Clerodendrum Chinensis Extracts; AeC and EeC Exerts Rapid Antihypertensive Effects in L-NAME Hypertensive Experimental Models

Abstract

Background: The rise in occurrence of hypertension, a non-communicable disease and a major factor for
chronic renal failure, cardiovascular disease, and stroke, which most times lead to sudden death is worrisome.
Resistant hypertension is more common and may have no symptoms at all for months or years, but then can
cause heart attack, stroke, and vision and kidney damage. Prevention and quick management of hypertension
are therefore essential in reducing the risk of these debilitating ailments. Aqueous and ethanolic extracts of the
leaves of Clerodendrum chinensis (AeC and EeC) are used by local communities of West Africa as medicine
for rapid antihypertensive actions. We aim to discover the scientific basis for the use of the herb as medicine.

Methods: This work investigates the antihypertensive effects of AeC and EeC in L-Arginine Methyl Ester
Hydrochloride (L-NAME)-induced hypertensive rats Acetylcholine, L-Arginine and Sodium Nitroprusside
were used as standards. All results were expressed as means ± standard error of mean . Differences were
considered significant at p <0.05.

Results: Intravenous administration of the extracts caused a significant decrease in the Mean Arterial Blood
Pressure (MABP) in a dose-dependent manner. AeC at 100mg/kg caused a significant decline in blood
pressure in a dose-related manner. Likewise at 100mg/kg, EeC reduced MABP steadily from 103.9± 2.55 to
34.1± 0.95mmHg. The two extracts; possess significant antihypertensive properties.

Conclusions: Both extracts show significant antihypertensive effects and at high doses could lead to
hypotension and so should be used with care. Further research is necessary to determine safe dosage forms.

Keywords: Clerodendrum chinensis, Herbal medicine, L-NAME-hypertensive rat and Resistant hypertension

Full text

Arch Pharmacol er. 2021
Volume 3, Issue 1
Archives of Pharmacology and Therapeutics Research Article
https://www.scienticarchives.com/journal/archives-of-pharmacology-and-therapeutics
21
Clerodendrum Chinensis Extracts; AeC and EeC Exerts
Rapid Antihypertensive Effects in L-NAME Hypertensive
Experimental Models
Joy I. Odimegwu1, Tolulope F. Okanlawon2, Noel Obumneme1, Ismail Ishola3
1Department of Pharmacognosy, Faculty of Pharmacy, University of Lagos, Nigeria
2Nutraceutical Aromatic and Pesticidal Plant Division (Federal Institute of Industrial Research Oshodi, Lagos), Nigeria
2Department of Pharmacology, College of Medicine, University of Lagos, Nigeria
*Correspondence should be addressed to Joy I. Odimegwu; jodimegwu@unilag.edu.ng
Received date: August 30, 2020, Accepted date: April 28, 2021
Copyright: © 2021 Odimegwu JI, et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author
and source are credited.
Abstract
Background: The rise in the occurrence of hypertension, a non-communicable disease and a major factor for chronic renal failure,
cardiovascular disease, and stroke, which most times lead to sudden death is worrisome. Resistant hypertension is more common
and may have no symptoms at all for months or years, but then can cause heart attack, stroke, and vision and kidney damage.
Prevention and quick management of hypertension is therefore essential in reducing the risk of these debilitating ailments. Aqueous
and ethanolic extracts of the leaves of Clerodendrum chinensis (AeC and EeC) are used by local communities of West Africa as
medicine for rapid anti-hypertensive actions. We aim to discover the scientic basis for the use of the herb as medicine.
Methods: This work investigates the anti-hypertensive eects of AeC and EeC in L-Arginine Methyl Ester Hydrochloride (L-NAME)-
induced hypertensive rats Acetylcholine, L-Arginine and Sodium Nitroprusside were used as standards. All results were expressed as
means ± standard error of mean. Dierences were considered signicant at p<0.05.
Results: Intravenous administration of the extracts caused a signicant decrease in the Mean Arterial Blood Pressure (MABP) in a
dose-dependent manner. AeC at 100 mg/kg caused a signicant decline in blood pressure in a dose-related manner. Likewise, at 100
mg/kg, EeC reduced MABP steadily from 103.9 ± 2.55 to 34.1 ± 0.95mmHg. The two extracts; possess signicant anti-hypertensive
properties.
Conclusions: Both extracts show signicant anti-hypertensive eects and at high doses could lead to hypotension and so should be
used with care. Further research is necessary to determine safe dosage forms.
Keywords: Clerodendrum chinensis, Herbal medicine, L-NAME-hypertensive rat and Resistant hypertension
Introduction
Cardiovascular diseases (CVDs) encompass
several coronary artery diseases (CAD) like Angina,
Myocardial infarction among others [1]. Other CVDs
are cardiomyopathy, hypertension, rheumatic heart
disease, heart arrhythmia, peripheral artery disease, and
venous thrombosis [1]. These diseases are being witnessed
in a larger percentage of the population and in younger
subjects too. Also, patients have reported a certain
resistance of the disease conditions to known drugs.
CVDs are the highest cause of deaths all over the world.
WHO, in 2008 reported that more than 17 million people
died from CVDs complications that year alone of which
more than 3 million of these could have been prevented
by changes in diet and lifestyle. Hypertension, the most
common CVD also known as high blood pressure, is a
medical condition in which the blood pressure in the
arteries is persistently elevated [2]. There has been an
increase in incidences of hypertension with the proportion
of the global burden of disease attributable to hypertension
increasing signicantly from 4.5% in 2000 to 7% in 2010

