Plants have been used traditionally for the treatment of diabetes mellitus all over the world. One such example is the bitter-tasting unripe fruit of Momordica charantia Linn. (Cucurbitaceae), commonly known as karela. Numerous studies in humans, animals and in vitro models have demonstrated a potential beneficial effect of karela juice or extracts in diabetes. However, the mode of action and active components of karela have not been satisfactorily explained. The present study aimed to use a systematic, relevant approach (bioassay-guided fractionation) to isolate and identify orally active anti-diabetic phytochemicals in karela, and to elucidate its mode of action. Our results showed that karela from different geographical origins varied in both their physical appearance and chemical constituents. Two varieties (Thai and Kenyan) of karela juice exhibited anti-hyperglycaemic (significant improvement in oral glucose tolerance) but not hypoglycaemic (no effect on basal glycaemia) activities in streptozotocin-induced non-insulin-dependent diabetic (NIDD) rats. Thai karela, being more potent, was studied further. We observed for the first time in vivo insulin secretagogue activity by karela juice. The water extract of karela juice significantly improved oral glucose tolerance but not intraperitoneal or intravenous glucose tolerance, implying that it inhibits glucose absorption from the gut or influences glucose sensitive gut hormones. The hexane extract improved oral and intraperitgneal but not intravenous glucose tolerance suggesting that it may possess a hepatic insulin sensitising effect, possibly in addition to an effect on the gut. This extract also inhibited in vitro intestinal glucose absorption in a brush border membrane vesicle model. Bioassay-guided fractionation of the hexane extract led to the isolation and identification of 3 compounds: 5,25-stigmastadien-3-ol (approx. 0.15%w/w yield), momordicine I (0.05%w/w) and ß-sitosterol. Both 5,25-stigmastadienol and ßsitosterol were shown to improve oral glucose tolerance at doses of 4.6mg/kg and 3.1mg/kg respectively in NIDD rats. Momordicine I was not tested. We concluded that karela is most likely to contain more than a single anti-diabetic component and it exhibits its anti-hyperglycaemic activity via a combination of modes of action

Introduction: Dark spots appearing on the skin caused by hyperpigmentation results from the action of tyrosinase, an enzyme whose activity leads to the production of the skin pigment melanin. Extracts of the plant Glycyrrhiza glabra, also known as liquorice, are commonly used to treat a range of conditions including skin hyperpigmentation. This study aimed at isolating and identifying compounds in extracts from South African liquorice root and assaying these compounds as to their antioxidant activity, their ability to inhibit the tyrosinase enzyme and their level of cytotoxicity. Methods: The ability of plant extracts to scavenge free radicals was tested using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonicacid)] (ABTS) and the ferric ion reducing power (FRAP) tests. The polyphenolic content of extract fractions was determined and extract compounds were identified using UHPLC-QToF-20 MS. In vitro anti-tyrosinase activity was also investigated as well as cytotoxicity in HepG2 liver and SK-MEL-1 melanoma cells using the MTT cell viability assay. Results: Of the four fractions prepared from the 70% methanolic extract of liquorice root, fraction 3 (F3) showed increased polyphenolic content and antioxidant properties with IC50 of 56.1 ± 6.32, 39.14 ± 1.1 and 66.34 ± 1.4 μg/ml against DPPH, ABTS and FRAP, respectively. The anti-tyrosinase activity of this fraction showed an IC50 of 358.54 μg/ml compared to Kojic acid (0.75 mM) used as the control. In addition, this fraction showed reduced liver toxicity as a higher percentage cell viability was noted in the HepG2 cells compared to the SK-MEL-1 skin melanoma cells. However, both cell types showed higher percentage viability compared to acetaminophen that was used as cytotoxic control. The LC-MS analysis revealed the presence of a wide variety of compounds including 4-azido-3-benzyl-coumarin, ferulic acid, glycyrrhizin, quercitrin, cirsilineol, gentioflavine and 4'',6,7-trihydroxyisoflavone. The literature indicates the use of these compounds regarding antioxidant and anti-tyrosinase activity. Significantly, cularidine was identified in this study, a compound not previously reported in studies involving liquorice root. Conclusion: The results from this study concur with previous reports as to the anti-tyrosinase and antioxidant activities associated with liquorice roots, activities perhaps due to the relatively high polyphenolic content in extracts from South African liquorice root. / Life and Consumer Sciences / M. Sc. (Life Sciences)