BON SUR ANTIDIAB
BON SUR ANTIDIAB
BON SUR ANTIDIAB
RESEARCH ARTICLE
Article History: Aim and objective: Clerodendrum thomsoniae leaves are used in Cameroon to
Received: 1 April 2021 manage diabetes and its related disorders. The study aimed at investigating the
Reviewed: 3 May 2021 antidiabetic effect of the aqueous extract on diet and dexamethasone induced
Accepted: 10 June 2021 diabetic rats.
Published: 15 July 2021 Methods: Young mature leaves of C. thomsoniae were dried, finely powdered and
_______________________________________________ submitted to aqueous extraction. The dehydrated extract was tested in rats at 3
doses 312.5, 625 and 1250 mg/kg based on the local use of the plant. The effect of
Cite this article: the extract on the fasting blood glucose in normoglycemic rats and MACAPOS 1
Ngounou EMD, Mang YD, Dongmo F, Malla type diet induced diabetic rats, using respectively glibenclamide and metformin as
OWI, Dongmo SS, Yanou NN. Effect of the positive control groups, were investigated.
aqueous extract of Clerodendrum thomsoniae
Results: AECT significantly reduced blood glucose levels in normoglycemic rats
linn (Verbenaceae) leaves on type 2 diabetic
wistar rats induced by the MACAPOS1 type diet (p<0.05) two hours after administration, from 83±2 mg/dL to 57.39±1.7 mg/dL
and dexamethasone. Universal Journal of with the dose of 1250 mg/kg given the highest reduction rate of 30.86%. In
Pharmaceutical Research 2021; 6(3):9-16. normoglycemic rats 30 minutes after oral glucose overload, the maximum
https://doi.org/10.22270/ujpr.v6i3.601 reduction rate was observed with glibenclamide 5 mg / kg and calculated at 49.90%
______________________________________________ followed by 36.39%, for the extract at 1250 mg/kg. After 30 days of repeated oral
administration, AECT produced a reduction on blood glucose levels (p<0.05) in
*Address for Correspondence: type 2 diabetic rats. This reduction in blood sugar was much more expressed with
Deutchoua Ngounou Eric Martial, Health the dose of 1250mg/kg (73.52±0.71 mg/dL) followed by metformin 38 mg/kg
Medicinal Plant Laboratory and Galenic (70.21±0.89 mg/dL) as the normal control with no significant difference (p < 0.05).
Formulation, Department of Biological Conclusion: These results show that the antidiabetic activity of AECT can be
Sciences, Faculty of Science, University of
Ngaoundere- PO BOX 454, Ngaoundere,
explained by insulin stimulating effect, also give support to the traditional use of
Cameroon. Tel-(237) 670683413; this plant.
E-mail: ericmartialdeutch@gmail.com Keywords: Antidiabetic, aqueous extract, Clerodendrum thomsoniae leaves,
Dexamethasone, hypoglycemic, MACAPOS 1 diet.
ureas and glinides6. These drugs do not only have and 125 mg/mL aqueous extract of C. thomsoniae
negative side effects, but also are expensive, in (AECT) corresponding to the 3 tested doses (312.5,
particular for individuals in developing countries given 625 and 1250 mg/kg).
