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The antiplasmodial and safety profile of alkaloid, flavonoid and phenol extracts of Sida acuta (300 and 600 mg/kgbw) on hepatic and renal integrity of rats were investigated. Alkaloid, flavonoid and phenol extracts produce parasitaemia suppression of 50.83%, 33.50% and 64.64%, respectively. Sub-chronic administration of the phytochemicals caused marked (p < 0.05) dose-dependent increase in erythrocytic and leucocytic indices while serum ALP, AST, ALT, albumin, urea and creatinine concentrations compared well (p > 0.05) with the controls. Total proteins, sodium and chloride levels were altered in rats treated with 300 mg/kgbw of the phytochemicals. The integrity of hepatocytes and renal cells increases with increase extract concentrations and no degenerative changes were observed in all treatment groups. However, flavonoid extract caused severe renal vacuolation at 300 mg/kgbw which cleared out at 600 mg/kgbw. Conclusively, phenol exhibited higher antiplasmodial activities and safety profile and thus could be considered a potential candidate for the development of a new drug.
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Antiplasmodial effect and sub-acute toxicity of
alkaloid, flavonoid and phenolic extracts of Sida
acuta leaf on Plasmodium berghei-infected animals
Daniel Anuoluwa Adesina , Sherifat Funmilola Adefolalu , Ali Audu Jigam &
Bashir Lawal
To cite this article: Daniel Anuoluwa Adesina , Sherifat Funmilola Adefolalu , Ali Audu Jigam &
Bashir Lawal (2020) Antiplasmodial effect and sub-acute toxicity of alkaloid, flavonoid and phenolic
extracts of Sida�acuta leaf on Plasmodium�berghei-infected animals, Journal of Taibah University
for Science, 14:1, 943-953, DOI: 10.1080/16583655.2020.1790912
To link to this article: https://doi.org/10.1080/16583655.2020.1790912
© 2020 The Author(s). Published by Informa
UK Limited, trading as Taylor & Francis
Group
Published online: 13 Jul 2020.
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JOURNAL OF TAIBAH UNIVERSITY FOR SCIENCE
2020, VOL. 14, NO. 1, 943–953
https://doi.org/10.1080/16583655.2020.1790912
Antiplasmodial effect and sub-acute toxicity of alkaloid, flavonoid and
phenolic extracts of Sida acuta leaf on Plasmodium berghei-infected animals
Daniel Anuoluwa Adesina a, Sherifat Funmilola Adefolalu a, Ali Audu Jigam aand Bashir Lawal a,b
aDepartment of Biochemistry, Federal University of Technology Minna, Minna, Nigeria; bPhD Program for Cancer Molecular Biology and
Drug Discovery, Taipei Medical University and Academia Sinica, Taipei, Taiwan
ABSTRACT
The antiplasmodial and safety profile of alkaloid, flavonoid and phenol extracts of Sida acuta
(300 and 600 mg/kgbw) on hepatic and renal integrity of rats were investigated. Alkaloid,
flavonoid and phenol extracts produce parasitaemia suppression of 50.83%, 33.50% and 64.64%,
respectively. Sub-chronic administration of the phytochemicals caused marked (p<0.05) dose-
dependent increase in erythrocytic and leucocytic indices while serum ALP, AST, ALT, albumin,
urea and creatinine concentrations compared well (p>0.05) with the controls. Total proteins,
sodium and chloride levels were altered in rats treated with 300 mg/kgbw of the phytochemicals.
The integrity of hepatocytes and renal cells increases with increase extract concentrations and no
degenerative changes were observed in all treatment groups. However, flavonoid extract caused
severe renal vacuolation at 300 mg/kgbw which cleared out at 600 mg/kgbw. Conclusively, phe-
nol exhibited higher antiplasmodial activities and safety profile and thus could be considered a
potential candidate for the development of a new drug.
ARTICLE HISTORY
Received 28 November 2019
Revised 5 May 2020
Accepted 17 June 2020
KEYWORDS
Sida acuta; alkaloid;
flavonoid; phenolic;
antiplasmodial activity;
sub-acute toxicity
1. Introduction
Malaria is a public health and life-threatening infectious
disease caused by a parasitic protozoan of the Plasmod-
ium genus and transmitted via the bite of Anopheles
mosquito [1]. Malaria is one of the major tropical dis-
eases with a global estimate of 219 million incidence
and 445,000 malarial deaths in 2017 [2]. The burden
of malaria is the greatest in Africa, representing 90%
of the estimated malaria-associated death [3]. It is the
greatest cause of mortality and hospitalization among
children <5 years of age in Sub-sahara Africa [4]. The
malaria incidence or burden is increasing rapidly, due to
the increase in parasite resistance to conventional drugs
[5] and side effects associated with conventional anti-
malarial drugs [6]. This global concern has, therefore,
called for an urgent need to search for new antimalarial
agents particularly from medicinal plant extracts which
are the potential source of new affordable and effective
antimalarial agents. This idea originated from the his-
torical use of medicinal plants in malaria treatment by
traditional healers. Moreover, artemisinin and quinine,
standardized antimalarial drugs, were derived from Cin-
chona species and Artemisia annua, respectively, thus
suggesting that other medicinal plant could also serve
as reservoir for new effective antimalarial agents [7].
A number of plants have been reportedly used in the
traditional management of malaria and have received
ample scientific validation in both in vivo and in vitro
models [8]. One of such plants is Sida acuta.
Sida acuta Burm.f (Malvaceae) is one of those plants
commonly used by traditional healers for the man-
agement of some health problems [9]. This plant is a
branched, erect, perennial herb of about 1.5 m height
[10]. S. acuta has been reportedly used as an antipyretic,
stomachic, antipyretic and diaphoretic. It is used as a
tonic and astringent and for treatments of urinary, bile,
hepatic and nervous disorders [11,12]. Pharmacologi-
cally, S. acuta has been reported for inhibitory activi-
ties against Anopheles stephensi [13], antioxidants [14],
antiulcer [15], wound healing [16] cardioprotective [17],
antidiabetic [18] and antibacterial activities [19,20]. Pre-
vious studies on the crude extract of S. acuta have
shown markedly antimalarial activities in both in vitro
(IC50 0.05 µg/ml compared to <0.042 µg/ml for chloro-
quine) and in vivo models [21,22].
Phytoconstituents are natural secondary metabo-
lites in plants, responsible for the plant odour, colour
and its therapeutic potencies. Most of the phytocon-
stituents have antioxidant, antimicrobial and antimalar-
ial properties and they protect cells against oxidative
stress damage [23,24]. Screening of phytochemicals
from medicinal plants is, therefore, an important tool in
identifying active metabolites of medicinal and indus-
trial application. Previous phytochemical studies of S.
CONTACT Bashir Lawal bashirlawal12@gmail.com Department of Biochemistry, Federal University of Technology Minna, Nigeria, PhD Program
for Cancer Molecular Biology and Drug Discovery, Taipei Medical University and Academia Sinica, Taipei 111, Taiwan
© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor& Francis Group
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted
use, distribution, and reproduction in any medium, provided the original work is properly cited.
944 D. A. ADESINA ET AL.
acuta have reported the presence of alkaloids (vasicine,
cryptolepine and ephedrine), phenolic compounds
(scopoletin, evofolin-A and B, 4-ketopinoresinol and
loliolide), polyphenol, flavonoids, coumarins, sapono-
sides, steroids (ecdysterone, β-sitosterol, stigmasterol,
ampesterol) and tannins as the major bioactive com-
ponents of the plant [14,19,25]. The present study
investigated the antimalarial potencies of alkaloid,
flavonoid and phenol extracts from Sida acuta against
P. bergehi–infected mice and also evaluated their
safety profile of on hepatic and renal integrity in
albino rats.
2. Materials and methods
2.1. Chemicals and reagents
Organic solvents (analytical grade) used for the extrac-
tion of the plant material (methanol, ethanol and n-
hexane) were products of Sigma Chemical Co St. Louis
M.O (USA). All analyses were performed with com-
mercial kits from Randox Laboratories Limited, United
Kingdom and Quimica Clinica Applicada, Spain. All
other chemicals used were also of analytical grade and
obtained from the Department of Biochemistry, Federal
University of Technology, Minna.
2.2. Plant materials
Sida acuta (broom weed) plant was randomly collected
in the environment of Zumba, Shiroro, Niger State. The
leaf was air-dried (36.5°C) for six days and was ground
into fine powder after which it was sieved and packaged
in air-tight containers.
2.3. Plasmodium parasite
P. berghei NK 65 chloroquine-sensitive strain was
obtained from the Institute for Medical Research and
Training, University of Ibadan, Nigeria and was main-
tained in the laboratory by serial passage in mice [3].
2.4. Experimental animals
Healthy albino animals (mice and rats) were procured
from Animal Breeding unit of Ahmadu Bello University
Zaria, Nigeria. The animals were maintained under stan-
dard laboratory conditions with access to commercial
feed pellets (growers) and water ad libitum. The princi-
ples, governing the use of laboratory animals as laid out
by the Federal University of Technology, Minna Com-
mittee on Ethics for Medical and Scientific Research
and also existing internationally accepted principles for
laboratory animal use and care as contained in the
Canadian Council on Animal Care Guidelines and Pro-
tocol Review and international standard (NIH Publica-
tion No. 85-23, 1985) were duly observed. The ani-
mals were fasted 12 h before the commencement of
any study.
2.5. Sample extraction
2.5.1. Alkaloid extraction
The extraction of the alkaloid was done by the continu-
ous extraction method using the Soxhlet apparatus, as
described by Gonzales and Tolentino [26]. Sida acuta-
powdered leaf (350 g) was moistened with 650 mL of
95% ethanol and alkalinified with 525 mL ammonia.
Following the overnight maceration, the sample was
extracted with ethanol; the extract was filtered and
concentrated in a water bath at 60°C. The crude alka-
loid was acidified with 1.0 N hydrochloric acid (30 mL),
filtered and the filtrate was alkalinified with ammo-
nia (40 mL), followed by chloroform (600 mL) partition-
ing. Extraction was continued with chloroform until the
last chloroform extract tested negative to Dragendorff’s
reagent. The extract was weighed and the percentage
yield (0.56%) was documented.
2.5.2. Flavonoid extraction
Flavonoid extraction was carried out according to the
method of Yahaya [27]. Sida acuta (175 g)-powdered
leaf sample was defatted with n-Hexane (250 mL) using
a Soxhlet extractor. The extraction was carried out for
six hours at 65°C. After the extraction, the thimbles were
driedinanovenat50
°C. The extracted marc was further
extracted with methanol (250 mL). The extract obtained
was then evaporated (40°C) using water bath to yield
concentrated flavonoids (6.78%).
