Preventive effect of artemisinin extract against cholestasis induced via lithocholic acid exposure

Abstract

Obstructive cholestasis characterized by biliary pressure increase leading to leakage of bile back that causes liver injury. The present study aims to evaluate the effects of artemisinin in obstructive cholestasis in mice. The present study was carried out on 40 adult healthy mice that were divided into 4 groups, 10 mice each; the negative control group didn’t receive any medication. The normal group was fed normally with 100 mg/kg of artemisinin extract orally. The cholestatic group fed on 1% lithocholic acid (LCA) mixed into control diet and cholestatic group co-treated with 100 mg/kg of artemisinin extract orally. Mice were treated for 1 month then killed at end of the experiment. A significant increase in alanine aminotransferase, aspartate aminotransferase, and total and direct bilirubin was detected in mice exposed to LCA toxicity. That increase was significantly reduced to normal values in mice co-treated with artemisinin. LCA toxicity causes multiple areas of necrosis of irregular distribution. However, artemisinin co-treatment showed normal hepatic architecture. Moreover, LCA causes down-regulation of hepatic mRNA expressions of a set of genes that are responsible for ATP binding cassette and anions permeability as ATP-binding cassette sub-family G member 8, organic anion-transporting polypeptide, and multidrug resistance-associated protein 2 genes that were ameliorated by artemisinin administration. Similarly, LCA toxicity significantly down-regulated hepatic mRNA expression of constitutive androstane receptor, OATP4, and farnesoid x receptor genes. However, artemisinin treatment showed a reasonable prevention. In conclusion, the current study strikingly revealed that artemisinin treatment can prevent severe hepatotoxicity and cholestasis that led via LCA exposure.

The Effect of Lithocholic Acid on the Gut-Liver Axis

“…For example, glycyrrhizin, the main component of licorice, can promote the detoxification process of LCA by accelerating CYP3A catalyzation ( Wang et al, 2012 ). Both juniperus procera extract and artemisinin treatment prevent hepatotoxicity and cholestasis caused by LCA exposure ( Alkhedaide, 2018 ; Alkhedaide et al, 2018 ). Lysimachia christinae Hance also improves LCA-induced cholecystitis ( Yang et al, 2011 ).…”

Comparative effect of ciprofloxacin and moxifloxacin on the modulation of bile acid profiles and gut microbiota in rats

“…Increased production of DCA is associated with the formation of hepatocellular carcinomas and intestinal cancers (Dong et al, 2018;Yoshimoto et al, 2013). LCA is implicated in intrahepatic cholestasis (Alkhedaide et al, 2018;Lucangioli et al, 2009). The toxicity of BAs is partially attributed to their detergent properties, which is dependent on their hydrophilicity.…”

Anti-malarial drug: the emerging role of artemisinin and its derivatives in liver disease treatment

“…This effect was mediated mainly by inhibiting the activation of NF-κB and MAPK pathways [ 109 ]. A later study suggested that oral exposure to lithocholic acid (LCA) caused liver injury, but the anti-inflammatory activity of artemisinin extract in liver tissues increased the expression of GSH in a LCA-induced mouse model [ 110 ]. Chen and colleagues reported that DHA treatment improved hepatic necrosis and infiltration of inflammatory cells, thus playing a protective role in bile duct ligation (BDL)-induced injury in a rat model.…”