{"title":"Multi-omics joint analysis reveals the mechanism underlying Chinese herbal Yougui Pill in the treatment of knee osteoarthritis.","authors":"Siyu Li, Yongju Yang, Yu Zhang, Fanyu He, Jie Chen, Yuanhe Fan, Hui Zhang, Xuefeng Guan","doi":"10.1016/j.jep.2024.119098","DOIUrl":"10.1016/j.jep.2024.119098","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Yougui Pill (YGP), originating from Jingyue Quanshu, comprises 10 traditional Chinese medicines (TCMs). This classic prescription is renowned for its ability to tonify the kidney, warm the kidney, promote yang, warm the interior, and dispel cold. YGP has proven effective in treating degenerative knee arthritis, osteoporosis, delayed fracture healing, and other orthopedic conditions, making it a widely used clinical prescription for knee osteoarthritis (KOA).</p><p><strong>Aim of the study: </strong>Although YGP is commonly used in clinical practice, its pharmacodynamic material basis and anti-arthritis mechanisms remain unclear. This study aims to comprehensively analyze the chemical constituents of YGP and elucidate its anti-arthritis mechanisms.</p><p><strong>Materials and methods: </strong>Ultra-high performance liquid chromatography coupled with electrospray ionization-triple quadrupole-linear ion trap mass spectrometry(ESI-Q TRAP-MS/MS) was used to identify the chemical constituents of YGP. The Hulth method was utilized to establish KOA rat model, and pathological examinations were performed to assess the anti-arthritis effects of YGP. Integrated metabolomics and transcriptomics analyses were conducted to explore the anti-arthritis mechanisms of YGP. Key targets were confirmed via immunohistochemistry.</p><p><strong>Results: </strong>A total of 1,981 chemical components were identified in YGP, predominantly phenolic acids and flavonoids. Compared with the model group, 422 differentially expressed metabolites and 214 differentially expressed genes were identified, primarily involving the MAPK signaling pathway, FoxO signaling pathway, and PI3K-Akt pathway. YGP exerted an anti-osteoarthritis effect by inhibiting the excessive activation of the EGFR/ERT/FOS signaling pathway.</p><p><strong>Conclusions: </strong>TCM offers significant advantages in the treatment of KOA, addressing the shortcomings of current clinical medications. YGP displayed exceptional pharmacodynamic effects. This study elucidated its pharmacodynamic material basis and anti-osteoarthritis mechanisms, providing substantial support for its clinical application and the development of related drugs.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119098"},"PeriodicalIF":4.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668081","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}
Taotao Wang, Xinyue Zhang, Kunmei Shan, Yan Luo, Ting Yu, Zhihui Liu, Jianxiu Zhai, Sikai Li, Jun Yin, Na Han
{"title":"Various crystalline forms of realgar exhibit differentiated anti-abscess and anticancer effects based on a PXRD analysis and biological evaluation.","authors":"Taotao Wang, Xinyue Zhang, Kunmei Shan, Yan Luo, Ting Yu, Zhihui Liu, Jianxiu Zhai, Sikai Li, Jun Yin, Na Han","doi":"10.1016/j.jep.2024.119122","DOIUrl":"10.1016/j.jep.2024.119122","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Realgar is a mineral medicine with a long history that can be used externally or internally. It is often used to treat skin diseases and leukemia in clinical practice. Realgar exhibits a polycrystalline phenomenon, and it remains unknown whether there is a difference in the efficacies of the different realgar crystalline forms.</p><p><strong>Purpose: </strong>The aim of this study is to investigate the pharmacodynamic differences of the different realgar crystalline forms (α-As<sub>4</sub>S<sub>4</sub> and β-As<sub>4</sub>S<sub>4</sub>) using in vivo and in vitro experiments.</p><p><strong>Material and methods: </strong>The in realgar crystalline patterns were initially identified using a powder x-ray diffractometer (PXRD). The antimicrobial activities of α-As<sub>4</sub>S<sub>4</sub> and β-As<sub>4</sub>S<sub>4</sub> were then assessed in vitro to elucidate their effectiveness against bacteria. Transdermal absorption and pharmacokinetic experiments were used to investigate the variances in the bioavailabilities between the in vitro and in vivo conditions. The effects of α-As<sub>4</sub>S<sub>4</sub> and β-As<sub>4</sub>S<sub>4</sub> for skin abscess healing were studied in mice using a subcutaneous injection of Staphylococcus aureus (S. aureus). HL-60 cells were exposed to a serum that contained different crystalline forms of realgar to evaluate the potential differences in the therapeutic effects of α-As<sub>4</sub>S<sub>4</sub> and β-As<sub>4</sub>S<sub>4</sub> on leukemia.