{"title":"Tenghuang Jiangu tablet in knee osteoarthritis therapy: a prospective multicenter registry study in China.","authors":"Zelu Zheng, Xiaohan Wang, Jun Zhou, Baohong Mi, Yan Yan, Shuwen Li, Yuxin Luo, Kaiqiang Tang, Yawei Dong, Rui Quan, Jiaming Lin, Jiawen Zhang, Jiachun Liu, Yuhang Shi, Rongtian Wang, Yanqiong Zhang, Na Lin, Xisheng Weng, Weiheng Chen","doi":"10.1016/j.jep.2025.119525","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119525","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Chinese patent medicine Tenghuang Jiangu tablet (THJGT) is frequently used to treat knee osteoarthritis (KOA).</p><p><strong>Aim: </strong>This prospective multicenter registry study investigated the effectiveness and safety of THJGT in treating KOA.</p><p><strong>Materials and methods: </strong>Patients with KOA aged 50-75 years were preferentially treated with THJGT, other nonsurgical conventional treatments (CTs), or both. The treatment duration was 8 weeks, with follow-ups at weeks 4 and 8. The visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were the efficacy assessments. Adverse events and drug reactions were evaluated to assess the safety of THJGT. Propensity score matching (PSM) was used for the subgroup analysis.</p><p><strong>Results: </strong>From September 2019 to January 2021, a total of 2,995 participants were included, with 1,471 in THJGT group, 490 in CT group and 1,034 in THJGT+CT group. After treatment, the VAS and WOMAC scores in the three groups improved significantly (P < 0.001). At week 8, the VAS scores in the THJGT group significantly improved, were lower than those in the CT group (P < 0.01), and were comparable to those in the THJGT + CT group (P = 0.623). The WOMAC scores significantly improved (P < 0.001), with no differences between groups (P > 0.05). The WOMAC pain and stiffness scores were better in the THJGT + CT than in the THJGT and CT groups. PSM revealed that the WOMAC pain and stiffness scores were significantly lower in the THJGT than in the nonsteroidal anti-inflammatory drugs (NSAID) group (P < 0.01 and 0.001). Adverse events were higher in the CT and THJGT + CT groups (P < 0.001).</p><p><strong>Conclusion: </strong>THJGT is effective and safe for treating KOA, particularly in improving stiffness symptoms.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119525"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Total Sanghuangporus vaninii extract inhibits hepatocyte ferroptosis and intestinal microbiota disturbance to attenuate liver fibrosis in mice.","authors":"Siqi Gao, Xingxing Wang, Qiuying Xu, Rongsheng Li, Lumeng Yao, Anna Zhang, Qun Zhou, Zhun Xiao, Shengsheng Li, Xiongyu Meng, Jianjun Wu, Luping Qin","doi":"10.1016/j.jep.2025.119571","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119571","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Sanghuangporus, the dried fruiting body of Sanghuangporus vaninii (Ljub) L.W.Zhou et Y.C.Dai. As the main species of Sanghuang, it has been well-known and used commonly as a traditional medicinal and edible macrofungi for thousands of years in many countries, including China, Korea and Japan. Although it has good hepatoprotective activity, its potential efficacy and mechanism on liver fibrosis remain elusive.</p><p><strong>Aim of the study: </strong>Total Sanghuangporus vaninii extract (TSH) was prepared by ethanol extraction to investigate its chemical components and to conduct an initial assessment of its efficacy and underlying mechanism in a murine model of liver fibrosis.