Hongxuan Tong , Jiale Zhang , Lijie Jiang , Rendong Qu , Tao Lu , Jingqing Hu
{"title":"Antiviral activity of HuaganJiedu decoction (HGJDD) against hepatitis B virus (HBV) through FOXO4/ERK/HNF4α signal pathway","authors":"Hongxuan Tong , Jiale Zhang , Lijie Jiang , Rendong Qu , Tao Lu , Jingqing Hu","doi":"10.1016/j.jep.2024.119238","DOIUrl":"10.1016/j.jep.2024.119238","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Chronic hepatitis B virus (HBV) infection is still a widespread global health issue. HuaganJiedu Decoction (HGJDD) is a common prescription for treating HBV in China, which has the effect of enhancing antiviral efficacy and improving clinical efficacy. However, its precise mechanism of action remains unclear, warranting further investigation to elucidate its therapeutic potential and integration into standard medical practices.</div></div><div><h3>Aim of the study</h3><div>This study aims to explore the therapeutic mechanism of HuaganJiedu Decoction (HGJDD) in HBV.</div></div><div><h3>Materials and methods</h3><div>We investigated the therapeutic potential of HGJDD, and LC-MS analysis characterized the chemical profile of HGJDD. In vitro, we utilized HepG2.2.15 cell line to assess cytotoxicity and treatment efficacy of HGJDD compared to Entecavir controls. In vivo, assessments included monitoring HBV-related biomarkers and viral load. Network pharmacology and RNA-seq analyses identified molecular pathways and targets influenced by HGJDD treatment. Immunofluorescence and Western blotting provided further insights into the therapeutic mechanisms underlying HGJDD for HBV.</div></div><div><h3>Results</h3><div>HGJDD showed no toxicity on HepG2.2.15 cells at 10%, 20%, 40%, and 80% serum concentrations. In vitro, HGJDD reduced HBsAg, HBeAg, and HBV DNA levels by dose-dependently and time-dependently. HGJDD can decrease the levels of HBsAg, HBeAg, and HBV DNA in serum and liver levels, meanwhile the therapeutic effect of high-dose HGJDD approach to EVT’s in HBV Tg mice. According to intersection of network pharmacology and transcriptome, FOXO signal pathway was highlighted as potential targets and Immunofluorescence find that FOXO4D protein expression lever was increased in three HGJDD group, especially in high-dose HGJDD group. Western blotting confirmed increased level of FOXO4, ERK, and p-ERK and decreased levels of HNF4α, which reflected that the therapeutic effect was closely to FOXO4/ERK/HNF4α signal pathway.</div></div><div><h3>Conclusions</h3><div>Traditional Chinese medicine (TCM) offers diverse herbal treatments for HBV, with HGJDD showing efficacy in reducing HBsAg, HBeAg, and HBV DNA levels at cellular and animal levels. This study identified that FOXO4/ERK/HNF4α signal pathway played an important role in HGJDD’s therapeutic effects. These findings support HGJDD’s potential in HBV treatment, providing a scientific basis for clinical use.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119238"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864301","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}
Hao Liu , Zhongkai Guo , Zhenjie Zang , Bin Jia , Yuhang Zhou , Hui Zhang , Qiang Fu
{"title":"Saffron extract alleviates D-gal-induced late-onset hypogonadism by activating the PI3K-Akt-Nrf2 signaling pathway","authors":"Hao Liu , Zhongkai Guo , Zhenjie Zang , Bin Jia , Yuhang Zhou , Hui Zhang , Qiang Fu","doi":"10.1016/j.jep.2024.119273","DOIUrl":"10.1016/j.jep.2024.119273","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Late-onset hypogonadism (LOH) is a common age-related condition in men, characterized by a decline in serum testosterone and a range of associated signs and symptoms, and is classified as impotence in traditional medicine. Saffron is the dried stigma of <em>Crocus sativus</em> L., which is used in traditional medicine as an aphrodisiac.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the effects of <em>saffron</em> extract (SE) on LOH using an aging mouse model and Leydig cells.