Inhibition of Angiotensin Converting Enzyme (ACE) by

16 Inhibition of Angiotensin Converting Enzyme (ACE) by Medicinal Plants Exhibiting Antihypertensive Activity JALAHALLI M. SIDDESHA1, CLETUS J.M. D'SOUZA1 AND BANNIKUPPE S. VISHWANATH1*

Abstract This chapter summarizes the screening of plants traditionally used against hypertension for ACE inhibitory activity. The maximum number of plant species (18) exhibiting ACE inhibition belongs to the family Fabaceae. Following Fabaceae, the plant species (6-7) that inhibit ACE activity belongs to Euphorbiaceae, Araliaceae, Lamiaceae, Oleaceae, Asteraceae and Malvaceae. While, only a few species belonging to other diversified families Amaranthaceae, Combretaceae, Rosaceae, Anacardiaceae, Apiaceae, Aristolochiaceae, Crassulaceae, Cucurbitaceae, Lauraceae, Liliaceae, Rubiaceae, Sapindaceae, Acanthaceae, Berberidaceae, Ericaceae, Myrsinaceae, Onagaraceae, Polygonaceae, Rutaceae, Solanaceae, Theaceae etc. showed ACE inhibition. The major class of compounds showing ACE inhibition is found to be flavonoids followed by peptides, alkaloids, phenylpropanoid glycosides, terpenes, iridoids, lipids, polyphenols, tannins and xanthones. In our ongoing research, methanolic and ethanolic leaf extracts of Artocarpus altilis exhibited potent ACE inhibition compared to aqueous and acetone extracts. The methanolic, ethanolic and aqueous leaf extracts of Catharanthus roseus, Pongamia pinnata and Azadirachta indica as well as that of Tamarindus indicus seed coat showed good ACE inhibition compared to acetone extracts, suggesting the benefit of polar compounds as potent ACE inhibitors. In conclusion, the scientific investigations of plants that are used in traditional antihypertensive medicine and the isolation of bioactive polar compounds will be helpful to develop safe and effective antihypertensive drugs. 1. Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore-570 006, India. * Corresponding author : E-mail : [email protected]

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RPMP Vol. 29 — Drug Plants III

Key words: Angiotensin Converting Enzyme Antihypertensive, Artocarpus altilis

inhibitor,

ACE,

Introduction Plants are the basis of life on earth and are central to people’s livelihoods. Over many years, the focus on plant research has increased all over the world and a plenty of evidences show immense potential of medicinal plants in the management of hypertension (Barbosa-Filho et al., 2006; Kwan et al., 2002; Wright et al., 2007 ). The concept of medicinal application of plants is based on the traditional medicine systems, which utilize plants as a therapeutic approach for the treatment of cardiovascular diseases and high blood pressure. Hypertension is a growing undesired symptom that damages health and threatens mostly the developed societies and is a significant health problem worldwide. It is one among the major independent risk factors for atherosclerosis, stroke, myocardial infarction and end stage renal disease (Lam le et al., 2007; Frantz, 2003). The main objective of hypertensive treatment is to reduce the blood pressure and to control other cardiovascular risk factors. Since, the angiotensin converting enzyme (ACE) catalyzes conversion of inactive angiotensin I to active angiotensin II and concomitant inactivation of bradykinin; suppression of its enzymatic activity is an ideal target in the treatment of hypertension. ACE inhibitors constitute an established therapy and play an important role as first-line therapy in hypertensive patients with cardiovascular complications, diabetic nephropathy and type II diabetes mellitus (Dostal et al., 1996; Lam le et al, 2007). ACE inhibitors have shown protection against stroke, coronary events, heart failure, progression of renal disease, progression to more severe hypertension and all-cause mortality (Psaty et al., 1997; Moser & Hebert, 1996). Despite this advantage, pharmaceutically designed ACE inhibitors have exhibited adverse effects such as cough, angioedema, taste disturbances, skin rashes and allergic reactions (de Lima, 1999). Therefore, worldwide the medicinal plants have gain more importance because of their better cultural acceptability and compatibility with the human body and lesser side effects. In this chapter, we are presenting the review data regarding the utility of plant extracts and plant-derived products as ACE inhibitors. We are also presenting the initial results of our ongoing phytoceutical research on angiotensin converting enzyme inhibitory activity of medicinal plants exhibiting antihypertensive effects.

Role of angiotensin converting enzyme in hypertension Angiotensin converting enzyme (EC 3.4.15.1) is a zinc-containing dipeptidyl carboxy-peptidase associated with the renin-angiotensin system. It is found

Inhibition of Angiotensin Converting Enzyme (ACE)

271

in a wide variety of mammalian tissues, principally as a membrane-bound ectoenzyme (Erdos, 1990). ACE plays a critical role in the control of blood pressure by virtue of its participation in the renin-angiotensin-aldosterone system. It removes C-terminal dipeptide from prohormone angiotensin I to generate the powerful, active vasoconstrictor octapeptide, angiotensin II. The same enzyme also degrades and inactivates the vasodilatory peptide, bradykinin by the sequential removal of dipeptides from the C-terminus (Ondetti & Cushman, 1982; Soffer, 1976). Thus produced, angiotensin II acts directly on vascular smooth muscle cells and causes the contraction of blood vessels and thereby raising blood pressure (Folkow et al., 1961). The angiotensin II interacts with the sympathetic nervous system both peripherally and centrally to increase vascular tone (Corvol, 1995). It is also known to stimulate both the synthesis and release of aldosterone from the adrenal cortex and this event increases blood pressure via sodium retention. The volume expansion takes place due to sodium retention via aldosterone and renal vasoconstriction (Zimmerman, 1984) as well as due to fluid retention via antidiuretic hormone (Biron, 1961). Apart from elevating the blood pressure, angiotensin II promotes migration, proliferation and hypertrophy at the cellular level (Padfield et al., 1977; Bell et al., 1990; Itoh et al., 1993). The mechanism of action of ACE and angiotensin II in elevating the blood pressure in human beings and animals is shown in Fig 1.

Fig 1. Mechanism of action of Angiotensin Converting Enzyme

272


Importance of ACE inhibition in hypertension Among the six major classes of antihypertensive drugs; diuretics, ACE inhibitors, adrenergic receptor blockers, calcium channel blockers, and blockers, ACE inhibitors constitute an established therapy in the management of high blood pressure (Cushman & Ondetti, 1991). This class of drugs effectively lowers the mean, systolic and diastolic pressures in hypertensive patients as well as in salt-depleted normotensive subjects (Vidt et al., 1982; Todd et al., 1986; Pool et al., 1987). ACE inhibitors alter the balance between the vasodilatory and natriuretic properties of bradykinin and the vasoconstrictive and salt-retentive properties of angiotensin II, by decreasing the formation of angiotensin II and the degradation of bradykinin. Since the original discovery of ACE inhibitors in snake venom, pharmacologically active ACE inhibitors captopril, enalapril, lisinopril, benazepril, fosinopril, ramipril, perindropil, quinapril and many more compounds have been developed and are currently in use (Brown & Vaughan, 1998). These synthetic ACE inhibitors have established themselves in the therapy of hypertension and congestive heart failure (Cheung, 1973). Synthetic ACE inhibitors are remarkably effective, but they cause adverse side effects such as cough, angioedema, taste disturbances, skin rashes and allergic reactions (de Lima, 1999). Therefore, in recent times, the trend has been set towards the development of natural, safe and effective ACE inhibitors with minimized adverse effects.

Utilization of plants as source of ACE inhibitors The screening for antihypertensive activity in traditional medicines has been performed over many years. The antihypertensive activity of the majority of the plants is found to be through the inhibition of ACE. From the different parts of the world, plants with antihypertensive activity have been reported. In this chapter we have reviewed the literature on ACE inhibitory activity of about 200 plant extracts and presented in Table 1. Many plant species belonging to diversified families shown to inhibit ACE activity. A total number of 18 plant species belonging to Fabaceae showed ACE inhibitory activity. Families like Euphorbiaceae, Araliaceae, Lamiaceae, Oleaceae, Asteraceae and Malvaceae, each included 6–7 species with ACE inhibitory activity. Whereas, only a few species belonging to other diversified families Amaranthaceae, Combretaceae, Rosaceae, Anacardiaceae, Apiaceae, Aristolochiaceae, Crassulaceae, Cucurbitaceae, Lauraceae, Liliaceae, Rubiaceae, Sapindaceae Acanthaceae, Berberidaceae, Ericaceae, Myrsinaceae, Onagaraceae, Polygonaceae, Rutaceae, Solanaceae, Theaceae etc. showed ACE inhibition. The inhibition of ACE activity has been shown from the different parts of the plants including leaves, stem, stem bark, root, fruit, aerial parts and even from the whole plant. The selection of the plants and their parts is made based on the previous knowledge about the usefulness of traditional medicine in combating the high blood pressure and other complications.

