期刊：
International Immunopharmacology,2024年130:111749 ISSN：1567-5769
通讯作者：
Wang, Hanqing;Peng, Qinghua
作者机构：
[Tian, Sainan; Zhu, Zhengqing] College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China;[Long, Hongping] Center for Medical Research and Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha 410002, China;[Wang, Hanqing] College of Pharmacy, Ningxia Medical University, Yinchuan 750003, China;[Guo, Dongwei] College of Clinical Medicine, Hunan University of Chinese Medicine, Changsha 410208, China;[Du, Ke; Wang, Yajing] College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China
通讯机构：
[Hanqing Wang; Qinghua Peng] C;College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China<&wdkj&>Center for Medical Research and Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha 410002, China<&wdkj&>College of Pharmacy, Ningxia Medical University, Yinchuan 750003, China
摘要：
AIMS: Saikosaponin F (SsF) is one of the major active ingredients of Radix Bupleuri, an herb widely used in the treatment of depression. Studies have shown that dry eye disease often occurs together with depression. The aim of this study is to investigate whether SsF can improve depression-associated dry eye disease and explore the underlying mechanism. METHODS: Behavioral test was used to verify the effect of SsF on CUMS-induced depression-like behaviors in mice. Corneal fluorescein staining, phenol red cotton thread test and periodic acid-Schiff (PAS) staining were used to observe the effect of SsF on depression-associated dry eye disease. Western blot (WB) was performed to observe the expression of TAK1 protein and key proteins of NF-κB and MAPK (P38) inflammatory pathways in the hippocampus and cornea. Immunohistochemical staining was used to observe the expression of microglia, and immunoprecipitation was used to observe K63-linked TAK1 ubiquitination. Subsequently, we constructed a viral vector sh-TAK1 to silence TAK1 protein to verify whether SsF exerted its therapeutic effect based on TAK1. The expression of inflammatory factors such as IL-1β, TNF-α and IL-18 in hippocampus and cornea were detected by ELISA. Overexpression of TRIM8 (OE-TRIM8) by viral vector was used to verify whether SsF improved depression-associated dry eye disease based on TRIM8. RESULTS: SsF treatment significantly improved the depression-like behavior, increased tear production and restored corneal injury in depression-related dry eye model mice. SsF treatment downregulated TAK1 expression and TRIM8-induced K63-linked TAK1 polyubiquitination, while inhibiting the activation of NF-κB and MAPK (P38) inflammatory pathways and microglial expression. In addition, selective inhibition of TAK1 expression ameliorated depression-associated dry eye disease, while overexpression of TRIM8 attenuated the therapeutic effect of SsF on depression-associated dry eye disease. CONCLUSION: SsF inhibited the polyubiquitination of TAK1 by acting on TRIM8, resulting in the downregulation of TAK1 expression, inhibition of inflammatory response, and improvement of CUMS-induced depression-associated dry eye disease.
摘要：
Ethnopharmacological relevance: Huang-Qi-Jian-Zhong-Tang (HQJZT) is a canonical traditional Chinese medicine (TCM) formula that has been widely used in both the prevention and treatment of gastrointestinal diseases, including gastric ulcer, duodenal ulcer, and chronic atrophic gastritis, in China. Aim of the study: In the present study, we investigated the gastroprotective potential of HQJZT in a rat model of indomethacin (IND)-induced gastric ulcer and explained the biochemical, cellular, and molecular mechanisms involved. Materials and methods: Observations were conducted at the macroscopic level to ascertain the ulcer index (UI) and the curative index (CI). Histopathological examinations were conducted, and a microscopic score (MS) was computed. The gastric juice volume, total acidity, pH value, and pepsin activity were quantified. Antioxidant and oxidative parameters were assessed, namely GSH, CAT, SOD, and MDA content. The RFLSI Pro instrument was employed to measure the blood flow within the gastric mucosa continuously. The mRNA levels of the inflam-matory cytokines were assessed using droplet digital PCR (ddPCR). Molecular docking was employed to examine the interaction between representative active components of HQJZT and the binding sites associated with the NF-kappa B and STAT signaling pathways. The protein expression and localization of p-JAK, p-STAT, p-I kappa B beta, and p-NF-kappa B were evaluated through immunofluorescence analysis. Results: The