology was used to predict DSS targets. Western blot and qPCR were employed to detect the activation status of the MAPK pathway. Metabolic assays and 16 S rRNA sequencing were applied to analyze metabolic indexes and gut microbiota structure.</div></div><div><h3>Results</h3><div>DSS inhibited overactivation of the MAPK pathway in both models, which is consistent with network pharmacology predictions. It restored lipid/steroid hormone homeostasis and increased the abundance of beneficial Lactobacillus in gut microbiota, while alleviating AD and PCOS pathological phenotypes.</div></div><div><h3>Conclusion</h3><div>DSS exerts \"homotherapy for heteropathy\" effects on AD and PCOS by synergistically regulating the MAPK pathway, metabolic balance, and gut microbiota, providing experimental evidence for its clinical application in these metabolically linked diseases.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121360"},"PeriodicalIF":5.4,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192004","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":"Standards for vinegar-processed Corydalis Rhizoma: Integrating morphological, chemical, and pharmacological properties","authors":"Yafei Li ,&nbsp;Rui Tang ,&nbsp;Mingfang Zhao ,&nbsp;Bing Zhu ,&nbsp;Lei Chen ,&nbsp;Yu Ye ,&nbsp;Weihong Ge ,&nbsp;Weifeng Du","doi":"10.1016/j.jep.2026.121369","DOIUrl":"10.1016/j.jep.2026.121369","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Because vinegar-processed Corydalis Rhizoma from Zhejiang Province is considered an authentic medicinal material, its grade evaluation lacks a rational basis. This study combined traits with efficacy, following the principle of “determining quality based on properties” and enhancing the rationality and applicability of quality control.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;To establish a standardized grade standard for Zhejiang (ZJ) vinegar-processed Corydalis Rhizoma (VCR) by integrating its external properties, quality, and efficacy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;First, based on existing standards, a preliminary classification of the external properties of ZJ VCR (Originating from Dongyang and Pan'an, Zhejiang Province, n = 80) was conducted. Second, trait evaluation indicators were established based on correlations among external properties. Third, liquid chromatography-mass spectrometry combined with chemometrics was used to screen the characteristic components of the processing. Subsequently, in vivo and in vitro experiments were conducted to evaluate the analgesic and immunomodulatory activities of different specifications of ZJ VCR, and spectral efficacy analysis was used to establish the quality core components among the characteristic components of processing. Finally, based on the evaluation indicators of external properties and the core components of quality, a formula for evaluating the quality constant of traditional Chinese medicine was established to standardize the grade standards of ZJ VCR.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The weight and thickness of the ZJ VCR slices were significantly positively correlated with the diameter. Based on this, diameter could serve as a trait evaluation index and was divided into three categories: VCR (Ungraded samples), VCR (Diameter &lt;0.85 cm), and VCR (Diameter ≥0.85 cm). In addition to diameter, tetrahydropalmatine (THP) can serve as an index for content evaluation. Therefore, specifications with VCR (Diameter ≥0.85 cm) and a THP≥ 0.054% could be designated as a superior grade. The analgesic effect of high-quality products is relatively strong (weight loss rate: 17%; torsion: 21 times; MDA: 0.36 nmol/ml; E&lt;sub&gt;2&lt;/sub&gt;: 1.70 pmol/ml; PGE&lt;sub&gt;2&lt;/sub&gt;: 104 pg/ml). Additionally, the immunomodulatory activity is good (cell vitality 127%, cell inhibition rate −28%, DPPH EC&lt;sub&gt;50&lt;/sub&gt; = 2.582, NO 2.37 μmol, TLR4 activation EC&lt;sub&gt;50&lt;/sub&gt; = 0.004, and cytokine expression promotion, including IL-1β, IL-6, and TNF-α).