Trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) purified from freshwater clams markedly alleviates dimethylnitrosamine-induced hepatic fibrosis
Ya-Ru Kuo a, Chen-Yu Tsai c, Wei-Sheng Lin a, Chi-I Chang b, Ching-Shu Lai c,
Min-Hsiung Pan a,d,e,*
a Institute of Food Sciences and Technology, National Taiwan University, Taipei 10617, Taiwan
b Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan
c Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 81157, Taiwan
d Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
e Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan
Liver fibrosis occurs due to injury or inflammation, which results in the excessive production of collagen and the formation of fibrotic scar tissue that impairs liver function. Despite the limited treatment options available, freshwater clams may hold promise in the treatment of liver fibrosis. In this study, we demonstrated the effects of ethanol extract of freshwater clam (FCE), ethyl acetate extract of FCE (EA-FCE), and trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) on liver fibrosis induced by dimethylnitrosamine (DMN). Administration of FCE and TNHD alleviated liver injury, including tissue damage, necrosis, inflammation scores, fibrosis scores, serum enzymes, and triglyceride levels. Furthermore, we analyzed the expression of fibrosis-related proteins, such as α-smooth muscle actin (α-SMA) and transforming growth factor (TGF-β), as well as the hydroxyproline content, which decreased after treatment with FCE and TNHD. Animal experiments revealed that FCE and TNHD can reduce liver fibrosis by inhibiting cytokines that activate stellate cells and decreasing extracellular matrix (ECM) secretion. Cell experiments have shown that TNHD inhibits the MAPK/Smad signaling pathway and TGF-β1 activation, resulting in a reduction in the expression of fibrosisrelated proteins. Therefore, freshwater clam extracts, particularly TNHD, may have potential therapeutic and preventive effects for the amelioration of liver fibrosis.
Keywords: DMN-induced liver injury, Freshwater clam, Hepatic stellate cells, Liver fibrosis
https://doi.org/10.38212/2224-6614.3491
(https://www.jfda-online.com/journal/vol32/iss1/1/)(