Portulaca oleracea-derived indoline amide ameliorates obesity and NAFLD in rats through Nrf2-dependent antioxidant and anti-inflammatory mechanisms

In this study, we evaluated the potential of indoline amide extract phenolic extract Portulaca oleracea (POIA-PE) in preventing obesity and non-alcoholic fatty liver disease (NAFLD) in rats and depicted the possible mechanism of action. Adult male Wistar rats were utilized in this study and were divided (8/groups) into control, POIA-PE, HFD, HFD + POIA-PE (100, 200, and 300 mg/kg), and HFD + POIA-PE (300 mg/kg) + brusatol (2 mg/kg). Treatments with POIA-PE were given by gavage, orally, and for 12 weeks (thrice/week). POIA-PE, at all tested doses, not only reduced body and fat weights but also lowered fasting plasma glucose and insulin, serum and hepatic levels of triglycerides and cholesterol, and serum levels of LDL-c in HFD-fed rats. They also prevented the increase in levels of malondialdehyde, tumor necrosis factor-α, interleukin-6, caspase-3, Bax, and mRNA, as well as the nuclear levels of NF-κB, but stimulated the levels of Bcl-2, total glutathione, heme oxygenase-1, and superoxide dismutase (SOD) in the livers of HFD-fed rats. The increasing doses of POIA-PE also reduced the hepatic transcription of SREBP1, fatty acid synthase, and acetyl-CoA carboxylase and stimulated those of PPARα in HFD-fed rats. Mechanistically, POIA-PE reduced the mRNA and expression of Keap1 but increased the mRNA, cytoplasmic, and nuclear levels of Nrf2. All these effects were dose-dependent and were prevented by co-treatment with brusatol. POIA-PE can alleviate NAFLD by attenuating obesity, hyperglycemia, hyperlipidemia, hepatic oxidative stress, inflammation, and apoptosis through the stimulation of the Keap1/Nrf2 pathways.