8ahernandez-singson-short com.pmd D.B. B. Singson and C.L. Chichioco-Hernandez 97 SCIENCE DILIMAN (JULY-DECEMBER 2017) 29:2, 97-101 Angiotensin-Converting Enzyme Inhibitory Action of Selected Plants Dionisio Bong B. Singson University of the Philippines Diliman Christine L. Chichioco-Hernandez* University of the Philippines Diliman _______________ *Corresponding Author ISSN 0115-7809 Print / ISSN 2012-0818 Online Hypertension is the fourth leading cause of morbidity in the Philippines affecting more than 20% of Filipino adults (DOH 2013). Recognized as the “silent killer”, it gradually destroys the body without any symptoms. Untreated hypertension may lead to stroke, blindness, heart attack, and kidney and heart failure (Chobanian et al. 2 0 0 3 ) . Angiotensin-converting enzyme (ACE) is a key metalloprotease in the renin- angiotensin-aldosterone system. It catalyzes two reactions: conversion of the inactive decapeptide Angiotensin I into the vasoconstrictor and salt-retaining octapeptide Angiotensin II, and the hydrolysis of the vasodilator bradykinin which is contributory in lowering blood pressure. These lead to the elevation of blood pressure in an individual (Ferrario 2010). Inhibition of ACE is central in preventing hypertension (Cushman et al. 1977). One way to lower blood pressure is through the use of ACE inhibitors (Chobanian et al. 2003).However, its usage is associated with unwanted side effects, such as nephrotoxicity and congenital malformations (Adhiyaman et al. 2001; Cooper et al. 2006).It is necessary to look for other blood pressure lowering compounds that are equally effective but with minimal side effects. Several studies have tried to look for other potential ACE inhibitors from various plant sources (Adsersen and Adsersen 1997; Tsutsumi et al. 1998; Duncan et al. 1999; Somanadhan et al. 1999; Oh et al. 2002; Loizzo et al. 2007). In this study, extracts from Bixa orellana (Bixaceae), Artocarpus heterophyllus (Moraceae), Morus alba (Moraceae), Nymphaea pubescens (Nymphaeacea) and Syzygium samarangense (Myrtaceae) were evaluated for their anti-hypertensive potential using an ACE- inhibitory colorimetric assay. Angiotensin-Converting Enzyme Inhibitory Action of Selected Plants 98 The yields of the different extracts from the f ive plants are reported in Table 1. Results of the ACE inhibitory assay are shown in Figure 1. Table 2 shows the outcomes of the phytochemical screening of the different methanol extracts. Figure 1. Average percent inhibition of the various extracts. A. heterophyllus 184.56 3.41 34.27 19.66 B. orellana 177.19 8.95 24.58 20.38 M. alba 171.21 6.61 17.31 5.77 N. pubescens 104.93 11.58 19.93 4.86 S. samarangense 162.3 5.67 16.54 16.54 Plant Weight of dried leaves (g) Yield methanol extract (%) Yield hexane extract (%) Yield ethyl acetate extract (%) Table 1. Percent yield of leaves and extracts A. heterophyllus + - + + + + + B. orellana + + + + - + - M. alba + - - + + + + N. pubescens + - + + + + + S. samarangense - + - - + + - Plant Saponins Flavonoids Card iac Glycosides Phenol ic Compounds Alkaloids Terpenoids Tannins Table 2. Phytochemical profile of the methanol extracts D.B. B. Singson and C.L. Chichioco-Hernandez 99 The hexane and ethyl acetate extracts of B. orellana and S. samarangense exhibited signif icant inhibition of ACE activity, with their percent inhibition values exceeding 50%. It is notable that these two plants are positive for the presence of flavonoids. This is consistent with previous f indings attributing effective ACE inhibitory activity to flavonoids (Lacaille-Dubois et al. 2001; Perez-Viscaino et al. 2009; Jimenez- Ferrer et al. 2010; Balasuriya and Rupasinghe 2011; Balasuriya and Rupasinghe 2012). Flavonoids were previously identif ied from the leaves of S. samarangense (Nair et