Improved Insulin Resistance through Cajanus cajan extract in Gestational Diabetes Mellitus of Wistar Rat

Author(s): Nikita Saraswat*, Pranay Wal, Ankita Wal, Rashmi Saxena Pal.

Journal Name: Current Women`s Health Reviews

Volume 15 , Issue 4 , 2019

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Abstract:

Background: Gestational Diabetes Mellitus (GDM) has a serious impact on maternal health as well as on the health of the infant. This is also very closely related to adverse outcomes in pregnancy. A mother suffering from gestational diabetes mellitus (GDM) has high incidences of showing significant risks to the fetus health, growth and development. As the incidences of GDM are increasing day by day, therefore, maternal health, age and obesity parameters are of major concern for reflecting GDM during their pregnancy conditions. It has been studied and investigated that IR (Insulin Resistance) is a common pathway in GDM and T2DM (Type 2 Diabetes Mellitus).

Objective: To explore the effect of Cajanus cajan in treating gestational diabetes mellitus (GDM) in Wistar rats.

Methods: The study was conducted on 30 female rats which were caged along with male rats. We obtained 26 pregnant rats which were weighed. The pregnant rats in the control group, intervention group, and GDM group were equally randomized. When the pregnancy was verified, the Intervention and the GDM (Gestational Diabetes Mellitus) group were given 45 mg/kg streptozotocin by the peritoneal injection for inducing GDM while the control group was given an equal volume of the citrate buffer. When the model was established accurately then the intervention group was administered orally with the extracts of leaves of Cajanus cajan chloroform extract (270mg/kg), Methanol extract (270mg/kg) and Ethyl acetate extract (270mg/kg). Whereas the other groups were administered with water and diet. The blood samples were collected and the fetal rats along with placental weight were recorded on the 19th day of the pregnancy. The serum glucose levels, serum insulin levels, and lipid levels were recorded in pregnant rats before the delivery.

Results: The rats were weighed before and after delivery, fetal weight was recorded, placental weight of the GDM group was found to be lower than the control group as well as the intervention groups. Treating with (Chloroform extract, Methanol extract, Ethyl acetate extract (270mg/kg) different extracts of Cajanus cajan leaf in the intervention groups the lipid levels of the intervention group significantly increased in case of the Methanolic extract whereas the other extracts were also effective. The levels of antioxidant enzymes of the GDM group in pancreas and liver tissue were lower in intervention groups as compared to control and GDM group whereas the antioxidant enzyme levels in the liver and pancreas were equivalent to the control group.

The results showed that the ethyl acetate and methanol extracts of the Cajanus cajan leaves might have bioactive and hypoglycemic nature. Further research is required for the complete evaluation of the active compound in various animal models to justify the nature of the compound.

Conclusion: Cajanus cajan leaf extract suppresses oxidative stress and insulin resistance, therefore, improves the blood glucose levels in GDM rats.

Keywords: Gestation diabetes mellitus (GDM), postnatal care, insulin, fetal macrosomia, diabetes mellitus, GDM treatment, adverse pregnancy outcomes.

