Sains Malaysiana 47(10)(2018): 2421–2428

http://dx.doi.org/10.17576/jsm-2018-4710-18

 

Antihypertensive Effect of Piper sarmentosum in L- NAME-Induced Hypertensive Rats

(Kesan Antihipertensi Piper sarmentosum pada Tikus Hipertensi Aruhan L-NAME)

 

NIK ALOESNISA NIK MOHD ALWI1,3, ZAITON ZAKARIA1, AMINUDDIN ABDUL HAMID KARIM2, NOR ANITA MEGAT MOHD NORDIN1 & AZIZAH UGUSMAN1*

 

1Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Federal Territory, Malaysia

 

2Physiology Unit, Universiti Pertahanan Nasional Malaysia, 57000 Kuala Lumpur, Federal Territory, Malaysia

 

3Basic Science and Oral Biology Unit, School of Dental Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan Darul Naim, Malaysia

 

Received: 25 March 2018/Accepted: 6 June 2018

 

ABSTRACT

Hypertension is one of the risk factors for cardiovascular diseases and has been associated with about 13% of global deaths worldwide. Oxidative stress and reduced nitric oxide (NO) bioavailability contribute to the development of endothelial dysfunction and subsequently hypertension. Nɷ-nitro-L-arginine methyl ester hydrochloride (L-NAME) inhibits NO synthesis; leading to hypertension. Piper sarmentosum (PS) is an herb with antioxidant, antiatherosclerosis and antiinflammation properties. PS also stimulated NO production by endothelial cells. The aim of this study was to determine the effects of aqueous extract of Piper sarmentosum (AEPS) on blood pressure, oxidative stress and the level of nitric oxide in L-NAME-induced hypertensive rats. Hypertension was induced by oral administration of L-NAME (100 mg/L) in drinking water for four weeks. The rats were concurrently treated with AEPS by oral gavage in serial doses (125, 250 and 500 mg/kg/day). Blood pressure was measured using non-invasive tail-cuff method at baseline and fortnightly thereafter. Serum level of NO and an oxidative stress marker, malondialdehyde (MDA) were measured at baseline and at the end of treatment. The results showed that treatment with three different doses of AEPS successfully reduced systolic blood pressure (p<0.001), diastolic blood pressure (p<0.05) and mean arterial pressure (p<0.05) in L-NAME-induced hypertensive rats. Treatment with AEPS also reduced MDA level (p<0.001) and increased serum NO (p<0.001) in L-NAME-induced hypertensive rats. The findings showed that AEPS decreased blood pressure by protecting against oxidative stress and increasing NO in L-NAME-induced hypertensive rats.

 

Keywords: Hypertension; nitric oxide; Nɷ-nitro-L-arginine methyl ester hydrochloride; oxidative stress; Piper sarmentosum

 

ABSTRAK

Hipertensi merupakan salah satu faktor risiko penyakit kardiovaskular dan ia dikaitkan dengan kira-kira 13% kematian di seluruh dunia. Stres oksidatif dan pengurangan ketersediaan biologi nitrik oksida (NO) menyumbang kepada terjadinya disfungsi endotelium yang seterusnya menyebabkan hipertensi. Nɷ-nitro-L-arginina metil ester hidroklorida (L-NAME) merencat sintesis NO dan menyebabkan hipertensi. Piper sarmentosum (PS) adalah herba yang mempunyai sifat antioksidan, antiaterosklerosis dan antiinflamasi. PS juga merangsang pengeluaran NO oleh sel endotelium. Tujuan kajian ini adalah untuk menentukan kesan ekstrak akueus Piper sarmentosum (AEPS) terhadap tekanan darah, stres oksidatif dan aras nitrik oksida dalam tikus hipertensi aruhan L-NAME. Hipertensi diaruh dengan pemberian L-NAME (100 mg/L) secara oral di dalam air minuman selama empat minggu. Dalam masa yang sama, rawatan tikus dengan AEPS turut diberi serentak melalui gavaj oral dalam dos bersiri (125, 250 dan 500 mg/kg/hari). Tekanan darah diukur menggunakan kaedah kuf ekor tidak invasif sebelum rawatan dimulakan dan setiap dua minggu selepas itu. Aras serum NO dan penanda stres oksidatif, malondialdehida (MDA) diukur sebelum uji kaji dimulakan dan selepas rawatan tamat. Keputusan menunjukkan rawatan dengan tiga dos AEPS yang berbeza berjaya menurunkan tekanan darah sistolik (p<0.001), tekanan darah diastolik (p<0.05) dan tekanan arteri purata (p<0.05) dalam tikus hipertensi aruhan L-NAME. AEPS juga menurunkan aras MDA (p<0.01) dan meningkatkan aras NO (p<0.001) dalam serum tikus hipertensi aruhan L-NAME. Keputusan yang diperoleh menunjukkan bahawa AEPS berupaya menurunkan tekanan darah dengan mengurangkan stres oksidatif dan meningkatkan aras NO pada tikus hipertensi aruhan L-NAME.