al. 1999). Other Syzygium species were found to contain flavonoids (Samy et al. 2014). Flavonoid bisulphates were previously identif ied from the extracts of B. orellana (Harborne 1975). Several ACE inhibitory flavonoids were isolated and identif ied from the ethanol extract of Erythroxylum laurifolium leaves (Hansen et al. 1996). Flavan-3-ols and procyanidins displayed inhibitory activity against ACE and the effect was observed to be dependent on the number of the epicatechin units forming the procyanidin (Actis-Goretta et al. 2003) Epidemiological studies have shown the link between food consumption and protective effect of compounds against cardiovascular disease. Several lines of evidence support that dietary intake of flavonoids from cocoa have a wide range of health benef its including endothelial function, blood pressure, inflammation, and oxidative stress (Grassi and Ferri 2014). In a double-blind, placebo-controlled, parallel trial, chokeberry flavonoids were shown to have a clinical potential in preventing ischemic heart disease because of their ability to reduce the severity of inflammation (Naruszewicz et al. 2007). Isolation and identification of the compounds responsible for the inhibition of ACE activity are ongoing. The activities of the B. orellana and S. samarangense extracts in hypertensive-induced mice will be evaluated using the non-invasive tail-cuff blood pressure measurement method. SUPPLEMENTARY MATERIAL Review of literature pertinent to the plants and experimental details relating to this paper are available online. ACKNOWLEDGEMENTS This work was partially funded by the Department of Science and Technology (DOST) through the Philippine Council for Health Research and Development (PCHRD). Angiotensin-Converting Enzyme Inhibitory Action of Selected Plants 100 REFERENCES Ac t i s - G o r e t t a L , O t t a v i a n i J I , Ke e n C L , F r a g a C G . 2 0 0 3 . I n h i b i t i o n of a n g i o te n s i n co n ve r t i n g e n z y m e ( AC E ) a c t i v i t y by f l a v a n - 3 - o l s a n d p r o cy a n i d i n s . F E B S Le t te r s . 555(3):597-600. Adhiyaman V, Asghar M, Oke A, White AD, Shah IU.2001.Nephrotoxicity in the elderly due to co-prescription of angiotensin converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs. Journal of the Royal Society of Medicine.94:512-514. Adsersen A, Adsersen H.1997. Plants from Réunion Island with alleged antihyper tensive a n d d i u r e t i c e f f e c t s — a n e x p e r i m e n t a l a n d e t h n o b o t a n i c a l e v a l u a t i o n . J o u r n a l o f Ethnopharmacology.58(3):189-206. Balasuriya BWN, Rupasinghe HPV. 2011. Plant flav onoids as angiotensin conver ting enzyme inhibitors in regulation of hypertension. Functional Foods for Health and Disease. 5:172-188. Balasuriya BWN, Rupasinghe HPV. 2012. Antihyper tensive proper ties of flavonoid-rich apple peel extract .Food Chemistry. 135(4):2320-2325. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright Jr. JT,Roccella EJ.2003. The seventh repor t of the joint national committee on prevention, detection, evaluation and treatment of high blood pressure. Hypertension. 42(6):1206-1252. Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, Hall K, Ray WA . 2 0 0 6 . M a j o r c o n g e n i t a l m a l fo r m a t i o n s a f t e r f i r s t t r i m e s t e r ex p o s u r e t o AC E inhibitors. The New England Journal of Medicine.354:2443-2451. Cushman DW, Cheung HS, Sabo EF, Ondetti MA . 1977.Design o f potent competitive inhibitors of angiotensin-converting enzyme. Caboxyalkanoyl and mercaptoalkanoyl amino acids. Biochemistry. 16(25):5484-5491. [ D O H ] D e p a r t m e n t o f H e a l t h . [ I n te r n e t ] . 2 0 0 3 . Le a d i n g c a u s e s o f m o r b i t y. M a n i l a : Depar tment of Health.