Sains Malaysiana 44(10)(2015): 1489–1500

Anti-malarial and Anti-inflammatory Effects of Gynura procumbens are Mediated by Kaempferol via Inhibition of Glycogen Synthase Kinase-3β (GSK3β)

(Kesan Anti-malaria dan Anti-inflamasi Gynura procumbens Diperantara oleh Kaempferol

melalui Perencatan Glikogen Sintase Kinase-3β)

SOK KUAN WONG¹, MICHELLE LEE SUE JANN¹, SUHAINI SUDI¹, WAN ROZIANOOR BT MOHD HASSAN¹, LEE PING CHIN², NOOR EMBI¹ & HASIDAH MOHD SIDEK¹*

¹School of Biosciences and Biotechnology, Faculty of Science and Technology

Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor Darul Ehsan, Malaysia

²School of Science and Technology, Universiti Malaysia Sabah, 88999 Kota Kinabalu, Sabah

Malaysia

Received: 27 November 2014/Accepted: 18 June 2015

ABSTRACT

Gynura procumbens is a medicinal plant, traditionally used to treat inflammation and fever. A yeast-based assay detected GSK3β-inhibitory activity in the aqueous extract of G. procumbens. GSK3β is now known to have a central role in the modulation of host inflammatory response during bacterial infections. In this study, we investigated the involvement of GSK3β in the anti-malarial and anti-inflammatory effects of an aqueous extract of G. procumbens. Our results showed that G. procumbens inhibited growth of P. falciparum 3D7. Consecutive four-day administration of 250 mg/kg body weight (b.w.) G. procumbens resulted in strong chemosuppression and improved survivability in P. berghei-infected mice. B. pseudomallei-infected mice treated with G. procumbens (50 mg/kg b.w.) showed increased survivability. TNF-α and IFN-γ levels in liver and serum of B. pseudomallei-infected mice were lowered by G. procumbens treatment. IL-10 level was higher in serum of G. procumbens-administered infected mice. G. procumbens treatment of P. berghei- and B. pseudomallei-infected animals each resulted in increased hepatic GSK3β (Ser9) phosphorylation. It is noteworthy that kaempferol (one of the compounds in G. procumbens) also inhibited the growth of P. falciparum 3D7; showed strong chemosuppression and improved survivability in P. berghei-infected mice at 5 mg/kg b.w. B. pseudomallei-infected mice treated with kaempferol (10 mg/kg b.w.) showed improved survivability. Concomitantly, the described effects due to kaempferol also involved enhanced GSK3β (Ser9) phosphorylation as observed with G. procumbens. In summary, the observed anti-malarial and anti-inflammatory effects of G. procumbens involved inhibition of GSK3β and kaempferol may in part be responsible for the pharmacological effects.

Keywords: Anti-inflammation; anti-malaria; glycogen synthase kinase-3β; Gynura procumbens; kaempferol

ABSTRAK

Gynura procumbens merupakan tumbuhan ubatan yang digunakan secara tradisi untuk merawat inflamasi dan demam. Pengasaian berasas-yis menunjukkan aktiviti perencatan GSK3ß dalam ekstrak akueus G. procumbens. GSK3ß kini diketahui berperanan dalam modulasi respons inflamasi hos semasa infeksi bakteria. Kajian ini dijalankan untuk menentukan penglibatan GSK3ß dalam kesan anti-malaria dan anti-inflamasi ekstrak akueus G. procumbens. Hasil kajian menunjukkan G. procumbens merencat pertumbuhan P. falciparum 3D7. Perlakuan 250 mg/kg berat tubuh (b.t.) G. procumbens selama empat hari berturut-turut menunjukkan aktiviti kemo-penekanan yang kuat dan peningkatan kemandirian dalam mencit terinfeksi-P. berghei. Mencit terinfeksi-B. pseudomallei yang diberi perlakuan G. procumbens (50 mg/kg b.t.) menunjukkan peningkatan kemandirian. Aras TNF-a dan IFN-? dalam hepar dan serum mencit terinfeksi-B. pseudomallei dicerap berkurangan dengan perlakuan G. procumbens. Aras IL-10 didapati lebih tinggi dalam serum mencit terinfeksi yang diberi perlakuan G. procumbens. Perlakuan G. procumbens terhadap mencit terinfeksi-P. berghei dan B. pseudomallei masing-masing menyebabkan peningkatan pemfosfatan GSK3ß (Ser9) hepar. Kaempferol (salah satu sebatian/kompoun daripada G. procumbens) juga mengakibatkan perencatan pertumbuhan P. falciparum 3D7; aktiviti kemo-penekanan yang kuat dan peningkatan kemandirian mencit terinfeksi-P. berghei pada dos 5 mg/kg b.t. Mencit terinfeksi-B. pseudomallei yang diberi perlakuan kaempferol (10 mg/kg b.t.) menunjukkan peningkatan kemandirian. Pada masa yang sama, kesemua kesan kaempferol tersebut juga melibatkan peningkatan pemfosfatan GSK3ß (Ser9) seperti yang dicerap dengan G. procumbens. Kesimpulannya, kesan anti-malaria dan anti-inflamasi G. procumbens melibatkan perencatan GSK3ß; dan kaempferol mungkin menyumbang kepada kesan farmakologi tersebut.

Kata kunci: Anti-inflamasi; anti-malaria; glikogen sintase kinase-3ß; Gynura procumbens; kaempferol

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*Corresponding author; email: hasidah@ukm.edu.my