Angelica gigas Angelica keiskei Antidesma madagascariense Antirrhea borbonica Aphloia theiformis

Amaranthus dubius Amaranthus hybridus Andrographis echioides Angelica acutiloba

Abrus precatorius Acacia nilotica Achyranthes aspera Actinida deliciosa Actinostemma lobatum Adenopodia spicata Agapanthus africanus Agave americana Alisma orientale Allium ursinum Allophylus edulis

Botanical names of plant Fabaceae Fabaceae Amaranthaceae Actinidiaceae Cucurbitaceae Mimosaceae Agapanthaceae Agavaceae Alismataceae Liliaceae Sapindaceae Amaranthaceae Amaranthaceae Acanthaceae Apiaceae Apiaceae Apiaceae Euphorbiaceae Rubiaceae Flacourtiaceae

Spiny splinter-bean Agapanthus Century plant, Agave Alisma, Ze xie Bear's garlic Cocú, Chal chal Spleen amaranth Smooth amaranth False waterwillow Japanese Angelica Korean Angelica Ashitaba Antidesma Not found Albino-berry

Family

Crab's eye Scented-pod acacia Devil's horsewhip Kiwifruit Goki-zuru

Common name

Leaf Leaf

Dried root Dried leaf Leaf

Dried root

Leaf Leaf Aerial parts

Aerial parts Thorn Aerial parts Fruit Dried entire plant Leaf Leaf Leaf Dried rhizome Fresh leaf Branches

Part used

Table 1. Antihypertensive plants exhibiting angiotensin converting enzyme inhibition

Acetone Acetone

Ethanol (95%) Decoction Ethanol (95%) Ethanol (80%) Acetone

Water, Ethanol Water, Ethanol Ethanol, Water Water Lyophilized Butanol, Ethanol (70%) Methanol Water Acetone

Water Ethanol, Acetone Ethanol (95%) Ethanol (70%), Water Methanol-Water (1:1)

Extract

Adsersen & Adsersen, 1997 Adsersen & Adsersen, 1997

Ham et al., 1996 Kanetoshi et al., 1993 Ham et al., 1996 Shimizu et al., 1999 Adsersen & Adsersen, 1997

Ramesar et al., 2008 Ramesar et al., 2008 Somanadhan et al., 1999

Duncan et al., 1999 Duncan et al., 1999 Duncan et al., 1999 Han, 1991 Sendl et al., 1992 Arisawa et al., 1989

Nymun et al., 1998 Nymun et al., 1998 Hansen et al., 1995 Jung et al., 2005 Inokuchi et al., 1984

Reference

Inhibition of Angiotensin Converting Enzyme (ACE) 273

Leaf Leaf Bark

Elaeocarpaceae Asteraceae Aristolochiaceae Aristolochiaceae Asteraceae Acanthaceae Myrsinaceae Nyctaginaceae Burseraceae Fabaceae Fabaceae Clusiaceae Clusiaceae

Macqui Davana Ginger Siebold wild ginger Not found Chinese violet Not found Spreading Hogweed Not found Forest flame Mountain ebony Santa maria Poon tree

Boerhavia diffusa Boswellia elongate Butea frondosa Butea parviflora Calophyllum brasiliense Calophyllum tacamahaca

Aspilia helianthoides Asystasia gangetica Badula barthesia

Bark Aerial parts Dried aerial parts Leaf

Aristolochiaceae Aristolochiaceae

Leaf

Root Bark Pulvinus Bark Stem

Dried rizhome Dried root Stem

Arecaceae

Himalayan cobra lily Pipe vine Birthwort

Arisaema consanguineum Aristolochia debilis Aristolochia manshuriensis Aristotelia chilensis Artemisia pallens Asarum heterotropoides Asarum sieboldii

Dried seed

Part used

Arecaceae

Family

Betel nut palm

Common name

Areca catechu

Botanical names of plant

Table 1. (Contd.)

Acetone, Ethanol, Water

Methanol Methanol Acetone, Ethanol, Water Ethanol Water Methanol Ethanol Acetone, Ethanol Ethanol

Water

Water Acetone, Ethanol (95%) Water Ethanol (95%) Ethanol Water

Chromatog. Fraction Methanol-Water (1:1) Tannin fraction Water

Extract

Adsersen & Adsersen, 1997

Alasbahi & Melzig, 2008 Ramesar et al., 2008 Adsersen & Adsersen, 1997 Adsersen & Adsersen, 1997 Hansen et al., 1995 Oleski et al., 2006 Nymun et al., 1998 Nymun et al., 1998 Braga et al., 2007

Han et al., 1991

Hansen et al., 1995 Somanadhan et al., 1999 Han et al., 1991

Han, 1991 Hansen et al., 1995

Inokuchi et al., 1984 Inokuchi et al., 1984 Inokuchi et al., 1996a Han, 1991

Reference

274 RPMP Vol. 29 — Drug Plants III

Asteraceae

Pepperback

Chrysanthemum lavandulaefolium

Dried flowers

Apiaceae

Gotu kola

Fruit

Casuarinaceae

Centella asiatica

Root Herb

Fabaceae Lauraceae

Bark, Fruit, Seed Aerial parts

Leaf Bark

Caricaceae Fabaceae

Celastraceae

Stem

Sapindaceae

Leaf, Stipule Leaf

Bark

Green leaf, Leaf

Part used

Burseraceae

Theaceae

Family

Cecropiaceae Cecropiaceae

Black tea, Indian Assam Broken Orange Pekoe Indian white mahogany Balloonvine heartseed Papaya Golden shower tree Sickle pod Devil's gut, Seashore dodder Australian Pine

Tea, Green tea, Japanese Sencha

Common name

Red cecropia Ambay pumpwood Black-oil tree

Casuarina equisetifolia Cecropia glaziovii Cecropia pachystachya Celastrus paniculatus

Cassia tora Cassytha filiformis

Canarium euphyllum Cardiospermum halicacabum Carica papaya Cassia fistula

Camellia sinensis


Table 1. (Contd.)

Acetone, Ethanol, Water Acetone, Ethanol, Water Water

Methanol Methanol

Ethanol, Water

Water Acetone, Ethanol, Water Acetone, Ethanol Acetone, Ethanol

Water

Acetone, Ethanol

Acetone, Phosphatebuffered saline Phosphatebuffered saline

Extract

Han et al., 1991

Hansen et al., 1995

Somanadhan et al., 1999

Dubois et al., 2001 Dubois et al. ,2001


Somanadhan et al., 1999 Adsersen & Adsersen, 1997

Adsersen & Adsersen, 1997 Somanadhan et al., 1999



Persson et al., 2006

Cho et al., 1993 Persson et al., 2006

Reference


Fresh fruit Leaf Dried fruit

Rubiaceae Combretaceae Euphorbiaceae Rosaceae Rosaceae Lytharaceae Cupressaceae Cucurbitaceae Fabaceae

Maroon coffee Chameleon vine Rushfoil, Croton Chinese haw Hawthorn Tenuissimum cigar flower Italian cypress Sweet tea vine Fragrant rosewood

Dried aerial parts Dried wood

Dried fruit

Bark

Leaf Leaf

Leaf Leaf Leaf

Rutaceae Rutaceae Verbenaceae

Dried bark

Lauraceae

Leaf

Cissus hamaderohensis Citrus limon Clausena anisata Clerodendrum infortunatum Coffea mauritanica Combretum fruticosum Cordemoya integrifolia Crataegus pinnatifida Crataegus sp. Cuphea cartagenesis Cupressus sempervirens Cynostemma pentaphylla Dalbergia odorifera

Dried bark

Lauraceae

Part used

Vitaceae

Chinese cinnamon Cinnamon

Cinnamomum cassia Cinnamomum zeylanicum

Family

Achira, African aloe Lemon Horsewood Bhantaka

Common name


Table 1. (Contd.)

Water

Infusion

Flavonoid fraction

Methanol-Water (1:1) ......

Acetone, Ethanol, Water Water

Water Ethanol

Water Water Water

Chromatog. Fraction, Water, MethanolWater (1:1) Methanol

Tannin fraction

Extract

Han et al., 1991

Chen et al., 1996

Meunier et al., 1987

Inokuchi et al., 1984 Castro Braga et al., 2000

Han et al., 1991


Adsersen & Adsersen, 1997 Braga et al., 2007

Adsersen & Adsersen, 1997 Duncan et al., 1999 Somanadhan et al., 1999

Oleski et al., 2006

Inokuchi et al., 1984


Reference


Fabaceae

Myrsinaceae Fabaceae Ephedraceae

Coat buttons Sea bean Ma huang Ephedra

Ephedra sp.

