Anti-malarial and anti-inflammatory effects of Gleichenia truncata mediated through inhibition of GSK3β
- Author:
Suhaini, S.a, Liew, S.Z.a, Norhaniza, J.b, Lee, P.C.b, Jualang, G.b, Embi, N.a and Hasidah, M.S.a
- Publication Type:Journal Article
- From:Tropical Biomedicine
2015;32(3):419-433
- CountryMalaysia
- Language:English
-
Abstract:
Gleichenia truncata is a highland fern from the Gleicheniaceae family known for
its traditional use among indigenous communities in Asia to treat fever. The scientific basis of
its effect has yet to be documented. A yeast-based kinase assay conducted in our laboratory
revealed that crude methanolic extract (CME) of G. truncata exhibited glycogen synthase
kinase-3 (GSK3)-inhibitory activity. GSK3β is now recognized to have a pivotal role in the
regulation of inflammatory response during bacterial infections. We have also previously
shown that lithium chloride (LiCl), a GSK3 inhibitor suppressed development of Plasmodium
berghei in a murine model of malarial infection. The present study is aimed at evaluating G.
truncata for its anti-malarial and anti-inflammatory effects using in vivo malarial and
melioidosis infection models respectively. In a four-day suppressive test, intraperitoneal
injections of up to 250 mg/kg body weight (bw) G. truncata CME into P.berghei-infected mice
suppressed parasitaemia development by >60%. Intraperitoneal administration of 150 mg/kg
bw G. truncata CME into Burkholderia pseudomallei-infected mice improved survivability
by 44%. G. truncata CME lowered levels of pro-inflammatory cytokines (TNF-α, IFN-γ) in
serum and organs of B. pseudomallei-infected mice. In both infections, increased
phosphorylations (Ser9) of GSK3β were detected in organ samples of animals administered
with G. truncata CME compared to controls. Taken together, results from this study strongly
suggest that the anti-malarial and anti-inflammatory effects elicited by G. truncata in part
were mediated through inhibition of GSK3β. The findings provide scientific basis for the
ethnomedicinal use of this fern to treat inflammation-associated symptoms.
