Novel Therapeutic Potentials of Taxifolin for Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis

Abstract

The molecular pathogenesis of nonalcoholic steatohepatitis (NASH) includes a complex interaction of metabolic stress and inflammatory stimuli. Considering the therapeutic goals of NASH, it is important to determine whether the treatment can prevent the progression from NASH to hepatocellular carcinoma. Taxifolin, also known as dihydroquercetin, is a natural bioactive flavonoid with antioxidant and anti-inflammatory properties commonly found in various foods and health supplement products. In this study, we demonstrated that Taxifolin treatment markedly prevented the development of hepatic steatosis, chronic inflammation, and liver fibrosis in a murine model of NASH. Its mechanisms include a direct action on hepatocytes to inhibit lipid accumulation. Taxifolin also increased brown adipose tissue activity and suppressed body weight gain through at least two distinct pathways: direct action on brown adipocytes and indirect action via fibroblast growth factor 21 production in the liver. Notably, the Taxifolin treatment after NASH development could effectively prevent the development of liver tumors. Collectively, this study provides evidence that Taxifolin shows pleiotropic effects for the treatment of the NASH continuum. Our data also provide insight into the novel mechanisms of action of Taxifolin, which has been widely used as a health supplement with high safety.

Vine tea total flavonoids activate the AMPK/mTOR pathway to amelioration hepatic steatosis in mice fed a high‐fat diet

“…In this study, 13 components of TF were identified by UHPLC-QTOF-MS. Dihydromyricetin, myricetin, and myricitrin are found to be the most abundant and bioactive flavonoids in Vine tea, which have ameliorative effect on NAFLD (Zhang et al, 2021). In addition, epigallocatechin, taxifolin, and hesperidin have ameliorative effects on NAFLD (Ding et al, 2023;Inoue et al, 2023;Li et al, 2022). To investigate whether flavonoids extracted from vine tea have an ameliorative effect on NAFLD, we administered TF through gavage in mice fed the HFD.…”

Taxifolin Suppresses Inflammatory Responses of High-Glucose-Stimulated Mouse Microglia by Attenuating the TXNIP–NLRP3 Axis

“…The antioxidant and radical scavenging activities of taxifolin reduced HG-induced ROS production, which further suppressed the TXNIP–NLRP3 axis, thereby inhibiting IL-1β production. Since taxifolin also has beneficial effects on glucose metabolism under diabetic conditions [ 30 ], it can indirectly suppress cognitive impairment by improving metabolism; therefore, the indirect effects and direct impact of taxifolin on the microglia can synergistically prevent and/or improve diabetes-related cognitive impairment. Future preclinical and clinical studies to address the in vivo effects of taxifolin on neuroinflammation in diabetic conditions would be helpful in developing novel strategies to prevent diabetes-related cognitive impairment.…”

“…We previously reported that orally administered taxifolin improves cerebral blood flow, promotes amyloid-β removal from the brain, and prevents cognitive decline [ 28 ]; it also demonstrated suppressive effects on neuroinflammation [ 29 ] in a mouse model of cerebral amyloid angiopathy. We further demonstrated the beneficial effects of taxifolin on the metabolism of obesogenic diet-fed mice; taxifolin improved glucose/lipid metabolism, obesity, and hepatic steatosis, thereby preventing nonalcoholic steatohepatitis [ 30 ]. Moreover, we recently revealed that the oral intake of taxifolin exhibits beneficial effects on the cognitive function in patients with mild cognitive impairment or mild dementia [ 31 ].…”

Identification of ribosomal protein family as immune-cell-related biomarkers of NAFLD by bioinformatics and experimental analyses

“…In addition, taxifolin displays pleiotropic effects for the treatment of the NASH continuum. It could alleviate obesity-induced hepatic steatosis, fibrosis, and tumorigenesis in rodent models (63). Sitagliptin is a selective inhibitor of dipeptidyl peptidase-4 (DPP-4I), which is widely used as a hypoglycemic agent.…”