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The evaluation method that combines external properties with active substances has enhanced the rationality of the classification of grades and specifications by the mass constant method of traditional Chinese medicine. The classification standard of ZJ VCR embodies the core concept of “judging the intrinsic quality based on the characteristics of the decoction piece","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121369"},"PeriodicalIF":5.4,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192381","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":"Recent advances in traditional Chinese medicine-mediated regulation of microglial metabolic reprogramming in neurological disease therapy","authors":"Zhenzhen Wu ,&nbsp;Fengyu Lv ,&nbsp;Siyu Shao ,&nbsp;Yongjun Chen ,&nbsp;Ning Weng ,&nbsp;Yucen Xia","doi":"10.1016/j.jep.2026.121355","DOIUrl":"10.1016/j.jep.2026.121355","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Neuroinflammation, driven by microglial metabolic reprogramming, underpins neurological diseases. Contrasting with the limitations of single-target therapies, TCM and acupuncture offer multi-targeted anti-inflammatory and antioxidant effects to modulate microglial activation, with TCM directly regulating microglial energy metabolism.</div></div><div><h3>Aim of the study</h3><div>This review aims to elucidate how TCM and acupuncture regulate microglial energy metabolism in neurological diseases, identify key metabolic enzymes and signaling pathways, and establish a scientific foundation for their translational applications.</div></div><div><h3>Materials and methods</h3><div>we systematically searched major scientific databases (PubMed, Web of Science, Sinomed, and CNKI) from January 2010 to December 2025 using predefined keywords including “TCM”, “acupuncture”, “microglia”, “glucose/lipid/amino acid metabolism”, and “neurological diseases” (e.g., Alzheimer's disease, depression). Our literature review focused on two main aspects: (1) direct mechanistic studies of TCM bioactive compounds and formulas on microglial energy metabolism; (2) related studies on acupuncture's effects on brain or astrocyte metabolism, providing indirect evidence for its potential effects on glial cell metabolism.</div></div><div><h3>Results</h3><div>TCM bioactive compounds and formulas regulate metabolic enzymes and pathways, correcting microglial metabolic disturbances. These interventions promote microglial polarization toward the anti-inflammatory M2 phenotype, reducing neuroinflammation and improving outcomes in neurological diseases. Acupuncture may modulate metabolic pathways in microglia, supporting its role as an auxiliary therapeutic modality in TCM.</div></div><div><h3>Conclusion</h3><div>TCM restores microglial metabolic homeostasis, enhancing M2 polarization and neuroprotection. These findings highlight TCM's potential for developing metabolism-immunity dual-target interventions for neurological diseases. Further research is needed to elucidate acupuncture's mechanisms and effects on microglial metabolism.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121355"},"PeriodicalIF":5.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180458","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":"Berberine alleviates DSS-induced colitis by modulating macrophage phenotype via PPAR-γ/ mTOR/HIF-1α signaling pathway","authors":"Long He ,&nbsp;Zhuotai Zhong ,&nbsp;Fengbin Liu ,&nbsp;Shuting Wen","doi":"10.1016/j.jep.2026.121350","DOIUrl":"10.1016/j.jep.2026.121350","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Berberine (BBR), an isoquinoline alkaloid derived from Chinese herbal drugs of <em>Coptis chinensis Franch.</em> and <em>Phellodendron chinense C.K. Schneid.</em>, has been traditionally extensively utilized in treating acute or chronic diarrhea and distension. In modern medical practice, BBR has also been developed to remit diarrhea of ulcerative colitis (UC). However, the potential mechanism remains not been fully elucidated.</div></div><div><h3>Aim of the study</h3><div>The present study aimed to explore the modulation effect of BBR on M2 macrophage polarization and elucidate the underlying mechanism.</div></div><div><h3>Materials and methods</h3><div>Mice with colitis were induced by dextran sulfate sodium (DSS) and administrated with BBR. The distribution of M2-like phenotype of macrophage in colon tissues was determined by flow cytometry and immunofluorescence. Additionally, the Seahorse real-time cell metabolic analysis was applied to measure the oxygen consumption rate on RAW264.7 cells cultured under M2 macrophage polarization conditions. Protein levels were measured using western blotting and immunohistochemistry. Finally, the GW9662 was used for reverse validation experiments.