Abstract:
Mangosteen, Garcinia mangostana L., has been used as a traditional medicine for the treatment of many diseases. Several reports show that crude extract and active constituents of mangosteen exhibit miscellaneous activities including antimicrobial, antioxidant, anti-inflammatory, cytotoxic and anticancer activities. Mangosteen contains a variety of phytochemicals in which xanthones are the principal constituents exhibiting these activities. Based on these reported activities, a large amount of products derived from mangosteen has been widely used to improve health status as well as treat many diseases. However, the immunomodulatory evidence of mangosteen is limited. This study, therefore, aimed to investigate the immunomodulatory activity of two mangosteen extracts, purified α-mangostin and partially purified crude water extract, on human immune cells and cytokines in vitro. Peripheral blood mononuclear cells (PBMCs) were cultured with the selected concentrations of α-mangostin (1, 2 and 4 μg/ml), crude water extract (50, 100 and 200 μg/ml), T cell mitogen concanavalin A (ConA; 10 μg/ml), and α-mangostin (or crude water extract) plus ConA. After 24 h of incubation, the treated cells were enumerated in the percentages of CD3+ (T cells), CD19+ (B cells) and CD3-CD16+/CD56+ (NK cells) by immunophenotypic method, while the cell cultured supernatants were evaluated the primary cytokine (TNF-α, IL-1β and IL-2) production by ELISA technique. The results demonstrated that three concentrations of α-mangostin or crude water extract could not change the expression level of three lymphocyte markers compared with unstimulated cells; moreover, the combinations of α-mangostin (or crude water extract) plus ConA could not change the expression level of these three lymphocyte markers compared with ConA-stimulated cells. On the contrary, α-mangostin could show an obvious tendency to inhibit IL-2 secretion; whereas, crude water extract could significantly induce TNF-α and IL-1β secretion as much as ConA-stimulated cells produced. The crude water extract was further examined the stimulatory activity on proinflammatory cytokine expression by measuring intracellular TNF-α of monocytes. The whole blood was incubated with 50 and 100 μg/ml of crude water extract, lipopolysaccharide (LPS), dexamethasone (Dex), and the combined substances between crude water extract and LPS (or Dex) for 4 h. The results showed that crude water extract could not induce intracellular TNF-α expression. This possibly suggested that crude water extract could exert its effect on other cells, but not monocytes, in whole blood to produce TNF-α. These results indicated that α-mangostin could be developed into an immunosuppressant, suppressing IL-2 secretion, and crude water extract could be employed as an immunostimulant triggering proinflammatory cytokine production without activating via monocytes. Nevertheless, further studies of both extracts on other immune cells and cytokines with an increase sample size are necessary to deeply understand their mechanisms of actions.