Odimegwu JI, Okanlawon TF, Obumneme N, Ishola I. Clerodendrum Chinensis Extracts; AeC and EeC Exerts Rapid
Antihypertensive Eects in L-NAME Hypertensive Experimental Models. Arch Pharmacol er. 2021; 3(1):21-28.
Arch Pharmacol er. 2021
Volume 3, Issue 1 22
[3]. Hypertension leads to complications with considerable
morbidity and mortality which is responsible for at least
45% of deaths due to heart disease and 51% of deaths due
to stroke [3]. The number of people with uncontrolled
hypertension has increased to about 1 billion worldwide in
the past 30 years [4]. The prevalence of hypertension cases
is increasing worldwide; in both developed and developing
worlds and seen more and more frequently in younger
patients [5]. Sustained high blood pressure is considered
responsible for many serious medical conditions such as
arteriosclerosis, heart failure, kidney failure, blindness,
and cognitive impairment, and also for many deaths from
stroke and heart disease. Systolic, diastolic, and pulse
pressure are important predictors of cardiovascular risk
[6].
Scientists are reverting to nature for solutions to ailments
hence the renewed great interest in plants with anti-
hypertensive compounds used locally but not certied
scientically. Clerodendrum chinensis [Osbeck] Mabb.
Figure 1 (Chinese glory bower, glory tree, Honolulu
rose, stick bush) is a species of owering plant in the
genus Clerodendrum. It is placed in the family Lamiaceae,
a native to Asian countries of China, Korea, Taiwan,
Japan, Vietnam, Western Samoa and American Samoa [7]
where it grows commonly as a weed along roadsides and
as an ornamental shrub with stout branches. The plant
has several synonyms; C. fragrans, C. japonicum etc [8].
The leaves’ tinctures are diuretic [9]. A decoction of the
leaves is used in the treatment of blenorrhoea (Chlamydial
conjunctivitis) and reputedly a remedy for dicult cases of
scabies. Juice from the leaves is an ingredient of herbal bath
for children with furuncles [7]. The plant is used for the
treatment of rheumatism and ague and as an ingredient of
a mixture for treating skin problems [10]. The root extracts
are considered antibacterial, and diuretic. It is used in the
treatment of abdominal pain, intestinal disease and kidney
dysfunctions. It is said to have been used successfully in
the treatment of jaundice, lumbago, and hypertension [7].
It is often grown as an ornamental, the double-owered
but sterile form being most commonly cultivated [11].
Chemicals frequently employed in hypertension
treatment includes; Sodium nitroprusside (SNP), a water-
soluble sodium salt comprised of Iron (Fe2+) complexed
with nitric oxide (NO) and ve cyanide anions. In the living
system, it functions as a pro-drug, reacting with sulfhydryl
groups on erythrocytes, albumin, and other proteins to
release Nitric Oxide [12,13]. Nitric Oxide, or endothelium-
derived relaxing factor, stimulates guanyl cyclase to
produce cyclic GMP, sequestering calcium and inhibiting
cellular contraction. At the tissue level, these eects of
Nitric Oxide result in reduced vascular tone in muscular
conduit arteries. Nitric Oxide released from nitroprusside
decreases cerebral vascular resistance [14].
L-arginine (L-ARG) is an amino acid with lipid
peroxidation-lowering eects which may account for its
benecial eect on Systolic Blood Pressure (SBP) and
vascular responsiveness [15]. The objectives of this work
are to study the anti-hypertensive eects of AeC and EeC
and evaluate its safety by acute toxicity of using L-NAME
induced hypertensive rats.
Figure 1: Leaves and owers of C. chinensis (From Tropical Plants Database [23]).