</div></div><div><h3>Methods</h3><div>The potential mechanisms and therapeutic targets of SE for the treatment of LOH were first identified using network pharmacology. An aging model was induced in mice by administration of D-galactose, followed by treatment with varying concentrations of SE. Subsequent assessments of serum testosterone levels, semen quality, testicular aging, oxidative stress, and apoptotic markers were performed to assess the impact of SE and to elucidate its mechanisms. In addition, in vitro experiments assessed the effect of SE on Leydig cell viability, oxidative stress, and apoptosis.</div></div><div><h3>Results</h3><div>The results showed that SE could modulate the PI3K-Akt-Nrf2 signaling pathway, enhancing Leydig cell resistance to oxidative stress and reducing Leydig cell apoptosis, thereby improving Leydig cell function and alleviating the decrease in serum testosterone associated with aging.</div></div><div><h3>Conclusion</h3><div><em>Saffron</em> is a promising strategy for the treatment of LOH and provides an effective approach to alleviate serum testosterone decline in older men.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119273"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ziyi Li , Hui Wu , Can Li , Yemei Wang , Jing Shao , Daqiang Wu , Tianming Wang , Changzhong Wang
{"title":"n-butanol extract of Pulsatilla decoction alleviates vulvovaginal candidiasis via the regulation of mitochondria-associated Type I interferon signaling pathways","authors":"Ziyi Li , Hui Wu , Can Li , Yemei Wang , Jing Shao , Daqiang Wu , Tianming Wang , Changzhong Wang","doi":"10.1016/j.jep.2024.119292","DOIUrl":"10.1016/j.jep.2024.119292","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Vulvovaginal candidiasis (VVC) is a relatively common fungal infectious disease in the female reproductive tract. The pathogenesis of VVC not only involves <em>Candida albicans</em> (<em>C. albicans</em>) infection, but also the improper immune response of the vaginal mucosal immune system to the fungus. As a classical formula, <em>Pulsatilla</em> decoction has been proven to exert protective effect in both clinical and experimental research in VVC. However, the specific mechanism of <em>Pulsatilla</em> decoction in VVC remains elusive. This study investigated the mechanism of n-butanol extract of <em>Pulsatilla</em> decoction (BEPD) in treating VVC from the perspective of type I interferon signaling and related mitochondrial function.</div></div><div><h3>Materials and methods</h3><div>A VVC-rat model was developed using an estrogen-based method to evaluate the effectiveness of BEPD in treating VVC, and the therapeutic efficacy of BEPD against VVC was comprehensively evaluated by fungal morphology and burden, neutrophil numbers, histopathology, pro-inflammatory and anti-inflammatory cytokines production, and LDH level. Immunohistochemistry (IHC), immune fluorescence (IF), Western Blot (WB) and RT-qPCR assays were conducted to assess type I interferon signaling and mitochondria functions. Candidalysin-induced vaginal epithelial inflammation in vitro, as cellular models, was employed to detect the changes in type I interferon signaling and mitochondria function before and after BEPD-containing serum intervention.</div></div><div><h3>Results</h3><div>BEPD could significantly improve the inflammation, reduce fungal loads and inhibit fungal growth, balance pro-inflammatory and anti-inflammatory cytokine levels in VVC model rats. The findings from IHC, IF, WB and RT-qPCR revealed that BEPD could promote type I interferon signaling and alleviate mitochondrial functional damage in VVC model rats, and BEPD-containing serum could play the same role in vitro.</div></div><div><h3>Conclusion</h3><div>The study findings generally demonstrated that BEPD could improve the inflammation and correct the immune imbalance in VVC through regulation of type I interferon signaling and mitochondrial function.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119292"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895002","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":"Icariin maintaining TMEM119-positive microglial population improves hippocampus-associated memory in senescent mice in relation to R-3-hydroxybutyric acid metabolism","authors":"Rong Ma, Yuge Zhou, Weifan Huang, Xiaoni Kong","doi":"10.1016/j.jep.2024.119287","DOIUrl":"10.1016/j.jep.2024.119287","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Epimedium</em> Tourn. ex L. is a traditional Chinese medicine used for thousands of years in China to treat forgetfulness. Icariin is a principal component of the genus <em>Epimedium</em>.