Abstract
The prevalence of hepatic diseases globally and in Egypt particularly necessitates an intensive search for natural hepatoprotective candidates. Despite the traditional use of Chrysophyllum oliviforme L. and C. cainito L. leaves in the treatment of certain ailments, evidence-based reports on their bioactivities are limited. In this work, in vivo and in silico studies were conducted to evaluate their methanol extracts potential to alleviate liver damage in CCl4-intoxicated rats, in addition to their antioxidant activity and identifying the molecular mechanisms of their phenolic constituents. The extracts restored the altered total cholesterol (TC), triglycerides (TG), high-density lipoproteins (HDL), alanine aminotransferase ALT, aspartate aminotransferase AST, total protein, and albumin. Histopathological architecture, DNA fragmentation, and mRNA expression level of TGF-β1 also confirmed the anti-fibrotic activity of the two extracts. The total phenolic content (TPC) in C. oliviforme ethanol extract exceeded that in C. caimito. Additionally, the malondialdehyde (MDA), reduced glutathione (GSH), and total antioxidant capacity (TAC) levels assured the antioxidant potential. Seven phenolics; quercetin, isoquercitrin, myricetin, kaempferol, and caffeic, trans-ferulic, and gallic acids were isolated from the ethanol extract of C. oliviforme. The molecular docking of isolated compounds revealed a low binding energy (kcal/mol with TGF-β1, thus confirming the hepatoprotctive activity of the extracts. In conclusion, the C. oliviforme leaves could be considered as potent safe raw material for the production of herbal formulations to alleviate hepatic toxicity after preclinical safety study.
Highlights
Oxidative chain reactions induce cellular damage and homeostatic disruption, causing a wide number of health problems, among them liver injury
The reduced glutathione (GSH) level and total antioxidant capacity (TAC) were significantly increased in all of the pretreated groups up to a near normal value compared to CCl4 intoxicated rats, with superior activity being exhibited by the defatted ethanolic extract of C. oliviforme L. (Oe) at the higher dose level (500 mg/kg), as shown in oliviforme (Oe) could be considered as the most effective in reversing the harmful effect of CCl4 -liver injury on ALT and AST raised levels when compared to the standard hepatoprotective drug, Silymarin with relative potencies 1.51 and 2.22, respectively (Table 2)
C. oliviforme leafsignificant extracts significantly fibrosis changesclearly and ademonstrated marked hepatoprotective effect that denoted by reduction in alleviated
Summary
Oxidative chain reactions induce cellular damage and homeostatic disruption, causing a wide number of health problems, among them liver injury. Hepatocyte damage promotes the secretion of inflammatory and profibrogenic cytokines, leading to the development of liver fibrosis. The transforming growth factor-β (TGF-β1) is the most potent profibrogenic cytokine that regulates the proliferation and differentiation of many cell types by directing the expression of hundreds of target genes [2]. In the hepatic stellate cells (HSCs) of liver, for instance, TGF-β1 stimulates the activation of SMADs (main signal transducers for receptors of TGF-B) and mitogen-activated protein kinases (MAPKs) signaling pathways [3]. Antioxidant compounds, among them plant polyphenols, can prevent cellular injury by inhibiting the initiation or propagation of such oxidative reactions [4]
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