Shanghai Engineering Research Center of Food Microbiology, School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, PR China.
Shanghai Engineering Research Center of Food Microbiology, School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, PR China.
J Ethnopharmacol. 2020 May 23;254:112681. doi: 10.1016/j.jep.2020.112681. Epub 2020 Feb 19.
Antrodia camphorata (A. camphorata) is a rare functional fungus in Taiwan and contains a variety of biologically active ingredients. Antrodin A (AdA) is one of the main active ingredients in the solid-state fermented A. camphorata mycelium. It protects the liver from alcohol damage by improving the antioxidant and anti-inflammatory capacity of the liver and maintaining the stability of the intestinal flora.
The aim of this study was to evaluate the hepatoprotective activities of ethyl acetate layer extract (EALE), AdA, and Antroquinonol (Aq) from mycelium of A. camphorata on alcoholic liver injury.
Mice were given with intragastrically vehicle (NC, 2% CMC-Na), alcohol (AL, 12 mL/kg bw), or different A. camphorata samples (EALE, AdA, Aq) at low (100 mg/kg bw) or high (200 mg/kg bw) dosages. The positive control (PC) group was given with silymarin (200 mg/kg bw). Except the NC group, each group of mice was fasted for 4 h after the last treatment and was intragastrically administrated with 50% alcohol (12 mL/kg bw). At the end of experiment, mouse serum was collected and the liver was excised. A portion of the liver was fixed in formalin and used for histopathological analysis, whereas the rest was used for biochemical analysis and real-time PCR analysis. The intestinal flora structure of feces was analyzed by determining the v3-v4 region sequence in 16S rDNA.
The high-dose groups of the three samples (EALEH, AdAH, and AqH) significantly alleviated the alcohol-induced increases in liver index, serum ALT, AST, and AKP activities. Serum TG level was significantly reduced in all treatment groups. The increase of HDL-C content indicated that active ingredients of A. camphorata could reduce the lipid content in serum. Furthermore, MDA contents of the AdAH and AqH groups in liver were significantly reduced, accompanying with the levels of SOD, CAT, and GSH elevated to various extents. Antioxidant and anti-inflammatory capabilities in the liver were increased in the AdAH group, as evidenced by the mRNA expression levels of Nrf-2 and HO-1 were significantly increased; while those of CYP2e1, TNF-α, and TLR-4 were significantly decreased. Analysis of intestinal flora of feces showed that alcohol treatment significantly changed the composition of intestinal flora. Supplementation with AdA could mitigate dysbiosis of intestinal flora induced by alcohol. Flora of Faecalibaculum, Lactobacillus, and Coriobacteriaceae_UCG-002 showed significantly negative correlations with ALT, AST, AKP, and MDA levels.
Antrodin A could improve the antioxidant and anti-inflammatory capacities of the liver and maintain the stability of intestinal flora. It is potentially a good candidate compound against acute alcoholic liver injury.
樟芝（Antrodia camphorata）是台湾地区一种罕见的功能性真菌，含有多种具有生物活性的成分。安特罗丁 A（AdA）是固态发酵樟芝菌丝体的主要活性成分之一。它通过提高肝脏的抗氧化和抗炎能力以及维持肠道菌群的稳定性来保护肝脏免受酒精损害。
本研究旨在评估樟芝菌丝体的乙酸乙酯层提取物（EALE）、AdA 和安托醌（Aq）对酒精性肝损伤的保肝活性。
小鼠经灌胃给予溶剂（NC，2% CMC-Na）、酒精（AL，12 mL/kg bw）或不同剂量（低剂量 100 mg/kg bw 和高剂量 200 mg/kg bw）的樟芝菌丝体的 EALE、AdA 和 Aq。阳性对照组（PC）给予水飞蓟素（200 mg/kg bw）。除 NC 组外，每组小鼠在最后一次处理后禁食 4 小时，并经灌胃给予 50%酒精（12 mL/kg bw）。实验结束时，采集小鼠血清，取出肝脏。一部分肝脏用福尔马林固定，用于组织病理学分析，其余部分用于生化分析和实时 PCR 分析。通过测定 16S rDNA 的 v3-v4 区序列分析粪便中的肠道菌群结构。
三种样品（EALEH、AdAH 和 AqH）的高剂量组均显著减轻了酒精引起的肝指数、血清 ALT、AST 和 AKP 活性升高。所有治疗组的血清 TG 水平均显著降低。HDL-C 含量的增加表明樟芝的活性成分可以降低血清中的脂质含量。此外，AdAH 和 AqH 组肝脏中的 MDA 含量显著降低，同时 SOD、CAT 和 GSH 的水平不同程度升高。AdAH 组的抗氧化和抗炎能力增强，Nrf-2 和 HO-1 的 mRNA 表达水平显著升高；而 CYP2e1、TNF-α 和 TLR-4 的表达水平则显著降低。粪便肠道菌群分析表明，酒精处理显著改变了肠道菌群的组成。补充 AdA 可以减轻酒精引起的肠道菌群失调。Faecalibaculum、Lactobacillus 和 Coriobacteriaceae_UCG-002 等菌群与 ALT、AST、AKP 和 MDA 水平呈显著负相关。
安特罗丁 A 可提高肝脏的抗氧化和抗炎能力，维持肠道菌群的稳定性。它可能是一种治疗急性酒精性肝损伤的良好候选化合物。
