Protective effect of geraniin against carbon tetrachloride induced acute hepatotoxicity in Swiss albino mice.

Geraniin is a hydrolysable tannin, widely present in many plant species, specifically used in traditional medicines. It has been shown to exhibit strong antioxidant activity in vitro. This study was performed to investigate hepatoprotective activity of geraniin against carbon tetrachloride (CCl4) induced damage in Swiss albino mice. Mice were treated with 30 and 60 mg/kg geraniin for 10 days followed by CCl4 administration for 24 h. Increase in Serum biochemical marker enzymes and histological deteriorative changes of liver tissue after CCl4 administration were attenuated by geraniin. Geraniin significantly reduced CCl4 induced lipid peroxidation, increase in amount of glutathione, glutathione reductase and Heme oxygenase-1 (HO-1). On the other hand it inhibited significant reduction in catalase activity and expression caused by CCl4 administration. Pre-treatment with geraniin reduced phosphorylation of translation initiation factor eIF2α, at serine 51, caused by CCl4 exposure and reduced elevated expression of its upstream kinase, Heme-regulated Inhibitor (HRI). These results clearly demonstrate hepatoprotective activity of geraniin against CCl4-induced acute hepatotoxicity via its free radical scavenging and antioxidant activities.

Cytoprotective effect exerted by geraniin in HepG2 cells is through microRNA mediated regulation of BACH-1 and HO-1.

Geraniin, a hydrolysable tannin, used in traditional medicine in Southeast Asia, is known to exhibit various biological activities. As an antioxidant it is known to up-regulate phase II enzyme Heme oxygenase-1 (HO-1). However its mechanism is not clearly understood. Nuclear factor erythroid-derived 2 related factor 2 (Nrf-2) is transcriptionally up-regulated by Extracellular signal-regulated kinase (ERK) 1/2 and retained in nucleus due to inactivated Glycogen synthase kinase 3 beta (GSK-3ß). Geraniin additionally down-regulates expression of microRNA 217 and 377 (miR-217 and miR-377) which target HO-1 mRNA. Expression of BTB and CNC homolog 1 (BACH-1), another regulator of HO-1, is also down-regulated by up-regulating microRNA 98 (miR-98), a negative regulator of BACH-1. Thus, geraniin up-regulates HO-1 expression both through activating its positive regulator Nrf-2 and by down-regulating its negative regulator BACH-1. Up-regulation of HO-1 also confers protection to HepG2 cells from tertiary butyl hydroperoxide (TBH) induced cytotoxicity. [BMB Reports 2017; 50(11): 560-565].