Garcinol enriched fraction of Garcinia morella (Gaertn.) Desr. fruit rind improves gut health and reduces the risk of nonalcoholic fatty liver disease by regulating PCK1/ACC/SREBP1/FASn pathway in a mouse model

Abstract

Nonalcoholic fatty liver disease (NAFLD), a fast-emerging global burden, is an umbrella term for several liver manifestations that result in excessive accumulation of fat in the liver. NAFLD leads to gut microbiome dysbiosis, loss in gut epithelia, increased gut permeability, etc. The limited availability of registered drugs for NAFLD highlights the urgent need to focus on understanding its pathogenesis and discovering new treatments, including the potential exploration of herbal therapies for managing the condition. In this study, we evaluated the bioactive potential of garcinol enriched fraction from Garcinia morella fruit rind in preventing NAFLD-associated increased gut permeability. Administration of garcinol-enriched fraction (GEF) significantly reduced body weight, serum lipids (triglyceride and total cholesterol) levels, and enzymes (alkaline phosphatase and aspartate aminotransferase) responsible for liver dysfunction in high-fat diet (HFD)-fed C57BL/6 mice. GEF treatment also regulated the alteration in signaling pathways of lipid metabolism in HFD-fed mice by inhibiting the overexpression of genes involved in de novo lipogenesis. Mice treated with GEF had increased gut microbial diversity, reduced pathogenic bacteria, and increased Lactococcus and Streptococcaceae genera. Additionally, GEF treatment could increase the expression of intestinal tight junction proteins, which were otherwise decreased in HFD-fed mice, stipulating its protective effect in maintaining gut barrier integrity. Our study demonstrated that GEF treatment reduces obesity in mice and improves gut health by keeping junctions tight and maintaining a healthy gut microbiome.