2.5.3. Phenolic extraction
Dried and powdered leaves of Sida acuta (100 g) were
solubilized in methanol:water 240:60 mL (80:20, v/v)
and homogenized at room temperature (36.5°C) for 1 h
30 min. The solution was filtered with Whatman filter
paper, using a separatory funnel under vacuum. The fil-
trate was then evaporated using a water bath at 40°C to
obtain the free phenol (5.24%) extract [28].
2.6. Acute toxicity test
The acute toxicity studies were conducted as per the
Organization for Economic Cooperation and Develop-
ment (OECD) guidelines 425 [29]. Five female mice (6–8
weeks) were fasted for three hours and orally given a
dose of 5000 mg/kg bw of the phytochemical extract.
The mice were observed for physical signs first for three
hours and further for 72 h. The experiment was termi-
nated after 2 weeks of observations.
JOURNAL OF TAIBAH UNIVERSITY FOR SCIENCE 945
2.7. Antiplasmodial screening (curative test)
Evaluation of the curative potential of the extract was
done using the method described by Ryley and Peters
[30]. On the first day (D0), standard inoculums of about
1×107P. berghei-infected red blood cells were injected
intraperitoneally into the mice. Seventy-two hours later,
eight groups (consisting of three mice each) were set
up. Groups A and B were treated with 300 mg/kg bw and
600 mg/kg bw of the alkaloid extract, groups C and D
were treated with 300 mg/kg bw and 600mg/kg bw of
the phenol extract, while groups E and F were treated
with 300 mg/kg bw and 600 mg/kg bw of the flavonoid
extract, respectively. Chloroquine (25 mg/kg bw) was
given to the positive control group (group G) and dis-
tilled water to the negative control group (group H). The
drugs/extracts were given once daily for 5 days. Each
day of treatment, blood samples were collected from
the tail prick of each mouse and thin smears were pre-
pared and stained with 10% Giemsa solution. The dried
slides were examined under the microscope at x100
magnification and parasitaemia level was determined
by counting the parasites in a field [23]. Percentage par-
asitaemia and percentage suppression were calculated
using the following formula.
Calculation
%Suppression =
Parasitaemia in
negative control
parasitaemia in
treated group
Parasitaemia in
negative control
×100
% Parasitaemia =
Number of parasitized
red blood cell
Total red
blood cell counted
×100
2.8. Sub-acute toxicity
Sub-acute toxicity was carried out according to OECD
guideline 410 [31]. Both sexes of the albino rats
(100–170 g) were divided into seven groups (5 animals
per group). 300 mg/kg bw and 600 mg/kg bw of each
phytochemical extract were administered orally to six
groups and the seventh group (positive control) was
given distilled water. All treatments were administered
orally with the aid of intubation cannula once daily for
21 days. All the animals were observed for clinical signs
at the time of onset, duration of these symptoms, if any,
were recorded. Body weights of the rats in all groups
were recorded once before the start of dosing and once
weekly.
2.8.1. Collection of blood, preparation of serum and
tissue homogenate
The methods described by Yusuf et al. [32] were used
for blood sample and liver collections. At the end of
the experiment (on the 21st day), the blood samples
were collected from overnight fasted rats (only water
allowed) by retro-orbital bleeding into heparinized and
non-heparinized tubes for haematological analysis and
biochemical analyses. Blood samples for biochemical
study were centrifuged at 3000 r.p.m. for 15 min, after
which the serum was transferred into a plain sample
bottle. The liver and kidney were carefully harvested
and stored in formalin for histological analysis.
2.8.2. Biochemical parameters
Spectrophotometric methods were used for the deter-
mination of aspartate transaminase and alanine trans-
aminase activities, as described by Reitman and Frankel
[33]. Urea in serum/plasma is hydrolyzed to ammonia
in the presence of urease. The ammonia is measur-
able photometrically by Berthelot’s reaction [34]. Cre-
atinine was analyzed as the amount of coloured com-
plex formed when alkaline solution reacts with picric
acid [35]. Determination of total protein was done, as
described by Weichselbaum [36]. Albumin measure-
ment was done with Bromocresol Green according to
the methods of Doumas et al. [37]. Sodium concen-
tration was estimated, as described by Maruna [38],
while serum chloride concentration was determined, as
described by Tietz [39].
2.8.3. Determination of haematological parameters
The haematological components including haemo-
globin (Hb), packed cell volume (PCV), red blood
cells (RBC), mean corpuscular volume (MCV), mean
corpuscular haemoglobin (MCH), mean corpuscular
haemoglobin concentration (MCHC), white blood cells
(WBC), platelate count (PLC), differential count (lym-
phocytes and neutrophils) and RBC Distribution Width
Count (RDWC) were determined using the automated
haematologic analyzer SYSMEX KX 21, a product of
SYSMEX Corporation, Japan employing the methods
described by Dacie and Lewis [40].
2.8.4. Histopathological studies
Ten percent formalin solution was used to fix the kid-
ney and liver tissues. Staining was done using Harri’s
haematoxylin and eosin method. The dried slides were
mounted with Distyrene Plasticizer Xylene (DPX) moun-
tant and cover slips and examined under the micro-
scope to verify histological details [41].
2.9. Statistical analysis
The analysis was performed using SPSS statistical pack-
age for WINDOWS (version 21.0; SPSS Inc, Chicago).
946 D. A. ADESINA ET AL.
Data were expressed as the Mean ±SEM of three deter-
minations. Results were subjected to ANOVA followed
by DMRT. Statistically significance was considered at
p<0.05.
3. Results
3.1. Acute toxicity
There was no death recorded in animals dosed with
alkaloid, flavonoid and phenolic extracts of S. acuta leaf
at 5000 mg/kg bw. No toxic symptom was observed
in any of the experimental animals. All animals in the
extract-treated groups were normal and did not display
any observable signs of toxicity on the skin, breathing,
food intake, water consumption, postural patterns and
hair loss.
3.2. In vivo antiplasmodial eect of the
phytochemicals
The % parasitaemia of P. bergei-infected mice treated
with alkaloid, flavonoid and phenolic extracts of S. acuta
are presented in Figures 1and 2. The negative con-
trol (infected untreated mice) had the highest % par-
asitaemia of 60.33 ±4.05. Alkaloid extract (300 mg/kg
bw) gave the lowest % parasitaemia and highest %
suppression of 25.00 ±7.00 and 58.56%, respectively,
while phenolic extract (600 mg/kg bw) gave the low-
est % parasitaemia and highest % suppression of
21.33 ±2.84 and 64.64%, respectively. However, chloro-
quine (25 mg/kg bw) had the loweR % parasitaemia
and higheR % suppression of 14.00 ±1.00 and 76.79%,
respectively when compared with the extracts-treated
groups.
There was loss of body weight in all the treated and
untreated mice (Table 1). The PCV of untreated mice as
well as those treated with the chloroquine (25 mg/kg
bw) and phytochemicals at 300 mg/kg bw had a loss
of PCV after treatments. Only mice treated with the
Tab le 1. Effect of alkaloid, flavonoid and phenolic extracts of S.
acuta leaf on the bodyweight of Plasmodium berghei-infected
mice.
Groups
Weight
before (g)
Weight
after (g)
Weight
gain/Loss (g)
Alkaloid 300 mg/kg bw 27.02 ±2.93b26.97 ±2.86b0.05
Flavonoid 300 mg/kg bw 29.85 ±1.51b29.04 ±1.37c0.81
Phenol 300 mg/kg bw 28.56 ±0.71b27.29 ±2.06c1.27
Alkaloid 600 mg/kg bw 28.07 ±2.01b21.50 ±1.98a6.57
Flavonoid 600 mg/kg bw 28.82 ±1.76b25.41 ±2.10b3.41
Phenol 600 mg/kg bw 27.76 ±1.56b26.06 ±2.35b1.7
Chloroquine 25 mg/kg bw 25.02 ±3.25ab 25.38 ±1.87b0.36
Negative control 25.96 ±0.75ab 22.94 ±0.29a3.02
Note: Values are mean ±SEM of 3 determinations. Values along the same
column with different superscripts are significantly different (p<0.05).
flavonoids and phenols at 600 mg/kg bw gain PCV of
1.74 and 6.61%, respectively, after treatments (Table 2).
3.3. Sub-chronic eect of avonoid, alkaloid and
phenolic extracts of S. acuta leaf
3.3.1. Haematological parameters
Red Blood Cell was significantly increased (p<0.05) in
rats treated with 600 mg/kg bw of alkaloids and phenol
extracts when compared with other treatment groups
and the control group. The result also showed a signif-
icant (p<0.05) increase in Hb, MCH, MCHC, PCV and
WBC in all the treatment groups (alkaloid, flavonoid and
phenol extracts of S. acuta leaf) when compared with
the control group. No significant difference (p>0.05)
was noted in MCV, LY, PLC and RDWC when compared
with the control group (Table 3).
3.3.2. Biochemical parameters
Serum aspartate transaminase (AST), alanine transam-
inase (ALT), alkaline phosphatase (ALP), albumin, urea
and creatinine concentrations were not significantly dif-
ferent (p>0.05) in all the treatment groups (alkaloid,
flavonoid and phenol extracts of S. acuta) when com-
pared with the control group, while sodium was signif-
icantly lowerd (p<0.05) in all treatment groups when
Figure 1. In vivo antiplasmodial effect of alkaloid, flavonoid and phenolic extracts (300 mg/kg bw) of S. acuta leaf on Plasmodium
berghei-infected mice.
JOURNAL OF TAIBAH UNIVERSITY FOR SCIENCE 947
Figure 2. In vivo antiplasmodial effect of alkaloid, flavonoid and phenolic extracts (600 mg/kg bw) of S. acuta leaf on Plasmodium
berghei-infected mice.
Tab le 2. Effect of alkaloid, flavonoid and phenolic extracts of
S. acuta leaf on packed cell volume of Plasmodium berghei-
infected mice.
Groups PCV before (%) PCV after (%)
PCV
Gain/Loss
Alkaloid 300 mg/kg bw 40.18 ±7.37b36.00 ±6.85b4.18
Flavonoid 300 mg/kg bw 50.17 ±5.26c45.57 ±4.42c4.59
Phenol 300 mg/kg bw 50.23 ±5.37c33.56 ±9.31b16.67
Alkaloid 600 mg/kg bw 43.76 ±3.29b42.22 ±1.90c1.54
Flavonoid 600 mg/kg bw 41.52 ±5.16b43.26 ±1.17c+1.74
Phenol 600 mg/kg bw 44.91 ±2.05b38.30 ±2.59b+6.61
Chloroquine 25 mg/kg bw 54.96 ±3.13c40.82 ±2.65c14.14
Negative control 36.17 ±7.41a23.83 ±2.53a12.34
Note: Values are mean ±SEM of three determinations. Values along
the same column with different superscripts are significantly different
(p<0.05).
compared with the control group. Total protein concen-
tration was significantly (p<0.05) lower in rats treated
with 300 mg/kg bw of flavonoid extract, while chlo-
ride was significantly (p<0.05) higher in rats treated
with 300 mg/kg bw of alkaloid and phenol extracts than
other treatment groups and the control group (Table 4).