</p><p><strong>Materials and methods: </strong>The chemical components of TSH were initially analyzed by UHPLC-Q-Orbitrap HRMS. To elucidate the effects of TSH, an in vivo model of fibrosis was established in mice using carbon tetrachloride (CCl<sub>4</sub>), followed by assessments of serum liver function and histopathological analysis. Besides, indicators related to liver fibrosis, hepatic stellate cells (HSCs) activation, inflammation response and ferroptosis related indicators were detected by western blotting, immunohistochemistry and real-time quantitative PCR (RT-qPCR) analysis. Additionally, the 16S rDNA sequencing and untargeted metabolomics analysis of intestinal microbiota were employed to investigating the role of TSH in gut microbiome. In vitro, the human hepatocyte line L02 was stimulated with erastin and treated with or without TSH to elucidate its underlying mechanism.</p><p><strong>Results: </strong>The administration of TSH significantly improved serum indicators of liver injury in CCl<sub>4</sub>-induced fibrosis mice, reduced HSCs activation and collagen deposition, while inhibiting the expressions of transforming growth factor-β1(TGF-β1)/Smad signaling pathway. Notably, TSH treatment attenuated hepatocyte ferroptosis and lipid peroxidation both in vivo and in vitro, as evidenced by a marked decrease in liver iron and malondialdehyde (MDA) contents. In particular, TSH was demonstrated to activate the nuclear factor erythroid 2-related factor 2 (Nrf2)-glutathione peroxidase 4 (GPX4) signaling pathway, thereby protecting hepatocytes from ferroptosis with a particular enhancement of Nrf2 nuclear transcription. Furthermore, TSH influenced gut microbiota composition and ameliorated intestinal metabolic disorders. The increased abundance of Parasutterella and Olsenellas due to TSH treatment was significantly positively correlated with elevated phosphatidylcholines involved in linoleic acid metabolism, and negatively correlated with the reduction of fatty acyls. And the enrichment of intestinal linoleic acid metabolism presented a negative correlation in the reduction of liver fibrosis biomarkers.</p><p><strong>Conclusions: </strong>Our findings indicate that the TSH treatment exerts a significantly protective ","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119571"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537035","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}
Xiaoqin Yang , Heng Zhang , Chenglin He , Di Wang , Jingjing Li , Chaomei Fu , Yitao Wang , Yihan Wu , Jinming Zhang
{"title":"Gegen Qinlian decoction remodels tumor immune microenvironment and inhibits aerobic glycolysis with the synergistic combination of CPT-11 chemotherapy in colorectal cancer therapy","authors":"Xiaoqin Yang , Heng Zhang , Chenglin He , Di Wang , Jingjing Li , Chaomei Fu , Yitao Wang , Yihan Wu , Jinming Zhang","doi":"10.1016/j.jep.2025.119538","DOIUrl":"10.1016/j.jep.2025.119538","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Although several traditional Chinese medicine formulas have demonstrated remarkable outcomes in suppressing the severe gastrointestinal toxicity induced by irinotecan (CPT-11), few studies have investigated whether enhanced anti-cancer efficacy and reduced intestinal toxicity can be achieved through co-administration. CPT-11, as a first-line drug for treating colorectal cancer, has the side effect of intestinal toxicity. Previous studies have primarily focused on using traditional Chinese medicine to alleviate diarrhea caused by CPT-11. The combination of the classic Chinese medicine prescription Gegen Qinlian decoction (GQD) extract and CPT-11 can significantly reduce its intestinal toxicity. However, the mechanism by which it enhances anti-cancer effects remains to be elucidated.</div></div><div><h3>Aim of study</h3><div>To investigate the combined effects of GQD and CPT-11 on colorectal cancer progression and intestinal toxicity.