Odimegwu JI, Okanlawon TF, Obumneme N, Ishola I. Clerodendrum Chinensis Extracts; AeC and EeC Exerts Rapid
Antihypertensive Eects in L-NAME Hypertensive Experimental Models. Arch Pharmacol er. 2021; 3(1):21-28.
Arch Pharmacol er. 2021
Volume 3, Issue 1 23
Materials and Methods
Reagents
L-NAME (Sigma Aldrich, USA). Heparin, Acetylcholine
and Sodium Nitroprusside was obtained from the
Department of Physiology, College of Medicine University
of Lagos, Nigeria. L-Arginine was obtained from the
Department of Pharmacology, College of Medicine
University of Lagos, Nigeria.
Plant collection
The leaves of Clerodendrum chinensis were originally
from plants collected from Abidjan, Ivory Coast and
cultivated in a private garden at Lekki, Lagos State, Nigeria
6°29′36″N 3°43′14″E. Verication of the plant identity
was carried out at the Herbarium of the Department of
Botany, University of Lagos, Nigeria and plant assigned
voucher number FIH 6974.
Extract preparation
Ethanol extract, EeC; leaves were air-dried and
ground then extracted with absolute ethanol, using
cold maceration. The mixture was ltered and extract
concentrated by evaporation, air-dried and stored at 20°C.
Aqueous extract, AeC; leaves were air-dried and
pulverized then macerated in distilled boiling water (100oC)
and the marc obtained was left to stand for 24 hours and
then ltered. The ltrate obtained was concentrated by
evaporation at 50°C and the extract stored at 20°C.
Phytochemical analysis
Phytochemical studies were conducted on AeC and
EeC for the presence or absence of Alkaloids, Flavonoids,
Anthraquinones (free or combined), Tannins, Steroids,
Saponins, Terpenoids, and Cardiac glycosides.
Experimental procedure
Male Wistar rats (8-10 weeks, weighing 130-170 g) were
used. All animals were housed under constant temperature
and exposed to a 12 hr light/12 hr dark cycle and were fed
a standard chow diet. Animal protocols were approved by
the ethics committee for the care and use of laboratory
animals at the University of Lagos, Nigeria. After 1 week of
acclimatization, the animals were randomly divided into
5 per group for Aqueous and Ethanolic extracts into the
following experimental groups;
A. Control Group received saline water
B. L-NAME only Group: received L-NAME (20 mg/kg)
Aqueous extracts grouping; AeC
C. L-NAME + 100 MG/KG
D. L-NAME + 200 MG/KG
E. L-NAME + 300 MG/KG
F. L-NAME + 400 MG/KG
Ethanolic Extracts grouping; EeC
G. L-NAME + 100 MG/KG
H. L-NAME + 200 MG/KG
I. L-NAME + 300 MG/KG
J. L-NAME + 400 MG/KG
Blood pressure measurement for the duration of
experiment was carried out with a power lab (TICE®).
Animals were anaesthetized humanely at the end of
the experiments according to established protocols. The
extracts and the standard agents were administered
twenty minutes (20 mins) after L-NAME administration.
Heparin solution was injected in the arterial catheter at
intervals to avoid possible blood coagulation. Readings
obtained were analyzed using the power lab and recorded.
The safety eects of AeC and EeC were studied In-vivo on
the systolic blood pressure, diastolic blood pressure and
mean arterial blood pressure of rats treated with L-NAME.
Acute toxicity test
A single dose test was carried out for acute toxicity of the
extracts. A dozen mice were fasted for 16 hours and then
administered 5000 mg/kg AeC and EeC separately. They
were observed for 24 to 72 hours for signs of behavioral
change and death.
Statistical analysis
Statistical analysis was performed and carried out by
student’s t-test using Graph Pad Prism 5.0. All results
were expressed as means ± standard error of mean (SEM).
Dierences were considered signicant at p<0.05.
Results and Discussion
Phytochemical analysis showed the presence of
avonoids, alkaloids, steroids, terpenoids, and cardiac
glycosides in the leaves of the test plant. The intravenous
administration of AeC and EeC to L-NAME induced
hypertensive rats caused a signicant decrease in systolic
blood pressure, diastolic blood pressure and Mean Arterial
Blood Pressure (Figures 2-5 and Appendices). Table 1
shows that the control groups were adequate as controls
as the saline group did not show any signicant increment
or decrease in the parameters of importance while