their low purchasing power. In this respect the Animal experiments
traditional pharmacopoeia offers a solution. To conduct this experiment, healthy Wistar rats all
Since ancient times, more than 80% of the world male aged between 6 -8 weeks old and weighing about
population used plant extracts or any other form to 150-200 g were raised in the animal house of the
threat many diseases including DM7,8. At least 12 000 Faculty of Science of the University of Ngaoundéré
plants in the world are used for medicinal purposes, but (Cameroon) at an ambient temperature of 22±3°C and
less than 10% of them are investigated from relative humidity of 54±2% under a 12 h/12 h
pharmacological point of view9. Many antidiabetic light/dark cycle. The animals were acclimatized to
wild plant species have been investigated for their laboratory condition for four days before the
hypoglycemic activity10 and actually recommended for experiment starts and were fed with a standard diet
therapeutic treatment of DM11. The anti-diabetic effects made of casein as a protein source and tap water ad
of plants have been attributed to their contents which libitum. The experiment was carried out as per the
include carotenoids, flavonoids, terpenoids, alkaloids, guidelines of Committee for the Purpose of Control
glycosides12,. Amongst plants studied for their and Supervision of Experiments on Animals
antidiabetic activies we may cite Anacardium (CPCSEA) and ethically approved by the Institutional
occidental13, Allium sativum14, Allium cepa15. Thought Committee of the Ministry of Scientific Research and
Clerodendrum sp. are granted strong therapeutic Innovation of Cameroon (Phone: 00(237)699870979
potentials16, Clerodendrum thomsoniae an ornamental Effect of single oral administration of AECT in
plant16 widely used by traditional healers in normal healthy rats
Ngaoundere-Cameroon to treat diabetes, has not yet This study was done as reported by Kouambou et al.,19
been investigated. According to the literature, the plant with some modifications. Twenty rats were divided
leaves are traditionally used in the treatment of into four experimental groups with five animals in each
intestinal worms and other illnesses. In addition, the group: normal control (NC) rats that received
hypolipidemic, the antioxidant activity17 and the only distilled water 10 mL/kg; 3 test groups as used by
toxicity18 of the aqueous extract of the leaves were traditional practitioners (AECT312.5 mg/kg; AECT625
studied. The plant activity of the plant was attributed to mg/kg; and AECT1250 mg/kg). For this study,
its high flavonoid and tannin contents17. administration of the aqueous extract was done by
The general objective of this work was to evaluate the gavage using a 2.5 mL goading probe. Blood samples
hypoglycemic and antidiabetic activities of aqueous were collected from the tail vein periodically at t=0, 60,
extracts of C. thomsoniae on type 2 diabetic rats 90 and 120 min after the administration of extract and
induced by MACAPOS 1 type diet and the glucose content determined using glucose oxidase
dexamethasone. method.
Oral Glucose Tolerance Test (OGTT) in normal
MATERIALS AND METHODS Rats
The anti-hyperglycemic effect of the AECT at doses of
Sampling and production of C. thomsoniae extract 312.5, 625 and 1250 mg/kg was studied as described
The plant material (leaves) was collected at Mbideng, a by Nkono et al.,20 with some modifications. In this
neighborhood of Ngaoundéré, in Adamawa region of respect, 25 rats were fasted for 16 h and treated with
Cameroon. The plant was identified at the national the AECT (test groups), glibenclamide 5mg/kg
herbarium (NO Letouzey 11090 from the herbarium (positive control group) and water (Normal control
collection NO 28476/SRF/Yaoundé, Cameroon). group, NC). At time 0 min, the animals were
Young mature leaves of the plant were carefully administered orally 10 mL of the extract,
cleaned, sorted, graded according to size and dried in a glibenclamide or water. After 30 min of the treatment,
ventilated electric turning dryer (brand Riviera & Bar) all groups received glucose (2.5 g/kg b.m) orally and
at 40±2°C for 48 h. After drying, the leaves were the blood glucose concentrations were determined from
ground to make a fine powder using an electric grinder the tip of a tail at time 0, 60, 90 and 150 min..
(Culatti, Polymix, France) equipped with a sieve of Induction and Treatment of Hyperglycemia
diameter 500 μm mesh. Diabetes induction
Preparation of C. thomsoniae aqueous extract Diabetes was induced in Rats using the MACAPOS 1
The obtained powder (2.5 g) was blended with 40 mL diet and dexamethasone according to Kamgang et al.,21
distilled water. The different mixtures were placed in a with some modifications.In the procedure, healthy rats
water bath at 70±2 °C and extracted for 30 min under were divided in two groups. One group (normal
stirring. The mixture was then cooled for 30 min and control) was submitted to standard diet, another group
centrifuged at 1500 g for 15 min at 20°C using was submitted per os to Sweetened high-calorie diet
refrigerated centrifuge. The supernatant was collected (SHCD) made of dextrose 0.8 g/kg (Gwaudan
and the residue was solubilized in 40 mL and re- Laviretteet Cie, Glucose pure Anhydre) and sucrose 4
extracted as mentioned above. The supernatants were g/kg (SOSUCAM, Bandjock-Cameroon) every two
combined and concentrated under vacuum in a rotary days. One month after the beginning of SHCD, the
evaporator and dried in a desiccator at 40°C. The crude animals received the dexamethasone (25 μg/kg b.m
extract was weighed and used to prepare 31.25, 62.5 i.m.) once every 2 days during 3 weeks. During the
induction period, fasting glycemia was estimated at the evaluated as previously described. In addition, animals
beginning and at the end to confirm the onset of were sacrificed and dissected and the visceral adipose,
diabetes. In this respect the oral glucose tolerance test hepatic, cardiac and testicular tissues were removed,
(OGTT) was carried out by administration of 4g/kg and weighed.
