THE MECHANISM STUDY OF ANTIHYPERTENSIVE MATOA LEAVES (POMETIA PINNATA J.R. FORSTER & J.G FORSTER)

• Main Author: Purwidyaningrum, Ika
• Format: Dissertations
• Language: Indonesia
• Subjects: Farmakologi dan terapeutik
• Online Access: https://digilib.itb.ac.id/gdl/view/32836
• Institution: Institut Teknologi Bandung

Hypertension is the most common cardiovascular disease that occurs. The prevalence of hypertension increases with age. Based on the results of blood pressure measurement, the prevalence of hypertension in the population aged 18 years and over in Indonesia is 25.8%. Treatment of hypertension with antihypertensive drug is done in a long period of time so that it can cause side effects. In addition there are different responses of each individual towards certain antihypertensive drug. Most patients with hypertension will require two or more antihypertensive medications to achieve blood pressure targets. Based on that can cause non-compliance in therapy so that a therapeutic target is not reached. Thus there's more opportunity to find antihypertensive drug which are safe, effective and qualified from plants. One source is from natural materials, namely plant. Many plants in Indonesia have effect in reducing blood pressure, such as matoa (Pometia pinnata), which have been used by people in Pajang- Surakarta. This study aims to determine the effect of antihypertensive matoa so its use as an antihypertensive is rational and its mechanism as antihypertensive agent. Diuretic test screening was performed as preliminary test of three matoa plant parts (leaves, seeds and peel) to determine the selected crude drug. The selected crude drug then was followed to the next separation, hence obtained fractions and subfractions. The research design which was used in each activity test in vivo and in vitro experimental was randomized control group design. The mechanism of antihypertensive agent were carried out in extract, fractions and selected subfraction included diuretic, ACEI, alpha-blocker, CCB, and nitric oxide levels by Griess reagent. Furthermore, acute toxicity was performed for selected crude drug. Diuretic test was performed in all matoa plant parts crude drug with doses of 50 mg/kg bw, 100 mg/kg bw and 150 mg/kg bw. Ethanol extract of leaves, peels and v seeds of matoa had diuretic activity in male Wistar rats and could increase sodium and potassium levels in urine of animal test. Matoa seeds extract 150 mg/kg bw provide the highest diuretic activity but its levels of sodium and potassium in urine were lower compared to the others groups. The effective dose of matoa leaves extract as diuretic was 100 mg/kg bw. Based on urine volume, percentage of EUV, sodium and potassium levels, availability and feasibility of crude drug, therefore matoa leaves was chosen to further research. Administration of ethanol leaves extract of matoa until dose of 5,000 mg/kg bw showed no death in mice and no different clinical symptoms compared to control group. The development of body weight of mice for 14 days showed similar pattern of body weight and no significant different compared to control. There was no death during acute toxicity test, hence the letal dose 50 (LD50) was higher than 5,000 mg/kg bw. So it can be concluded that ethanol leaves extract of matoa was save and practically not toxic. Fractionation of etanol leaves extract of matoa was conducted by liquid-liquid extraction, by using n-hexane and ethyl acetate solvent, so there were n-hexane fraction, ethyl actetae fraction and wáter fraction. Subfraction of ethyl acetate fraction was performed by vacuum liquid chromatograpy.The result of diuretic mechanism test revealed that etanol extract and all fractions of matoa leaves had diuretic effect, except ethyl acetate fraction had diuretic and saluretic effects. Antihypertensive effect test of matoa extract and its fractions presented that the extract and fractions had anthypertensive effect. Heart organ index parameter test exposed that there was no significant different between treatment group and normal group, but decreasing in heart organ index was presented by HCT 0.45 mg/kg bw, various doses of extracts and fractions of matoa leaves. It can be concluded that treatment by HCT, extract and fractions of matoa leaves with various doses could not decrease heart organ index of hypertension rats which induced by NaCl-prednison for 28 days and followed by 28 days treatment. ACEI test which was determined using modified of Cushman and Cheung’s method expressed that IC50 of ethanol extract 57.21 ± 3.78 ppm, ethyl acetate fraction 60.28 ± 4.97 ppm, wáter fraction 95.52 ± 4.43 ppm, subfraction which contain quercetin-quercitrin (SQQ) 26.78 ± 1.41 ppm, subfraction which contain quercitrin (SFQ) 29.64 ± 1.34 ppm, quercetin 73.11 ± 3.08 ppm dan captopril 1.79 ± 0.49 ppm. It presented that the ability of all simple to inhibit ACE were lower than captopril. Alpha blocker mechanism test using vasodilator test towards aortic of rabbit showed that matoa leaves extract 50 mg/kg bw (EDM 1), matoa leaves extract 100 mg/kg bw (EDM 2), ethyl acetate fraction of matoa leaves 8.71 mg/kg bw (FEM 2), ethyl acetate fraction of matoa leaves 13.06 mg/kg bw (FEM 3) had as resources of nitrite oxide (NO), threfore it can be folllowed to determine NO content using Griess reagent. The group having activity as alpha blockers are FEM 2 and FEM 3. vi Based on CCB mechanism test using vasodilator test towards aortic of rabbit, it can be concluded that matoa leaves extract with dose of 150 mg/kg bw (EDM 3) had vasodilator effect and significanttly different compared (p<0.05), and no significant different compared to nifedipin, means EDM 3 had CCB effect. The other groups were EDM 2, wáter fraction 10.94 mg/kg bw (FAM 1), wáter fraction 21.88 mg/kg bw FAM 2, wáter fraction 32.82 mg/kg bw (FAM 3), FEM 3, SFQ and quercetin gave vasodilator effect which significant different to control and nifedipin (p<0.05), means their vasodilator effect was lower than nifedipin. Meanwhile EDM 1, ethyl acetate fraction 4.35mg/kg bw (FEM 1), FEM 2, SQQ had no vasodilator effect. This confirmed that EDM 1, FEM 1, FEM 2, SQQ had no CCB effect. The result determination NO content of using Griess reaction demonstrated that there were increasing in NO level in all treatment groups 15 minutes after giving sample, however there was no significant different compared to negative control. Based on research, it can be conluded that three parts of matoa (peel, seeds and leaves) had antihypertensive activity by screening using diuretic test. Ekstrak daun matoa dan fraksi memiliki aktivitas sebagai antihipertensi. Ethyl acetate fraction 9.71 mg/kg bw (FEM 2) and 12.06 g/ kg bw (FEM 3) had mechanism as diuretic; subfraction which contained quercetin-quecitrin (SQQ) as ACEI; ethyl acetate fraction 4.25 mg/kg bw (FEM 1) dan SQQ as alpha blocker; ethanol extracts 100 mg/kg bw (EDM 2) dan 150 mg/kg bw (EDM 3), water fractions at doses of 10.94 mg/ kg bw (FAM 1), 21.88 mg/kg bw (FAM 2), 32.82 mg/kg bw (FAM 3), ethyl acetate fraction 12.06 mg/kg bw (FEM 3) and subfraction which contained quercitrin (SFQ) as CCB; ethanol extracts of matoa leaves 50 mg/kg bb (EDM 1), 100 mg/kg bw (EDM2) and ethyl acetate fractions 9.71 mg/kg bw (FEM 2) dan 12.06 mg/kg bw (FEM 3) as NO content inducer. Ethanol extract of matoa leaves was save and practically not toxic.