</p><p><strong>Results: </strong>Realgar is composed of α-As<sub>4</sub>S<sub>4</sub> and β-As<sub>4</sub>S<sub>4</sub> crystalline forms. The soluble arsenic content in α-As<sub>4</sub>S<sub>4</sub> generally exceeded that of β-As<sub>4</sub>S<sub>4</sub>, and the antimicrobial activity showed a positive correlation with the soluble arsenic content. α-As<sub>4</sub>S<sub>4</sub> demonstrated a higher in vivo and in vitro bioavailability and a faster elimination rate in vivo compared to β-As<sub>4</sub>S<sub>4</sub>. The pharmacodynamic experimental investigations showed that α-As<sub>4</sub>S<sub>4</sub> exhibited a superior healing effect on subcutaneous abscesses. Furthermore, serum pharmacology experiments revealed that α-As<sub>4</sub>S<sub>4</sub> induced significantly higher membrane damage and apoptosis in HL-60 cells compared to β-As<sub>4</sub>S<sub>4</sub>.</p><p><strong>Conclusion: </strong>The different realgar crystalline forms had distinct pharmacodynamics. α-As<sub>4</sub>S<sub>4</sub> demonstrated higher bioavailability in vitro and in vivo and superior effects on skin abscess healing compared to β-As<sub>4</sub>S<sub>4</sub>. It also possessed anti-leukemia properties. It is the first time to report the differences in the efficacy between two crystalline forms of realgar, which is helpful to improve the knowledge of the real chemical substances for realgar.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119122"},"PeriodicalIF":4.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668084","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}
De-Hua Wu, Chao-Geng Lyu, Dan Zhao, Chang-Gui Yang, Si-Qi Liu, Ji-Tong Zhu, Ya-Ling Yang, Lan-Ping Guo, Chuan-Zhi Kang
{"title":"Ardisia Crispae Radix et Rhizoma: A review of botany, traditional uses, phytochemistry, pharmacology, and toxicology.","authors":"De-Hua Wu, Chao-Geng Lyu, Dan Zhao, Chang-Gui Yang, Si-Qi Liu, Ji-Tong Zhu, Ya-Ling Yang, Lan-Ping Guo, Chuan-Zhi Kang","doi":"10.1016/j.jep.2024.119093","DOIUrl":"10.1016/j.jep.2024.119093","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Ardisia Crispae Radix et Rhizoma comprises three primary source plants: Ardisia crenata Sims, Ardisia crispa (Thunb.) A. DC., and Ardisia crenata Sims var. bicolor (Walk) C. Y. Wu et C. Chen. These species are prevalent in mid-to-low-latitude regions and are traditionally utilized as herbal medicines in East Asia and India. They have demonstrated notable efficacy in anti-inflammatory properties and possess potential anti-tumor, antimicrobial, antioxidant, and anti-angiogenic activities.</p><p><strong>Aim: </strong>This review systematically evaluated the botany, traditional uses, phytochemistry, pharmacology, and toxicity of Ardisia Crispae Radix et Rhizoma to assist future innovative research and facilitate the development of new therapeutic agents.</p><p><strong>Materials and methods: </strong>Literature was sourced from both library and electronic databases, including Web of Science, PubMed, Elsevier, Google Scholar, and CNKI. The review focuses on phytochemistry, pharmacological research, and toxicity studies related to Ardisia Crispae Radix et Rhizoma.</p><p><strong>Results: </strong>Ardisia Crispae Radix et Rhizoma is traditionally used to treat inflammation and injuries. Current pharmacological studies suggest its potential anti-tumor, anti-inflammatory, antimicrobial, antioxidant, and anti-angiogenic activities. This review identified approximately 161 compounds in Ardisia Crispae Radix et Rhizoma, such as saponins, flavonoids, coumarins, essential oils, lignans, and terpenes.</p><p><strong>Conclusions: </strong>Ardisia Crispae Radix et Rhizoma is a promising medicinal plant resource with a diverse range of specialized metabolites. However, existing research predominately addresses phytochemistry and pharmacological activities, with limited exploration of underlying mechanisms. Further systematic evaluations of its efficacy and clinical safety are required.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119093"},"PeriodicalIF":4.