School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
J Ethnopharmacol. 2021 Aug 10;276:114200. doi: 10.1016/j.jep.2021.114200. Epub 2021 May 11.
Traditional Chinese medicine suggests the use of natural extracts and compounds is a promising strategy to prevent irinotecan (CPT-11)-induced gut toxicity and resulting diarrhea. Previous work from our lab indicated the protective effect of Gegen Qinlian decoction; given this, we further speculated that Gegen Qinlian Pill (GQP) would exhibit similar therapeutic effects. The effective material basis as well as potential mechanisms underlying the effect of GQP for the treatment of CPT-11-induced diarrhea have not been fully elucidated.
The application of natural extracts or compounds derived from Chinese medicine is deemed to a promising strategy to prevent irinotecan (CPT-11)-induced gut toxicity. The aim of this study was to investigated the beneficial effects of GQP on CPT-11-induced gut toxicity and further explored its anti-diarrheal mechanism.
First, the beneficial effect of GQP in alleviating diarrhea in mice following CPT-11 administration was investigated. We also obtained the effective ingredients in GQP from murine serum samples using HPLC-Q-TOF-MS analysis. Based on these active components, we next established an interaction network linking "compound-target-pathway". Finally, a predicted mechanism of action was obtained using in vivo GQP validation based on Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses.
A total of 19, GQP-derived chemical compounds were identified in murine serum samples. An interaction network linking "compound-target-pathway" was then established to illuminate the interaction between the components present in serum and their targets that mitigated diarrhea. These results indicated GQP exerted a curative effect on diarrhea and diarrhea-related diseases through different targets, which cumulatively regulated inflammation, oxidative stress, and proliferation processes.
Taken together, this study provides a feasible strategy to elucidate the effective constituents in traditional Chinese medicine formulations. More specifically, this work detailed the basic pharmacological effects and underlying mechanism behind GQP's effects in the treatment of CPT-11-induced gut toxicity.
传统中医认为使用天然提取物和化合物是预防伊立替康（CPT-11）诱导的肠道毒性和由此产生的腹泻的一种很有前途的策略。我们实验室之前的工作表明了葛根芩连汤的保护作用；鉴于此，我们进一步推测葛根芩连丸（GQP）将表现出类似的治疗效果。GQP 治疗 CPT-11 诱导的腹泻的有效物质基础和潜在机制尚未完全阐明。
应用源自中药的天然提取物或化合物被认为是预防伊立替康（CPT-11）诱导的肠道毒性的一种很有前途的策略。本研究旨在探讨 GQP 对 CPT-11 诱导的肠道毒性的有益作用，并进一步探讨其抗腹泻机制。
首先，研究了 GQP 对 CPT-11 给药后小鼠腹泻的缓解作用。我们还使用 HPLC-Q-TOF-MS 分析从鼠血清样品中获得 GQP 的有效成分。基于这些活性成分，我们接下来建立了一个“化合物-靶标-途径”相互作用网络。最后，基于基因本体（GO）功能和京都基因与基因组百科全书（KEGG）富集分析的体内 GQP 验证，获得了一个预测的作用机制。
从鼠血清样品中鉴定出 19 种 GQP 衍生的化学化合物。然后建立了一个“化合物-靶标-途径”相互作用网络，以阐明血清中存在的成分与其减轻腹泻的靶标之间的相互作用。这些结果表明，GQP 通过不同的靶点对腹泻及其相关疾病发挥治疗作用，这些靶点共同调节炎症、氧化应激和增殖过程。
总之，本研究为阐明中药配方中的有效成分提供了一种可行的策略。更具体地说，这项工作详细说明了 GQP 治疗 CPT-11 诱导的肠道毒性的基本药理作用和潜在机制。
