DOI: https://dx.doi.org/10.4314/jaaps.v11i2.

2
Antidiabetic and thrombolytic activities of medicinal plants

J. Afr. Ass. Physiol. Sci. 11(2): 12-24, December 2023

Journal of African Association of Physiological Sciences
Official Publication of the African Association of Physiological Sciences
https://www.ajol.info/index.php/jaaps
Antidiabetic and Thrombolytic Activities of Some Selected Medicinal Plants in
High Fat Diet and Dexamethasone-Induced Type 2 Diabetic Rats
Kasimu Ghandi Ibrahim 1,2,3,4*, Sagir Kaka Shinkafi5, Aminu Ishaka6,7 and Suleiman Ahmed Isa5
1
Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, P.O.BOX 2000, Zarqa
13110, Jordan
2
School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193,
Johannesburg, South Africa.
3
Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo
University, Sokoto P.M.B 2346, Nigeria
4
Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto 2254, Nigeria
5
Department of Biochemistry & Molecular Biology, Faculty of Chemical & Life Sciences, Usmanu Danfodiyo
University, Sokoto P.M.B 2346, Nigeria
6
Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu
Danfodiyo University, Sokoto P.M.B 2346, Nigeria
7
Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Health Sciences, Nile University
of Nigeria, Abuja lot 681, Cadastral Zone C-OO, Research & Institution Area, Jabi Airport Bypass, Abuja FCT,
900001 Nigeria.
Keywords: ABSTRACT

Clot lysis; Streptokinase; Background: Type-2 diabetes (T2D) is a hypercoagulable and hypofibrinolytic condition
Thrombolytic agents; Type that predisposes to cardiovascular and thrombotic complications. We screened three
medicinal plants (Albizzia chevalieri, Newbouldia laevis and Leptadenia hastate) for their
2 Diabetes mellitus
antidiabetic and thrombolytic activities.
Methods: T2D was induced with high fat diet and dexamethasone. Following induction,
rats were grouped into 6 (n=8 rats); control, untreated, treated (500mg/kg body weight
(BW) metformin only) or treated (300mg/kg BW leaf extracts). The rats were treated for
two weeks and euthanized. About 2ml of the collected blood was used for thrombolytic
* Address for Correspondence: activity assay while the rest was processed, and the recovered serum utilised for
biochemical and hormonal assays.
Email: kibrahim@zu.edu.jo Results: Rats treated with extracts had significantly (p<0.05) lowered concentrations of
serum glucose, TG, LDL-cholesterol, VLDL-cholesterol and increased HDL-cholesterol
compared to untreated rats. Extracts also lowered (p<0.05) the serum insulin concentration
on day 14 compared to untreated rats. Albizzia chevalieri, Newbouldia laevis and
Leptadenia hastata showed 48.90%, 39.20% and 37.69% clot lysis activities respectively
Received: 3 October 2023 which was significantly higher (p<0.001) than distilled water, while streptokinase
produced a substantial clot lysis of 93.70%.
Revised: 13 November 2023 Conclusions: The leaf extracts of Albizzia chevalieri, Newbouldia laevis and Leptadenia
hastata have antidiabetic and thrombolytic activities in type-2 diabetic rats and thus, can
Accepted: 3 December 2023
be potentially used as combined antidiabetic and thrombolytic agents with in vivo effects
in type-2 diabetic patients.
All articles published in this journal are licensed under the Creative Commons
Attribution 4.0 International (CC BY 4.0) license.

© Copyright 2023 African Association of Physiological Sciences -ISSN: 2315-9987. All