</div></div><div><h3>Results</h3><div>BBR notably alleviated colitis and resettled inflammatory macrophages toward M2 phenotype in a mouse model. Additionally, BBR significantly promoted peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in mice with colitis. In vitro findings demonstrated BBR significantly enhanced M2 macrophage polarization and increased the oxygen consumption and ATP production of RAW 264.7 cells cultured in M2 macrophage polarization condition. BBR also exerted a negative regulatory effect on the mTOR/HIF-1α signaling pathway. Nevertheless, the modulation efficiency of BBR on M2 macrophage polarization and mTOR/HIF-1α pathway were abrogated upon the application of GW9662 both <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Conclusion</h3><div>BBR significantly contribute to drive M2 macrophage polarization via the PPAR-γ/mTOR/HIF-1α axis, and further confirmed the considerable approach of BBR for the clinical treatment of UC.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121350"},"PeriodicalIF":5.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180478","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":"Qingluo Tongbi Formula attenuates Tripterygium wilfordii Hook. f.-induced hepatic metabolic dysfunction and oxidative stress via the SIRT1/HIF-1α pathway","authors":"Weijue Nie ,&nbsp;Minghao Lu ,&nbsp;Xin Sun ,&nbsp;Hong Zhu ,&nbsp;Baoping Jiang ,&nbsp;Lingling Zhou ,&nbsp;Xueping Zhou","doi":"10.1016/j.jep.2026.121352","DOIUrl":"10.1016/j.jep.2026.121352","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Tripterygium wilfordii</em> Hook. f. (TW) is widely used to treat autoimmune and inflammatory diseases, but its clinical utility is limited by hepatotoxicity. Qingluo Tongbi Formula (QTF), a classic multi-herb prescription for rheumatoid arthritis containing TW, has shown good efficacy with fewer liver adverse effects in clinical practice.</div></div><div><h3>Aim of the study</h3><div>To evaluate whether QTF alleviates TW-induced hepatotoxicity and to elucidate the underlying metabolic and molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>A TW-induced hepatotoxicity model was established in C57BL/6J mice treated with TW alone, QTF, or TW combined with individual constituent herbs. Liver injury, oxidative stress, and lipid peroxidation were evaluated by serum biochemistry and histopathology. Untargeted metabolomics was performed to profile hepatic energy metabolism. <em>In vitro</em>, triptolide-injured AML12 hepatocytes were used to evaluate the protective effects of catalpol (CAT) and <em>Panax notoginseng</em> saponins (PNS) on cellular bioenergetics and the sirtuin 1 (SIRT1)/hypoxia-inducible factor-1α (HIF-1α) axis.</div></div><div><h3>Results</h3><div><em>In vivo</em>, QTF significantly attenuated TW-induced hepatotoxicity, hypoglycaemia, oxidative stress, and lipid peroxidation, and partially normalized amino acid and glucose metabolism. <em>In vitro</em>, combined CAT and PNS restored mitochondrial respiration, rebalanced glycolysis and oxidative phosphorylation, improved glycogen utilization, and upregulated SIRT1 while suppressing HIF-1α in AML12 hepatocytes.</div></div><div><h3>Conclusions</h3><div>QTF protects against TW-induced hepatotoxicity, at least in part by modulating the SIRT1/HIF-1α axis, thereby alleviating oxidative stress and restoring hepatic energy and glucose metabolism. These findings provide a mechanistic basis for the detoxifying compatibility of QTF and support safer clinical application of TW-containing formulations.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121352"},"PeriodicalIF":5.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180476","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":"Sangbaipi Decoction mitigates influenza pneumonia in mice by inhibiting ZBP1-mediated PANoptosis","authors":"Chengcheng Zhang ,&nbsp;Guofeng Yu ,&nbsp;Miaomiao Liu ,&nbsp;Ruikun Du ,&nbsp;Jing Ma ,&nbsp;Xuran Gu ,&nbsp;Lijun Rong ,&nbsp;Xuxiao Lv ,&nbsp;Qinghua Cui","doi":"10.1016/j.jep.2026.121348","DOIUrl":"10.1016/j.jep.2026.121348","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Viral pneumonia remains a major global health concern. Sangbaipi Decoction (SBPD), a traditional Chinese medicine formula, which is used clinically to treat pneumonia, exhibits antiviral and anti-inflammatory effects. However, its pharmacological basis and mechanism of action (MOA) <em>in vivo</em> remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to evaluate the therapeutic efficacy of SBPD on viral pneumonia and to elucidate its underlying MOA.