期刊：
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING,2024年 ISSN：1386-2073
作者机构：
[Li, Qing; Li, Xiao Ling; Hou, Chao Wen; Shi, Yuhe; Zhu, Jue; Tong, Qiao Zhen; Liu, Xiang Dan] Department of Hunan University of Chinese Medicine, School of Pharmacy, Changsha 410208, Hunan Province, P.R.China
摘要：
AIMS AND OBJECTIVE: This study aimed to identify the bioactive compounds and explore the multi-target mechanisms of Salvia miltiorrhiza Bunge (SMB) against coronary heart disease (CHD) using an integrated serum pharmacochemistry and network pharmacology approach. MATERIALS AND METHODS: The chemical constituents of SMB were characterized by UPLC-MS. The absorbed ingredients and metabolites after oral SMB administration were identified in rat serum. Therapeutic targets of SMB against CHD were predicted by intersecting the targets of absorbed compounds from databases and CHD-associated genes. Protein-protein interaction network, pathway analysis, molecular docking, and molecular dynamic simulation were performed. RESULTS: A total of 61 SMB-derived compounds were identified in rat serum. Network analysis revealed 111 candidate targets highly related to CHD pathways. Further topological analysis identified 10 hub targets and 20 key active compounds, constructing an informative compoundtarget- pathway network. PTGS2 and TNF were predicted as primary targets of SMB against CHD based on molecular dynamic simulation. CONCLUSION: This integrated approach identified bioactive compounds and multi-target mechanisms of SMB against CHD. The results provide scientific evidence supporting SMB's clinical efficacy and reveal potential anti-CHD targets.
期刊：
CURRENT NEUROPHARMACOLOGY,2024年22(10):1672-1696 ISSN：1570-159X
作者机构：
Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and
Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese Medicine and Western Medicine,
Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Third-Grade
Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine,
College of Medicine and Health Sciences, China Three Gorges University, Yichang, Hubei 443002, China;Department of Neurosurgery, First Affiliated
Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410007, China;School
of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[Gong, Lipeng; Liang, Junjie; Xie, Letian] Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and
Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese Medicine and Western Medicine,
Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
摘要：
Ischemic stroke is a leading cause of disability and death worldwide. However, the clinical efficacy of recanalization therapy as a preferred option is significantly hindered by reperfusion injury. The transformation between different phenotypes of gliocytes is closely associated with cerebral ischemia/ reperfusion injury (CI/RI). Moreover, gliocyte polarization induces metabolic reprogramming, which refers to the shift in gliocyte phenotype and the overall transformation of the metabolic network to compensate for energy demand and building block requirements during CI/RI caused by hypoxia, energy deficiency, and oxidative stress. Within microglia, the pro-inflammatory phenotype exhibits upregulated glycolysis, pentose phosphate pathway, fatty acid synthesis, and glutamine synthesis, whereas the anti-inflammatory phenotype demonstrates enhanced mitochondrial oxidative phosphorylation and fatty acid oxidation. Reactive astrocytes display increased glycolysis but impaired glycogenolysis and reduced glutamate uptake after CI/RI. There is mounting evidence suggesting that manipulation of energy metabolism homeostasis can induce microglial cells and astrocytes to switch from neurotoxic to neuroprotective phenotypes. A comprehensive understanding of underlying mechanisms and manipulation strategies targeting metabolic pathways could potentially enable gliocytes to be reprogrammed toward beneficial functions while opening new therapeutic avenues for CI/RI treatment. This review provides an overview of current insights into metabolic reprogramming mechanisms in microglia and astrocytes within the pathophysiological context of CI/RI, along with potential pharmacological targets. Herein, we emphasize the potential of metabolic reprogramming of gliocytes as a therapeutic target for CI/RI and aim to offer a novel perspective in the treatment of CI/RI.
