Lipid-lowering and hepatoprotective effects of Ocimum sanctum L. (Thai holy basil) flower against MASLD and liver inflammation in rats.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has been defined as the fatty liver disease associated with systemic metabolic dysregulation, lipid dysregulation, and inflammation. Although the U.S. FDA has approved semaglutide and resmetirom as the options for treatment of non-alcoholic steatohepatitis or metabolic dysfunction-associated steatohepatitis, warnings on hepatotoxicity and drug interactions remain. Therefore, alternative candidates exhibiting lipid-lowering activity against MASLD are still required. Aqueous extract from Ocimum sanctum L. flowers (OSLE) has recently been reported to interfere with choline metabolism in high-fat diet (HFD)-induced MASLD rats. However, the hepatoprotective mechanisms of OSLE against MASLD remain inconclusive. This study aims to clarify the mechanisms of OSLE in HFD-induced MASLD rats. Normal and MASLD rats were supplemented for 12 weeks with OSLE (1000 mg/kg BW), atorvastatin (10 mg/kg BW), or their combination. The molecular mechanisms underlying the effects of OSLE were identified using histological analyses, qPCR, and western blotting. The results demonstrated that OSLE improved lipid profiles and reduced hepatic lipid accumulation by increasing cholesterol excretion. Additionally, OSLE activated AMPK and promoted hepatic lipophagy, as evidenced by increased transcription factor EB, lysosomal associated membrane protein 2, light chain 3 bII/bI, and decreased p62 protein expression. OSLE also exhibited hepatoprotection by upregulating antioxidant genes (SOD1, GPx, and CAT), and suppressing pro-inflammatory genes (TNF-α, IL-6, IL-1β, and TGF-β). In summary, OSLE restored lipid homeostasis and exhibited hepatoprotection by modulating lipid metabolism, inflammation, and oxidative stress, demonstrating the potential of OSLE for development as a nutraceutical candidate for prevention and treatment of MASLD.