</div></div><div><h3>Materials and methods</h3><div>The CT-26 xenograft tumor-bearing mouse model was established to evaluate the synergistic antitumor effects of GQD extract and CPT-11. Tumor size and tumor tissue changes were assessed, and flow cytometry was employed to analyze immune cell populations, thereby evaluating the impact of the combined treatment on tumor growth inhibition and immune modulation. Under anaerobic glycolysis conditions, glucose uptake and cell viability of CT26 cells were measured, and Western blotting analysis was used to determine the protein expression of PKM2 and GAPDH in tumors, assessing the metabolic impact of GQD extract on cancer cells. Flow cytometry was also used to assess the polarization of macrophages in colon tissue, and ELISA was employed to measure cytokine levels in colon tissue, evaluating the protective effect of GQD extract on the colon.</div></div><div><h3>Results</h3><div>The combination of GQD extract and CPT-11 significantly increased tumor growth suppression and decreased intestinal toxicity in the mouse model. The anti-cancer synergy was reduced Treg cell immunosuppression and increased CD4<sup>+</sup> and CD8<sup>+</sup> T cell populations. GQD extract regulated glucose uptake and cell viability in CT-26 cells under anaerobic glycolysis, potentially disrupting cancer cell glycolysis. GQD also alleviated intestinal toxicity by modulating cytokine levels and promoting macrophage polarization from M1 to M2 in colon tissues.</div></div><div><h3>Conclusion</h3><div>The study indicates that GQD extract improves CPT-11 efficacy in treating colorectal cancer and provides insights into the synergistic effects of TCM formulas in cancer treatment.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119538"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536861","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}
Jin-Qiu Li , Xiao-Han Ma , Hui Dai, Cheng-Cheng Wang, Jing Zhang, Xue-Lian Meng
{"title":"Isoliensinine ameliorates cognitive dysfunction in AlCl3/D-gal-induced Alzheimer’s disease-like mice by inhibiting the calcium signaling pathway","authors":"Jin-Qiu Li , Xiao-Han Ma , Hui Dai, Cheng-Cheng Wang, Jing Zhang, Xue-Lian Meng","doi":"10.1016/j.jep.2025.119567","DOIUrl":"10.1016/j.jep.2025.119567","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The embryos of lotus (<em>Nelumbo nucifera</em> Gaertn.) is a famous traditional Chinese medicine used to treat insomnia, memory decline, and dementia for a long time. However, the underlying material basis and mechanisms of this medicine are still unclear. Isoliensinine (IL) is a major alkaloid derived from lotus embryos. Our previous research has demonstrated that IL can exert strong anti-inflammatory and neuroprotective effects <em>in vitro</em>.</div></div><div><h3>Aim of the study</h3><div>To reveal the underlying therapeutic effect and mechanism of IL on Alzheimer’s disease (AD)-like mice induced by AlCl<sub>3</sub> and D-galactose (D-gal) <em>in vivo</em>.</div></div><div><h3>Materials and methods</h3><div>The AD-like mice were modeled by intragastric injection (<em>i.g</em>.) of AlCl<sub>3</sub> (20 mg/kg/day) and intraperitoneal injection (<em>i.p</em>.) of D-gal (120 mg/kg/day) for 8 weeks. Starting from the third week, AD-like mice were treated with IL (1, 3, or 10 mg/kg/day; <em>i.p</em>.) for 6 weeks. Cognitive impairment in AD-like mice was evaluated through some behavioral experiments including nest building, open field, novel object recognition, Y maze, and Morris water maze tests. The cortex and hippocampus (DG, CA1, and CA3) regions were analyzed as follows: Neuronal pathological changes and neurofibrillary tangles (NFTs) formation were observed by hematoxylin-eosin (HE) and silver staining, respectively; The production of Aβ plaques and the activation of microglia and astrocytes were detected by immunohistochemistry; The levels of Ca<sup>2+</sup> levels were determined by the ortho-cresolphtalein complexone method. The levels of inflammatory cytokines (TNF-α, IL-6, and IL-1β) were analyzed using the ELISA kits. The expression of CaM, p-CaMKII, Calpain, CDK5, p35/p25, p-Tau, ADAM10, BACE1, PSEN1, APP, Aβ<sub>1-42</sub>, p-IκBα, and IκBα were evaluated by western blotting.