</div></div><div><h3>Aim of the study</h3><div>The metabolic mechanism of icariin treating forgetfulness is explored.</div></div><div><h3>Materials and methods</h3><div>A D-galactose-induced senescent mouse model was employed. The cognitive performance of mice was assessed in the fear conditioning test. Hippocampal pathology was assessed in the immunohistochemistry assay. Plasma metabolome was analyzed using GC-MS method, and the differential metabolites were further identified by UPLC-MS/MS or GC-MS method. The liver function, including ALT and AST, was assessed by enzyme reaction. Icariin was administered intraperitoneally at 50 and 100 mg/kg. Mice were administered five consecutive days per week for 8 weeks.</div></div><div><h3>Results</h3><div>Icariin treatment improved hippocampus-related fear memory but not amygdala-related memory, whereas Pexidartinib (PLX3397), a microglial scavenger, did not. Icariin treatment maintained the TMEM119-positive microglial population and decreased the accumulation of the senescent biomarker p16 in the dorsal hippocampus in senescent mouse brains, whereas PLX3397 did not. Notably, p16 in the CA2 subregion significantly decreased in icariin-treated mice than the other hippocampal subregions. The senescent mice exhibited the circulating metabolic characteristics of mild ketoacidosis, active tricarboxylic acid (TCA) cycle, lactic acidosis, hyperglycemia, active detoxification, active cis-oleic acid metabolism, and inhibitory GABA shut. R-3-Hydroxybutyric acid primarily produced in the liver was selectively and robustly decreased by icariin treatment, which was not observed with PLX3397 treatment. The TCA cycle was rescued in senescent mice by icariin treatment. Icariin also protected liver function (plasma ALT) in D-gal-induced senescent mice.</div></div><div><h3>Conclusions</h3><div>Icariin may protect mouse hippocampal cognition from D-gal-induced senescence by protecting microglial homeostasis, and facilitating the utilization of R-3-hydroxybutyric acid is one of the underpins.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119287"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907087","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}
Ke-Gang Linghu , Guan Ding Zhao , Wei Xiong , Wei Sang , Shi Hang Xiong , Anfernee Kai Wing Tse , Yuanjia Hu , Zhaoxiang Bian , Yitao Wang , Hua Yu
{"title":"Corrigendum to “Comprehensive comparison on the anti-inflammatory effects of three species of Sigesbeckia plants based on NF-κB and MAPKs signal pathways in vitro” [J. Ethnopharmacol. 250, 25 March (2020), 112530]","authors":"Ke-Gang Linghu , Guan Ding Zhao , Wei Xiong , Wei Sang , Shi Hang Xiong , Anfernee Kai Wing Tse , Yuanjia Hu , Zhaoxiang Bian , Yitao Wang , Hua Yu","doi":"10.1016/j.jep.2024.119266","DOIUrl":"10.1016/j.jep.2024.119266","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119266"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932021","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}
Pu Wu , Long-Hui Cheng , Yan-Lei Liu , Jiu-Long Zhang , Xue-Man Dong , Lin Chen , Yu-Xin Xu , Ying-Ying Ren , Hua-Min Zhang , Zhao-Qian Liu , Jian-Liang Zhou , Tian Xie
{"title":"Elemene mitigates oxidative stress and neuronal apoptosis induced by cerebral ischemia-reperfusion injury through the regulation of glutathione metabolism","authors":"Pu Wu , Long-Hui Cheng , Yan-Lei Liu , Jiu-Long Zhang , Xue-Man Dong , Lin Chen , Yu-Xin Xu , Ying-Ying Ren , Hua-Min Zhang , Zhao-Qian Liu , Jian-Liang Zhou , Tian Xie","doi":"10.1016/j.jep.2024.119166","DOIUrl":"10.1016/j.jep.2024.119166","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Chinese materia medica (CMM) has a long history and extensive experience in treating ischemic stroke. Wen Ezhu, the rhizome of <em>Curcuma wenyujin</em> Y.H. Chen et C. Ling, is renowned for promoting blood circulation, dispersing blood stasis, alleviating pain, and eliminating masses. Promoting blood circulation and removing blood stasis are essential principles in Traditional Chinese Medicine for treating stroke. Consequently, Wen Ezhu is frequently used in clinical practice as a key CMM for treating stroke. The Elemene active fraction (ELE), a sesquiterpene compound extracted from Wen Ezhu, primarily consists of β-Elemene. It also contains β-Caryophyllene, γ-Elemene, and δ-Elemene isomers. ELE has shown potential pharmacological effects in various diseases, including ischemic stroke. However, its precise mechanism of action in treating stroke remains to be confirmed.