ANGIOTENSIN CONVERTING ENZYME INHIBITORY ACTIVITY OF MELINJO (GNETUM GNEMON L.) SEED EXTRACTS AND MOLECULAR DOCKING OF ITS STILBENE CONSTITUENTS
DOI:
https://doi.org/10.22159/ajpcr.2017.v10i3.16108Abstract
ABSTRACT
Objectives: To evaluate the angiotensin converting enzyme (ACE) inhibitory activity of melinjo (Gnetum gnemon) seed extract and to study molecular
docking of stilbene contained in melinjo seeds.
Methods: Melinjo seed powders were extracted with n-hexane, dichloromethane, ethyl acetate, methanol, and water successively. The extracts were
evaluated ACE inhibitory activities using ACE kit-Wist and the phenolic content using Folin–Ciocalteu method. The extract demonstrated the highest
ACE inhibitory activity was subjected to liquid chromatography-mass spectrometry (LC-MS) to know its stilbene constituent. The stilbene constituents
in melinjo seed were performed molecular docking using AutoDock Vina, and ligand-receptor Interactions were processed using Ligand Scout.
Results: The ethyl acetate extract demonstrated the highest ACE inhibition activity with inhibitory concentration 50% value of 9.77 × 10−8 μg/mL
and the highest total phenolic content (575.9 mg gallic acid equivalent/g). Ultra-performance LC-MS analysis of ethyl acetate extract has detected the
existency of resveratrol, gnetin C, ε-viniferin, and gnemonoside A/B. These compounds displayed similar physiochemical properties to lisinopril (ACE
inhibitor), as in silico molecular docking studies demonstrated that they fit into the lisinopril receptors.
Conclusion: In vitro analysis ethyl acetate extract from melinjo seeds demonstrated the highest ACE inhibitory activity. Molecular docking analysis
indicated that resveratrol dimers, gnetin C and gnemonoside A can be considered ACE inhibitor.
Keywords: Angiotensin converting enzyme inhibitor, Gnetum gnemon, Melinjo, Total phenolic, Antihypertension, Molecular docking.
Downloads
References
REFERENCES
Departemen Kehutanan. Lokakarya Obat Tradisional Indonesia. 2011.
Ito T, Akao Y, Tanaka T, Iinuma M, Nozawa Y. Vaticanol C, a novel resveratrol tetramer, inhibits cell growth through induction of apoptosis in colon cancer cell lines. Biol Pharm Bull 2002;25(1):147-8.
Huang KS, Wang YH, Li RL, Lin M. Five new stilbene dimers from the lianas of Gnetum hainanense. J Nat Prod 2000;63(1):86-9.
Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;16(7117):337-42.
King RE, Bomser JA, Min DB. Bioactivity of resveratrol. Compr Rev Food Sci Food Saf 2006;5(3):65-70.
En F. In search of better methods to evaluate natural antioxidants and oxidative stability in food lipids. Trends Food Sci Technol 1993;4(7):220-5.
Pace-Asciak CR, Hahn S, Diamandis EP, Soleas GD. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: Implications for protection against coronary heart disease. Clin Chim Acta 1995;235(2):207-19.
Huang KS, Wang YH, Li RL, Lin M. Stilbene dimers from the lianas of Gnetum hainanense. Phytochemistry 2000;54:875-81.
Li GH, Liu H, Shi YH, Le GW. Direct spectrophotometric measurement of angiotensin I-converting enzyme inhibitory activity for screening bioactive peptides. J Pharm Biomed Anal 2005;37(2):219-24.
Bradamante S, Barenghi L, Villa A. Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev 2004;22(3):169-88.
Le Corre L, Chalabi N, Delort L, Bignon YJ, Bernard-Gallon DJ. Resveratrol and breast cancer chemoprevention: Molecular mechanisms. Mol Nutr Food Res 2005;49:462-71.
Wolter F, Ulrich S, Stein J. Molecular mechanisms of the chemopreventive effects of resveratrol and its analogs in colorectal cancer: key role of polyamines? J Nutr 2004;134:3219-22.
Ratan HL, Steward WP, Gescher AJ, Mellon JK. Resveratrol – A prostate cancer chemopreventive agent? Urol Oncol 2002;7(6):223-7.
Kato E, Tokunaga Y, Sakan F. Stilbenoids isolated from the seeds of Melinjo (Gnetum gnemon L.) and their biological activity. J Agric Food Chem 2009;57:2544-9.