b.m. of D-glucose in rats of different groups. Blood Statistical analysis
sugar was monitored for 120 min. The animals with All data were expressed as mean±standard deviation
fasting total blood glycemia≥126 mg/dL were and were statistically analyzed using one-way analysis
considered as diabetic and were selected for the next of variance (ANOVA). When statistical differences
stage of experiment. were found, the Duncan’s Multiple Range Test was
Evaluation of antidiabetic activity of AECT applied in order to classify samples at the significance
The rats were organized into 6 groups of 5 animals level of 5%. The Statgraphics Program (Statically
each: normal control, negative control group made of Graphics Educational, version 6.0, 1992, Manugistics,
diabetic rats receiving water, positive control group Inc. and Statistical Graphics Corp., USA) was used for
made of diabetic rats treated with Metformin (38 the statistical analysis.
mg/kg b.m: Met38), test groups composed of diabetic
rats treated with aqueous extract of C. thomsoniae RESULTS
doses 312.5, 625 and 1250 mg/kg b.m (AECT312.5,
AECT625, AECT1250). The animals were treated once Hypoglycemic effect of aqueous extract of C.
daily by intra-gastric gavages for 30 consecutive days. thomsoniae on normoglycaemic rats
During the treatment, fasting glycemia was estimated The effect of AECT on blood glucose levels in fasting
at the beginning and every fifteen days. Other normal rats is presented in Figure 1. A single
parameters such as food intake, water intake and administration of AECT at all the doses exhibited a
change in body mass were also measured. At the end of significant hypoglycemic effect after 2 hours (p<0.05).
treatment, OGTT and organ to body mass were
Figure 1: Effect of the aqueous extract of C. thomsoniae on blood glucose of normoglycemic rats.
Value are means ±SD (n=5) significantly different (p< 0.05) as determined by Duncan’s multiple range test. Normal: group of normal rats received
distilled water; AECT312.5: group of rats receiving C. thomsoniae extract at dose of 312.5 mg/kg; AECT625: group of rats receiving C.
thomsoniae extract at dose of 625 mg/kg; AECT1250: group of rats receiving C. thomsoniae extract at dose of 1250 mg/kg. b.m=body mass.
The extract at 1250 mg/kg produced the most decreases in blood glucose level 2 hours after glucose
significant reduction (29.1 %) (p<0.05) comparatively administration as shown in Figure 2. In particular, the
to the effect of the two others doses (15.5 %, 21.8 % rats receiving glibenclamide and AECT at 1250 mg/kg
respectively) 90 min after administration. dose showed significant reductions in blood glucose
Consequently, blood sugar tended to stabilize until the level 30 min after glucose administration compared
120th minute when there has been no significant change with the normal control rats.
compared to the 90th minute regardless. In the acute test, the glucose load increased blood sugar
Effects of AECT on Glucose-Induced in the normal control group. The basal glucose in rats
Hyperglycemia in normal rats in this group increased from 85.8±2 to 149.6±1.43
Blood glucose levels returned to baseline or even lower mg/dL at 30 min after glucose administration and
2 hours after glucose administration in all animals. returned to 111.0±1.1 mg/dL after 150 min.
Animals treated with glibenclamide and AECT showed
Glibenclamide significantly prevented the rise in blood and compared to normal rats. OGTT in normal rats
glucose throughout the experiment followed by AECT resulted in an increase in blood sugar at 60 min (122.50
at dose of 1250 mg/kg. mg/dL), then a decrease within 120 min to an identical
Oral glucose tolerance test at the end of induction of value (72.33±2.80 md/dL) at baseline blood sugar. In
type 2 diabetes diabetic rats, the glycemia significantly linearly
Figure 3 shows the glycemic response of rats submitted increased (p<0.05) from 130±2 to 148±2 mg/dL,
to sweetened high-calorie and dexamethasone regime passing by a value of 137.33 mg/dL at 60 min.
Figure 3: Change in blood sugar after an oral overload of a glucose solution at the end of induction period
(4g/kg b.m).
