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OM attenuated hepatic fibrosis by inhibiting viability and inducing apoptosis of HSCs. The RGD-labeled formulation enhanced the targeting efficiency for HSCs and the therapeutic effect.

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Food components with the ability to suppress preadipocyte proliferation and intracellular lipid accumulation may be helpful in the prevention of obesity, which is a worldwide health concern. Casein glycomacropeptide (GMP), which has pronounced gastric inhibitory activity, could potentially possess fat synthesis inhibition properties and an obesity-alleviating capacity. The objective of the present study was to investigate the effect of GMP on the proliferation and differentiation of preadipocytes as well as triglyceride accumulation and glycerol-3-phosphate dehydrogenase activity in preadipocytes isolated from Sprague-Dawley rats. Different dosages (0, 0.31, 0.625, 1.25, 2.5, and 5.0 mg/mL) of GMP were co-incubated with preadipocytes. The proliferation activity of preadipocytes significantly decreased in the GMP-treated group compared with that of the control group without GMP supplementation. The GMP exhibited an inhibitory effect against preadipocyte proliferation in a dose-dependent manner; the maximal antiproliferative effect was obtained with 2.5 mg/mL. The GMP also attenuated differentiation, as revealed by decreased lipid content, and the effect was more pronounced when cells were treated with GMP before or at the beginning of differentiation induction than at later stages of cell differentiation. Cultured preadipocytes treated with GMP accumulated fewer triglycerides and had lower glycerol-3-phosphate dehydrogenase activity than did the control cells without GMP supplementation. In conclusion, GMP can inhibit the proliferation, differentiation, and lipid accumulation of preadipocytes in vitro.

It is recognized that endogenous cannabinoids, which signal through CB1 receptors in hepatic stellate cells (HSCs), exert a profibrotic effect on chronic liver diseases. In this study, we suppressed CB1 expression by lentivirus mediated small interfering RNA (CB1-RNAi-LV) and investigated its effect on hepatic fibrosis in vitro and in vivo. Our results demonstrated that CB1-RNAi-LV significantly inhibited CB1 expression, and suppressed proliferation and extracellular matrix production in HSCs. Furthermore, CB1-RNAi-LV ameliorated dimethylnitrosamine induced hepatic fibrosis markedly, which was associated with the decreased expression of mesenchymal cell markers smooth muscle α-actin, vimentin and snail, and the increased expression of epithelial cell marker E-cadherin. The mechanism lies on the blockage of Smad signaling transduction induced by transforming growth factor β1 and its receptor TGF-β RII. Our study firstly provides the evidence that CB1-RNAi-LV might ameliorate hepatic fibrosis through the reversal of epithelial-to-mesenchymal transition (EMT), while the CB1 antagonists AM251 had no effect on epithelial-mesenchymal transitions of HSCs. This suggests that CB1 is implicated in hepatic fibrosis and selective suppression of CB1 by small interfering RNA may present a powerful tool for hepatic fibrosis treatment.