Ephedraceae

Fruit stem Seed Dried aerial parts Dried entire plant

Leaf

Myrsinaceae

Siberian ginseng Liane soap

Araliaceae

Dried stem, Bark Dried stem

Araliaceae

Eleutherococcus divaricatus Eleutherococcus senticosus Embelia angustifolia Embelia basal Entada pursaetha Ephedra sinica

Leaf, Root

Ebenaceae Leaf

Native hop, Hop bush Oni ukogi

Leaf

Iridaceae

Root

Sapindaceae

Diospyros melanoxylon Dodonea viscosa

Leaf

Fabaceae

Coin-leaf desmodium Sickle bush African iris, Fortnight lily Ebony

Leaf, Stem

Fabaceae

Famola kantsy

Root

Fabaceae

Trefle gros

Desmodium triquetrum Desmodium gangeticum Desmodium styracifolium Dichrostachys cinerea Dietes iridioides

Part used

Family

Common name


Table 1. (Contd.)

Chromatog fraction

Ethanol, Acetone Ethanol (95%), Water Tannin fraction

Acetone, Ethanol

Chloroform

Butanol

Acetone

Water, Ethanol

Water

Acetone, Ethanol (95%) Water Water

Ethanol, Acetone, Water Ethanol (95%), Water

Extract


Somanadhan et al., 1999 Hansen et al., 1995 Inokuchi et al., 1985


Takashari et al., 1993

Leem, 1990


Nymun et al., 1998

Duncan et al., 1999

Nymun et al., 1998

Hansen et al., 1995

Hansen et al., 1995

Nymun et al., 1998

Reference


Epilobium angustifolium Epimedium alpinum Epimedium brevicornum Epimedium macranthum Equisetum hyemale Erythroxylum laurifolium Eugenia heyneana Euodia simplex Euphorbia hirta Euphorbia humifusa Fritillaria sp. Fritillaria ussuriensis Fuchsia magellanica Galinsoga parviflora Geranium core-core Gunnera tinctoria


Table 1. (Contd.)

Dried entire plant Dried stem Dried leaf

Leaf Aerial parts Leaf

Berberidaceae Equisetaceae Erythroxylaceae Myrtaceae Rutaceae Euphorbiaceae Euphorbiaceae Liliaceae Liliaceae Onagraceae Asteraceae Geraniaceae Gunneraceae

Horsetail Bois de ronde Katjamun Not found Cats hair Trailing spurge Fritillaria Ping bei mu Fuchsia Gallant soldier, Potato weed Geranium core-core Gunnera

Aerial parts

Root Leaf Dried leaf Dried aerial parts Dried bulb Bulb

Dried aerial parts Not specified

Berberidaceae Berberidaceae

Herb

Part used

Onagraceae

Family

Willow herb, Fire weed Alpine epimedium Horny goat weed Barrenwort

Common name

Han et al., 1991 Hansen et al., 1996a Adsersen & Adsersen, 1997 Nymun et al., 1998 Adsersen & Adsersen, 1997 Williams et al., 1997 Han et al., 1991


Han et al., 1991


Kiss et al., 2004

Reference

Butanol, Ethanol (95%), Ethyl acetate

Water

Methanol

Hansen et al., 1995

Hansen et al., 1995

Ramesar et al., 2008

Methanol-Water (1:1) Inokuchi et al., 1984 Butanol, Ethylacetate, Kang et al., 2002 Water Water Hansen et al., 1995

Chromatog. Fraction Methanol-Water (1:1) Water Ethanol (100%) Ethanol, Acetone Ethanol, Water Ethanol, Acetone Methanol Water

Methanol-Water (1:1) Tannin fraction Water

Ethylacetate

Extract


Justicia flava Kalanchoe farinacea Leea guinenis Leea rubra

Jatropha curcas

Jasminun grandiflorum Jasminum multiflorum Jasminum sambac

Houttuynia cordata Humboldtia vahliana Jasminun azoricum

Gynura procumbens Hedysarum polybotrys Hexachlamys edulis Hibiscus sabdariffa


Table 1. (Contd.)

Leaf Leaf Leaf Aerial parts Leaf Aerial parts

Fabaceae Oleaceae

Oleaceae Oleaceae Oleaceae Euphorbiaceae Acanthaceae Crassulaceae Leeaceae Leeaceae

Jelavedesa Jasmine

Spanish jasmine Downy jasmine, Star jasmine Arabian jasmine, Mogra Barbados nut, Physic nut Yellow justicea Mealy kalanchoe Léia-alaranjada Hawaiian Holly, Red Leea

Water Methanol Ethanol, Acetone Ethanol

Water, Ethanol

Water

Acetone, Water, Ethanol (95%) Bark Ethanol, Acetone Dried aerial parts Dichloromethane, Chromatog. Fraction, Ethyl acetate, Water Aerial part Ethanol, Acetone, Water Fresh leaf Acetone

Saururaceae

Chameleon plant

Entire plant

Calyx

Malvaceae

Acetone-Water (1:1), Ethanol (95%) Water

Leaf

Dried root

Fabaceae

Aqueous fraction (FA-1) Water

Extract

Myrtaceae

Leaf

Part used

Asteraceae

Family

Pessegueirodo-mato Roselle

Sambung nyawa Not found

Common name

Somanadhan et al., 1999 Adsersen & Adsersen, 1997 Ramesar et al., 2008 Oleski et al., 2006 Adsersen & Adsersen, 1997 Braga et al., 2007



Somanadhan et al., 1999 Somanadhan et al., 1998

Herrera-Arellano et al., 2007 Hansen et al., 1995

Hansen et al., 1995

Han et al., 1991

Hoe et al., 2007

Reference


Oenothera biennis

Morus alba Musanga cecropioides

Moringa oleifera

Monimia ovalifolia Monimia rotundifolia

Machilus thunbergii Mangifera indica Mansoa hirsuta Merremia tridentate Marrubium radiatum Mesembruanthemum spp Molinaea alternifolia Momordica balsamina

Common evening primrose

White wood gaulettes Balsam apple, Bitter melon Mapou Mapou with large sheets Drumstick, Horseradish tree White mulberry African Corkwood, Umbrella Tree

Japanese climbing fern Tabu-no-ki tree Indian mango Cipó-de-alho Mogra Hoarhound Ice plant

Lygodium japonicum

Lycium chinese

Roundhead lespedeza Chinese boxthorn

Common name

Lespedeza capitata


Table 1. (Contd.)

Leaf Leaf Leaf fruit Dried leaf Leaf, Bark Leaf Seed

Monimiaceae Monimiaceae Moringaceae Moraceae Moraceae

Onagraceae

Leaf Leaf

Sapindaceae Cucurbitaceae

Lauraceae Anacardiaceae Bignoniaceae Convolvulaceae Lamiaceae Aizoaceae

Dried aerial parts Bark Bark Leaf Aerial parts Aerial parts Leaf

Dried root bark

Solanaceae Schizaeaceae

Dried leaf

Part used

Fabaceae

Family

Seed oil

Methanol-Water (1:1) Water, Methanol

Water

Ethanol, Water Ethanol, Acetone

Ethanol, Water Water

Methanol, Chloroform Acetone, Ethanol ...... Ethanol (95%), Water Decoction Water, Ethanol

Chloroform Not stated Water

Flavonoid fraction

Extract

Somanadhan et al., 1999 Adsersen & Adsersen, 1997 Inokuchi et al., 1984 Dongmo et al., 2002 Adeneye et al., 2006 Dubois et al., 2001 Scholkens et al., 1982

Adsersen & Adsersen, 1997 Adsersen & Adsersen, 1997

Adsersen & Adsersen, 1997 Ramesar et al., 2008

Oh et al., 1997 Somanadhan et al., 1999 Castro Braga et al., 2000 Hansen et al., 1995 Loizzo et al., 2008 Duncan et al., 1999

Morota et al., 1987 Yahara et al., 1993 Han et al., 1991

Wagner & Elbl, 1992

Reference


Phoenix roebelinii Pinellia ternata Piper betle Piper futokadsura

Phyllanthus phillyreifolius Physalis viscosa

Panax ginseng Passiflora edulis Passiflora quadrangularis Pavonia odorata Philippia montana Phyllanthus niruri

Olea europaea ssp. africana Olea lancea Origanum vulgare Ouratea semiserrata Oxygonum sinuatum Paeonia albiflora Paeonia moutan


Table 1. (Contd.)

