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Muhamad Azrul Amir Yusri,1 Mahendran Sekar,2,3 Ling Shing Wong,4 Siew Hua Gan,2 Subban Ravi,5 Vetriselvan Subramaniyan,6 Nur Najihah Izzati Mat Rani,7 Kumarappan Chidambaram,8 M Yasmin Begum,9 Mohankumar Ramar,10 Sher Zaman Safi,11 Siddharthan Selvaraj,12 Yuan Seng Wu,13 Palanisamy Revathy,14 Shivkanya Fuloria,15 Neeraj Kumar Fuloria,15 Pei Teng Lum,1 Sinouvassane Djearamane16 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, Malaysia; 2School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, Malaysia; 3Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, India; 4Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia; 5Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; 6Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, Malaysia; 7Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, Malaysia; 8Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia; 9Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia; 10Department of Surgical Research, Rhode Island Hospital, Alpert Medical School, Brown University, Providence, RI, USA; 11Faculty of Medicine, Bioscience and Nursing, MAHSA University, Bandar Saujana Putra, Jenjarom, Selangor, Malaysia; 12Faculty of Dentistry, AIMST University, Bedong, Kedah, Malaysia; 13Department of Biological Sciences and Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Subang Jaya, Selangor, Malaysia; 14Department of Computer Applications, Gobi Arts & Science College, Gobichettipalayam, Tamil Nadu, India; 15Faculty of Pharmacy, AIMST University, Bedong, Kedah, Malaysia; 16Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, Perak, MalaysiaCorrespondence: Ling Shing Wong, Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia, Tel +6014 3034057, Email lingshing.wong@newinti.edu.my Sinouvassane Djearamane, Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, Perak, Malaysia, Tel +6016 4037685, Email biochsinouvas07@gmail.comAbstract: Celastrol is a naturally occurring chemical isolated from Tripterygium wilfordii Hook. f., root extracts widely known for their neuroprotective properties. In this review, we focus on the efficacy of celastrol in mitigating memory impairment (MI) in both in vivo and in vitro models. Scopus, PubMed and Web of Science databases were utilised to locate pertinent literatures that explore the effects of celastrol in the brain, including its pharmacokinetics, bioavailability, behavioral effects and some of the putative mechanisms of action on memory in many MI models. To date, preclinical studies strongly suggest that celastrol is highly effective in enhancing the cognitive performance of MI animal models, particularly in the memory domain, including spatial, recognition, retention and reference memories, via reduction in oxidative stress and attenuation of neuro-inflammation, among others. This review also emphasised the challenges and potential associated enhancement of medication delivery for MI treatment. Additionally, the potential structural alterations and derivatives of celastrol in enhancing its physicochemical and drug-likeness qualities are examined. The current review demonstrated that celastrol can improve cognitive performance and mitigate MI in several preclinical investigations, highlighting its potential as a natural lead molecule for the design and development of a novel neuroprotective medication.Graphical Abstract: Keywords: celastrol, memory impairment, neuroprotection, drug discovery, natural products |