[1]
Lee AJ, Hiscock RJ, Wein P, Walker SP, Permezel M. Gestational diabetes mellitus: Clinical predictors and long-term risk of developing type 2 diabetes: A retrospective cohort study using survival analysis. Diabetes Care 2007; 30(4): 878-83.
[2]
Lappsa M. GSK3β is increased in adipose tissue and skeletal muscle from women with gestational diabetes where it regulates the inflammatory response. PLoS One 2014; 9(12)e115854
[3]
Committee on Practice Bulletins--Obstetrics. Practice Bulletin No. 137: Gestational diabetes mellitus. Obstet Gynecol 2013; 122(2): 406-16.
[4]
Ferrara A. Increasing prevalence of gestational diabetes mellitus: A public health perspective. Diabetes Care 2007; 30(Suppl. 2): S141-6.
[5]
Catalano PM, Nizielski SE, Shao J, Preston L, Qiao L, Friedman JE. Downregulated IRS-1 and PPARgamma in obese women with gestational diabetes: Relationship to FFA during pregnancy. Am J Physiol Endocrinol Metab 2002; 282(3): E522-33.
[6]
Colomiere M, Permezel M, Lappas M. Diabetes and obesity during pregnancy after insulin signalling and glucose transporter expression in maternal skeletal muscle and subcutaneous adipose tissue. J Mol Endocrinol 2010; 44(4): 213-23.
[7]
American Diabetes Association. Gestational diabetes mellitus. Diabetes Care 2003; 26(Suppl. 1): S103-5.
[8]
NICE Guideline Diabetes and pregnancy: management of diabetes and its complications from preconception to the postnatal period 2015. Available from. http://www.nice.org.uk/guidance/ng3/ resources/diabetes-in-pregnancy-management-of-diabetes-and-its-complications-from-preconception-to-the-postnatal-period-51038446021 (Accessed on: Nov 10, 2018).
[9]
International Diabetes Federation Global guideline on pregnancy and diabetes. Available from. http://www.idf.org/webdata/docs/ Pregnancy_EN_RTP.pdf. (Accessed on: Nov 10, 2018).
[10]
Rahman AU, Zaman K. Medicinal plants with hypoglycemic activity. J Ethnopharmacol 1989; 26(1): 1-55.
[11]
Marles RJ, Farnsworth NR. Antidiabetic plants and their active constituents. Phytomedicine 1995; 2(2): 137-89.
[12]
Pal RS, Pal Y, Wal P. A review on post pregnancy healer herbs. Curr Womens Health Rev 2019; 15(2): 102-8.
[13]
Kesari AN, Gupta RK, Watal G. Hypoglycemic effect of the Murraya koenigii on normal and alloxan diabetic rabbits. J Ethnopharmacol 2005; 97(2): 247-51.
[14]
Gupta RK, Kesari AN, Murthy PS, Chandra R, Tandon V, Watal G. Hypoglycemic and antidiabetic effect of ethanolic extract of leaves of Annona squamosa L. experimental animals. J Ethnopharmacol 2005; 99(1): 75-81.
[15]
Kesari AN, Gupta RK, Singh SK, Diwakar S, Watal G. Hypoglycemic and antihyperglycemic activity of Aegle marmelos seeds extract in normal and diabetic rats. J Ethnopharmacol 2006; 107(3): 374-9.
[16]
Kirtikar KR, Basu BD. Indian Medicinal Plants Dehradun Periodical, Bishen Singh Mahendra Pal Singh: Vol-I. 2nd ed. Periodical Experts Book Agency London 1981; pp. 809-11.
[17]
Kanjilal UN, Das PC. Flora of Assam, Printed at Jay Offset Press, Delhi-6. Vol. II, 1982; pp. 97-98.
[18]
Chadha YR. The Wealth of India, Publication and Information Directorate CSIR: New Delhi, 1976, vol II: 18pp. Available from http://www.niscair.res.in/activitiesandservices/products/wealth-of-indiaFolder2010.pdf (Accessed on: Nov 10, 2018).
[19]
Pulse crops of India, 14; Handbook of agriculture: Indian Council of Agricultural Research, pp. 855
[20]
Abbiw DK. Useful Plants of Ghana; Richmond Intermediate Technology Publications and Royal Botanic Gardens. Kew, London, UK 1990; pp. S154-7.
[21]
Duke JA, Vasquez R. Amazonian Ethnobotanical Dictionary. CRC Press Boca Raton, FL, USA 1994.
[22]
Amalraj T, Ignacimuthu S. Evaluation of the hypoglycaemic effect of Cajanus cajan (seeds) in mice. Indian J Exp Biol 1998; 36: 1032-3.
[23]
