AIM OF STUDY: Although anticancer activity has been reported for the plant, the goal of the study was designed to isolate and characterize the active metabolites from G. mangostana and measure their cytotoxic properties. In this research, the mechanism of antiproliferative/cytotoxic effects of the tested compounds was investigated.
MATERIALS AND METHODS: The CHCl3 fraction of the air-dried fruit hulls was repeatedly chromatographed on SiO2, RP18, Diaion HP-20, and polyamide columns to furnish fourteen compounds. The structures of these metabolites were proven by UV, IR, 1D, and 2D NMR measurements and HRESIMS. Additionally, the cytotoxic potential of all compounds was assessed against MCF-7, HCT-116, and HepG2 cell lines using SRB-U assay. Antiproliferative and cell cycle interference effects of potentially potent compounds were tested using DNA content flow cytometry. The mechanism of cell death induction was also studied using annexin-V/PI differential staining coupled with flow cytometry.
RESULTS: The CHCl3 soluble fraction afforded two new xanthones: mangostanaxanthones V (1) and VI (2), along with twelve known compounds: mangostanaxanthone IV (3), β-mangostin (4), garcinone E (5), α-mangostin (6), nor-mangostin (7), garcimangosone D (8), aromadendrin-8-C-β-D-glucopyranoside (9), 1,2,4,5-tetrahydroxybenzene (10), 2,4,3`-trihydroxybenzophenone-6-O-β-glucopyranoside (11), maclurin-6-O-β-D-glucopyranoside (rhodanthenone) (12), epicatechin (13), and 2,4,6,3`,5`-pentahydroxybenzophenone (14). Only compound 5 showed considerable antiproliferative/cytotoxic effects with IC50's ranging from 15.8 to 16.7µM. Compounds 3, 4, and 6 showed moderate to weak cytotoxic effects (IC50's ranged from 45.7 to 116.4µM). Using DNA content flow cytometry, it was found that only 5 induced significant cell cycle arrest at G0/G1-phase which is indicative of its antiproliferative properties. Additionally, by using annexin V-FITC/PI differential staining, 5 induced cells killing effect via the induction of apoptosis and necrosis in both HepG2 and HCT116 cells. Compound 3 produce necrosis and apoptosis only in HCT116 cells. On contrary, 6 induced apoptosis and necrosis in HepG2 cells and moderate necrosis in HCT116 cells.
CONCLUSION: Fourteen compounds were isolated from chloroform fraction of G. mangostana fruit hulls. Cytotoxic properties exhibited by the isolated xanthones from G. mangostana reinforce the avail of it as a natural cytotoxic agent against various cancers. These evidences could provide relevant bases for the scientific rationale of using G. mangostana in anti-cancer treatment.
METHODS: Galactagogue activity was evaluated in terms of quantity of milk produced from the rats treated with petroleum ether, ethanol or water extracts of the flower. Lactating rats (n = 5) of Spraque Dawley with six pups each were administered with the extracts in the amount of 500 mg/kg body weight, while the control rats were given an equivalent amount of distilled water. The rats were daily administered via oral feeding starting from Day 5 until Day 14 and the performance of milk production was measured along the experimental period by weight-suckle-weight method. Results were statistically analyzed using SPSS by means of ANOVA at 0.05 and was expressed as their mean?standard deviation. The rates of pups' growth were measured as the weight gain along the experimental period.
RESULTS: The rats treated with aqueous extract produced higher milk than control and ethanol groups. Aqueous extract was identified to increase milk production by 25%, while petroleum ether extract by 18%. The mean of yields produced by the rats during suckling period for aqueous, petroleum ether, ethanol and control were 4.62±2.45, 4.37±1.93, 3.65±1.89 and 3.69±1.79, respectively. Growth rates of pups for the rats treated with control, aqueous, ethanol extract and petroleum ether were (1.85±0.49), (1.78±0.56), (1.65±0.46) and (1.56±0.42) g/pup, respectively.
CONCLUSIONS: The present study reveals the potential of M. x paradisiaca flower to enhance milk production of nursing mothers which could be exploited for commercialization of the isolated extract.