rights reserved

12
 DOI: https://dx.doi.org/10.4314/jaaps.v11i2.2
Antidiabetic and thrombolytic activities of medicinal plants

1. Introduction insulin. But the cost of this polypharmacy is

There is currently an epidemic of diabetes prohibitive and constitutes a heavy financial
mellitus across the globe (Sun et al., 2022). The burden especially in poor communities. Orthodox
statistics have multiplied several fold over the medications are also associated with side effects.
past few decades and are projected to increase These necessitate the search for agents, such as
further. Data from the International Diabetes natural products, with medicinal value and
Federation (IDF) showed a global prevalence of activity against T2DM and its complications.
10.5%, representing about 537 million adults Natural products are identified to be safe, more
with diabetes and an alarming projection that this affordable and widely available (Rahaman et al.,
figure would rise to about 643 million and 783 2023). The WHO advocates for the use of natural
million by 2030 and 2045 respectively (IDF, products in the management of ailments (Süntar,
2021). The figures from the World Health 2020). Several plants have been shown to have
Organization (WHO) also portray a gloomy antidiabetic properties, among them the trio of
picture. From 108 million people with diabetes in Leptadenia hastata, Newbouldia laevis and
1980 to about 422 million people in 2014, with Albizzia chevalieri which were previously
the increase in prevalence being more reported to have antidiabetic action in type 1
pronounced in the developing compared to the diabetic rodent models (Saidu et al., 2010; Bello
developed nations (World Health Organisation, et al., 2011; Kabir et al., 2021; Mbagwu et al.,
2016). 2021).
Diabetes mellitus (DM), a chronic endocrine Thus, we aimed to determine whether the
disease results from either a deficiency of, or a methanolic extracts of these plants would have an
lack of effective insulin action (Glovaci et al., antidiabetic and thrombolytic effect in a rat
2019). Because the body cells require insulin for model of high fat diet and dexamethasone
the uptake and utilization of glucose, its induced T2DM. This will help in the formulation
deficiency results in persistently elevated levels of a safe, affordable combined medication for
of glucose in the blood (Cole and Florez, 2020). T2DM and thrombolytic agent.
These high levels of blood glucose eventually
lead to adverse consequences on vital organs such 2. Materials and methods
as the eyes, kidneys, heart and brain (Tomic et al., 2.1. Ethical clearance
2022). Depending on its aetiology, DM is The protocols used in this study were approved
classified into either type 1 (Insulin-dependent) by the Central University Animal Research
or T2DM (Kononenko et al., 2020). T1DM Ethics Committee of Usmanu Danfodiyo
results from the auto-immune destruction of the β University Sokoto (UDUS), Nigeria
cells of the pancreas consequently leading to the (UDUS/AEC/2020/0321) and conducted in line
absence of insulin secretion (Syed, 2022), while with the National Institute of Health Guide for the
in T2DM insulin secretion may be normal but Care and Use of Laboratory Animals. The
there is a decreased sensitivity to its action. ARRIVE guidelines were also used in the
T2DM is more prevalent, accounting for more conduct and reporting of this study.
than 80% of diabetic patients (Ong et al., 2023).
It is closely associated with environmental factors 2.2. Plants collection
and obesity, sedentary lifestyle and diets rich in Samples were collected from plants grown on
carbohydrates and fats. farms in Sokoto metropolis, Sokoto state, North-
The sustained elevated levels of glucose, damage western Nigeria (13.0059oN, 5.2476oE), which
the vascular endothelium and alter several falls within the savannah zone with mean annual
proteins thereby predisposing to thrombotic rainfall ranging between 500mm to 1,300mm.
tendencies, making DM a hypercoagulable We authenticated samples at the herbarium of the
condition (Vaidya et al., 2021). Consequently, Botany unit, Biological Sciences Department,
DM patients are frequently treated with UDUS and deposited voucher specimens for each
thrombolytic agents (Siasos et al., 2020) in plant with voucher numbers as follows:
addition to the usual treatment with lifestyle Leptadenia hastata (UDUH/ANS/0847),
modification, oral hypoglycaemic agents and

13 J. Afr. Ass. Physiol. Sci. 11 (2):2023 Ibrahim et al.

 DOI: https://dx.doi.org/10.4314/jaaps.v11i2.2
Antidiabetic and thrombolytic activities of medicinal plants

