Periplaneta americana extract attenuates hepatic fibrosis progression by inhibiting collagen synthesis and regulating the TGF-β1/Smad signaling pathway

Introduction. Liver fibrosis is the damage repair response following chronic liver diseases. Activated hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)-producing cells and key regulators in liver fibrosis. Periplaneta americana shows prominent antifibrotic effects in liver fibrosis; however, the underlying mechanisms remain undetermined. This study aimed to elucidate the therapeutic effects of P. americana extract (PA-B) on liver fibrosis based on the regulation of the TGF-O1/Smad signal pathway. Material and methods. HSCs and Sprague Dawley rats were treated with TGF-O1 and CCl4, respectively, to establish the hepatic fibrosis model in vitro and in vivo. The effect of PA-B on liver rat fibrosis was evaluated by biochemical (serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hyaluronic acid (HA), laminin (LN), collagen type IV (Col-IV), pro-collagen type III (PC-III)) and histological examinations. Further, fibrogenic markers expression of alpha smooth muscle actin (alpha-SMA), collagen type I (Col-I), and collagen type III (Col-III), and the TGF-O1/Smad pathway-related factors were assessed by immunofluorescence (IF), real time quantitative polymerase chain reaction (RT-qPCR), and western blotting (WB). Results. Treatment of HSC-T6 cells with PA-B suppressed the expression of alpha-SMA, Col-I, and Col-III, downregulated the expression of TGF-O1 receptors I and II (TOR I and TOR II, respectively), Smad2, and Smad3, and upregulated Smad7 expression. PA-B mitigates pathologic changes in the rat model of liver fibrosis, thus alleviating liver index, and improving liver function and fibrosis indices. The effects of PA-B on the expression of alpha-SMA, Col-I, Col-III, TOR I, TOR II, Smad2, Smad3, and Smad7 were consistent with the in vitro results, including reduced TGF-O1 expression. Conclusions. The therapeutic effect of PA-B on liver fibrosis might involve suppression of the secretion and expression of TGF-O1, regulation of the TGF-O1/Smad signaling pathway, and inhibition of collagen production and secretion. (Folia Histochemica et Cytobiologica 2023, Vol. 61, No. 4, 231-243)