AUTHOR=Kumar Ajay , Kaur Varinder , Pandit Kritika , Tuli Hardeep Singh , Sak Katrin , Jain Subheet Kumar , Kaur Satwinderjeet 

TITLE=Antioxidant Phytoconstituents From Onosma bracteata Wall. (Boraginaceae) Ameliorate the CCl4 Induced Hepatic Damage: In Vivo Study in Male Wistar Rats

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.01301

DOI=10.3389/fphar.2020.01301

ISSN=1663-9812

ABSTRACT=<p><italic>Onosma bracteata</italic> Wall. (Boraginaceae) is a highly valuable medicinal herb that is used for the treatment of fever, bronchitis, asthma, rheumatism, stomach irritation, and other inflammatory disorders. The present study aims to explore the hepatoprotective potential of ethanolic extract (<italic>Obeth</italic>) from <italic>O. bracteata</italic> aerial parts against carbon tetrachloride (CCl<sub>4</sub>) which causes hepatic damage in the male Wistar rats. <italic>Obeth</italic> showed effective radical quenching activity with an EC<sub>50</sub> of 115.14 and 199.33 µg/mL in superoxide radical scavenging and lipid peroxidation analyses respectively along with plasmid DNA protective potential in plasmid nicking assay. The <italic>Obeth</italic> modulated mutagenicity of 2 Aminofluorine (2AF) in the pre-incubation mode of investigation (EC<sub>50</sub> 10.48 µg/0.1 mL/plate) in TA100 strain of <italic>Salmonella typhimurium</italic>. In <italic>in vivo</italic> studies, pretreatment of <italic>Obeth</italic> (50, 100, and 200 mg/kg) had the potential to normalize the biochemical markers aggravated by CCl<sub>4</sub> (1mL/kg b.wt.) including liver antioxidative enzymes. Histopathological analysis also revealed the restoration of CCl<sub>4</sub>-induced liver histopathological alterations. Immunohistochemical studies showed that the treatment of <italic>Obeth</italic> downregulated the expression levels of p53 and cyclin D in hepatocytes. and downregulation in the Western blotting analysis revealed the downregulation of p-NF-kB, COX-2, and p53. HPLC data analysis showed the supremacy of major compounds namely, catechin, kaempferol, epicatechin, and Onosmin A in <italic>Obeth</italic>. The present investigation establishes the hepatoprotective and chemopreventive potential of <italic>O. bracteata</italic> against CCl<sub>4</sub>-induced hepatotoxicity <italic>via</italic> antioxidant defense system and modulation of the expression of proteins associated with the process of carcinogenesis in hepatic cells.</p>