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.