Bacopa monnieri prevents colchicine-induced dementia by anti-inflammatory action
- 24 Downloads
Inflammation is considered as an early event in the development of Alzheimer’s disease (AD) that precedes the formation of Aβ plaques and neurofibrillary tangles. Therefore, strategies aimed at attenuating inflammation by phytochemicals may be a potential therapeutic intervention against AD. The present study was designed to evaluate if colchicine-induced inflammation and Aβ production could be prevented by Bacopa monnieri (BM) supplementation. Dementia was induced by a single intracerebroventicular injection of colchicine (15 μg/5 μl), whereas, BM extract was administered orally (50 mg/kg body weight, daily) for 15 days. Assessment of cognitive functions using Morris water maze revealed deficits in colchicine administered animals. This was accompanied by significant increase in oxidative stress in terms of accentuated ROS and NO production. Expression of pro-inflammatory cytokines (IL-6, TNF-α) and chemokine (MCP-1) increased in the brain regions. Furthermore, COX-2 and iNOS expression also increased significantly in the brain regions of colchicine-administered animals. In addition, BACE-1 activity increased in the colchicine treated animals, which was accompanied by enhanced Aβ production. On the other hand, BM supplementation was able to improve cognitive functions, suppress Aβ formation by reducing BACE-1 activity. Inflammatory and oxidative stress markers were attenuated in the brain regions of BM supplemented animals. Taken together, the findings reveal that BM reverses colchicine-induced dementia by its anti-inflammatory and anti-oxidant action suggesting that it may be an effective therapeutic intervention to ameliorate progression of AD.
KeywordsAlzheimer’s disease Amyloid β Bacopa monnieri BACE-1 Cholchicine Oxidative stress Inflammation
Amyloid precursor protein
β-site amyloid precursor protein cleaving enzyme 1
Glycogen synthase kinase-3β
Inducible Nitric oxide synthase
Reactive Oxygen species
Reactive Nitrogen Species
The financial assistance provided to Dr. Neetu Saini by the Department of Science and Technology (DST), New Delhi, under women scientist fellowship scheme is acknowledged.
Compliance with ethical standards
Conflicts of interest
The authors have no conflicts of interest to declare.
- Aditya GN, Chattopadhyay RN, Mandal S, Roy RK, Lahiri HL, Maitra SK (1997) Possible mechanism of anti-inflammatory activity of calcium channel blockers. Indian J Pharm 29:325–326Google Scholar
- Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O'Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T (2000) Inflammation and Alzheimer's disease. Neurobiol Aging 21:383–421CrossRefGoogle Scholar
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
- McGeer PL, McGeer EG (2002) Local neuroinflammation and the progression of Alzheimer's disease. J Neuro-Oncol 8:529–538Google Scholar
- Rehman MU, Tahir M, Khan AQ, Lateef A, Khan R, Hamiza OO, Qamar W, Kazim S, Ali F, Sultana S (2012) Methanolic extract of Bacopa monnieri protects against KBrO3 -induced renal damage in Wistar rats by restoring antioxidant enzyme activities and suppressing inflammation and apoptosis. J Pharm Res 5:5231–5238Google Scholar
- Simpson T, Pase M, Stough C (2015) Bacopa monnieri as an antioxidant therapy to reduce oxidative stress in the aging brain. Evid Based Complement Alternat Med 615384. https://doi.org/10.1155/2015/615384