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Asian Pacific Journal of Tropical Biomedicine
journal homepage: www.elsevier.com/locate/apjtb
Original article http://dx.doi.org/10.1016/j.apjtb.2016.10.002
Hypoglycemic and anti-hyperglycemic study of Ocimum tenuiflorum L. leaves extract in normal
and streptozotocin-induced diabetic rats
Leila Mousavi1, Rabeta Mohd Salleh1*, Vikneswaran Murugaiyah2, Mohd Zaini Asmawi2
1
Food Technology Division, School of Industrial Technology, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
2
Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
ARTICLE INFO
Article history: Received 6 Feb 2016 Received in revised form 1 Mar, 2nd revised form 11 Mar, 3rd revised form 16 Mar, 4th
revised form 24 Mar 2016 Accepted 10 Aug 2016 Available online 15 Oct 2016
Keywords: Ocimum tenuif lorum L. Streptozotocin-induced diabetes Antidiabetic Fasting blood glucose Subcutaneous glucose
tolerance test Phytochemical analysis
2221-1691/Copyright © 2016 Hainan Medical University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
(http:// creativecommons.org/licenses/by-nc-nd/4.0/).
ABSTRACT
Objective: To investigate the antidiabetic activity of Ocimum tenuiflorum L. (O. tenui- f
lorum) leaves used in the traditional
medicine management of diabetes in Malaysia. Methods: O. tenuiflorum leaves were extracted sequentially with hexane,
chloroform, ethyl acetate, methanol, and water. The extracts were evaluated in terms of antidiabetic activity by using acute,
subcutaneous glucose tolerance, and sub-chronic tests in streptozotocin- induced diabetic rats. The extracts were also subjected to
phytochemical analyses. Results: With an acute dose (1 g/kg), the methanol extracts showed significant reduction (31%) in
fasting blood glucose (FBG) of the streptozotocin-induced diabetic rats. The FBG-decreasing effect of ethyl acetate extract was
more rapid than that of the other extracts; the decreasing rates were 20% after 2 h, 21% after 3 h, and 8% after 5 and 7 h. After 7 h
(31%), the effect of methanol extract on FBG was significantly lower than that of metformin. In the subcutaneous glucose
tolerance test, only methanol and hexane extracts showed the similarity of metformin in diabetic rats. After 14 days, the effects of
these extracts were similar to those of metformin (63.33%). The total flavonoid and phenolic contents of extracts decreased as the
polarity of the extraction solvent increased. Conclusions: The results obtained provide support for a possible use of O.
tenuiflorum l eaves in managing hyperglycemia and preventing the complications associated with it in type 2 diabetic.
1. Introduction
Dietary substrates play a key role in physiological mechanisms controlling intermediary metabolism and various abnormalities in
different human diseases, including cardiovascular and other metabolic diseases, hyperlipidemia, thrombosis, hypertension,
and diabetes [ 1]. Diabetes mellitus is caused by several abnormalities in intermediary metabolism, such as dis- arrangements in
carbohydrates, proteins, and fat metabolism resulting from the complete or relatively insufficient insulin secretion and activity [ 2].
Diabetes is categorized into two types: types 1 and 2. Type 1 diabetes is also called insulin- dependent diabetes mellitus. In this
condition, the body does
*Corresponding author: Rabeta Mohd Salleh, Food Technology Division, School of Industrial Technology, Universiti Sains Malaysia, 11800 Minden, Penang,
Malaysia.
not produce insulin; therefore, patients with type 1 diabetes must receive daily insulin injections to remain alive. Type 1 diabetes
also accounts for 5%–10% of diabetes cases. Type 2 diabetes is Tel: +60 04 653 5211, ext. 5211 Fax: +60 04 653 6375 E-mail: rabeta@usm.my All
experimental procedures involving animals were conducted in accordance
also known as non-insulin-dependent diabetes mellitus; in this condition, the body does not produce enough amounts of insulin or
does not properly use this substance. Type 2 diabetes is the with the guidelines for the care and use of laboratory animals, as approved by the
most common type of this disease. In adults, this type of diabetic Animal Ethical Committee, Universiti Sains Malaysia Penang, Malaysia
(USM/Ani- mal Ethics Approval/2013/(89) (479) and Animal Research and Service Center, USM (Main Campus).
accounts for about 90%–95% of all diagnosed. However, 9 out of 10 people of this group don't know that they have pre-diabetes
Foundation Project: Funded by a grant of USM (101/PTEKIND/812176).
