ISOLASI DAN PENENTUAN STRUKTUR SERTA MEKANISME AKSI SENYAWA VASODILATOR DARI DAUN Dracontonelon dao (Blanco) Merr. & Rolfe (DAHU) SECARA In Vitro

SJARIF ISMAIL, DR., M.KES, Prof. Dr. Mustofa, M.Kes., Apt ; Prof. dr. Ngatidjan, M.Sc., Sp.FK(K) ; Prof. Dr. Ratna Asmah Susidanti, M.Si., Apt

2015 | Disertasi | S3 Ilmu Kedokteran

serta diperlukan pengobatan jangka panjang agar tekanan darah dapat terkontrol. Tumbuhan merupakan sumber bahan baku untuk obat. Ekstrak etanol daun Dracontomelon dao (D. dao) telah diketahui memiliki aktivitas vasodilatasi pada pembuluh darah aorta tikus secara in vitro, tetapi belum diketahui senyawa aktif dan mekanisme aksi di pembuluh darah. Tujuan penelitian: mengisolasi dan mengetahui struktur senyawa aktif dari daun D. dao sebagai vasodilator dan mengkaji mekanisme aksinya. Metode: isolasi daun D. dao secara bioassay guided fractionation dengan meggunakan metode organ terpisah aorta tikus dengan endotel yang diprekontraksi menggunakan fenilefrin. Senyawa aktif terpilih dilakukan elusidasi struktur dan uji mekanisme aksi. Uji mekanisme aksi digunakan: (1) aorta dengan endotel dan tanpa endotel yang diprekontraksi dengan fenilefrin dan KCl; (2) aorta dengan endotel yang diinkubasi atropin, indometasin, NG-nitro-L-arginin metil ester dan metilen biru; (3) aorta tanpa endotel dalam larutan bebas ion kalsium. Hasil: didapatkan senyawa aktif terpilih metil galat dengan aktivitas vasodilatasi. Mekanisme aksi vasodilatasi metil galat di pembuluh darah dapat melalui endotel dan otot polos pembuluh darah, tetapi lebih utama di otot polos pembuluh darah melalui regulasi ion kalsium intraseluler. Kesimpulan: kandungan aktif daun D. dao adalah metil galat dengan mekanisme aksi vasodilatasi melalui regulasi ion kalsium intraseluler.

Background: hypertension is a major health issue in Indonesia and the world and long-term treatments is required to keep the blood pressure in control. Plants could be a source of raw material for medicine. The ethanol extract of Dracontomelon dao (D. dao) leaves has a vasodilatation activity in rat aorta in vitro, but its active isolates and mechanism of action in the blood vessels are yet to be known. The objective of research is to find the active compound from the D. dao leaves that act as the vasodilator and examine its mechanism of action. Methods: D. dao leaves was isolated with bioassay-guided fractionation, method bioassay with isolated organ of rat aortic rings with intak-endothelium, precontracted with phenylephrine. Active compound were conducted to elucidate the structure and mechanisms of action. Bioassay mechanisms of action are used: (1) aortic rings with endothelium-intak and endothelium-denuded were precontraction with phenylephrine and KCl; ( 2 ) aortic rings with endotheliumintak incubated with atropine, indomethacin, NG-nitro-L-arginine methyl ester and methylene blue; (3) aortic rings endothelium-denuded in ion calcium free medium. Result: methyl gallate was active compound isolated from D. dao leaves; it had exhibited vasodilatation activity on the blood vessels. The mechanism of action of methyl gallate can occur in endothelial and vascular smooth muscle, but more prominently in vascular smooth muscle through the regulation of intracellular calcium ions. Conclusion: the active compound of D. dao leaves was methyl gallate with mechanisms of action vasodilatation primarily on vascular smooth muscle

Kata Kunci : daun Dracontomelon dao, bioassay guided fractionation, metil galat, vasodilator, mekanisme aksi.