Sains Malaysiana 41(12)(2012): 1535–1542

 

In vitro and in vivo Anti-plasmodial Activities of Gynura procumbens

(Kajian in vitro dan in vivo Aktiviti Anti-plasmodium Gynura procumbens)

 

Visalini Vejanan1, Jalifah Latip2, Lee Ping Chin3, Noor Embi1 & Hasidah Mohd Sidek1,*

 

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

Universiti Kebangsaan Malaysia, 43600 UKM  Bangi

Selangor Darul Ehsan, Malaysia

 

3School of Science and Technology, Universiti Malaysia Sabah,

88999 Kota Kinabalu, Sabah, Malaysia

 

2School of Chemical Sciences and Food Technology, Faculty of Science and Technology

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

 

Diserahkan: 13 Jun 2012 / Diterima: 6 Ogos 2012

 

ABSTRACT

Gynura procumbens, locally known in Malaysia as Sambung Nyawa is a medicinal plant belonging to the Asteraceae (Compositae) family. G. procumbens have been traditionally used by the local and indigenous populations to treat an array of ailments ranging from skin conditions and fever to kidney disease, inflammation and diabetes. In the present investigation, aqueous and ethanol extracts of G. procumbens were evaluated for anti-plasmodial activities in vitro and in vivo. Survival of two chloroquine-sensitive strains of malarial parasites; rodent Plasmodium berghei NK65 and human Plasmodium falciparum 3D7 was determined following incubations in vitro with extracts. Based on parasite lactate dehydrogenase (pLDH) assay, both extracts were shown to inhibit parasite proliferation to varying degrees. The aqueous extract was more potent than the ethanol extract at suppressing growth of both parasites in vitro; each displaying IC50 values of 12.40 ± 6.02 and 14.38 ± 7.53 μg/mL towards P. berghei NK65; and 25.69 ± 4.34 and 42.23 ± 7.19 μg/mL towards P. falciparum 3D7, respectively. The aqueous extract was found to be selective for P. falciparum (Selectivity Index 64.30). Four-day suppressive tests in ICR mice showed dose-dependent chemo-suppressive activities of both plant extracts tested towards P. berghei NK65. Daily intra-peritoneal injections of the aqueous extract of G. procumbens at 25, 50 or 100 mg/kg for four consecutive days showed chemo-suppression of 50.42 ± 3.17, 65.95 ± 5.48 and 81.92 ± 3.07%, respectively. At the same dosages, the ethanol plant extract resulted in 44.97 ± 3.44, 55.21 ± 3.87 and 64.44 ± 4.05% chemo-suppression respectively. At 250 mg/kg/day, only the aqueous plant extract gave >90% chemo-suppression (93.06 ± 5.46%). Treatment of P. berghei-infected mice with extracts improved the median survival time compared to non-treated infected mice. This represents the first report showing anti-plasmodial activity of G. procumbens.

 

Keywords: Anti-plasmodial; Asteraceae; Gynura procumbens; in vitro; in vivo

 

ABSTRAK

Gynura procumbens, yang lebih dikenali di Malaysia sebagai pokok Sambung Nyawa, merupakan tumbuhan ubatan daripada famili Asteraceae (Compositae). G. procumbens digunakan secara tradisional oleh penduduk tempatan termasuk Orang Asli untuk merawat jurang penyakit yang luas iaitu daripada penyakit kulit dan demam ke penyakit ginjal, inflamasi dan diabetes. Dalam kajian ini, ekstrak akueus dan etanol G. procumbens dinilai untuk aktiviti anti-plasmodium secara in vitro dan in vivo. Kemandirian dua strain parasit malaria sensitif-klorokuin iaitu strain roden Plasmodium berghei NK65 dan strain manusia Plasmodium falciparum 3D7 ditentukan selepas eraman in vitro bersama ekstrak. Berdasarkan pengasaian laktat dehidrogenase plasmodium (pLDH), kedua-dua ekstrak didapati merencat proliferasi parasit dengan perkadaran berbeza. Ekstrak akueus mempamerkan potensi perencatan parasitemia in vitro lebih baik berbanding dengan ekstrak etanol; setiap satu mempamerkan nilai IC50 12.40 ± 6.02 dan 14.38 ± 7.53 μg/mL terhadap P. berghei NK65; dan 25.69 ± 4.34 dan 42.23 ± 7.19 μg/mL terhadap P. falciparum 3D7. Ekstrak akueus didapati bersifat memilih terhadap P. falciparum (Indeks Pemilihan 64.30). Ujian kemo-penekanan empat hari dalam mencit ICR menunjukkan aktiviti kemo-penekanan terhadap P. berghei NK65 yang berkadaran dos bagi kedua-dua ekstrak tumbuhan yang diuji. Penyuntikan ekstrak akueus G. procumbens secara intra-peritonium selama empat hari berturut-turut ke atas mencit terinfeksi-P. berghei NK65 pada dos 25, 50 dan 100 mg/kg/hari masing-masing menunjukkan kemo-penekanan 50.42 ± 3.17, 65.95 ± 5.48 dan 81.92 ± 3.07%. Pada dos yang sama, ekstrak etanol masing-masing menyebabkan kemo-penekanan 44.97 ± 3.44, 55.21 ± 3.87 dan 64.44 ± 4.05%. Pada dos 250 mg/kg/hari, hanya ekstrak akueus memberi kemo-penekanan >90% (93.06 ± 5.46%). Perlakuan ekstrak akueus kepada mencit terinfeksi-P. berghei juga mampu meningkatkan median tempoh kemandirian mencit berbanding mencit terinfeksi tanpa perlakuan ekstrak. Penemuan ini merupakan laporan pertama mengenai aktiviti anti-plasmodium G. procumbens.