[3,4]. Reasons for this rise include the increase in sedentary Peer review under responsibility of Hainan Medical University. The journal implements
double-blind peer review practiced by specially invited international editorial board members.
lifestyle, consumption of energy-rich diet, obesity, higher life span, etc. [5]. Type 2 diabetes is widely distributed in Asia and
Africa, where diabetes mellitus rates increase by 2-fold to 3-foldhigher than the present rates [2]. Synthetic hypoglycemic agents and
insulin can produce serious side effects. They are also inappropriateat 4 C (Toshiba, GR- M48MP, Minato-ku, Japan) until further
for use during pregnancy. As traditional medicine, plants represent aanalysis [14].
valuable alternative to control and treat diabetes mellitus with minimal2.2. Preparation of plant extracts
or no side effects in clinical settings; plants also entail relatively lower
costs than oral synthetic hypoglycemic agents [ 6,7]. According to
The powdered leaves (200 g) were placed in an extraction
ethnobotanical reports, approximately 800 plants may exhibit
chamber and soaked in 800 mL of each of the non-polar and polar
antidiabetic properties [ 8]. As such, many plants have been
solvents for 7 days at room temperature. The solvents were then
recommended to treat diabetes [ 5,6]. The principal chemical compounds
filtered using Whatman No. 1 filter paper [ 15]. The filtrate was
isolated and identified from plants are glycans, proteins, and
concentrated in vacuum in a rotary evaporator (EYELA, N1200B, Ser:
mucilages. Other compounds, such as phenolics, flavonoids, steroids,
triterpenoids, and alkaloids, with hypoglycemic activity, have been1101348) at 30 C. The residue of the plant material from the above
extracted from traditional medicinal plants by using different organicwas dried and re-extracted with next sol- vent using the same
solvents [ 9]. Ocimum sanctum (O. sanctum) as one of the main genusprocedure until the last solvent re-extracted.
of Ocimum (Lamiaceae) is medicinally used to treat diuresis,
cardiopathy, hemopathy, leucoderma, asthma, bronchitis, catarrhal2.3. Chemicals
fever, otalgia, hepatopathy, lumbago, ophthalmia, and gastropathy in
children, as well as gastrointestinal disorders, ringworm, verminosis,
As a standard anti-diabetic drug, metformin (500 mg/kg;
and skin diseases [ 10]. Previous studies indicated that the ®
Glucophage , Lipha Pharma Ltd., United Kingdom) was used as
hydroalcoholic and chloroform extracts of O. sanctum a erial part are
effectively used to treat diabetes. Hydroalcoholic extracts are morepositive control. Streptozotocin (STZ; Sigma–Aldrich Chemical Co.,
potent than chloroform extracts [ 11]. Ocimum tenuif lorum L .USA) was used to induce diabetes. Other chemicals and reagents were
(Lamiaceae) (O. tenuiflorum), called “ruku” in Malaysia, is usuallyof analytical grade and were procured from approved organizations.
cultivated as an ornamental plant because of its yellowish flowers.
In Malaysia, young O. tenuiflorum leaves are used to make2.4. Induction of diabetes
Nasi Ulam. O. tenuiflorum is classified as a herb because of its
medicinal properties [12]. Its leaves contain essential oil with various Diabetes was induced by intraperitoneally injecting 55 mg/kg
compounds exhibiting medicinal values [13]. body weight of STZ (Sigma–Aldrich Chemical Co., USA) recon-
In India, plants are highly sacred because of their numerousstituted in 0.1 mol/L cold citrate buffer (pH 4.5) after the rats were
curative uses [12]. Notwithstanding the usage of this plant, it has notsubjected to fasting overnight. After 3 days of STZ administration,
been attending to make the study of the effects of O. tenuiflorumglucose level was measured in the blood collected from the tail vein
leaves extract by non-polar to polar solvent with antidiabetic potential.punctured by using an Accu-check Advantage II clinical glucose meter
These studies were thus initiated with the aim of evaluating the effect(Roche Diagnostics Co., USA). In this study, the rats with fasting
of n- hexane, chloroform, ethyl ace- tate, and methanol and aqueousblood glucose (FBG) > 15 mmol/L (270 mg/dL) were considered
extracts of O. tenuif lorum leaves on blood glucose level, short-termdiabetic and induced in the study. The percentage change in blood
treatment, sub-chronic toxicity, single oral glucose tolerance test, andglucose was calculated thus:
the toxic effect and measuring the total phenolics and total flavonoids
of different crude extracts. Percentage of glycemic change = (Gx − Gi) /Gx × 100 where
Gx is the
2. Materials and methods glycemia at time x and Gi is the glycemia at initial
time (i).