NIG: Non-Induced Group; IG: Induced Group; min: minute; The means are significantly different (P <0.05); Values were expressed as
mean±standard deviation; n = 5.
parameters on induced type 2 diabetic rats are aqueous extract suggested that C. thomsoniae extract
summarized in Table 1. During 30 days of the contains compounds with a mechanism of action that
treatment of diabetic rats, the body mass of rats in may be similar to that of glibenclamide. Therefore,
positive control group (PC) and test groups irrespective AECT may be considered insulin-secreting agent
of the dose gradually decreased at the end of the which stimulates the beta cells of the Langerhan islets
treatment, these groups also showed significant of the pancreas for insulin production. According to
reductions (p<0.05). The drop in body mass was higher Arumugam et al.,28, plants may act as antihypergly-
with the extract at the dose 1250 mg/kg and metformin cemic agent through two mechanisms: increasing
(respectively -16.07±10.00 g and -18.39±4.74 g). It has insulin secretions or reducing intestinal absorption of
also been observed a significant reduction in food glucose. These activities may be associated to their
intake and water intake in groups administered AECT content in some bioactive components revealed earlier
as compared to the diabetic group (NC) (p<0.05). in the plant extract17. The role of polyphenols in the
Assessment of abdominal fat at the end of treatment complexation, and therefore inhibition of α-glucosidase
The effects of AECT administration on the abdominal and α-amylase has been pointed as a mechanism
fat of diabetic rats are presented in Figure 4. It appears involved in hypoglycemic effect of some plants29.
from this figure that the relative mass of abdominal fat In the current work, a relative stability was found in
decreased during treatment. Administration of AECT blood glucose in the diabetic control group which may
reduced abdominal fat with the magnitude increasing be due to the insulin resistance very often encountered
with the dose with 1250 mg/kg inducing reduction in obese or type 2 diabetes30. However, oral administra-
64.52% while reduction in Metformime group was tion of AECT exhibited significant increase in blood
59%. glucose levels. Current results indicated that AECT
dose 1250 mg/kg significantly (p<0.05) reduced the
DISCUSSION level of blood glucose within the third and fourth week
of the experimental period. This result strongly
Plants have always been the major source of drugs, supports the antidiabetic property of AECT. However,
thanks to their content in secondary metabolites22,23. In increasing insulin secretion and maintaining its level
this vein, thousands of plants are traditionally used for within the normal physiological range are very
the treatment of diabetes mellitus and its important for antidiabetic therapy. In this experiment,
complications, however to the best of the knowledge, hyperglycemia induced in 10 weeks by the combined
no study has been conducted on the hypoglycemic and effect of MACAPOS 1 type diet and dexamethasone
antidiabetic properties of AECT in vivo. The effect of was associated with increase food intake and water
the AECT on normoglycemic animals suggested that intake body mass. Current results are in accordance
the leaves of C. thomsoniae has a mild lowering effect with many other 31. Glucocorticoids are known to have
on normal glucose levels. This effect was comparable particularly significant metabolic side effects on
to that of glibenclamide, an insulin secretagogue, carbohydrate metabolism32.
which also lowers blood glucose in normal animals. Dexamethasone (exogenous glucocorticoid) provokes
Provided the β-cells are fully functional, the insulin resistance thereby induces chronic
sulphonylureas, such as glibenclamide, can cause hyperglycemia and other metabolic disorders such as
hypoglycemia since insulin release is initiated even increase neo-glucogenesis from amino acid and
when glucose concentrations are below the normal glycerol in the liver, and lipolysis in adipocytes33.
threshold for glucose stimulated insulin release Dexamethasone also acts by inhibiting the gene
(approximately 5 mmol/L or 90 mg/dl)24. The results of expression of adiponectin, a hormone produced by
this study showed a dose-dependent hypoglycemic adipocytes which promotes insulin resistance through
activity of the aqueous extract of C. thomsoniae in dysfunction of hormon receptor in the liver, muscle and
normoglycemic rats. These results also suggested that adipose tissue34,35. Fortunately, AECT significantly (p
the hypoglycemic effect may be due to water-soluble <0.05) decreased blood sugar levels of diabetic rats to
compounds. It has been established by many studies normal value with a maximum decrease observed with
that the genus Clerodendrum is rich in total phenolic the highest dose of AECT 1250 mg/kg dose. This result
compounds, flavonoids, terpenoids, alkaloids, tannins, suggested that AECT may act among others like
saponosides and anthraquinones25,26. Our previous metformin, by decreasing hepatic glucose production
studies also revealed that AECT contains these and ameliorating the peripheral insulin sensitivity36.