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668003","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":"Eriocitrin ameliorates hepatic fibrosis and inflammation: The involvement of PPARα-mediated NLRP1/NLRC4 inflammasome signaling cascades.","authors":"Jin-Jin Zhang, Jia-Xin Zhang, Qi-Yuan Feng, Li-Qiang Shi, Xin Guo, Hai-Ming Sun, Jian Song","doi":"10.1016/j.jep.2024.119119","DOIUrl":"10.1016/j.jep.2024.119119","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Citri Reticulatae Pericarpium (Chenpi) is a traditional Chinese medicine and recorded to have hepatoprotective therapeutic and condition value. Eriocitrin (ER) a natural compound isolated from Citri Reticulatae Pericarpium may ameliorate hepatic inflammation in chronic liver diseases.</p><p><strong>Aim of the study: </strong>The current study investigates the hepatoprotective effect and potential mechanism of ER against hepatic fibrosis.</p><p><strong>Materials and methods: </strong>The hepatic fibrosis mouse model was constructed by intraperitoneally injecting thioacetamide (TAA) for five weeks. Hepatic stellate cells (HSCs) were treated with transforming growth factor-β (TGF-β). Meanwhile, lipopolysaccharide/adenosine triphosphate (LPS/ATP) was given to excite the normal mouse bone marrow-derived macrophages (BMDMs), and thus the cells could acquire the conditioned medium. Moreover, LX-2 cells were administrated with PPARα knockdown vector (siRNA-PPARα).</p><p><strong>Results: </strong>RNA sequencing studies revealed that in mice induced by TAA, the PPARα/NOD-like receptor/ neutrophil extracellular traps (NETs) significantly influence ER-based hepatic protection. In TAA-induced mice, ER could up-regulate PPARα and down-regulate NLRP1/NLRC4 and the development of NETs. Our findings indicated that ER significantly up-regulated PPARα, inhibited NLRP1/NLRC4 inflammasome in HSCs. Deficiency of PPARα in the activated LX-2 weakened the regulatory effect of ER on inhibiting the NLRP1/NLRC4 inflammasome. In addition, ER might hinder the activation of BMDMs and also obstruct IL-1β and IL-6 passage in the extracellular space.</p><p><strong>Conclusions: </strong>The results indicated that ER decreased inflammation by controlling the PPARα-NLRP1/NLRC4 signaling pathway and inhibiting fibril formation. Collectively, our results underscore the therapeutic potential of ER in addressing hepatic fibrosis.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119119"},"PeriodicalIF":4.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668066","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":"Kushen Gel Combined with Antifungal Drugs for the Treatment of Vulvovaginal Candidiasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Fanya Yu, Lina Zhang, Xudong Zhang, Juwen Zhang, Junhong Yu, Chuwei Tang, Ling Xiong, Xia Liu, Yun Li, Wei Chen","doi":"10.1016/j.jep.2024.119107","DOIUrl":"10.1016/j.jep.2024.119107","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Vulvovaginal candidiasis (VVC) represents the most prevalent form of candidal infections, imposing a significant societal burden. Kushen gel, a chinese patent medicine, has demonstrated favorable outcomes in the treatment of VVC. In clinical practice, Kushen gel is often used in conjunction with antifungal drugs. However, the clinical evidence supporting the combined use of Kushen gel with antifungal drugs for the treatment of VVC is currently limited.</p><p><strong>Aim of the study: </strong>This study aimed to evaluate the effectiveness and safety of Kushen gel combined with antifungal drugs in the treatment of vulvovaginal candidiasis (VVC).</p><p><strong>Materials and methods: </strong>Databases namely CNKI, Wanfang Database, VIP Database, CBM, PubMed, Cochrane Library, and Embase were searched from their inception to January 2024. Randomized controlled trials (RCTs) applying Kushen gel combined with antifungal drugs for the treatment of VVC were included. Methodological quality assessment was performed using the Cochrane risk of bias assessment tool (RoB 1.0). A Meta-analysis was performed using RevMan 5.4 software. The primary outcomes were total efficacy rate, recurrence rate, secondary outcomes included adverse events and time to clinical symptom resolution.</p><p><strong>Results: </strong>A Meta-analysis of 42 RCTs, encompassing a total of 4259 VVC patients was conducted. The results indicated that compared to antifungal drugs alone, Kushen gel combined with antifungal drugs increased the effectiveness (RR=1.20, 95%CI [1.17, 1.23], P<0.00001) and reduced the recurrence rate (RR=0.21, 95%CI [0.13, 0.34], P<0.00001), with no significant difference in safety (RR=0.56, 95%CI [0.30, 1.03], P=0.11).