100806040200
130.26
( t nelaviuqed icac illa 105.36
G98.21
72.47
lorum l eaves extract (n = 3).
otal phenolic content of O. tenuif
Hexane Chloroform Ethyl acetate Methanol Aqueous Figure 1. T
4. Discussion In our study, 1 g/kg of O. tenuiflorum extracts was admin-
istered daily to STZ-induced diabetic rats for 14 days. Body weight
Various in vivo models, such as diazoxide, alloxan, or STZ-and blood glucose were monitored within 14 days of treatment. The
induced diabetic rats, have been traditionally used to evaluatebody weight of the diabetic control rats was lower than that of the
medicinal plants with suspected hypoglycemic potentials. normal control rats. Body weight gain is an indicator of efficient
glucose homeostasis. Other alternative fats and tissue proteins are
In this study, diabetes mellitus was induced by intraperito-
broken down to produce energy ac- counting for the loss in body
neal injection of STZ at single dose of 55 mg/kg body weight in rats.
weight [ 22]. Of the five treatments in our study, the methanol extract
This dose reliably induced diabetes mellitus in the treated rats 7 days
induced a significant recovery in body weight after 7 and 14 days of
post incubation. This result is consistent with that described in
treatment compared with that observed in the diabetic control rats.
previous studies on the treated rats with STZ- induced hyperglycemia
This result indicated improvement in insulin secretion, and control of
5–7 days after intraperitoneal injection [ 20]. Our study demonstrated
glycemic levels [ 14,15,23].
that the minimum hyperglycemic dose was 1 mg/kg body weight of
All of the extracts except the aqueous extract significantly
the rats in all of the extracts. This finding is consistent with that
reduced the blood glucose levels of the diabetic rats 14 days after the
observed in a previous study [ 21]. Using this diabetic model, we
screened serial non- polar to polar O. tenuif lorum extracts totreatment. All of the diabetic rats treated with the hexane extract died 1
day before sacrificed date on Day 13. By contrast, the normal rats
determine their hy- poglycemic and anti-hyperglycemic effects. The
treated with the same dose of the hexane extract survived until the last
glucose- lowering test in normal rats aimed to evaluate the tendency of
day of treatment. In additional result, the body weight of rats showed
an extract/drug to produce hypoglycemia or side effects of some
reduction be- tween 7 and 14 days after treatment.
anti-diabetic drugs. The glucose-lowering test in diabetic rats aimed to
examine the anti-diabetic property of an extract/ drug. In this study, O. However, among the extracts, the methanol extract induced the highest
tenuiflorum extracts did not signifi- cantly affect FBG at an acute decrease on blood glucose level at Days 7 (53.14%) and 14 (64.20%).
dose of 1 g/kg until 2 h; after 7 h, these extracts significantly decreased This decrease was almost greater than that induced by metformin. The
FBG (P < 0.0001). This feature is desirable because hypoglycemia, a polarity of methanol is 5.1 compared with that of other solvents
side effect of most oral hypoglycemic agents, can lead to seizures and characterized by moderate polarity. Therefore, regarding this result it
even death; in other cases, hypoglycemia induces permanent brain is expected that the extracts with a moderate concentration of active
damage. The response to acute dose of glucose of the diabetic rats compounds elicit anti- hyperglycemic effects compared with high and
indicated that all of the five extracts of O. tenuif lorum d ecreased low polarity concentration of active compound that extracted by other
FBG at some points within 7 h. The methanol extract induced sol- vents. The present study also supports most of previous reports
reduction of FBG until 7 h to a greater extent than metformin did. This that polar leaves extract can decrease blood glucose level [ 22,24].