secondary metabolites17. As reported by Mamadou27, This further indicates the role phytochemicals present
the lowering blood glucose property of Clerodendrum in AECT which need investigations in order to identify
capitatum is dose dependent and based to its level in the molecules responsible for the activity observed. In
secondary metabolites. OGTT measures the ability of anticipation, flavonoids have been shown to improve
the body to stabilize the blood glucose to its normal the sensitivity to insulin and thereby reduced the
level. The glycemic status of rats was shown to incidence of type 2 diabetes37,38. Concerning abdominal
improve as the AECT dose increased in a dose- fat, AECT reduce the quantity in a dose-dependent
dependent manner. OGTT study revealed diabetic rats manner with the highest reduction observed at 1250
treated AECT and glibenclamide exhibited significant mg/kg of AECT compared to the group of rats treated
(p<0.05) improvements in their blood glucose levels, with metformin.
with the effect being more effective as the dose of
AECT increased. The antihyperglycemic activity of the
AECT312.5 269±1.14a 135.71±0.84b 130.57±0.55c 136.87±1.14a 73.36±0.84b 74.29±0.55b 262.9±10.4ab 240.1±5.8ac 236.4±3.9bc 131.00±1.14b 126.4±0.84c 102.4±0.55bc
AECT625 260±1.30a 137.57±1.00b 132.28±1.14c 135.83±1.30a 74.85±1.00b 75.26±1.14b 260.1±13.6ab 244.8±7.5bc 231.7±2.4c 131.00±1.3b 125.4±1ab 98.6±1.11d
AECT1250 260±1.14a 135.71±0.84ab 130.85±0.71b 135.9±1.14a 76.09±0.84b 74.59±0.71c 260.2±12.8ab 239.9±8.6ac 221.8±5.1ac 131.00±1.14b 123.8±0.84ab 73.5±0.71a
The values entered in the table are means±standard deviation, with a sample number of "n = 5. The means with different letters are significantly different (P <0.05). AECT: aqueous extract of Clerodendrum thomsoniae
(1250mg/kg m.c; 625mg/kg m.c; 312mg/kg b.m) N.C: Negative Control (subjected to a Normal Diet + Distilled Water during treatment); P.C: Positive control subjected to a Normal Diet + metformin.
albino rats, Rattus norvegicus (Muridae). J Pharmacog stress, proinflammation, and insulin resistance through
Phytochem 2020; 9(1): 595-602 metabolic reprogramming of mitochondria in adipose
18. Ngounou EMD, Dongmo F, Mang YD, Dongmo SS, Yanou tissue. Antioxid Redox Signal 2020; 33(2):1–60.
NN. Evaluation of the acute and subchronic toxicity of the https://doi.org/10.1089/ars.2019.7737
aqueous extract of the leaves of Clerodendrum thomsoniae 31. Mvongo C, Mfopa A, Kamgang R, Essame Oyono JL.
Linn in oral route. Asian J Pharm Pharmacol 2020; 6(6): Antidiabetic and Antioxidant Activities of Crinum jagus
375-382. https://doi.org/10.31024/ajpp.2020.6.6.2 Extracts on Induced Diabetes Rats MACAPOS 1. Int J
19. Kouambou CCN, Dimo T, Dzeufiet PDD, et al. Pharm Phytochem Ethnomed 2016; 5: 86-95
Antidiabetic and hypolipidemic effects of Canarium 32. Beaupere C, Liboz A, Fève B, Blondeau B, Guillemain G.
schweinfurthii hexane bark extract in streptozotocin- Molecular mechanisms of glucocorticoid-induced insulin
diabetic rats. Pharmacol Online 2007;1: 209-219 resistance. Int J Mol Sci 2021; 22, 623.
20. Nkono BLNY, Sokeng SD, Désiré DDP, Kamtchouing P. https://doi.org/10.3390/ ijms22020623
Antihyperglycemic and antioxydant properties of Alstonia 33. Sidibeh CO. Novel mechanisms of glucocorticoid-induced
boonei De Wild. (Apocynaceae) stem bark aqueous extract insulin resistance in human adipose tissue. Digital
in dexamethasone-induced hyperglycemic rats. Int J comprehensive summaries of uppsala dissertations from the
Diabetes Res 2014; 3: 27-35. Faculty of Medicine 1408. 52 Uppsala: Acta Universitatis
https://doi.org/10.5923/j.diabetes.20140303.01 Upsaliensis 2018; ISBN 978-91-513-0180-8.