Odimegwu JI, Okanlawon TF, Obumneme N, Ishola I. Clerodendrum Chinensis Extracts; AeC and EeC Exerts Rapid
Antihypertensive Eects in L-NAME Hypertensive Experimental Models. Arch Pharmacol er. 2021; 3(1):21-28.
Arch Pharmacol er. 2021
Volume 3, Issue 1 24
Figure 2: Eects of Standard drug agents and AeC and EeC on MABP. Key: ACH: Acetylcholine; L-ARG: L-Arginine; SNP:
Sodium Nitroprusside (all in Moles); AeC: Aqueous extract; EeC: Ethanol extract.
Figure 3: Eects of Standard drug agents and AeC and EeC on SBP. Key: Standard Agents (P<0.01). ACH: Acetylcholine; L-ARG:
L-Arginine; SNP: Sodium Nitroprusside (all in Moles) AeC: Aqueous extract; EeC: Ethanol extract.

Odimegwu JI, Okanlawon TF, Obumneme N, Ishola I. Clerodendrum Chinensis Extracts; AeC and EeC Exerts Rapid
Antihypertensive Eects in L-NAME Hypertensive Experimental Models. Arch Pharmacol er. 2021; 3(1):21-28.
Arch Pharmacol er. 2021
Volume 3, Issue 1 25
Figure 4: Eects of AeC on SBP, DBP, HR, PP and MABP.
Figure 5: Eects of EeC on SBP, DBP, HR, PP and MABP.
Groups SYSTOLIC BP
(mmHg)
DIASTOLIC BP
(mmHg)
MEAN
ARTERIAL BP
(mmHg)
HEART
RATE
PULSE
PRESSURE
Saline Group 106.47 ± 21.9 80.53 ± 33.86 95.9 ± 24.1 272± 7.9 25.89 ± 12.39
L-NAME only Group 150.9 ± 9.5 128.8 ± 8.4 136.85 ± 11.8 315 ± 0.6 22.18 ± 2.81
Values are expressed in Mean ± SEM. L-NAME group = P<0.05
Table 1: Eect of Saline and L-NAME on the Control animals.

