Phosphoinositide 3-kinase inhibitor AS605240 ameliorates streptozotocin-induced Alzheimer’s disease like sporadic dementia in experimental rats

Authors

  • Ramesh Alluri Cognitive Science Research Initiative Lab, Dept. of Pharmacology, Vishnu Institute of Pharmaceutical Education and Research, Narsapur, Medak Dist., Telangana, 502313. Tel.: +919701683444, E-mail: rameshcology@gmail.com
  • Siva Mallikarjuna Reddy Ambati Aodh Lifesciences Pvt. Ltd., Tarnaka, Secunderabad-500017, Telangana, India
  • Kasiviswanath Routhu Incozen Therapeutics Pvt. Ltd., Hyderabad-500078, Telangana, India
  • Spandana Rajendra Kopalli Department of Bioscience and Biotechnology, Sejong University, Gwangjin-gu, Seoul 05006, Korea
  • Sushruta Koppula College of Biomedical and Health Science, Konkuk University, Chungju-Si, Chungbuk Do, 27478, Republic of Korea, Tel: +824384403609, E-mail: koppula@kku.ac.kr

DOI:

https://doi.org/10.17179/excli2019-1997

Keywords:

Alzheimer’s Disease, PI3K inhibitor, streptozotocin, intra-cerebroventricular injection, oxidative stress, cognition, AS605240

Abstract

The quest for chemical entities able to curb the action of the phosphoinositide 3-kinase, (PI3K)/protein kinase B (AKT) signaling pathways is evolving as a potential therapeutic strategy for the treatment and/or prevention of neurodegenerative disorders including Alzheimer’s disease (AD). In this study, the effects of a PI3K inhibitor, AS605240 on cognitive dysfunction and antioxidative defense parameters against intra-cerebroventricular-streptozotocin (ICV-STZ)-induced rat model of sporadic AD was evaluated. ICV administration of a single dose of STZ (3 mg/kg) was performed to induce behavioral and biochemical changes in rats using the stereotaxic technique. Animals were administered with varying doses of AS605240 (5, 10 and 15 mg/kg) orally, 1 h before ICV-STZ on day 1 and continued once daily for four weeks. The behavioral parameters (passive avoidance and Morris water maze), antioxidative defense parameters, amyloid-beta (Aβ) protein expression by Western blotting and immunostaining technique were estimated in brain tissue. AS605240 dose-dependently and significantly (p < 0.05 and p < 0.01 and p < 0.001) improved ICV-STZ-induced cognitive impairment and attenuated the altered antioxidative related parameters including superoxide dismutase, lipid peroxidation, glutathione and nitrite levels. Further, the increased Aβ protein expression levels in brain tissue were markedly restored with AS605240 treatment. In conclusion, our study demonstrated that AS605240 exhibited immense potential in attenuating STZ-induced sporadic AD features in rats and may be developed as a therapeutic agent in the treatment and management of sporadic AD.

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Published

2020-01-06

How to Cite

Alluri, R., Ambati, S. M. R., Routhu, K., Kopalli, S. R., & Koppula, S. (2020). Phosphoinositide 3-kinase inhibitor AS605240 ameliorates streptozotocin-induced Alzheimer’s disease like sporadic dementia in experimental rats. EXCLI Journal, 19, 71–85. https://doi.org/10.17179/excli2019-1997

Issue

Vol. 19 (2020)

Section

Original articles

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