 

Kata kunci: Hipertensi; nitrik oksida; Nɷ-nitro-L-arginina metil ester hidroklorida; Piper sarmentosum; stres oksidatif

REFERENCES

Amran, A.A., Zakaria, Z., Othman, F., Das, S., Raj, S. & Nordin, N.A.M. 2010. Aqueous extract of Piper sarmentosum decreases atherosclerotic lesions in high cholesterolemic experimental rabbits. Lipids in Health and Disease 9: 44.

Ariffin, S.H.Z., Omar, W.H.H.W., Ariffin, Z.Z., Safian, M.F., Senafi, S. & Wahab, R.M.A. 2009. Intrinsic anticarcinogenic effects of Piper sarmentosum ethanolic extract on a human hepatoma cell line. Cancer Cell International 9: 6.

Arora, S., Das, N. & Srivastava, K. 2009. Nitric oxide and eNOS gene in essential hypertension. International Journal of Collaborative Research on Internal Medicine and Public Health (IJCRIMPH) 1: 56-71.

Azlina, A.A., Farihah, H., Qodriyah, H. & Nur, A. 2009. Effects of Piper sarmentosum water extract on 11-β hydroxysteroid dehydrogenase Type 1 bioactivity in ovariectomy-induced obese rats. IJP-International Journal of Pharmacology 5: 362-369.

Azlina, M., Qodriyah, H., Hamizah, A. & Kamisah, Y. 2014. Effects of methanolic extract of Piper sarmentosum on paracetamol-induced hepatic oxidative injury in rats. Sains Malaysiana 43(3): 415-421.

Baradaran, A., Nasri, H. & Rafieian-Kopaei, M. 2014. Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences 19(4): 358-367.

Bernátová, I., Pechánová, O., Babál, P., Kyselá, S., Stvrtina, S. & Andriantsitohaina, R. 2002. Wine polyphenols improve cardiovascular remodeling and vascular function in NO-deficient hypertension.  American Journal of Physiology- Heart and Circulatory Physiology 282: H942-H948.

Borges, A., Piassăo, J., Paula, M., Sepp, S., Bez, C., Hepp, L., Valduga, A., Pereira, A. & Cansian, R. 2018. Characterization of oxidative stress biomarkers in a freshwater anomuran crab. Brazilian Journal of Biology 78: 61-67.

Chen, J., Zeng, L., Xia, T., Li, S., Yan, T., Wu, S., Qiu, G. & Liu, Z. 2015. Toward a biomarker of oxidative stress: A fluorescent probe for exogenous and endogenous malondialdehyde in living cells. Analytical Chemistry 87: 8052-8056.

Davidge, S.T., de Groot, C.J. & Taylor, R.N. 2015. Endothelial cell dysfunction. Chesley’s Hypertensive Disorders in Pregnancy (4th ed.) Elsevier. pp. 181-207.

Dohi, Y., Thiel, M.A., Bühler, F. & Lüscher, T. 1990. Activation of endothelial L-arginine pathway in resistance arteries. Effect of age and hypertension. Hypertension 16: 170-179.

Drummond, G.R. & Sobey, C.G. 2014. Endothelial NADPH oxidases: Which NOX to target in vascular disease? Trends in Endocrinology & Metabolism 25: 452-463.

García-Redondo, A.B., Aguado, A., Briones, A.M. & Salaices, M. 2016. NADPH oxidases and vascular remodeling in cardiovascular diseases. Pharmacological Research 114: 110-120.

Hafizah, A.H., Zaiton, Z., Zulkhairi, A., Ilham, A.M., Anita, M.M.N.N. & Zaleha, A.M. 2010. Piper sarmentosum as an antioxidant on oxidative stress in human umbilical vein endothelial cells induced by hydrogen peroxide. Journal of Zhejiang University SCIENCE B 11: 357-365.

Hogg, N., Zielonka, J. & Kalyanaraman, B. 2017. Detection of nitric oxide and peroxynitrite in biological systems: A state-of-the-art review. Nitric Oxide. 3rd ed. Elsevier. pp. 23-44.

Hussain, K., Ismail, Z., Sadikun, A., Ibrahim, P. & Malik, A. 2015. In vitro antiangiogenesis activity of standardized extracts of Piper sarmentosum roxb. Jurnal Riset Kimia 1: 146.

Kumar, K.V. & Das, U. 1993. Are free radicals involved in the pathobiology of human essential hypertension? Free Radical Research 19: 59-66.

Mendis, S. 2014. Global Status Report on Noncommunicable Diseases 2014. World Health Organization.

Mohamad Asri, S.F., Mohd Ramli, E.S., Soelaiman, I.N., Mat Noh, M.A., Abdul Rashid, A.H. & Suhaimi, F. 2016. Piper sarmentosum effects on 11β-Hydroxysteroid dehydrogenase type 1 enzyme in serum and bone in rat model of glucocorticoid-induced osteoporosis. Molecules 21(11): 1523.

Mohd Zainudin, M., Zakaria, Z., Nordin, M.M., Anita, N. & Othman, F. 2013. Does oral ingestion of Piper sarmentosum cause toxicity in experimental animals? Evidence-Based Complementary and Alternative Medicine 2013: 705950.