Leaf Leaf Dried rhizome Leaf Dried aerial parts

Araliaceae Passifloraceae Passifloraceae Malvaceae Ericaceae Euphorbiaceae Euphorbiaceae Solanaceae Arecaceae Araceae Piperaceae Piperaceae

Asian ginseng Passion fruit Giant granadilla Pavonia Branle white Stone breaker Wood negresse Starhair groundc herry Pigmy date palm Crowdipper Betel Kasura stem

Root Leaf Dried entire plant Entire plant Leaf Dried entire plant Bark

Leaf ..... Stem Leaf Dried root Dried bark

Oleaceae Lamiaceae Ochnaceae Polygonaceae Paeoniaceae Paeoniaceae

Bois malaya Oregano Not found Mbigili, Song'e Chinese peony Moutan

Leaf

Part used

Oleaceae

Family

Wild olive

Common name

Ethanol Water Water, Ethanol Water

Ethanol, Acetone, Water Methanol

Ethanol Ethanol, Water Chromatog. Fraction

Water, Ethanol Water ....... Water Water Chromatog. Fraction Methanol-Water (1:1) Tannin fraction Water Water, Acetone Water

Water

Extract

Braga et al., 2007 Han et al., 1991 Somanadhan et al., 1999 Han et al., 1991

Adsersen & Adsersen, 1997 Ramesar et al., 2008

Somanadhan et al., 1999 Adsersen & Adsersen, 1997 Ueno et al., 1988

Adsersen & Adsersen, 1997 Apostolidis et al., 2006 Castro Braga et al., 2000 Ramesar et al., 2008 Han et al., 1991 Inokuchi et al., 1984 Inokuchi et al., 1984 Inokuchi et al., 1985 Persson et al., 2006a Adsersen & Adsersen, 1997 Okamot et al., 1994


Reference


Root Entire plant

Rubiaceae Fabaceae Fabaceae Fabaceae Polypodiaceae Santalaceae

Brittle wood Velvet bean Moovila, Long pepper Kudzu vine Japanese felt fern Quinchamali

Psathura borbonica Pseudarthria hookeri

Pseudarthria viscida

Quinchamalium chilense

Pueraria lobata Pyrrosia lingua

Root

Anacardiaceae

Bios de poupart

Poupartia borbonica

Aerial parts

Leaf Root

Rosaceae

Cinquefoil

Fruit body Dried aerial parts Dried entire plant Dried root Dried aerial parts Dried entire plant Bark

Potentilla sp.

Oyster mushroom Polyporaceae Birdgrass, Doorweed Liliaceae

Pleurotus sajor-caju Polygonatum aviculare

Polygalaceae Rosaceae

Plantaginaceae

Chinese plantain

Plantago asiatica

Dried aerial parts Entire plant

Part used

Polygonum multiflorum Tuber fleece flower Potentilla chinensis Chinese cinquefoil

Anacardiaceae

Mastic tree

Pistacia lentiscus

Family

Common name


Table 1. (Contd.)

Ethanol (95%) Acetone, Ethanol (95%), Water Ethanol (95%)

Chromatog. Fraction, Methanol-Water (1:1) Ethanol, Water, Acetone Ethanol, Water Acetone, Ethanol (95%) Ethanol (95%), Water

Hansen et al., 1995

Hansen et al., 1995 Hansen et al., 1995

Hansen et al., 1995

Adsersen & Adsersen, 1997 Hansen et al., 1995



Han et al., 1991 Inokuchi et al., 1985


Methanol-Water (1:1) Water Tannin fraction

Ikemizu et al., 1995 Inokuchi et al., 1985

Hansen et al., 1995

Sanz et al., 1993

Reference

Acetone, Ethanol (95%), Water Not stated Tannin fraction

Flavonoid fraction

Extract


Santalaceae Crassulaceae Malvaceae

Stringy stonecrop Common wireweed

Sida acuta

Root

Entire plant

Nut shell

Aerial parts ...... Dried root Dried root Bark

Dried rhizome Dried rhizome

Polygonaceae Polygonaceae

Lamiaceae Lamiaceae Rosaceae Asteraceae Anacardiaceae

......

Crassulaceae

...... Aerial parts Aerial parts Unripe seed

......

Crassulaceae

Lamiaceae Amaranthaceae Amaranthaceae Salvadoraceae

......

Part used

Lamiaceae

Family

Not found

Rosemary Tumbleweed Tumbleweed Salt bush, Toothbrush tree Not found Danshen Burnet bloodwort Costus, Kuth Chilean pepper tree

Duo mao bian zhong Da hua hong jing tian Golden root, Roseroot Turkey rhubarb Rhubarb

Common name

Scleropyrum pentandrum Sedum sarmentosum

Salvia acetabulosa Salvia miltiorrhiza Sanguisorba officinalis Saussurea lappa Schinus latifolius

Rosmarinus officinalis Salsola oppositifolia Salsola soda Salvadora persica

Rheum palmatum Rheum sp.

Rhodiola rosea

Rhodiola crenulata

Rabdosia coetsa


Table 1. (Contd.)

Decoction Water Methanol-Water (1:1) Methanol-Water (1:1) Butanol, Ethyl acetate, Ethanol (95%), Ethanol- Water (7:3) Acetone, Ethanol, Water Acetone, Water, Ethanol (95%) Acetone, Water

Tannin fraction Chromatog. Fraction, Methanol-Water (1:1) Water Ethylacetate Ethylacetate Water

Ethanol, Water

Water

Ethylacetate

Extract

Hansen et al., 1995

Hansen et al., 1995

Nymun et al., 1998

Loizzo et al., 2008 Kang et al., 2002a Inokuchi et al., 1984 Inokuchi et al., 1984 Hansen et al., 1995

Apostolidis et al., 2006 Loizzo et al., 2007 Loizzo et al., 2007 Nymun et al., 1998

Inokuchi et al., 1985 Inokuchi et al., 1984

Kwon et al., 2006

Kwon et al., 2006

Li et al., 2008

Reference


Root Leaf, Leaf root

Stangeriaceae Combretaceae Combretaceae Combretaceae

Myrobalan, Hardad Combretaceae Bullhead, Gokshura Zygophyllaceae

Tiliaceae Alliaceae Rubiaceae Ericaceae Ericaceae

Natal grass cycad Catappa benzoin Silver greywood Indian almond

Snakegourd, Chinese cucumber Burr bush, Diamond burrbark Wild garlic Cat's Claw

Stangeria eriopus Terminalia bentzoe Terminalia bialata Terminalia catappa

Terminalia chebula Tribulus terrestris

Trichosanthes kirilowii

Uncaria rhynchophylla

Vaccinium ashei reade Blueberry Vaccinium macrocarpon Cranberry

Tulbaghia violacea

Triumfetta rhomboidea

Leaf .......

Dried branches, Root

Dried root Dried aerial parts Leaf Leaf Bark Aerial parts, Leaf Fruit Aerial parts, Fruit Dried fruit

Menispermaceae Solanaceae

Sinomenium acutum Solanum nigrum

Cucurbitaceae

Root

Sida retusa

Sida cordifolia Malvaceae

Part used Root

Family Malvaceae

Common name Heart-leaf sida, Indian hemp Paddy's lucern, Jelly leaf Chinese moonseed Black nightshade


Table 1. (Contd.)

Methanol, Water Water, Ethanol Methanol-Water (1:1) Acetone, Ethanol (95%) Water Water Water

Ethanol (95%), Water

Water

Acetone Water

Water Water Ethanol Ethanol, Water

Water Water

Acetone, Water

Acetone, Water

Extract

Sakaida et al., 2007 Apostolidis et al., 2006

Ramesar et al., 2008 Duncan et al., 1999 Inokuchi et al., 1984 Hansen et al., 1995

Hansen et al., 1995

Han et al., 1991

Duncan et al., 1999 Adsersen & Adsersen, 1997 Somanadhan et al., 1999 Braga et al., 2007 Adsersen & Adsersen, 1997 Somanadhan et al., 1999 Somanadhan et al., 1999

Han et al., 1991 Han et al., 1991

Hansen et al., 1995

Hansen et al., 1995

Reference


European cranberrybush viburnum, Crampbark Mistletoe fruit Wine grape Arbre mouche a miel Pala indigo, Indrajao

Common name

Leaf Dried fruit Leaf Seed

Loranthaceae Vitaceae Cunoniaceae Apocynaceae

Astragalin Atractylodinol Butein

Afzelin Ala-Tyr Apigenin Arrivacin A & B Asperoside Flavonoid Oxygen heterocycle Polyphenol

Phenylpropanoid glycoside Phenylpropanoid glycoside Flavonoid Peptide Flavonoid Sesquiterpene Cardenolide

Acteoside

Acteoside isomer

Class of the chemical co mpou nd

Chemical n am e

Diospyros kaki Atractyloides japonica Plant compound

Erythroxylum laurifolium Zea mays Ailanthus excelsa Ambrosia psilostachya Eucommia ulmoides

Clerodendron trichotomum Abeliophyllum distichum Clerodendron trichotomum

Botanical name (Source)

Japanese Persimmon Chinese Atractylodes …..

Bois de ronde Corn Ailanthus, Ardu Cuman ragweed Hardy rubber tree

Reference

Ebenaceae Asteraceae …..

Erythroxylaceae Poaceae Simaroubaceae Asteraceae Eucommiaceae

Hansen et al., 1995 Yang et al., 2007 Loizzo et al., 2007 Chen et al., 1991 Yamadaki et al., 1992 Kameda et al., 1987 Sakurai et al., 1993 Kang et al., 2003b

Kang et al., 2003 Oh et al., 2003a Kang et al., 2003

Ref erence

Adsersen & Adsersen, 1997 Meunier et al., 1987 Adsersen & Adsersen, 1997 Nymun et al., 1998

Jonader et al., 1989

Harlequin glorybower Verbenaceae White forsythia Oleaceae Harlequin glorybower Verbenaceae

Family

Water, Acetone Flavonoid fraction Ethanol, Acetone Water

Ethanol-Water (1:1)

Extract

Common n am e

Dried bark

Part used

Caprifoliaceae

Family

Table 2. List of plant-derived ACE inhibitory compounds.

Viscum triflorum Vitis vinifera Weinmannia tinctoria Wrightia tinctoria

Viburnum opulus


Table 1. (Contd.)


Daphne odora Lycium chinense Frittilaria verticillata Frittilaria verticillata Cuscuta japonica Cuscuta japonica Phyllanthus niruri Camellia sinensis Camellia sinensis Camellia sinensis Camellia sinensis Oenothera paradoxa

Lipid Lipid Phenolic acid Phenolic acid Coumarin Flavonoid

(-)-Epicatechin gallate

Flavonoid

Phyllanthus niruri Fritillaria verticillata Microtoena prainiana

Tannin Lipid Phenylpropanoid glycoside Flavonoid Lipid

Daphnodorin A & B Dimorphecolic acid, alpha Dimorphecolic acid, alpha (DL) Dimorphecolic (DL) acid, beta 3,4-Di-Ocaffeoylquinic acid 3,5-Di-OEllagic acid (-)-Epicatechin

Allophylus edulis Camellia sinensis

Flavonoid Flavonoid

Catechin, (+) Catechin-3-Ogallate, epi (-) Corilagin Coriolic acid, (DL) Crenatoside

…… Capsicum sp. Capsicum sp.

Tannin Diterpene Diterpene

Caffeoylquinates Capsianoside A Capsianoside C



Chemical n am e

Table 2. (Contd.)

Japanese dodder Stone breaker Green tea Black tea Green tea Black tea Evening primerose

Japanese dodder

Fritillary

Fritillary

Winter daphne Chinese boxthorn

Stone breaker Fritillary Prain microtoena

Cocú, Chal chal Korean green tea

Chinese herbs Chilli pepper Chilli pepper

Common n am e

Cuscutaceae Euphorbiaceae Theaceae Theaceae Theaceae Theaceae Onagraceae

Cuscutaceae

Liliaceae

Liliaceae

Thymelaeaceae Solanaceae

Euphorbiaceae Liliaceae Lamiaceae

Sapindaceae Theaceae

….. Solanaceae Solanaceae

Family

Oh et al., 2002 Ueno et al., 1988 Persson et al., 2006 Persson et al., 2006 Persson et al., 2006 Persson et al., 2006 Kiss et al., 2008

Oh et al., 2002

Niitsu et al., 1987

Niitsu et al., 1987

Takai et al., 1999 Morota et al., 1987

Liu et al., 2003 Yahara et al., 1990 Izumitani et al., 1990 Cho et al., 1993 Cho et al., 1993 Uchida et al., 1987 Ueno et al., 1988 Niitsu et al., 1987 Li et al., 2004

Reference


Peptide

Isorhamnetin3-betalucopyranoside Isoquercitrin

Isoorientin

Isomartynoside

Isocrenatoside

Flavonoid

Phenylpropanoid glycoside

Peptide Peptide Phenylethanoid glycoside Phenylethanoid glycoside Phenylpropanoid glycoside Flavonoid

Triticum spp.

Peptide Alkoloid

HHL 2"-hydroxy -nicotianamine IAP

IAYKPAG IFL Isoacteoside

Glycine max Fagopyrum esculentum

Sesquiterpene

Gossypol

Diospyros kaki

Cecropia glaziovii Cecropia hololeuca Musanga cecropioide Sedum sarmentosum

Clerodendron trichotomum

Microtoena prainiana

Spinacia oleracea Glycine max Abeliophyllum distichum

...... Phyllanthus niruri Allophylus edulis Phyllanthus urinaria Gossypium sp.

Tannin Tannin

Gallotannins Geraniin



Chemical n am e

Table 2. (Contd.)

Lamiaceae

Amaranthaceae Fabaceae Oleaceae

Poaceae

Fabaceae Polygonaceae

…... Euphorbiaceae Sapindaceae Euphorbiaceae Malvaceae

Family

Japanese persimmon

Red cecropia Silver cecropia African Corkwood Stringy Stonecrop

Ebenaceae

Cecropiaceae Cecropiaceae Moraceae Crassulaceae

Harlequin glorybower Verbenaceae

Prain microtoena

Spinach Soybean White forsythia

Wheat

Korean soybean Buckwheat

Chinese herbs Stone breaker Cocú, Chal chal Gripeweed Cotton

Common n am e

Kameda et al., 1987

Dubois et al., 2001 Dubois et al., 2001 Dubois et al., 2001 Oh et al., 2004

Kang et al., 2003

Li et al., 2004

Motoi & Kodama, 2003 Yang et al., 2003 Kuba et al., 2003 Oh et al., 2003a

Liu et al., 2003 Ueno et al., 1988 Arisawa et al., 1989 Lin et al., 2008 Krassnigg et al., 1984 Shin et al., 2001 Aoyagi, 2006

Reference


Camellia sinensis Camellia sinensis Rabdosia coetsa Evodia rutaecarpa Fagopyrum sp. Stephania tetrandra Stephania tetrandra Ficus carica Ficus carica Helianthus annuus Phyllanthus niruri Camellia sinensis Camellia sinensis Camellia sinensis Camellia sinensis

Flavonoid Flavonoid

Alkaloid Alkaloid Peptide Peptide Peptide Benzenoid Flavonoid Flavonoid Flavonoid Flavonoid

Epigallocatechin gallate (-)-Epigallocatechin gallate Ethyl caffeate Evocarpine Fagopyrum tripeptide Fangchinolium hydroxide Fenfangjine F, H and I Ficus oligopeptide FLP-1, -2 & -3 Ficus peptide FLP-1, -2 & -3 FVNPQAGS Gallic acid Gallocatechin, (+) Gallocatechin, epi (-) Gallocatechin, epi, 3-O-gallate (-) Gallocatechin-3-Ogallate (-), epi (-) Phenolic Alkaloid Peptide

Camellia sinensis Camellia sinensis Camellia sinensis

Flavonoid

(-)-Epigallocatechin



Chemical n am e

Table 2. (Contd.)