21. Kamgang R, Mboumi R, N’dillé G, Yonkeu J. Cameroon 34. Della Bella E, Buetti-Dinh A, Licandro G, et al.
local diet-induced glucose intolerance and dyslipidemia in Dexamethasone induces changes in osteogenic
adult Wistar rat. Diabetes Res Clin 2005; 69. 224-30. differentiation of human mesenchymal stromal cells via
https://doi.org/10.1016/j.diabres.2005.02.005 SOX9 and PPARG, but Not RUNX2. Int J Mol Sci 2021;
22. Hoang-Nam Pham, 2017. Impact of secondary plant 22: 4785. https://doi.org/10.3390/ijms2209478
metabolites on rhizosphere pathogenic bacteria: is there a 35. Wego MT, Poualeu SL, Miaffo D, Nchouwet ML, Kamanyi
link between metal resistance and antibiotic resistance A, Wansi SL. Protective effects of aqueous extract of
modulation? Agricultural Sciences. Paul Sabatier Baillonella toxisperma stem bark on dexamethasone-
University - Toulouse III. French. NNT: 2017TOU30153. induced insulin resistance in rats. Adv Pharm Sce 2019; 6.
23. LOUGBEGNON TO, GBESSO F, LOGBO J, et al. https://doi.org/10.1155/2019/8075163
Ethnobotanical study of plants with therapeutic value in the 36. Itamar Raz. Guideline approach to therapy in patients with
commune of Glazoué in Benin (West Africa). Int J Innov newly diagnosed type 2 diabetes. Diabetes Care 2013; 36
App Stud; Rabat 2018; 24, N° 2: 644-655. 139-144. https://doi.org/10.2337/dcS13-2035
https://doi.org/10.1186/s12906-020-03080-6 37. Russo B, Picconi F, Malandrucco I, Frontoni S. Flavonoids
24. Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role and insulin-resistance: from molecular evidences to clinical
in type 2 diabetes mellitus. Drugs; 2005; 65 (3): 385-411. trials. Int J Mol Sci 2019; 20(9): 2061.
https://doi.org/10.2165/00003495-200565030-00005 https://doi.org/10.3390/ijms20092061
25. Adeneye AA, Adeleke TI, Adeneye AK Hypoglycemic and 38. Guasch-Ferré M, Merino J, Sun Q, Fitó M, Salas-Salvadó J.
hypolipidemic effects of the aqueous fresh leaves extract of Dietary polyphenols, mediterranean diet, prediabetes, and
Clerodendrum capitatum in wistar rats. J Ethnopharmacol type 2 diabetes: a narrative review of the evidence. Oxid
2008; 116:7–10.https://doi.org/10.1016/j.jep.2007.10.029 Med Cell Longev 2017.https://doi.org/10.1155/2017/6723931
26. Linn. Pharm Res 2009; 1:294–298. 39. Zeka K, Ruparelia K, Arroo R, Budriesi R, Micucci M.
27. Mamadou Balde, 2018. Physico-chemical study and Flavonoids and their metabolites: prevention in
valorisation of bioactive compounds of Parinari macro- cardiovascular diseases and diabetes. Diseases 2017; 5:19.
phylla Sabine (Chrysobalanaceae). Theoretical and/or https://doi.org/10.3390/diseases5030019
physical chemistry. University of Strasbourg; Cheikh Anta 40. Jia Zhao, YaYun Wu, XiangLu Rong, CuiWen Zheng, Jiao
Diop University (Dakar). French. NNT: 2018STRAF013. Guo. Anti-Lipolysis Induced by Insulin in Diverse
28. Arumugam G, Manjula P, Paari N. A review: Anti diabetic Pathophysiologic Conditions of Adipose Tissue. Diabetes,
medicinal plants used for diabetes mellitus. J Acute Dis Metabolic Syndrome and Obesity: Targets and Therapy
2013; 2:196–200. 2020; 13:1575-1585.
https://doi.org/10.1016/S2221-6189(13)60126-2 https://doi.org/10.2147/DMSO.S250699
29. Sharma R, Kumari S, Elancheran R, Deori M, Devi R. 41. Mahdi H S, Robert H H, Azuwerus V B, Maaike Goris, Leo
Polyphenol rich extract of Garcinia pedunculata fruit ED, Hendrik B., 2017. Metformin improves endothelial
attenuates the hyperlipidemia induced by high fat diet. function and reduces blood pressure in diabetic
Front Pharmacol 2016 ;7. spontaneously hypertensive rats independent from glycemia
https://doi.org/10.3389/fphar.2016.00294 control: comparison to vildagliptin. Sci Reports 2017;
30. Lin HY, Shao-Wen W, Shen FC, 2020. Abrogation of Toll- 7:10975.https://doi.org/10.1038/541598-01-1130
like receptor 4 (TLR4) mitigates obesity-induced oxidative