</p><p><strong>Conclusions: </strong>Based on the available results, it appears that the combination of Kushen gel with antifungal drugs may increase the effectiveness and reduce the recurrence rate. However, due to the poor methodological quality of the included studies, more high-quality evidence from large-sample and well-designed research is needed in the future.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119107"},"PeriodicalIF":4.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668069","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}
Ji Zhou, Zhenyu Guo, Xiaozhen Peng, Ben Wu, Qingxin Meng, Xingjun Lu, Liyuan Feng, Tianyao Guo
{"title":"Chrysotoxine regulates Ferroptosis and the PI3K/AKT/mTOR pathway to prevent cervical cancer.","authors":"Ji Zhou, Zhenyu Guo, Xiaozhen Peng, Ben Wu, Qingxin Meng, Xingjun Lu, Liyuan Feng, Tianyao Guo","doi":"10.1016/j.jep.2024.119126","DOIUrl":"10.1016/j.jep.2024.119126","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Dendrobium (commonly known as Shihu in China), a traditional Chinese medicinal herb recognized in the Pharmacopoeia of China (2020 edition), boasts a rich history of medicinal application. Extensive research has been conducted on its Chinese medicinal prescription due to its demonstrated anti-tumour effects in clinical settings. Dendrobium is comprised of a diverse range of chemical compounds, notably the Bibenzyls, Erianin, and Gigantol, which have exhibited significant inhibitory and therapeutic effects on cervical cancer, thereby suggesting potential therapeutic value. However, the comprehensive investigation of Chrysotoxine, a naturally occurring active ingredient of Bibenzyls in Dendrobium, remains incomplete in treatment of cervical cancer.</p><p><strong>Aims of the study: </strong>This study aimed to conduct a comprehensive investigation of Chrysotoxine and its regulatory impact on ferroptosis in cervical cancer.</p><p><strong>Materials and methods: </strong>Initially, the effects of chrysotoxine on the cervical cancer cell line HeLa were assessed using CCK-8, transwell, colony formation, and flow cytometry to evaluate cell proliferation, invasion, migration, and apoptosis. Subsequently, network pharmacology and molecular docking techniques were employed to identify the molecular targets of chrysotoxine in cervical cancer. Finally, confocal microscopy assessed the expression levels of ROS and lipid compounds in response to chrysotoxine treatment, and the influence of chrysotoxine on signaling pathways was investigated using western blot analysis, guided by KEGG pathway analysis.</p><p><strong>Results: </strong>Our cell-based experiments revealed that CTX effectively suppresses the cell proliferation, migration, invasion, and apoptosis in CC. Subsequently, we comprehensively analyzed that HSP90AA1, ESR1, PIK3CA, mTOR and MAPK1 may be the possible targets of CTX in CC by combining network pharmacology with molecular docking techniques. Finally, we observed that CTX enhances the production of intracellular ROS and excessive lipid peroxides. Simultaneously, we detected that CTX promotes ferroptosis-based p53/GPX4/SLC7A11 pathway and inhibits PI3K/AKT/mTOR pathway-induced cell death of CC by western blot.</p><p><strong>Conclusion: </strong>Our study indicates that chrysotoxine shows promise as a novel medication for treating CC. The findings provide a scientific foundation for the regulation of cervical cancer by chrysotoxine, presenting new insights into the application of traditional Chinese medicine for fighting CC.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119126"},"PeriodicalIF":4.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668063","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}
Qiao Gao, Yi Li, Yao Zhong, Shu-Xian Zhang, Chang-Yuan Yu, Guang Chen