Newbouldia laevis (UDUH/ANS/0845) and intraperitoneal injection of dexamethasone

Albizzia chevalieri (UDUH/ANS/0846). (1mg/kg BW) from day 15 to day 21 of the
experiment (Martínez et al., 2016; Danboyi et al.,
2.3. Extracts Preparation 2020). Thereafter, rats were returned to standard
The plants leaves were washed under a running feed for the remainder of the experiment. Blood
tap, air dried at 27oC for 7days and then ground was taken from rats’ tail veins via a pin prick
using laboratory pestle and mortar into fine using a 25G needle and fasting blood glucose
powder. Five hundred (500g) grams of each plant (FBG) levels of all the animals was determined
sample were separately macerated with 2.5L of using a calibrated portable glucometer (Accu-
methanol for 72h. The resulting homogenate was Chek®, Germany). FBG > 11.4 mmol/l was
filtered twice, first with a piece of muslin cloth indicator of diabetes. Following the successful
(white, clean and sterile) and then again with induction of T2DM, we randomly allocated the
Whatman grade 1 filter paper (Sigma Aldrich rats into six groups, each with at least eight rats.
Germany, Retention of 11µm at 98% efficiency). Group 1: Non-diabetic controls administered
The filtrates were concentrated using a rotary distilled water
evaporator device (RE 100, Stone Staffordshire, Group 2: Diabetic control, administered with a
England) set at 40oC after which a freeze drier high fat diet and dexamethasone only with no
(BK-FD 10 series, Jinan, Shandong, China) was treatment
used to obtain a constant dry weight of the Groups 3 to 6 were the diabetic groups treated as
extracts. The dried extracts were weighed, follows:
covered with aluminium foil, labelled, and stored Group 3: Metformin 500mg/kg body weight
in a fridge at 4oC for use in anti-diabetic test and Group 4: A. Chevalieri 300mg/kg body weight
clot lysis determination. The yield following (Saidu et al., 2010).
extraction was determined for each of the extracts Group 5: N. laevis 300mg/kg body weight
(Eneh et al., 2018). (Osigwe et al., 2017).
Group 6: L. Hastata 300mg/kg body weight
2.4. Experimental Animals (Bello et al., 2011).

Wistar rats (n=50) of both sexes that weighed The treatments were constituted in distilled water
between 170-180g and aged between 10-12 and administered once daily via oral gavage for 2
weeks were used for this study. The rats housed weeks. FBG was measured on days 0, 7 and 14.
in steel cages were acquired from the Department The weights of the rats were recorded twice
of Biological Sciences, UDUS, Nigeria. Prior to weekly to ensure their wellbeing and any impact
experimentation, rats were transferred and the treatments may have on their body weights.
allowed to habituate for seven days at the animal Following an overnight fast (12 hr), the rats were
house, Department of Biochemistry and euthanized using chloroform inhalation. Blood
Molecular Biology, UDUS. The rats were samples were collected through cardiac puncture
maintained at room temperature with 12 hr light using a 21G needle. About 2ml of the collected
cycle, adequate ventilation, fed normal rat chow blood sample was transferred into plain blood
with ad libitum access to clean drinking water. collecting tubes for clot lysis determination. The
According to the manufacturers label (Vital remaining blood samples were subsequently
feeds, Jos, Nigeria), diet composition provides 54 transferred into plain tubes and left to stand for
% carbohydrates, 13 % fat, 10 % proteins, 20 % approximately 30 minutes and then centrifuged at
fibre, 2 % normal supplement (calcium, 3000rpm for 15 minutes. Thereafter, serum was
phosphorus, ash & moisture) and 1% vitamin. harvested and transferred into labelled micro
tubes and stored in a freezer at -20˚C for
2.5. Study Design downstream biochemical analysis.
Like previously reported, T2DM was induced in
apparently healthy rats using high fat diet (58% 2.6. Determination of Blood Glucose
animal fat, 25% protein-soya beans and 17% Concentration
carbohydrates-maize) for 21 days and daily

14 J. Afr. Ass. Physiol. Sci. 11 (2):2023 Ibrahim et al.

 DOI: https://dx.doi.org/10.4314/jaaps.v11i2.2
Antidiabetic and thrombolytic activities of medicinal plants

