Therapeutic Effects of Heterotrigona itama (Stingless Bee) Bee Bread in Improving Hepatic Lipid Metabolism through the Activation of the Keap1/Nrf2 Signaling Pathway in an Obese Rat Model
Zaida Zakaria, Zaidatul Akmal Othman, Joseph Bagi Suleiman, Khairul Mohd Fadzli Mustaffa, Nur Asyilla Che Jalil, Wan Syaheedah Wan Ghazali, Ninie Nadia Zulkipli, Mahaneem Mohamed, Khaidatul Akmar Kamaruzaman
Abstract
Bee bread (BB) has traditionally been used as a dietary supplement to treat liver problems. This study evaluated the therapeutic effects of Heterotrigona itama BB from Malaysia on obesity-induced hepatic lipid metabolism disorder via the regulation of the Keap1/Nrf2 pathway. Male Sprague Dawley rats were fed with either a normal diet or high-fat diet (HFD) for 6 weeks to induce obesity. Following 6 weeks, obese rats were treated either with distilled water (OB group), BB (0.5 g/kg body weight/day) (OB + BB group) or orlistat (10 mg/kg body weight/day) (OB + OR group) concurrent with HFD for another 6 weeks. BB treatment suppressed Keap1 and promoted Nrf2 cytoplasmic and nuclear translocations, leading to a reduction in oxidative stress, and promoted antioxidant enzyme activities in the liver. Furthermore, BB down-regulated lipid synthesis and its regulator levels (SIRT1, AMPK), and up-regulated fatty acid β-oxidation in the liver of obese rats, being consistent with alleviated lipid levels, improved hepatic histopathological changes (steatosis, hepatocellular hypertrophy, inflammation and glycogen expression) and prevented progression to non-alcoholic steatohepatitis. These results showed the therapeutic potentials of H. itama BB against oxidative stress and improved lipid metabolism in the liver of obese rats possibly by targeting the Keap1/Nrf2 pathway, hence proposing its role as a natural supplement capable of treating obesity-induced fatty liver disease.