Obesity is a driving factor in the onset of metabolic disorders. This study aims to investigate the effects of the
myricetin derivative-rich fraction (MD) from Syzygium malaccense leaf extract on high-fat diet (HFD)-induced
obesity and its associated complications and its influence on uncoupling protein-1 (UCP-1) and gut microbiota in C57BL/6J mice. Mice were randomly assigned into four groups (n = 6) and given a normal diet (ND) or high-fat diet (HFD) for 10 weeks to induce
obesity. The HFD groups (continued with HFD) were administered 50 mg kg-1 MD (treatment), 50 mg kg-1
metformin (positive control) and
normal saline (HFD and ND controls) daily for four weeks via oral gavage. The ten-week HFD-feeding resulted in
hyperglycemia and elevated urinary oxidative indices. The subsequent MD administration caused significant
weight reduction without appetite suppression and amelioration of
insulin resistance, steatosis and
dyslipidemia. Besides, MD significantly reduced
lipid hydroperoxides and
protein carbonyls in tissue homogenates and urine and elevated
Trolox equivalent
antioxidant capacity (TEAC), ferric reducing
antioxidant power (FRAP) and
reduced glutathione (GSH) and thus, alleviated oxidative stress. The
weight reduction was correlated with downregulation of inflammatory markers and the increased UCP-1 level, suggesting
weight loss plausibly through thermogenesis. The Akkermansia genus (reflects improved metabolic status) in the HFD50 group was more abundant than that in the HFD group while the non-enzymatic
antioxidant markers were strongly associated with UCP-1. In conclusion, MD ameliorates
obesity and its related complications possibly via the upregulation of UCP-1 and increased abundance of Akkermansia genus and is promising as a therapeutic agent in the treatment of
obesity and its associated metabolic disorders.