Effects of Adhatoda vasica leaf extract in depression co‑morbid with alloxan‑induced diabetes in mice

Deepali Gupta, Mahesh Radhakrishnan, Yeshwant Kurhe


Context: Increased neuronal oxidative stress as a consequence of diabetes may result in neuropsychological complications such as depression. Depression co‑morbid with diabetes further hampers the quality life years in diabetic patients. Aim: Thus, the present study was aimed at investigating the effects of Adhatoda vasica leaf extract (EAV), as a natural remedy, in alloxan‑induced diabetes and co‑morbid depression in mice. Materials and Methods: Experimentally, mice were rendered diabetic with a single dose of alloxan of 200 mg/kg, intraperitoneally (i.p.). After 3 weeks of having chronic diabetic state, mice were given EAV (100-400 mg/kg, orally)/
vehicle/standard control (escitalopram, ESC; 10 mg/kg, orally) for 7 days. After dosing, anti‑diabetic effect was detected by the fasted blood glucose levels and anti‑depressant effect was evaluated by behavioural despair tests, followed by monoamine oxidase (MAO) activity and oxidative stress analysis. Results and Discussion: EAV treatment effectively reduced the elevated blood glucose levels and reversed co‑morbid depressive behaviour. Furthermore, EAV inhibited diabetes induced increased oxidative stress and MAO activity in the brain. Thus, EAV demonstrated the potential protective action against oxidative stress and revealed monoamine modulatory activity in the brain, which may contribute to its anti‑depressant effect. Conclusion: This work demonstrates the efficacious effect of EAV in reversing the depression co‑morbid with alloxan‑induced diabetes in mice.
Key words: Adhatoda vasica, co‑morbid depression, diabetes, forced swim test, monoamine oxidase activity, oxidative stress

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Egede LE, Zheng D, Simpson K. Comorbid depression is associated

with increased health care use and expenditures in individuals

with diabetes. Diabetes Care 2002;25:464‑70.

Lustman PJ, Anderson RJ, Freedland KE, de Groot M, Carney RM,

Clouse RE. Depression and poor glycemic control: A meta‑analytic

review of the literature. Diabetes Care 2000;23:934‑42.

Hamdy NM, Taha RA. Effects of Nigella sativa oil and thymoquinone

on oxidative stress and neuropathy in streptozotocin‑induced

diabetic rats. Pharmacology 2009;84:127‑34.

Fernyhough P, Roy Chowdhury SK, Schmidt RE. Mitochondrial

stress and the pathogenesis of diabetic neuropathy. Expert Rev

Endocrinol Metab 2010;5:39‑49.

Miller AH, Maletic V, Raison CL. Inflammation and its discontents:

The role of cytokines in the pathophysiology of major depression.

Biol Psychiatry 2009;65:732‑41.

Lenzen S. The mechanisms of alloxan and streptozotocin induced

diabetes. Diabetologia 2008;51:216‑26.

Ceretta LB, Reus GZ, Stringari RB, Ribeiro KF, Zappellini G, Aguiar BW,

et al. Imipramine treatment reverses depressive‐like behavior in

alloxan‐diabetic rats. Diabetes Metab Res Rev 2012;28:139‑44.

Volchegorskii IA, Rassokhina LM, Miroshnichenko I.

Antidepressant action of emoxipin and mexidol in mice with

alloxan diabetes. Eksp Klin Farmakol 2009;72:11‑5.

Kumar P, Kale RK, Baouer NZ. Antihyperglycemic and protective

effects of Trigonella foenum graecum seed powder on biochemical

alterations in alloxan diabetic rats. Eur Rev Med Pharmacol Sci


Volchegorskii IA, Tseilikman VE, Ship SA, Bubnov NV, Sinitskii AI.

The effects of anxiogenic stress on glucocorticoid sensitivity,

glucose tolerance, and alloxan resistance in rats. Neurosci Behav

Physiol 2003;33:595‑9.

Ceretta LB, Reus GZ, Abelaira HM, Ribeiro KF, Zappellini G,

Felisbino FF, et al. Increased oxidative stress and imbalance in

antioxidant enzymes in the brains of alloxan‑induced diabetic

rats. Exp Diabetes Res 2012;2012:302682.

Siddiqui MR, Taha A, Moorthy K, Hussain ME, Basir SF,

Baquer NZ. Amelioration of altered antioxidant status and

membrane linked functions by vanadium and Trigonella in alloxan

diabetic rat brains. J Biosci 2005;30:483‑90.

Claeson UP, Malmfors T, Wikman G, Bruhn JG. Adhatoda vasica:

A critical review of ethnopharmacological and toxicological data.

J Ethnopharmacol 2000;72:721‑20.

Jagetia GC, Rao SK, Baliga MS, Babu KS. The evaluation of nitric

oxide scavenging activity of certain herbal formulations in vitro:

A preliminary study. Phytother Res 2004;18:561‑5.

Gacche RN, Dhole NA. Aldose reductase inhibitory, anti‑cataract

and antioxidant potential of selected medicinal plants from the

Marathwada region, India. Nat Prod Res 2011;25:760‑3.

