Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, PR China; Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, 100102, PR China.
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, PR China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, PR China.
Biochem Biophys Res Commun. 2022 Dec 3;632:129-138. doi: 10.1016/j.bbrc.2022.09.097. Epub 2022 Oct 1.
Recently, with increasing awareness of health issues, non-alcoholic fatty liver disease (NAFLD) has become an epidemic attracting global attention. As a serious chronic disease, NAFLD is clinically managed with pharmacological interventions that are usually associated with poor long-term efficacy and adverse effects. In this scenario, traditional Chinese medicine (TCM) characterized by "multiple ingredients-multiple targets-multiple pathways" shows promise as a potential option to treat NAFLD. Zexie decoction (ZXD) is a classical TCM formula that possesses favorable lipid-lowering and anti-inflammatory activities. Accumulating evidence indicates that ZXD displays robust efficacy in treating NAFLD. The effectiveness of ZXD against NAFLD has been evaluated in our previous studies. This study further examines its probable mechanism of action in an in-depth manner using multi-omic analysis based on the gut-liver axis and sheds light on the potential relationship among genes, hepatic lipid metabolites, and gut microbiotas. Totally, 71 differentially expressed genes (34 upregulated and 37 downregulated genes), 31 differential lipid molecules (8 upregulated and 23 downregulated), and 56 differential gut microbiotas (37 upregulated and 19 downregulated) were identified in the ZXD-treated group rats compared with the negative control group rats. Of these, owing to their key role in the association analysis, g_Blautia, g_Romboutsia, and g_Lactobacillus were hypothesized to be crucial gut microbiotas in the ZXD-mediated treatment of NAFLD. These microbiotas were found to synergize with key genes, such as AKR1B8, CCN1, and TNKS2, and hepatic lipid metabolites, such as glycerophospholipid and sphingomyelin, which might play a therapeutic role by regulating fatty acid synthesis, correcting lipid metabolism disorder, or reducing the inflammatory response. Overall, the present study provides fresh insights into the ZXD-mediated treatment of NAFLD, which, in turn, is expected to give a push to the modernization of TCM.
近年来，随着人们健康意识的提高，非酒精性脂肪性肝病（NAFLD）已成为一种全球性关注的流行病。作为一种严重的慢性疾病，NAFLD 的临床治疗采用药物干预，通常与疗效不佳和不良反应相关。在这种情况下，以“多成分-多靶点-多途径”为特点的中药（TCM）显示出作为治疗 NAFLD 的潜在选择的潜力。泽泻汤（ZXD）是一种经典的 TCM 配方，具有良好的降脂和抗炎活性。越来越多的证据表明，ZXD 对 NAFLD 具有强大的疗效。我们之前的研究已经评估了 ZXD 治疗 NAFLD 的效果。本研究进一步通过基于肠-肝轴的多组学分析，深入研究其可能的作用机制，并揭示基因、肝脂质代谢物和肠道微生物群之间的潜在关系。总的来说，与阴性对照组大鼠相比，ZXD 治疗组大鼠有 71 个差异表达基因（34 个上调和 37 个下调基因）、31 个差异脂质分子（8 个上调和 23 个下调）和 56 个差异肠道微生物群（37 个上调和 19 个下调）。在关联分析中，由于其关键作用，g_Blautia、g_Romboutsia 和 g_Lactobacillus 被假设为 ZXD 介导的 NAFLD 治疗中的关键肠道微生物群。这些微生物群与关键基因（如 AKR1B8、CCN1 和 TNKS2）和肝脂质代谢物（如甘油磷脂和神经鞘磷脂）协同作用，可能通过调节脂肪酸合成、纠正脂质代谢紊乱或减少炎症反应发挥治疗作用。总的来说，本研究为 ZXD 介导的 NAFLD 治疗提供了新的见解，这反过来有望推动 TCM 的现代化。