{"title":"Chemical profiling and anti-inflammatory effect of phenolic extract of Gentiana rigescens Franch.","authors":"Qiao Gao, Yi Li, Yao Zhong, Shu-Xian Zhang, Chang-Yuan Yu, Guang Chen","doi":"10.1016/j.jep.2024.119115","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119115","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Gentiana rigescens Franch. (G. rigescens), known as \"Dian Long Dan\" in Southern Yunnan Herbal, has a long history in traditional Chinese medicine for treating hepatitis, allergies, postherpetic neuralgia, cholecystitis and rheumatism.</p><p><strong>Aim of the study: </strong>This study aims to comprehensively analyze the phenolic composition of G. rigescens, evaluate its potential anti-inflammatory effects, elucidate underlying mechanisms, and identify its in vivo bioactive phenolic constituents.</p><p><strong>Materials and methods: </strong>The extraction of G. rigescens phenolic compounds (GRP) was optimized using the Box-Behnken response surface method, with four phenolic compounds (mangiferin, esculetin, ferulic acid and kaempferol) used as quality index markers. GRP's phytochemical composition was subsequently profiled via UPLC-Q-TOF-MS/MS analysis. Anti-inflammatory activity and mechanisms were assessed in LPS-stimulated RAW264.7 cells and murine models, utilizing NO production assays, ELISA, qRT-PCR, Western blotting and histopathological analysis. Bioactive phenolic compounds in blood were identified post-oral administration for in vivo activity prediction.</p><p><strong>Results: </strong>The optimal extraction conditions for GRP were determined as follows: Soxhlet extraction using acetone with hydrochloric acid 0.06 mol/L, at a liquid-to-solid ratio of 132: l. for 6.6 h. Seventy-one of phenolic compounds were identified in GRP using UPLC-Q-TOF-MS/MS. GRP significantly inhibited LPS-induced NO production in RAW 264.7 macrophages and reduced pro-inflammatory cytokines IL-6, IL-1β, and TNF-α while increasing anti-inflammatory IL-10. In the carrageenan-induced inflammatory model, GRP exhibited a 69.81% inhibition rate of toe swelling at high doses (1 g/kg), along with protective effects against joint injury, as observed in histological assessments. Mechanistically, GRP downregulated mRNA levels of inflammatory cytokines and reduced the expression of inflammatory proteins iNOS, COX-2, p65, p-p65 and P-IκB as shown by Western blotting. Twenty-five of phenolic compounds, including mangiferin, swertianolin, acacetin, umbelliferone and caffeic acid, were identified in vivo in the blood, indicating potential bioactive roles.</p><p><strong>Conclusions: </strong>This study provides the first comprehensive profile of the phenolic composition of G. rigescen, alongside a detailed investigation of its anti-inflammatory activity, mechanisms, and in vivo bioactive components. These findings highlight the therapeutic potential of Dian Long Dan's phenolic constituents and support further research on G. rigescens.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119115"},"PeriodicalIF":4.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648284","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":"Antidepressant and anxiolytic effects of Wuling Capsule in CSDS mice: Alleviating HPA axis hyperactivity via the Nesfatin-1/NF-κB signaling pathway.","authors":"Jiayuan Zheng, Jing Han, Yu Wang, Yunhua Xu, Jin Yu, Bing Han, Zhanzhuang Tian","doi":"10.1016/j.jep.2024.119111","DOIUrl":"10.1016/j.jep.2024.119111","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Wuling capsule, composed of the traditional Chinese medicine Wuling mycelia powder, is made by fermenting and processing Xylaria nigripes (Kl.) Sacc. Clinically, it is commonly used to alleviate depression and anxiety. However, the mechanisms through which Wuling capsule exerts its therapeutic benefits have not been clearly defined.</p><p><strong>Aim of the study: </strong>This study aims to elucidate the mechanisms by which Wuling capsule alleviates depression and anxiety like behaviors induced by chronic social defeat stress (CSDS) in mice.</p><p><strong>Materials and methods: </strong>High-performance liquid chromatography-tandem mass spectrometry system was used to identify the components of the Wuling capsule. Mice were subjected to CSDS to induce depression and anxiety-like behaviors. The expression of hypothalamic corticotropin-releasing hormone (CRH) and Nesfatin-1, as well as serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were quantified. Behavioral assessments included the open field test, elevated plus maze, sucrose preference test, and forced swim test to evaluate depression and anxiety levels. Specific manipulation of Nesfatin-1 in the paraventricular nucleus of the hypothalamus (PVN) or cells was achieved through stereotaxic virus injection or plasmid transfection. Intracerebral cannula implantation was used for PVN-specific drug administration.