3.3.3. Bodyweight
The effects of the administration of alkaloid, flavonoid
and phenolic extracts of S. acuta on the bodyweight
of albino rats are shown in Table 5. The bodyweight
gains of the rats administered with alkaloid, flavonoid
and phenol extracts of S. acuta were not significantly
(p>0.05) different from each other but were signifi-
cantly (p<0.05) lower than those of the control group.
3.4. Histopathology
3.4.1. Effect of phytochemical extracts of S. acuta
leaf on the kidney histopathology of albino rats
The histological features as regards to renal vacuola-
tion, integrity of renal corpuscles, degenerative changes
and general appearances of kidney in the albino rats
treated with alkaloid, flavonoid and phenol extracts
of S. acuta are presented in Tables 6and 7. There
were no renal vacuolation in rats treated with phe-
nol and alkaloid extracts of Sida acuta when com-
pared with the control group. However, rat treated
with flavonoid extract had severe renal vacoulation at
300 mg/kg bw (Table 6) which clears out at 600 mg/kg
bw (Table 7) when compared with the control group.
The integrity of renal corpuscles is better as the
administered doses increases. There were also mild
degenerative changes in rats treated with 300 mg/kg
bw phenol and flavonoids; however, normal cellu-
lar kidney appearance was observed in all treatment
groups.
3.4.2. Effect of phytochemical extract of S. acuta
leaf on the liver histopathology of albino rats
The histological features, as regards to central vein,
integrity of hepatocyte, degenerative changes and gen-
eral appearances of liver in albino rats treated with
alkaloid, flavonoid and phenol extracts of S. acuta,
are presented in Tables 8and 9. Severe conges-
tion with flavonoid at 300 mg/kg bw (Table 8)which
cleared out at 600 mg/kg bw (Table 9) when compared
with the control group was observed. The integrity
of hepatocytes is better as the administered doses
increase; no any degenerative changes were observed
in all treatment groups. Also, normal hepatocellu-
lar appearance was observed in all treatment groups
(Figures 3and 4).
4. Discussion
Phytochemicals are secondary metabolites of plants
known to exhibit diverse pharmacological and bio-
chemical effects on living organisms [42]. The acute tox-
icity of the alkaloids, flavonoids and phenols was mea-
sured to obtain information regarding the oral safety of
the secondary metabolites. Interestingly, it was discov-
ered that all phytochemicals tested had LD50 >than
5000 mg/kg bw, thus exhibiting a wide safety margin
upon acute oral administration. However, Konaté et al.
948 D. A. ADESINA ET AL.
Tab le 3. Effects of alkaloid, flavonoid and phenolic extracts of S. acuta leaf on haematological parameters of albino rats.
Groups RBC Hb MCH MCHC PCV WBC MCV PLC N L RDWC
Alkaloid 300 mg/kg bw 6.75 ±0.35a13.05 ±0.35b19.50 ±0.50b30.50 ±0.50b42.00 ±2.0b9.95 ±0.55b63.50 ±1.50a387.50 ±24.50a7.00 ±1.00a73.50 ±2.50a16.50 ±0.50a
Flavonoid 300 mg/kg bw 6.75 ±0.45ab 13.45 ±0.85b18.50 ±1.50b28.50 ±0.50ab 43.00 ±5.0b8.10 ±3.00b64.50 ±3.50a525.00 ±7.00a10.50 ±1.50b60.00 ±18.00a16.50 ±0.40a
Phenol 300 mg/kg bw 6.75 ±0.25ab 12.55 ±0.50b19.50 ±0.50b29.00 ±1.00b40.00 ±0.0b10.15 ±0.05b65.50 ±0.50a416.50 ±17.50a10.50 ±6.50b64.50 ±18.50a16.95 ±0.15a
Alkaloid 600 mg/kg bw 7.60 ±0.00b13.75 ±0.75b18.00 ±1.00b31.00 ±1.00b43.00 ±3.0b8.05 ±0.05b60.00 ±0.00a382.00 ±71.00a10.00 ±0.00b80.00 ±2.00a17.12 ±0.12a
Flavonoid 600 mg/kg bw 6.95 ±0.15ab 13.10 ±0.30b18.00 ±2.00b30.00 ±0.00b39.50 ±0.5b5.60 ±0.50b61.50 ±2.50a522.00 ±99.01a6.00 ±1.00a76.00 ±4.00a17.30 ±0.40a
Phenol 600 mg/kg bw 7.75 ±0.55b14.15 ±0.75b20.50 ±0.50b31.50 ±0.50b43.50 ±3.5b9.20 ±1.80b62.50 ±3.50a514.00 ±27.00a6.00 ±1.00a72.50 ±3.50a19.00 ±0.40a
Positive Control 6.05 ±0.65a9.10 ±3.70a16.00 ±4.00a26.00 ±4.00a32.50 ±9.5a5.95 ±1.8a64.50 ±0.50a410.00 ±11.09a6.00 ±1.00a75.00 ±5.00a16.95 ±0.67a
Standard Value 7.2-10.1 10.36-13.9 13.0-19.0 26.5-58 33–50 10.2-13.8 46.5-65.0 385–610 20–70 20–70 15–20
Note: Hb-Haemoglobin, PCV-Packed Cell Volume, MCH-Mean Cell Haemoglobin, MCHC-Mean Cell Haemoglobin Concentration, RBC-Red Blood Cell Count, WBC-Total White Blood Cell Count, MCV-Mean Cell Volume, PLC-Platelet Count, N-
Neutrophils, L-Lymphocytes, RDWC-RBC Distribution Width. Values are mean ±SEM of 3 determinations. Values along the same column with different superscripts are significantly different (p<0.05). Standard Value Source: University of
Pennylsavania, School of Veterinary Medicine (2002).
Tab le 4. Effects of alkaloid, flavonoid and phenolic extracts of S. acuta leaf on biochemical parameters of albino rats.
Groups AST ALT ALP TP Albumin Sodium Chloride UREA Creatinine
Alkaloid 300mg 10.80 ±0.00a37.60 ±4.00a87.9 ±3.52a36.10 ±1.90b2.28 ±0.30a89.36 ±5.58a89.09 ±0.37bc 76.84 ±3.66a3.14 ±1.43a
Flavonoid 300mg 10.80 ±3.60a43.24 ±5.64a85.09 ±3.41a18.05 ±8.50a2.01 ±0.03a77.79 ±1.19a73.68 ±3.00ab 93.31 ±1.83a4.28 ±1.42a
Phenol 300mg 18.00±3.60ab 45.12 ±3.76a82.09 ±3.48a29.45 ±0.95ab 1.82 ±0.19a99.73 ±2.39a98.87 ±10.90c100.62 ±27.44a3.71 ±0.28a
Alkaloid 600mg 7.20±3.60a44.18 ±4.70a91.77 ±3.36ab 26.60 ±3.80ab 2.01 ±0.22a53.45 ±13.56a84.96 ±0.75abc 87.82±3.66a6.00 ±1.43a
Flavonoid 600mg 16.20 ±1.80ab 47.94 ±0.94a88.02 ±3.59a38.00 ±5.70b2.12 ±0.08a74.60 ±34.71a70.30 ±1.88a84.16 ±7.32a5.42 ±0.28a
Phenol 600mg 12.60 ±5.40a46.06 ±2.82a79.91 ±3.65a31.35 ±2.85ab 1.56 ±0.90a104.12 ±3.59a79.70 ±3.76ab 75.01 ±98.15a6.00 ±0.29a
Positive Control 18.00 ±0.00ab 46.06 ±2.82a80.67 ±3.79a34.09 ±0.11b1.56 ±0.38a176.73 ±15.56b75.18 ±1.50ab 84.16 ±7.32a6.00 ±2.57a
Standard Value 10–45 10–35 15–45 11–25 3.6-5.3 140–160 90–110 25–45 0.5-2.2
Note: Values are mean ±SEM of three determinations. Values along the same column with different superscripts are significantly different (p<0.05).
Standard Value Source: University of Pennylsavania, School of Veterinary Medicine (2002).
JOURNAL OF TAIBAH UNIVERSITY FOR SCIENCE 949
Tab le 5. Effect of alkaloid, flavonoid and phenolic extracts of S. acuta leaf on the bodyweight of
albino rats.
Groups Week 1 Week 2 Week 3 Total weight gain
Alkaloid 300 mg/kg bw 141.30 ±1.80bc 148.90 ±4.50bc 160.00 ±2.00c18.70 ±1.73a
Flavonoid 300 mg/kg bw 117.80 ±8.00ab 131.80 ±7.30b137.00 ±1.00ab 19.20 ±0.96a
Phenol 300 mg/kg bw 115.85 ±2.36ab 127.30 ±1.00ab 138.50 ±1.50ab 22.65 ±1.06ab
Alkaloid 600 mg/kg bw 126.40 ±4.10b134.30 ±20.80b144.50 ±19.50b18.10 ±0.95a
Flavonoid 600 mg/kg bw 121.50 ±6.20b126.65 ±11.95ab 134.00 ±19.00ab 12.50 ±0.02a
Phenol 600 mg/kg bw 93.35 ±2.95a100.75 ±0.95a113.00 ±4.00a19.65 ±1.31a
Positive Control 107.90 ±7.40ab 132.30 ±1.40b144.00 ±4.00b36.10 ±2.09b
Tab le 6. Effect of alkaloid, flavonoid and phenolic extracts of S. acuta (300 mg/kg bw) Leaf on the
kidney histopathology of albino rats.
Kidney Control
300 mg/kg bw
Phenolic
300 mg/kg bw
Flavonoid
300 mg/kg bw
Alkaloid
Renal vacuolation Nil Mild Severe Nil
Integrity of renal corpuscles Excellent Mild distortion Poor/severe distortion Good with no distortion
Degenerative changes Nil Mild Mild Nil
General appearances Excellent Good Mild distortion Excellent
Tab le 7. Effect of alkaloid, flavonoid and phenolic extracts of S. acuta (600 mg/kg bw) leaf on the kidney histopathology of albino
rats.
Kidney Control
600 mg/kg
bw Phenolic
600 mg/kg bw
Flavonoid
600 mg/kg
bw Alkaloid General remarks
Renal vacuolation Nil Nil Mild Nil Severe renal vacuolation with flavonoid
(300 mg) which clears out at 600 mg
when compared with control
Integrity of renal corpuscles Excellent Excellent Mild cellular integrity Good Integrity of renal corpuscles is better as the
administered doses increase
Degenerative changes Nil Nil Nil Nil Generally, degenerative changes seen at
lower doses
General appearances Excellent Excellent Good Excellent Generally normal cellular appearance
Tab le 8. Effect of alkaloid, flavonoid and phenolic extracts of S. acuta (300 mg/kg bw)leaf on the
liver histopathology of albino rats.
