INVOLVEMENT OF NITRIC OXIDE IN THE ADAPTOGENIC EFFECT OF BACOPA MONNIERA (BRAHMI)
Abstract
Bacopa monniera (BM) is an Ayurvedic medicine, used for centuries as nootropoic, anxiolytic, antidepressant, analgesic, antipyretic, antiepileptic agent and adaptogen. Adaptogens are drugs that promote non-specific resistance of the body and recognized as useful anti-stress agents. Although, the adaptogenic effect of BM is well documented, its mechanism is still not well defined. Stress is known to increase nitric oxide (NO) level in brain tissues, moreover, BM reported to inhibit iNOS expression in vitro. Hence, the present investigation was designed to evaluate the involvement of NO in adaptogenic effect of BM. Mice were exposed to overnight audiogenic stress from day 1 to 10. Various drugs treatments were given before the exposure on each day. Effects of stress were assessed interms of anxiety by social interaction and depression by forced swim test. Results showed that exposure to audiogenic stress significantly induced anxiety and depression on day 1 and 4, whereas, no difference after day 7 and 10, indicated adaptation to stress. Administration of BM (40 and 80 mg/kg, p.o.) attenuated the effect of audiogenic stress and facilitated the adaptation to stress. L-arginine impaired the adaptation to stress. In addition, concomitant administration of BM and L-NAME or 7-NI produced synergistic effect in audiogenic stress mice. Moreover, BM attenuated the effects of L-arginine. Further, BM administration significantly decreased audiogenic stress-induced increased NOx levels in cortex, hypothalamus and hippocampus. Thus, BM has significant adaptogenic activity and this effect is probably medicated through nitrergic system.
Keywords:
Audiogenic stress, anxiety, depression, adaptation to stressDOI
https://doi.org/10.25004/IJPSDR.2014.060408References
2. Lazarev NV. 7th All-union Congress of Physiology, Biochemistry, Pharmacology. Medgiz, Moscow, 1947, pp. 579.
3. Rege NN, Thatte UM, Dhanukar SA. Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine. Phytother Res. 1999; 13:275– 91.
4. Singh HK, Dhawan BN. Neuropsychopharmacological effects of the Ayurvedic nootropic Bacopa monniera Linn. (Brahmi). Indian J Pharmacol. 1997; 29:359–65.
5. Bhattacharya SK, Ghosal S. Anxiolytic activity of a standardized extract of Bacopa monniera: an experimental study. Phytomedicine 1998; 5:77–82.
6. Bhattacharya SK, Kumar A, Ghosal S. Effect of Bacopa monniera on animal models of alzheimer’s disease and perturbed central cholinergic markers of cognition in rats. Research Communications in Pharmacology and Toxicology 1999; 4:II1–II12.
7. Sairam K, Dorababu M, Goel RK, Bhattacharya SK. Antidepressant activity of standardized extract of Bacopa monniera in experimental models of depression in rats. Phytomedicine 2002; 9:207–211, 3.
8. Das A, Shanker G, Nath C, Pal R, Singh S, Singh H. A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba. Pharmacology Biochemistry Behaviour 2002; 73:893–900.
9. Russo A, Borrelli F. Bacopa monniera, a reputed nootropic plant: an overview. Phytomedicine 2005; 12:305–17.
10. Rai D, Bhatia G, Palit G, Pal R, Singh S, Singh HK. Adaptogenic effect of Bacopa monniera (Brahmi). Pharmacol Biochem Behav. 2003; 75(4):823-30.
11. Sheikh N, Ahmad A, Siripurapu KB, Kuchibhotla VK, Singh S, Palit G. Effect of Bacopa monniera on stress induced changes in plasma corticosterone and brain monoamines in rats. J Ethnopharmacol. 2007; 111(3):671-6. Epub 2007 Jan 30.
12. Pandareesh MD, Anand T. Neuroprotective and anti-apoptotic propensity of Bacopa monniera extract against sodium nitroprusside induced activation of iNOS, heat shock proteins and apoptotic markers in PC12 cells. Neurochem Res. 2014; 39(5):800-14.
13. Elliott GR, Eisdorfer C. Stress and human health. New York: Springer Publishing; 1982.
14. Madrigal JL, Moro MA, Lizasoain I, Lorenzo P, Castrillo A, Bosca L, et al. Inducible nitric oxide synthase expression in brain cortex after acute restraint stress is regulated by nuclear factor kappa B-mediated mechanisms. J Neurochem 2001; 76(2):532–8.
15. Gądek-Michalska A, Tadeusz J, Rachwalska P, Spyrka J, Bugajski J. Effect of repeated restraint on homotypic stress-induced nitric oxide synthases expression in brain structures regulating HPA axis. Pharmacol Rep. 2012; 64(6):1381-90.
16. Wegener G, Volke V, Harvey BH, Rosenberg R. Local, but not systemic, administration of serotonergic antidepressants decreases hippocampal nitric oxide synthase activity. Brain Research 2003; 959:128–134.