作者机构：
[Luo, Hongshan; Lin, Limei; Zhang, Zhimin; Li, Yamei; Xia, Bohou; Xu, Chunfang; Xie, Jingchen; Shi, Zhe; Li, Minjie] College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China;[Luo, Hongshan] Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, Changsha, 410208, China. Electronic address: luohongshanxc@163.com;[Li, Yamei] Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, Changsha, 410208, China. Electronic address: yameili@hnucm.edu.cn;[Xie, Jingchen] Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, Changsha, 410208, China. Electronic address: 190478360@qq.com;[Xu, Chunfang] Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, Changsha, 410208, China. Electronic address: xcf200002@163.com
通讯机构：
[Limei Lin] C;Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, Changsha, 410208, China. Electronic address:
关键词：
Acute mastitis;Blood-milk barrier;Lipopolysaccharides;Prunella vulgaris L.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: According to ancient literature, Prunella vulgaris L. (P vulgaris) alleviates mastitis and has been used in China for many years; however, there are no relevant reports that confirm this or the mechanism of its efficacy. AIM OF THE STUDY: To explore the anti-acute mastitis effect and potential mechanism of P vulgaris extract. MATERIALS AND METHODS: First, the active ingredients and targets of P vulgaris against mastitis were predicted using network pharmacology. Next, the relevant active ingredients were enriched using macroporous resins and verified using UV and UPLC-Q-TOF-MS/MS. Lastly, a mouse model of acute mastitis was established by injecting lipopolysaccharides into the mammary gland and administering P vulgaris extract by oral gavage. The pathological changes in mammary tissue were observed by HE staining. Serum and tissue inflammatory factors were measured by ELISA method. MPO activity in mammary tissue was measured using colorimetry and MPO expression was detected by immunohistochemistry. The expression of tight junction proteins (ZO-1, claudin-3, and occludin) in mammary tissue was detected by immunofluorescence and Western blot. iNOS and COX-2 in mammary tissue were detected by Western blot. MAPK pathway and NF-κB pathway related proteins were also detected by Western blot. RESULTS: Network pharmacology predicted that phenolic acids and flavonoids in P vulgaris had anti-mastitis effects. The contents of total flavonoids and total phenolic acids in P vulgaris extract were 64.5% and 29.4%, respectively. UPLC-Q-TOF-MS/MS confirmed that P vulgaris extract contained phenolic acids and flavonoids. The results of animal experiments showed that P vulgaris extract reduced lipopolysaccharide-induced inflammatory edema, inflammatory cell infiltration, and interstitial congestion of mammary tissue. It also reduced the levels of serum and tissue inflammatory factors TNF-α, IL-6, and IL-1β, and inhibited the activation of MPO. Furthermore, it downregulated the expression of MAPK and NF-κB pathway-related proteins. The expressions of ZO-1, occludin, and claudin-3 in mammary gland tissues were upregulated. CONCLUSIONS: P vulgaris extract can maintain the integrity of mammary connective tissue and reduce its inflammatory response to prevent acute mastitis. Its mechanism probably involves regulating NF-κB and MAPK pathways.
通讯机构：
[Tan, Y; Pei, G ] H;Hunan Univ Chinese Med, Coll Pharm, Changsha 410000, Peoples R China.;Educ Dept Hunan Prov, Key Lab Modern Res TCM, Changsha 410000, Peoples R China.
关键词：
H3K18la;LDHA;histone lactylation;liver injury;macrophages;salvianolic acid B
摘要：
Salvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from the roots of Salvia miltiorrhiza Bunge. This research was designed to reveal the potential mechanism of Sal B anti-liver injury from the perspective of macrophages. In our lipopolysaccharide-induced M1 macrophage model, Sal B showed a clear dose-dependent gradient of inhibition of the macrophage trend of the M1 type. Moreover, Sal B downregulated the expression of lactate dehydrogenase A (LDHA), while the overexpression of LDHA impaired Sal B's effect of inhibiting the trend of macrophage M1 polarization. Additionally, this study revealed that Sal B exhibited inhibitory effects on the lactylation process of histone H3 lysine 18 (H3K18la). In a ChIP-qPCR analysis, Sal B was observed to drive a reduction in H3K18la levels in the promoter region of the LDHA, NLRP3, and IL-1β genes. Furthermore, our in vivo experiments showed that Sal B has a good effect on alleviating CCl(4)-induced liver injury. An examination of liver tissues and the Kupffer cells isolated from those tissues proved that Sal B affects the M1 polarization of macrophages and the level of histone lactylation. Together, our data reveal that Sal B has a potential mechanism of inhibiting the histone lactylation of macrophages by downregulating the level of LDHA in the treatment of liver injury.
通讯机构：
[Wu, P; Lin, LM ] H;Hunan Univ Chinese Med, Coll Pharm, 300 Xueshi Rd, Changsha 410208, Peoples R China.
关键词：
AMPK;Diabetes mellitus;Medicinal and edible homologous;PI3K/Akt;Plant polysaccharides
摘要：
Medicinal and edible homologs (MEHs) can be used in medicine and food. The National Health Commission announced that a total of 103 kinds of medicinal and edible homologous plants (MEHPs) would be available by were available in 2023. Diabetes mellitus (DM) has become the third most common chronic metabolic disease that seriously threatens human health worldwide. Polysaccharides, the main component isolated from MEHPs, have significant antidiabetic effects with few side effects. Based on a literature search, this paper summarizes the preparation methods, structural characterization, and antidiabetic functions and mechanisms of MEHPs polysaccharides (MEHPPs). Specifically, MEHPPs mainly regulate PI3K/Akt, AMPK, cAMP/PKA, Nrf2/Keap1, NF-κB, MAPK and other signaling pathways to promote insulin secretion and release, improve glycolipid metabolism, inhibit the inflammatory response, decrease oxidative stress and regulate intestinal flora. Among them, 16 kinds of MEHPPs were found to have obvious anti-diabetic effects. This article reviews the prevention and treatment of diabetes and its complications by MEHPPs and provides a basis for the development of safe and effective MEHPP-derived health products and new drugs to prevent and treat diabetes.