</div></div><div><h3>Materials and methods</h3><div>The protective effects of SBPD were assessed in H1N1 (A/Puerto Rico/8/1934)-infected mice using histopathology, Western blot, and RT-qPCR. RNA sequencing was performed to identify key pathways modulated by SBPD. PANoptosis-related markers were examined both <em>in vivo</em> and <em>in vitro</em>, and Z-DNA-binding protein 1 (ZBP1) overexpression assays were conducted to verify its role in SBPD-mediated regulation of PANoptosis. A Poly(I:C)-induced acute lung injury model was used for further validation. Blood-absorbed constituents of SBPD were screened to identify bioactive components.</div></div><div><h3>Results</h3><div>SBPD treatment greatly reduced pulmonary viral load, lung index, and pro-inflammatory cytokine levels in H1N1-infected mice, alleviating lung injury. Transcriptomic analysis identified the ZBP1-mediated PANoptosis as a major regulatory target of SBPD. <em>In vivo</em> and <em>in vitro</em> studies demonstrated that SBPD downregulated the expression of ZBP1 and its downstream effectors, suppressing excessive inflammatory cell death. SBPD also attenuated Poly(I:C)-induced acute lung injury through the same pathway. Screening of blood-absorbed constituents of SBPD identified peimine, peiminine, chrysin, wogonin, and apigenin as active constituents that inhibit ZBP1-mediated PANoptosis.</div></div><div><h3>Conclusion</h3><div>SBPD mitigates influenza-induced pneumonia by suppressing ZBP1-mediated PANoptosis and excessive inflammation, highlighting its host-directed therapeutic potential for viral pneumonia.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121348"},"PeriodicalIF":5.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180484","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":"Gancao decoction ameliorated senecionine-induced Hepatic Sinusoidal Obstruction Syndrome in mice by inhibiting NET formation and senecionine bioactivation in liver","authors":"Shuang Zhang ,&nbsp;Dongming Yan ,&nbsp;Si Cheng ,&nbsp;Jingyi Jin ,&nbsp;Jiamin Cui ,&nbsp;Chenghai Liu ,&nbsp;Yue Li ,&nbsp;Furong Qiu","doi":"10.1016/j.jep.2026.121356","DOIUrl":"10.1016/j.jep.2026.121356","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>In China, pyrrolizidine alkaloid (PA)-induced hepatic sinusoidal obstruction syndrome (HSOS) accounts for approximately 50.0-88.6% of all HSOS cases, primarily resulting from inadvertent ingestion of <em>Gynura japonica</em> (Thunb.) Juel. (Tǔ sān qī). <em>Glycyrrhiza uralensis</em> Fisch. (Gān cǎo), a classical hepatoprotective herb in Traditional Chinese Medicine (TCM), has recently demonstrated significant protective effects against PA-induced HSOS in murine models. However, its underlying mechanisms remain poorly understood.</div></div><div><h3>Aim of study</h3><div>This study aimed to assess the therapeutic efficacy of Gancao decoction (GCD) and elucidate its underlying mechanisms in PA-induced HSOS.</div></div><div><h3>Materials and methods</h3><div>HSOS was induced in mice by senecionine (SEN), followed by treatment with GCD or enoxaparin (ENO, positive control). Histopathological and therapeutic efficacy was assessed by histopathological examination and serum biochemical analyses. Neutrophil depletion was employed to investigate the contribution of neutrophil extracellular traps (NETs) to the protective effects of GCD. Transcriptomic analysis was performed to identify potential targets of GCD. Mechanistic studies were investigated using quantitative real-time PCR (qPCR), Western blotting (WB), and immunofluorescence (IF). In addition, the inhibitory effect of GCD on SEN bioactivation was evaluated using human liver microsomes (HLMs).</div></div><div><h3>Results</h3><div>GCD improved serum biochemistry and hepatic histopathology in SEN-induced HSOS mice. Mechanistically, GCD suppressed intrahepatic neutrophil chemotaxis, thereby reducing NET formation and alleviating immunothrombosis. Furthermore, GCD inhibited the hepatic formation of dehydropyrrolizidine (DHP), the reactive metabolite responsible for SEN-induced HSOS.</div></div><div><h3>Conclusion</h3><div>GCD attenuated SEN-induced HSOS through dual mechanisms: (1) suppression of chemokine-driven neutrophil chemotaxis, leading to reduced NET formation and immunothrombosis; (2) inhibiting of SEN bioactivation. These findings provide mechanistic support for the ethnopharmacological use of Gancao in PA-HSOS and highlight its potential for clinical translation.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121356"},"PeriodicalIF":5.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165541","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}