This was determined with a calibrated portable HOMA-IR =

[Fasting blood glucose (FBG) (mg/dl) x fasting plasma insulin (FPI) (µU/mL)]
glucometer (Accu-Chek®, Germany) with drops 405
of blood obtained via a prick to the tail vein after
sterilization of the area with alcohol impregnated 2.9. Thrombolytic assay
swabs. The method for examining clot lysis has been
previously described by Prasad et al. (2007).
2.7. Estimation of lipid profile of the rats Briefly, 200µl of blood was placed into 500µl
The lipid profile of the experimental rats was micro-tubes that were weighed earlier. The tubes
determined using Randox lipid kits. The were allowed to stand for 45 minutes at 37°C to
parameters measured were serum total allow for clot formation. With caution, serum
cholesterol (based on the enzymatic method was aspirated out with a pipette leaving the clot
earlier described by Allain et al. (1974)) with the intact. Each of the tubes was then weighed again
absorbance of this dye was measured to determine the weight of the clot, and then
spectrophotometrically at 500nm. Serum labelled. From each of the leaf extract powder, 5g
triglycerides were measured using the method of was dissolved in 5ml of distilled water and then
Tietz (1990). Serum HDL-cholesterol levels were to each of the labelled tubes, 100 µl of leaf extract
determined using methods described by Burstein was added and then incubated at 37°C in order to
et al. (1970) with absorbance was measured observe for clot lysis. After 90 minutes, we
spectrophotometrically at 500nm. Serum removed the fluid obtained and weighed the tubes
concentration of LDL-cholesterol and VLDL- to calculate the change in weight following the
cholesterol were derived using the Friedwald disruption of the clot. The observed changes in
formula (Friedewald et al., 1972) as below: the weights of the microtubes, before and after
𝑇𝐺
LDL-C (mg/dl) = TC – (HDL-C) - 5 clot lysis, were then expressed as a percentage of
𝑇𝐺 clot lysis. Samples were compared to
VLDL-C (mg/dl) = streptokinase (Sigma Aldrich, Missouri, USA;
5
Where: HDL-C= high-density lipoprotein specific activity: ≥3500 unit/ mg solid) and
cholesterol, LDL-C = low-density lipoprotein distilled water. Values were analysed from 3
cholesterol, TC= total cholesterol, TG= independent experiments. Percentage clot lysis
triacylglyceride and VLDLC = very low-density (%) = (Weight of the released clot /Weight of
lipoprotein cholesterol. clot) ×100.
The plasma atherogenic index was determined
using the formula: 2.9. Data Analysis
AI= log (TG/HDL-C) (Niroumand et al., 2015). Datasets were analysed with GraphPad Instat
statistical package (version 3.0) and presented as
mean ± standard deviation (SD). Changes in body
2.8. Determination of serum concentration of weights and serial blood glucose concentration
insulin and calculation of HOMA-IR measurements were analysed by repeated
measures analysis of variance (ANOVA). Other
The serum concentration of insulin was datasets were analysed using a one-way ANOVA
determined using a double sandwich rat insulin followed by Bonferroni post hoc test. A
enzyme-linked immunosorbent assay (ELISA) significance threshold of p < 0.05 (95% CI) was
Kits (Nanjing Pars Biochem CO., Ltd) according adopted.
to the instructions of the manufacturer. The result
of the fasting insulin concentration was then used 3. Results
together with the FBG to calculate the 3.1. Yield of the Extracts
homeostatic model assessment of insulin Following methanolic extractions, the extracts
resistance (HOMA-IR) as a measure of beta cell gave the following yields:
function and IR. This was determined using the  yield for Albizzia chevalieri was 8.51%
formula provided by Matthews et al. (1985) as  yield for Leptadenia hastate was 5.09%
follows:  yield for Newbouldia laevis was 8.79%

15 J. Afr. Ass. Physiol. Sci. 11 (2):2023 Ibrahim et al.

 DOI: https://dx.doi.org/10.4314/jaaps.v11i2.2
Antidiabetic and thrombolytic activities of medicinal plants