Liver Control
300 mg/kg bw
Phenolic
300 mg/kg bw
Flavonoid
300 mg/kg bw
Alkaloid
Central vein congestion Nil Nil Severe congestion Nil
Integrity of hepatocytes Excellent Mild distortion Poor/severe distortion Good with no distortion
Degenerative changes Nil Mild Mild to moderate Nil
General appearances Excellent Good Mild distortion Excellent
Tab le 9. Effect of alkaloid, flavonoid and phenolic extracts of S. acuta (600 mg/kg bw) leaf on the liver histopathology of albino rats.
Liver Control
600 mg/kg bw
Phenolic
600 mg/kg bw
Flavonoid
600 mg/kg bw
Alkaloid General remarks
Central vein congestion Nil Nil Mild Nil Severe congestion with flavonoid which clears
out at 600mg when compared with the
control group
Integrity of hepatocytes Excellent Excellent Good with improved integrity Good Integrity of hepatocytes is better as the
administered doses increase
Degenerative changes Nil Nil Nil Nil Generally, no degenerative changes seen.
General appearances Excellent Excellent Good Excellent Generally normal cellular appearance
[43] reported LD50 values of 3.2 g/kg for crude extract of
S. acuta in mice, thus suggesting negligible level of tox-
icity of the crude extract. Results of the present study
indicated that alkaloids, flavonoids and phenols exhib-
ited active antiplasmodial activity in accordance with
the reports of Carvalho [44] who stated that a com-
pound with reduction in parasitaemia 30% is consid-
ered active. This suggests that alkaloid, flavonoid and
phenolic extracts of S. acuta leaf may be considered as
a bioactive metabolite with potential for the develop-
ment of a novel antimalarial drug.
However, the higher % suppression of the parasite
produce by phenol extract (64.64% at 600 mg/kg bw)
compared to alkaloid and flavonoid extracts indicated
that the phenol extracts would be better antimalarial
than the other phytochemicals. Chloroquine has been
reported for the disruption of the parasite’s cell mem-
brane and induction of auto-parasite digestion via the
formation of FP-chloroquine complex which impaired
the haeme polymerization [45]. The lower percentage
suppression observed in the extract-treated group than
that of the chloroquine-treated group may be because
950 D. A. ADESINA ET AL.
Figure 3. Histomicrogram of the kidney of alkaloid, flavonoid and phenolic extracts of S. acuta leaf in albino rats. (Arrow indicates
renal vacuolation at 300 mg/kg bw which was corrected at 600 mg/kg bw).
Figure 4. Histomicrogram of the liver of alkaloid, flavonoid and phenol extracts of S. acuta leaf in albino rats. (Arrow indicates central
vein congestion at 300 mg/kg bw which was corrected at 600 mg/kg bw).
the phytochemicals in its current form and at the doses
administered had not accumulated sufficiently to bring
about considerable suppression [46]orithasalower
speed of action than that of chloroquine. This is similar
to the study of Builder [47] who reported 83% inhi-
bition of parasitaemia for chloroquine. Although the
activities demonstrated by each phytochemical extract
were lower than those of a standard drug (chloroquine)
(76.79%), it is possible that a combination of 2 or 3
of these phytochemicals would act synergistically to
exhibit higher antimalarial activities comparable to or
better than the chloroquine.
Anaemia is one of the recognized effects of malaria
that occurs due to the destruction of red blood cell.
Therefore, effective antimalariaL agents are expected to
reverse or prevent the parasite-induced anaemic con-
dition. The increases in PCV (1.74 and 6.61%) of mice
treated with the flavonoid and phenol extracts of S.
acuta (Table 2) are an indication of enhanced resis-
tance to erythrocyte haemolysis [48]. The flavonoids
and phenols, therefore, prevented the parasite-induced
anaemic condition in mice. The high loss of body weight
in mice treated with high dose (600 mg/kg bw) of
each phytochemical extract could be attributed to the
JOURNAL OF TAIBAH UNIVERSITY FOR SCIENCE 951
depressing effect of the phytochemical extracts on feed
uptake/appetite [49] with consequent effects on the
phytochemicals.
Hematological parameters are widely used markers
in assessing the toxicity or safety of a drug/extract as
well as assessing the health status of an animal [50]. The
significant increase in the WBC count in the rats treated
with alkaloid, flavonoid and phenolic extracts could be
an indication of leucopoetic potentials and possible
immunomodulatory properties of the phytochemical
extract which enhances the production of more WBC
[51]. This will enhance the antibody-generating poten-
tial of the animals via phagocytosis and will have high
resistance to infection and diseases [52] Similarly, the
significant (p<0.05) increase in erythrocytic indices,
including HGB, PCV, MCH, MCHC, in all the treatment
groups (alkaloid, flavonoid and phenolic extracts of S.
acuta) when compared with the control is an indication
of stimulation of erythropoiesis by the phytochemicals.
The phytochemicals must have enhanced the release of
erythropoietin in the kidney, a humoral mediator of RBC
production [53].
Analyses of biochemical parameters, such as transa-
minases, phosphatase, albumins and total proteins,
have been identified as a reliable indicator of organ
function and healthy or disease status of animals dur-
ing subacute administration of extracts or phytochemi-
cals to animals [54,55,56]. Alterations in serum levels of
these markers are indicators of hepatocellular impair-
ments, cell membrane impairment, liver hepatitis or
cirrhosis.
Interestingly, the serum aspartate transaminase
(AST), alanine transaminase (ALT), alkaline phosphatase
(ALP) and albumin concentrations were not significantly
altered by the treatment with alkaloid, flavonoid and
phenol extracts of S. acuta. This is an indication that
the administration of phytochemicals to the rats has
not compromised the integrity of the liver, i.e. the func-
tional integrity of the liver has been preserved. How-
ever, the alterations in total protein concentrations in
rats treated with 300 mg/kg bw of flavonoid extract
could be attributed to protein turnover during the
metabolism of the flavonoid, such an increase in total
proteins could lead to dehydration which is detrimental
to cellular homeostasis, thus effecting the health of the
animals [57].
Serum electrolytes, urea and creatinine, on the other
hand, indicate the function integrity of the kidney [55].
In this study, urea and creatinine concentrations were
not affected by the administration of the phytochem-
icals, thus suggesting that the functional capacity of
the kidney has not been compromised [58] However,
the significant alterations (p>0.05) in the concentra-
tions of sodium and chloride in the albino rats dosed
with the phytochemical extracts are an indication that
the functional integrity of the kidney as regards to this
metabolite has been compromised. Nevertheless, the
mild alterations recorded in the electrolyte may not be
of clinical relevance without histopathological backup
[59]. Fortunately, it was observed that the alkaloid and
phenol extracts of Sida acuta do not alter the normal cel-
lular architectures of the liver and kidney. In fact, the
integrity of the hepatocytes and renal corpuscles was
improved at higher doses of the alkaloid and pheno-
lic extracts better than the control group. It is, there-
fore, reasonable to conclude that the mild alteration
observed in some of the biochemical parameters could
be attributed to the initial metabolic adaptations of the
animals [60] to the phytochemicals and are not of clin-
ical significance as regards to the integrity of the liver
and kidney.
5. Conclusion
The study suggests that alkaloid, flavonoid and phe-
nolic extracts of Sida acuta leaf possess antiplasmodial
properties with phenolic extract (600 mg/kg bw) pos-
sessing the highest plasmodial suppression (64.64%)
among other extracts and close to the positive con-
trol (chloroquine) which caused plasmodial suppres-
sion of 76.79%. The phytochemicals were also found
to be safe as revealed by biochemical, haematological
and histopathological findings of sub-chronic toxicity
studies.
Disclosure statement
No potential conflict of interest was reported by the author(s).
ORCID
Daniel Anuoluwa Adesina http://orcid.org/0000-0002-6619-
3656
Sherifat Funmilola Adefolalu http://orcid.org/0000-0002-
6923-1304
Ali Audu Jigam http://orcid.org/0000-0001-6586-8087
Bashir Lawal http://orcid.org/0000-0003-0676-5875
References
[1] Ounjaijean S, Kotepui M, Somsak V. Antimalarial activ-
ity of Tinospora baenzigeri against Plasmodium berghei-
infected mice. J Trop Med. 2019:16.doi:10.1155/2019/
5464519.
[2] WHO. World Malaria Report, World Health Organization,
Geneva, Switzerland, 2017, http://wwwwhoint/malaria/
world_malaria_report_2017/en/indexhtml.
[3] Mzena T, Swai H, Chacha M. Antimalarial activity of
Cucumis metuliferus and Lippia kituiensis against Plas-
modium berghei infection in mice. Res Rep Trop Med.
2018;9:81–88.
[4] Ajayi EIO, Adeleke MA, Adewumia TY, et al. Antiplas-
modial activities of ethanol extracts of Euphorbia hirta
whole plant and Vernonia amygdalina leaves in Plas-
modium berghei-infected mice. J Taibah Univ Sci. 2017;1:
831–835.
[5] Lawal B, Shittu OK, Abubakar A, et al. Human genetic
markers and structural prediction of plasmodium falci-
parum multi-drug resistance gene (Pfmdr1) for ligand
952 D. A. ADESINA ET AL.
binding in pregnant women attending General Hospital
Minna. J Environ pub Health. 2018;2018:1–13.
[6] Rout S, Mahapatra RK. Plasmodium falciparum: multi-
drug resistance. Chem Biol Drug Des. 2019;93:737–759.
[7] Pan WH, Xu XY, Xu N, et al. Antimalarial activity of plant
metabolites. Intern J Mol Sci. 2018;19(5):1382–1389.
[8] Lawal B, Shittu OK, Kabiru AY, et al. Potential antimalar-
ials from African natural products: A review. J. Intercult
Ethnopharmacol. 2015;4(4):318–343.
[9] Benjumea DM, Gómez-Betancur IC, Vásquez J, et al.
Neuropharmacological effects of the ethanolic extract
of Sida acuta. Revista Brasileira de Farmacognosia.
2016;26(2):209–215.
[10] Mohideen S, Sasikala E, Gopal V. Pharmacognostic stud-
ies on Sida acuta Burm.f. Ancient sci of Life. 2002;22(1):57.
[11] Khare M, Srivastava SK, Singh AK. Chemistry and phar-
macology of genus Sida (Malvaceae); a review. J. Med.
Aromatic Plant Sci. 2002;24:430–440.
[12] Olivier TT, Armel JS, Francis NT. Ethnomedicinal uses,
phytochemical and pharmacological profiles, and toxic-
ity of Sida acuta Burm. F.: a review article. The Pharma
Innovat J. 2017;6(6):1–6.
