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7,8-Dihydroxyflavone improves cognitive functions in ICV-STZ rat model of sporadic Alzheimer's disease by reversing oxidative stress, mitochondrial dysfunction, and insulin resistance.
Psychopharmacology (Berl). 2021 Jul; 238(7):1991-2009.P

Abstract

RATIONALE

Intracerebroventricular (ICV) streptozotocin (STZ) mimics sporadic Alzheimer's disease (SAD) characterized by tau pathology and neurodegeneration arising from oxidative stress, mitochondrial dysfunction, and insulin resistance. 7,8-Dihydroxyflavone (7,8-DHF) is a flavonoid having antioxidant property interlinked with mitochondrial functioning and insulin actions.

OBJECTIVES

To evaluate the neuroprotective and cognitive enhancement properties of 7,8-DHF in an ICV-STZ rat model of SAD.

METHODS

ICV-STZ (3 mg/kg) was injected into male Wistar rats. Cognitive functions were evaluated by Morris water maze (MWM) and novel object recognition (NOR). 7,8-DHF (5 mg/kg, 10 mg/kg, and 20 mg/kg) and rivastigmine (2 mg/kg) were given orally for 21 days. Reduced glutathione (GSH), catalase, superoxide dismutase (SOD), glutathione peroxidase (GPX), lipid peroxidation (LPO), protein carbonylation (PCO), and nitrite assays were performed. Mitochondrial enzyme complex I, II, III, and IV, and acetylcholinesterase (AchE) activities were determined. ELISA for the insulin-degrading enzyme (IDE) and p-tau was done. Histopathology was investigated by hematoxylin and eosin staining.

RESULTS

7,8-DHF treatment attenuated ICV-STZ-induced cognitive deficit in MWM and NOR. Moreover, in the cortex and hippocampus regions of the brain, GSH, catalase, SOD, GPX, LPO, PCO, and nitrite levels were reversed. Mitochondrial enzyme complex I, II, III, and IV, and acetylcholinesterase (AchE) activities were also normalized. IDE and p-tau protein were found to be significantly altered. 7,8-DHF provided protection from neuronal cell death examined in histopathology.

CONCLUSIONS

Conclusively, 7,8-DHF was found to be neuroprotective in the ICV-STZ rat model by ameliorating oxidative stress, mitochondrial dysfunction, and insulin resistance, thereby improving cognitive functions evident with the behavioral results.

Authors+Show Affiliations

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India.Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India.Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India. spilkhwal@rediffmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33774703

Citation

Akhtar, Ansab, et al. "7,8-Dihydroxyflavone Improves Cognitive Functions in ICV-STZ Rat Model of Sporadic Alzheimer's Disease By Reversing Oxidative Stress, Mitochondrial Dysfunction, and Insulin Resistance." Psychopharmacology, vol. 238, no. 7, 2021, pp. 1991-2009.
Akhtar A, Dhaliwal J, Sah SP. 7,8-Dihydroxyflavone improves cognitive functions in ICV-STZ rat model of sporadic Alzheimer's disease by reversing oxidative stress, mitochondrial dysfunction, and insulin resistance. Psychopharmacology (Berl). 2021;238(7):1991-2009.
Akhtar, A., Dhaliwal, J., & Sah, S. P. (2021). 7,8-Dihydroxyflavone improves cognitive functions in ICV-STZ rat model of sporadic Alzheimer's disease by reversing oxidative stress, mitochondrial dysfunction, and insulin resistance. Psychopharmacology, 238(7), 1991-2009. https://doi.org/10.1007/s00213-021-05826-7
Akhtar A, Dhaliwal J, Sah SP. 7,8-Dihydroxyflavone Improves Cognitive Functions in ICV-STZ Rat Model of Sporadic Alzheimer's Disease By Reversing Oxidative Stress, Mitochondrial Dysfunction, and Insulin Resistance. Psychopharmacology (Berl). 2021;238(7):1991-2009. PubMed PMID: 33774703.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 7,8-Dihydroxyflavone improves cognitive functions in ICV-STZ rat model of sporadic Alzheimer's disease by reversing oxidative stress, mitochondrial dysfunction, and insulin resistance. AU - Akhtar,Ansab, AU - Dhaliwal,Jatinder, AU - Sah,Sangeeta Pilkhwal, Y1 - 2021/03/27/ PY - 2020/11/13/received PY - 2021/03/15/accepted PY - 2021/3/29/pubmed PY - 2021/7/6/medline PY - 2021/3/28/entrez KW - 7,8-Dihydroxyflavone KW - Cholinergic dysfunction KW - ICV-STZ KW - Insulin resistance KW - Mitochondrial dysfunction KW - Neurodegeneration KW - Oxidative stress KW - Sporadic Alzheimer’s disease KW - Tau pathology SP - 1991 EP - 2009 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 238 IS - 7 N2 - RATIONALE: Intracerebroventricular (ICV) streptozotocin (STZ) mimics sporadic Alzheimer's disease (SAD) characterized by tau pathology and neurodegeneration arising from oxidative stress, mitochondrial dysfunction, and insulin resistance. 7,8-Dihydroxyflavone (7,8-DHF) is a flavonoid having antioxidant property interlinked with mitochondrial functioning and insulin actions. OBJECTIVES: To evaluate the neuroprotective and cognitive enhancement properties of 7,8-DHF in an ICV-STZ rat model of SAD. METHODS: ICV-STZ (3 mg/kg) was injected into male Wistar rats. Cognitive functions were evaluated by Morris water maze (MWM) and novel object recognition (NOR). 7,8-DHF (5 mg/kg, 10 mg/kg, and 20 mg/kg) and rivastigmine (2 mg/kg) were given orally for 21 days. Reduced glutathione (GSH), catalase, superoxide dismutase (SOD), glutathione peroxidase (GPX), lipid peroxidation (LPO), protein carbonylation (PCO), and nitrite assays were performed. Mitochondrial enzyme complex I, II, III, and IV, and acetylcholinesterase (AchE) activities were determined. ELISA for the insulin-degrading enzyme (IDE) and p-tau was done. Histopathology was investigated by hematoxylin and eosin staining. RESULTS: 7,8-DHF treatment attenuated ICV-STZ-induced cognitive deficit in MWM and NOR. Moreover, in the cortex and hippocampus regions of the brain, GSH, catalase, SOD, GPX, LPO, PCO, and nitrite levels were reversed. Mitochondrial enzyme complex I, II, III, and IV, and acetylcholinesterase (AchE) activities were also normalized. IDE and p-tau protein were found to be significantly altered. 7,8-DHF provided protection from neuronal cell death examined in histopathology. CONCLUSIONS: Conclusively, 7,8-DHF was found to be neuroprotective in the ICV-STZ rat model by ameliorating oxidative stress, mitochondrial dysfunction, and insulin resistance, thereby improving cognitive functions evident with the behavioral results. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/33774703/78_Dihydroxyflavone_improves_cognitive_functions_in_ICV_STZ_rat_model_of_sporadic_Alzheimer's_disease_by_reversing_oxidative_stress_mitochondrial_dysfunction_and_insulin_resistance_ L2 - https://dx.doi.org/10.1007/s00213-021-05826-7 DB - PRIME DP - Unbound Medicine ER -