3.2. Impact of Methanol leaf extracts on body Table 2 highlights the effect of methanol leaf
mass changes of type 2 diabetic rats extracts on serial fasting blood glucose
concentrations of high fat diet and
Table 1 shows the changes in body mass of rats dexamethasone induced type-2 diabetic rats. For
at several time points following the all treatments, there was a reduction of blood
administration of methanol extract of Albizzia glucose concentration as time progressed. At day
chevalieri, Newbouldia laevis and Leptadenia zero (0), normal control recorded 5.41 mmol/l,
hastata and Metformin for two weeks. The diabetic control was 14.64mmol/l, metformin
untreated diabetic rats showed significantly 14.92mmol/l, Albizzia chevalieri, Newbouldia
(p<0.001) decreased body weight when laevis and Leptadenia hastate, 13.87mmol/l,
compared with normal control rats. This weight 14.79mmol/l and 14.84mmol/l respectively. On
difference was present at all the time points the the 7th day, the following values were recorded;
rats were weighed. Treatment with methanol normal control (4.57mmol/l), diabetic control
extract of Albizzia chevalieri, Newbouldia laevis (16.48mmol/l), metformin (9.78mmol/l),
and Leptadenia hastata for two weeks resulted in Albizzia chevalieri (9.47mmol/l), Newbouldia
increased body weight in the first and second laevis (10.71mmol/l) and Leptadenia hastata
weeks of extract/drug administration as (11.04mmol/l). By day 14, relatively stable
compared to diabetic control rats. levels were observed in the normal control
(6.95mmol/l) but a progressive decrease was
recorded in all treated groups compared to the
Table 1: Effect of treatments on weight across high resting values of diabetic controls
the experimental period. (13.97mmol/l). However, the blood glucose
concentration of the rats determined after 14
Treatment Body mass Day Daywith metformin,Day
days of treatment Albizzia
(Per Kg BM) before 0 chevalieri, Newbouldia
7 laevis and14
Leptadenia
dexamethasone hastata were within the same range (7.1 - 8.4
injection mmol/l).
Control (distilled water) 173.4±2.73 178.8±1.96 179.4±1.57 183.0±1.64
3.4. Effect of treatment with leaf extracts on the
a a a
Diabetic (Untreated) 175.0±1.84 166.6±1.44
fasting blood160.6±1.08 156.4±1.21
glucose concentration, insulin
Metformin (500mg) 171.6±2.48 concentration167.2±1.72
164.2±1.92 and HOMA-IR* of 171.4±1.44
diabetic rats**
The results of the FBG, insulin levels and
A. chevalieri (300mg) 170.2±2.58 164.4±1.81 167.4±1.72of* type-2173.0±1.79
computed HOMA-IR **
diabetic rats
N. laevis (300mg) 170.6±2.87 treated
163.8±2.69 with methanol
167.0±2.63 * extract of Albizzia
172.2±2.22 **
chevalieri, Newbouldia laevis and Leptadenia
L. hastate (300mg) 173.0±3.11 166.0±2.78 169.2±2.35
hastata are presented in **
Table 3.173.6±2.02 ***
The diabetic
*= p<0.05, **= p<0.01, *** = p<0.001 compared to untreated rats had significantly higher FBG
diabetic controls, a = P<0.001 from normal controls. (P<0.05), insulin concentration (P<0.05) and
Data analysed using repeated measures ANOVA HOMA-IR (p<0.05) when compared to the
followed by Bonferroni post hoc test and expressed controls. However, the administration of
as mean ± Standard deviation (SD), n= 7-8 rats. methanol extracts of Albizzia chevalieri,
Newbouldia laevis and Leptadenia hastata and
3.3. Effect of Methanol Extract of Albizzia metformin significantly reduced the FBG
chevalieri, Newbouldia laevis and Leptadenia (P<0.05), insulin concentration (P<0.05) and
hastata on serial fasting blood glucose levels of HOMA-IR (p<0.05) compared to the diabetic
type 2 diabetic rats untreated group.

16 J. Afr. Ass. Physiol. Sci. 11 (2):2023 Ibrahim et al.

 DOI: https://dx.doi.org/10.4314/jaaps.v11i2.2
Antidiabetic and thrombolytic activities of medicinal plants

Table 2. Fasting Blood Glucose Concentration (mmol/l) at Time Interval.

Treatment Day Day Day

(Per Kg BW) 0 7 14

Control (distilled water) 5.1±0.31 4.5±1.57 6.6±0.35

Diabetic (Untreated) 13.2±1.44a 15.44±1.08b 13.9±0.24a

Metformin (500mg) 14.2±0.92 a 8.78±1.72** 7.3±-0.18***

A. chevalieri (300mg) 12.3±1.81 a 9.27±0.20* 7.1±0.26***

N. laevis (300mg) 13.7±1.69 a 9.71±1.63* 8.4±0.18**

L. hastate (300mg) 14.8±0.40 a 10.73±0.34* 8.2±0.32**

*= p<0.05, **= p<0.01, *** = p<0.001 compared to diabetic controls, a = P<0.001 from normal controls. Data
analysed using repeated measures ANOVA followed by Bonferroni post hoc test and expressed as mean ± Standard
deviation (SD), n= 7-8 rats.