</div></div><div><h3>Aim of the study</h3><div>To explore the therapeutic potential of ELE in acute ischemic stroke and elucidate its underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>A rat model of middle cerebral artery occlusion reperfusion (MCAO/R) was used to evaluate ELE's effects. Therapeutic efficacy was assessed through mNSS scoring, magnetic resonance imaging (MRI), tetrazolium chloride (TTC) staining, Hematoxylin and eosin (H&E), and Nissl staining. Non-targeted metabolomics identified key pathways, confirmed using biochemical analysis, immunohistochemistry, and Western blotting. ROS levels and apoptosis-related proteins were also evaluated.</div></div><div><h3>Results</h3><div>Our findings show that ELE administration significantly reduced the cerebral infarct area and lowered modified neurological severity scores (mNSS) in animals, indicating a strong neuroprotective effect. Metabolomics results highlight the glutathione (GSH) metabolic pathway as a key mechanism through which ELE exerts its therapeutic effects. Specifically, ELE upregulates glutathione reductase (GR) protein expression and downregulates glutathione peroxidase (GPX) expression. The regulatory process of ELE decreases oxidized glutathione (GSSG) levels and increases GSH levels, effectively reducing oxidative stress damage (lower reactive oxygen species levels) during CI/RI. This results in the downregulation of the pro-apoptotic protein Bax and the upregulation of the pro-survival protein Bcl-2, thus reducing neuronal apoptosis.</div></div><div><h3>Conclusions</h3><div>ELE protects neurons in MCAO/R rats through the GSH metabolism pathway, balancing GSH and GSSG levels to mitigate oxidative stress and enhance neuroprotection in cerebral ischemia/reperfusion injury.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119166"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769282","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}
Yujie Yang , Shen Zhang , Jin Yang , Changheng Yao , Xue Li , Wenling Dai , Jihua Liu
{"title":"The aqueous extract of Armadillidium vulgare Latreille alleviates neuropathic pain via inhibiting neuron-astrocyte crosstalk mediated by the IL-12-IFN-γ-IFNGR-CXCL10 pathway","authors":"Yujie Yang , Shen Zhang , Jin Yang , Changheng Yao , Xue Li , Wenling Dai , Jihua Liu","doi":"10.1016/j.jep.2024.119173","DOIUrl":"10.1016/j.jep.2024.119173","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Armadillidium vulgare</em> Latreille (AV), the dried body of pillbug, was originally described in <em>Shennong's Classic of Materia Medica</em>. As a common analgesic in animal-based traditional Chinese medicine, it is mainly used to relieve pain, promoting diuresis, relieving fatigue and so on. Our work demonstrated that AV could alleviate various types of acute and chronic pain including neuropathic pain (NP). And transcriptome sequencing analysis revealed that AV could suppress CXCL10 to alleviate NP, however, the upstream mechanisms governing CXCL10 synthesis remain vague.</div></div><div><h3>Aim of the study</h3><div>The research's goal was to identify the mechanism via which AV regulates CXCL10 to ameliorate NP.</div></div><div><h3>Materials and methods</h3><div>Chronic constriction injury (CCI) to the sciatic nerve was used to induce the NP model 14 days following surgery. To identify cell signaling pathways, various approaches were used, including transcriptome sequencing, western blotting, immunofluorescence, as well as ELISA. The <em>in vitro</em> assay involved the cultivation of neuron PC12 cells and astrocyte C6 cells.</div></div><div><h3>Results</h3><div>Both <em>in vivo</em> and <em>in vitro</em> results demonstrated that IL-12/IL-18 enhanced IFN-γ production in spinal neurons, which acted on IFN-γ receptors on neurons and astrocytes to upregulate CXCL10 expression in these cells, illustrating the pivotal role of IL-12 in the crosstalk between neurons and astrocytes. The role of IL-12 in pain regulation was elucidated for the first time within the nervous system. Additionally, its synergistic interaction with IL-18 on the downstream IFN-γ-CXCL10 pathway dramatically altered the activation of neurons and astrocytes. And AV could suppress CXCL10 to alleviate NP by mediating the IL-12-IFN-γ-IFNGR signaling pathway.</div></div><div><h3>Conclusions</h3><div>We explored a new target for NP by regulating neuron-astrocyte crosstalk and provided a theoretical basis for AV in clinical use.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119173"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769327","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}