Korean green tea

Sunflower Stone breaker Korean green tea Korean green tea Korean green tea

Common fig

Common fig

Han fang ji

Han fang ji

Green tea Black tea Duo mao bian zhong Evodia, Wu-Zhu-Yu Buckwheat

Green tea Black tea Green tea

Common n am e

Persson et al., 2006 Persson et al., 2006 Li et al., 2008 Lee et al., 1998 Koyama et al., 1993

Persson et al., 2006 Persson et al., 2006 Persson et al., 2007

Reference

Theaceae

Asteraceae Euphorbaceae Theaceae Theaceae Theaceae

Moraceae

Moraceae

Cho et al., 1993

Maruyama et al., 1990 Maruyama et al., 1989 Megías et al., 2004 Ueno et al., 1988 Cho et al., 1993 Cho et al., 1993 Uchida et al., 1987

Menispermaceae Ogino et al., 1998

Menispermaceae Ogino et al., 1986

Theaceae Theaceae Lamiaceae Rutaceae Polygonaceae

Theaceae Theaceae Theaceae

Family


Ailanthus excelsa

Ailanthus excelsa

Diospyros kaki Vigna radiata Vigna radiata Schinus molle Schinus molle Clerodendron trichotomum

Peptide Flavonoid Flavonoid Flavonoid

Flavonoid

Flavonoid Peptide Peptide Triterpene Triterpene Phenylpropanoid glycoside Iridoid Lignan

IY Kaempferol

Kaempferol-3-alphaarabinopyranoside Kaempferol-3-Oalpha-ara binopyranoside Kaempferol-3-Obetagalactopyranoside Kaempferol-3O-galloyl-glucose KDYRL KLPAGTLF Lanosten (20-R) Lanosten (20-S) Leucosceptoside

Ligstroside aglycones Liriodendrin

Sedum sarmentosum

Peptide

IVY

Ligustrum vulgare Eucommia ulmoides

Musanga cecropioides Cecropia pachystachya Sesamum indicum Triticum spp. Brassica napus …..

Flavonoid

Isovitexin



Chemical n am e

Table 2. (Contd.)

Mung bean Mung bean Peruvian pepper Peruvian pepper Wild privet, European privet Danshen, Red sage Hardy rubber tree

Japanese persimmon

Ailanthus, Ardu

Ailanthus, Ardu

Stringy Stonecrop

African Corkwood Ambay pumpwood Sesame wheat Rapeseed Greens

Common n am e

Lamiaceae Eucommiaceae

Fabaceae Fabaceae Anacardiaceae Anacardiaceae Oleaceae

Ebenaceae

Simaroubaceae

Simaroubaceae

Crassulaceae

Moraceae Cecropiaceae Pedaliaceae Poaceae Brassicaceae …..

Family

Kiss et al., 2008 Yamadaki et al., 1992

Li et al., 2006 Li et al., 2006 Olafsson et al., 1997 Olafsson et al., 1997 Kang et al., 2003

Kameda et al., 1987

Loizzo et al., 2007

Loizzo et al., 2007

Dubois et al., 2001 Dubois et al., 2001 Hong et al., 2008 Matsui et al., 1999 Marczak et al., 2003 Olszanecki et al., 2008 Oh et al., 2004

Reference


Lycium chinense

Spinacia oleracea Zea mays Sesamum indicum Clerodendron trichotomum Cuscuta japonica Cuscuta japonica Rabdosia coetsa Jasminum azoricum

Peptide Peptide Peptide Peptide Peptide Phenylpropanoid glycoside Tannin Tannin Polyphenol Iridoid Alkaloid Peptide Pepide Peptide Xanthone

Lyciumin B

LRIPVA LRP, LSP, LQP, LPP LVY, LSA, LQP, LKY Martynoside

Methyl 3,4-Di-Ocaffeoylquinate Methyl 3,5-Di-Ocaffeoylquinate Methyl rosmarinate Molihuaside A

Monocrotaline MRW MRWRD Nicotinamide Norathyriol

Crotalaria sp. Spinacia oleracea Spinacia oleracea Corchorus olitorius Trypterospermum lanceolatum

Lycium chinense

Salviae miltiorrhiza Ailanthus excelsa Ailanthus excelsa

Polyphenol Flavonoid Flavonoid

Lithospermic acid B Luteolin Luteolin-7-O-glucopyranoside Lyciumin A



Chemical n am e

Table 2. (Contd.)

Rattle pod Spinach Spinach Jute …..

Duo mao bian zhong Jasmine

Japanese dodder

Japanese dodder

Spinach Maize Sesame Harlequin glorybower

Wolfberry, goji berry

Wolfberry, goji berry

Red sage, Danshen Ailanthus, Ardu Ailanthus, Ardu

Common n am e

Fabaceae Amaranthaceae Amaranthaceae Tiiaceae …..

Lamiaceae Oleaceae

Cuscutaceae

Cuscutaceae

Amaranthaceae Poaceae Pedaliaceae Verbenaceae

Solanaceae

Solanaceae

Lamiaceae Simaroubaceae Simaroubaceae

Family

Li et al., 2008 Somanadhan et al., 1998 Molteni et al., 1984 Yang et al., 2003 Yang et al., 2003 Kimoto et al., 1998 Sutter & Wang, 1993

Oh et al., 2002

Oh et al., 2002

Yahara et al., 1989 Morita et al., 1996 Yahara et al., 1989 Yahara et al., 1993 Yang et al., 2003 Hong et al., 2008 Hong et al., 2008 Kang et al., 2003

Kang et al., 2003a Loizzo et al., 2007 Loizzo et al., 2007

Reference


Fritillaria ussuriensis Oenothera paradoxa Rhei rhizoma/ Rheum palmatum Oenothera paradoxa Lespedeza capitata Camellia sinensis Lespedeza capitata

Alkoloid Flavonoid Flavonoid

Flavonoid

Flavanol Flavonoid Flavonoid

Glycine max Glycine max Microtoena prainiana

Oenothera paradoxa Olea europaea Ligustrum vulgare

Ellagitannin Iridoid Iridoid Isoflavone Isoflavone Glycoside

Fritillaria verticillata

Lipid

6"-O-malonyldaidzin 6"-O-malonylgenistin 3"'-Omethylcrenatoside Peimisine Penta-O-g alloyl-beta-D-glucose Procyanidins (dimer and hexamer) Proanthocyanidin B3 Procyanidin B-1 Procyanidin B-2, 3,3'-di-O-gallate Procyanidin B-3

Lycium chinensis

Lipid

Octadeca-10trans-12-cis-15cis-trienoic acid, 9-hydroxy Octadeca-9trans-11-transdienoic acid, 13-hydroxy Oenothein B Oleacein Oleuropein



Chemical n am e

Table 2. (Contd.)

Roundhead lespedeza

Evening primerose Roundhead lespedeza Korean green tea

Rhubarb

Ping bei mu Evening primerose

Evening primerose Olive Wild privet, European privet Soybean Soybean Prain microtoena

Fritillary

Wolfberry, Goji berry

Common name

Fabaceae

Onagraceae Fabaceae Theaceae

Polygonaceae

Liliaceae Onagraceae

Fabaceae Fabaceae Lamiaceae

Onagraceae Oleaceae Oleaceae

Liliaceae

Solanaceae

Family

Wagner et al., 1992

Kiss et al., 2008 Wagner et al., 1992 Uchida et al., 1987

Uchida et al., 1987

Oh et al., 2003 Kiss et al., 2008

Wu & Muir, 2008 Wu & Muir, 2008 Li et al., 2004

Kiss et al., 2008 Hansen et al., 1996 Kiss et al., 2008

Niitsu et al., 1987

Morota et al., 1987

Reference


Sedum sarmentosum

Sedum sarmentosum

Diospyros kaki

Flavonoid

Flavonoid

Flavonoid Flavonoid

Procyanidin C-2 Procyanidin glycoside Pycnogenol Quercetin-3-O-alphaarabinopyranoside Quercetin-3-O-alpha(6"'-caffeoylglucosylbeta-1,2-rhamnoside), Quercetin 3-O-alpha(6"'-p-coumaroyl glucosyl-beta-1, 2-rhamnoside) Quercetin-3-O(2"-O-galloyl)glucoside Flavonoid

Flavonoid

Procyanidin C-1, 3,3',3"-tri-O-gallate

Flavonoid Flavonoid

Flavonoid Flavonoid

Camellia sinensis Rhei rhizoma/ Rheum palmatum Lespedeza capitata Cecropia glaziovii Cecropia hololeuca Camellia sinensis Rhei rhizoma/ Rheum palmatum Lespedeza capitata Rhei rhizoma/ Rheum palmatum Ailanthus excelsa Pinus maritima

Flavonoid

Procyanidin B-6 Procyanidin C1

Camellia sinensis

Flavonoid

Procyanidin B-3, 3-O-gallate Procyanidin B-5, 3,3'-di-O-gallate



Chemical n am e

Table 2. (Contd.)

