The Hepatoprotective Effect of Piperine Against Thioacetamide-Induced Liver Fibrosis in Mice: The Involvement of miR-17 and TGF-β/Smads Pathways

Abstract

Liver fibrosis is characterized by a series of events including activation of quiescent hepatic stellate cells (HSCs) into proinflammatory, contractile, and fibrogenic myofibroblasts, which is the primary trigger for the fibrogenesis process. HSC activation involves many signaling pathways such as the TGF-β/smads pathway. Specific microRNAs have been identified to play a crucial role in the activation of HSCs via various signaling pathways. Piperine has recently been studied as a promising anti-fibrotic agent against pancreatic fibrosis through altering the TGF-β1/Smad pathway. Hence, the current study evaluated the beneficial effects of piperine in thioacetamide-induced liver fibrosis in mice through the modulation of miRNA-17 and TGF-β/smads pathways. Mice were allocated into three groups randomly. Thioacetamide was used to induce liver fibrosis for 6 weeks. Starting from the fourth week of the experiment, mice were treated with piperine daily for 21 days. Piperine treatment resulted in a significant downregulation of miRNA-17 expression, leading to the restoration of smad-7 accompanied with marked inhibition of TGF-β/smads signaling with further suppression of the activated HSCs and collagen deposition in the hepatocytes. In conclusion, piperine has the potential to be a promising therapeutic drug for the treatment of liver fibrosis through inhibiting the TGF-β/smads pathway.

Prophylactic Resveratrol Ameliorates Thioacetamide Hepatotoxicity in A Dose-Dependent Fashion Through the Regulation of Gene Expression Levels of MiR-155 and MiR-21

“…The detected increased plasma levels of miR-155 and miR-21 and their relation to TAA-toxicity are coincident with the results evaluated the role of another microRNA in TAA toxicity; where one study reported the presence of higher levels of microRNAs; 122, 192, and 194 in the experimental group has given TAA (Teksoy et al,2020). Further, other studies detected deregulated expression levels of MiR-17 and 378 due to TAA toxicity, and this induced hepatic fibrosis through activation of hepatic stellate cells via altering Wnt/βcatenin and TGF-β/smads pathways (Zaafan and Abdelhamid.,2022;Abdelhamid et al,2021).…”

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

“…(11) Targets the FXR-miR-29a signaling pathway in HSC: Sweroside [235] . (12) Improves HSC activation by inhibiting NLRP3 inflammatory vesicle activation: Dehydromevalonolactone [236] , Palmitic acid [237] . (13) Targeting FGF19/FGFR4 signaling to block LPS-induced HSC proliferation and activation: Salvianolic acid B [238] .…”

“…Hence, modulation of miR-130b-5p may be a key curative maneuver to LF [11] . It has been demonstrated that upregulation of miRNA-17 expression and inhibition of smad-7 recovery are accompanied by significant activation of TGF-β/smads signaling, further promoting activated HSCs and collagen deposition in hepatocytes [12] . Mmu-miR-137-3p addresses Ppic directly as well as creates a modulatory axis with Ppic to regulate HSCs stimulation in TGF-β-induced mice [13] .…”

Efficacy of curcumin plus piperine co‐supplementation in moderate‐to‐high hepatic steatosis: A double‐blind, randomized, placebo‐controlled clinical trial

“…The low bioavailability of curcumin can be enhanced with the coadministration with piperine (Shoba et al, 1998), an alkaloid compound extracted from the seeds of Piper nigrum . Piperine alone has intrinsic anti‐oxidant, anti‐inflammatory and hepatoprotective effects (Abdelhamid, Selim, & Zaafan, 2021; Derosa, Maffioli, & Sahebkar, 2016).…”