Sains Malaysiana 43(9)(2014): 1295–1304

 

Antidiabetic Activity of Aqueous Extract of Leptospermum flavescens

in Alloxan Induced Diabetic Rats

(Aktiviti Antidiabetik Ekstrak Akues Leptospermum flavescens dalam Tikus Diinduksi Aloksan)

 

 

ASMAWATI ABD RAHIM, JAMALUDIN MOHAMAD* & ZAZALI ALIAS

 

Institute of Biological Sciences, Faculty of Science, University of Malaya

50603 Kuala Lumpur, Malaysia

 

Received: 28 December 2012/Accepted: 28 January 2014

 

ABSTRACT

Leptospermum flavescens, commonly known as ‘Gelam bukit’ has been used by the Malays as traditional plants in Malaysia for antidiabetic treatment. However, at this moment there is no scientific evidence and data available to validate such claim. In the present study, the aqueous extract of leaves and stems were studied for its antidiabetic activity. The total phenols and flavonoids were determined and correlated with antidiabetic activity. The detection of aqueous leaves extract with LCMS/MS showed the presence of flavonoids aromadendrin glucoside, kaempferol rhamnoside, quercetin rhamnoside and vindoline. The extract has significantly inhibited glycogen phosphorylase at 85% with IC50 = 0.18 mg/mL. In the alloxan induced diabetic rats showed that extract at 500 mg/kg decreased significantly fasting plasma glucose level by 61.9% (p<0.001) on the 20th day as compared to diabetic control. The treatment with Leptospermum flavescens at 500 mg/kg showed that it decreased the total cholesterol and triglycerides but restored the HDL level. The high antidiabetic activity was correlated with high total phenol at 1.57±0.01 GAE/g and total flavonoids at 1.41±0.01 mg QE/g. Thus, the high antidiabetic activity of the aqueous leaves extract attributed due to the presence of aromadendron glucoside, kaempferol rhamnoside, quercetin rhamnoside and vindoline in aqueous extract of Leptospermum flavescens.

 

Keywords: Antidiabetics; flavonoids; glycogen phosphorylase; Leptospermum flavescens; phenols

 

 

ABSTRAK

Leptospermum flavescens yang lazimnya dikenali sebagai Gelam bukit telah digunakan oleh orang Melayu dalam perubatan tradisi untuk rawatan diabetes. Walau bagaimanapun, pada masa ini tiada bukti saintifik dan data tersedia untuk mengesahkan dakwaan tersebut. Dalam kajian ini, ekstrak akues daun dan batang dikaji untuk aktiviti antidiabetiknya. Jumlah fenol dan flavonoid ditentukan dan berkorelasi dengan aktiviti antidiabetik. Pengesanan ekstrak akues daun dengan LCMS/MS menunjukan kehadiran flavonoid glikosida aromadendrin, kaempferol rhamnoside, quercetin rhamnoside dan vindoline. Ekstrak mempunyai rencatan signifikan glikogen fosforilase pada 85% dengan IC50 = 0.18 mg/mL. Di dalam tikus induksi diabetik aloksan menunjukkan ekstrak pada 500 mg/kg signifikan menurunkan paras glukosa plasma puasa sebanyak 61.9% (p<0.001) pada hari ke 20 berbanding dengan kumpulan kawalan. Perlakuan dengan Leptospermum flavescens pada 500 mg/kg menunjukkan penurunan jumlah kolesterol dan trigliserida tetapi mengekalkan paras HDL. Aktiviti antidiabetik yang tinggi berkorelasi dengan jumlah fenol pada 1.57±0.01 GAE/g dan jumlah flavonoid pada 1.41±0.01 mg QE/g. Maka, aktiviti antidiabetik yang tinggi ekstrak akues daun adalah disebabkan kehadiran glikosida aromadendron, kaempferol rhamnoside, quercetin rhamnoside dan vindoline di dalam ekstrak akues Leptospermum flavescens.

 

Kata kunci: Antidiabetik; fenol; flavonoids; glikogen fosforilase; Leptospermum flavescens

 

REFERENCES

 

Ahmed, I., Adequate, E., Cummings, E., Sharma, A.K. & Singh, J. 2004. Beneficial effects and mechanism of action of Momordica charantia juice in the treatment of streptozotocin-induced diabetes mellitus in rat. Molecular Cell Biochemistry 261: 63-70.

Asano, N. 2003. Glycosidase inhibitors: Update and perspectives on practical use. Glycobiology 13: 93R-104R.

Atta-Ur-Rhemann & Khurshid Zaman. 1989. Medicinal plants with hypoglycemic activity. Journal of Ethnopharmacology 26: 1-55.

Bailey, C.J. 1992. Biguanides and NIDDM. Diabetes Care 15: 755-772.

Barnett, D., Craig, J.G., Robinson, D.S. & Perenna Rogers, M. 1977. Effect of clofibrate on glucose tolerance in maturity onset diabetes. British Journal of Clinicallogy Pharmacology 4: 455-458.