Lam le H, Shimamura T, Sakaguchi K, Noguchi K, Ishiyama M, Fujimura Y, et al. Assay of angiotensin I-converting enzyme-inhibiting activity based on the detection of 3-hydroxybutyric acid. Anal Biochem 2007;364(2):104-11.
Lam LH, Shimamura T, Manabe S, Ishiyama M, Ukeda H. Assay of angiotensin I-converting enzyme-inhibiting activity based on the detection of 3-hydroxybutyrate with water-soluble tetrazolium salt. Anal Sci 2008;24(8):1057-60.
Lam le H, Shimamura T, Ishiyama M, Ukeda H. Flow injection analysis of angiotensin I-converting enzyme inhibitory activity with enzymatic reactors. Talanta 2009;79(4):1130-4.
Borkataky M. Antioxidant activity, total phenolic content and total flavonoid content of Perilla ocymoides Linn. Der Pharm Lett 2015;7(5):69-72.
Wolber G, Dornhofer AA, Langer T. Efficient overlay of small organic molecules using 3D pharmacophores. J Comput Aided Mol Des 2006;20(12):773-88.
Harborne J. In: Soediro I, editor. Metode Fitokimia: Penuntun Cara Modern Menganalisis Tumbuhan. 2nd ed. Bandung: Penerbit ITB; 1987.
Departemen Kesehatan Republik Indonesia. Farmakope Indonesia. Jilid IV. Jakarta: Departemen Kesehatan Republik Indonesia; 1995. p. 1995.
Chan HH, Sun HD, Reddy MV, Wu T. Potent α-glucosidase inhibitors from the roots of Panax japonicus C. A. Meyer var.major. Phytochemistry 2010;71(11):1360-4.
Bhat R, binti Yahya N. Evaluating belinjau (Gnetum gnemon L.) seed flour quality as a base for development of novel food products and food formulations. Food Chem 2014;156:42-9.
Bayarsaikhan D, Yamaki K, Enkhtaivan G, Ichinkhorloo Z. Identification of angiotensin I-converting enzyme inhibitory activities from traditional Mongolian fermented milk products. Mong J Chem 2011;12(38):65-8.
Su PS, Doerksen RJ, Chen SH, Sung WC, Juan CC, Rawendra RD, et al. Screening and profiling stilbene-type natural products with angiotensin-converting enzyme inhibitory activity from Ampelopsis brevipedunculata var. hancei (Planch.) Rehder. J Pharm Biomed Anal 2015;108:70-7.
Ibadallah BX, Abdullah N, Shuib AS. Identification of angiotensin-converting enzyme inhibitory proteins from mycelium of Pleurotus pulmonarius (oyster mushroom). Planta Med 2015;81(2):123-9.
Robinson T. In: Padmawinata K, editor. Kandungan Organik Tumbuhan Tinggi. Edisi 6. Bandung: Penerbit ITB; 1995.
Mongkolsilp M, Pongbupakit I, Sae-Lee N, Sitthithaworn W. Radical scavenging activity and total phenolic content of medicinal plants used in primary health care. SWUJ PharmSci 2004;9:32-5.
Andrade TU, Lenz D, Endringer C. Pavonia alnifolia A. St. Hil. in vivo hypotensive effect and in vitro ACE inhibitory activityY. Int J Pharm Pharm Sci 2012;4(1):124-6.
Rohman A, Riyanto S, Utari D. Aktivitas antioksidan, kandungan fenolik total dan kandungan flavonoid total ekstrak etil asetat buah Mengkudu Serta Fraksi-fraksinya. J MFI 2006;17(3):136-42.
Samin AA, Bialangi N, Salimi YK. Penentuan kandungan fenolik total dan aktivitas antioksidan dari rambut jagung (Zea mays L.) yang tumbuh di daerah Gorontalo 2011;Thesis:1-15.
Kato E, Tokunaga T, Iiyama M, Furusawa M, Nakaya K, Murata J, et al. Four new stilbene oligomers in the root of Gnetum gnemon. Helv Chim Acta 2002;85(8):2538-46.
Laskar MA, Choudhury MD. Computational study on the angiotensin converting enzyme inhibitory potential of the tea polyphenols-cathechins: Relevance to cardiovascular diseases. Int J Pharm Pharm Sci 2015;7(1):345-9.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
