College of Pharmacy, Jiamusi University, Jiamusi, 154007, Heilongjiang, PR China.
College of Pharmacy, Jiamusi University, Jiamusi, 154007, Heilongjiang, PR China; Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Hainan Medical University, Haikou, 571199, PR China.
J Ethnopharmacol. 2022 Jun 28;292:115225. doi: 10.1016/j.jep.2022.115225. Epub 2022 Mar 25.
The therapeutic properties of Hippophae rhamnoides L. were already known in ancient Greece as well as in Tibetan and Mongolian medicine. Modern studies have indicated that Hippophae rhamnoides L. fermentation liquid protected against alcoholic fatty liver disease (AFLD). However, the underlying mechanism of Hippophae rhamnoides L. flavonoids extract (HLF) treating AFLD remains elusive.
This study aimed to investigate the hepatoprotective effect of HLF in mice with AFLD and the interaction between AFLD and gut microbiota.
Chemical constituents of HLF were analyzed by Liquid Chromatography-Ion Trap-ESI-Mass Spectrometry. The Hepatoprotective effect of HLF was evaluated in mice with AFLD induced by alcohol (six groups, n = 10) daily at doses of 0.1, 0.2, and 0.4 g/kg for 30 consecutive days. At the end of experiment, mice were sacrificed and the liver, serum and feces were harvested for analysis. The liver histological changes were observed by H&E staining and oil red O staining. Moreover, the alterations of fecal microflora were detected by 16S rRNA gene sequencing. The inflammatory related genes were determined by qRT-PCR and western blotting respectively.
The results showed that the oral administration of HLF remarkably alleviated hepatic lipid accumulation by decreasing the levels of ALT, AST, TG and TC. The levels of TNF-α, TGF-β, and IL-6 were also reduced after treatment with HLF. Meanwhile, the protein and mRNA expression of NF-kB p65, MAPK p38 and TAK-1 in the liver of mice with AFLD were all reduced by HLF compared with model group. Furthermore, the 16S rRNA gene sequencing analysis demonstrated that HLF treatment can help restore the imbalance of intestinal microbial ecosystem and reverse the changes in Fimicutes/Bacterodietes, Clostridiales, Lachnospiraceae, S24-7, and Prevotella in mice with AFLD.
HLF can effectively ameliorate liver injury in mice with AFLD, and regulate the composition of gut microbiota. Its regulatory mechanism may be related to TAK1/p38MAPK/p65NF-κB pathway. This study may provide novel insights into the mechanism of HLF on AFLD and a basis for promising clinical usage.
早在古希腊以及藏医和蒙医中，沙棘就已被证实具有治疗功效。现代研究表明，沙棘发酵液可预防酒精性脂肪肝疾病（AFLD）。然而，沙棘类黄酮提取物（HLF）治疗 AFLD 的潜在机制仍难以捉摸。
本研究旨在探讨 HLF 对 AFLD 小鼠的保肝作用及其与肠道微生物群的相互作用。
采用液相色谱-离子阱-ESI-MS 分析 HLF 的化学成分。采用酒精（六组，每组 n=10）诱导 AFLD 小鼠，每日分别给予 0.1、0.2 和 0.4 g/kg HLF 连续 30 天，评估 HLF 的保肝作用。实验结束时，处死小鼠，采集肝脏、血清和粪便进行分析。采用 H&E 染色和油红 O 染色观察肝组织学变化。此外，通过 16S rRNA 基因测序检测粪便微生物群的变化。通过 qRT-PCR 和 Western blot 分别测定炎症相关基因。
结果表明，HLF 口服可通过降低 ALT、AST、TG 和 TC 水平显著减轻肝脂质堆积。HLF 治疗后，TNF-α、TGF-β 和 IL-6 水平也降低。同时，与模型组相比，HLF 可降低 AFLD 小鼠肝组织中 NF-kB p65、MAPK p38 和 TAK-1 的蛋白和 mRNA 表达。此外，16S rRNA 基因测序分析表明，HLF 治疗可帮助恢复肠道微生物生态系统的失衡，并逆转 AFLD 小鼠中 Fimicutes/Bacterodietes、Clostridiales、Lachnospiraceae、S24-7 和 Prevotella 的变化。
HLF 可有效改善 AFLD 小鼠的肝损伤，并调节肠道微生物群的组成。其调节机制可能与 TAK1/p38MAPK/p65NF-κB 通路有关。本研究可为 HLF 治疗 AFLD 的机制提供新的见解，并为其临床应用提供依据。
