Antileptospiral activity of xanthones from Garcinia mangostana and synergy of gamma-mangostin with penicillin G.

BACKGROUND: Leptospirosis, one of the most widespread zoonotic infectious diseases worldwide, is caused by spirochetes bacteria of the genus Leptospira. The present study examined inhibitory activity of purified xanthones and crude extracts from Garcinia mangostana against both non-pathogenic and pathogenic leptospira. Synergy between γ-mangostin and penicillin G against leptospires was also determined. METHODS: Minimal inhibitory concentrations (MIC) of crude extracts and purified xanthones from G. mangostana and penicillin G for a non-pathogenic (L. biflexa serovar Patoc) and pathogenic (L. interrogans serovar Bataviae, Autumnalis, Javanica and Saigon) leptospires were determined by using broth microdilution method and alamar blue. The synergy was evaluated by calculating the fractional inhibitory concentration (FIC) index. RESULTS: The results of broth microdilution test demonstrated that the crude extract and purified xanthones from mangosteen possessed antileptospiral activities. The crude extracts were active against all five serovars of test leptospira with MICs ranging from 200 to ≥ 800 µg/ml. Among the crude extracts and purified xanthones, garcinone C was the most active compound against both of pathogenic (MIC =100 µg/ml) and non-pathogenic leptospira (MIC = 200 µg/ml). However, these MIC values were higher than those of traditional antibiotics. Combinations of γ-mangostin with penicillin G generated synergistic effect against L. interrogans serovars Bataviae, Autumnalis and Javanica (FIC = 0.52, 0.50, and 0.04, respectively) and no interaction against L. biflexa serovar Patoc (FIC =0.75). However, antagonistic activity (FIC = 4.03) was observed in L. interrogans serovar Saigon. CONCLUSIONS: Crude extracts and purified xanthones from fruit pericarp of G. mangostana with significant antibacterial activity may be used to control leptospirosis. The combination of xanthone with antibiotic enhances the antileptospiral efficacy.

Highly potent cholinesterase inhibition of geranylated xanthones from Garcinia fusca and molecular docking studies.

Three new oxygenated xanthones, fuscaxanthones L-N (1-3), and 14 known xanthones 4-17, together with the other known metabolites 18-20 were isolated from the stem barks of Garcinia fusca Pierre. Their chemical structures were determined based on NMR and MS spectroscopic data analysis, as well as single X-ray crystallography. The geranylated compounds, cowanin (13), cowagarcinone E (15), norcowanin (16) and cowanol (17) exhibited potent inhibitions against acetylcholinesterase (AChE) (IC50 0.33-1.09 µM) and butyrylcholinesterase (BChE) (IC50 0.048-1.84 µM), which were more active than the reference drug, galanthamine. Compound 15 was highly potent BChE inhibitor (IC50 0.048 µM) and was 76-fold more potent than the drug. Structure-activity relationship studies indicated that the C-2 prenyl and C-8 geranyl substituents in the tetraoxygenated scaffold are important for high activity. Molecular docking studies revealed that the leads 13 and 15-17 showed similar binding orientations on both enzymes and very well-fitted at the double binding active sites of PAS and CAS with strong hydrophobic interactions from both isoprenyl side chains.

Effects of α-mangostin on apoptosis induction of human colon cancer.

AIM: To investigate the effect of α-mangostin on the growth and apoptosis induction of human colon cancer cells. METHODS: The three colorectal adenocarcinoma cell lines tested (COLO 205, MIP-101 and SW 620) were treated with α-mangostin to determine the effect on cell proliferation by MTT assay, cell morphology, chromatin condensation, cell cycle analysis, DNA fragmentation, phosphatidylserine exposure and changing of mitochondrial membrane potential. The molecular mechanisms of α-mangostin mediated apoptosis were further investigated by Western blotting analysis including activation of caspase cascade, cytochrome c release, Bax, Bid, p53 and Bcl-2 modifying factor. RESULTS: The highest inhibitory effect of α-mangostin on cell proliferation of COLO 205, MIP-101 and SW 620 were 9.74 ± 0.85 µg/mL, 11.35 ± 1.12 µg/mL and 19.6 ± 1.53 µg/mL, respectively. Further study showed that α-mangostin induced apoptotic cell death in COLO 205 cells as indicated by membrane blebbing, chromatin condensation, DNA fragmentation, cell cycle analysis, sub-G1 peak (P < 0.05) and phosphatidylserine exposure. The executioner caspase, caspase-3, the initiator caspase, caspase-8, and caspase-9 were expressed upon treatment with α-mangostin. Further studies of apoptotic proteins were determined by Western blotting analysis showing increased mitochondrial cytochrome c release, Bax, p53 and Bmf as well as reduced mitochondrial membrane potential (P < 0.05). In addition, up-regulation of tBid and Fas were evident upon treatment with α-mangostin (P < 0.01). CONCLUSION: α-Mangostin may be effective as an anti-cancer agent that induced apoptotic cell death in COLO 205 via a link between extrinsic and intrinsic pathways.