finding suggested that the methanol extract combination may be used Phenolic compounds, such as flavonoids, phenolic acids, and tannins
to isolate the active anti-diabetic compound in O. tenuif lorum. are considered as major contributors to the antioxidant ca- pacity of
Therefore, the methanol extract could be considered as a good plant foods. These antioxidants also exhibit diverse bio- logical
candidate to develop novel anti-diabetic natural products or activities. It seems that these activities are related to their antioxidant
standardized herbal formulation. O. tenuif lorum e xtracts were also activity and a-amylase and a-glucosidase inhibitory activity. S olanum
evaluated to determine the influence on the tolerance level of xanthocarpum, O. sanctum, and Acacia pennata c an be used in the
parenteral glucose administration in non-diabetic and diabetic rats. In dietary management of type 2 diabetes mellitus because of high
this model, glucose loading was administered subcutaneously rather contents of polyphenolics like, caffeic acid and p- coumaric acid [25,26].
than orally to prevent the possibility of a false positive response that Polyphenolic compounds, especially flavonoids, are widely
could result from delayed glucose absorption because of its interaction investigated because of their anti-diabetic properties [ 27]. Flavonoids
with sticky or waxy components and various extracts, especially are natural polyphenolic molecules from plants known for their
hexane and chloroform extracts. However, the extracts except hexane antioxidant, anti-inflammatory, and anti-carcinogenic properties [ 28].
significantly retained the same blood glucose level in the normal rats Flavonoids may be included in diets as an effective alternative
within 15–90 min of glucose loading. This effect in SGTT test was treatment for diabetes; these substances may also be administered to
also repli- cated in the STZ-induced diabetic rats. reduce the risk of diabetes [ 29].
Thus, the total phenolic and total flavonoid contents ofacetate extracts but were approximately similar to those of the
different O. tenuiflorum leaf extracts were also evaluated [29].methanol extract. The phenolic and flavonoid contents also increased
Polyphenolic compounds likely stabilize lipid oxidation and participatethe polarity of solvents, and this finding is similar to the observed
in antioxidant activity [ 30]. Polyphenolic compounds also elicitanti-hyperglycemic activity of the extracts. The aqueous extract with a
inhibitory effects on mutagenesis and carcinogenesis in humans; at 1.0high phenolic content and the ethyl acetate extract with high flavonoid
g, these compounds are ingested daily from a diet rich in fruits andcontent elicited an anti- hyperglycemic effect to a less extent than the
vegetables [27]. Owing to previous result, the flavonoids have beenmethanol extract did. Thefluctuation enhanced interaction of hydroxyl
shown to have an important antidiabetic activity and are able to affectand/ or carboxylic groups in polar solvent to promote the dissolution of
the regeneration of pancreatic beta cells in additional phenolicphenolics in the solvent [ 32]. However, the interaction is decreased by
compounds of plants extracts which have been reported to reducethe benzene ring present in the structure, thus restricting the solubility
blood glucose level [31]. Our results also revealed that the phenolic andof phenolic compounds. Plant extracts contain numerous compounds,
flavonoid contents were respectively the highest in aqueous and ethylwhose net observed pharmacological
1036 1034
Leila Mousavi et al./Asian Pac J Trop Biomed 2016; 6(12): 1029–
actions or interaction largely depend on synergistic or antagonistic Sin KK. Processing and consumer acceptance of fruit leather from the
interactions among these compounds [33]. The selective and unfertilised floral parts of jackfruit. J Sci Food Agric 1 997; 75(1): 102-8. [4]
non-predictive interaction of compounds in the methanol extract of O. Guillén A, Granados S, Rivas KE, Estrada O, Echeverri LF, Balcázar N.