Table 3: Fasting Blood Glucose Concentration, Insulin Concentration and HOMA-IR Following Oral
Administration of Methanol Extract of Albizzia chevalieri, Newbouldia laevis and Leptadenia hastata in
Diabetic Rats

Glucose Insulin
Group HOMA-IR
(mmol/l) (µU/ml)

Control (distilled water)

6.6±0.35 3.9±0.22 1.14±0.21
Diabetic (Untreated)
13.9±0.24a 12.6±1.51a 7.78±0.06a
Metformin (500mg)
7.3±-0.18*** 5.6±0.37*** 1.82±0.06***

A. chevalieri (300mg) 7.1±-0.26*** 5.3±0.35*** 1.67±0.12***

8.4±0.18** 6.9±0.23*** 2.57±0.08**
N. laevis (300mg)

L. hastate (300mg) 8.2±0.32** 7.4±0.23** 2.69±0.08**

a
*= p<0.05, **= p<0.01, *** = p<0.001 compared to diabetic controls, = P<0.001 compared to normal controls.
HOMA-IR, homeostatic model assessment- insulin resistance. Data analysed using one way ANOVA followed by
Bonferroni post hoc test and expressed as mean ± Standard deviation (SD), n= 7-8 rats.

17 J. Afr. Ass. Physiol. Sci. 11 (2):2023 Ibrahim et al.

 DOI: https://dx.doi.org/10.4314/jaaps.v11i2.2
Antidiabetic and thrombolytic activities of medicinal plants

3.5. The impact methanol leaf extract of Albizzia concentration of HDL- cholesterol was decreased
chevalieri, Newbouldia laevis and Leptadenia in the diabetic controls. Following the
hastata on serum lipid profiles of type 2 diabetic administration of Albizzia chevalieri,
rats Newbouldia laevis and Leptadenia hastata and
the standard metformin, we observed
Table 4 shows the serum lipid profile of type-2 significantly (P<0.05) decreased levels of TC,
diabetic rats treated with methanol extract of TG, LDL- cholesterol and VLDL-cholesterol.
Albizzia chevalieri, Newbouldia laevis and These treatments also increased levels of HDL-
Leptadenia hastate. The diabetic untreated group cholesterol as compared with diabetic control.
had significantly higher (P<0.05) concentrations The atherogenic index of the rats administered
of total cholesterol (TC), triglycerides (TG), low with metformin (p<0.01) and Albizzia chevalieri
density lipoprotein (LDL)- cholesterol and very (P<0.001) were significantly lower than that of
low density lipoprotein (VLDL)-cholesterol the diabetic control.
compared with normal control. Conversely, the

Table 4: Serum Lipid Profile (mg/dl) of High Fat Diet and Dexamethasone Induced Type-2 Diabetic Rats
Treated with Methanol Extract of Albizzia chevalieri, Newbouldia laevis and Leptadenia hastata

Group TC TG HDL-C VLDL-C LDL-C AI

Control (distilled 82.6±3.64 89.8±1.77 63.6±3.05 17.9±0.35 20.0±1.28 0.4±0.03

water)

Diabetic (Untreated) 137.4±3.97a 152.4±1.36a 44.6±2.70a 30.4±0.27a 43.3±1.72a 0.7±0.03

Metformin (500mg) 84.2±3.89** 86.2±1.39** 51.2±2.58** 17.2±0.28*** 15.7±2.63*** 0.3±0.06**

A. chevalieri (300mg) 77.4±6.42*** 80.6±1.57** 48.2±3.42* 16.1±0.31*** 13.1±1.56*** 0.2±0.03***

N. laevis (300mg) 93.8±3.70** 110.4±1.81* 48.0±4.47* 22.1±0.36** 23.7±0.86*** 0.5±0.03

L. hastate (300mg) 88.2±5.07** 99.2±2.13* 45.0±4.74* 18.6±0.86** 23.6±3.79*** 0.5±0.11

Abbreviations: TC-total cholesterol; TG-triacylglycerol; HDL-C-high density lipoprotein cholesterol; LDL-C- low
density lipoprotein cholesterol; VLDL-C- very low density lipoprotein cholesterol; AI-atherogenic Index. *=
p<0.05, **= p<0.01, *** = p<0.001 compared to diabetic controls, a = P<0.001 from normal controls. Data analysed
using one way ANOVA followed by Bonferroni post hoc test and expressed as mean ± Standard deviation (SD), n=
7-8 rats.