[13] Aarthi A, Murugan K, Madhiyazhagan P, et al. Studies on
the effect of sida acuta and Vetiveri azizanioides against
the malarial vector, anopheles stephensi and malarial
parasite, plasmodium berghei. Inter J Pure Appl Zool.
2014;2(1):51–60.
[14] Konate K, Souza A, Coulibaly AY, et al. In vitro antioxi-
dant, lipoxygenase and xanthine oxidase inhibitory activ-
ities of fractions from Cienfuegosia digitata Cav, Sida
alba L. and Sida acutaBurn f. (Malvaceae). Pak J Biol Sci.
2010;13:1092–1098.
[15] Malairajan P, Gopalakrishnan G, Narasimhan S, et al.
Antiulcer activity of Sida acuta Burm. Nat Prod Sci.
2006;12:150–152.
[16] Akilandeswari S, Senthamarai R, Valarmathi R, et al.
Wound healing activity of Sida acuta in rats. Int J Pharm
Technol. 2010;2:585–587.
[17] Ramachandran AV. Cardioprotective effect of Sida rhom-
boidea. Roxb extract against isoproterenol induced
myocardial necrosis in rats. Exp Toxicol Pathol. 2011;63:
351–356.
[18] Arciniegas A, Pérez-Castorena A, Nieto-Camacho A. Anti-
hyperglycemic, antioxidant, and anti-inflammatory activ-
ities of extracts and metabolites from Sida acuta and Sida
rhombifolia. Química. 2017;40:176–181.
[19] Karou SD, Savadogo A, Canini A, et al. Antibacterial
activity of alkaloids from Sida acuta. Afr J Biotechnol.
2005;4:1452–1457.
[20] Jindal A, Kumar PA. Antibacterial activity of Sida acuta
Burm. f. against human pathogens. Asian J Pharm Clin.
Res. 2012;5:33–35.
[21] Karou D, Mamoudou H, Sanon S, et al. Antimalarial
activity of Sida acuta Burm. f. (Malvaceae) and Ptero-
carpus erinaceus Poir. (Fabaceae). J Ethnopharmacol.
2003;89:291–294.
[22] Banzouzi JT, Prado R, Menan H, et al. Studies on
medicinal plants of Ivory Coast: investigation of Sida
acuta for in vitro antiplasmodial activities and identifi-
cation of an active constituent. Phytomedicine. 2004;11:
338–341.
[23] Jigam AA, Mahmood F, Lawal B. Protective effects
of crude and alkaloidal extracts of Tamarindus indica
against acute inflammation andnociception in rats.
J Acute Dis. 2017;6(2):78–81.
[24] Umar SI, Lawal B, Mohammed BA, et al. Antioxidant and
antimicrobial activities of naturally occurring flavonoids
from M. heterophylla and the safety evaluation in Wistar
rats. Iran J Toxicol. 2019;13(4):39–44.
[25] Prakash A, Varma RK, Ghosal S. Alkaloid constituents
of Sida acuta, Sida humilis, Sida. rhombifolia and Sida
spinosa. Planta Med. 1981;43:384–388.
[26] Gonzales MVM, Tolentino AG. Extraction and isolation of
the alkaloids from the Samanea Saman (Acacia) Bark: its
antiseptic potential. Inter J Sci Technol. 2014;3:1–6.
[27] Yahaya MM. Isolation and purification of flavonoids from
the leaves of locally produced Carica Papaya. Intern J Sci
Technol Res. 2015;4(12):282–284.
[28] Atansuyi K, Ibukun EO, Ogunmoyole T. Antioxidant
properties of free and bound phenolic extract of the
leaves of Jatropha tanjorensis In vitro. J Med Plants Res.
2012;6(31):4667–4674.
[29] OECD. (2008). OECD guideline for testing of chemicals.
Test No. 425: acute oral toxicity: up-and-down procedure.
doi:10.1787/9789264071049-en.
[30] Ryley JF, Peters W. The antimalarial activity of some
Quinolone Esters. Annals of Trop Med Parasitol. 1970;64
(2):209–222.
[31] Organization for Economic Cooperation and Develop-
ment. (1981). Repeated dose dermal toxicity: 21/28-day
oral toxicity study in rodents. Guidelines for the Testing of
Chemicals/Draft Updated Test Guideline 410.
[32] Yusuf AA, Lawal B, Yusuf MA, et al. Free radical scav-
enging, antimicrobial activities and effect of sub-acute
exposure to Nigerian Xylopia Aethiopica seed extract on
liver and kidney functional indices of albino rat. Iran J
Toxicol. 2018;12(3):51–58.
[33] Reitman S, Frankel S. A colorimetric method for the
determination of serum glutamic oxalacetic and glu-
tamic pyruvic transaminases. Am J Clin Pathol. 1957;28:
56–63.
[34] Weatherburn MW. Phenol-hypochlorite reaction for
determination of ammonia. Analyt Chem. 1967;39:
971–974.
[35] Bartels H, Bohmer M, Heierli C. Serum creatinine deter-
mination without protein precipitation. Clin Chem Acta.
1972;37:193–197.
[36] Weichselbaum TE. An accurate and rapid method for
the determination of proteins in small amounts of blood
serum and plasma. Amer J Clin Pathol. 1946;10:40–49.
[37] Doumas BT, Watson WA, Biggs HG. Albumin standards
and the measurement of serum albumin with Bromcresol
Green. Clin Chem Acta. 1971;31(1):87–96.
[38] Maruna RFL. Quantitative estimation of sodium (Na),
potassium (K) in human serum by colorimetric methods.
Clin Chem Acta. 1958;2:581–585.
[39] Tietz NW. Clinical guide to laboratory tests. 3rd ed.
Philadelphia (PA): WB Saunders Company; 1996;
pp. 286–288.
[40] Dacie JV, Lewis SM. Practical Haematology. 11th Edn.
London: Elsevier; 2002; pp: 380-382.
[41] Igwebuike UM, Eze UU. Morphology of the caeca of
the african pied crow (corvus albus). Anim Res Inter.
2010;7(1):1121–1124.
[42] Sultana B, Anwar F, Ashraf M. Effect of extraction sol-
vent/technique on the antioxidant activity of selected
medicinal plants extracts. Molecules. 2009;14(6):
2167–2180.
[43] Konaté K, Bassolé I, Hilou A, et al. Toxicity assessment
and analgesic activity investigation of aqueous acetone
extracts of Sida acuta Burn f. and Sida cordifolia L. (Mal-
vaceae), medicinal plantsof Burkina Faso. BMC comple-
ment. Altern. Med. 2012;12:120, doi:10.1186/1472-6882-
12-120.
JOURNAL OF TAIBAH UNIVERSITY FOR SCIENCE 953
[44] Carvalho LH, Brandao MGL, Santos-Filho D, et al. Anti-
malarial activity of crude extracts from Brazilian plants.
Studied in vivo in Plasmodium berghei-infected mice and
in vitro against Plasmodium falciparum in culture. Braz J
Med Biol Res. 1991;24:1113–1123.
[45] Noedl H, Wongsrichanalai C, Wernsdorfer WH. Malaria
drug sensitivity testing: new assays, new perspectives.
Trends in Parasitol. 2003;19:175–181.
[46] Adebayo JO, Yakubu MT, Egwim EC, et al. Effect of
ethanolic extract of Khaya senegalensis stem bark on
some biochemical parameters on rat kidney. J Ethno-
pharmacol. 2003;88:69–72.
[47] Builders M, Alemika T, Aguiyi J. Antimalarial activity and
isolation of phenolic compound from Parkia biglobosa.
J Pharm Biol Sci. 2014;9(3):78–85.
[48] Awoke N, Arota A. Profiles of hematological parameters
in Plasmodium falciparum and Plasmodium vivax malaria
patients attending Tercha General Hospital, Dawuro
Zone, South Ethiopia. Infect Drug Resist. 2019;12:
521–527.
[49] Chinchilla M, Guerrero OM, Abarca G, et al. An in
vivo model to study the anti-malariac capacity of plant
extracts. Rev Biol Trop. 1998;46(1):1–7.
[50] Berinyuy EB, Lawal B, Olalekan AA, et al. Hematologi-
cal status and organs/body-weight parameters in Wister
rats during chronic administration of Cassia occidentalis.
Inter Blood Res Rev. 2015;4(3):1–7.
[51] Ozkan C, Kaya A, Akgul Y. Normal values of haema-
tological and some biochemical parameters in serum
and urine of New Zealand white rabbits. World Rab Sci.
2012;20:253–259.
[52] Lawal B, Shittu OK, Rotimi AA, et al. Effect of methanol
extract of Telfairia occcidentalis on haematological
parameters in Wister rats. J Med Sci. 2015;15(5):246–250.
[53] Mishra N, Tandon VL. Haematological effects of aqueous
extract of ornamental plants in male Swiss albino mice.
Vet World. 2012;5:19–23.
[54] Umar SI, Ndako M, Jigam AA, et al. Anti-plasmodial,
Anti-inflammatory, antinociceptive and safety profile of
Maytenus senegalensis root bark extract on hepato-renal
integrity in experimental animals. Comp Clin Pathol.
2019;28(8):1–8.
[55] Shittu OK, Lawal B, Blessing Uchenna AB, et al. Alter-
ation in biochemical indices following chronic admin-
istration of methanolic extract of Nigeria bee propo-
lis in Wister rats. Asian Pac J Trop Dis. 2015;5(8):654–
657.
[56] Yusuf AA, Lawal B, Abubakar AN, et al. In-vitro antiox-
idants, antimicrobial and toxicological evaluation of
Nigerian Zingiber officinale. Clin Phytosci. 2018;4(12):
1–8.
[57] Akanji MA, Salau AK, Yakubu MT. Safety evaluation of
aqueous extract of Cratevaadansonii leaves on selected
tissues of rats. Fount Nat Appl Sci. 2013;2(1):
17–28.
[58] Bashir L, Shittu OK, Busari MB, et al. Safety evaluation
of giant African land snails (Archachatina marginata)
Haemolymph on hematological and biochemical param-
eters of albino rats. J Adv Med Pharm Sci. 2015;3(3):
122–130.
[59] Ogunlana OO, Ogunlana OE, Ntube CA, et al. Phytochem-
ical screening and in vivo antioxidant activity of ethano-
lic extract of Caesalpinia bonduc (L.) Roxb. Global Res J
Pharm. 2012;1(1):1–4.
[60] da Silva G, Tanica M, Rocha J. In vivo anti-inflammatory
effect and toxicological screening of Maytenus hetero-
phylla and Maytenus senegalensis extracts. Human and
Exp Toxicol. 2010;30(7):693–700.
... That represent A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, and p that represents control liver, treated liver, control heart, treated heart, control kidney, treated kidney, control spleen, treated spleen, control lung, treated lung, control stomach, treated stomach, control testes, treated testes and control ovary, treated ovary respectively. [11,12,13]. The difference in the lethal dose 50 may be due to different solvent, extraction method and rout of administration. ...
