Suppression of nitric oxide production by compounds from Garcinia mangostana in HAPI microglial cells

AN Thampithak1, YU Sanvarinda2, SU Suksamrarn3. 1Faculty of Pharmaceutical Sciences Burapha University, Chonburi 20131, Thailand, 2Faculty of Science Mahidol University, Department of Pharmacology Bangkok 10400, Thailand, 3Faculty of Science Srinakharinwirot University, Department of Chemistry Bangkok 10110, Thailand

Activated microglia produce a variety of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) and implicate in various neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease. Inhibition of microglial activation may have potential anti-inflammatory effects. Garcinia mangostana (mangosteen) has traditionally been used in Thailand for treatment of skin infection, diarrhea and wounds for several years. In this study, we examined the effect of α-, β- and γ-mangostin, a xanthone compound purified from mangosteen, on NO production by lipopolysaccharide (LPS)-activated microglia. Results are expressed as means ± S.E.M. Statistical analysis was performed using one-way ANOVA followed by a Tukey comparison test. Our studies showed that pretreatment of the highly aggressively proliferating immortalized (HAPI), rat microglial cell line, with α-, β- and γ-mangostin for 1 h, at the concentrations of 0.1, 0.5, 1, 5 and 10 μM markedly suppressed the LPS (0.1 μg/ml)-induced activation of microglia by reducing the production of NO in a concentration-dependent manner. Moreover, the protein expression of inducible nitric oxide synthase (iNOS) was also significantly inhibited by α-, β- and γ-mangostin. These results indicate that α-, β- and γ-mangostin potently inhibited LPS-induced NO production and may have therapeutic potential in the treatment of neuro-inflammatory diseases through the inhibition of overproduction of NO.