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Naunyn Schmiedebergs Arch Pharmacol. 2014 Mar;387(3):251-61. doi: 10.1007/s00210-013-0937-1. Epub 2013 Nov 21.

Hepatoprotective effect of limonin, a natural limonoid from the seed of Citrus aurantium var. bigaradia, on D-galactosamine-induced liver injury in rats.

Author information

1
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt, mona_pharmacology@yahoo.com.

Abstract

Toll-like receptors have been implicated in inflammation and injury in various tissues and organs including the liver. We have investigated the effects of limonin isolated from the dichloromethane fraction of the seeds of bittersweet orange (Citrus aurantium var. bigaradia) in two dose levels (50 and 100 mg/kg) against D-galactosamine (D-GalN)-induced liver toxicity in comparison with standard silymarin treatment on Toll-like receptors expression and hepatic injury, using a well-established rat model of acute hepatic inflammation. The limonoids in the seeds of bittersweet orange were identified. Oral administration of limonin before D-GalN injection, significantly attenuated markers of hepatic damage (elevated liver enzyme activities and total bilirubin) and hepatic inflammation (TNF-α, infiltration of neutrophils), oxidative stress and expression of TLR-4 but not TLR-2 in D-GalN-treated rats. Limonin effects were similar in most aspects to that of the lignan silymarin. The higher dose of limonin (100 mg/kg) performed numerically better for AST and bilirubin, and both doses yielded similar results for ALT and GGT. While the lower dose of limonin (50 mg/kg) performed better against oxidative stress and liver structural damage as compared to the higher dose. Limonin exerts protective effects on liver toxicity associated with inflammation and tissue injury via attenuation of inflammation and reduction of oxidative stress.

PMID:
24258286
DOI:
10.1007/s00210-013-0937-1
[Indexed for MEDLINE]

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