Trans-zeatin and its derivatives: Cytokinins present in various TCM preparations as promising candidate moclecules for the management of Alzheimer's and Parkinson's disease

Introduction

Alzheimer's disease (AD) and Parkinson's disease (PD), characterized by their progressive nature and debilitating impact on individuals' cognitive and motor functions, pose a significant challenge to public health. Despite extensive research efforts, the severity of cognitive dysfunction remains formidable, with gaps persisting in understanding its underlying mechanisms and developing effective therapeutic interventions. Natural phytohormones have emerged as promising candidates for managing neurodegenerative diseases, offering potential avenues for therapeutic intervention. The phytohormone trans-zeatin (tZ) is a derivative of the cytokinin zeatin (6-isopentenylaminopurine). tZ derivatives such as N6-isopentyl adenosine (iPR), t-zeatin riboside (tZR), kinetin (K), and kinetin riboside (KR) are the active components available in coconut water and are also isolated from many plant extracts that aid in plant growth.

Methods

We searched the various online databases (Pub-Med, WOS, and Google Scholar) for the last twenty years using keywords such as Alzheimer's disease, Parkinson's disease, phytohormones, trans-zeatin, and cytokinins, paired with traditional Chinese plants. This literature review sought to illuminate the therapeutic role of cytokinins in AD and PD. In addition, this article talked about the biological importance of cytokinins to understand how trans-zeatin and its derivatives, which are cytokinins, protect neurons. We searched and screened 75 articles. Results were summarized, compared, and research gaps identified throughout the data collection and interpretation.

Results

TZ and its derivatives have garnered attention for their notable biological activities such as antioxidant, anti-aging, cytoprotective, anti-inflammatory, and particularly their anti-Alzheimer and anti-Parkinson effects. tZ may be useful as a treatment for Alzheimer's disease because it stops cholinesterase from working, stops amyloid beta (Aβ) from clumping together, and changes the Nrf2/ARE pathway. In Parkinson's disease (PD), tZ prevents the degeneration of dopaminergic neurons by lowering JNK/P38 phosphorylation, moderating Bax-mediated apoptosis, and blocking caspase 3/7 activation.

Discussion and conclusion

Dietary foods could incorporate trans-zeatin, derived from coconut (Cocos nucifera) and other natural sources, to provide a variety of health benefits. Because they can change important cellular pathways like Nrf2, NF-κB, and PI3K/Akt, they may be able to protect neurons from damage and slow down its growth. By evaluating trans-zeatin's efficacy in preclinical and clinical studies, it holds the promise of becoming a valuable therapeutic agent for combating neurodegeneration in AD and PD.