</div></div><div><h3>Results</h3><div>IL (1, 3, and 10 mg/kg) treatment effectively ameliorated cognitive impairment in AD-like model mice. IL inhibited the decrease of brain index and body weight in AD-like mice and alleviated neuronal damage in the cortex and hippocampus (DG, CA1, and CA3). IL decreased the levels of Ca<sup>2+</sup> and reduce high expression of CaM and Calpain in the cortex and hippocampus of AD-like mice. IL treatment did not affect the expression of CDK5 but inhibited the expression of p-CaMKII and p25/p35, and reduced Tau phosphorylation and NFTs formation. IL also down-regulated the high expression of Aβ<sub>1-42</sub> and APP and regulated the expression of APP-cleavage secretase (reducing the expression of BACE1 and PSEN1, while increasing the expression of ADAM10), thereby inhibited the production of Aβ plaques in AD-like mouse brain. Moreover, IL inhibited the phosphorylation and degradation of IκBα, as well as the production of inflammatory cytokines (TNF-α, IL-6, and IL-1β), and preve","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119567"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529401","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}
Meiqi Guo , Wenwen Fu , Xiaoze Zhang , Tianlang Li , Wenli Ma , Huifeng Wang , Xinjie Wang , Shuting Feng , Han Sun , Zihao Zhang , Shunfang Zuo , Zhanpeng Wang , Huali Xu
{"title":"Total flavonoids extracted from the leaves of Murraya paniculata (L.) Jack prevents acetaminophen-induced liver injury by activating Keap1/Nrf2 and PI3K/AKT/mTOR signaling pathway","authors":"Meiqi Guo , Wenwen Fu , Xiaoze Zhang , Tianlang Li , Wenli Ma , Huifeng Wang , Xinjie Wang , Shuting Feng , Han Sun , Zihao Zhang , Shunfang Zuo , Zhanpeng Wang , Huali Xu","doi":"10.1016/j.jep.2025.119562","DOIUrl":"10.1016/j.jep.2025.119562","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>In regions such as China and Southeast Asia, leaves of the traditional Chinese medicinal herb <em>Murraya paniculata</em> (L.) Jack are highly valued for their ability to detoxify and reduce swelling, promote blood circulation, and alleviate pain. These properties are harnessed in traditional healing practices, where the herb is aligned with the liver and stomach meridians in Chinese medicine. Consequently, extracts from the leaves of <em>Murraya paniculata</em> (L.) Jack are believed to ameliorate various liver-related ailments. Despite its widespread use, there is a paucity of research demonstrating the protective effect of total flavonoids extracted from the leaves of <em>Murraya paniculata</em> (L.) Jack (TFMP) in relieving acetaminophen-induced acute liver injury (ALI).</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the hepatoprotective effects and probable mechanisms of action of TFMP in acetaminophen-induced acute liver damage.</div></div><div><h3>Materials and methods</h3><div>Experimental animals were randomized into four groups of 10 each and then orally pretreated with 0.5% carboxymethyl cellulose or TFMP for seven consecutive days. ALI was induced using acetaminophen (APAP, 300 mg/kg). Hematoxylin and eosin (H&E) staining and serum markers were used to evaluate liver damage. Immunofluorescence, western blotting, biochemical kit testing, immunohistochemistry, and qPCR were used to evaluate acetaminophen metabolism, oxidative damage, and hepatocyte death.</div></div><div><h3>Results</h3><div>TFMP considerably lowered the liver-related transaminase activity and reduced pathological liver damage. By triggering the kelch-like ECH-associated protein 1 (Keap1)/nuclear erythroid related factor 2 (Nrf2) signaling pathway in hepatic tissue, antioxidative enzymes, such as superoxide dismutase (SOD) and catalase (CAT), and glutathione (GSH) were elevated and malondialdehyde (MDA) content was diminished. Based on western blotting and immunohistochemistry examinations, TFMP could boost Nrf2 accumulation within liver tissue and modulate Nrf2 entry into the nucleus, increasing the proteins involved in heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1) expression. Furthermore, TFMP promoted the expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) while reducing the expression of pro-apoptotic proteins such as Bcl2-associated X (Bax). Overall, TFMP attenuated hepatocyte apoptosis by activating the PI3K/AKT/mTOR pathway.