Benwahhoud, M., Jouad, H., Eddouks, M. & Lyoussi, B. 2001. Hypoglycemic effect of Suaeda fruticosa in streptozotocin-induced diabetic rats. Journal of Ethnopharmacology 76: 35-38.

Buse, J., Hart, K. & Minasi, L. 1998. The PROTECT study: Final results of a large multicentre postmarketing study in patients with type 2 diabetes. Precose resolution of optimal titration to enhance current therapies. Clinical Therapeutic 20: 257-269.

Chakravarthy, B.K., Gupta, S., Gambir, S.S. & Gode, K.D. 1980. Pancreatic beta cell regeneration. A novel antidiabetic mechanism of Pterocarpus marsupium Roxb. Indian Journal of Pharmacology 12: 123-127.

Chattopadhyay, R.R., Banerjee, R.N., Sarkar, S.K., Ganguly, S. & Basu, T.K. 1992. Anti-inflammatory and acute toxicity studies with leaves of Vinca rosea Linn. in experimental animals. Indian Journal of Physiology Pharmacology 36: 291-292.

Chattopadhyay, R.R., Sarkar, S.K., Ganguly, S., Banerjee, R.N. & Basu, T.K. 1991. Hypoglycemic and antihyperglycemic effects of leaves of Vinca rosea Linn. Indian Journal of Physiology Pharmacology 35: 145-151.

Chattopadhyay, R.R. 1999. A comparative evaluation of some blood sugar lowering agents of plant origin. Journal of Ethanopharmacology 67: 367-372.

Chen, Y., Gong, M., Zhang, C., Song, Y. & Yu, P. 2010. Determination of aromadendrin in Euonymus alatus by HPLC. Zhongguo Zhong Yao Za Zhi 35(19): 2565-2567.

Day, C. 1998. Traditional plant treatments for diabetes mellitus: pharmaceutical foods. British Journal of Nutrition 80: 203- 208.

Del Prato, S. & Pulizzi, N. 2006. The place of sulfonylureas in the therapy for type 2 diabetes mellitus. Metabolism 55(1): S20-S27.

El Hilaly, J. & Lyoussi, B. 2002. Hypoglycemic effect of the lyophilized aqueous extract of Ajugaiva in normal and streptozotocin in diabetic rats. Journal of Ethnopharmacology 80: 109-113.

Ghosh, R.K. & Gupta, I. 1980. Effect of Vinca rosea and Ficus racemososus on huperglycemia in rats. Indian Journal Animal Health 19: 145-148.

Hyun, Y.K., Jeong, D.M., Jung, H.J., Jung, Y.J., Yokozawa, T. & Choi, J.S. 2008. Hypolipidemic effects of Sophora flavescens and its constituents in poloxamer 407-induced hyperlipidemic and cholesterol-fed rats. Biological & Pharmaceutical Bulletin 31(1): 73-78.

Ivorra, M.D., Paya, M. & Villar, A. 1989. A review of natural products and plants as potent antidiabetic drugs. Journal of Ethnopharmacology 27(3): 243-275.

Jiyin Zhou, Shiwen Zhou, Jianlin Tang, Kebin Zhang, Lixia Guang, Yongping Huang, Ying Xu, Yi Ying, Le Zhang & Dandan Li. 2009. Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. European Journal of Pharmacology 606(1-3): 262-268.

Kameswara Roa, B., Giri, R., Kesavulu, M.M. & Appa Rao, Ch. 1997. Herbal medicine: In the management of diabetis mellitus. Manphar Vaidhya Patrika 1(4): 33- 35.

Karunanayake, E.H. & Tennekoon, K.H. 1993. Search of novel hypoglycemic agents from medicinal plants. In Diabetes Mellitus and Its Complications: An update, edited by Sharma A.K. New Delhi, India: Macmillan India Ltd.

Liu, X., Dong, M., Chen, X., Jiang, M., Lv, X. & Yan, G. 2007. Antioxidant activity and phenolics of endophytic Xylaria sp. From Ginkgo biloba. Food Chemistry 105: 548-554.

Lu, H., Chen, J., Li, W.L., Ren, B.R., Wu, J.L. & Zhang, H.Q. 2009. Hypoglycemic effect of the total flavonoid fraction from Folium eriobotryae. Phytomedicine 16(10): 967-971.

Manickam, M., Ramanathan, M., Farboodinay Jahromi, M.A., Chansouria, J.P.N. & Ray, A.B. 1997. Antihyperglycemic activity of phenolics from Pterocarpus marsupium. Journal of Natural Products 60: 609-610.

Mankil, J., Moonsoo, P., Hyun, C.L., Yoon-Ho, K., Eun, S.K. & Sang, K.K. 2006. Antidiabetic agents from medicinal plants. Current Medicine Chemistry 13: 1203-1218.