[cited 2016 November 23].Available from:http: //www.doh.gov.ph/ node/1482. D u n c a n A C , J ä g e r A K , v a n S t a d e n J . 1 9 9 9 . S c r e e n i n g o f Z u l u m e d i c i n a l p l a n t s f o r angiotensin conver ting enzyme (ACE) inhibitors. Journal of Ethnopharmacology. 68(1- 3):63-70 Ferrario C.2010. Addressing the theoretical and clinical advantages of combination therapy with inhibitors of the renin-angiotensin-aldosterone system: Antihypertensive effects and benef its beyond BP control. Life Science.86(9-10):289-299. Grassi D, Ferri C. 2014.Chapter 78 – Cocoa, flavonoids and cardiovascular protection. Polyphenols in Human Health and Disease. 2:1009-1023. Hansen K, Adsersen A , Smitt U W, N y m a n U , C h r i s t e n s e n S B , S c h w a r t n e r C , Wa g n e r H.1996. Angiotensin converting enzyme (ACE) inhibitory flavonoids from Erythroxylum D.B. B. Singson and C.L. Chichioco-Hernandez 101 laurifolium .Phytomedicine. 2(4):313-317. Harborne J. 1975. Flavonoid bisulphates and their co-occurrences with ellagic acid in the Bixaceae, Frankeniaceae and related families.Phytochemistry. 14(5-6):1331-1337. J i m e n e z- F e r r e r E , B a d i l l o F H , G o n z a l e z- Co r t a z a r M , To r t o r i e l l o J , H e r r e r a - R u i z M . 2010.Antihyper tensive activity of Salvia elegans Vahl (Lamicaceae): ACE inhibition and angiotensin II antagonism. Journal of Ethnopharmacology.130(2):340-346. L a c a i l l e - D u b o i s M A , F r a n c k U , W a g n e r H . 2 0 0 1 . S e a r c h f o r p o t e n t i a l A n g i o t e n s i n Conver ting Enzyme (ACE) inhibitors from plants. Phytomedicine. 8(1):47-52. Loizzo MR, Said A, Tundis R, Rashed K, Statti GA , Hufner A, Menichini F.2007.Inhibition of angiotensin converting enzyme (ACE) by flavonoids isolated from Ailanthus excelsa (Roxb) (Simaroubaceae). Phyt otherapy Research.21:32-36. Nair AGR, Krishnan S, Ravikrishna C, Madhusudanan KP. 1999.New and rare flavonol glycosides from the leaves of Syzygium samarangense. Fitoterapia.70(2):148-151. Narusze wicz M , La n i ew s k a I , M i l l o B , D l u z n i e w s k i M . 2 0 0 7. Co m b i n a t i o n t h e r a py of s t a t i n w i t h f l a v o n o i d s r i c h e x t r a c t f r o m c h o k e b e r r y f r u i t s e n h a n c e d r e d u c t i o n i n cardiovascular risk markers in patients after myocardial infarction (MI). Atherosclerosis. 194(2):e179-e184. Oh H, Kang DG, Lee S, Lee SH.2002.Angiotensin conve r ting enzyme inhibitors from Cuscuta japonica Choisy. Journal of Ethnopharmacology.83(1-2):105-108. Perez-Vizcaino F, Duarte J, Jimenez R, Santos-Buelga C, Osuna A. 2009.Antihypertensive effects of the flavonoid quercetin. Pharmacological Repor ts. 61(1):67-75. Samy MN, Sugimoto S, Matsunami K, Otsuka H, Kamel MS. 2014.One new flavonoid glycoside and one new natural triterpene rhamnoside from the leaves of Syzygium grande. Phytochemistry Letters. 10:86-90. Somanadhan B , Varughese G, Palpu P, Sre edharan R, Gudiksen L, Smitt UW, Nyman U.1999.An ethnopharmacological survey for potential angiotensin converting enzyme inhibitors from Indian medicinal plants. Journal of Ethnopharmacology.65(2):103-112. Tsutsumi Y, Shimada A , Miyano A , Nishida T, Mitsunaga T.1998.In vitro screening of a n g i o t e n s i n - I c o n v e r t i n g e n z y m e i n h i b i t o r s f r o m J a p a n e s e c e d a r ( C r y p t o m e r i a japonica).Journal of Wood Science.44(6):463-468. _____________ Dionisio Bong B. Singson is a BS Chemistry graduate of the University of the Philippines Diliman and a former instructor of the Institute of Chemistry. Christine L. Chichioco-Hernandez is an Associate Professor and Director of the Institute of Chemistry, University of the Philippines Diliman. Her research area focuses on bioactive compounds from terrestrial plants.