tenuiflorum leaves may account for its potent anti-hyperglycemic Antihyperglycemic activity of Eucalyptus tereticornis in insulin-resistant cells
effect rather than the actual phenolic and flavonoid contents. and a nutritional model of diabetic mice. Adv Pharmacol Sci 2015; 2015:
418673. [5] Yajnik CS. The insulin resistance epidemic in India: fetal origins,
The hypoglycemic and anti-hyperglycemic activities of the methanol
later lifestyle, or both. Nut Rev 2 001; 59: 1-9. [6] G
upta RK, Kesari
extract and metformin were similar. This finding may provide insights
AN, Murthy PS, Chandra R, Tandon V, Watal G. Hypoglycemic and
into the anti-diabetic mechanism of the meth- anol extract. Metformin
antidiabetic effect of ethanolic extract of leaves of Annona squamosa L. in
elicits its anti-hyperglycemic effect primarily by inhibiting the increase experimental animals. J Ethnopharmacol 2 005; 99(1): 75-81. [7]
in the rates of hepatic gluconeogenesis and by improving insulin Balamurugan K, Nishanthini A, Mohan VR. Antidiabetic and
sensitivity through the stimulation of peripheral glucose uptake in antihyperlipidaemic activity of ethanol extract of Melastoma malabathricum
skeletal muscles and adipose tissues [ 34]. The methanol extract may Linn. leaf in alloxan induced diabetic rats. Asian Pac J Trop Biomed 2014; 4:
induce its effect via similar mechanisms. However, the rapid S442-8. [8] Patel DK, Kumar R, Laloo D, Hemalatha S. Diabetes mellitus: an
normalization of blood glucose level in the rats treated with the overview on its pharmacological aspects and reported medicinal plants having
methanol extract relative to the control rats suggested the existence of antidiabetic activity. Asian Pac J Trop Biomed 2 012; 2(5): 411-20. [9] Gupta
residual b-cells, which must have been sensitized by compounds, such S, Mediratta PK, Singh S, Sharma KK, Shukla R. Antidia- betic,
antihypercholesterolaemic and antioxidant effect of Ocimum sanctum (Linn)
asflavonoids and phenolics in the extract [35]. Thus, O. tenuiflorum
seed oil. Indian J Exp Biol 2006; 44: 300-4.
must be considered as an excellent candidate for future studies on
[10] Patil R, Patil R, Ahirwar B, Ahirwar D. Isolation and character- ization of
diabetes mellitus. Further compre- hensive pharmacological
anti-diabetic component (bioactivity-guided fraction- ation) from Ocimum
investigations, including active crude extract fractionation and
sanctum L. (Lamiaceae) aerial part. Asian Pac J Trop Med 2011; 4(4): 278-82.
bioactive compound studies, should be performed.[11] Patil RN, Patil R, Ahirwar D. Study of some medicinal plants for
antidiabetic activity in alloxan induced diabetes. Pharmacolo- gyonline 2010; 1:
Conflict of interest statement 53-60. [12] K othari SK, Bhattacharya K, Ramesh S. Essential oil yield and
quality of methyl eugenol rich Ocimum tenuif lorum L .f. (syn. O. sanctum L.)
grown in south India as influenced by method of harvest. J Chromatogr A 2004;
We declare that we have no conflict of interest.
1054(1–2 ): 67-72. [13] Rai V, Vajpayee P, Singh SN, Mehrotra S. Effect of
chromium accumulation on photosynthetic pigments, oxidative stress defense
Acknowledgments system, nitrate reduction, proline level and eugenol content of Ocimum
lorum L
tenuif . Plant Sci 2004; 167(5): 1159-69. [14] Nabi SA, Kasetti RB,
This work was funded by a grant of USM (101/PTEKIND/ Sirasanagandla S, Tilak TK, Kumar MVJ, Rao CA. Antidiabetic and
812176). The financial support of PhD fellowship from USM for antihyperlipidemic activity of Piper longum r oot aqueous extract in STZ
induced diabetic rats. BMC Complement Altern Med 2013; 13: 37. [15] Kumar
author Leila Mousavi was gratefully acknowledged.
R, Pate DK, Prasad SK, Sairam K, Hemalatha S. Antidia- betic activity of
alcoholic leaves extract of Alangium lamarckii Thwaites on
References streptozotocin-nicotinamide induced type 2 diabetic rats. Asian Pac J Trop Med
2011; 4(11): 904-9. [16] Shirwaikar A, Rajendran K, Barik R. Effect of aqueous
bark extract of Garuga pinnata Roxb. in streptozotocin-nicotinamide induced
[1] Banerjee SK, Maulik SK. Effect of garlic on cardiovascular dis-
type-II diabetes mellitus. J Ethnopharmacol 2006; 107(2): 285-90. [17]
orders: a review. Nutr J 2002; 1: 4. [2] American Diabetes Eknayake S, Jansz ER, Nair BM. Proximate composition, mineral and amino
Association. Diagnosis and classification of
acid content of mature Canavalia gladiata seeds. Food Chem 1 999; 66(1):
diabetes mellitus. Diabetes Care 2 012; 35: S64-71. [3] Man YBC, 115-9. [18] M oreno DA, Carvajal M, L opez-Berenguer C, García-Viguera C.