18 J. Afr. Ass. Physiol. Sci. 11 (2):2023 Ibrahim et al.

 DOI: https://dx.doi.org/10.4314/jaaps.v11i2.2
Antidiabetic and thrombolytic activities of medicinal plants

3.6. Thrombolytic effects of Albizzia chevalieri, lipid disorders. Thus, agents that ameliorate IR
Newbouldia laevis and Leptadenia hastate in can potentially mitigate against the development
type 2 diabetic rats of T2DM and related conditions. Compared to
current antidiabetic agents, natural herbs can
The thrombolytic activity of diabetic rats impart lesser side effects. Among the potentially
administered Albizzia chevalieri, Newbouldia antidiabetic plants, leaf extracts of Albizzia
laevis and Leptadenia hastate is shown in figure chevalieri demonstrated significant ameliorative
1. Treatment of the clot with streptokinase effect on type-1 diabetes (Saidu et al., 2010).
produced the maximum clot lysis (93.70%)). Newbouldia laevis (Eneh et al., 2018) and
Whereas treatments with A chevalieri, N laevis Leptadenia hastate (Bello et al., 2011) have also
and L hastate triggered 48.90%, 39.02% and shown anti-hyperglycaemic activity in T1DM
37.69% clot lysis, respectively, distilled water rats. In this study, untreated diabetic rats showed
produced only 4.83% clot lysis. All the plant significantly lowered insulin sensitivity, as
extracts produced significantly greater (p<0.001) indicated by HOMA-IR. This was an indication
thrombolytic activity when compared to distilled of successfully induced the pathogenesis that can
water and significantly lower (p<0.001) activity lead to T2DM.
compared to streptokinase.
Weight loss seriously impacts the management of
diabetes mellitus (Brown et al., 2019; Magkos et
al., 2020). It may be due to degeneration in
adipocytes or muscle tissues, which could be in
compensation for the energy lost with frequent
micturition and/or the excess conversion of
glycogen to glucose. Our data showed marked
differences between the body weight of normal
and diabetic rats. Though both diabetic untreated
and treated rats lost weight throughout the study,
it was less severe in the treated rats. Individuals
with diabetes mellitus may face alteration in body
weight; for T1DM this comes as sudden weight
loss but this scenario is seldom the case with
Figure 1: Thrombolytic potential of Albizzia T2DM. Over time, T2DM only triggers
chevalieri, Newbouldia laevis and Leptadenia hastate significant weight loss if left undiagnosed and
Leaf extracts. a,b,c,d= significantly different at untreated (Mbara et al., 2022). In this study,
p<0.001.Data analysed using one-way ANOVA, n=3 dexamethasone, and exposure to high fat diet for
replicates. 21 days resulted in reduced body weight. A
previous study by Shalam et al. (2006) also
4. Discussion showed a similar finding of reduced body weight.
In the current study, we investigated some Interestingly, methanol extracts of Albizzia
selected medicinal plants for their antidiabetic chevalieri, Newbouldia laevis and Leptadenia
and thrombolytic activities of in type 2 diabetic hastata reversed this progressive loss in body
rats. Following a successful induction of T2DM, weight caused by dexamethasone and high fat
treatment with the leaf extracts lowered the blood diet.
glucose level of type 2 diabetic rats. Interestingly, An initial increase in glucose and then circulating
the leaf extracts also showed a substantial degree insulin levels can indicate a greater degree of
thrombolytic activities in vitro. insulin resistance. After treatment with
The combination of HFD and dexamethasone dexamethasone and high fat diet, rats developed
used in this study successfully induced T2DM hyperglycaemia and reduced insulin sensitivity as
and insulin resistance (IR) in the rats. IR is determined by the HOMA-IR. However, our
observed in conditions like T2DM, obesity and treatments of T2D rats with Albizzia chivalieri,

19 J. Afr. Ass. Physiol. Sci. 11 (2):2023 Ibrahim et al.

 DOI: https://dx.doi.org/10.4314/jaaps.v11i2.2
Antidiabetic and thrombolytic activities of medicinal plants

