Sains Malaysiana 51(3)(2022): 847-858

http://doi.org/10.17576/jsm-2022-5103-18

 

Oral Administration of Garcinia dulcis Flower Extract Lowers Arterial Blood Pressure

of 2-kidneys-1-clip Renovascular Hypertensive Rat

(Pemberian Oral Ekstrak Bunga Garcinia dulcis Menurunkan Tekanan Darah Arteri daripada 2-buah pinggang-1-klip Tikus Hipertensi Renovaskular)

 

NATTAYA THONGSEPEE1,2,*, WILAWAN MAHABUSARAKAM3, SOPHAPUN EKARATTANAWONG1, UMARAT SRISAWAT1, PONGSAKORN MARTVISET1,2, NOPPADON SUTTIRAK4 & SIRIPHUN HIRANYACHATTADA5

 

1Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathum Thani, 12120, Thailand

  2Thammasat University Research Unit in Nutraceuticals and Food Safety, Thammasat University, Pathum Thani, 12120, Thailand

3Division of Physical Science, Faculty of Science, Prince of Songkla University, Songkhla, 90110, Thailand

4Laboratory Animal Center, Thammasat University, Pathum Thani, 12120, Thailand

5School of Pharmacy, Walailak University, Nakhon Si Thammarat, 80160, Thailand

 

Diserahkan: 4 November 2020/Diterima: 12 Ogos 2021

 

Abstract

The hexane insoluble fraction of the Garcinia dulcis (GD) flower extract comprises mainly camboginol and morelloflavone which possess potent in vivo and in vitro antioxidant properties. This study aimed to evaluate the effects of 4-week oral administration of GD flower extract on the arterial blood pressure (ABP) and the excretory function of the kidney in the 2-kidneys-1-clip (2K1C) renovascular hypertensive rats (total=12) compared to sham operated (SO) normotensive Wistar rats (total=12). Four weeks after hypertensive-induced surgery, either 50 mg/kg BW GD flower extract or vehicle was orally administered to the 2K1C or SO groups (n=6/group) daily for four weeks. ABP and the renal excretory function were studied in anesthetized rats, and expression of endothelial nitric oxide synthase (eNOS) mRNA in the isolated thoracic aorta were measured. In the 2K1C rats, GD flower extract significantly decreased ABP while increased significantly eNOS mRNA levels. GD flower extract did not exert a diuretic effect in either SO and 2K1C rats since there was no change in observed urine excretion, but it did tend to attenuated the renal tubular damage caused by renovascular hypertension. GD flower extract was anti-hypertensive in this model of renovascular hypertension and problably acts via the endothelial nitric oxide signaling pathway.

 

Keywords: Anti-hypertension; camboginol; Garcinia dulcis; morelloflavone; renovascular hypertension

 

ABSTRAK

Pecahan tidak larut heksana daripada ekstrak bunga Garcinia dulcis (GD) mengandungi kamboginol dan moreloflavon yang mempunyai sifat antioksidan in vivo dan in vitro yang kuat. Kajian ini bertujuan untuk menilai kesan pemberian secara oral ekstrak bunga GD selama 4 minggu pada tekanan darah arteri (ABP) dan fungsi perkumuhan buah pinggang pada tikus hipertensi renovaskular 2-buah pinggang-1-klip (2K1C) (jumlah= 12) berbanding tikus Wistar normotensif kendalian palsu (SO) (jumlah=12). Empat minggu selepas pembedahan akibat hipertensi, sama ada 50 mg/kg BW ekstrak bunga GD atau wahana diberikan secara oral kepada kumpulan 2K1C atau SO (n=6/kumpulan) setiap hari selama empat minggu. ABP dan fungsi perkumuhan buah pinggang telah dikaji pada tikus yang telah dibius dan pengekspresan mRNA nitrik oksida sintase (eNOS) endotelium dalam aorta toraks terpencil diukur. Pada tikus 2K1C, ekstrak bunga GD menurunkan ABP dengan ketara manakala paras mRNA eNOS meningkat dengan ketara. Ekstrak bunga GD tidak memberikan kesan diuretik sama ada pada tikus SO dan 2K1C kerana tiada perubahan dalam perkumuhan air kencing yang diperhatikan, tetapi ia cenderung untuk melemahkan kerosakan tiub buah pinggang yang disebabkan oleh hipertensi renovaskular. Ekstrak bunga GD adalah anti-hipertensi dalam model hipertensi renovaskular ini dan berkemungkinan bertindak melalui laluan isyarat nitrik oksida endotelium.

 

Kata kunci: Anti-hipertensi; Garcinia dulcis; hipertensi renovaskular; kamboginol; moreloflavon

 

RUJUKAN

Anderson, W.P., Kline, R.L. & Woods, R.L. 1985. Systemic and renal hemodynamic changes during acute unilateral renal arterial stenosis. American Journal of Physiology 249(5 Pt 2): H956-H967.