... The body weight is acceptable if did not exceed ± 20% depending on organization for economic cooperation and development guideline 423 . [14,13] So, there is no significant change between control and treated one. P> 0.05. ...
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Rosa canina belongs to rosacea family. Rosa. canina has a high concentration of phyto-constituents such as flavonoids, carotenoids, triterpene and vitamins as vitamin C, E, and A Rosa canina have an anti-inflammatory and antioxidant effects. The antioxidant effect belongs to presence of large quantities of phytochemicals such as flavonoids and polyphenols. Rosa canina has been used for arthritis gout, osteoarthritis, urinary tract disorder, diabetes, inflammation and cancer. After grinding the leaves of Rosa canina, they are extracted by using ethanol solvent (cold extraction method), then the extract concentrated by rotary evaporator at 40 c° and leaving it to dry. Median lethal dose (LD50) has been examined on 84 mice (male and female) divided into seven groups, each one contains 12 (6 male and 6 female). The animals were monitored for signs and any behavior changes after administration of Rosa canina ethanol extract. Acute toxicity study was done on 20 rats (male and female for fourteen days. The weight of animals was taken at day 0, 7, and 14. At day fourteen, relative organ weight as well as histopathological examination for (heart, liver, spleen, kidney, lung, abdominal stomach, testes and ovaries) were taken. In addition to the serum biochemical tests for) blood glucose, urea, creatinine, ALT, AST and total bilirubin (were done at day fourteen. The result of this study, indicated that lethal dose 50 was 16.527 gram/kilogram. Acute toxicity study, revealed that there is no significant difference between relative organ weight of controlled and treated groups for all organs that were selected and mentioned above. In addition, there is no significant difference between serum biochemical tests for both controlled and treated groups. Finally, no changes have been found between controlled and treated groups regarding histopathology examination due to the p value was P ˃ 0.05. Conclusion According to the presented study, ethanol extract of Rosa canina showed wide range of safety depending on the result of lethal dose 50h (16.527 g/kg). Therefore, the extract considered nontoxic. No cytotoxic effect appeared by using ethanol extract of Rosa canina in acute toxicity study. This belongs to the results obtained, which include no significant difference between control and treated male and female rats in biochemistry tests and histopathological examination.
... Filtrates from the extraction chambers were dried (rotary evaporator at 45°C), obtaining crude ethanol leaf extract of S. acuta (EESAL) (13.32%). Ethanol was used as a solvent in this study based on the traditional practice where the leaves are soaked in ethanol for 2-3 days and the decoction orally taken for 4-7 days to treat malaria [16,26,27]. In addition, results of pilot study conducted using different solvent extracts showed that ethanol extract has significantly higher activity compared to n-hexane, ethyl acetate, water and chloroform extracts (data not shown). ...
... Interestingly, some Sida secondary metabolites including stigmasterol and its derivative, stigmasterol-3-O-β-D-glucopyranoside, have been shown to exhibit antimalarial properties [53,78]. Similarly, the presence of high levels of flavonoids, alkaloids, terpenoids and tannins which have been known to have antimalarial and chemoprotective activities could be responsible for the findings of the present study [27,79,80]. This study has some limitations such as the inability to track the specific compounds responsible for the antimalarial activities of EESAL and characterize them and inability to evaluate the specific mechanism of killing the parasites by EESAL. ...
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Background: Malaria has continued to be a threat to man and his wellbeing, especially Africans and Asians. New antimalarial drugs are urgently needed to mitigate malaria treatment failure due to resistant Plasmodium species. Medicinal plants used by indigenous Nigerians for treating fever and malaria such as Sida acuta Burm.f. (Malvaceae) could be a promising source of lead compounds for developing new generations of antimalarial drugs. The effects of ethanol extract of S. acuta leaves (EESAL) on malaria parasitemia, haematological and biochemical status of P. berghei-infected mice were investigated, using the 4-day curative test.
... Conventional drugs that are used to treat and manage diabetes are costly, not readily available, and not completely effective [22]. Therefore, due to the ease of accessibility and high therapeutic values in the clinics with little or no side effects [23,24], medicinal plants have been in use since time immemorial for preventing, treating, and managing different types of human diseases including parasites, infections, inflammation, oxidative stress, diabetes, and associated complications [25][26][27][28][29][30]. ...
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Tridax procumbens (cotton buttons) is a flowering plant with a medicinal reputation for treating infections, wounds, diabetes, and liver and kidney diseases. The present research was conducted to evaluate the possible protective effects of the T. procumbens methanolic extract (TPME) on an experimentally induced type 2 diabetes rat model. Wistar rats with streptozotocin (STZ)-induced diabetes were randomly allocated into five groups of five animals each, viz., a normal glycemic group (I), diabetic rats receiving distilled water group (II), diabetic rats with 150 (III) and 300 mg/kg of TPME (IV) groups, and diabetic rats with 100 mg/kg metformin group (V). All treatments were administered for 21 consecutive days through oral gavage. Results: Administration of the T. procumbens extract to diabetic rats significantly restored alterations in levels of fasting blood glucose (FBG), body weight loss, serum and pancreatic insulin levels, and pancreatic histology. Furthermore, T. procumbens significantly attenuated the dyslipidemia (increased cholesterol, low-density lipoprotein-cholesterol (LDL-C), triglycerides, and high-density lipoprotein (HDL) in diabetic rats), serum biochemical alterations (alanine transaminase (ALT), aspartate transaminase (AST), alanine phosphatase (ALP), blood urea nitrogen (BUN), creatinine, uric acid, and urea) and full blood count distortion in rats with STZ-induced diabetes. The TPME also improved the antioxidant status as evidenced by increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and decreased malondialdehyde (MDA); and decreased levels of cholinesterases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)), and proinflammatory mediators including nuclear factor (NF)-κB, cyclooxygenase (COX)− 2, and nitrogen oxide (NOx) in the brain of rats with STZ-induced diabetes compared to rats with STZ-induced diabetes that received distilled water. However, TPME treatment failed to attenuate the elevated monoamine oxidases and decreased dopamine levels in the brain of rats with STZ-induced diabetes. Extract characterization by liquid chromatography mass spectrometry (LC-MS) identified isorhamnetin (retention time (RT)= 3.69 min, 8.8%), bixin (RT: 25.06 min, 4.72%), and lupeol (RT: 25.25 min, 2.88%) as the three most abundant bioactive compounds that could be responsible for the bioactivity of the plant. In conclusion, the TPME can be considered a promising alternative therapeutic option for managing diabetic complications owing to its antidiabetic, antihyperlipidemic, antioxidant, and anti-inflammatory effects in rats with STZ-prompted diabetes.
... Natural products are an important source of novel drugs for the treatment of many diseases [11][12][13][14][15]. Plants that are known to have medicinal value have potential applications in biomedical [16][17][18]. Nowadays, most pharmaceutical drugs originated from traditional alternative medicine [19]. The Food and Drug Administration (FDA) approved more than one-third (39.1%) of drugs that are of natural origin [20]. ...
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Inflammatory diseases are normally treated with non-steroidal anti-inflammatory drugs which may cause adverse effects if used for prolonged periods. Thus, there is a need to search for alternative anti-inflammatory medicine. This study investigated the phytochemical characteristics, cytotoxic, and anti-inflammatory activities of C. iria Linn. roots ethanol extract. The extract was subjected to preliminary phytochemical screening using standard procedures. The anti-inflammatory activities were determined using the egg albumin denaturation assay and the human red blood cell membrane stabilization method while the cytotoxic activity was investigated using the brine shrimp lethality assay. Preliminary phytochemical screening revealed the presence of flavonoids, phenolic acids, terpenoids, and saponins in the extract. Anti-inflammatory assays revealed that the extract has comparable results with the positive control (250 µg/ml Celecoxib) while being non-toxic. These results suggest that the synergetic actions of identified phytochemicals may contribute to the anti-inflammatory effect on egg albumin and human red blood cells.
... Blood was allowed to coagulate and then was centrifuged at 3000 ×g for 15 min to separate the serum [43,44]. Serum was aspirated and kept frozen at − 20 • C [45]. The liver, kidneys, and pancreas were gently excised, rinsed in ice-cold KCl, and blotted with filter paper. ...
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The current study evaluated the protective role of Solanum torvum Swartz against diabetes-induced oxidative stress and tissue impairment in streptozotocin (STZ)-intoxicated rats. Rats with STZ (40 mg/kg intraperitoneally (i.p.))-induced diabetes were divided into five groups (n = 5) and treated with (i) normal saline, (ii) 150 mg/kg body weight (BW) of the ethanol extract of S. torvum leaf (EESTL), (ii) 300 mg/kg BW EESTL, (iv) 100 mg/kg BW metformin, and (v) 50 m/kg BW metformin + 100 mg/kg BW EESTL orally for 21 days. Our results revealed that the EESTL displayed dose-dependent ferric-reducing antioxidant power (FRAP) activity, scavenged DPPH radicals (IC50) = 13.52 ± 0.45 µg/mL), and inhibited lipid peroxidation in an in vitro models. In addition, the EESTL demonstrated dose-dependent inhibitory activity against α-amylase (IC50 =138.46 ± 3.97 µg/mL) and promoted glucose uptake across plasma membranes of yeast cells in a manner comparable to that of metformin. Interestingly, the extract demonstrated in vivo blood glucose normalization effects with concomitant increased activities of antioxidant parameters (superoxide dismutase (SOD), catalase, and reduced glutathione (GSH)) while decreasing malondialdehyde (MDA) levels when compared to untreated rats. Similarly, serum biochemical alterations, and tissues (liver, kidney, and pancreases) histopathological aberrations in untreated rats with STZ-induced diabetes were attenuated by treatment with the EESTL. Biometabolite characterization of the extract identified gallic acid (45.81 ppm), catechin (1.18 ppm), p-coumaric acid (1.43e⁻¹ ppm), DL-proline 5-oxo-methyl ester (9.16 %, retention time (RT): 8.57 min), salicylic acid (3.26% and 7.61 min), and butylated hydroxytoluene (4.75%, RT: 10.18 min) as the major polyphenolic compounds in the plant extract. In conclusion, our study provides preclinical evidence of the antioxidant properties and oxidative stress-preventing role of S. torvum in STZ-dosed diabetic rats. Taken together, the EESTL represents a reserve of bioactive metabolites for managing diabetes and associated complications.
... indicates that SC exposure in the plateau zokor elicits a certain degree of liver injury and metabolic response as part of the adaptation process (Adesina et al., 2020). In addition to AST and ALT, the effect of SC on oxidative stress in plateau zokors was also tested. ...
