Aloe vera gel extract and bone marrow mesenchymal stem cells ameliorate thioacetamide-induced liver fibrosis via modulating lincRNA-p21/miR-17-5p axis

Abstract

Thioacetamide (TAA)-induced liver fibrosis, triggered by inflammation and oxidative stress, is prompted by hepatic stellate cells (HSCs) activation via several pathways. This study explores the hepatoprotective effect of aloe vera gel (AVG) extract and bone marrow mesenchymal stem cells (BM-MSCs) transplantation on regulating long intergenic non-coding RNA (lincRNA-p21) and microRNA (miR-17-5p) expressions and their impact on TGF-β1/Smad-3 and Wnt-10a/β-Catenin cascades in TAA-induced liver damage. The study involved 48 adult male albino rats divided into four groups: control, TAA, TAA treated with BM-MSCs, and TAA treated with BM-MSCs+AVG extract. After 8 weeks, liver enzymes and hepatic oxidative parameters were evaluated alongside lincRNA-p21, miR-17-5p, TGF-β1, Smad-3, Wnt-10a, and β-Catenin expressions. Liver tissue sections were examined by light and electron microscopes and analyzed morphometrically. Group II showed increased aspartate aminotransferase, alanine aminotransferase, malondialdehyde, reduced glutathione levels, and deteriorated hepatocytes with distorted mitochondria and dilated rough endoplasmic reticulum. Group IV restored lincRNA-p21 expression, which downregulated miR-17-5p and suppressed activated HSCs by inhibiting TGF-β1/Smad-3 and Wnt-10a/β-Catenin pathways, and improved hepatic tissue architecture. Additionally, immunohistochemically, alpha-smooth muscle actin and cyclin D1 expressions were markedly decreased in group IV compared to group II. We concluded that AVG suppresses fibrotic pathways, boosts BM-MSCs differentiation, and reduces HSCs activation in liver fibrosis caused by TAA.