Sains Malaysiana 46(9)(2017): 1479–1490

http://dx.doi.org/10.17576/jsm-2017-4609-17

Diuretic and Hypotensive Effect of Morelloflavone from Garcinia dulcis in Two-Kidneys-One-Clip (2K1C) Hypertensive Rat

(Kesan Diuretik dan Hipotensif Moreloflavon daripada Garcinia dulcis dalam Dua Buah Pinggang Satu Klip (2K1C) Tikus Hipertensi)

NATTAYA THONGSEPEE, WILAWAN MAHABUSARAKAM & SIRIPHUN HIRANYACHATTADA*

Department of Physiology, Faculty of Science, Prince of Songkla University

Hat Yai, Songkhla, 90112, Thailand

Diserahkan: 31 Ogos 2016/Diterima: 10 April 2017

ABSTRACT

Morelloflavone, a biflavonoid from Southeast Asian folk medical plant Garcinia dulcis, possesses powerful antioxidant activity both in vivo and in vitro. We aimed to evaluate the hypotensive and diuretic effect of morelloflavone in two-kidneys-one-clip (2K1C) renovascular hypertensive rats together with its vasorelaxant mechanism. Male Wistar rats (175±4 g) were undergone 2K1C and sham operation (SO) (n=6, each group). Four weeks after the rats were anesthetized and clearance markers (0.5% para-aminohippuric acid and 1% inulin) were given via a jugular vein (1.6 mL/h/100 g BW) to estimate renal blood flow (RBF) and glomerular filtration rate. The arterial blood pressure (AP) was monitored via a carotid artery and urine samples were collected. After equilibration, either morelloflavone or vehicle (DMSO) was given (0.1 mg/kg BW+5 μg/min/kg BW). Baroreflex sensitivity (BRS) (ΔHR/ΔMAP) was performed by an intravenous injection of 1, 2, 4, 8, 16 and 32 μg/kg BW phenylephrine (PE) or sodium nitroprusside. The PE-preconstricted isolated thoracic aortic rings (intact and denuded) relaxation were experimented using organ bath technique by cumulative additions of morelloflavaone (10-13-10-5 M) in the presence of specific vasorelaxant inhibitors and expressed as %relaxation from pre-contraction tension. In 2K1C rats, morelloflavone significantly lowered mean AP, increased RBF and increased urine flow rate when compared to vehicle control (138±6 vs. 152±1 mmHg, 3.44±0.49 vs. 2.29±0.25 mL/min/g KW and 42.0±9.4 vs. 18.2±3.9 μL/min/g KW, p<0.05), respectively and also restored the blunt BRS. Nitric oxide signaling pathway triggered by morelloflavone might be responsible for its diuretic and hypotensive effect.

Keywords: Diuretic; hypotensive; Garcinia dulcis; morelloflavone; two-kidneys-one-clip

ABSTRAK

Moreloflavon, biflavonoid tumbuhan perubatan tempatan Garcinia dulcis dari Asia Tenggara mempunyai aktiviti antioksidan yang kuat secara in vivo dan in vitro. Tujuan penyelidikan ini ialah untuk menilai kesan hipotensif dan diuretik moreloflavon renovascular tikus hipertensi dua buah pinggang satu klip (2K1C) bersama-sama dengan mekanisme vasorelaksan. Tikus jantan Wistar (175±4 g) telah menjalani pembedahan 2K1C dan sham (SO) (n=6, setiap kumpulan). Empat minggu selepas itu, tikus telah dianestetik dan penanda pelepasan (0.5% asid para-aminohipurik dan 1% inulin) diberikan melalui urat jugulum (1.6 mL/jam/100 g BW) untuk menganggar aliran darah ginjal (RBF) dan kadar penurasan glomerulus. Tekanan darah arteri (AP) dipantau melalui arteri karotid dan sampel air kencing diambil. Selepas penyeimbangan, moreloflavon atau wahana (DMSO) telah diberikan (0.1 mg/kg BW+5 μg/min/kg BW). Sensitiviti barorefleks (BRS) (ΔHR/ΔMAP) telah dijalankan melalui suntikan intravena 1, 2, 4, 8, 16 dan 32 μg/kg BW fenilefrina (PE) atau sodium nitroprusida. PE-praberkuncup yang dipencilkan oleh pengenduran gegelang aorta toraks (utuh dan tersulah) telah dieksperimentasi menggunakan teknik mandian organ dengan penambahan kumulatif moreloflavon (10-13-10-5M) dengan kehadiran perencatan vasorelaksan tertentu dan dinyatakan sebagai %pengenduran daripada ketegangan pra-pengecutan. Pada tikus 2K1C, moreloflavon dengan ketara menurunkan min AP, meningkatkan RBF serta meningkatkan kadar aliran air kencing berbanding wahana kawalan masing-masing (138±6 vs 152±1 mmHg, 3.44±0.49 vs 2.29±0.25 mL/min/g KW dan 42.0±9.4 vs 18.2±3.9 μL/min/g KW, p<0.05) dan juga memulihkan BRS yang tumpul. Oksida nitrik yang memberi isyarat laluan dicetuskan oleh moreloflavon mungkin bertanggungjawab terhadap kesan diuretik dan hipotensif.

Kata kunci: Diuretik; dua buah pinggang satu-klip; Garcinia dulcis; hipotensif; moreloflavon

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*Pengarang untuk surat-menyurat; email: siriphun.h@psu.ac.th