ABSTRACT
In our previous research, Khat has been shown to be associated with hepatic hypertrophy and hepatotoxicity in male and female SD-rats. However, no in vitro studies have been previously done to test on hepatotoxicity of khat on human experimental models. In vitro toxicological evaluation system plays an important role in the early phase of pharmaceutical development and drug safety. Therefore, the current study was designed to examine the in vitro hepatotoxic effect of phenolic-rich extract of khat (Catha edulis Forsk.). Khat was randomly collected from different places in Yemen [Dhamar (DMR), Ibb (IB), Taiz (TZ) cities] and Ethiopia (HAR). Phenolic-rich extraction was performed using 60% methanol. The effects of khat on HepG2 human hepatocyte cell line were measured using the MTT assay. HepG2 cells are a suitable in vitro model system for the study of human hepatocytes. The potency of cell growth inhibition for khat was expressed as an IC50 value. Cellular proliferation following 24h of exposure to khat samples showed considerable inhibition in khat-treated cells compared to nontreated cells (controls). The IC50 values of DMR, IB, TZ and HAR were 5.1±0.03, 15.3±0.12, 10.2±0.20 and 8.7±0.47 μg/mL, following 24 h of treatment, respectively. The proliferation of khat-treated cells decreased as the khat concentration increased. The method used appears to be a useful and reproducible technique for the in vitro assessment of the khat-induced cytotoxicity in a human liver cell line. Further studies are recommended to understand the molecular mechanism of Khat induced HepG2 cytotoxicity.
ABSTRACT
Boesenbergia rotunda is a medicinal plant that used traditionally in South East Asia as a healing for various ailments including neurological disorders. Therefore, this research was designed to describe the biological evaluation pertaining to anti-human cholinesterase (hAChE) activities, molecular docking and in silico prediction of Boesenbergin A (BA), a natural chalcone isolated from B. rotunda. The anti-hAChE activity of BA was evaluated using acetylthiocholine as a substrate and 5,5-dithiobis[2-nitrobenzoic acid] (DTNB) as chromogen. Docking study with flexible boesenbergin A was done using Autodock 4.2 software and A Lamarkian Genetic Algorithm search method. ADME/Tox analysis was also performed using ADMET Descriptors software. The inhibitory activities of BA and the standard drugs tacrin and propidium iodide on human acetylcholinesterase are 70.1±5.43, 76.6±5.11 and 28.2±2.47, respectively. Molecular docking investigation showed that BA occupies the active site of hAChE and this strongly suggests that it acts as a competitive inhibitor and ultimately reduces the activity of the enzyme. BA also exhibited good ADMET properties indicating capacity for further studies towards developing this compound into a potent drug candidate for the treatment of Alzheimer’s disease. The present study extends the understanding on the molecular mechanism underlying the diverse biological activities of Boesenbergia rotunda.