Oxidative Stress and Natural Antioxidants: Back and Forth in the Neurological Mechanisms of Alzheimer’s Disease

Article type: Review Article

Authors: Mani, Shalini^{a; 1; *} | Dubey, Rajni^{b; 1} | Lai, I-Chun^{c; d; e; 1} | Babu, M. Arockia^f | Tyagi, Sakshi^a | Swargiary, Geeta^a | Mody, Deepansh^a | Singh, Manisha^a | Agarwal, Shriya^g | Iqbal, Danish^h | Kumar, Sanjayⁱ | Hamed, Munerah^j | Sachdeva, Punya^k | Almutary, Abdulmajeed G.^l | Albadrani, Hind Muteb^m | Ojha, Shreesh^{n; *} | Singh, Sandeep Kumar^{o; *} | Jha, Niraj Kumar^{p; q; r; s; *}

Affiliations: [a] Centre for Emerging Diseases, Department of Biotechnology, Jaypee Institute of Information Technology, Noida, UP, India | [b] Division of Cardiology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan | [c] School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan | [d] Division of Radiation Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan | [e] The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan | [f] Institute of Pharmaceutical Research, GLA University, Mathura, India | [g] Department of Molecular Sciences, Macquarie University, Sydney, Australia | [h] Department of Health Information Management, College of Applied Medical Sciences, Buraydah Private Colleges, Buraydah, Saudi Arabia | [i] Department of Life Sciences, School of Basic Sciences and Research (SBSR), Sharda University, Greater Noida, Uttar Pradesh, India | [j] Department of Pathology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia | [k] GloNeuro, Vishwakarma Road, Noida, India | [l] Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi, United Arab Emirates | [m] Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, Kingdom of Saudi Arabia | [n] Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Abu Dhabi, United Arab Emirates | [o] Indian Scientific Education and Technology Foundation, Lucknow, India | [p] Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Greater Noida, Uttar Pradesh, India | [q] School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India | [r] Department of Biotechnology, School of Applied & Life Sciences (SALS), Uttaranchal University, Dehradun, Uttarakhand, India | [s] Department of Biotechnology Engineering and Food Technology, Chandigarh University, Mohali, India

Correspondence: [*] Correspondence to: Niraj Kumar Jha, Assistant Professor, Department of Biotechnology, School of Engineering & Technology (SET) Sharda University, Knowledge Park III, Greater Noida, Uttar Pradesh-201310, India. Tel.: +91 7488019194; E-mails: nirajkumarjha2011@gmail.com; niraj.jha@sharda.ac.in; ORCID: 0000-0001-9486-4069. Sandeep Kumar Singh, E-mail: sandeeps.bhu@gmail.com; Shreesh Ojha, E-mail: shreeshojha@uaeu.ac.ae; Shalini Mani, E-mail: mani.shalini@gmail.com.

Note: [1] These authors contributed equally to this work.

Abstract: Alzheimer’s disease (AD) is characterized by the progressive degeneration of neuronal cells. With the increase in aged population, there is a prevalence of irreversible neurodegenerative changes, causing a significant mental, social, and economic burden globally. The factors contributing to AD are multidimensional, highly complex, and not completely understood. However, it is widely known that aging, neuroinflammation, and excessive production of reactive oxygen species (ROS), along with other free radicals, substantially contribute to oxidative stress and cell death, which are inextricably linked. While oxidative stress is undeniably important in AD, limiting free radicals and ROS levels is an intriguing and potential strategy for deferring the process of neurodegeneration and alleviating associated symptoms. Therapeutic compounds from natural sources have recently become increasingly accepted and have been effectively studied for AD treatment. These phytocompounds are widely available and a multitude of holistic therapeutic efficiencies for treating AD owing to their antioxidant, anti-inflammatory, and biological activities. Some of these compounds also function by stimulating cholinergic neurotransmission, facilitating the suppression of beta-site amyloid precursor protein-cleaving enzyme 1, α-synuclein, and monoamine oxidase proteins, and deterring the occurrence of AD. Additionally, various phenolic, flavonoid, and terpenoid phytocompounds have been extensively described as potential palliative agents for AD progression. Preclinical studies have shown their involvement in modulating the cellular redox balance and minimizing ROS formation, displaying them as antioxidant agents with neuroprotective abilities. This review emphasizes the mechanistic role of natural products in the treatment of AD and discusses the various pathological hypotheses proposed for AD.

Keywords: Alzheimer’s disease, antioxidants, neuroprotection, oxidative stress, therapeutics, vitamins

DOI: 10.3233/JAD-220700

Journal: Journal of Alzheimer's Disease, vol. 96, no. 3, pp. 877-912, 2023