Anil Kumar1, Jitendriya Mishra2, Kanwaljit Chopra2, Dinesh K Dhull2. 1. Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study (UGC-CAS), Panjab University, Chandigarh, 160014, India. kumaruips@yahoo.com. 2. Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study (UGC-CAS), Panjab University, Chandigarh, 160014, India.
Abstract
RATIONALE: The therapeutic potential of berberine has been well documented in various neurological problems. However, the neurological mechanism of berberine remains untapped in the light of its P-glycoprotein (P-gp)-mediated gut efflux properties responsible for reduced bioavailability. Verapamil, a well known L-type calcium channel blocker, has additional inhibitory activity against P-gp efflux pump. Thus, there is a strong scientific rationale to explore the interaction of berberine with verapamil as a possible neuroprotective strategy. OBJECTIVE: The present study was designed to evaluate the effect of berberine, verapamil, and their combination on behavioral alterations, oxidative stress, mitochondrial dysfunction, neuroinflammation, and histopathological modifications in intracerebroventricular streptozocin (ICV-STZ)-induced sporadic dementia of Alzheimer's type in rats. METHODS: Single bilateral ICV-STZ (3 mg/kg) administration was used as an experimental model of sporadic dementia of Alzheimer's type. RESULTS: Berberine (25, 50, and 100 mg/kg, oral gavage) or verapamil (2.5 and 5 mg/kg, intraperitoneally) were used as treatment drugs, and memantine (5 mg/kg, intraperitoneally) was used as a standard. Berberine and verapamil significantly attenuated behavioral, biochemical, cellular, and histological alterations, suggesting their neuroprotective potential. Further, treatment of berberine (25 and 50 mg/kg) with verapamil (2.5 and 5.0 mg/kg) combinations respectively significantly potentiated their neuroprotective effect which was significant as compared to their effect per se in ICV-STZ-treated animals. CONCLUSION: The augmentative outcome of verapamil on the neuroprotective effect of berberine can be speculated due to the inhibition of P-gp efflux mechanism and the prevention of calcium homeostasis alteration. Additionally, anti-inflammatory and antioxidant effects of both berberine and verapamil could also contribute in their protective effect.
RATIONALE: The therapeutic potential of berberine has been well documented in various neurological problems. However, the neurological mechanism of berberine remains untapped in the light of its P-glycoprotein (P-gp)-mediated gut efflux properties responsible for reduced bioavailability. Verapamil, a well known L-type calcium channel blocker, has additional inhibitory activity against P-gp efflux pump. Thus, there is a strong scientific rationale to explore the interaction of berberine with verapamil as a possible neuroprotective strategy. OBJECTIVE: The present study was designed to evaluate the effect of berberine, verapamil, and their combination on behavioral alterations, oxidative stress, mitochondrial dysfunction, neuroinflammation, and histopathological modifications in intracerebroventricular streptozocin (ICV-STZ)-induced sporadic dementia of Alzheimer's type in rats. METHODS: Single bilateral ICV-STZ (3 mg/kg) administration was used as an experimental model of sporadic dementia of Alzheimer's type. RESULTS:Berberine (25, 50, and 100 mg/kg, oral gavage) or verapamil (2.5 and 5 mg/kg, intraperitoneally) were used as treatment drugs, and memantine (5 mg/kg, intraperitoneally) was used as a standard. Berberine and verapamil significantly attenuated behavioral, biochemical, cellular, and histological alterations, suggesting their neuroprotective potential. Further, treatment of berberine (25 and 50 mg/kg) with verapamil (2.5 and 5.0 mg/kg) combinations respectively significantly potentiated their neuroprotective effect which was significant as compared to their effect per se in ICV-STZ-treated animals. CONCLUSION: The augmentative outcome of verapamil on the neuroprotective effect of berberine can be speculated due to the inhibition of P-gp efflux mechanism and the prevention of calcium homeostasis alteration. Additionally, anti-inflammatory and antioxidant effects of both berberine and verapamil could also contribute in their protective effect.
Authors: Brian C Shonesy; Kariharan Thiruchelvam; Kodeeswaran Parameshwaran; Engy Abdel Rahman; Senthilkumar S Karuppagounder; Kevin W Huggins; Carl A Pinkert; Rajesh Amin; Muralikrishnan Dhanasekaran; Vishnu Suppiramaniam Journal: Neurobiol Aging Date: 2011-01-21 Impact factor: 4.673
Authors: Xiongwei Zhu; Arun K Raina; Hyoung-Gon Lee; Gemma Casadesus; Mark A Smith; George Perry Journal: Brain Res Date: 2004-03-12 Impact factor: 3.252