Srivastava S, Verma RK, Gupta MM, Singh SC, Kumar S. HPLC

determination of vasicine and vasicinone in Adhatoda vasica with

photo diode array detection. J Liq Chromatogr Relat Technol


Kennedy DO, Veasey R, Watson A, Dodd F, Jones E, Maggini S,

et al. Effects of high‑dose B vitamin complex with vitamin C and

minerals on subjective mood and performance in healthy males.

Psychopharmacology 2010;211:55‑68.

Kumar A, Ram J, Samarth RM, Kumar M. Modulatory influence

of Adhatoda vasica Nees leaf extract against gamma irradiation in

Swiss albino mice. Phytomedicine 2005;12:285‑93.

N a z ı r o g l u M , K o z l u S , Yo r g a n c ı g i l E , U g u z A C ,

Karakus K. Rose oil (from Rosax damascena Mill.) vapor attenuates

depression‑induced oxidative toxicity in rat brain. J Nat Med


Payne ME, Steck SE, George RR, Steffens DC. Fruit, vegetable,

and antioxidant intakes are lower in older adults with depression.

J Acad Nutr Diet 2012;112:2022‑7.

Gulfraz M, Ahmed A, Asad MJ, Sadiq A, Afzal U, Anwar P.

Antidiabetic activities of leaves and root extracts of Justica adhatoda

Linn. against alloxan induced diabetes in rats. Afr J Biotechnol


Yadav AK, Tangpu V. Anticestodal activity of Adhatoda vasica extract

against Hymenolepis diminuta infections in rats. J Ethnopharmacol


OECD. Acute oral toxicity‑Modified up and down procedure,

OECD Guidelines 425. Paris: Organization for Economic

Co‑operation and Development; 1985.

Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: A primary

screening test for antidepressants. Arch Int Pharmacodyn Ther


Steru L, Chermat R, Thierry B, Simon P. The tail suspension

test: A new method for screening antidepressant drugs.

Psychopharmacolgy (Berl) 1985;85:367‑70.

Boissier JR, Simon P. Action of caffeine on the spontaneous motility

of the mouse. Arch Int Pharmacodyn Ther 1965;158:212‑21.

Schurr A, Livne A. Differential inhibition of mitochondrial

monoamine oxidase from brain by hashish components. Biochem

Pharmacol 1976;25:1201‑3.

Wills ED. Mechanism of lipid peroxide formation in animal tissues.

Biochem J 1966;99:667‑76.

Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS,

Tannenbaum SR. Analysis of nitrate, nitrite, and [15N] nitrate in

biological fluids. Anal Biochem 1982;126:131‑8.

Claiborne A. Catalase activity. In: Greenwald RA, editor. Handbook

of Methods for Oxygen Radical Research. Boca Raton: CRC press;

p. 283 ‑284.

Park CR. Cognitive effects of insulin in the central nervous system.

Neurosci Biobehav R 2001;25:311‑23.

Sima AA, Kamiya H, Li ZG. Insulin, C‑peptide, hyperglycemia, and

central nervous system complications in diabetes. Eur J Pharmacol


Patil MY, Vadivelan R, Dhanabal SP, Satishkumar MN, Elango K,

Antony S. Anti‑oxidant, anti‑inflammatory and anti‑cholinergic

action of Adhatoda vasica Nees contributes to amelioration of

diabetic encephalopathy in rats: Behavioral and biochemical

evidences. Int J Diabetes Dev Ctries 2013:1‑8.

Modak AT, Rao MR. Hypoglycemic activity of a non‑nitrogenous

principle from the leaves of Adhatoda vasica Nees. Indian J Pharm


Gao H, Huang YN, Gao B, Li P, Inagaki C, Kawabata J. Inhibitory

effect on α‑glucosidase by Adhatoda vasica Nees. Food Chem


Castagne V, Moser P, Roux S, Porsolt RD. Rodent models of

depression: Forced swim and tail suspension behavioral despair

tests in rats and mice. Curr Protoc Neurosci 2011;55:11‑8.

Kamei J, Miyata S, Morita K, Saitoh A, Takeda H. Effects of

selective serotonin reuptake inhibitors on immobility time in

the tail suspension test in streptozotocin‑induced diabetic mice.

Pharmacol Biochem Behav 2003;75:247‑54.

Cryan JF, Page ME, Lucki I. Differential behavioral effects of

the antidepressants reboxetine, fluoxetine, and moclobemide

in a modified forced swim test following chronic treatment.

Psychopharmacology (Berl) 2005;182:335‑44.

Sacher J, Wilson AA, Houle S, Rusjan P, Hassan S, Bloomfield PM,

et al. Elevated brain monoamine oxidase A binding in the early

postpartum period. Arch Gen Psychiatry 2010;67:468‑74.

Tuzcu M, Baydas G. Effect of melatonin and vitamin E on

diabetes‑induced learning and memory impairment in rats. Eur J

Pharmacol 2006;537:106‑10.

Landar A, Zmijewski JW, Dickinson DA, Le Goffe C, Johnson MS,

Milne GL, et al. Interaction of electrophilic lipid oxidation

products with mitochondria in endothelial cells and formation

of reactive oxygen species. Am J Physiol Heart Circ Physiol


Szabo C, Ischiropoulos H, Radi R. Peroxynitrite: Biochemistry,

pathophysiology and development of therapeutics. Nat Rev Drug

Discov 2007;6:662‑80.

DOI: http://dx.doi.org/10.22377/ijgp.v8i2.369


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