</div></div><div><h3>Conclusion</h3><div>This study shows that TFMP reduces APAP-induced acute liver damage by a mechanism that affected the APAP metabolic process in vivo and activated the PI3K/AKT/mTOR and Keap1/Nrf2 signaling pathways to exert anti-apoptotic and antioxidant effects. Thus, TFMP may be a viable option for preventing APAP-induced liver damage.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119562"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531003","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}
Kerui Ren , Bo Niu , Huaduan Liang , Chuchu Xi , Mengmeng Song , Jingyi Chen , Fang Zhao , Zhengyu Cao
{"title":"Zhichuanling injection improves bronchial asthma by attenuation airway inflammation and epithelia-mesenchymal transition","authors":"Kerui Ren , Bo Niu , Huaduan Liang , Chuchu Xi , Mengmeng Song , Jingyi Chen , Fang Zhao , Zhengyu Cao","doi":"10.1016/j.jep.2025.119540","DOIUrl":"10.1016/j.jep.2025.119540","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Zhichuanling (ZCL) Injection, is a compound formulation containing extracts of mahuang (<em>Herba Ephedrae</em>, dried stem or aerial part of <em>Ephedra sinica Stapf</em>), bitter almond (<em>Semen Armeniacae Amarum</em>, seeds of <em>Prunus armeniaca</em> var. <em>sibirica</em> (L.) K. Koch), yangjinhua (flower of <em>Datura metel</em> L.) and Fructus Forsythiae (fruits of <em>Forsythia suspensa</em> (Thunb.) Vahl). Intramuscular injection of ZCL has been used in the clinical practice to control asthma. The aerosol inhalation of ZCL has been shown to be effective on allergic bronchial asthma. However, the underlying mechanisms remain established.</div></div><div><h3>Aim of the study</h3><div>To investigate the underling mechanism by which ZCL inhibits the pathogenesis of bronchial asthma.</div></div><div><h3>Methods</h3><div>The guinea pig tracheal rings and human bronchial epithelial (16HBE) cells were used to assess ZCL’s impact on acetylcholine (Ach) induced tracheal contraction, tumor necrosis factor α (TNF-α) induced bronchial inflammation, and transforming growth factor-β1 (TGF-β1) induced airway remodeling. Cell viability and gene expression were assessed using MTT assays, qPCR. RNA-seq (gene expression analysis) was employed to explore the novel mechanisms of ZCL in OVA-induced bronchial asthma.</div></div><div><h3>Results</h3><div>In this study, we found that ZCL reduces Ach-induced contraction of isolated guinea pig trachea, suppress TNF-α-induced interleukin (<em>IL)-1β</em>, <em>IL-6</em>, and <em>IL-8</em> and TGF-β1-induced <em>E-cadherin</em>, <em>α-SMA</em>, <em>Vimentin</em>, <em>N-cadherin</em> mRNA expression in the 16HBE. Transcriptomic analysis of lung tissue from mice with OVA-induced bronchial asthma suggests that ZCL may alleviate asthma symptoms by modulating <em>BPIFA1</em>, <em>HIF3Α</em>, <em>CTXN3</em>, <em>GRFA3</em>, <em>PPEF1</em>, <em>KSR2</em>, and <em>CDSN</em>.</div></div><div><h3>Conclusion</h3><div>ZCL alleviates asthma by suppressing tracheal contractions, inflammation, and epithelial-to-mesenchymal transition. ZCL effect on asthma is likely through the upregulation of <em>BPIFA1</em> expression thus providing the molecular insight for the treatment of asthma. The findings suggest that ZCL holds promise as a asthma therapeutic approach, and further research is needed to explore its full clinical potential. Future studies should focus on optimizing dosage, evaluating long-term efficacy, and investigating potential synergistic effects with existing treatments to enhance asthma management and patient outcomes.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119540"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526850","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}