administration of HQJZT treatment demonstrated a significant reduction in gastric lesions induced by IND, leading to a notable decrease in the UI. Additionally, HQJZT treatment significantly decreased gastric juice volume, acidity, and pepsin activity, accompanied by increased pH value. IND-treated stomachs exhibited severe hemorrhagic necrosis, submucosal edema, and epithelial cell destruction. However, the administration of HQJZT effectively counteracted these pathological changes. Furthermore, HQJZT administration significantly increased blood flow to the gastric mucosa. HQJZT enhanced antioxidant defenses and modulated oxidative stress by increasing SOD, CAT, and GSH activities while reducing MDA levels. Moreover, HQJZT reversed IND-induced increases in mRNA expression levels of inflammatory cytokines. Molecular docking analysis revealed that the representative active components of HQJZT could bind to the NF-kappa B and STAT signaling pathways. In addition, immunofluorescence microscopy revealed that HQJZT markedly attenuated the phosphorylation of I kappa & Vcy;beta, NF-kappa B, JAK, and STAT. Conclusions: The therapeutic and protective effect of HQJZT on gastric ulcers is attributed to its ability to suppress gastric acid secretion, enhance antioxidative defenses and blood flow, mitigate proinflammatory cytokines, and inhibit the activation of NF-kappa B and STAT signaling pathways.
作者机构：
[Ning, Bo] First Clinical Medical College, Shaanxi University of Chinese Medicine, Xi'an, 712046, China. Electronic address: ningbo9803@163.com;[Ge, Teng] First Clinical Medical College, Shaanxi University of Chinese Medicine, Xi'an, 712046, China. Electronic address: 221020921302@email.sntcm.edu.cn;[Zhao, Qiang-Qiang] First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address: 20221110519@stu.gzucm.edu.cn;[Feng, Lan-Shuan] First Clinical Medical College, Shaanxi University of Chinese Medicine, Xi'an, 712046, China. Electronic address: fls9504@163.com;[Wu, Yong-Qing] First Clinical Medical College, Shaanxi University of Chinese Medicine, Xi'an, 712046, China. Electronic address: Wuyongqing07062023@163.com
通讯机构：
[Ge, Teng; Zhao, Qiang-Qiang; Wu, Yong-Qing; Feng, Lan-Shuan; Chen, Huan; Ning, Bo] F;[Lian, Kun] C;[Zhao, Ming-Jun] S;First Clinical Medical College, Shaanxi University of Chinese Medicine, Xi'an, 712046, China. Electronic address:;First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address:
关键词：
Anxiety or depression after PCI;Mechanism;Therapeutic drugs;Traditional Chinese medicine
摘要：
ETHNIC PHARMACOLOGICAL RELEVANCE: Anxiety or depression after percutaneous coronary intervention (PCI) is a common clinical disease. Currently, conventional pharmacotherapy primarily involves the administration of anxiolytic or antidepressant medications in conjunction with anticoagulants, antiplatelet agents, and other cardiovascular drugs. However, challenges such as drug dependence, adverse reactions and related concerns persist in the treatment of this disease. Numerous pertinent studies have demonstrated that Traditional Chinese Medicine (TCM) exhibits significant therapeutic efficacy and distinctive advantages in managing post-PCI anxiety or depression. AIM OF THIS REVIEW: This review attempted to summarize the characteristics of TCM for treating anxiety or depression after PCI, including single Chinese herbs, Chinese medicine monomers, compound TCM prescriptions, TCM patented drugs, and other TCM-related treatment methods, focusing on the analysis of the relevant mechanism of TCM treatment of this disease. METHODS: By searching the literature on treating anxiety or depression after PCI with TCM in PubMed, Web of Science, CNKI, and other relevant databases, this review focuses on the latest research progress of TCM treatment of this disease. RESULTS: In the treatment of anxiety or depression after PCI, TCM exerts significant pharmacological effects such as anti-inflammatory, antioxidant, anti-anxiety or anti-depression, cardiovascular and cerebrovascular protection, and neuroprotection, mainly by regulating the levels of related inflammatory factors, oxidative stress markers, neurotransmitter levels, and related signaling pathways. TCM has a good clinical effect in treating anxiety or depression after PCI with individualized treatment. CONCLUSIONS: TCM has terrific potential and good prospects in the treatment of anxiety or depression after PCI. The main direction of future exploration is the study of the mechanism related to Chinese medicine monomers and the large sample clinical study related to compound TCM prescriptions.
