Ferulic Acid Alleviates Hepatic Lipid Accumulation and Inflammation by Improving Proximal and Distal Intestinal Barriers in NAFLD Mice

Ferulic Acid Alleviates Hepatic Lipid Accumulation and Inflammation by Improving Proximal and Distal Intestinal Barriers in NAFLD Mice

Jiaojiao Fu,^1,2 Jingyan Yang,^1,2 Liying He,³ Caixia Yang,³ Jing He,^1,2 Yanan Hua,^1,2 Jinlin Guo^1,2,3 and Sijing Liu^1,2

¹College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
²Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Chengdu, Sichuan, China
³Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China

Non-alcoholic fatty liver disease (NAFLD) is closely associated with low-grade chronic inflammation which is usually induced by intestinal dysbiosis. As ferulic acid (FA) has been proven effective at improving the intestinal integrity, we aimed to determine the effect of dietary FA on NAFLD development in high-fat dieted (HFD) mice, a well-established model of NAFLD. Male C57BL/6J mice were fed either a normal chow diet (ND) or HFD with or without FA (40 mg/kg) orally for 6 weeks. FA significantly alleviated lipid metabolism disorder and reduced liver inflammation in HFD mice (P <02C2> 0.05). As expected, FA improved the ileal intestinal integrity likely via the Nuclear factor E2-related factor 2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling pathway. Importantly, we found that FA also relieved HFD-induced gut microbiota dysbiosis by inhibiting the growth of harmful bacteria such as Helicobacter and increased the abundance of many short-chain fatty acids (SCFAs)-producing bacteria (P <02C2> 0.05). Our data indicated that FA not only increased the colonic levels of SCFAs, but also maintained the colonic barrier integrity by up-regulating the expression of the epithelial tight junction protein. These data indicated that FA alleviated NAFLD by reducing circulating lipopolysaccharide levels. These effects may be due to improved proximal and distal intestinal barriers, which presumably mediated through the interaction of FA with the gut microbiota.

Key words —— ferulic acid; gut microbiota-liver axis; intestinal barrier; non-alcoholic fatty liver disease; short chain fatty acid

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Tohoku J. Exp. Med., 2023 June, 260(2), 149-163.

*These two authors contributed equally to this work.

Correspondence: Sijing Liu, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, No.1166, Liutai Dadao, Wenjiang District, Chengdu, Sichuan 610075, China.

e-mail: liusijing@cdutcm.edu.cn