期刊：
Frontiers in Microbiology,2024年15:1354823 ISSN：1664-302X
作者机构：
[Guo, Mingmin] School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China;[Shen, Junxi; Tan, Zhoujin; Fang, Leyao] School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China;[Chen, Meili] Changsha Hospital of Traditional Chinese Medicine, Changsha, China;[He, Wenzhi] School of Stomatology, Hunan University of Chinese Medicine, Changsha, China
关键词：
CutC;TMAO;adenine;cecal microbiota;diarrhea with kidney-yang deficiency syndrome;folium sennae;inflammatory factors
摘要：
OBJECTIVE: Previous studies have indicated that diarrhea with kidney-yang deficiency syndrome leads to a disorder of small intestine contents and mucosal microbiota. However, the relationship of TMA-lyase (CutC) activity and TMAO with diarrhea with kidney-yang deficiency syndrome remains unexplored. Therefore, this study explores the relationship between cecal microbiota and choline TMA-lyase (CutC) activity, as well as the correlation between trimethylamine oxide (TMAO), inflammatory index, and CutC activity. METHOD: Twenty SPF-grade male KM mice were randomly divided into the normal group (CN) and the diarrhea model group (CD). Diarrhea mouse models were established by adenine combined with Folium sennae administration. CutC activity, TMAO, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were detected, and the cecal content microbiota was sequenced. RESULT: After 14 days, diarrhea occurred in the CD group. Compared with the CN group, there was no significant change in the activity of CutC in the small intestine of the CD group, while the activity of CutC in the cecum was significantly increased, and the levels of TMAO, IL-6, and TNF-α showed a significant increase. The Chao1 index, Observed_species index, Shannon index, and Simpson index all exhibited a decreasing trend. The main changes at the bacterial genus level were Alistipes, Enterorhabdus, Desulfovibrio, Bacteroides, Candidatus_Saccharimonas, and [Ruminococcus]_torques_group. The results of LEfSe analysis, random forest analysis and ROC curve analysis revealed Paludicola, Blautia, Negativibacillus, Paraprevotella, Harryflintia, Candidatus_Soleaferrea, Anaerotruncus, Oscillibacter, Colidextribacter, [Ruminococcus]_torques_group, and Bacteroides as characteristic bacteria in the CD group. Correlation analysis showed a significant negative correlation between cecal CutC activity and Ligilactobacillus, and a significant positive correlation with Negativibacillus and Paludicola. The level of TMAO was significantly positively correlated with CutC activity and IL-6. CONCLUSION: Diarrhea with kidney-yang deficiency syndrome significantly affects the physiological status, digestive enzyme activity, CutC activity, TMAO levels, and inflammatory response in mice. Additionally, there are changes in the composition and function of cecal microbiota, indicating an important impact of diarrhea with kidney-yang deficiency syndrome on the host intestinal microbiota balance. The occurrence of diarrhea with kidney-yang deficiency syndrome may be associated with dysbiosis of intestinal microbiota, increased CutC activity, elevated TMAO levels, and heightened inflammatory factor levels.
摘要：
目的 分析中药注射剂（traditional Chinese medicine injections,TCMIs）致类过敏反应（anaphylatiod reactions,ARs）相关研究文献，了解其研究脉络、热点和发展趋势。方法 检索中国知网（CNKI）、维普（VIP）、万方（Wanfang）、Web of Science（WOS）、PubMed数据库中建库至2023年5月1日收录的TCMIs相关ARs的中、英文文献，采用VOSviewer1.6.18绘制核心作者、机构合作及关键词共现网络，运用CiteSpace 5.7.R5进行关键词聚类及突现展示。结果 共纳入中文文献190篇，英文文献48篇，文献发文量总体呈波浪式上升又缓慢下降趋势；发表机构以中国中医科学院中药研究所为主，发表文献高达41篇；形成了52位核心作者及梁爱华、易艳等代表性研究团队；研究机构间的合作以中医药大学及附属医院为主；关键词共现与聚类分析显示研究内容侧重于TCMIs相关ARs的作用机制、模型建立、评价方法、检测指标、质量控制；关键词突现分析提示大分子物质、G蛋白偶联受体B2（Mas-related G protein-coupled receptor B2,MRGPRB2）、安全性评价是TCMIs相关ARs未来研究领域的发展趋势。结论 TCMIs相关ARs研究热点主要围绕其作用机制、安全性评价展开，体现在TCMIs致ARs成分的筛选、剂量选择及相关通路、受体分析，但此方面研究尚浅，需要借助新的技术手段进行系统挖掘，促进TCMIs相关ARs研究领域的深入发展。
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.