摘要：
Objective Based on metabolomics,it explored the differential metabolites screened by Chinese herbal medicines(compound/single decoction pieces)for the treatment of coronary heart disease with blood stasis syndrome in different species and summarized the biomarkers and related metabolic pathways after the intervention of Chinese herbal medicines.Methods The metabonomics study of traditional Chinese medicine(compound/single decoction pieces)in the treatment of coronary heart dis-ease with blood stasis syndrome was retrieved from CNKI,Wanfang database,VIP database,EMBASE,PubMed,the Cochrane Li-brary and web of science database.The differential metabolites included in the study were summarized.The metabolites were anno-tated by HMDB,PubChem subs and KEGG,and the metabolite path visualization was analyzed by metPA network software.Re-sults A total of eight publications were included in this study,and a total of 89 differential metabolites were counted after counting the recurring metabolites in both species that were mainly involved in 132 metabolic pathways.Through the analysis of pathway to-pology and the statistics of repeated metabolic pathways,16 metabolic pathways with P values less than 0.05 were selected as the metabolic pathways of traditional Chinese medicine(compound/single decoction pieces)in the treatment of coronary heart disease with blood stasis syndrome in different species.For the metabolites enriched in various differential metabolic pathways,the metab-olites repeatedly screened in different studies included phenylalanine,glutamine,glycine,citric acid,choline,creatine,lactic acid,β-glucose,α-glucose and arachidonic acid.Conclusion The herbs(compound/single decoction pieces)used for the treatment of coronary heart disease with blood stasis syndrome in various studies were represented by Xuefu Zhuyu Decoction(血府逐瘀汤),Taohong Siwu Decoction(桃红四物汤),Yangxin Tongmai Formula(养心通脉方)and Suhexiang(Styrax).Bioinformatics analysis based on metabolomics of Chinese herbal medicines(compound/single decoction pieces)for the treatment of coronary heart disease with blood stasis showed that the mechanism of action involves various aspects of glucose metabolism,amino acid metabolism,energy metabolism,choline metabolism and fatty acid metabolism,in which the basic tricarboxylic acid cycle is in-volved.The differential metabolites related to coronary heart disease with blood stasis syndrome,including lactic acid,glucose,cit-ric acid,arachidonic acid,creatine,phenylalanine,choline,glutamine and glycine,were summarized.
摘要：
目的筛选家系早发冠心病血瘀证的特异性蛋白,为今后临床早期诊断和预防疾病提供潜在生物标志物。方法通过同位素相对标记与绝对定量技术(isobaric tags for relative and absolute quanti...展开更多 目的筛选家系早发冠心病血瘀证的特异性蛋白,为今后临床早期诊断和预防疾病提供潜在生物标志物。方法通过同位素相对标记与绝对定量技术(isobaric tags for relative and absolute quantification,i TRAQ)分析家系早发冠心病血瘀证患者、家系早发冠心病非血瘀证患者及健康人的血浆蛋白表达,数据分析后得到各组间的差异蛋白表达情况,再经差异蛋白筛选标准初步得到疾病的预测蛋白,并使用Western blot验证预测蛋白。结果通过i TRAQ技术共得到差异蛋白75个,其中家系早发冠心病血瘀证组与健康对照组之间共得到32个差异蛋白,包括22个上调蛋白与10个下调蛋白,共涉及429个生物学过程,其与角质化、皮肤发展、蛋白质激活级联反应等关系最为密切;在代谢途径金黄色葡萄球菌感染、补体和凝血级联、血小板激活等KEGG通路上富集。与健康对照组相比,家系早发冠心病血瘀证组差异蛋白补体因子H(complement factor H,CFH)表达水平差异有统计学意义(P<0.01)。结论经差异蛋白筛选标准得到的CFH蛋白,可作为家系早发冠心病血瘀证早期诊断的潜在生物标志物。收起