Newbouldia laevis and Leptadenia hastata leaf diabetogenic diet and increased the HDL-
extracts restored the glucose concentration cholesterol level compared to the untreated
towards normal and improved insulin sensitivity. diabetic rats. These findings emphasize the
This is comparable to results obtained for prospective role of plants in the prevention and
Albizzia chivalieri (Saidu et al., 2010), treatment of cardiovascular disease. The extracts'
Newbouldia laevis (Eneh et al., 2018) and potential to lower not only blood glucose but also
leptadenia hastata (Bello et al., 2011) when they total cholesterol and triglycerides may thus be of
were administered to alloxan-induced type-1 great benefit.
diabetic rats. To our knowledge, there is currently
no report on the potential of methanol extract of Various medicinal plants have been shown to
Albizzia chevalieri, Newbouldia laevis and possess anti-diabetic potential in T1DM and mild
Leptadenia hastate to exert antidiabetic activity thrombolytic actions (Kianian et al., 2021; Yadav
in an animal model of T2DM, thus, making our et al., 2022). To compare the clot lysis effects of
findings novel. The antidiabetic activity our selected plant leaf extracts, we used
demonstrated by the leaf extracts could be a result Streptokinase, a novel thrombolytic drug, as a
of their action on the B cells of the pancreas positive control. The novelty of this study lies in
causing both an increased insulin secretion and the fact that the thrombolytic activity of these
enhanced sensitization of the insulin receptors plants, Albizzia chevalieri, Newbouldia laevis
(Semwal et al., 2021). Alternatively, this may be and Leptadenia hastata, has not been previously
explained by enhanced blood glucose delivery to reported. T2DM increases the risk of building-up
peripheral tissues or an inhibition of the action of plaques in arteries. This can trigger harmful blood
alpha-glucosidase (Bhatia et al., 2019). Thus, the clots as a result of pro-thrombotic changes and
methanol leaf extracts of Albizzia chivalieri, contributes to the high incidence of thrombotic
Newbouldia laevis and Leptadenia hastata events in type 2 diabetic individuals. The
possess potent hypoglycaemic activity. activities exhibited by Albizzia chevalieri,
Newbouldia laevis and Leptadenia hastata may
Dexamethasone stimulates lipolysis, which result in the stimulation of insulin sensitivity
results in the production of free fatty acids, which receptors and stimulation of pancreatic B-cells to
then compete with glucose for intracellular produce enough insulin with additional benefit of
oxidation (Olivas-Aguirre et al., 2023). This lysing blood clots (thrombolytic activity).
leads to the development of IR via the fatty acid Therefore, if these results are validated then the
cycle (Lee et al., 2022). Dexamethasone also plants extracts might prove useful as therapy for
increases triglyceride levels, causing a disordered insulin resistance and artery-thrombotic events in
lipid metabolism that triggers hyperlipidaemia type-2 diabetic patients.
(Dzinyela et al., 2021). In diabetes, free fatty
acids are increasingly mobilised from peripheral 5. Conclusion
fat depots because of the inability of insulin to
inhibit hormone-sensitive lipase (Tella et al., In this study, we showed that methanol leaf
2019). As a result, the severe hyperlipidaemia extracts of the selected medicinal plants have
that precedes diabetes may be seen as a side effect anti-diabetic effects in high fat diet and
of unrestrained lipolytic hormone activities on fat dexamethasone induced model of type-2
depots. When compared to normal control, 21 diabetes. The extracts produced almost similar
days of a high fat diet and dexamethasone decrease in blood glucose concentration as the
resulted in increased triglyceride, increased total, standard drug, metformin. This could be the
LDL- and VLDL-cholesterol but decreased explanation for the use of these plants to treat
HDL-cholesterol. Interestingly, Shalam et al. diabetes mellitus in some societies. Additionally,
(2006) had previously reported similar findings. the extracts of Albizzia chevalieri, Newbouldia
However, the administration of the leaf extracts laevis and Leptadenia hastata have shown a great
in our study reversed the effects of the potential for blood clots lysis (thrombolytic)

activity in vitro. Future studies to demonstrate in components responsible for clot lysis should be
vivo clot dissolving properties and the bioactive considered. The goal of the management of

20 J. Afr. Ass. Physiol. Sci. 11 (2):2023 Ibrahim et al.

 DOI: https://dx.doi.org/10.4314/jaaps.v11i2.2
Antidiabetic and thrombolytic activities of medicinal plants

T2DM is not limited to reduction of the high Burstein, M., Scholnick, H. R. and Morfin, R.
blood glucose level, but also the prevention of (1970). Rapid method for the isolation of
complications such as hypercoagulation and lipoproteins from human serum by
mortality associated with it. precipitation with polyanions. Journal of
Lipid Research, 11, 583-95.Cole, J. B. and
Acknowledgment Florez, J. C. (2020). Genetics of diabetes
The authors thank the Department of mellitus and diabetes complications.
Biochemistry and Molecular Biology, Faculty of Nature Reviews Nephrology, 16, 377-390;
Chemical and Life Sciences, Usmanu Danfodiyo https://doi.org/10.1038/s41581-020-0278-
University Sokoto, Nigeria for support with 5.
laboratory space. Danboyi, T., Alhassan, A. W., Jimoh, A. and
Hassan-Danboyi, E. (2020). Effect of L-
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