Naringenin prevents non‐alcoholic steatohepatitis by modulating the host metabolome and intestinal microbiome in MCD diet‐fed mice

Abstract

Non‐alcoholic steatohepatitis (NASH) is a severe inflammatory phase of the non‐alcoholic fatty liver disease (NAFLD) spectrum and can progress to advanced stages of NAFLD if left untreated. This study uses multi‐omics data to elucidate the underlying mechanism of naringenin's reported benefit in alleviating (NASH). Male mice were fed a NASH‐inducing (methionine‐choline‐deficient) MCD diet with or without naringenin supplementation for 6 weeks. Naringenin prevented NASH‐induced histopathological liver damage and reversed the abnormal levels of hepatic triglyceride (TG)/total cholesterol (TC), serum TG/TC, serum alanine aminotransferase/aspartate transaminase, and hepatic malondialdehyde and glutathione. Importantly, naringenin intervention significantly modulated the relative abundance of gut microbiota and the host metabolomic profile. We detected more than 700 metabolites in the serum and found that the gut genus levels of Anaeroplasma and the [Eubacterium] nodatum group were closely associated with xanthine, 2‐picoline, and securinine, respectively. Tuzzerella alterations showed the highest number of associations with host endogenous metabolites such as FAHFA (8:0/10:0), FFA (20:2), carnitine C8:1, tridecanedioic acid, securinine, acetylvaline, DL‐O‐tyrosine, and Phe‐Asn. This study indicates that the interplay between host serum metabolites and gut microbiota may contribute to the therapeutic effect of naringenin against NASH.

Mulberry and Hippophae‐based solid beverage attenuate hyperlipidemia and hepatic steatosis via adipose tissue–liver axis

“…Although NAFLD/NASH is now a global health issue, the pathogenesis that results in lipid accumulation, cell apoptosis, inflammation, and fibrosis is yet to be comprehensively elucidated, while pharmacological treatments—completely safe and effective—are not currently known. Nevertheless, an increasing number of studies have been done on bioactive phytochemical compounds, for example, hesperidin (Morshedzadeh et al., 2023 ), naringenin (Cao et al., 2023 ), and curcumin (Baziar & Parohan, 2020 ), for their potentials to prevent the onset and progression of NAFLD (Frasinariu et al., 2022 ). As a result, plant‐based dietary supplements are growingly recognized to play an important role in the management of NAFLD, especially at its initial stage (Perumpail et al., 2018 ).…”

Identification of m6A-associated autophagy genes in non-alcoholic fatty liver

“…For example, diosgenin (improving mitochondrial function), pomegranate (anti-inflammatory), curcumin (antioxidant) ( Chen et al, 2023 ; Zamanian et al, 2023 ; Beheshti Namdar et al, 2023 ). The latest research shows that the interaction and regulation between serum metabolites and intestinal flora may help naringenin’s therapeutic effect on NASH ( Cao et al, 2023 ), and related studies targeting the intestinal-liver axis and regulating intestinal flora are constantly emerging ( Zhai et al, 2023 ; Wang et al, 2023 ). On the other hand, another research evaluated disease-related circRNA and competitive endogenous RNA networks as potential biomarkers for NAFLD using functional gain and loss methods, reflecting the important role of targeted biomarker research in the progression of NAFLD ( Zeng et al, 2024 ).…”