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Phenolic Constituents of Chrysophyllum oliviforme L. Leaf Down-Regulate TGF-β Expression and Ameliorate CCl4-Induced Liver Fibrosis: Evidence from In Vivo and In Silico Studies

1
Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 12613, Egypt
2
Department of Biochemistry, Faculty of Veterinary Medicine, Cairo University, Cairo 12613, Egypt
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Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Cairo 12613, Egypt
4
Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Cairo 12613, Egypt
5
AgroBioSciences Research Division, Mohammed VI Polytechnic University, Lot 660–Hay MoulayRachid, Ben-Guerir 43150, Morocco
*
Authors to whom correspondence should be addressed.
Antioxidants 2019, 8(12), 646; https://doi.org/10.3390/antiox8120646
Received: 14 October 2019 / Revised: 17 November 2019 / Accepted: 12 December 2019 / Published: 15 December 2019
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. View Full-Text
Keywords: Chrysophyllum oliviforme; Chrysohyllum cainito; hepatoprotective; antioxidant; TGF-β; phenolic compounds Chrysophyllum oliviforme; Chrysohyllum cainito; hepatoprotective; antioxidant; TGF-β; phenolic compounds
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El-Hawary, S. .-D.; El Zalabani, S.M.; Selim, N.M.; Ibrahim, M.A.; Wahba, F.A.; El Badawy, S.A.; Mahdy, N.E.S.; Yasri, A.; Sobeh, M. Phenolic Constituents of Chrysophyllum oliviforme L. Leaf Down-Regulate TGF-β Expression and Ameliorate CCl4-Induced Liver Fibrosis: Evidence from In Vivo and In Silico Studies. Antioxidants 2019, 8, 646.

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