School of Traditional Chinese Medicine and School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Center for Innovative Engineering Technology in Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China; Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China; Key Laboratory of Liaoning Province for TCM Spleen-Viscera-State Modern Research, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China.
J Ethnopharmacol. 2023 Dec 5;317:116811. doi: 10.1016/j.jep.2023.116811. Epub 2023 Jun 17.
Erchen decoction (ECD) is a traditional Chinese medicine formula comprising six distinct herbs and has been documented to possess a protective effect against obesity. The study conducted previously demonstrated that ECD has the potential to effectively modulate the composition of gut microbiota and levels of short-chain fatty acids (SCFAs) in obese rat. However, the regulatory mechanism of ECD on gut microbiota and SCFAs and further improvement of obesity have not been thoroughly explained.
The objective of this study was to examine the therapeutic effect and molecular mechanism of ECD in a rat model of high-fat diet (HFD) feeding.
Rats with HFD-induced obesity were treated with ECD. Upon completion of the study, serum and liver samples were procured to conduct biochemical, pathological, and Western blotting analyses. The investigation of alterations in the gut microbiota subsequent to ECD treatment was conducted through the utilization of 16S rRNA sequencing. The metabolic alterations in the cecal contents were examined through the utilization of mass spectrometry-ultraperformance liquid chromatography.
ECD treatment improved lipid metabolic disorders and reduced hepatic steatosis in HFD-induced obese rats. Obese rat treated with ECD showed a higher abundance of SCFA-producing bacteria, including Lactobacillus, Bifidobacterium, and Butyricicoccus, and lower abundance of disease-related bacteria, such as Bacteroides, Parabacteroides, and Sediminibacterium. Additionally, ECD caused an increase in total SCFAs levels; in particular, butyric acid was dramatically increased in the HFD group. Rats treated with ECD also exhibited significantly increased butyric acid concentrations in the serum and liver. The subsequent reduction in histone deacetylase 1 expression and increase in acetyl-histone 3-lysine 9 (H3K9ac) levels contributed to the promotion of fatty acid β-oxidation (FAO) in liver by ECD.
This study demonstrates that ECD regulates the gut microbiota and promotes butyric acid production to ameliorate obesity-related hepatic steatosis. The mechanism might be related to the promotion of FAO via a butyric acid-mediated increase in H3K9ac levels in the liver.
二陈汤（ECD）是一种由六种不同草药组成的中药方剂，已被证明具有预防肥胖的作用。之前的研究表明，ECD 有可能有效调节肥胖大鼠肠道微生物群的组成和短链脂肪酸（SCFA）水平。然而，ECD 对肠道微生物群和 SCFA 的调节机制以及肥胖的进一步改善尚未得到充分解释。
本研究旨在研究 ECD 在高脂肪饮食（HFD）喂养肥胖大鼠模型中的治疗效果和分子机制。
用 ECD 治疗 HFD 诱导肥胖的大鼠。研究完成后，采集血清和肝脏样本进行生化、病理和 Western blot 分析。通过 16S rRNA 测序研究 ECD 治疗后肠道微生物群的变化。通过质谱-超高效液相色谱法检测盲肠内容物的代谢变化。
ECD 治疗改善了 HFD 诱导肥胖大鼠的脂质代谢紊乱和肝脂肪变性。ECD 处理的肥胖大鼠中，产生 SCFA 的细菌（如乳杆菌、双歧杆菌和丁酸梭菌）丰度增加，而与疾病相关的细菌（如拟杆菌、副拟杆菌和 Sediminibacterium）丰度降低。此外，ECD 导致总 SCFA 水平升高；特别是在 HFD 组中，丁酸显著增加。ECD 处理的大鼠血清和肝脏中的丁酸浓度也显著增加。随后，组蛋白去乙酰化酶 1 表达减少，乙酰化组蛋白 3-赖氨酸 9（H3K9ac）水平增加，这有助于 ECD 促进肝脏脂肪酸β氧化（FAO）。
本研究表明，ECD 通过调节肠道微生物群和促进丁酸生成来改善肥胖相关的肝脂肪变性。其机制可能与通过丁酸介导增加肝脏 H3K9ac 水平促进 FAO 有关。
