| Description: |
Alpha-Mangostin has neuroprotective, anti-cancer, antifungal, neuroprotective, renoprotective, antioxidant and anti-inflammatory activities. Alpha-Mangostin exhibits peripheral and central antinociception through modulation of opioid and vanilloid receptors, the glutamatergic system, and the larginine/NO/cGMP/PKC/K(+)-ATP pathways; it suppresses phorbol 12-myristate 13-acetate-induced MMP-2/MMP-9 expressions via alphavbeta3 integrin/FAK/ERK and NF-kappaB signaling pathway in human lung adenocarcinoma A549 cells. Alpha-Mangostin is also a novel competitive histamine H1 receptor antagonist in smooth muscle cells. |
| In vitro: |
| Biochem Biophys Res Commun. 2014 Oct 10;453(1):75-80. | | Inhibition of CHOP accentuates the apoptotic effect of α-mangostin from the mangosteen fruit (Garcinia mangostana) in 22Rv1 prostate cancer cells.[Pubmed: 25261723] | The mangosteen (Garcinia mangostana) fruit has been a popular food in Southeast Asia for centuries and is increasing in popularity in Western countries.
METHODS AND RESULTS:
We identified alpha-Mangostin as a primary phytochemical modulating ER stress proteins in prostate cancer cells and propose that alpha-Mangostin is responsible for exerting a biological effect in prostate cancer cells. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells procured from two patients undergoing radical prostatectomy were treated with alpha-Mangostin and evaluated by RT-PCR, Western blot, fluorescent microscopy and siRNA transfection to evaluate ER stress. Next, we evaluated alpha-Mangostin for microsomal stability, pharmacokinetic parameters, and anti-cancer activity in nude mice. alpha-Mangostin significantly upregulated ER stress markers in prostate cancer cells. Interestingly, alpha-Mangostin did not promote ER stress in prostate epithelial cells (PrECs) from prostate cancer patients. CHOP knockdown enhanced alpha-Mangostin-induced apoptosis in prostate cancer cells. alpha-Mangostin significantly suppressed tumor growth in a xenograft tumor model without obvious toxicity.
CONCLUSIONS:
Our study suggests that alpha-Mangostin is not the only active constituent from the mangosteen fruit requiring further work to understand the complex chemical composition of the mangosteen. | | Evid Based Complement Alternat Med. 2015;2015:740238. | | α-Mangostin Improves Glucose Uptake and Inhibits Adipocytes Differentiation in 3T3-L1 Cells via PPARγ, GLUT4, and Leptin Expressions.[Pubmed: 25873982] | Obesity has been often associated with the occurrence of cardiovascular diseases, type 2 diabetes, and cancer. The development of obesity is also accompanied by significant differentiation of preadipocytes into adipocytes.
METHODS AND RESULTS:
In this study, we investigated the activity of alpha-Mangostin, a major xanthone component isolated from the stem bark of G. malaccensis, on glucose uptake and adipocyte differentiation of 3T3-L1 cells focusing on PPARγ, GLUT4, and leptin expressions. alpha-Mangostin was found to inhibit cytoplasmic lipid accumulation and adipogenic differentiation. Cells treated with 50 μM of alpha-Mangostin reduced intracellular fat accumulation dose-dependently up to 44.4% relative to MDI-treated cells. Analyses of 2-deoxy-D-[(3)H] glucose uptake activity showed that alpha-Mangostin significantly improved the glucose uptake (P < 0.05) with highest activity found at 25 μM. In addition, alpha-Mangostin increased the amount of free fatty acids (FFA) released. The highest glycerol release level was observed at 50 μM of alpha-Mangostin. qRT-PCR analysis showed reduced lipid accumulation via inhibition of PPARγ gene expression. Induction of glucose uptake and free fatty acid release by alpha-Mangostin were accompanied by increasing mRNA expression of GLUT4 and leptin.
CONCLUSIONS:
These evidences propose that alpha-Mangostin might be possible candidate for the effective management of obesity in future. | | J Pharmacol Sci. 2004 May;95(1):33-40. | | Alpha-mangostin induces Ca2+-ATPase-dependent apoptosis via mitochondrial pathway in PC12 cells.[Pubmed: 15153648] | We investigated the cell death effects of eight xanthones on PC12 rat pheochromocytoma cells.
METHODS AND RESULTS:
Among these compounds, alpha-Mangostin, from the fruit hull of Garcinia mangostana L., had the most potent effect with the EC(50) value of 4 microM. alpha-Mangostin-treated PC12 cells demonstrated typical apoptotic DNA fragmentation and caspase-3 cleavage (equivalent to activation). The flow cytometric analysis indicated that this compound induced apoptosis in time-and concentration-dependent manners. alpha-Mangostin showed the features of the mitochondrial apoptotic pathway such as mitochondrial membrane depolarization and cytochrome c release. Furthermore, alpha-Mangostin inhibited the sarco(endo)plasmic reticulum Ca(2+)-ATPase markedly. There was a correlation between the Ca(2+)-ATPase inhibitory effects and the apoptotic effects of the xanthone derivatives. On the other hand, c-Jun NH(2)-terminal kinase (JNK/SAPK), one of the signaling molecules of endoplasmic reticulum (ER) stress, was activated with alpha-Mangostin treatment.
CONCLUSIONS:
These results suggest that alpha-Mangostin inhibits Ca(2+)-ATPase to cause apoptosis through the mitochondrial pathway. |
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