Table 1.

Summary of the different pharmacological activities and the responsible mechanisms for cytokinins.

Activity	Mechanism
Antioxidant [81,86,87,88,89,90,91,92,93,94,95]	Kinetin controls the level of ROS via -Scavenging the ROS (due to the presence of furan ring); -Production of complexes which have SOD-like action. Kinetin and BA protect against oxidative damage via -Attenuation of GSH-PX activity; -Decreasing the membrane phospholipid peroxidation and MDA production; -Increasing the activities of SOD and HO-1. Kinetin increases the expression levels of anti-apoptotic (BCL2) and protamine-related (PRM2 and PRM3) genes and decreases the expression of pro-apoptotic (BAX) and mitochondrial reactive oxygen species-modulating (ROMO1) genes
Antithrombotic [93]	Kinetin suppressed hydroxyl radical formation
Anti-aging [52,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114]	Kinetin -Increases the expression of different markers of cell differentiation; -Improves skin texture, reduces wrinkling and pigmentation, decreases the thickness of the corneal layer, and increases numbers of collagen and elastic fibers in the dermis; -Decreases the skeletal muscle aging by its antioxidant activity and its ability to modulate intracellular calcium levels. trans-zeatin -Down-regulates UVB-induced MMP expression resulting in enhanced cell viability of the radiated fibroblasts; -Modulates AQP3 expression; -Inhibits UV-induced MEK/ERK pathway activation.
Anticancer [77,98,115,116,117,118,119,120,121,122,123,124,125,126,127]	Kinetin, 2iP and BA show antiproliferative activity via -Induction of differentiation by the phosphorylation of ERK1/2 and the expression of S100P and CEBPD proteins; - Induction of apoptosis by ▪ modulating the mitochondrial membrane potential; ▪ depleting cellular ATP; ▪ stimulating the release of cytochrome c; ▪ activation of caspase-3; reducing the ratio of Bcl-2/Bax; ▪ interrupting the cell cycle at G1/S restriction point; -Inhibition of the growth of the cancer cells by modulating the expression of different proteins such as N-cadherins, Vimentin, Snail, Twist, p-Akt, and MMPs.
Neuroprotective [43,128,129,130,131,132,133,134,135,136,137,138]	Kinetin -Acts as a phosphate donor maintaining the N17 phosphorylation in Huntington’s disease; - Attenuates the anxiety and improved the memory impairment by ▪ Promoting the nuclear translocation of NrF2; ