Journal of Ethnopharmacology 65 (1999) 103 – 112

An ethnopharmacological survey for potential angiotensin

converting enzyme inhibitors from Indian medicinal plants

Brinda Somanadhan a, George Varughese a, Pushpangadan Palpu a,

Rajasekharan Sreedharan a, Lene Gudiksen b, Ulla Wagner Smitt b, Ulf Nyman b,*
a
Tropical Botanic Garden and Research Institute, Pacha-Palode, Thiru6ananthapuram-695562, Kerala, India
b
Department of Medicinal Chemistry, The Royal Danish School of Pharmacy, Uni6ersitetsparken 2, DK-2100,
Copenhagen, Denmark

Received 9 June 1997; received in revised form 16 October 1998; accepted 28 October 1998

Abstract

Plants used in different traditional systems of Indian medicine and some relatives/substitutes have been investigated
for their angiotensin converting enzyme (ACE) inhibitory activity. They were selected on the basis of their usage as
cardiotonics, diuretics and other uses related to the symptoms of hypertension. Out of the 73 species investigated, 22
showed more than 50% ACE inhibitory activity. © 1999 Elsevier Science Ireland Ltd. All rights reserved.

Keywords: Indian medicinal; Cardiotonic; Diuretic; Angiotensin converting enzyme (ACE) inhibition

1. Introduction According to the Ayurvedic system of medicine,

In India, the different traditional medicine sys-
tems make use of a number of plants in the
treatment of hypertension. As part of our ongoing
programme on the evaluation of biological activ-
ity of Indian medicinal plants, a study was con-
ducted to evaluate the antihypertensive activity of
some of these plants, based on an in vitro
bioassay for angiotensin converting enzyme
(ACE) inhibition.
* Corresponding author.
hypertension in itself is not considered as a dis-
ease but severe forms of hypertension generally
leads to the development of certain other diseases.
The clinical conditions described in Ayurveda that
can be related to hypertension are classified into
six groups: (1) Rakta 6ridhi indicative of redness
of skin and eye and fullness of veins; (2) Rakta
prakopajanya indicative of haemorrhage,
headache, nausea, tremors, giddiness and haema-
turia; (3) Rakta6rita 6ata indicative of severe pain
between muscle and bone, body ache, burning
sensation, oedema, generalised red colour of the

0378-8741/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 3 7 8 - 8 7 4 1 ( 9 8 ) 0 0 2 0 1 - 3
104 B. Somanadhan et al. / Journal of Ethnopharmacology 65 (1999) 103–112
skin and generalised red eruption; (4) Raktagata
6ata indicative of severe pain, feeling of ill health,
weakness, flushing of the skin and loss of appetite;
(5) Siragata 6ata indicative of mild body ache,
oedema, emaciation, pulsation, numbness, pain/
spasm in the veins and (6) Vyana6ata 6ridhi in-
dicative of fullness of veins and yawning (Pandey,
1986). In Ayurveda, the treatment is mainly based
on this classification.
All these symptoms are based on the overall
health aspects of the individual in a broad man-
ner, and the management of hypertension in
Ayurvedic medicine often involves several plants.
Prior to the screening of plants for their ACE
activity, a selection criterion was exercised. This
included plants used as cardiotonics, diuretics,
blood purifiers and those used for diseases related
to the heart and oedema. Some rarely used spe-
cies, related to the ones selected for their eth-
nomedical use, were also included in the study.
2. Methodology
2.1. Plant material
Collections were made throughout the years
1992 –1995 from different parts of South India
along with two species from the Andaman Is-
lands. They were identified by taxonomists in
Tropical Botanic Garden and Research Institute
(TBGRI) and voucher specimens are deposited in
the TBGRI herbarium (TBGT). The plants were
shade dried under the prevailing climatic condi-
tions in Trivandrum. After grinding, extracts were
prepared in water, ethanol and acetone.
2.2. Determination of ACE inhibitory acti6ity
The HPLC bioassay developed by Elbl and
Wagner (1991) and modified by Hansen et al.,
(1995) for the screening of ACE inhibitors was
utilised for the screening of the selected plants.
One gram of the dried plant material was ex-
tracted with 10 ml water, acetone or ethanol
(96%) respectively for 30 min on an ultrasonic
bath. After filtration the extracts were concen-
trated in vacuo except for the water extracts
which were lyophilised. One mg concentrated ex-
tract is dissolved in HEPES assay buffer, or
buffers with 10% ethanol or acetone. This corre-
sponds to a final concentration of 0.33 mg plant
extract in 1 ml assay volume. The chosen concen-
tration has been found suitable from a solubility
point of view but also as extracts with an ACE
inhibition above 50% under these conditions have
proven to be worthy of further investigations
(isolation of active constituents). All determina-
tions were made in duplicate.
3. Results
The results of the screening are presented in
Tables 1 and 2. Table 1 represents those plants
which were selected on the basis of their tradi-
tional use. Out of the 51 plant samples, 16
(31.3%) gave more than 50% ACE inhibition,
while seven out of the 30 (23.3%) plant samples,
selected due to a close relationship with tradition-
ally used plants, gave more than 50% ACE in-
hibiton (Table 2). This small difference in positive
hits show the relevance of testing species closely
related to traditionally used plants or plants used
as substitutes. In total, 22 species out of the 73
(30.1%) screened, gave more than 50% ACE
inhibition.
As far as possible, the traditionally used part of
the plant was employed for the screening. How-
ever, in certain cases other parts were also tested.
A literature survey on the pharmacological ac-
tivity of all the plants screened for ACE inhibitory
activity was carried out and the effects observed
relevant to hypertension have been listed in Table
3.
4. Discussion
Species resulting in a high ACE inhibition and
with a reported hypotensive/cardiovascular activ-
ity are designated as (a) in Table 3 and include;
Piper betle, Jasminum sambac, Cardiospermum
halicacabum and Tribulus terrestris. Besides the
different mechanisms reported, these results indi-
cate that ACE inhibition may be an alternative
Table 1
Results of the ACE screening of plant species, selected on the basis of their traditional use

Scientific name Plant part used and the traditional Plant part % ACE inhibition Collection Collection time Voucher specimen
usage with referenced in parenthesis screenedc siteb no. TBGT

Wa E A

ACANTHACEAE

B. Somanadhan et al. / Journal of Ethnopharmacology 65 (1999) 103–112

Nilgirianthus ciliatus (Nees) Bre- LF, blood purifier (9) LF 30 9 10 2 May, 1995 15545
mek.
ALOACEAE
Aloe 6era L. LF, diuretic (8) LF 39 32 21 2 February, 1993 18883
AMARANTHACEAE
Aer6a lanata Juss. WP, diuretic (1,2,4,5) LF 20 23 14 2 April, 1993 18884
ANACARDIACEAE
Mangifera indica L. PX, dropsy (5) BK 20 43 61 2 May, 1995 29580
APIACEAE
Heracleum candolleanum (W. et RT, diuretic (10) RT 30 32 26 6 February, 1994 25991
A.) Gamble
Hydrocotyle ja6anica Thunb. WP, diuretic (2) WP 31 29 19 6 August, 1994 25992
APOCYNACEAE
Holarrhena antidysenterica (L.) SD, diuretic (4) SD 16 24 19 8 May, 1993 18885
Wall.
ASCLEPIADACEAE
Hemidesmus indicus R. Br. ST, RT, diuretic (4) LF 6 25 17 2 May, 1995 22578
H. indicus R. Br. ST, RT, diuretic (4) RT 25 15 21 2 April, 1993 12707
ASTERACEAE
Elephantopus scaber L. WP, heart disease (4) WP 18 20 11 2 February, 1993 18887
BIGNONIACEAE
Stereospermum sua6eolens DC. BK, diuretic (1) BK 9 6 5 2 February, 1993 18888
BOMBACACEAE
Bombax malabaricum L. BK, diuretic (1,4) BK 7 46 23 2 February, 1993 18889
BORAGINACEAE
Coldenia procumbens L. LF, rheumatic swellings (1,2,4) AP 15 8 8 2 May, 1995 29583
CELASTRACEAE
Celastrus paniculatus Willd. SD, diuretic (8) SD 50 8 0 8 April, 93 18890

105
 106
Table 1 (Continued)

Scientific name Plant part used and the traditional Plant part % ACE inhibition Collection Collection time Voucher specimen
usage with referenced in parenthesis screenedc siteb no. TBGT

Wa E A

COMBRETACEAE
Terminalia bialata Steud. BK, cardiac stimulant (2,4) BK 30 86 10 5 May, 1994 25993

B. Somanadhan et al. / Journal of Ethnopharmacology 65 (1999) 103–112

T. chebula Retz. FT, heart disease (4) FT 33 42 68 8 April, 1993 18891
CAESALPINIACEAE
Cassia fistula L. BK, heart disease (8) BK 53 82 90 2 February, 1993 18892
C. tora L. WP, removes urine obstruction (9) RT 14 90 97 2 February, 1993 18893
FABACEAE
Vigna mungo (L.) Hepper SD, diuretic (2,4) SD 15 15 6 8 March, 1993 18894
LAMIACEAE
Ocimum sanctum L. WP, heart diseases (4) AP 37 26 23 2 March, 1993 18895
LOGANIACEAE
Strychnos nux-6omica L. SD, cardiac stimulant (1) SD 15 4 0 8 April, 1993 18896
MALVACEAE
Pa6onia odorata Willd. RT, diuretic (1) WP 8 51 21 2 May, 1995 29581
Urena lobata L. RT, diuretic (2,4) RT 10 34 16 2 February, 1993 18897
MORACEAE
Ficus benghalensis L. BK, urinary complaints (5) AR 10 29 20 1 February, 1994 25994
F. religiosa L. SD, urinary complaints (5) AP 0 25 22 2 May, 1995 22576
MORINGACEAE
Moringa oleifera Lam. WP, cardiac stimulant (1,2) SD 28 0 0 10 March, 1995 29582
M. oleifera Lam. WP, cardiac stimulant (1,2) FS 72 10 6 10 March, 1995 29582
M. oleifera Lam. WP, cardiac stimulant (1,2) BK 36 12 7 2 April, 1993 18898
NYCTAGINACEAE
Boerhaa6ia diffusa L. WP, heart diseases (1,5) WP 33 44 23 2 February, 1993 18899
OLEACEAE
Jasminum multiflorum (Burm.f.) FL, cardiotonic (4,8) L 13 23 21 12 April, 1995 15800
Andr.
J. multiflorum (Burm.f.) Andr. FL, cardiotonic (4,8) FR.L nd 31 92 12 March, 1994 20072
J. multiflorum (Burm.f.) Andr. FL, cardiotonic (4,8) FR.FL nd 4 12 12 March, 1994 20072
Jasminum azoricum L. LF, oedema (11) AP 86 16 26 13 May, 1995 13190
var.tra6ancorense (Gamble) M.
Mohanan
Table 1 (Continued)

Scientific name Plant part used and the traditional Plant part % ACE inhibition Collection Collection time Voucher specimen
usage with referenced in parenthesis screenedc siteb no. TBGT

Wa E A

J. grandiflorum L. WP, diuretic (4,8) AP 46 60 78 2 May, 1995 13107

J. grandiflorum L. (triploid) WP, diuretic (4,8) AP 20 28 60 2 May, 1995 13112
J. auriculatum Vahl FL, cardiotonic (8) L 4 14 10 14 April, 1995 13141
PERIPLOCACEAE

B. Somanadhan et al. / Journal of Ethnopharmacology 65 (1999) 103–112

Janakia arayalpathra Joseph et RT, blood purifier (3) RT 14 5 43 11 January, 1994 25995
Chandrasekharan
PINACAEAE
Cedrus deodara (Roxb.) Loud. WD, cardiotonic (8) WD 6 26 33 8 April, 93 18900
PIPERACEAE
Piper betle L. LF, heart tonic (4) LF 56 48 41 2 February, 1993 18872
P. longum L. FT, diuretic (1,4) SPK 40 30 11 8 April, 1993 18873
RUTACEAE
Aegle marmelos (L.) Corr. FT, heart tonic (4) FSL 43 9 21 4 February, 1994 25996
Murraya exotica L. LF, dropsy (2,6) LF 45 32 2 2 May, 1995 22575
SAPINDACEAE
C. halicacabum L. WP, heart disease (3) ST 50 11 28 15 April, 1993 12919
VERBENACEAE
Clerodendron indicum (L.) Kuntze RT, heart disease (3) AP 0 12 18 2 February, 1994 25997
Vitex negundo L. LF, chest pain (3) LF 31 44 23 2 February, 1993 18875
Gmelina arborea Roxb. WP, cardiotonic (9) RT 6 21 21 2 February, 1993 18876
ZINGIBERACEAE
Alpinia galanga Willd. RHZ, incontinence of urine (1) RHZ 29 42 31 2 February, 1993 18877
Elettaria cardamomum Maton SD, diuretic (2,6,8) SD 40 27 10 6 October, 1992 23000
Zingiber officinale Rosc. RHZ, incontinence of urine (1) RHZ 31 13 13 8 May, 93 18878
ZYGOPHYLLACEAE
Tribulus terrestris L. WP, diuretic (1) AP 50 37 28 1 February, 1994 25998
T. terrestris L. WP, diuretic (1) FT 56 17 11 1 February, 1994 25998

a
W, water extract; E, ethanol extract; A, acetone extract.
b
Collection site: 1, Maruthuamalai; 2, Tropical Botanic Garden and Research Institute (TBGRI); 3, Chemungi; 4, Mookampetty; 5, Andaman, 6, Munnar; 7,
Madurai; 8, Local market; 9, Pamba valley; 10, Prakkulam; 11, Ponmudi; 12, Nilambur; 13, Kallar forest; 14, Mannanthala; 15, Kulathupuzha
c
Abbreviations for plant parts are as follows: AR, aerial root; LF, leaf; RT, root; ST, stem; BK, bark; WP, whole plant; FL, flower; FR. FL, fresh flower; FR.
L, Fresh leaf; SD, seed; AP, aerial part; FT, fruit; SPK, spike; RHZ, rhizome; FSL, fruit shell; WD, wood; PX, part not specified; nd, not determined; TBGT, name
of the herbarium where the voucher specimen is deposited.

107
d
References: 1, Nadkarni (1992); 2, Ambasta (1992); 3, Saradamma et al. (1990); 4, Kirthikar and Basu (1991a,b); 5, Jain (1991); 6, Chopra et al. (1992); 7, Sharma
(1990); 8, Varier (1995); 9, Sivarajan and Balachandran (1994); 10, Saradamma et al. (1989); 11, Saradamma et al. (1994).
 108
Table 2
Results of the ACE screening of plant species selected, based on the properties shown by related species

Scientific name Plant part % ACE inhibitona Collection Collection time Voucher specimen no. TBGT
testeda sitee

W E A

ACANTHACEAE
Andrographis echioides Nees AP nd 16 55 1 February, 1994 25976

B. Somanadhan et al. / Journal of Ethnopharmacology 65 (1999) 103–112

Nilgirianthus barbatus (Nees) Bremek. LF 23 9 0 2 May, 1995 14723
N. foliosus (Wt.) Bremek. LF 5 7 0 3 May, 1995 22563
N. heyneanus (Nees) Bremek. LF 16 0 0 4 May, 1995 22562
Phlebophyllum lanatum (Nees) Bremek. LF 25 3 0 2 May, 1995 14722
P. lawsonii (Gamble) Bremek. LF 11 2 0 2 May, 1995 22572
Strobilanthes asperimmus Nees LF 16 9 3 2 May, 1995 22570
S. kunthianus (T. Anders.) ex Benth. LF 0 10 9 2 May, 1995 22571
ARALIACEAE
Schefflera racemosa (Wight) Harms LF 42 27 6 3 February, 1994 25978
APOCYNACEAE
Alstonia 6enenata R. Br. AP 0 27 38 2 May, 1995 22568
ASTERACEAE
Artemisia pallens Wall. ex DC. AP 14 51 11 7 July, 1994 25979
BURSERACEAE
Canarium euphyllum Kurz BK 20 91 100 5 May, 1994 25980
CAESALPINIACEAE
Humboldtia 6ahliana Wight BK 26 93 51 9 May, 1995 22569
MALVACEAE
Mal6a6iscus arboreus Cav. FL 31 15 9 2 May, 1993 18879
MORACEAE
Ficus pumila L. AP 9 15 16 2 May, 95 22577
MYRSINACEAE
Embelia basaal (Roem et Schultes) LF 6 0 46 1 February, 1994 25999
A.DC.
E. basaal (Roem et Schultes) A.DC. ST 36 87 78 1 February, 1994 25999
E. basaal (Roem et Schultes) A.DC. FT 5 100 100 1 February, 1994 25999
OLEACEAE
Jasminum sambac (L.) Ait.b LF 77 25 31 14 March, 1995 29578
J. sambac (L.) Ait.c LF 26 32 7 14 March, 1995 29576
J. sambac (L.) Ait.d LF 20 40 5 14 March, 1995 29577
Jasminum frutescens L. LF 23 5 12 2 March, 1995 13174
 B. Somanadhan et al. / Journal of Ethnopharmacology 65 (1999) 103–112
Table 2 (Continued)

Scientific name Plant part % ACE inhibitona Collection Collection time Voucher specimen no. TBGT
testeda sitee

W E A

J. angustifolium Willd. LF 20 27 41 2 March, 1995 13122

J. humile L. LF 35 17 39 2 March, 1995 30204
J. sessiliflorum Vahl LF 14 0 25 2 April, 1995 13140
J. cordifolium Wall.ex. G. Don. LF 28 21 19 2 April, 1995 13163
RUBIACEAE
Geophila reniformis D.Don. WP 22 11 0 2 May, 1995 22574
SELAGINELLACEAE
Selaginella willdeno6ii Baker AP 22 17 18 2 May, 1995 29116
TRICHOPODACEAE
Trichopus zeylanicus Gaertner WP 14 15 9 2 February, 1994 26000
VERBENACEAE
Clerodendrum infortunatum L. LF 48 15 16 2 May, 1995 22564

109
110 B. Somanadhan et al. / Journal of Ethnopharmacology 65 (1999) 103–112

Table 3
Reported effect on blood pressure and heart of some of the screened plants

Scientific name Part testede Reported pharmacological activity

A. marmelos LF Aqueous and alcoholic extracts appeared to have cardiotonic effect like digitalis on amphib-
(L.) Corr.c ian and mammalian hearts; Haravey (1968)
A. marmelos RTBK Methanolic extract at a concentration of 100 mg/ml inhibited the beating rate of mouse
(L.) Corr.c myocardial cells by 50%. Aurapten isolated was comparable to Verampril, a calcium antago-
nist; Kakiyuchi et al. (1991)
A. marmelos RT 50% alcohol extract showed cardiovascular effect; Dhar et al. (1968)
(L.) Corr.c
A. 6era L.d LF Patients with ischemic heart disease showed an improvement in their clinical profile; Agarwal
(1985)
A. galanga RHZ 50% alcohol extract showed cardiovascular effect; Bhaukuni et al. (1969)
Willd.d
B. diffusa L.c RT Liriodendrin isolated from the methanol extract showed calcium channel antagonistic effect
in frog heart cell; Lami et al. (1991)
C. tora L.b SD Aqueous and methanol extract showed hypotensive effect in rats; Koo et al. (1976)
C. halicacabum WP 50% alcohol extract showed cardiovascular effect; Dhar et al. (1968)
L.a
C. halicacabum LF Alcoholic extract produced hypotension and bradycardia; Gopalakrishnan et al. (1976)
L.a
C. deodara WD Intravenous injection of himachalol isolated from the alcohol extract produced a dose depen-
(Roxb.) dant fall in blood pressure in cat; Kar et al. (1975)
Loud.d
E. scaber L.d WP Intravenous injection of water and 50% alcoholic extracts showed dose dependant reduction
in blood pressure and heart rate in rats; Poli et al. (1992)
F. benghalensis BK, LF Aqueous extracts exhibited negative inotropy and hypotension in dogs; Vohora and Parasar
L.c (1969)
H. antidysen- BK 50% alcohol extract showed cardiovascular effect; Dhar et al. (1968). Hypotension was found
terica (L.) as a side effect; Chaturvedi and Singh (1983)
Wall.c
J. sambac AP 50% alcohol extract showed cardiovascular effect; Dhar et al. (1973)
(L.)Ait.a
M. oleifera LF Isothiocyanate and thiocarbamate glycosides isolated from the ethanol extract showed hy-
Lam. b potensive activity; Faisi et al. (1994)
M. exotica L. d LF A crystalline principle isolated from the pet. ether extract showed mild stimulant effect on
the isolated frog heart; Khosa et al. (1970)
O. sanctum L.d LF The water extract possessed hypotensive activity with a direct depressant effect on rabbit
heart; Singh et al. (1970)
P. betle L.a LF The alcoholic extract showed cardiotonic effect over anaesthetised dogs; Deshpande et al.
(1970). The essential oil from leaves was found to show hypotensive and cardiac effects; Ali
and Mehta (1970)
P. betle L.a INFL Intravenous injection of the water extract induced hypotensive and bradycardiac effects; Chen
et al. (1995)
T. lobata L.c FT The water soluble extract showed a potent stimulant effect on rabbit and frog heart; Seth
and Jagadeesh (1976)
U. lobata L.c WP 50% alcohol extract showed cardiovascular effect; Bhaukuni et al. (1969)
Z. officinale RHZ Gingerols as cardiotonic principles were isolated from the methanol extract of the rhizome;
Rosc.d Shoji et al. (1982)

a
Plant part that was found active in the ACE screening and the same part tested for its pharmacological activity.
b
Plant part found active in the ACE screening but different part reported for its pharmacological activity.
c
Plant part found inactive in the ACE screening but different part tested for its pharmacological activity.
d
Plant part found inactive in the ACE screening but the same part reported for its pharmacological activity.
e
AP, aerial part; BK, stem bark; FT, fruit; INFL, inflorescence; LF, leaf; RHZ, rhizome; RTBK, root bark; RT, root; SD, seed;
WD, wood; WP, whole plant.
 B. Somanadhan et al. / Journal of Ethnopharmacology 65 (1999) 103–112
mechanism leading to the hypotensive activity of
these four species. Leaf, fruit shell and bark of
Moringa oleifera were tested for their ACE in-
hibitory activity, but only the fruit shell was
found positive whereas from the literature, the
leaf was reported for its hypotensive activity. A
similar observation was made for Cassia tora.
Both species are designated as (b) and requires
further investigation to clarify these differences.
Group (c) in Table 3 constitute species, where the
plant parts tested for ACE inhibiton differ from
those reported in the literature. The pharmacolog-
ical activity of the other species in Table 3
grouped as (d) imply that their effect on blood
pressure and heart is probably not due to ACE
inhibiton.
Acknowledgements
The authors wish to thank Mathew Dan and
P.A. Jose, Tropical Botanic Garden and Research
Institute, Trivandrum, India, for their help with
the plant collection and identification. Bente Gau-
guin is thanked for her skillful technical assis-
tance. Financial support from Danish
International Development Agency (DANIDA) is
gratefully acknowledged.
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