Bacopa monniera ameliorates cognitive impairment and neurodegeneration induced by intracerebroventricular-streptozotocin in rat: behavioral, biochemical, immunohistochemical and histopathological evidences
- 442 Downloads
The standardized extract of Bacopa monniera (BM) is a complex mixture of ingredients with a uniquely wide spectrum of neuropharmacological influences upon the central nervous system including enhanced learning and memory with known antioxidant potential and protection of the brain from oxidative damage. The present study demonstrates the therapeutic efficacy of BM on cognitive impairment and oxidative damage, induced by intracerebroventricular injection of streptozotocin (ICV-STZ) in rat models. Male Wistar rats were pre-treated with BM at a selected dose (30 mg/Kg) given orally for 2 weeks and then were injected bilaterally with ICV-STZ (3 mg/Kg), while sham operated rats were received the same volume of vehicle. Behavioral parameters were subsequently monitored 2 weeks after the surgery using the Morris water maze (MWM) navigation task then were sacrificed for biochemical, immunohistochemical (Cu/Zn-SOD) and histopathological assays. ICV-STZ-infused rats showed significant loss in learning and memory ability, which were significantly improved by BM supplementation. A significant increase in thiobarbituric acid reactive species and a significant decrease in reduced glutathione, antioxidant enzymes in the hippocampus were observed in ICV-STZ rats. Moreover, decrease in Cu/Zn-SOD expression positive cells were observed in the hippocampus of ICV-STZ rats. BM supplementation significantly ameliorated all alterations induced by ICV-STZ in rats. The data suggest that ICV-STZ might cause its neurotoxic effects via the production of free radicals. Our study demonstrates that BM is a powerful antioxidant which prevents cognitive impairment, oxidative damage, and morphological changes in the ICV-STZ-infused rats. Thus, BM may have therapeutic value for the treatment of cognitive impairment.
KeywordsBacopa monniera Streptozotocin Oxidative damage Cognitive impairment Morris water maze Antioxidant
We are grateful to the Department of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homeopathy (AYUSH), ministry of health and family welfare, Government of India, for financial assistance. Authors are grateful to Mr. Dharamvir and the late Mr. Anil Kumar for assistance and cooperation and positively acknowledge Ms. Laura Lemley (Medical College of Georgia), for her help in the language preparation of the manuscript.
Conflict of interest
We have no conflict of interest and certify hereby that this work has never been published.
- Ceballos I, Javoy-Agid F, Delacourte A, Defossez A, Lafon M, Hirsch E, Nicole A, Sinet PM, Agid Y (1991) Neuronal localization of copper-zinc superoxide dismutase protein and mRNA within the human hippocampus from control and Alzheimer’s disease brains. Free Radic Res Commun 12–13(Pt 2):571–580PubMedCrossRefGoogle Scholar
- Claiborne A (1985) Catalase activity. In: Greenwald RA (ed) Handbook of methods for oxygen radical research. CRC, Boca Raton, pp 283–284Google Scholar
- Fiske CH, Subbarow Y (1925) The colorimetric determination of phosphorus. J Biol Chem 66:375–400Google Scholar
- Glover V, Sandler M (1993) Neurotoxins and monoamine oxidase B inhibitors: possible mechanisms for the neuroprotective effect of (-) deprenyl. In: Szelenyi I (ed) Inhibitors of monoamine oxidase B, pharmacology and clinical use in neurodegenerative disorders. Birkhauser Verlag, Basel, pp 169–181CrossRefGoogle Scholar
- Halliwell B, Gutteridge JMC (1989) Free radicals in biology and medicine, 2nd edn. Clarendon, OxfordGoogle Scholar
- Jee YS, Ko IG, Sung YH, Lee JW, Kim YS, Kim SE, Kim BK, Seo JH, Shin MS, Lee HH, Cho HJ, Kim CJ (2008) Effects of treadmill exercise on memory and c-Fos expression in the hippocampus of the rats with intracerebroventricular injection of streptozotocin. Neurosci Lett 443:188–192PubMedCrossRefGoogle Scholar
- Khan MB, Khan MM, Khan A, Ahmed ME, Ishrat T, Tabassum R, Vaibhav K, Ahmad A, Islam F (2012b) Naringenin ameliorates Alzheimer’s disease (AD)-type neurodegeneration with cognitive impairment (AD-TNDCI) caused by the intracerebroventricular-streptozotocin in rat model. Neurochem Int 61:1081–1093PubMedCrossRefGoogle Scholar
- Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic, SydneyGoogle Scholar
- Satyavati GV, Raina MK, Sharma M (1976) Medicinal plants of India. Vol. 1. Indian Council of Medical Research, New Delhi, pp 112–118Google Scholar
- Singh HK, Dhawan BN (1992) Drugs affecting learning and memory. In: Tandon PN, Bijiani V, Wadhwa S (eds) Lectures in neurobiology. Wiley Eastern, New Delhi, pp 189–207Google Scholar
- Tripathi S, Mahdi AA, Hasan M, Mitra K, Mahdi F (2011) Protective potential of Bacopa monniera (Brahmi) extract on aluminum induced cerebellar toxicity and associated neuromuscular status in aged rats. Cell Mol Biol (Noisy-le-grand) 57:3–15Google Scholar
- Utely HC, Bernheim F, Hochslein P (1967) Effect of sulfhydryl reagent on peroxidation in microsome. Arch Biochem Biophys 260:521–531Google Scholar