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Protective effect of betulinic acid against intracerebroventricular streptozotocin induced cognitive impairment and neuronal damage in rats: Possible neurotransmitters and neuroinflammatory mechanism.
Pharmacol Rep. 2018 Jun; 70(3):540-548.PR

Abstract

BACKGROUND

The purpose of the study was to explore the therapeutic potential of Betulinic acid (BA) in streptozotocin (STZ) induced memory damage in experimental rats.

METHODS

STZ (3mg/kg bilaterally) as intracerebroventrical (icv) route was administered on day 1 and 3 in rats. Donepezil (5mg/kg/day po), used as standard, and BA (5, 10 and 15mg/kg/day po) were administered after 1h of 1st STZ infusion up to 21days. Object recognition task (ORT) for non-spatial, Morris water maze (MWM) for spatial and locomotor activity were performed to evaluate behavioral changes in rats. On 22nd day, animals were decapitated and hippocampus was separated to perform biochemical (AChE, LPO, GSH, nitrite), neuroinflammatory (TNF-α, IL-1β, and IL-6), neurotransmitters (NTs) (dopamine, norepinephrine and serotonin) analysis.

RESULTS

STZ infusion significantly impaired memory as observed in MWM and ORT, increased oxidative stress, pro-inflammatory cytokine's level and altered NTs level. Moreover, BA demonstrated a neuroprotective effect in a dose-dependent manner. BA dose dependently (5, 10 and 15mg/kg) significantly restore STZ induced memory changes and pathological abnormalities in rat brain.

CONCLUSIONS

The findings of the current study suggests that BA protect rat brain from STZ induced neuronal damage via acting through multiple mechanisms and would be used to curb cognitive decline associated with neurodegenerative disorders especially AD.

Authors+Show Affiliations

Department of Pharmacology, School of Pharmaceutical Education and Research Formerly, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, India.Department of Pharmacology, School of Pharmaceutical Education and Research Formerly, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, India.Department of Pharmacology, School of Pharmaceutical Education and Research Formerly, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, India. Electronic address: makhtar_ph@jamiahamdard.ac.in.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29674241

Citation

Kaundal, Madhu, et al. "Protective Effect of Betulinic Acid Against Intracerebroventricular Streptozotocin Induced Cognitive Impairment and Neuronal Damage in Rats: Possible Neurotransmitters and Neuroinflammatory Mechanism." Pharmacological Reports : PR, vol. 70, no. 3, 2018, pp. 540-548.
Kaundal M, Deshmukh R, Akhtar M. Protective effect of betulinic acid against intracerebroventricular streptozotocin induced cognitive impairment and neuronal damage in rats: Possible neurotransmitters and neuroinflammatory mechanism. Pharmacol Rep. 2018;70(3):540-548.
Kaundal, M., Deshmukh, R., & Akhtar, M. (2018). Protective effect of betulinic acid against intracerebroventricular streptozotocin induced cognitive impairment and neuronal damage in rats: Possible neurotransmitters and neuroinflammatory mechanism. Pharmacological Reports : PR, 70(3), 540-548. https://doi.org/10.1016/j.pharep.2017.11.020
Kaundal M, Deshmukh R, Akhtar M. Protective Effect of Betulinic Acid Against Intracerebroventricular Streptozotocin Induced Cognitive Impairment and Neuronal Damage in Rats: Possible Neurotransmitters and Neuroinflammatory Mechanism. Pharmacol Rep. 2018;70(3):540-548. PubMed PMID: 29674241.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effect of betulinic acid against intracerebroventricular streptozotocin induced cognitive impairment and neuronal damage in rats: Possible neurotransmitters and neuroinflammatory mechanism. AU - Kaundal,Madhu, AU - Deshmukh,Rahul, AU - Akhtar,Mohd, Y1 - 2017/12/06/ PY - 2017/02/08/received PY - 2017/11/27/revised PY - 2017/11/29/accepted PY - 2018/4/21/pubmed PY - 2018/10/10/medline PY - 2018/4/21/entrez KW - Alzheimer’s disease KW - Betulinic acid KW - Neuroinflammation KW - Neurotransmitters SP - 540 EP - 548 JF - Pharmacological reports : PR JO - Pharmacol Rep VL - 70 IS - 3 N2 - BACKGROUND: The purpose of the study was to explore the therapeutic potential of Betulinic acid (BA) in streptozotocin (STZ) induced memory damage in experimental rats. METHODS: STZ (3mg/kg bilaterally) as intracerebroventrical (icv) route was administered on day 1 and 3 in rats. Donepezil (5mg/kg/day po), used as standard, and BA (5, 10 and 15mg/kg/day po) were administered after 1h of 1st STZ infusion up to 21days. Object recognition task (ORT) for non-spatial, Morris water maze (MWM) for spatial and locomotor activity were performed to evaluate behavioral changes in rats. On 22nd day, animals were decapitated and hippocampus was separated to perform biochemical (AChE, LPO, GSH, nitrite), neuroinflammatory (TNF-α, IL-1β, and IL-6), neurotransmitters (NTs) (dopamine, norepinephrine and serotonin) analysis. RESULTS: STZ infusion significantly impaired memory as observed in MWM and ORT, increased oxidative stress, pro-inflammatory cytokine's level and altered NTs level. Moreover, BA demonstrated a neuroprotective effect in a dose-dependent manner. BA dose dependently (5, 10 and 15mg/kg) significantly restore STZ induced memory changes and pathological abnormalities in rat brain. CONCLUSIONS: The findings of the current study suggests that BA protect rat brain from STZ induced neuronal damage via acting through multiple mechanisms and would be used to curb cognitive decline associated with neurodegenerative disorders especially AD. SN - 1734-1140 UR - https://www.unboundmedicine.com/medline/citation/29674241/Protective_effect_of_betulinic_acid_against_intracerebroventricular_streptozotocin_induced_cognitive_impairment_and_neuronal_damage_in_rats:_Possible_neurotransmitters_and_neuroinflammatory_mechanism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1734-1140(17)30096-8 DB - PRIME DP - Unbound Medicine ER -