Grover JK, Yadav S, Vats VJ. Medicinal plants of India with antidiabetic potential. J Ethnopharmacol 2002; 81(1): 81-100.
[24]
Tang Y, Wang B, Zhou XJ. Effect of external application of herbal cajani preparation on the fibronection content during healing process of open wound. J Guangzhou Univ Tradit Chin Med 1999; 16(1): 302-4.
[25]
Chen DSH, Li HY, Lin H. Studies on chemical constituents in pigeonpea leaves. Chin Tradit Herbal Drugs 1985; 16: 134-6.
[26]
Li ZH, Zhou CH, Gu Y, et al. The present status of study and utilization of pigeon pea in China and its prospects. For Res 2001; 14: 674-81.
[27]
Luo QF, Sun L, Chen DH. Hypocholesterolemic effect of stilbenes containing extract-fraction from Cajanus cajan L. on diet-induced hypercholesterolemia in mice. Phytomedicine 2008; 15(11): 932-9.
[28]
Huang GY, Liao XZ, Liao HF, et al. Studies on water-soluble extracts from Cajanus cajan leaf against hypoxic-ischemic brain damage. Tradit Chin Drug Res Clin Pharmacol 2006; 17: 172-4.
[29]
Wu N, Fu K, Fu YJ, et al. Antioxidant activities of extracts and main components of pigeon pea [Cajanus cajan (L.) Mill sp.] leaves. Molecules 2009; 14(3): 1032-43.
[30]
Alqasoumi SI. ‘Okra’ Hibiscus esculentas L: A study of its hepatoprotective activity. Saudi Pharm J 2012; 20(2): 135-41.
[31]
Zhou L, An XF, Teng SC, et al. Pretreatment with the total flavone glycosides of Flos Abelmoschus manihot and hyperoside prevents glomerular podocyte apoptosis in streptozotocin-induced diabetic nephropathy. J Med Food 2012; 15(5): 461-8.
[32]
Junod A, Lambert AE, Orci L, Pictet R, Gonet AE, Renold AE. Studies of the diabetogenic action of streptozotocin. Proc Soc Exp Biol Med 1967; 126(1): 201-5.
[33]
Rakieten N, Rakieten ML, Nadkarni MV. Studies on the diabetogenic action of streptozotocin (NSC-37917) cancer. Chemother Rep 1963; 29: 91-8.
[34]
Blondel O, Bailbe D, Portha B. Insulin resistance in rats with non-insulin-dependent diabetes induced by neonatal (5 days) streptozotocin: Evidence for reversal following phlorizin treatment. Metabolism 1990; 39: 787-93.
[35]
Bonner-Weir S, Trent DF, Honey RN, Weir GC. Responses of neonatal rat islets to streptozotocin: Limited B-cell regeneration and hyperglycemia. Diabetes 1981; 30: 64-9.
[36]
Movassat J, Saulnier C, Portha B. Insulin administration enhances growth of the beta-cell mass in streptozotocin-treated newborn rats. Diabetes 1997; 46: 1445-52.
[37]
Portha B, Kergoat M. Dynamics of glucose-induced insulin release during the spontaneous remission of streptozocin diabetes induced in the newborn rat. Diabetes 1985; 34: 574-9.
[38]
Triadou N, Portha B, Picon L, Rosselin G. Experimental chemical diabetes and pregnancy in the rat. Evolution of glucose tolerance and insulin response. Diabetes 1982; 31: 75-9.
[39]
Blondel O, Bailbe D, Portha B. In vivo insulin resistance in streptozotocin-diabetic rats--evidence for reversal following oral vanadate treatment. Diabetologia 1989; 32(3): 185-90.
[40]
El Hilaly J, Lyoussi B. Hypoglycaemic effect of the lyophilised aqueous extract of Ajuga iva in normal and streptozotocin diabetic rats. J Ethnopharmacol 2002; 80(2-3): 109-13.
[41]
Capobianco E, Jawerbaum A, White V, Pustovrh C, Sinner D, Gonzalez ET. Elevated levels of endothelin-1 and prostaglandin E2 and their effect on nitric oxide generation in placental tissue from neonatal streptozotocin-induced diabetic rats. Prostaglandins Leukot Essent Fatty Acids 2003; 68: 225-31.
[42]
Murali B, Goyal RK. Improvement in insulin sensitivity by losartan in non-insulin-dependent diabetic (NIDDM) rats. Pharmacol Res 2001; 44: 385-9.
[43]
Portha B, Levacher C, Picon L, Rosselin G. Diabetogenic effect of streptozotocin in the rat during the perinatal period. Diabetes 1974; 23: 889-95.
[44]
Tsuji K, Taminato T, Usami M, et al. Characteristic features of insulin secretion in the streptozotocin-induced NIDDM rat model. Metabolism 1988; 37: 1040-4.