Balasubramanyam, K., Altaf, M., Varier, R.A., Swaminathan, V., Ravindran, A., Sadhale, P.P. & Kundu, T.K. 2004. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J. Biol. Chem. 279(32): 33716-33726.

Das, D., Bandyopadhyay, D., Bhattacharjee, M. & Banerjee, R.K. 1997. Hydroxyl radical is the major causative factor in stress-induced gastric ulceration. Free Radical Biology and Medicine 23(1): 8-18. doi:10.1016/S0891-5849(96)00547-3.

Davidson, W.D. & Sackner, M.A. 1963. Simplification of anthrone method of the determination of inulin in clearance studies. Journal of Laboratory and Clinical Medicine 62: 351-356.

Deachathai, S., Phongpaichit, S. & Mahabusarakam, W. 2008. Phenolic compounds from the seeds of Garcinia dulcis. Natural Product Research 22(15): 1327-1232.

Deachathai, S., Mahabusarakam, W., Phongpaichit, S., Taylor, W.C., Zhang, Y.J. & Yang, C.R. 2006. Phenolic compounds from the flowers of Garcinia dulcis. Phytochemistry 67(5): 464-469.

Deachathai, S., Mahabusarakam, W., Phongpaichit, S. & Taylor, W.C. 2005. Phenolic compounds from the fruit of Garcinia dulcis. Phytochemistry 66(19): 2368-2375.

Gil, B., Sanz, M.J., Terencio, M.C., Gunaseqaran, R., Payá, M. & Alcaraz, M.J. 1997. Morelloflavone, a novel biflavonoid inhibitor of human secretory phospholipase A2 with anti-inflammatory activity. Biochemical Pharmacology 53: 733-740.

Goldblatt, H., Lynch, J., Hanzal, R.F. & Summerville, W.W. 1934. Studies on experimental hypertension: I. The production of persistent elevation of systolic blood pressure by means of renal ischemia. Journal of Experimental Medicine 59(3): 347-379.

Harris, P.J. & Young, J.A. 1977. Dose-dependent stimulation and inhibition of proximal tubular sodium reabsorption by angiotensin II in the rat kidney. European Journal of Physiology 367(3): 295-297.

Hong, J., Sang, S., Park, H.J., Park, H.J., Kwon, S.J., Suh, N. & Yang, C.S. 2006. Modulation of arachidonic acid metabolism and nitric oxide synthesis by garcinol and its derivatives. Carcinogenesis 27(2): 278-286.

Hutadilok-Towatana, N., Kongkachuay, S. & Mahabusarakam, W. 2007. Inhibition of human lipoprotein oxidation by morelloflavone and camboginol from Garcinia dulcis. Natural Product Research 21(7): 655-662.

Julius, S. & Nesbitt, S. 1996. Sympathetic overactivity in hypertension. A moving target. American Journal of Hypertension 9(11): 113S-120S.

Kim, S.Y., Kim, T.B., Moon, K.A., Kim, T.J., Shin, D., Cho, Y.S. & Lee, K.Y. 2008. Regulation of pro-inflammatory responses by lipoxygenases via intracellular reactive oxygen species in vitro and in vivo. Experimental & Molecular Medicine 40(4): 461-476.

Lamai, J., Mahabusarakam, W., Ratithammatorn, T. & Hiranyachattada, S. 2013. Effects of morelloflavone from Garcinia dulcis on vasorelaxation of isolated rat thoracic aorta. Journal of Physiological and Biomedical Sciences 26(1): 13-17.

Liao, C.H., Sang, S., Liang, Y.C., Ho, C.T. & Lin, J.K. 2004. Suppression of inducible nitric oxide synthase and cyclooxygenase-2 in downregulating nuclear factor-kappa B pathway by Garcinol. Molecular Carcinogenesis 41(3): 140-149. doi:10.1002/mc.20050.

Lin, Y-M., Anderson, H., Flavin, M.T., Pai, Y-H.S., Mata-Greenwood, E., Pengsuparp, T., Pezzuto, J.M., Schinazi, R.F., Hughes, S.H. & Chen, F.C. 1997. In vitro anti-HIV activity of biflavonoids isolated from Rhus succedanea and Garcinia multiflora. J. Nat. Prod. 60: 884-888.

Lu, M., Liu, Y.H., Goh, H.S., Wang, J.J., Yong, Q.C., Wang, R. & Bian, J.S. 2010. Hydrogen sulfide inhibits plasma renin activity. Journal of the American Society of Nephrology 21(6): 993-1002.

Mahabusarakam, W., Mecawun, P. & Phongpaichit, S. 2016. Xanthones from the green branch of Garcinia dulcis. Natural Product Research 20: 2323-2328.

Manrique, C., Lastra, G., Gardner, M. & Sowers, J.R. 2009. The renin angiotensin aldosterone system in hypertension: Roles of insulin resistance and oxidative stress. Medical Clinics of North America 93(3): 569-582.

Martinez-Maldonado, M. 1991. Pathophysiology of renovascular hypertension. Hypertension 17(5): 707-719.