́
Chemical and biological characterisation of nutraceutical com- pounds of 37-43. [24] A lgariri K, Atangwho IJ, Meng KY, Asmawi MZ, Sadikun A,
broccoli. J Pharm Biomed Anal 2006; 41: 1508-22. [19] G ursoy N, Sarikurkcu Murugaiyah V. Antihyperglycaemic and toxicological evaluations of extract
C, Cengiz M, Solak MH. Antioxidant ac- tivities, metal contents, total and fractions of Gynura procumbens leaves. Trop Life Sci Res 2 014; 25: 75-93.
phenolics and flavonoids of seven Morchella species. F ood Chem Toxicol 2009;[25] O rhan N, Aslan M, S ̈uk ̈uro ̆glu M, Deliorman Orhan D. In vivo a nd
47(9): 2381-8. [20] Junod A, Lambert AE, Stauffacher W, Renold AE. in vitroa ntidiabetic effect of Cistus laurifolius L. and detection of major
Diabetogenic action of streptozotocin: relationship of dose to metabolic phenolic compounds by UPLC-TOF-MS analysis. J Ethnopharmacol 2 013;
response. J Clin Invest 1969; 48(11): 2129-39. [21] Khan MRI, Islam MA, 146: 859-65. [26] C hung KT, Wong TY, Wei CI, Huang YW, Lin Y. Tannins
Hossain MS, Asadujjaman M, Wahed MII, Rahman BM, et al. Antidiabetic and human health: a review. Crit Rev Food Sci Nutr 1 998; 38(6): 421-64. [27]
effects of the different fractions of ethanolic extracts of Ocimum sanctum in Coman C, Rugina OD, Socaciu C. Plants and natural compounds with
normal and alloxan induced diabetic rats. J Sci Res 2010; 2(1): 158-68. [22] antidiabetic action. Not Bot Horti Agrobot 2 012; 40(1): 314-25. [28] Khan RA,
Atangwho IJ, Ebong PE, Eyong EU, Asmawi MZ, Ahmad M. Synergistic Khan MR, Sahreen S, Ahmed M. Evaluation of phenolic contents and
antidiabetic activity of Vernonia amygdalina a nd Azadirachta indica: antioxidant activity of various solvent extracts of Sonchus asper (L.) Hill. Chem
biochemical effects and possible mechanism. J Ethnopharmacol 2 012; 141(3): Cent J 2 012; 6(1): 12. [29] P inent M, Castell A, Baiges I, Montagut G, Arola L,
878-87. [23] Pandhare RB, Sangameswaran B, Mohite PB, Khanage SG. Ardévol A. Bioactivity of flavonoids on insulin-secreting cells. Compr Rev
Antidiabetic activity of aqueous leaves extract of Sesbania sesban ( L) Merr. in Food Sci Food Saf 2008; 7: 299-308.
streptozotocin induced diabetic rats. Avicenna J Med Biotechnol 2011; 3(1):
1036 1035
Leila Mousavi et al./Asian Pac J Trop Biomed 2016; 6(12): 1029–
[30] Kelm MA, Nair MG, Strasburg GM, DeWitt DL. Antioxidant and versus single compounds for the treatment of malaria: synergy and positive
cyclooxygenase inhibitory phenolic compounds from Ocimum sanctum Linn. interactions. Malar J 2 011; 10: S4. [34] Hui H, Tang G, Go VL. Hypoglycemic
Phytomedicine 2000; 7(1): 7-13. [31] Shewamene Z, Abdelwuhab M, Birhanu herbs and their action
Z. Methanolic leaf exctract of Otostegia integrifolia Benth reduces blood mechanisms. Chin Med 2009; 4: 11. [35] Islam MA, Akhtar MA,
glucose levels in diabetic, glucose loaded and normal rodents. BMC Islam MR, Hossain MS, Alam MK, Wahed MI, et al. Antidiabetic and
Complement Altern Med 2 015; 15: 19. [32] Mota FL, Queimada AJ, Pinho SP, hypolipidemic effects of different fractions of Catharanthus roseus (Linn.) on
Macedo EA. Aqueous solubility of some natural phenolic compounds. Ind Eng normal and streptozotocin-induced diabetic rats. J Sci Res 2 009; 1(2): 334-44.
Chem Res 2008; 47(15): 5182-9.
[33] Rasoanaivo P, Wright CW, Willcox ML, Gilbert B. Whole plant extracts
1036 1036
Leila Mousavi et al./Asian Pac J Trop Biomed 2016; 6(12): 1029–