[45]
Caluwaerts S, Holemans K, van Bree R, Verhaeghe J, Van Assche FA. Is low-dose streptozotocin in rats an adequate model for gestational diabetes mellitus? J Soc Gynecol Investig 2003; 10: 216-21.
[46]
Eriksson U, Dahlstrom E, Larsson KS, Hellerstrom C. Increased incidence of congenital malformations in the offspring of diabetic rats and their prevention by maternal insulin therapy. Diabetes 1982; 31: 1-6.
[47]
Kervran A, Guillaume M, Jost A. The endocrine pancreas of the fetus from diabetic pregnant rat. Diabetologia 1978; 15: 387-93.
[48]
Kinney BA, Rabe MB, Jensen RA, Steger RW. Maternal hyperglycemia leads to gender-dependent deficits in learning and memory in offspring. Exp Biol Med (Maywood) 2003; 228: 152-9.
[49]
Heinze E, Vetter U. Skeletal growth of fetuses from streptozotocin diabetic rat mothers: in vivo and in vitro studies. Diabetologia 1987; 30: 100-3.
[50]
Lopez-Soldado I, Herrera E. Different diabetogenic response to moderate doses of streptozotocin in pregnant rats, and its long-term consequences in the offspring. Exp Diabesity Res 2003; 4: 107-18.
[51]
Merzouk H, Madani S, Boualga A, Prost J, Bouchenak M, Belleville J. Age-related changes in cholesterol metabolism in macrosomic offspring of rats with streptozotocin-induced diabetes. J Lipid Res 2001; 42: 1152-9.
[52]
Merzouk H, Madani S, Chabane Sari D, Prost J, Bouchenak M, Belleville J. Time course of changes in serum glucose, insulin, lipids and tissue lipase activities in macrosomic offspring of rats with streptozotocin-induced diabetes. Clin Sci (Lond) 2000; 98: 21-30.
[53]
Merzouk H, Madani S, Hichami A, Prost J, Belleville J, Khan NA. Age-related changes in fatty acids in obese offspring of streptozotocin-induced diabetic rats. Obes Res 2002; 10: 703-14.
[54]
Mulay S, Philip A, Solomon S. Influence of maternal diabetes on fetal rat development: Alteration of insulin receptors in fetal liver and lung. J Endocrinol 1983; 98: 401-10.
[55]
Oh W, Gelardi NL, Cha CJ. Maternal hyperglycemia in pregnant rats: Its effect on growth and carbohydrate metabolism in the offspring. Metabolism 1988; 37: 1146-51.
[56]
Oh W, Gelardi NL, Cha CJ. The cross-generation effect of neonatal macrosomia in rat pups of streptozotocin-induced diabetes. Pediatr Res 1991; 29: 606-10.
[57]
Plagemann A, Harder T, Janert U, et al. Malformations of hypothalamic nuclei in hyperinsulinemic offspring of rats with gestational diabetes. Dev Neurosci 1999; 21: 58-67.
[58]
Soulimane-Mokhtari NA, Guermouche B, Yessoufou A, et al. Modulation of lipid metabolism by n-3 polyunsaturated fatty acids in gestational diabetic rats and their macrosomic offspring. Clin Sci (Lond) 2005; 109: 287-95.
[59]
Gelardi NL, Cha CJ, Oh W. Glucose metabolism in adipocytes of obese offspring of mild hyperglycemic rats. Pediatr Res 1990; 28(6): 641-5.
[60]
Lorke D. A new approach to practical acute toxicity testing. Arch Toxicol 1983; 53: 275-89.
[61]
Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959; vol. 82, no. 1, pp. 70-77.
[62]
Koroliuk MA, Ivanova LI, Maĭorova IG, Tokarev VE. A method of determining catalase activity. Lab Delo 1988; (1): 16-9.
[63]
Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes 1991; 40(4): 405-12.
[64]
Collier A, Rumley A, Rumley AG, et al. Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria. Diabetes 1992; 41(8): 909-13.
[65]
Jaiswal D, Rai PK, Kumar A, Watal G. Study of glycemic profile of Cajanus cajan leaves in experimental rats. Indian J Clin Biochem 2008; 23(2): 167-70.
[66]
Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 2003; 52(1): 1-8.


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VOLUME: 15
ISSUE: 4
Year: 2019
Page: [257 - 269]
Pages: 13
DOI: 10.2174/1573404815666190128155057
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