Chenxi Liu , Jing Zhang , Kunjun Mao , Huaping Xu , Yu He
{"title":"Astragalus membranaceus-Carthamus tinctorius herb pair antagonizes parthanatos in cerebral ischemia/reperfusion injury via regulating PARP-1/TAX1BP1-mediated mitochondrial respiratory chain complex I","authors":"Chenxi Liu , Jing Zhang , Kunjun Mao , Huaping Xu , Yu He","doi":"10.1016/j.jep.2024.119260","DOIUrl":"10.1016/j.jep.2024.119260","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The combination of <em>Astragalus membranaceus</em> (Huang Qi in Chinese, HQ) and <em>Carthamus tinctorius</em> (Hong Hua in Chinese, HH) is commonly employed for treating ischemic stroke (IS). The heavily oxidative environment of cerebral ischemia/reperfusion injury (CI/RI) promotes activation of poly (ADP-ribose) polymerase-1 (PARP-1), which initiates parthanatos, a regulated cell death mode. Reactive oxygen species (ROS) bursting in mitochondrial respiratory chain complex I (Complex I) is a key cause of CI/RI. Nevertheless, the intrinsic mechanism of its involvement in Complex I in the parthanatos cascade remains obscure.</div></div><div><h3>Aim of the study</h3><div>This experiment aimed to investigate that HQ-HH antagonized parthanatos via regulating PARP-1/TAX1BP1-mediated Complex I to attenuate CI/RI.</div></div><div><h3>Materials and methods</h3><div>The HPLC fingerprint of HQ-HH was established, and the contents of 9 components were determined. The neuroprotective effect of HQ-HH in CI/RI was evaluated by rat middle cerebral artery occlusion/reperfusion (MCAO/R) and BV2 cell oxygen glucose deprivation/reoxygenation (OGD/R) models. Pathological changes in brain tissue of MCAO/R rats were observed using TTC staining, HE staining, and TEM. Complex I activity was measured in MCAO/R rats and OGD/R-treated BV2 cells. qRT-PCR and Western blot were performed to detect the expressions of related genes and proteins of parthanatos and Complex I as well as tax1 binding protein 1 (TAX1BP1). Immunofluorescence staining was employed to certify the nuclear translocation of apoptosis-inducing factor (AIF) in MCAO/R rats.</div></div><div><h3>Results</h3><div>The HPLC fingerprint of HQ-HH with 25 common peaks and the contents of 9 components were obtained. HQ-HH improved behavioral function and alleviated cerebral infarction in MCAO/R rats in a dose-dependent manner. HQ-HH alleviated parthanatos and exhibited the same repressive effect on PARP-1 transcription and translation as PJ34 (PARP-1 inhibitor). Moreover, the migration of TAX1BP1 to the mitochondria was restrained with HQ-HH treatment as a downstream of PARP-1, resulting in the inhibition of Complex I activity and less ROS production, accompanied by a decrease in mRNA and protein levels of ND1 and ND2. Subsequently, the nuclear translocation of AIF and the generation of poly(ADP-ribose) (PAR) polymers were suppressed.</div></div><div><h3>Conclusions</h3><div>HQ-HH mitigated CI/RI by regulating PARP-1/TAX1BP1 to inhibit the Complex I activity with less ROS production, further impeding nuclear translocation of AIF, and ultimately antagonizing parthanatos. By emphasizing the link between parthanatos and Complex I, we anticipate providing new empirical evidence for HQ-HH therapy of IS.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119260"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864306","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}
Xiao-ke Shi , Ting Peng , Bahtigul Azimova , Xiao-li Li , Shan-shan Li , Dong-yi Cao , Nai-jie Fu , Guo-lin Zhang , Wei-lie Xiao , Fei Wang
