Preclinical Medicine College, Shanghai University of Traditional Chinese Medicine, 1200# Cailun Rd., Pudong District, Shanghai, 201203, PR China.
Department of Biological Medicines, Shanghai Engineering Research Center of ImmunoTherapeutics, School of Pharmacy, Fudan University, 3728# Jinke Rd., Pudong District, Shanghai, 201203, PR China.
J Ethnopharmacol. 2022 Nov 15;298:115649. doi: 10.1016/j.jep.2022.115649. Epub 2022 Aug 17.
Xuanbai-Chengqi decoction (XBCQ) is a traditional Chinese medicine (TCM) compound used in the treatment of pulmonary infection in China. Despite the popular usage of XBCQ, its underlying protective roles and the associated molecular mechanisms with the gut-lung axis in influenza remain unclear.
We aimed to explore the protective effects and the underlying mechanism of XBCQ efficacy on lung and intestine injuries induced by influenza A virus as well as to identify the main active components through integrated network pharmacology, intestinal flora analysis and pathway validation.
The potential active components and therapeutic targets of XBCQ in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including components screening, targets prediction and bioinformatics analysis. Inflammatory cytokines and pathway proteins were assayed to validate the results of network pharmacology. Then the mechanism of XBCQ alleviating lung and intestine injuries was further explored via intestinal flora analysis. The important role of Rhubarb in the formula was verified by removing Rhubarb.
XBCQ could significantly improve the survival rate in IAV-infected mice. The network pharmacology results demonstrated that JUN, mitogen-activated protein kinase (MAPK), and tumor necrosis factor (TNF) are the key targets of XBCQ that can be useful in influenza treatment as it contains the core components luteolin, emodin, and aloe-emodin, which are related to the pathways of TNF, T-cell receptor (TCR), and NF-κB. Verification experiments demonstrated that XBCQ could significantly alleviate the immune injury of the lungs and the gut of the mice, which is attributable to the inhibition of the release of inflammatory cytokines (such as TNF-α, IL-6, and IL-1β), the downregulation of the protein expression levels of Toll-like receptors-7 (TLR7), MyD88, and p-NF-κB65, and the reduction in the relative abundance of Enterobacteriaceae and Proteus, while an increase in that of Firmicutes and Lachnospiraceae. The overall protective role of XBCQ contributing to the treatment of the lungs and the gut was impaired when Rhubarb was removed from XBCQ.
Our results suggest that the efficacy of XBCQ is related to the inhibition of the immune injury and remodeling of the intestinal flora, wherein Rhubarb plays an important role, which cumulatively provide the evidence applicable for the treatment of viral pneumonia induced by a different respiratory virus with XBCQ.
玄柏承气汤（XBCQ）是一种中药复方，在中国用于治疗肺部感染。尽管 XBCQ 被广泛使用，但它在流感方面对肠道-肺部轴的潜在保护作用及其相关分子机制仍不清楚。
本研究旨在探讨 XBCQ 对流感病毒诱导的肺和肠损伤的保护作用及其机制，并通过整合网络药理学、肠道菌群分析和途径验证来确定主要的活性成分。
通过一系列网络药理学策略，包括成分筛选、靶点预测和生物信息学分析，假设 XBCQ 治疗流感的潜在活性成分和治疗靶点。通过测定炎症细胞因子和通路蛋白来验证网络药理学的结果。然后通过肠道菌群分析进一步探讨 XBCQ 缓解肺和肠损伤的机制。通过去除大黄验证配方中大黄的重要作用。
XBCQ 能显著提高 IAV 感染小鼠的存活率。网络药理学结果表明，JUN、丝裂原活化蛋白激酶（MAPK）和肿瘤坏死因子（TNF）是 XBCQ 的关键靶点，可用于流感治疗，因为它含有核心成分木犀草素、大黄素和芦荟大黄素，这些成分与 TNF、T 细胞受体（TCR）和 NF-κB 途径有关。验证实验表明，XBCQ 能显著减轻小鼠肺部和肠道的免疫损伤，这归因于抑制炎症细胞因子（如 TNF-α、IL-6 和 IL-1β）的释放，下调 Toll 样受体-7（TLR7）、MyD88 和 p-NF-κB65 的蛋白表达水平，减少肠杆菌科和变形菌属的相对丰度，增加厚壁菌门和lachnospiraceae 的相对丰度。当从 XBCQ 中去除大黄时，XBCQ 对肺部和肠道的整体保护作用受损。
我们的研究结果表明，XBCQ 的疗效与抑制免疫损伤和肠道菌群重塑有关，其中大黄起着重要作用，这为 XBCQ 治疗不同呼吸道病毒引起的病毒性肺炎提供了证据。
