The Second Central Laboratory, Key Lab of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China.
The Second Central Laboratory, Key Lab of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China; Preparation Center, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China.
Biomed Pharmacother. 2021 Mar;135:111183. doi: 10.1016/j.biopha.2020.111183. Epub 2021 Jan 2.
Our previous studies found that Pure total flavnoids from citrus (PTFC) can effectively improve non-alcoholic steatohepatitis (NASH) in mice. Here, we discuss on the mechanism of PTFC in treating NASH with focus on the regulation of the gut microbiota and bile acid metabolism.
C57BL/6 J mice were randomly divided into three groups: normal diet group (Normal), high-fat diet group (HFD) and high-fat + PTFC treatment group (PTFC). Mice in the Normal group were fed chow diet, while the other groups were fed high fat diet (HFD) for 16 weeks. In the 5th week, the mice in the PTFC group were treated with 50 mg/kg/day PTFC for an additional twelve weeks. After sacrifice, histopathology of the liver was assessed, and the gut microbial composition was analyzed by 16S rDNA gene sequencing. Bile Acid profiles in serum were determined by ultraperformance liquid chromatography (UPLC-MS/MS).
PTFC intervention significantly attenuated HFD-induced NASH symptoms compared with the HFD group in mice. 16S rDNA sequencing showed that PTFC treatment increased the phylogenetic diversity of the HFD-induced microbiota dysbiosis. PTFC intervention significantly increased the relative abundances of Bacteroidaceae and Christensenellaceae. Furthermore, PTFC reduced the content of toxic bile acids, such as TDCA, DCA, TCA, CA and increased the ratio of secondary to primary bile acids. FXR and TGR5 deficiency were significantly alleviated.
PTFC can improve NASH via the the gut microbiota and bile acid metabolism.
我们之前的研究发现，陈皮总黄酮（PTFC）可有效改善非酒精性脂肪性肝炎（NASH）。在这里，我们探讨了 PTFC 通过调节肠道微生物群和胆汁酸代谢来治疗 NASH 的机制。
将 C57BL/6J 小鼠随机分为三组：正常饮食组（Normal）、高脂肪饮食组（HFD）和高脂肪+PTFC 治疗组（PTFC）。正常组给予常规饮食，其余组给予高脂肪饮食（HFD）喂养 16 周。第 5 周时，PTFC 组开始给予 50mg/kg/天 PTFC 治疗，共 12 周。处死小鼠后，评估肝脏组织病理学变化，通过 16S rDNA 基因测序分析肠道微生物组成。采用超高效液相色谱-串联质谱法（UPLC-MS/MS）测定血清中胆汁酸谱。
与 HFD 组相比，PTFC 干预可显著减轻 HFD 诱导的 NASH 症状。16S rDNA 测序显示，PTFC 治疗增加了 HFD 诱导的微生物群失调的系统发育多样性。PTFC 干预显著增加了拟杆菌科和克里斯滕森菌科的相对丰度。此外，PTFC 降低了毒性胆汁酸如 TDCA、DCA、TCA、CA 的含量，增加了次级胆汁酸与初级胆汁酸的比值。FXR 和 TGR5 缺乏也得到了显著改善。
PTFC 可通过肠道微生物群和胆汁酸代谢改善 NASH。
