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丹参酮 I:药理活性、疾病防治的分子机制及未来展望

Tanshinone I: Pharmacological activities, molecular mechanisms against diseases and future perspectives.

作者信息

Ke Liyuan, Zhong Chenhui, Chen Zhijie, Zheng Ziyao, Li Shaoguang, Chen Bing, Wu Qiaoyi, Yao Hong

机构信息

Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, China.

Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, China; Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), School of Pharmacy, Fujian Medical University, Fuzhou, China.

出版信息

Phytomedicine. 2023 Feb;110:154632. doi: 10.1016/j.phymed.2022.154632. Epub 2022 Dec 27.

DOI:10.1016/j.phymed.2022.154632
PMID:36608501
Abstract

BACKGROUND

Tanshinone I (Tan I) is known as one of the important active components in Salvia miltiorrhiza. In recent years, Tan I has received a substantial amount of attention from the research community for various studies being updated and has been shown to possess favorable activities including anti-oxidative stress, regulation of cell autophagy or apoptosis, inhibition of inflammation, etc. PURPOSE: To summarize the investigation progress on the anti-disease efficacy and effect mechanism of Tan I in recent years, and provide perspectives for future study on the active ingredient.

METHOD

Web of Science and PubMed databases were used to search for articles related to "Tanshinone I" published from 2010 to 2022. Proteins or genes and signaling pathways referring to Tan I against diseases were summarized and classified along with its different therapeutic actions. Protein-protein interaction (PPI) analysis was then performed, followed by molecular docking between proteins with high node degree and Tan I, as well as bioinformactic analysis including GO, KEGG and DO enrichment analysis with the collected proteins or genes.

RESULTS

Tan I shows multiple therapeutic effects, including protection of the cardiovascular system, anti-cancer, anti-inflammatory, anti-neurodegenerative diseases, etc. The targets (proteins or genes) affected by Tan I against diseases involve Bcl-2, Bid, ITGA2, PPAT, AURKA, VEGF, PI3K, AKT, PRK, JNK, MMP9, ABCG2, CASP3, Cleaved-caspase-3, AMPKα, PARP, etc., and the regulatory pathways refer to Akt/Nrf2, SAPK/JNK, PI3K/Akt/mTOR, JAK/STAT3, ATF-2/ERK, etc. What's more, AKT1, CASP3, and STAT3 were predicted as the key action targets for Tan I by PPI analysis combined with molecular docking, and the potential therapeutic effects mechanisms against diseases were also further predicted by bioinformatics analyses based on the reported targets, providing new insights into the future investigation and helping to facilitate the drug development of Tan I.

摘要

背景

丹参酮Ⅰ(Tan I)是丹参中重要的活性成分之一。近年来,随着各项研究的不断更新,Tan I受到了研究界的广泛关注,并已被证明具有多种有益活性,包括抗氧化应激、调节细胞自噬或凋亡、抑制炎症等。目的:总结近年来Tan I抗疾病疗效及作用机制的研究进展,为该活性成分的后续研究提供展望。

方法

利用Web of Science和PubMed数据库检索2010年至2022年发表的与“丹参酮Ⅰ”相关的文章。对涉及Tan I抗疾病的蛋白质或基因以及信号通路进行总结分类,并归纳其不同的治疗作用。随后进行蛋白质-蛋白质相互作用(PPI)分析,接着对高节点度蛋白质与Tan I进行分子对接,并对收集到的蛋白质或基因进行包括基因本体(GO)、京都基因与基因组百科全书(KEGG)和疾病本体(DO)富集分析在内的生物信息学分析。

结果

Tan I具有多种治疗作用,包括保护心血管系统、抗癌、抗炎、抗神经退行性疾病等。Tan I抗疾病所影响的靶点(蛋白质或基因)涉及Bcl-2、Bid、整合素α2(ITGA2)、磷酸核糖焦磷酸酰胺转移酶(PPAT)、极光激酶A(AURKA)、血管内皮生长因子(VEGF)、磷脂酰肌醇-3-激酶(PI3K)、蛋白激酶B(AKT)、蛋白激酶R(PRK)、应激活化蛋白激酶(JNK)、基质金属蛋白酶9(MMP9)、ATP结合盒转运蛋白G2(ABCG2)、半胱天冬酶3(CASP3)、裂解的半胱天冬酶-3、腺苷酸活化蛋白激酶α(AMPKα)、聚(ADP-核糖)聚合酶(PARP)等,其调控通路涉及Akt/核因子E2相关因子2(Nrf2)、应激激活蛋白激酶/应激活化蛋白激酶(SAPK/JNK)、PI3K/Akt/哺乳动物雷帕霉素靶蛋白(mTOR)、Janus激酶/信号转导及转录激活因子3(JAK/STAT3)、活化转录因子2/细胞外信号调节激酶(ATF-2/ERK)等。此外,通过PPI分析结合分子对接预测AKT1、CASP3和STAT3为Tan I的关键作用靶点,并基于已报道的靶点通过生物信息学分析进一步预测了其潜在的抗疾病治疗作用机制,为后续研究提供了新的思路,有助于推动Tan I的药物研发。

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