通过分析加味麻杏石甘煎剂对 COVID-19 的作用,发现基于疾病进化的特异性靶标(DESTD)

IF 1.9 4区 医学 Q3 INTEGRATIVE & COMPLEMENTARY MEDICINE
Beiyan Li, Chaoqun Liu, Zhan Shu, Shijie Bi, Yue Ren, Kaiyang Liu, Anlei Yuan, Lulu Zheng, Zhenzhen Xu, Zewen Wang, Yanling Zhang
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引用次数: 0

摘要

导言:冠状病毒 2019 疾病(COVID-19)的发病过程多种多样,每种疾病都有其独特的病理生理机制。深入研究发现治疗COVID-19的特异性靶点对了解疾病演变的发病机制具有重要意义。中医药在不同时期治疗COVID-19表现出独特的优势,可为靶点的发现提供新的线索。为了实现提供基于疾病演变的特异性靶点发现(DESTD)的目标,本文旨在对COVID-19各周期的靶点加权值差异进行分析。研究选取了三个加味麻杏石甘汤(MS Decoction)作为样本,包括汉防己汤(HY Decoction)、十味防己汤(SY Decoction)和益都防己汤(YB Decoction)。这些煎剂的核心成分相同,而不同之处则对应于 COVID-19 的不同时期。DESTD方法由几个部分组成:网络药理学分析以确定潜在靶点,分子对接模拟以研究作用于潜在靶点的中药成分,以及生物学验证。该研究采用了多个细胞系模型,包括RAW264.7(小鼠单核巨噬细胞)、16HBE(人支气管上皮细胞)和HUVECC(人脐静脉内皮细胞),以探索发现关键靶点的新方法。结果在 COVID-19 的轻度阶段,HY Decoction 通过特异性下调 RAW264.7 中热休克蛋白 HSP 90-alpha(HSP90AA1)、转录因子 JUN(JUN)和其他五个基因的表达,表现出抗炎作用。在一般情况下,通过下调白细胞介素-10(IL10)和丝裂原活化蛋白激酶 14(MAPK14)的表达,SY Decoction 可分别作用于 RAW264.7 和 16HBE 细胞系,从而有针对性地缓解炎症和纤维化。在严重病例中,YB Decoction 能特异性下调前列腺素内过氧化物合成酶-2(PTGS2)、Caspase-3(CASP3)和其他三个基因的表达,保护血管内皮细胞免受氧化损伤。此外,YB 还通过特异性下调雌激素受体 beta(ESR2)、血管细胞粘附蛋白 1(VCAM1)和其他三个基因的表达,以及上调严重时期前列腺素内过氧化物合成酶-1(PTGS1)的表达,在抗纤维化方面发挥作用。结论这项研究提出了一种基于疾病进化的特异性靶点发现(DESTD)新策略,以确定不同疾病阶段的特异性靶点以及 COVID-19 演变过程中的特异性靶点和机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Disease Evolution-based Specificity Target Discovery (DESTD) by analyzing Jiawei-Maxing-Shigan Decoctions against COVID-19

Introduction

Diverse disease courses, each corresponding to a unique pathophysiological mechanism, characterize the coronavirus 2019 disease (COVID-19). Intensive research on discovering specificity targets for treating COVID-19 has significant implications for understanding pathogenesis mechanisms in disease evolution. Traditional Chinese medicine (TCM) has shown distinctive advantages in treating COVID-19 in different periods, which may provide new clues for target discovery. In order to accomplish the goal of providing a Disease Evolution-based Specificity Target Discovery (DESTD), the purpose of this paper was to conduct an analysis of the difference in target weighted value during each cycle of COVID-19.

Methods

Our study employed a comprehensive methodology combining TCM pharmacology with modern biological techniques. Three Jiawei-Maxing-Shigan Decoctions (MS Decoction), were selected as samples, including Hanshi-Yufei decoction (HY Decoction), Shidu-Yufei decoction (SY Decoction), and Yidu-Bifei decoction (YB Decoction). The core components of these decoctions are the same, while the differences correspond to different periods of COVID-19. The DESTD approach consists of several parts: network pharmacology analysis to identify potential targets, molecular docking simulation to investigate TCM components acting on potential targets, and biological validation. This study employed several cell line models, including RAW264.7 (Mouse Mononuclear Macrophages Cells), 16HBE (Human Bronchial Epithelial Cells), and HUVECC (Human Umbilical Vein Endothelial Cells), to explore new approaches for key target discovery.

Results

During the mild phase of COVID-19, HY Decoction exhibited anti-inflammatory effects by specifically down-regulating the expression of heat shock protein HSP 90-alpha (HSP90AA1), transcription factor JUN (JUN) and other five genes in RAW264.7. In the common phrase, inflammation and fibrosis could be specifically alleviated by down-regulating the expression of interleukin-10 (IL10) and mitogen-activated protein kinase 14 (MAPK14) by SY Decoction respectively acting on RAW264.7 and 16HBE cell lines. In severe cases, YB Decoction specifically down-regulated the expression of prostaglandin endoperoxide synthase-2 (PTGS2), caspase-3 (CASP3), and three other genes to protect vascular endothelial cells from oxidative damage. Moreover, YB also played a role in anti-fibrosis by specifically down-regulating the expression of estrogen receptor beta (ESR2), vascular cell adhesion protein 1 (VCAM1), and other three genes, and up-regulating the expression of prostaglandin endoperoxide synthase-1 (PTGS1) in the severe period. These targeted actions align with a holistic treatment approach and provide tailored therapies for different stages of COVID-19.

Conclusion

This research proposed a novel strategy for Disease Evolution-based Specificity Target Discovery (DESTD) to identify specific targets of different stages of disease and specific targets and mechanisms throughout the evolution of COVID-19.

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来源期刊
European Journal of Integrative Medicine
European Journal of Integrative Medicine INTEGRATIVE & COMPLEMENTARY MEDICINE-
CiteScore
4.70
自引率
4.00%
发文量
102
审稿时长
33 days
期刊介绍: The European Journal of Integrative Medicine (EuJIM) considers manuscripts from a wide range of complementary and integrative health care disciplines, with a particular focus on whole systems approaches, public health, self management and traditional medical systems. The journal strives to connect conventional medicine and evidence based complementary medicine. We encourage submissions reporting research with relevance for integrative clinical practice and interprofessional education. EuJIM aims to be of interest to both conventional and integrative audiences, including healthcare practitioners, researchers, health care organisations, educationalists, and all those who seek objective and critical information on integrative medicine. To achieve this aim EuJIM provides an innovative international and interdisciplinary platform linking researchers and clinicians. The journal focuses primarily on original research articles including systematic reviews, randomized controlled trials, other clinical studies, qualitative, observational and epidemiological studies. In addition we welcome short reviews, opinion articles and contributions relating to health services and policy, health economics and psychology.
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