4.5. Hepatoprotective Activity
Further study on hepatotoxicity potential of RZZ demonstrated that the crude AEZZ, at the doses of 50 and 500 mg/kg, did not cause hepatotoxicity effect in mice, which concurred with the insignificant changes in the serum level of ALT and AST after treatment for 4 weeks [45]. Although the AEZZ did cause elevation in serum creatinine level, there are no pathological renal disorders seen. This is further supported by the insignificant changes in the serum blood-urea-nitrogen (BUN) levels between the parallel control (PC) and treated mice indicating normal renal function. In anti-inflammatory study, the AEZZ significantly inhibited the release of TNF-α in murine peritoneal macrophages following LPS stimulation, which occurred in a dose-dependent manner, and TNF-α expression by 55% and 38%, respectively. The AEZZ was also found to inhibit inteleukin-4 (IL4) production in EL-4 lymphocytes at the dose of 500 μg/mL. Compounds like 6-gingerol, kaempferol glycosides and kaempferol derivatives, and chromenone, but not zerumbone, were suggested to contribute to the observed anti-inflammatory activity of the crude AEZZ. The authors suggested that zerumbone was not one of them as it did not dissolve easily in water-soluble fractions. In antipulmonary inflammatory study, the AEZZ was also found to significantly reduce cysteinyl leukotriene (LTC4) (39% reduction) release by the lung tissue of treated mice when compared to the control mice (429 ± 69 versus 261 ± 23 ρg/lung) without affecting the serum level as interleukin-1α (IL1α) suggesting that the extract is not inducing any inflammatory effect upon long-term oral administration to mice and is not causing any harmful effect to the liver or to renal function. LTC4 plays a significant role in the pathophysiology of asthma.