Sains Malaysiana 41(8)(2012): 969–975

Hypoglycemic Effects of Gynura procumbens Fractions on

Streptozotocin-induced Diabetic Rats involved Phosphorylation of GSK3β (Ser-9) in Liver

(Kesan Hipoglisemik Fraksi Gynura procumbens di dalam Tikus Diabetes Aruhan- Streptozotocin

Melibatkan Pemfosfatan GSK3β (Ser-9) Hepar)

Chong Ching June, Lee Hui Wen, Halimah Abdullah Sani, Noor Embi & Hasidah Mohd Sidek*

School of Biosciences and Biotechnology, Faculty of Science and Technology

Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia

Jalifah Latip

School of Chemical Sciences and Food Technology, Faculty of Science and Technology

Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia

Lee Ping Chin & Jualang Azlan Gansau

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

Diserahkan: 16 Ogos 2011 / Diterima: 15 Mac 2012

ABSTRACT

Gynura procumbens, a medicinal plant locally known as Sambung nyawa, is widely used traditionally in South East Asia as a remedy to alleviate symptoms of various ailments including diabetes mellitus. Previous investigators reported that the ethanol plant extract was hypoglycemic in streptozotocin (STZ)-induced diabetic rats and suggested the blood glucose-reducing effect could be due to G. procumbens mimicking insulin effects. Our present study aimed to reevaluate the hypoglycemic effect(s) of G. procumbens and to ascertain the involvement of glycogen synthase kinase (GSK3), a key component of insulin biosignaling in the plant activity. A cell-based assay showed that the three G. procumbens fractions tested did not exhibit anti-GSK3 activities. Oral administrations of hexane, ethyl acetate, n-butanol fractions of G. procumbens (250 mg/kg b.w.) and Glibenclamide (5 mg/kg b.w.) for 14 days in STZ-induced diabetic rats reduced blood glucose levels by 29.7%, 60.1%, 33.5% and 61.7% (p<0.05), respectively compared to diabetic control. Liver glycogen contents were elevated (p<0.05), following administration of the three fractions of G. procumbens in diabetic rats when analysed after 14 days of treatment. Western blot analysis also showed GSK3β in the liver of G. procumbens fractions-treated and Glibenclamide-treated animals were phosphorylated at Ser-9. The above findings indicated that the hypoglycemic action of G. procumbens fractions resulted in the inactivation of GSK3β in liver of diabetic rats. Since G. procumbens fractions did not exhibit GSK3 inhibitory properties, it is possible that the hypoglycemic action of the fractions observed here could be due to direct or indirect effects on upstream components of the insulin biosignaling pathway.

Keywords: GSK3; Gynura procumbens; hypoglycemic activity; streptozotocin

ABSTRAK

Gynura procumbens, sejenis tumbuhan ubatan yang lazimnya dikenali sebagai Sambung nyawa digunakan secara meluas di Asia Tenggara untuk meringankan simptom pelbagai penyakit termasuk diabetes mellitus. Kajian-kajian sebelum ini menunjukkan ekstrak etanol tumbuhan tersebut bersifat hipoglisemik terhadap tikus diabetes aruhan-streptozotocin (STZ) dan mencadangkan kesan pengurangan glukosa darah ini kemungkinannya disebabkan keupayaan G. procumbens memberikan kesan menyerupai insulin. Kajian ini bertujuan untuk menilai semula kesan hipoglisemik fraksi etanol G. procumbens serta menentukan sama ada GSK3, sebagai satu komponen utama pengisyaratan insulin, terlibat. Tiga fraksi G. procumbens yang diuji melalui pengasaian berasas-sel tidak menunjukkan aktiviti anti-GSK3. Pemberian secara oral fraksi heksana, etil asetat, n-butanol G. procumbens (250 mg/kg b.w.) dan Glibenklamida (5 mg/kg b.w.) selama 14 hari kepada tikus diabetes aruhan-STZ mengurangkan aras glukosa darah masing-masing sebanyak 29.7%, 60.1%, 33.5% dan 61.7% (p<0.05) berbanding kawalan diabetes. Kandungan glikogen hepar tikus diabetes yang diperlakukan dengan ketiga-tiga fraksi G. procumbens didapati meningkat (p<0.05) apabila dianalisis selepas 14 hari perlakuan. Analisis pemblotan western juga menunjukkan GSK3β dalam hepar tikus diabetes yang diperlakukan dengan fraksi G. procumbens dan Glibenklamida adalah dalam keadaan terfosfat pada Ser-9. Secara keseluruhannya, hasil kajian ini menunjukkan tindakan hipoglisemik fraksi G. procumbens mengakibatkan penyahaktifan GSK3β dalam hepar tikus diabetes. Oleh sebab fraksi tumbuhan ini sendiri tidak mempamerkan sifat perencatan GSK3, aktiviti hipoglisemik fraksi tersebut mungkin secara langsung atau tidak melibatkan satu atau lebih komponen huluan tapak jalan pengisyaratan insulin.

Kata kunci: Aktiviti hipoglisemik; GSK3; Gynura procumbens; streptozotocin

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*Pengarang untuk surat-menyurat; email: hasidah@ukm.my