Ethanol extract of Nymphaea lotus Linn. inhibited hepatic fibrogenesis in carbon tetrachloride-intoxicated Wistar rats

Abstract

BackgroundNymphaea lotus is a plant used as food and to manage various ailments including liver diseases. Liver fibrosis is a pathological state which progresses to more chronic and fatal liver diseases but without any approved drug yet. This study thus aimed to investigate the anti-liver fibrosis mechanism of N. lotus.MethodologyLiver fibrosis was induced by carbon tetrachloride (CCl4:Olive oil, 1:1 ip). Fibrotic animals were treated with 50, 100 and 200 mg/kg b.wt. N. lotus extract. The activities of alanine aminotransaminase (ALT), aspartate aminotransferase (AST), in the serum, and levels of Malondialdehyde (MDA), superoxide dismutase (SOD), catalase, and reduced glutathione (GSH) in the liver, and histopathology of the liver were determined. The expression of fibrosis-related proteins namely alpha-smooth muscle actin (α-SMA), Collagen-4 (COL4A), Transforming growth factor-β1 (TGFβ1), Mothers against decapentaplegic homolog 2 (SMAD2), SMAD3 and matrix metalloproteinase 2 (MMP2) in the liver was also evaluated. Molecular docking and simulation analysis of N. lotus-derived phytochemicals to TGFβ1 and SMAD3 was also performed.ResultsThe extract significantly reduced the levels of ALT, AST, and MDA, increased the expression of antioxidant enzymes namely; SOD and GSH, and downregulated the expression of fibrosis-related proteins namely α-SMA, COL4A, TGFβ1, SMAD3 and MMP2. It also ameliorated CCl4-induced hepatic lesions. N. lotus-derived phytochemicals also showed a good binding affinity and interaction with the active sites of TGFβ1 and SMAD3.ConclusionN. lotus inhibited liver fibrosis by inhibiting oxidative stress and the TGFβ/SMAD signalling pathway. This demonstrates its beneficial and protective effect against CCl4-induced hepatoxicity and thus supports its use for the traditional management of liver diseases.