Poster Presentation First Malaria World Congress 2018

GSK3β: a plausible therapeutic target of medicinal plant-derived bioactive compounds for cytokine modulation during malarial infection (#461)

Hasidah Mohd Sidek 1 , Suhaini Sudi 1 , Amatul Hamizah Ali 1 , Wan Rozianoor Mohd Hassan 2
  1. Universiti Kebangsaan Malaysia, UKM Bangi, SELANGOR, Malaysia
  2. Universiti Teknologi MARA , Shah Alam, Selangor , Malaysia

The pathogenesis of malaria involves among others, uncontrolled or excessive cytokine production arising from dysregulated immune responses mounted by the host to eliminate the plasmodial parasite. Modulation of immune responses using medicinal plants and their products is a potential effective therapeutic strategy for inflammation-related diseases. Many therapeutic effects of plant extracts and their bioactive compounds appear to be due to their wide array of immunomodulatory effects and influence on the host immune system involving various mechanisms of action including protein phosphorylation. Protein kinases are recognised as potential therapeutic targets for malaria. The ubiquitous serine/threonine kinase, glycogen synthase kinase-3β (GSK3β) is a crucial regulator of the balance between pro- and anti-inflammatory cytokine productions in the inflammatory response to pathogenic infections. Inhibition of GSK3β is potentially useful to modulate the cytokine imbalance during infection. We were first to demonstrate that lithium chloride, a GSK3 inhibitor was found to suppress parasitaemia development in a murine model of malarial infection. This poster represents recent findings on the anti-malarial and cytokine-modulating effects of andrographolide and our on-going evaluations of medicinal plant-derived bioactive compounds (e.g. kaempferol, methyl-4-hydroxycinnamate, curcumin and quercetin) for cytokine modulation during malarial infection. Our findings demonstrate that the underlying mechanism of the cytokine-modulating effects of the above bioactive compounds studied involve at least in part inhibition of host GSK3β. In conclusion, GSK3β is a plausible therapeutic target of medicinal plant-derived bioactive compounds for cytokine modulation during malarial infection.