</p><p><strong>Results: </strong>A total of 123 different components were identified in Wuling capsule. CSDS induced depression and anxiety-like behaviors in mice, along with hyperactivation of the HPA axis, increased hypothalamic Nesfatin-1 levels, and elevated nuclear factor kappa-B (NF-κB) phosphorylation. Overexpression of Nesfatin-1 in the hypothalamus mimicked the effects of CSDS. Conversely, knockdown of hypothalamic Nesfatin-1 or PVN-specific administration of Nesfatin-1 antibody or NF-κB antagonist mitigated CSDS-induced depression and anxiety-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. In neuroblastoma-2a (N2a) cells, overexpression of Nesfatin-1 led to increased NF-κB phosphorylation and CRH levels, whereas knockdown of Nesfatin-1 produced the opposite effects. Treatment with Wuling capsule alleviated CSDS-induced depression and anxiety-like behaviors, HPA axis hyperactivity, and activation of the hypothalamic Nesfatin-1/NF-κB pathway.</p><p><strong>Conclusions: </strong>The hypothalamic Nesfatin-1/NF-κB pathway plays a significant role in depression by modulating the HPA axis and is involved in the antidepressant and anxiolytic effects of Wuling capsule.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119111"},"PeriodicalIF":4.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648234","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":"Clinical efficacy of Chinese herbal medicine formula for Graves' hyperthyroidism: A multicentre, randomized, double-blind, placebo-controlled clinical trial.","authors":"Di Gan, Tian-Shu Gao, Li Ma, Hao Lu, Hong Dai, Qing-Yang Liu, Yi-Wen Lai, Xin-Hui Liu, Ze-Dong Peng, Ru-Yu Chen, Zi-Yang Qiu, Yu Tong, Ruo-Xuan Yan, Jia-Hui Liu, Qing Shen, Chen Wang, Shan-Shan Yu, Si-Wei Chen, Xiao-Wei Liu, Xue-Ying Chen, Feng-Nuan Zhang, Zhi-Min Wang, Ying-Na Wang, Xiao Yang","doi":"10.1016/j.jep.2024.119106","DOIUrl":"10.1016/j.jep.2024.119106","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>According to the theory of traditional Chinese medicine, Graves' disease (GD) is called 'Ying Bing', which is a kind of goiter. Haizao Yuhu decoction, originated from the medical book of the Ming Dynasty 'Waikezhengzong', is a classic Chinese herbal formula for the treatment of 'Ying Bing' for more than 400 years. Pingkang granules, modified from the Chinese herbal formula Haizao Yuhu decoction specialized in GD, has shown effectiveness in several single-centre studies. However, high-quality clinical evidence for the management of GD using Pingkang granules remains insufficient.</p><p><strong>Aim of the study: </strong>To obtain high-quality medical evidence for the treatment of GD with Pingkang granules through randomized controlled clinical trial.</p><p><strong>Materials and methods: </strong>A multicentre, randomized, double-blinded, placebo-controlled clinical trial was designed. A total of 186 patients with Graves' hyperthyroidism from five medical centers were randomly assigned to receive methimazole [MMI] and Pingkang granules placebo (group A), MMI and Pingkang granules (group B), or MMI placebo and Pingkang granules (group C) in a 1:1:1 ratio for 12 weeks. The primary clinical outcomes were serum free triiodothyronine (FT<sub>3</sub>) and free thyroxine (FT<sub>4</sub>) levels from baseline until the end of the research. Secondary clinical outcomes included serum thyrotrophin receptor antibody (TRAb) levels at 4- and 12-weeks post-intervention, thyroid volume, peak systolic velocity of the superior thyroid artery (STA-PSV), 39-item version of Thyroid-Related Patient-Reported Outcome (ThyPRO39) scores, and safety assessment included blood routine, liver and kidney function tests from baseline to the endpoint.