17. Salunke BP, Umathe SN, Chavan JG. Experimental evidence for involvement of nitric oxide in low frequency magnetic field induced obsessive compulsive disorder-like behavior. Pharmacol Biochem Behav. 2014; 122:273-8.
18. Rivier C. Endogenous nitric oxide participates in the activation of the hypothalamic–pituitary–adrenal axis by noxious stimuli, Endocrine J. 2 1994; 367–373.
19. Sembulingam K, Sembulingam P, Namasivayam A. Effect of Ocimum sanctum Linn on noise induced changes in plasma corticosterone. Indian Journal of Physiology and Pharmacology 1997; 41:139–143.
20. Archana R, Namasivayam A. Antistressor effect of Withania somnifera. J Ethnopharmacol. 1999; 64(1):91-3.
21. Umathe SN, Bhutada PS, Jain NS, Shukla NR, Mundhada YR, Dixit PV. Gonadotropin releasing hormone agonist blocks anxiogenic-like and depressant-like effect of corticotrophin-releasing hormone in mice. Neuropeptides 2008; 42:399–410.
22. Glowinski J, Iversen LL. Regional studies of catecholamines in the rat brain-I. J Neurochem. 1966; 13:655-669.
23. Konsman JP. The mouse brain in stereotaxic coordinates: Second Edition (Deluxe) By Paxinos G and Franklin KBJ, Academic Press, New York, 2001, ISBN 0-12-547637-X. Psychoneuroendocrinology. 2003; 28:827-828.
24. Sastry KV, Moudgal RP, Mohan J, Tyagi JS, Rao GS. Spectrophotometric determination of serum nitrite and nitrate by copper-cadmium alloy. Anal Biochem. 2002; 306(1):79-82.
25. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J. Biol. Chem. 1951; 193: 265– 275.
26. Chrousos GP, Gold PW. The concepts of stress and stress system disorders, overview of physical and behavioral homeostasis. JAMA 1992; 267: 1244– 52.
27. Smith M. Hippocampal vulnerability to stress and aging: possible role of neutrophic factors. Behav Brain Res. 1996; 78:25–36.
28. Ueyama T, Kawai Y, Nemoto K, Sekimoto M, Tone S, Senba E. Immobilization stress reduced the expression of neurotrophins and their receptors in the rat brain. Neurosci Res. 1997; 28:103– 10.
29. Fujino K, Yoshitake T, Inoue O, Ibii N, Kehr J, Ishida J, Nohta H, Yamaguchi M. Increased serotonin release in mice frontal cortex and hippocampus induced by acute physiological stressors. Neuroscience Letters 2002; 320:91–95.
30. Gulati K, Chakraborti A, Ray A. Differential role of nitric oxide (NO) in acute and chronic stress induced neurobehavioral modulation and oxidative injury in rats. Pharmacol Biochem Behav. 2009; 92:272–276.
31. Joca SR, Guimaraes FS. Inhibition of neuronal nitric oxide synthase in the rat hippocampus induces antidepressant-like effects. Psychopharmacology 2006; 185: 298–305.
32. Kiss JP. Role of nitric oxide in the regulation of monoaminergic neurotransmission. Brain Res Bull. 2000; 52: 459-466.
33. Lafuente A, Gonzalez-Carracedo A, Romero A, Cano P, Esquifino AI. Effect of nitric oxide on prolactin secretion and hypothalamic biogenic amine contents. Life Sci. 2004; 74: 1681-1690.
34. Stern JE. Nitric oxide and homeostatic control: an intracellular signaling molecule contributing to autonomic and neuroendocrine integration? Prog Biophys Mol Biol. 2004; 84: 197-215.
35. Prevot V, Bouret S, Stefano GB, Beauvillain J. Median eminence nitric oxide signaling. Brain Res Brain Res Rev. 2000; 34: 27-41.
36. Wei T, Chen C, Hou J, Xin W, Mori A. Nitric oxide induces oxidative stress and apoptosis in neuronal cells. Biochim Biophys Acta. 2000; 1498(1):72-9.
37. Xiong H, Yamada K, Han D, Nabeshima T, Enikolopov G, Carnahan J, Nawa H. Mutual regulation between the intercellular messengers nitric oxide and brain-derived neurotrophic factor in rodent neocortical neurons. Eur J Neurosci. 1999; 11(5):1567-76.
38. Dimmeler S, Hermann C, Galle J, Zeiher AM. Upregulation of superoxide dismutase and nitric oxide synthase mediates the apoptosis-suppressive effects of shear stress on endothelial cells. Arterioscler Thromb Vasc Biol. 1999; 19(3):656-64.
39. Trevor AJ, Way WL. Sedative–hypnotic drugs. In: Katzung BG, editor. Basic and clinical pharmacology. New York: Lange Medical; 2001, pp. 364– 81.
Published