Panth, N., Paudel, K.R. & Parajuli, K. 2016. Reactive oxygen species: A key hallmark of cardiovascular disease. Advances in Medicine 2016: 9152732.

Panza, J.A., Quyyumi, A.A., Brush Jr, J.E. & Epstein, S.E. 1990. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. New England Journal of Medicine 323: 22-27.

Park, K.H. & Park, W.J. 2015. Endothelial dysfunction: Clinical implications in cardiovascular disease and therapeutic approaches. Journal of Korean Medical Science 30: 1213- 1225.

Pessoa, L.M.B., Lima, M.G.d.M., Carneiro, F.T., Zanani, N.S., Scalon, M.C., Silva, T.F., Lima, M.A., Abrahim, M.A. & Paludo, G.R. 2017. Refractometry as an alternative to the biuret method for measuring total serum proteins in Podocnemis expansa (Podocnemididae) and Phrynops geoffroanus (Chelidae). Acta Amazonica 47: 83-86.

Raja, B. 2010. Antihypertensive and antioxidant potential of borneol-a natural terpene in L-NAME-induced hypertensive rats. International Journal of Pharmaceutical & Biological Archive 1: 271-279.

Ridtitid, W., Ruangsang, P., Reanmongkol, W. & Wongnawa, M. 2007. Studies of the anti-inflammatory and antipyretic activities of the methanolic extract of Piper sarmentosum Roxb. leaves in rats. Songklanakarin Journal of Science & Technology 29: 1519-1526.

Rincon, J., Correia, D., Arcaya, J., Finol, E., Fernández, A., Pérez, M., Yaguas, K., Talavera, E., Chávez, M. & Summer, R. 2015. Role of angiotensin II type 1 receptor on renal NAD (P) H oxidase, oxidative stress and inflammation in nitric oxide inhibition induced-hypertension. Life Sciences 124: 81-90.

Rodrigo, R., Brito, R. & González, J. 2016. Oxidative stress and essential hypertension. In Update on Essential Hypertension. InTech.

Si, H. & Liu, D. 2008. Genistein, a soy phytoestrogen, upregulates the expression of human endothelial nitric oxide synthase and lowers blood pressure in spontaneously hypertensive rats. The Journal of Nutrition 138: 297-304.

Sinha, N. & Kumar Dabla, P. 2015. Oxidative stress and antioxidants in hypertension - A current review. Current Hypertension Reviews 11: 132-142.

Tsai, I.C., Pan, Z.C., Cheng, H.P., Liu, C.H., Lin, B.T. & Jiang, M.J. 2016. Reactive oxygen species derived from NADPH oxidase 1 and mitochondria mediate angiotensin II-induced smooth muscle cell senescence. Journal of Molecular and Cellular Cardiology 98: 18-27.

Ugusman, A., Zakaria, Z., Chua, K.H., Nordin, M.M., Anita, N. & Abdullah Mahdy, Z. 2014. Role of rutin on nitric oxide synthesis in human umbilical vein endothelial cells. The Scientific World Journal 2014: 169370.

Ugusman, A., Zakaria, Z., Hui, C.K., Nordin, N.A.M.M. & Mahdy, Z.A. 2012. Flavonoids of Piper sarmentosum and its cytoprotective effects against oxidative stress. EXCLI Journal 11: 705.

Ugusman, A., Zakaria, Z., Hui, C.K. & Nordin, N.A.M.M. 2010. Piper sarmentosum increases nitric oxide production in oxidative stress: A study on human umbilical vein endothelial cells. Clinics 65: 709-714.

Vanhoutte, P., Shimokawa, H., Feletou, M. & Tang, E. 2017. Endothelial dysfunction and vascular disease - a 30th anniversary update. Acta Physiologica 219: 22-96.

Wheal, A., Bennett, T., Randall, M. & Gardiner, S. 2007. Effects of chronic nitric oxide synthase inhibition on the cardiovascular responses to cannabinoids in vivo and in vitro. British Journal of Pharmacology 150: 662-671.

WHO. 2012. World Health Statistic 2012.

Yang, H.Y., Yang, S.C., Chen, S.T. & Chen, J.R. 2008. Soy protein hydrolysate ameliorates cardiovascular remodeling in rats with L-NAME-induced hypertension. The Journal of Nutritional Biochemistry 19: 833-839.

Zainudin, M.M., Zakaria, Z. & Nordin, N.A.M.M. 2015. The use of Piper sarmentosum leaves aqueous extract (Kadukmy™) as antihypertensive agent in spontaneous hypertensive rats. BMC Complementary and Alternative Medicine 15: 54.

Zakaria, Z., Patahuddin, H., Mohamad, A., Israf, D. & Sulaiman, M. 2010. In vivo anti-nociceptive and anti-inflammatory activities of the aqueous extract of the leaves of Piper sarmentosum. Journal of Ethnopharmacology 128: 42-48.

 

 

*Corresponding author; email: dr.azizah@ppukm.ukm.edu.my

 

 

 

 

 

 

 

previous