Prophylactic role of Premna herbacea, a dietary leafy vegetable in managing hepatic steatosis via regulating AMPK/SREBP1/ACC/HMGCR signaling pathway

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Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of liver dysfunction ranging from hepatic steatosis (intracellular triglyceride accumulation) to steatohepatitis. This study investigated the beneficial effect of Premna herbacea (a dietary leafy vegetable of North East India) and its active constituent in managing hepatic steatosis using high fat diet (HFD)-fed male Wistar rat and hepatocyte (CC1) cell culture models. Administration with methanolic leaf extract of Premna herbacea (PHME) (250 mg/kg body weight, oral gavage, 20 weeks) reduced the gain in body weight and rise in serum lipid (triglyceride and total cholesterol) levels and enzymes (alkaline phosphatase and aspartate aminotransferase) responsible for liver dysfunction in high fat diet (HFD)-fed rats. PHME administration further upregulated the phosphorylation of AMPK, ACC, and HMGCR, downregulated SREBP1 signaling pathways of lipid metabolism, and prevented hepatic steatosis in liver tissues of HFD-fed rats. Moreover, studies on cultured hepatocytes revealed that treatment with both crude extract and its ethyl acetate fraction (PHEA) significantly reduced intracellular lipid accumulation in palmitate (PA, 0.75 mM)-treated cells. Chemical profiling (HPLC, HRMS, 1H and 13C NMR) of PHEA demonstrated the presence of Verbascoside, a caffeoyl phenylethanoid glycoside as a major phyto-constituent, which prevented cellular lipid accumulation and regulated the alteration in AMPK/SREBP/ACC/HMGCR signaling pathways of lipid metabolism in PA-treated cells. In conclusion, this study showed the prophylactic role of Premna herbacea and its active molecule, Verbascoside as a potential functional food in ameliorating hepatic steatosis by regulating AMPK/SREBP/ACC/HMGCR signaling cascade.