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Herbivores rarely consume toxic plants. An increase in the proportion of toxic plant secondary metabolites (PSMs) in poisonous plants can promote detoxification and related metabolic capacity of animals. Poisonous plants with thick taproots like Stellera chamaejasme (SC) are important stored food for the plateau zokor (Eospalax baileyi) during the winter and promote the development of detoxification mechanisms in this animal. In this study, plateau zokors were administered gavages of 0.2, 1.05, and 2.10 ml/kg SC water extracts. Serum samples were collected from plateau zokors to measure the levels of transaminases and oxidative stress. Transcriptome analysis was conducted to evaluate the differential genes of multiple metabolic pathways to investigate the relationship between the physiological processes and metabolic adaptation capacity of these animals in response to SC. After SC administration, plateau zokors showed significant hepatic granular degeneration and inflammatory reactions in the liver and aspartate aminotransferase, alanine aminotransferase, and malondialdehyde levels increased in a dose-dependent manner. Further, differential expression was also found in the plateau zokor livers, with most enrichment in inflammation and detoxification metabolism pathways. The metabolic adaptation responses in P450 xenobiotic clearance, bile secretion, and pancreatic secretion (Gusb, Hmgcr, Gstm1, Gstp1, and Eobag004630005095) were verified by mRNA network analysis as key factors related to the mechanism. Plateau zokors respond to SC PSMs through changes in liver physiology, biochemistry, and genes in multiple metabolic pathways, validating our hypothesis that plateau zokors can metabolize PSMs when they ingest toxic plants.
... The effect of VCO on reducing parasitemia was due to the phenol compounds as anti-oxidants that have anti-plasmodium activity which are able to inhibit the growth of parasite. Some phenolic compounds have been tested against P. berghei in mice [15] as well as P. falciparum in vitro [16] [17]. ...
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Malaria remains a health problem in various parts of the world. A decrease in antioxidant levels during malaria infection cause oxidative stress, therefore exogenous antioxidant is needed. Virgin Coconut Oil (VCO) can be a source of exogenous antioxidants due to the antioxidant activity of VCO, which was contributed majority by phenolic acids content. Antioxidants play a role in countering the effects of free radicals by inhibiting fat peroxidation that cause erythrocyte cell wall stronger and not easily ruptured. Pharmacological properties of VCO including anti-inflammatory, anti-oxidant, antiviral, and antiprotozoal properties have been reported. Therefore, this study aimed to find out the antimalarial activity of VCO by evaluating the parasitemia and percentage of inhibition to the growth of parasite. Thirty male BALB/c mice were infected intraperitonially with 1×106 Plasmodium berghei ANKA-infected erythrocytes. The mice were than randomly divided into five groups: positive control (PC) group was given 187.2m g/kg BW of dihydroartemisinin phosphate, negative control (NC) group was only given sterile water; G1, G2, and G3 groups were given 1 ml, 5 ml, and 10 ml/kg BW of VCO, respectively. VCO treatments were given for 4 consecutive days started from 24 hours post infection. Parasitemia was determined daily on Giemsa-stained tail blood smear, further the percentage inhibition was calculated. The results showed that parasitemia in VCO-treated mice were lower than that of NC group, but higher than that of PC group, indicated the antimalarial activity of VCO. The inhibition of VCO to the growth of parasite showed that G2 was higher (48.70%) than that of G1 (13.04%) and G3 (33.9%). The use of antioxidant therapy as a supportive therapy is one of alternatives in supporting the healing process of malaria patients and may reduce various risks that could potentially occur in patients.
... The blood samples were allowed to clot for 30 min and thereafter centrifuged at 4000 rpm for 5 minutes at 25°C [39]. The resulting sera were aspirated and kept frozen at -20°C till used for biochemical analysis [40]. Furthermore, the mice were quickly dissected, and the liver was isolated and weighed. ...
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... In drug discovery pipelines, natural products, particularly medicinal plants, serve as an important source of natural therapeutic agents for treating several diseases [25][26][27][28]. Garlic (Allium sativum L. of the Amaryllidaceae family) is an aromatic herbaceous annual spice with various biological activities [29][30][31][32][33]. ...
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The multi-domain non-structural protein 3 (NSP3) is an oncogenic molecule that has been concomitantly implicated in the progression of coronavirus infection. However, its oncological role in lung cancer and whether it plays a role in modulating the tumor immune microenvironment is not properly understood. In the present in silico study, we demonstrated that NSP3 (SH2D3C) is associated with advanced stage and poor prognoses of lung cancer cohorts. Genetic alterations of NSP3 (SH2D3C) co-occurred inversely with Epidermal Growth Factor Receptor (EGFR) alterations and elicited its pathological role via modulation of various components of the immune and inflammatory pathways in lung cancer. Our correlation analysis suggested that NSP3 (SH2D3C) promotes tumor immune evasion via dysfunctional T-cell phenotypes and T-cell exclusion mechanisms in lung cancer patients. NSP3 (SH2D3C) demonstrated a high predictive value and association with therapy resistance in lung cancer, hence serving as an attractive target for therapy exploration. We evaluated the in silico drug-likeness and NSP3 (SH2D3C) target efficacy of six organosulfur small molecules from Allium sativum using a molecular docking study. We found that the six organosulfur compounds demonstrated selective cytotoxic potential against cancer cell lines and good predictions for ADMET properties, drug-likeness, and safety profile. E-ajoene, alliin, diallyl sulfide, 2-vinyl-4H-1,3-dithiin, allicin, and S-allyl-cysteine docked well into the NSP3 (SH2D3C)-binding cavity with binding affinities ranging from –4.3~–6.70 Ă and random forest (RF) scores ranging from 4.31~5.26 pKd. However, S-allyl-cysteine interaction with NSP3 (SH2D3C) is unfavorable and hence less susceptible to NSP3 ligandability. In conclusion, our study revealed that NSP3 is an important onco-immunological biomarker encompassing the tumor microenvironment, disease staging and prognosis in lung cancer and could serve as an attractive target for cancer therapy. The organosulfur compounds from A. sativum have molecular properties to efficiently interact with the binding site of NSP3 and are currently under vigorous preclinical study in our laboratory.
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Malaria is a global problem, as treatment failure has hampered the efficacy of most anti-malarial medications. The goal of this study was to see if stem bark extract from Zanthoxylum zanthoxyloides had antiplasmodial properties that could be used to treat both susceptible and resistant parasites. The stem bark of Z. zanthoxyloides (500g) was crushed and extracted with ethanol. The extract was tested for antiplasmodial activity in vitro against the chloroquine-sensitive (CQS) strain NF54 and chloroquine-resistant strains (CQR) K1 of P. falciparum, as well as in vivo against the CQS(NK65) strain of P. berghei at 100, 200, and 400 mg/kg bw. Bioassay-guided fractionation of the extract was performed. The crude extract had an in vitro activity of 1076.4 56.4 and 1315.1 121.6 ng/ml against chloroquine sensitive and resistant parasites, respectively while standard drugs (chloroquine and artesunate) were 10.94 nM (3478.92 ng/ml) and 9.24 nM (3215.52ng/ml) for CQS and 310.68 nM (98796 ng/ml) and 10.94 nM (3650.52 ng/ml) for CQR respectively. At Day 7, mice treated with 100, 200, and 400 mg/kg bw crude extract had parasite densities of 1159, 928, and 869 parasites/ µl, respectively (compared to positive control that had 123 parasites /µl). In vitro antiplasmodial activity was best in the K2, K4, and K6 fractions (IC50 were 6670, 6890, and 6480 ng/ml), but in vivo antiplasmodial activity was best in the K4 fraction (1183 parasites/ µl).The stem bark extract of Z. zanthoxyloides have remarkable antiplasmodial activity against both chloroquine sensitive and drug resistant P. falciparum supporting it ethnomedicinal use in malaria treatment.The extract of Z. zanthoxyloides has promising antiplasmodial activity and could be used to generate therapeutic leads against the multidrug-resistant K1 strain of P. falciparum, in addition to providing an alternative allopathic antiplasmodial medication.
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Background: Xylopia aethiopica is highly reputed for its numerous medicinal properties. In the present study, antioxidant, antimicrobial, and toxicity profile of methanol seed extract of Nigerian X. aethiopica in rat were evaluated. Methods: Phytochemical compositions were evaluated using standard procedures. The antibacterial study was carried out using agar well diffusion method, while antioxidant activities were evaluated by DPPH and FRAP assay. Twenty-five rats (5 each) were given 0, 75, 150, 300 and 600 mg/kg bwt of the extract orally for 28 days. Results: The extract had total phenolic and total flavonoid contents of 15.98±0.03mg GAE/g and 2.29±0.02 mg/g CE respectively. The extract had IC50 values of 52.45±3.05 µg/mL and 73.45±3.89 μg/mL in DPPH and FRAP assay respectively. The E. coli showed the highest susceptibility (20.27±0.90mm) while P. aeuruginisa showed the least (15.08±0.20mm). The MIC ranged from 25-50 µg/mL while MBC ranged between 50µg/mL and 100 µg/mL. In comparison with the control rats, the levels of serum creatinine, bicarbonate total proteins, albumin, and ALP were significantly higher in rat dosed 600 mg/kg bwt while urea decreases in rat dose 300 and 600 mg/kg. However, serum concentration of ALT, AST, bilirubin, Na+, K+ and Cl- compared favorably (P>0.05) with control at all doses. Conclusion: The study revealed the antioxidant and antimicrobial activities of Nigerian X. aethiopica, the extract at 75, 150 and 300 mg/kg/b.wt did not provoke toxic effects to the animals’ liver and kidney; however, caution should be exercised when using as a prolonged oral remedy at high doses.