Martin, W.H., Hoover, D.J., Armento, S.J., Stock, I.A., McPherson, R.K., Danley, D.E., Stevenson, R.W., Barrett, E.J. & Treadway, J.L. 1998. Discovery of a human glycogen phosphorylase inhibitor that lowers blood glucose in vivo. Proceeding National. Academy of Science U.S.A 95: 1776e1781.

Min-Jia Tan, Ji-Ming Ye, Nigel Turner, Cordula Hohnen- Behrens, Chang-Qiang Ke, Chun-Ping Tang, Tong Chen, Hans-Christoph Weiss, Ernst-Rudolf Gesing, Alex Rowland, David E. James & Yang Ye. 2008. Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK pathway. Chemistry & Biology 15(3): 263-273.

Moller, D.E. 2001. New drug targets for type 2 diabetes and the metabolic syndrome. Nature 414: 821-827.

Obatomi, D.K., Bikomo, E.O. & Temple, V.J. 1994. Anti-diabetic properties of the African mistletoe in streptozotocin-induced diabetic rats. Journal of Ethnopharmacol 43(1): 13-17.

Oikonomakos, N.G. 2002. Glycogen phosphorylase as a molecular target for type 2 diabetes therapy. Current Protein and Peptide Science 3: 561-586.

Oliver-Bener, B. 1986. Medicinal Plants in Tropical West Africa. London: Cambridge University Press. pp. 245-267.

Patel, S.S., Shah, R.S. & Goyal, R.K. 2009. Antihyperglycemic, antihyperlipidemic and antioxidant effects of Dihar, a polyherbal ayurvedic formulation in streptozotocin induced diabetic rats. Indian Journal of Experimental Biology 47(7): 564-570.

Park, K.W., Lee, J.E. & Park, K.M. 2009. Diets containing Sophora japonica L. prevent weight gain in high-fat diet-induced obese mice. Nutrition Research 29(11): 819-824.

Prakash R. Itankar, Sarika J. Lokhande, Prashant R. Verma, Sumit K. Arora, Rajesh A. Sahu & Arun T. Patil. 2011. Antidiabetic potential of unripe Carissa carandas Linn. fruit extract. Journal of Ethnopharmacology 135(2): 430-433.

Riley, M. 1994. Maori Healing and Herbal. New Zealand Ethnobotanical Sourcebook. Paraparaumu, New Zealand: Viking Sevenseas.

Rodriquez, P., Gonzalez-Mujica, F., Bermudez, J. & Hasegawa, M. 2010. Inhibition of glucose intestinal absorption by kaemferol 3-O-alpha-rhamnoside purified from Bauhinia megalandra leaves. Fitoterapia 81(8): 1220-1223.

Ross, S.A., Gulve, E.A. & Wang, M. 2004. Chemistry and biochemistry of Type 2 diabetes. ChemInform 35(21): no. doi: 10.1002/chin.200421298.

Salahuddin, M. & Jalalpure, S.S. 2010. Antidiabetic activity of aqueous fruit extract of Cucumis trigonus Roxb. in streptozotocin-induced-diabetic rats. Journal of Ethnopharmacology 127(2): 565-567.

Sancheti, S., Bafna, M. & Seo, S.Y. 2010. Antihyperglycemic, antihyperlipidemic, and antioxidant effects of Chaenomeles sinensis fruit extract in streptozotocin-induced diabetic rats. European Food Research and Technology 231(3): 415-421.

Shankar, M.B., Parikh, J.R., Geetha, M., Mehta, R.S. & Saluja, A.K. 2007. Anti-diabetic activity of novel androstane derivatives from Syzygium cuminii Linn. Journal of Natural Remedies 7:214-219.

Shirwaikar, A., Rajendran, K. & Barik, R. 2006. Effect of aqueous bark extract of Garuga pinnata Roxb. in streptozotocin-nicotinamide induced type-II diabetes mellitus. Journal of Ethnopharmacology 107(2): 285-290.

Spanos, G.A. & Wrosltad, R.E. 1990. Influence of processing and storage on the phenolic composition of Thompson seedless grape juice. Journal of Agricultural & Food Chemistry 38: 1565-1571.

Wei Yun Zhang, Jung-Jin Lee, In-Su Kim, Yohan Kim & Chang-Seon Myung. 2011. Stimulation of glucose uptake and improvement of insulin resistance by aromadendrin. Pharmacology 88: 266-274.

Yun, H-Y., Park, H-C., Kang, W. & Kwon, K-I. 2006. Pharmacokinetic and harmacodynamic modelling of the effects of glimepiride on insulin secretion and glucose lowering in healthy humans. Journal of Clinical Pharmacy and Therapeutics 31: 469-476.

Zhang, J.H. & Cheng, Y.S. 2009. Studies on the lowering blood sugar substances from agrimony. Zhong Yao Cai 32(10): 1537-1539.

Zimmet, P., Alberti, K.G. & Shaw, J. 2001. Global and societal implications of the diabetes epidemic. Nature 414(6865): 782-787.

 

 

*Corresponding author; email: jamal@um.edu.my

 

 

previous