Shidan Liu , Chenjie Li , Xianyun Fu , Minmin Chen , Meiling Wang , Kun Wang , Lin Du
{"title":"Regulation on mitophagy in adenomyosis by Guizhi Fuling Wan","authors":"Shidan Liu , Chenjie Li , Xianyun Fu , Minmin Chen , Meiling Wang , Kun Wang , Lin Du","doi":"10.1016/j.jep.2025.119570","DOIUrl":"10.1016/j.jep.2025.119570","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Guizhi Fuling Wan (GZFLW), a canonical herbal formulation originating from <em>Synopsis of the Golden Chamber</em>, has been widely utilized in managing pain-associated disorders. While its therapeutic efficacy in adenomyosis (AM) characterized by severe dysmenorrhea is well-documented, the underlying pharmacological mechanisms remain elusive. Emerging evidence suggests that hypoxic mitochondrial damage in endometrial tissue constitutes a pathological hallmark of AM, wherein mitophagy regulation through the PINK1/Parkin signaling pathway plays a pivotal role in mitochondrial quality control. Although certain phytomedicines have demonstrated mitophagy-modulating properties under hypoxic conditions, the specific regulatory effects of GZFLW on this process in AM pathogenesis warrant systematic investigation.</div></div><div><h3>Aim of the study</h3><div>To elucidate the mitophagy-modulating mechanism of GZFLW in AM through integrated in vivo and in vitro approaches.</div></div><div><h3>Materials and methods</h3><div>An allogeneic pituitary transplantation-induced AM mouse model was established. Pharmacodynamic assessment included hotplate testing and serum cancer antigen 125 (CA125) quantification, while blood urea nitrogen (BUN) and alanine aminotransferase (ALT) levels were monitored for hepatorenal toxicity screening. Histopathological characterization employed hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM) for ultrastructural analysis. Protein expression of PINK1/Parkin pathway components (PINK1, Parkin, OPTIN, NDP52, P62) were determined by Western blot. Primary endometrial stromal cells (ESCs) isolated from clinical AM specimens underwent functional assessment via transwell migration/invasion assays, complemented by flow cytometric quantification of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). Molecular docking simulations evaluated ligand-receptor interactions between GZFLW bioactive constituents and PINK1/Parkin proteins. This study protocol was approved by the Medical Ethics Committee of China Three Gorges University (No. 2022CA002).</div></div><div><h3>Results</h3><div>Histopathological validation confirmed successful AM model establishment. ELISA revealed significantly elevated CA125 levels in AM mice versus controls (<em>P</em> < 0.05), with notable reductions in GZFLW-treated groups (GET: <em>P</em> < 0.05, GZFLW-L: <em>P</em> < 0.01). No intergroup differences emerged in ALT/BUN levels, indicating absence of hepatorenal toxicity. Post-modeling pain threshold depression (<em>P</em> < 0.05 vs control) was attenuated by GZFLW treatment (<em>P</em> < 0.05). TEM analysis demonstrated mitochondrial pathology in AM endometrium, including structural deformation, reduced mitochondrial quantity, and autophagosome accumulation, all ameliorated by GZFLW-L intervention. Western blot showed upregulated PINK1 (<em>P</em> < ","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119570"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529432","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}
Ling Li, Jia Wang, Li Feng, Junting Fan, Jing Wang, Ninghua Tan, Zhe Wang
{"title":"Corrigendum to \"Rubioncolin C, a natural naphthohydroquinone dimer isolated from Rubia yunnanensis, inhibits the proliferation and metastasis by inducing ROS-mediated apoptotic and autophagic cell death in triple-negative breast cancer cells\" [J. Ethnopharmacol. 277 (2021) 114184].","authors":"Ling Li, Jia Wang, Li Feng, Junting Fan, Jing Wang, Ninghua Tan, Zhe Wang","doi":"10.1016/j.jep.2025.119494","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119494","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119494"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523578","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}