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Background: Maytenus heterophylla (M. heterophylla) is commonly used in African traditional medicine for the management of various ailments. The present study evaluated the antioxidant, antimicrobial and safety properties of the Flavonoid extract of M. heterophylla in Wister rats. Methods: The Flavonoid was subjected to antibacterial study via agar well diffusion method, and antioxidant study using 2, 2′-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant properties (FRAP) assays. Subacute toxicity were carried out by the oral administration of the extract at a daily dose of 50 or 100mg/kg for 28 days. Results: The extract produced significant antioxidants activities with IC50 of 33.07±0.84 μg/mL & 38.08±0.89 μg/mL in DPPH and FRAPS models respectively. It produced a dose-dependent inhibition of S. aureus, E.coli, P. aeruginosa, K. pneumonia and S. Typhi with MIC between 12.5μg/mL to 25μg/mL. The flavonoid was safe on acute exposure to rats (LD50> 5000 mg/kg). However, the chronic exposure significantly (p<0.05) decreased the creatinine, bilirubin concentrations and increased aspartate transaminase (AST) activities while the total protein, albumin, alanine transaminase (ALT), alkaline phosphatise (ALP), urea, chloride, potassium and sodium concentrations were comparable with those in the controls. The organs-body weights ratios also compared well with the controls (p<0.05). Conclusions: The findings showed that the Flavonoid extract of M. heterophylla was relatively non-toxic following acute or chronic exposures at 50-100 mg/kg. The flavonoid extract may potentially serve as a candidate agent for the development of an anti-microbial drug and to enhance the antioxidant capacity in rats. Keywords: Antibacterial; Anti-Oxidants; Flavonoids; Maytenus Heterophylla; Toxicity
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Plant species of the genus Tinospora (Menispermaceae) possess several pharmacological properties, and T. crispa has been reported to have antimalarial activity. T. baenzigeri (Chingcha Chalee) is a rich source of terpenes and quinoline alkaloids; however, it still has not yet been investigated the antimalarial activity of this plant extract. Hence, this study was aimed to evaluate the antimalarial activity of T. baenzigeri stem extract against Plasmodium berghei- infected mice. The aqueous crude extract of T. baenzigeri stem was prepared using a microwave-assisted method and tested for acute toxicity in mice. For evaluating the antimalarial activity in vivo , the standard 4-day test was carried out using groups of ICR mice infected with P. berghei ANKA administered orally by gavage with the extract (100, 250, and 500 mg/kg) for 4 consecutive days. Parasitemia, body weight, packed cell volume, and mean survival time were then measured. It was found that the aqueous crude extract of T. baenzigeri stem did not exhibit any sign of toxicity up to the dose of 2,000 mg/kg. The extract significantly ( P<0.01 ) inhibited parasitemia in a dose-dependent manner, with 22.02%, 50.81%, and 74.95% inhibition. Moreover, the marked prevention of body weight loss and packed cell volume reduction was observed at doses of 100, 250, and 500 mg/kg of extract-treated mice. Additionally, the extract prolonged the mean survival time of P. berghei- infected mice, compared to the untreated group. In conclusion, the aqueous crude extract of T. baenzigeri stem has demonstrated potent antimalarial activity against P. berghei- infected mice with prolonged mean survival time and prevention of body weight loss and packed cell volume reduction.
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Maytenus senegalensis is a plant with several medicinal claims in folk medicine. Methanol root extract of the plant was evaluated for antiplasmodial, anti-inflammatory, anti-nociceptive, and safety profile. Antiplasmodial, anti-inflammatory (egg albumin induced paw edema), and analgesic (hot plate test) experiments were set up, each consisting of four (4) groups (A-D) of five mice each. Groups A–C of each experiment were treated with 2.0 ml/kg bw normal saline, 400 and 800 mg/kg bw of the extract according to the procedures. Chloroquine, acetyl salicylic, and aspirin respectively were used as the reference drugs. Hematological and biochemical parameters were evaluated after 4-week administration of the extract to four groups of five rats each at oral daily doses of 0, 200, 400, and 800 mg/kg bw, respectively. At 400 and 800 mg/kg bw, the extract caused 58.88% and 58.49% inhibition of parasitemia, and 51.92% and 54.66% inhibition of paw edema, respectively. The reaction time to the thermal stimuli increased (p < 0.05) with increased extract concentrations. All the doses of the extract significantly (p < 0.05) increased the concentration urea, creatinine, alkaline phosphatase (ALP), and white blood cell (WBC) count, while aspartate transaminases (AST), alanine transaminase (ALT), sodium, potassium, chloride, packed cell volume (PCV), red blood cell (RBC), and hemoglobin (HGB) compared well (p > 0.05) with their reference values. The extract alters some functional integrity of kidney, and thus caution should be exercised when using the extract for the above pharmacological activities or other oral remedy.
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The purpose of the present study was to define the normal haematologic values and some biochemical parameters in serum and in urine in both male and female New Zealand white rabbits and to determine the effect of gender on these parameters. Blood and urine samples from a total of 40 New Zealand white rabbits were investigated. The haematologic parameters were determined in whole blood samples, while serum and urine (urine protein, glucose, creatinine, urea, GGT, nitrite, Na, K, Cl, creatinine clearance) biochemical parameters were determined in serum and urine samples. Normal values of these parameters were determined and statistical comparisons between male and female animals performed. No statistically significant differences were found between male and female animals for the parameters analysed except HCT, HGB, granulocyte %, L/M and serum K concentration. As a result, it was judged that defining the normal values of given haematological factors and serum and urine biochemical parameters in this study in New Zealand white rabbits would be helpful for both clinicians and researchers.
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Background Malaria is a major health problem in the tropics, with 300–500 million cases and 1.1–2.7 million deaths occurring annually. The hematological alterations associated with malaria infection may vary depending on: level of malaria endemicity, background hemoglobinopathy, malaria immunity, host genetic factors, and parasite strain variations. Objective The aim of the study was to determine the profiles of hematologic parameters in Plasmodium falciparum and Plasmodium vivax malaria infections at Tercha General Hospital, Dawuro Zone, South Ethiopia. Methodology A total of 340 study participants were included in the study, out of which 170 were malaria cases, and the remaining 170 were malaria negatives. An institution-based cross-sectional study was conducted. Malaria diagnosis was based on thick and thin blood films microscopy. Hematological parameters were determined by using an automated, CELL-DYN 1800 hematology analyzer. Malaria parasite density was determined by counting the asexual parasites against 200 WBCs, and then calculated by using the standard formula. The diagnostic accuracy of hematological parameters was measured by computing sensitivity, specificity, and likelihood ratios. Results The mean values of Hgb, Hct, platelet, WBC, RBC, and lymphocyte were significantly lower in malaria patients than malaria negatives. The prevalence of thrombocytopenia and anemia in malaria patients was 84% and 67%, respectively. There was an inverse correlation between P. falciparum and P. vivax parasite density and lymphocyte count, as well as platelet count. Conclusion and recommendation Thrombocytopenia and anemia were the two common hematological abnormalities observed in malaria cases. The platelet count during malaria infection was inversely correlated with the asexual stage parasite density. Patients with acute febrile illness having thrombocytopenia should alert the treating physician about the possibility of malaria infection. Malaria patients should be checked for the presence of hematological abnormalities such as anemia and have to be managed for those abnormalities.
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Background The search for new antimalarial drugs has become progressively urgent due to plasmodial resistance to most of the commercially available antimalarial drugs. As part of this effort, the study evaluated the antimalarial activity of Cucumis metuliferus and Lippia kituiensis, which are traditionally used in Tanzania for the treatment of malaria. Materials and methods In vivo antimalarial activity was assessed using the 4-day suppressive antimalarial assay. Mice were infected by injecting via tail vein 1×10⁷ erythrocytes infected by Plasmodium berghei ANKA. Extracts were administered orally; chloroquine (10 mg/kg/day) and dimethyl sulfoxide (5 mL/kg/day) were used as positive and negative controls, respectively. The level of parasitemia, survival time, packed cell volume (PCV) and variation in body weight of mice were used to determine the antimalarial activity of the extract. Results The ethyl acetate, methanolic and chloroform extracts of C. metuliferus and L. kituiensis significantly (p<0.05) inhibited parasitemia in a dose-dependent manner and prevented loss of body weight at the dose levels of 600 mg/kg and 1500 mg/kg, respectively. In addition, the extracts prolonged the mean survival time of P. berghei-infected mice compared to the non-treated control. The plant extracts did not show reduction of PCV except at the low dose of 300 mg/kg. The highest suppression was recorded at the dose level of 1,500 mg/kg. At this dose, C. metuliferus in chloroform, methanolic and ethyl acetate extracts had percentage suppression of 98.55%, 88.89% and 84.39%, respectively, whereas L. kituiensis in ethyl acetate, chloroform and methanolic extracts exhibited suppression of the pathogens of 95.19%, 93.88% and 74.83%, respectively. Conclusion It is worth reporting that the two plants induced suppression which is equivalent to that induced by chloroquine (C. metuliferus chloroform and L. Kituiensis ethyl acetate). The two plants have been demonstrated to be potential sources of antimalarial templates.
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The study aims to determine the association of malaria infection with ABO blood groups and genotype and also to detect point mutations at positions 86, 184, 1034, and 1042 of the Plasmodium falciparum multidrug resistance gene (pfmdr1) in blood samples collected from pregnant women attending General Hospital Minna. Out of 250 pregnant women screened, 39 (15.60%) had malaria infection. Prevalence was higher in women, during the third trimester (46.15%), genotype AA (64.10%), and O blood group (53.84%) individuals when compared with others. There was significant ( p<0.05 ) decrease in Packed Cell Volume (PCV), hemoglobin (HGB), Red Blood Cells (RBC), and platelet (PLC) count in infected group when compared with noninfected group. Although, two of the isolates showed disrupted protein sequence at codon 1034–1042, no mutation was found in any of the P. falciparum isolates. Structural prediction of chemical ligand led to the identification of Neu5Ac α 2-3Gal β 1-3/ β 1-4Glc/GlcNAc. This compound can theoretically bind and change the functional integrity of the pfmdr1 protein, thus providing a new window for malaria drug target.
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Malaria, as a major global health problem, continues to affect a large number of people each year, especially those in developing countries. Effective drug discovery is still one of the main efforts to control malaria. As natural products are still considered as a key source for discovery and development of therapeutic agents, we have evaluated more than 2000 plant extracts against Plasmodium falciparum. As a result, we discovered dozens of plant leads that displayed antimalarial activity. Our phytochemical study of some of these plant extracts led to the identification of several potent antimalarial compounds. The prior comprehensive review article entitled “Antimalarial activity of plant metabolites” by Schwikkard and Van Heerden (2002) reported structures of plant-derived compounds with antiplasmodial activity and covered literature up to the year 2000. As a continuation of this effort, the present review covers the antimalarial compounds isolated from plants, including marine plants, reported in the literature from 2001 to the end of 2017. During the span of the last 17 years, 175 antiplasmodial compounds were discovered from plants. These active compounds are organized in our review article according to their plant families. In addition, we also include ethnobotanical information of the antimalarial plants discussed.
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Malaria is the most lethal and debilitating disease caused by the protozoan parasite Plasmodium worldwide. The most severe forms of disease and the incidence rates of mortality are associated with P. falciparum infections. With the identification of disease source and symptoms, many chemical entities were developed naturally and synthetically for administration as a potential anti‐malarial drug. The major classes of approved anti‐malarial drugs that are governed as first‐line treatment in tropical and sub‐tropical areas include quinolines, naphthoquinones, antifolates, 8‐aminoquinolines, and endoperoxides. However, the efficacy of anti‐malarial drugs has decreased due to ongoing multidrug resistance problem to current drugs. With increasing resistance to the current anti‐malarial artemisinin and its combination therapies, malaria prophylaxis has declined gradually. New generation anti‐malarial and novel drug target are required to check the incidence of malaria resistance. This review summarizes the emergence of multidrug resistance to known anti‐malarial and development of new anti‐malarial to resolve drug resistance condition. Few essential proteins are also discussed that can be considered as novel drug target against malaria in future. This article is protected by copyright. All rights reserved.