Japanese Persimmon

Stringy Stonecrop

Ailanthus, Ardu Cluster pine, Maritime pine Stringy Stonecrop

Roundhead lespedeza Rhubarb

Roundhead lespedeza Red cecropia Silver cecropia Korean green tea Rhubarb

Korean green tea Rhubarb

Korean green tea

Common name

Ebenaceae

Crassulaceae

Crassulaceae

Simaroubaceae Pinaceae

Fabaceae Polygonaceae

Fabaceae Cecropiaceae Cecropiaceae Theaceae Polygonaceae

Theaceae Polygonaceae

Theaceae

Family

Kameda et al., 1987 Arisawa et al., 1989

Oh et al., 2004

Oh et al., 2004

Loizzo et al., 2007 Packer et al., 1999

Wagner et al., 1992 Uchida et al., 1987

Wagner et al., 1992 Dubois et al., 2001 Dubois et al., 2001 Uchida et al., 1987 Uchida et al., 1987

Uchida et al., 1987 Uchida et al., 1987

Cho et al., 1993

Reference


Evodia rutaecarpa

Oryza sativus Rabdosia coetsa Abeliophyllum distichum Brassica napus Salvia miltiorrhiza Salvia miltiorrhiza Jasminum azoricum Jasminum azoricum

Alkaloid

Peptide Polyphenol Flavonoid glycoside Peptide Polyphenol Polyphenol Iridoid Iridoid

Diospyros kaki

Flavonoid Evodia rutaecarpa

Erythroxylum laurifolium

Flavonoid

Alkaloid

Sedum sarmentosum

Flavonoid

Quinolone, 1methyl-2-[(cis-4-cis7)-4,7-tridecadienyl] Quinolone, 1-methyl2-[pentadeca-cis6-cis-9-dienyl] RDHP Rosmarinic acid Rutin RIY Salvianolic acid Salvianolic acid B Sambacein I, II and III Sambacoside A

Allophylus edulis

Flavonoid

Quercetin-3-Obeta-D-glucoside Quercetin-3beta-glucopyranoside Quercitrin 1996a Quercitrin, iso



Chemical n am e

Table 2. (Contd.)

Jasmine

Asian rice Duo mao bian zhong White forsythia Rapeseed Red sage, Danshen Red sage, Danshen Jasmine

Evodia, Wu-Zhu-Yu

Evodia, Wu-Zhu-Yu

Japanese Persimmon

Bois de ronde

Stringy Stonecrop

Cocú, Chal chal

Common name

Oh et al., 2004

Arisawa et al., 1989

Reference

Oleaceae

Poaceae Lamiaceae Oleaece Brassicaceae Lamiaceae Lamiaceae Oleaceae

Rutaceae

Rutaceae

Ebenaceae

Hong et al., 2008 Li et al., 2008 Oh et al., 2003a Marczak et al., 2003 Gao et al., 2004 Gao et al., 2004 Somanadhan et al., 1998 Somanadhan et al., 1998

Lee et al., 1998

Lee et al., 1998

Kameda et al., 1987

Erythroxylaceae Hansen et al.,

Crassulaceae

Sapindaceae

Family


Zea mays Sesamum indicum Glycine max Glycine max Vigna radiata Brassica napus Brassica napus Glycine max Tripterospermum lanceolatum Tripterospermum lanceolatum

Peptide Alkaloid Alkoloid Alkoloid Flavonoid Flavonoid Flavonoid Flavonoid Peptide Peptide Peptide Peptide Peptide Peptide Peptide Peptide Xanthone

TQVY Veratridine Verticine Verticinone Vicenin 2 Vitexin Vitexin, iso Vitexin-2"-Oalpha-L-rhamnoside VHLPP VHLPPP VIY VLIVP VTPALR VW VWIS WL Xanthone, 1,3,5, 6-tetrahydroxy Xanthone, 3,4, 6,7-tetrahydroxy Xanthone

Oryza sativus Veratrum sp. Fritillaria ussuriensis Fritillaria ussuriensis Allophylus edulis Allophylus edulis Allophylus edulis Allophylus edulis

Diterpene

Taxol Taxus brevifolia

Eucommia ulmoides

Phenylpropanoid

Syringin



Chemical n am e

Table 2. (Contd.)

…..

Maize Sesame Soybean Soybean Mung bean Rapeseed Rapeseed Soybean …..

Pacific yew, Western yew Asian rice Corn lily Ping bei mu Ping bei mu Cocú, Chal chal Cocú, Chal chal Cocú, Chal chal Cocú, Chal chal

Hardy rubber tree

Common name

…..

Poaceae Pedaliaceae Fabaceae Fabaceae Fabaceae Brassicaceae Brassicaceae Fabaceae …..

Poaceae Liliaceae Liliaceae Liliaceae Sapindaceae Sapindaceae Sapindaceae Sapindaceae

Taxaceae

Eucommiaceae

Family

Chen et al., 1992

Arisawa et al., 1989 Hong et al., 2008 Hong et al., 2008 Hong et al., 2008 Li et al., 2006 Marczak et al., 2003 Marczak et al., 2003 Kuba M et al., 2003 Chen et al., 1992

Hong et al., 2008 Ball et al., 1986 Oh et al., 2003 Oh et al., 2003 Arisawa et al., 1989 Okamot et al., 1994 Arisawa et al., 1989 Arisawa et al., 1989

Yamadaki et al., 1992 Sauru et al., 1995

Reference



295

The ACE inhibitory activity of the plants or plant extracts is attributed to their diversified chemical composition. Since, the plants contain a number of different chemical compounds, isolation and characterization of the bioactive compounds responsible for antihypertensive cum ACE inhibitory activity is essential. In this regard, a number of chemical compounds with ACE inhibitory activity have been isolated and characterized from different plant species. The detailed phytochemical studies of various plant species have reported more than 150 chemical compounds as ACE inhibitors. The major class of compounds showing ACE inhibition is found to be flavonoids followed by peptides, alkaloids, phenylpropanoid glycosides, terpenes, iridoids, lipids, polyphenols, tannins and xanthones. Majority of them are characterized to be polar in nature. Table 2 summarizes the information on plant-derived ACE-inhibitory compounds. Although, most of the isolated compounds possess fairly high IC50 values in comparison with the commercial ACE inhibitors, we still consider plantderived inhibitors to be of value in developing both traditional and modern medicine (Nyman et al., 1998). The utilization of plants as a source of ACE inhibitors is worth due to their tolerability and minimized side effects compared to the western medicine in humans. The results obtained from the earlier studies signify the possible usefulness of isolation and purification of potent Table 3a. Description of Azadirachta indica A. Juss Botanical name Common name Family Origin and distribution

Parts used Description of the plant

Chemical composition

Azadirachta indica A. Juss. Neem, Bevu, Nimba, DogonYaro, Vempu etc Meliaceae Native to India, Mayanmar, Bangladesh and Pakistan. Distributed throughout India, deciduous forests, tropical and semi-tropical regions. Bark, leaves, flowers, seeds, oil. A medium to large sized tree, 15–20 m in height with a clear bole of 7 m having grayish to dar k grey t ubercled bark; le aved co mpo und, imparipinnate , le af lets, subopposite, serrate, very oblique at base; flowers cream or yellowish white in axillary panicles, staminal tubes conspicuous, cylindric, widening above, 9–10 lobed at the apex; fruits one-seeded drupes with woody endocarp greeninsh yellow when ripe, seeds ellipsoid, cotyledons thick, fleshy and oily. Tannin, red dye, nimbin, nimbinin, nimbidin, 6- de sace tylnimbine ne , n- he xaco sano l, nonc osane , nimbic idine , nimbi nol, nimbandiol, quercetin, beta-sitosterol, azadirachtin, salannin, gedunin, azadirone etc.


296 Table 3a. (Contd.) Reference

A Handbook of Medicinal plants: A complete Source Book by Narayan Das Prajapati et al., Agrobios India publications.Mahesware, J.K. 1963; The flora of Delhi. Council of Scientific and Industr ial Re se arch, Ne w De lhi. http://www.ayurhelp.com

Table 3b. Description of Artocarpus altilis Fosb Botanical name Common name Family Origin and distribution



Reference

Artocarpus altilis Fosb Breadfruit, Seemapanasa, Seema pila etc Moraceae Native to the region including Southeast Asia, New Guinea and the South Pacific, although the exact location is uncertain. Widely cultivated throughout the humid tropics. Bark, leaves and root. It is a large tree, 10–35 m tall with sticky, white latex and large spirally or alternately arranged lobed leaves. Flower monoecious. Mature fruits (Syncarps) relatively large, yellow-green to yellow-brown, fleshy, with numerous moderate sized seeds, exuding latex where damaged. Ripe fruit are often available throughout the year.

Pectins, starch, artocarpin, hydrocynic acid, bet a amyr in ac etate, alph a amyr in, flavonoids, lectin, oleic, linoleic and linolenic acids (seed oil), cycloratenol, cycloartenone, cycloartenyl acetate, folic acid, cycloaltilisin, cyclomorusin. A Handbook of Medicinal plants: A complete Source Book by Narayan Das Prajapati et al., Agrobios India publications.