{"title":"Corrigendum to “Luteolin and its analog luteolin-7-methylether from Leonurus japonicus Houtt. Suppress aromatase-mediated estrogen biosynthesis to alleviate polycystic ovary syndrome by the inhibition of tumor progression locus 2” [J. Ethnopharmacol. (331), (2024) 118279]","authors":"Xiao-ke Shi , Ting Peng , Bahtigul Azimova , Xiao-li Li , Shan-shan Li , Dong-yi Cao , Nai-jie Fu , Guo-lin Zhang , Wei-lie Xiao , Fei Wang","doi":"10.1016/j.jep.2024.119262","DOIUrl":"10.1016/j.jep.2024.119262","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119262"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864329","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}
Min Zhang , Yaling Li , Hao Liu , Guoxiong Hao , Huijuan Zhang , Mi Li , Chenghao Li , Lu Qiu , Yehu Hou , Jintian Li , Weiwei Xue , Yongqi Liu , Xiaojie Jin
{"title":"Systematic insight into the dual COX-2/5-LOX inhibitory mechanism of Duhuo Jisheng decoction for treatment of osteoarthritis based on in silico and bioassay","authors":"Min Zhang , Yaling Li , Hao Liu , Guoxiong Hao , Huijuan Zhang , Mi Li , Chenghao Li , Lu Qiu , Yehu Hou , Jintian Li , Weiwei Xue , Yongqi Liu , Xiaojie Jin","doi":"10.1016/j.jep.2024.119263","DOIUrl":"10.1016/j.jep.2024.119263","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Traditional Chinese medicine (TCM) is frequently used to treat osteoarthritis (OA). Duhuo Jisheng decoction (DHJSD), a Chinese patent medicine, was commonly used Chinese herbal formula for the treatment of OA. In Western medicine, dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzyme has been proved to be a promising strategy to treat inflammatory diseases with reduced side effects.</div></div><div><h3>Aim of the study</h3><div>To elucidate the dual action mechanism of DHJSD targeting COX-2 and 5-LOX against OA.</div></div><div><h3>Materials and methods</h3><div>DHJSD, containing 1495 compounds was screened using a virtual screening approach based on molecular docking. The inhibitory effect of hit compounds against COX-2 and 5-LOX was validated using enzyme-based assays. <em>In vitro,</em> rat chondrocytes were treated with IL-1β (10 ng/mL) for 24 h to induce OA model <em>in vitro</em>. The chondrocyte viability was evaluated using an CCK-8 assay. ELISA was used to detect inflammatory factors expression. Immunofluorescence was used to assess the expression level of collagen II and MMP-13. In addition, a rat cartilage explants culture model was established, and safranin O and HE staining analysis were carried to assess cartilage matrix degradation and cartilage damage, respectively. <em>In vivo</em>, carrageenan-induced paw edema assay was used to examine anti-inflammatory activity, and the gastric ulcerogenic effect was further detected. Finally, Molecular dynamics simulations and binding free energy analysis were carried to explore the binding mechanism.</div></div><div><h3>Results</h3><div>13 compounds from DHJSD were identified as promising candidates by a virtual screening approach. Among these candidates, three hits 7,4′-dimethoxyisoflavone, genistein, and fraxetin displayed dual inhibition of COX-2 and 5-LOX. Further <em>in vitro</em> assay indicated that 7,4′-dimethoxyisoflavone, genistein, and fraxetin could inhibit PGE2, LTB4, TNF-α, IL-6, or NO production in IL-1β-induced chondrocytes. In addition, the three compounds reduced IL-1β-induced degradation of collagen II and expression of MMP-13 in rat chondrocytes. The results of anti-inflammatory activity of the three compounds <em>in vivo</em> showed that the highest anti-inflammatory activity with edema inhibition percentages of 50.00%, 56.00%, and 51.00% after 3 h, respectively. Moreover, it was found that 7,4′-dimethoxyisoflavone, genistein, and fraxetin have a superior gastric safety profile comparable to indomethacin. Finally, molecular dynamics simulations, binding free energy analysis, and detailed interaction mode demonstrated that 7,4′-dimethoxyisoflavone, genistein, and fraxetin interacted well with both COX-2 and 5-LOX.</div></div><div><h3>Conclusions</h3><div>7,4′-dimethoxyisoflavone, genistein, and fraxetin from DHJSD with excellent anti-inflammatory effects and no gastric ulceration effects, which helps","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119263"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864406","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}