THE EFFECTS OF THUNBERGIA LAURIFOLIA LINN, MORINGA OLEIFERA LAM EXTRACTS ON HEPATOCELLULAR DETOXICATION AND ENERGY METABOLISM GENE EXPRESSION

Abstract

Oxidative stress is a redox imbalance arises from the excess of free radicals which potentially lead to damage of cellular components. Oxidative stress has been implicated in the pathogenesis of many human diseases, as well as to the aging process. Antioxidants are one way that the body uses to defense and repair in order to minimize damage. Herbal plants become increasing use because they are the excellent sources of antioxidants and easy availability. However, quality, toxicological data and the cellular responses for these plants are rarely known and remained very little data. This present study was designed to investigate the most popular herbs widely used in Thailand: Thunbergia laurifolia (TL) and Moringa oleifera (MO) in the proposed understanding their pharmacological activity and toxicity. It was found that TL and MO extracts possessed high antioxidant levels and ability to scavenging some of the most common reactive species in cellular system including; superoxide radicals, hydroxyl radicals, nitric oxide radicals and hydrogen peroxide. Their antioxidant activities are associated with the phenolic compounds contain in the extracts. Also, both herbal extracts were significantly lowering the oxidative damage of lipid, protein, DNA molecules and could induce endogenous antioxidant molecules. Their other beneficial effects such as anti-diabetic and antidote against pesticide were observed. TLE significant inhibit α-amylase and α-glucosidase - enzymes related to hyperglycemia and lowering AGE formation while MOE is significantly protective effects against organophosphate-induced acetylcholinesterase activity inhibition. The crude extracts were subsequently investigated for the effects in HepG2 cell culture system. The data was indicated at high concentrations over 1000 μg/ml for both extracts induced cytotoxicity. The toxicity of these herbal extracts was evidently associated with mitochondrial dysfunction, partially, by interrupted energy production and calcium homeostasis. Both TLE and MOE could reduce intracellular oxidative levels but only TLE could maintain redox balance when cell face oxidative injury. Finally, the data showed that TLE significantly altered biotransformation system. TLE significantly changed phase I, cytochrome P450 isoenzymes (CYP450s) gene expression profile, enzyme activities and induced excretion process though up-regulated P-glycoprotein activity. These results support the traditional medicinal use of TLE for detoxification. Unlike TLE, MOE would rather to modulating lipid metabolism than the effect on transformation of xenobiotic. MOE was significantly found to modulated lipid biosynthesis by down-regulated mRNA expression of HMG-CoAR, and it regulatory transcription factor, PPARα1 and PPAR. Our results would be the index for further use by exploration for the molecular evidences about their toxicological information. Caution must be taken when mixing herbal supplement with drugs in order to assure the safety of these plants and avoid the adverse effect of the herb-drug interaction.