Table 3c. Description of Catharanthus roseus (L.) G.Don Botanical name Common name

Family Origin and distribution

Parts used

Catharanthus roseus (L.) G.Don Madagascar periwinkle, Rosy-flowered Indian periwinkle, Cape periwinkle, Old maid etc. Apocynaceae Nativ e t o t he Indian Oce an island of Madagascar. This herb is common in many tropical and subtropical regions worldwide, inc luding t he southern Unit ed States. Common wild plant in coastal areas and is cultivated as an ornamental plant. Leaves and root.

Inhibition of Angiotensin Converting Enzyme (ACE) Table 3c. (Contd.) Description of the plant


Reference

297

It is a fleshy perennial herb growing to 30–80 cm height. St ems pinkish-red, muchbranched. Leaves opposite, obovate, glabrous on both sides, dark shining above. Flowers pink or white in the axil of the leaves. Follicle cylindrical, narrow, slightly arched-recurved in pairs; seeds numerous, tiny, blackishbrown. Alkoloids; serpentine, ajmaline, ajmalicine, catharanthine, catharanthinole, vindoline, vindolinine, vincaleucoblastine. Leurosidine, vincristine. A Handbook of Medicinal plants: A complete Source Book by Narayan Das Prajapati et al., Agrobios India publications.

Table 3d. Description of Morus alba L. Botanical name Common name Family Origin and distribution


Chemical compounds

Morus alba L. Mulberry, White mulberry, Hipnerle etc. Moraceae Native of China, cultivated throughout the world wherever silkworms are raised, and is occasionally cultivated elsewhere in Europe, North America, and Africa. Having escaped, trees often appear on roadsides, along fencerows, and as ornamentals. Root bark and leaves It is small to medium-sized monoecious or dioecious shrub or tree, up to 15 m tall, widespreading, round-topped, trunk attaining 60 cm in diameter; leaves alternate, stipulate, variable in shape, lobed or unlobed, cordate, dentate, acuminate, long-petiolate, 12 × 8 cm on fruiting branches, up to 25 × 20 cm on vigorous nonfruiting branches, usually smooth above, glabrous or pubescent along veins beneath, thin, light green; flowers small, greenishyellow, in dense spikes to 2 cm long; sepals 4; stamens 4; pistils with two styles; staminate spikes soon deciduous; pistillate spikes maturing into an aggregate fruit (syncarp) of drupelets; syncarp ovoid to oblong-cylindric, 1–5 cm long, white, pinkish or purplish to nearly black, edible long before ripe, sweet, but insipid; seeds brown, 1–1.2 mm long. Citral, linalyl acetate, linalol, terpinyl acetate, hexenol, -sitosterol, sterols, pipecolic acid, 5-hydroxy pipecolic acid.

298 Table 3d. (Contd.) Reference


Council of Scientific and Industrial Research. 1948–1976. The wealth of India. 11 vols. New De lhi .ht tp: //w ww. ho rt. pur due .ed uA Handbook of Medicinal plants: A complete Source Book by Narayan Das Prajapati et al., Agrobios India publications.

Table 3e. Description of Pongamia pinnata (L.) Pierre Botanical name Common name Family Origin and distribution


Chemical compounds

Pongamia pinnata (L.) Pierre Indian beech, Poongam oil tree, Karanj, Honge, Ponge etc. Fabaceae An Indomalaysian species, a medium-sized subevergreen tree, common throughout India, in tidal and beach forests, cultivated often as avenue trees. Now found in Australia, Florida, Hawaii, India, Malaysia, Oceania, Philippines, and Seychelles. Root, bark, leaves, flowers, seeds oil. It is a fast growing, medium-sized semievergreen glabrous, deciduous tree with a short bole and spreading crown upto 18m or more in height, bark grayish green or brown, very often mottled with bark brown dots, specks, lines or streaks; leaves compound, leaflets 5–9, ovate acuminate or elliptic, the terminal leaflet larger than the others; stipules caducous. Flowers fragrant, white to pinkish, paired along rachis in axillary, pendent, long racemes or panicles; calyx campanulate or cup-shaped, truncate, shortdentate, lowermost lobe sometimes longer; standard suborbicular, broad, outside; wings oblique, long, somewhat adherent to the obtuse keel; keel petals coherent at apex; stamens monadelphous, vexillary stamen free at the base but joined with others into a closed tube; ovary subsessile to short-stalked, pubescent; ovules 2, rarely 3; style filiform, upper half incurved, glabrous; stigma small, terminal. Pod short stalked, oblique-oblong, flat, smooth, thickly leathery to subwoody, indehiscent, 1- seeded; seed thick, reniform to nearly round, smooth or wrinkled. alkaloids, pongaglabrone, glabrin, karangin, pongapin, diketonepongamol, pongamol, demethoxy-kanugin, gamatay, glabro sapo nin, kae mpf e ro l, kanjone , kanugin, neoglabrin, pinnatin, pongapin, quercitin, saponin, -sitosterol, and tannin

Inhibition of Angiotensin Converting Enzyme (ACE) Table 3e. (Contd.) Reference

299

http://www.hort.purdue.edu, Council of Scientific and Industrial Research. 1948–1976. The wealth of India. 11 vols. New Delhi.A Handbook of Medicinal plants: A complete Source Book by Narayan Das Prajapati et al., Agrobios India publications.

Table 3f. Description of Tamarindus indicus L. Botanical name Common name Family Origin and distribution



Reference

Tamarindus indicus L. Tamarind tree, Imli, Hunase etc Fabaceae Possibly native to western Madagascar, tropical Africa. Today it has a worldwide distribution and has been adopted in several countries due to its culinary properties, as an ornamental tree and for its environmental characteristics. It is found in Asia, Africa, the Pacific and America. It is distr ibuted throughout India, particularly in the South India, often cultivated. Roots, fruits, seeds It is a large to very large evergreen, droughtresistant tree upto 30 m in height with dark grey bark having longitudinal fissures and deep cracks; leaves paripinnate upto 15 cm long, rachis slender, channeled, leaflets 10–20 pairs, subsessile, oblong; flowers yellow, striped with red in laxz, few flowered racemes at the ends of the banchlets; fruit pods, brownish ash coloured, slightly curved, subcompressed, with a shallow oblong pit on each side of the flat faces; seeds enveloped by a toughy leathery membrane (the endocarp) and pulpy mesocarp, tests shining, hard. Tartaric acid, citric maleic acid, potassium bitartarate, oxalic acid, flavonoid glycosides saponaretin, vitexin, orientin, homoorientin, hordenine. A Handbook of Medicinal plants: A complete Source Book by Narayan Das Prajapati et al., Agrobios India publications. California Rare Fruit Growers www Site.

ACE inhibitory molecule in combating the cardiovascular complications associated with the hypertension. The isolation of pure plant compound might be a lead molecule for developing a newer, safe and effective antihypertensive drug. In our ongoing phytoceutical research, as an initial step to isolate ACE inhibitory molecules, we have selected Artocarpus altilis, Azadirachta

300


indica, Catharanthus roseus, Morus alba, Pongamia pinnata and Tamarindus indicus, based on their use in traditional medicine as antioxidant as well as antihypertensive. The information regarding these plants with botanical and common names, family, origin and distribution, description of different parts of the plants, parts used for the medicinal purpose and chemical composition is summarized in Table 3a-f. The leaf extracts of A. altilis, A. indica, C. roseus, M. alba, P. pinnata and seed coat extract of T. indicus were screened for their ACE inhibitory activity in vitro. The successive solvent extracts of plant materials (acetone, ethanol, methanol and water) exhibited differential ACE inhibitory activity differential in vitro. The methanolic and ethanolic leaf extract of A. altilis exhibited potent ACE inhibition while the aqueous and acetone extracts poorly inhibited ACE activity. The methanolic, ethanolic and aqueous leaf extracts of A. indica, C. roseus, and P. pinnata as well as that of T. indicus seed coat extract showed fairly good ACE inhibition compared to acetone extracts (Table 4). Thus, in our study the ACE inhibition was found to be higher in polar solvents, suggesting the benefit of polar compounds as potent ACE-inhibitors compared to non-polar compounds. Among, all the plant extracts studied, M. alba extracts did not show ACE-inhibitory activity.

Conclusions Determination of the ACE-inhibitory activity of plants and their derived compounds that are used in traditional medicine is helpful for the development of modern medicine. Although, many plant extracts have been characterized for their ACE inhibitory activity, further scientific investigations and isolation of bioactive polar compounds from plants will be supportive to develop safe and effective antihypertensive drugs.

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