</p><p><strong>Results: </strong>150 patients were included in the full analysis set for efficacy analysis, including 48, 50, and 52 in groups A, B, and C, respectively. At the endpoint, three regimens significantly reduced serum FT<sub>3</sub> levels (group A, p=0.0027; group B, p < 0.0001; group C, p=0.0028) and FT<sub>4</sub> levels (group A, p < 0.0001; group B, p < 0.0001; group C, p < 0.0001), and the combination of MMI and Pingkang granules markedly reduced serum TRAb levels (p = 0.0014). The thyroid volume in group A was significantly larger than that at baseline at week 12 (p=0.0370), and there were no statistically significant differences in the thyroid volume among groups at week 4 (p=0.7485) and 12 (p=0.1333). STA-PSV values in group B were significantly higher than those in group A at week 4 (p=0.0409). The STA-PSV levels in groups A (p < 0.0001) and C (p=0.0025) were significantly lower than those at baseline at week 4, and STA-PSV levels in all groups were significantly lower than those at baseline at week 12 (group A, p=0.0095; group B, p=0.0138; group C, p=0.0423). Pingkang granule monotherapy significantly ameliorated symptoms related to hyperthyroidism (p < 0.0001)","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119106"},"PeriodicalIF":4.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643951","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":"Banxia Baizhu Tianma Decoction alleviates pentylenetetrazol-induced epileptic seizures in rats by preventing neuronal cell damage and apoptosis and altering serum and urine metabolic profiles.","authors":"Lv Gao, Ran Xie, Xiujuan Yang, Yuling Liu, Rong Lin, Zhengyu Yao, Yingxuan Wang, Baokai Dou, Jing Meng, Xiaoyu Hu, Lixia Song, Jinlai Cheng, Zhenggang Shi, Hairu Huo, Feng Sui, Qi Song","doi":"10.1016/j.jep.2024.119112","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119112","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Epilepsy (EP) is one of the most prevalent chronic neurological disorders in children, characterised by a prolonged course and a propensity for recurrence. Banxia Baizhu Tianma Decoction (BBTD), a traditional Chinese medicine formula, is commonly employed in the clinical management of EP and has demonstrated satisfactory therapeutic effects.</p><p><strong>Aim of the study: </strong>This study aimed to evaluate the anti-epileptic effects of BBTD and to explore its molecular mechanisms.</p><p><strong>Materials and methods: </strong>EP rat model was induced by pentylenetetrazol (PTZ) and treated with BBTD. Parameters such as seizure grade and duration were recorded to evaluate the improvement of BBTD on epileptic behavior. Nissl staining was used to observe the pathological changes in the cerebral motor cortex. The expression levels of the Bax and Bcl-2 in the motor cortex were measured by western blot analysis to assess neuronal damage and apoptosis. The therapeutic action of BBTD was evaluated by examining the levels of neurotransmitters γ-aminobutyric acid (GABA) and glutamate (Glu) in the brain tissue of EP rats, along with assessments of neuronal damage and apoptosis. Non-targeted metabolomics techniques were employed to conduct a comprehensive analysis of serum and urine metabolites, and network analysis of metabolite-related targets was performed to enhance understanding of the anti-epileptic effects and mechanisms of BBTD.</p><p><strong>Results: </strong>After BBTD treatment, the EP model rats exhibited reduced seizure severity and shortened seizure duration. Moreover, BBTD mitigated PTZ-induced neuronal damage, as evidenced by a significant increase in the number of Nissl bodies in the motor cortex following treatment. At the same time, BBTD inhibited neuronal apoptosis, as demonstrated by the up-regulation of the anti-apoptotic protein Bcl-2 and down-regulation of the pro-apoptotic protein Bax in the brain tissue of treated rats. In addition, BBTD reversed the decreased levels of GABA and the increased levels of Glu in the brain tissue of the model group. Metabolomics analyses suggested that BBTD treatment for EP may be closely associated with alterations in urinary metabolites related to vitamin B6 and pyrimidine metabolism, as well as serum metabolites involved in purine metabolism, glycerophospholipid metabolism and vitamin B6 metabolism. Finally, network analysis of metabolite targets indicated that dopamine and alpha-linolenic acid metabolites may play significant roles in the therapeutic effects of BBTD on EP.</p><p><strong>Conclusion: </strong>BBTD demonstrated anti-epileptic effects in PTZ-induced seizure rats by regulating neurotransmitter balance, reducing neuronal damage and inhibiting apoptosis, suggesting its potential for the development of novel AEDs. This is the first time that UHPLC-MS-based urine and serum metabolomics have been used to elucidate the anti-epileptic mecha","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119112"},"PeriodicalIF":4.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648235","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}