Jixuan Xu , Lulu Kang , Badalahu Tai , Changxin Liu , Zefeng Zhang , Qiuyuan Ding , Guodong Yang , Yiru Shen , Xingyun Chai , Xiaoli Gao
{"title":"The stems of Syringa oblata Lindl. exert cardioprotective effects against acute myocardial ischemia by inhibiting the TLR4/MyD88/NF-κB and NLRP3 inflammasome signaling pathways in mice","authors":"Jixuan Xu , Lulu Kang , Badalahu Tai , Changxin Liu , Zefeng Zhang , Qiuyuan Ding , Guodong Yang , Yiru Shen , Xingyun Chai , Xiaoli Gao","doi":"10.1016/j.jep.2025.119563","DOIUrl":"10.1016/j.jep.2025.119563","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The stripped roots and stems of <em>Syringa oblata</em> Lindl. (SO), a Mongolian and Tibetan folk medicinal plant, are renowned for their traditional use against “Khii”, pain relief, and heat clearing. It is used to treat cardiovascular diseases (CVDs), upset, insomnia, and other symptoms and is commonly used as a substitute for another plant known as <em>S. pinnatifolia</em>, which is used in Mongolian folk medicine.</div></div><div><h3>Objective</h3><div>This study analyzed the cardioprotective effect of SO against myocardial ischemia and the underlying mechanism through cardiac inflammation and the pyroptosis pathway.</div></div><div><h3>Materials and methods</h3><div>This study developed an acute myocardial infarction (AMI) model by ligating the left anterior descending coronary artery (LAD) in mice. Additionally, the cardioprotective effect was determined via echocardiography, detection of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin-I (cTnI) detection, and hematoxylin and eosin (HE) staining. Lipopolysaccharide (LPS) plus adenosine triphosphate (ATP) was used to stimulate RAW264.7 mouse monocyte macrophages to induce pyroptosis. The cell morphology was monitored by scanning electron microscopy. The underlying mechanisms were assessed via immunohistochemistry, immunofluorescence staining, and western blotting (WB).</div></div><div><h3>Results</h3><div>SO (40–160 mg/kg) significantly decreased the values of left ventricular internal dimension diastole (LVID; d) and left ventricular internal dimension systole (LVID; s), increased the ejection fraction (EF) and fractional shortening (FS), reduced serum levels of CK-MB, LDH, and cTnI, and mitigated microstructural destruction of MI tissue. SO at concentrations of 1.25–10 μg/mL significantly inhibited nitrogen monoxide (NO) production. At 10 μg/mL, it strongly suppressed pyroptosis while maintaining the morphological features of RAW264.7 cells. These findings suggest that SO has significant anti-myocardial ischemic effects. Administration of SO (40–160 mg/kg) in mice significantly reduced interleukin-1β (IL-1β) and interleukin-18 (IL-18) levels, accompanied by decreased fluorescence intensities of the apoptosis speck-like protein containing a caspase recruitment domain (ASC), NOD-like receptor family pyrin domain-containing 3 (NLRP3), and cysteinyl aspartate-specific protease-1 (caspase-1) proteins. WB analysis revealed that SO (40–160 mg/kg) treatment reduced inflammatory protein levels, including toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). Additionally, the phosphorylation levels of nuclear factor-kappa-B (NF-κB) and inhibitors of NF-kappa-Bα (IκBα) were suppressed. Moreover, levels of pyroptosis-related proteins, including ASC, caspase-1, NLRP3, and gasdermin D (GSDMD), were reduced.</div></div><div><h3>Conclusions</h3><div>SO may protect against myocardial ischemia through modulati","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119563"},"PeriodicalIF":4.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523588","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}