Mazzolai, L., Pedrazzini, T., Nicoud, F., Gabbiani, G., Brunner, H.R. & Nussberger, J. 2000. Increased cardiac angiotensin II levels induce right and left ventricular hypertrophy in normotensive mice. Hypertension 35(4): 985-991.

Pang, X., Yi, T., Yi, Z., Cho, S.G., Qu, W., Pinkaew, D., Fujise, K. & Liu, M. 2009. Morelloflavone, a biflavonoid, inhibits tumor angiogenesis by targeting rho GTPases and extracellular signal-regulated kinase signaling pathways. Cancer Research 69(2): 518-525.

Pinkaew, D., Hutadilok-Towatana, N., Teng, B.B., Mahabusarakam, W. & Fujise, K. 2012. Morelloflavone, a biflavonoid inhibitor of migration-related kinases, ameliorates atherosclerosis in mice. American Journal of Physiology (Heart and Circulatory Physiology) 302: H451-H458.

Ploth, D.W., Roy, R.N., Huang, W.C. & Navar, L.G. 1981. Impaired renal blood flow and cortical pressure autoregulation in contralateral kidneys of Goldblatt hypertensive rats. Hypertension 3(1): 67-74.

Sánchez, M., Galisteo, M., Vera, R., Villar, I.C., Zarzuelo, A., Tamargo, J., Pérez-Vizcaíno, F. & Duarte, J. 2006. Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats. Journal of Hypertension 24(1): 75-84.

Schmittgen, T.D. & Livak, K.J. 2008. Analyzing real-time PCR data by the comparative C(T) method. Nature Protocols 3(6): 1101-1108.

Smith, H.W., Finkelstein, N., Aliminosa, L., Crawford, B. & Graber, M. 1945. The renal clearances of substituted hippuric acid derivatives and other aromatic acids in dog and man. Journal of Clinical Investigation 24(3): 388-404.

Sumalee, A., Mahabusarakam, W., Kirirat, P. & Hiranyachattada, S. 2017. Effects of morellofavone from Garcinia dulcis on the relaxation response, malondialdehyde levels and histology of cisplatin-treated rat aorta. Journal of Physiological and Biomedical Sciences 30(1): 23-30.

Tanaka, T., Kohno, H., Shimada, R., Kagami, S., Yamaguchi, F., Kataoka, S., Ariga, T., Murakami, A., Koshimizu, K. & Ohigashi, H. 2000. Prevention of colonic aberrant crypt foci by dietary feeding of garcinol in male F344 rats. Carcinogenesis 21(6): 1183-1189.

Thongsepee, N., Srisawat, U., Mahabusarakam, W., Ekarattanawong, S., Suttirak, N. & Hiranyachattada, S. 2020. Effects of oral administration of Garcinia dulcis flower extract on arterial blood pressure and renal excretory functions in rats. ScienceAsia 46(6): 671-678.

Thongsepee, N., Mahabusarakam, W. & Hiranyachattada, S. 2018. Vasorelaxant mechanisms of camboginol from Garcinia dulcis in normotensive and 2-kidneys-1-clip hypertensive rat. Songklanakarin Journal of Science and Technology 40(6): 1248-1258.

Thongsepee, N., Mahabusarakam, W. & Hiranyachattada, S. 2017a. Diuretic and hypotensive effect of morelloflavone from Garcinia dulcis in two-kidneys-one-clip (2K1C) hypertensive rat. Sains Malaysiana 46(9): 1479-1490.

Thongsepee, N., Mahabusarakam, W. & Hiranyachattada, S. 2017b. Diuretic effect of camboginol from Garcinia dulcis in 2-kidneys-1-clip hypertensive rat. Proceedings of the Burapha University International Conference 2017, Chonburi, Thailand. pp. 613-622.

Tuansulong, K.A., Hutadilok-Towatana, N., Mahabusarakam, W., Pinkaew, D. & Fujise, K. 2011. Morelloflavone from Garcinia dulcis as a novel biflavonoid inhibitor of HMG-CoA reductase. Phytotherapy Research 25: 424-428.

Ulker, S., McMaster, D., McKeown, P.P. & Bayraktutan, U. 2003. Impaired activities of antioxidant enzymes elicit endothelial dysfunction in spontaneous hypertensive rats despite enhanced vascular nitric oxide generation. Cardiovascular Research 59(2): 488-500.

Yamaguchi, F., Ariga, T., Yoshimura, Y. & Nakazawa, H. 2000a. Antioxidative and anti-glycation activity of garcinol from Garcinia indica fruit rind. J. Agric. Food Chem. 48(2): 180-185.

Yamaguchi, F., Saito, M., Ariga, T., Yoshimura, Y. & Nakazawa, H. 2000b. Free radical scavenging activity and antiulcer activity of garcinol from Garcinia indica fruit rind. J. Agric. Food Chem. 48(6): 2320-2325.

 

*Pengarang untuk surat-menyurat; email: nattayat@tu.ac.th

 

 

   

sebelumnya