Odimegwu JI, Okanlawon TF, Obumneme N, Ishola I. Clerodendrum Chinensis Extracts; AeC and EeC Exerts Rapid
Antihypertensive Eects in L-NAME Hypertensive Experimental Models. Arch Pharmacol er. 2021; 3(1):21-28.
Arch Pharmacol er. 2021
Volume 3, Issue 1 26
the L-NAME control group showed an increase in the
parameters. It is well known that L-NAME, administered
either acutely by intravenous route or chronically through
oral route induce sustained hypertension [16,17]. The
genus Clerodendrum is well documented to have benecial
eects on the cardiovascular system of mammals due to its
signicant avonoid content [18,19]. Indeed, avonoids
from a great variety of plants have hypotensive and vaso-
relaxant activities [20,21]. Wang et al., [22] conducted an
extensive study of the diverse phytochemicals in aqueous
and methanolic fractions of dierent plant parts and
published them with relevant structures.
AeC at 400 mg/ml appears to be the most eective
dosage statistically (Figures 2-5) comparing very favorably
with the standards ACH and SNP (Figures 2 and 3).
L-NAME, when administered, induces a sustained mean
arterial hypertension which persisted for over 30 minutes
as observed in the experiments with MABP of 136.85 ±
11.8 mmHg (Table 1). MABP was further elevated on the
administration of the lowest dose (100 mg/kg) of the AeC
from 136.85 ± 11.8 mmHg to 188.8 ± 0.8 mmHg. There
was however a decline as the concentration increases from
95.8 ± 1.2 mmHg to 86.3 ± 0.9 mmHg respectively (Figure
2). The heart rate was also aected (Table 2, Figures 4 and
5).
MABP dropped suddenly after administration of 400
mg/ml to 27± 1.5 mmHg. The immediate fall in blood
pressure induced by the doses (100, 200, 300 and 400
mg/ml) of the AeC was followed by a short-lasting eect
indicating that the anti-hypertensive eects of the AeC are
dose-related.
The speed of the blood pressure drop is accounted for
in local usage where the patients reported that they are
careful about the number of times in a day they consume
the decoction. 100 mg/ml of the EeC reduced MABP to
103.9± 2.55 mmHg. 200 mg/ml, 300 mg/ml, 400 mg/ml
reduced MABP to 75.5 mmHg ± 0.75, 58.7 ± 1.5, 34.1 ±
0.95 mmHg respectively (Figure 2).
The eects were more lasting than that of the AeC and
are observed to also be dose-related. The result, however,
shows that the elevated MABP was reduced more by the
EeC when compared to the AeC in the L-NAME induced
hypertensive rats. AeC, at 100 mg/ml, 200 mg/ml and 300
mg/ml reduced blood pressure and did not go below 90
mmHg/60 mmHg and can be considered as appropriate
doses in reducing high blood pressure. For the EeC, only
100 mg/kg was identied to reduce high blood pressure
below 90 mmHg/ 60 mmHg and can be considered
appropriate in reducing blood pressure also (Figures 3 and
4).
As in previous studies [17], SNP administration leads to
a rapid reduction in ABP (Figure 2) and when compared
to both extracts, it can be said that SNP and the plants
extracts successfully reduced the blood pressure (Figure
2). The eects of Acetylcholine, when compared to that
of the extracts, was better but also shows a signicant
decrease in blood pressure by the extracts (Figures 2-4).
Both extracts showed a signicant decrease in blood
pressure when compared to the standard agents (Table 2).
PARAMETERS HEART-RATE PULSE PRESSURE
Saline group 272± 7.9 25.89 ± 12.39
L-NAME only group 315 ± 0.6 22.18 ± 2.81
Extracts at 100 mg/ml to
L-NAME group
AeC 324 ± 0.5 13.11 ± 0.9
EeC 204 ± 28 5.52 ± 0.2
Extracts at 200 mg/ml to
L-NAME group
AeC 346 ± 1.0 7.1 ± 1.1
EeC 288 ± 6.5 12.46 ± 1.2
Extracts at 300 mg/ml to
L-NAME group
AeC 312 ± 0.5 19.7 ± 1.2
EeC 300 ± 1.5 19.42 ± 0.94
Extracts at 400 mg/ml to
L-NAME group
AeC 312 ± 1.0 6.97 ± 0.7
EeC 204 ± 3.0 13.77 ± 0.62
Values are expressed in Mean ± SEM.
Table 2: Eect of AeC and EeC on Heart rate and Pulse Pressure of L-NAME animals.

Odimegwu JI, Okanlawon TF, Obumneme N, Ishola I. Clerodendrum Chinensis Extracts; AeC and EeC Exerts Rapid
Antihypertensive Eects in L-NAME Hypertensive Experimental Models. Arch Pharmacol er. 2021; 3(1):21-28.
Arch Pharmacol er. 2021
Volume 3, Issue 1 27
Conclusion
This study demonstrated the acute anti-hypertensive
properties of the AeC and EeC in Nitric Oxide decient
hypertensive rats. The observed eects could partially
be due to the reduction of the peripheral resistance by
thwarting the acute inhibitory eect of L-NAME on
endothelial Nitric Oxide Synthase. The recorded results
authenticate its use in traditional medicine for the treatment
of hypertension. Clerodendrum chinensis leaves extract,
have shown to exhibit more potent anti-hypertensive
properties when compared to known standards. Further
studies are however required to check specic mechanisms
of action and best and eective dosage forms.
Ethical Approval and Consent to
Participate
Not applicable.
Consent for Publication
All the authors have seen the manuscript and agree to the
publication.
Competing Interests
The authors declare no conict of interest.
Funding
This research did not receive any specic grant from
funding agencies in the public, commercial, or not-for-
prot sectors.
Authors’ Contributions
Odimegwu JI Conceptualized the research, designed the
methodology, wrote up the original draft and corrected the
nal manuscript.
Okanlawon TF worked at Data curation and corrected
Manuscript
Obumneme Noel NE carried out laboratory work and
contributed to editing and review
Ishola IO supervised the laboratory work and data
curation.
Acknowledgment
We are grateful to Prof. Chantal Epie who collected
the plants and told us about its actions and also to Mme
Rosemary Ossai for cultivating and multiplying the plant
for more sample materials for this work.
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