 

Kata kunci: Anti-plasmodium; Asteraceae; Gynura procumbens; in vivo; in vitro

RUJUKAN

Akowuah, G.A., Amirin, S., Mariam, A. & Aminah, I. 2001. Blood sugar lowering activity of Gynura procumbens leaf extracts. Journal of Tropical Medicinal Plants 2: 5-10.

Akowuah, G.A., Sadikun, A. & Mariam, A. 2002. Flavonoid identification and hypoglycaemic studies of butanol fraction from Gynura procumbens. Pharmaceutical Biology 40: 405-410.

Becker, J.V., Merwe, M.M., Brummelen, A.C., Pillay, P., Crampton, B.G., Mmutlane, E.M., Parkinson, C., Heerden, F.R., Crouch, N.R., Smith, P. J., Mancama, D.T. & Maharaj, V. J. 2011. In vitro anti-plasmodial activity of Dicoma anomala subsp. gerrardii (Asteraceae): identification of its main active constituent, structure-activity relationship studies and gene expression profiling. Malaria Journal 10(295): 1-11.

Bhore, S.J., Nithya, R. & Loh, C.Y. 2010. Screening of endophytic bacteria isolated from leaves of Sambung nyawa [Gynura procumbens (Lour.) Merr.] for cytokinin-like compounds. Bioinformation 5(5): 191-197.

Chen, P., Gu, Z., Liu, W. & Yan, Z. 2007. Glycogen synthase kinase 3 regulates N-methyl-D-aspartate receptor channel trafficking and function in cortical neurons. Molecular Pharmacology 72: 40-51.

Choi, E.M. 2010. Kaempferol protects MC3T3-E1 cells through antioxidant effect and regulation of mitochondrial function. Food Chemistry Toxicology 49(8): 1800-1805.

Chong, C.J., Lee, H.W., Halimah, A.S., Jalifah, L., Jualang, A.G., Lee, P.C., Embi, N. & Hasidah, M.S. 2012. Hypoglycemic effects of Gynura procumbens fractions on streptozotocin-induced diabetic rats involved phosphorylation of gsk3 β (ser-9) in liver. Sains Malaysiana 41(8): 969-975.

Dikasso, D., Makonnen, E., Debella, A., Abebe, D., Urga, K., Makonnen, W., Melaku, D., Assefa, A. & Makonnen, Y. 2006. In vivo anti-malarial activity of hydroalcoholic extracts from Asparagus africanus Lam. In: Mice infected with Plasmodium berghei. Ethiopian Journal of Health Development 20(2): 112-118.

Elufioye, T.O. & Agbedahunsi, J.M. 2004. Antimalarial activities of Tithonia diversifolia (Asteraceae) and Crossopteryx febrifuga (Rubiaceae) on mice in vivo. Journal of Ethnopharmacology 93: 167-171.

Embi, N., Rylatt, D.B. & Cohen, P. 1980. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMPdependent protein kinase and phosphorylase kinase. European Journal of Biochemistry 107: 519-527.

Gathirwa, J.W., Rukunga, G.M., Njagi, E.N.M., Omar, S.A., Guantai, A N., Muthaura, C.N., Mwitari, P.G., Kimani, C.W., Kirira, P.G., Tolo, F.M., Ndunda, T.N. & Ndiege, I.O. 2007. In vitro anti-plasmodial and in vivo anti-malarial activity of some plants traditionally used for the treatment of malaria by the Meru Community, Journal Nature Medicine 61: 261-268.

Hilou, A., Nacoulma, O.G. & Guiguemde, T.R. 2006. In vivo antimalarial activities of extracts from Amaranthusspinosus L. and Boerhaaviaerecta L. in mice. Journal of Ethnopharmacology 103: 236-240.

Hout, S., Chea, A., Bun, S.S., Elias, R., Gasquet, M., Timon-David, P., Balansard, G. & Azas, N. 2006. Screening of selected indigenous plants of Cambodia for antiplasmodial activity. Journal of Ethnopharmacology 107: 12-18.

Iskander, M.N., Song, Y., Coupar, I.M. & Jiratchariyakul, W. 2002. Antiinflammatory screening of the medicinal plant Gynura procumbens. Plant Foods for Human Nutrition 57: 233-244.

Jiratchariyakul, W., Jarikasem, S., Siritantikorn, S., Somanabandhu, A. & Frahm, W. 2000. Antiherpes Simplex Viral Compounds from Gynura procumbens Merr. Mahidol University Annual Research Abstracts, 28, Abstract No. 498.

Lee, K.M., Lee, D.E., Seo, S.K., Hwang, M.K., Heo, Y.S., Lee, K.W. & Lee, H.J. 2010. Phosphatidylinositol 3-kinase, a novel target molecule for the inhibitory effects of kaempferol on neoplastic cell transformation. Carcinogenesis 31(8): 1338-1343.

Kayano, A.C.A., Lopes, S.C., Bueno, F.C., Cabral, E.C., Souza-Neiras, W. C., Yamauchi, L. M., Foglio, M. A., Eberlin, M. N., Mello, J. C. P. & Costa, F. T. 2011. In vitro and in vivo assessment of the antimalarial activity of Caesalpinia pluviosa. Malaria Journal 10 (112): 1-11.

Kaur, K., Jain, M., Kaur, T. & Jain, R. 2009. Review: Antimalarials from nature. Bioorganic & Medicinal Chemistry 17: 3229-3256.

Lehane, A.M. & Saliba, K.J. 2008. Common dietary flavonoids inhibit the growth of the intraerythrocytic malaria parasite. BioMed Central Research Notes 1: 26.

Lusakibanza, M., Mesia, G., Tona, G., Karemere, S., Lukuka, A., Tits, M., Angenot, L. & Frédérich, M. 2010. In vitro and in vivo antimalarial and cytotoxic activity of five plants used in congolese traditional medicine. Journal of Ethnopharmacology 129: 398-402.

Nkhoma, S., Molyneux, M. & Ward, S. 2007. In vitro antimalarial susceptibility profile and prcrt/Pfmdr-1 genotypes of Plasmodium falciparum field isolates from Malawi. American Journal Tropical Medicine Hygiene 76(6): 1107-1112.

Noedl, H. 2002. Nonlinear evaluation of malaria drug sensitivity data (HN-NonLin V1.1). Armed Forces Research Institute for Medical Sciences, Bangkok, Thailand: [http://www.meduniwien.ac.at/user/harald.noedl/malaria/download.html].

Nurul Aiezzah, Z., Embi, N. & Hasidah, M.S. 2010. Suppression of Plasmodium berghei parasitemia by LiCl in an animal infection model. Tropical Biomedicine 27(3): 624-631.

Perry, L.M. 1980. Medicinal Plants of East and Southeast Asia: Attributed Properties and Uses. Boston: The MIT Press.

Peters, W. & Robinson, B.L. 1992. The chemotherapy of rodent malaria XLVII. Studies on puronaridine and other manich base antimalaria. Annals of Tropical Medicine and Parasitology 86: 455-465.

Ramazani, A., Zakeri, S., Sardari, S., Khodakarim, N. & Djadidt, N.D. 2010. In vitro and in vivo anti-malarial activity of Boerhavia elegans and Solanum surattense. Malaria Journal 9(124): 1-8.

Tamez, P.A., Lantvit, D., Lim, E. & Pezzuto, J.M. 2005. Chemosensitizing action of cepharanthine against drug-resistant human malaria, Plasmodium falciparum. Journal of Ethnopharmacology 98: 137-142.

Trager, W. & Jensen, J.B. 1976. Human malaria parasites in continuous culture. Science 193: 673-675.

Wang, H., Brown, J. & Martin, H. 2011. Glycogen synthase kinase 3: A point of convergence for the host inflammatory response. Cytokine 53(2): 130-140.

Yoo, J.K., Kwon, H., Khil, L.Y., Zhang, L., Jun, H. S. & Yoon, J.W. 2005. IL-18 induces monocyte chemotactic protein-1 production in macrophages through the phosphatidylinositol 3-kinase/Akt and MEK/ERK1/2 pathways. Journal of Immunology 175 (12): 8280-8286.

Zhang, X.F. & Tan, B.K. 2000. Effects of an ethanolic extract of Gynura procumbens on serum glucose, cholesterol and triglyceride levels in normal and streptozotocin-induced diabetic rats. Singapore Medical Journal 41: 9-13.

Zurina, H., Yam, F., Ahmad, M. & Yusof, A.P.M. 2010. Antidiabetic properties and mechanism of action of Gynura procumbens Water Extract in Streptozotocin-Induced Diabetic Rats. Molecules 15: 2008-2023.

 

 

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

 

 

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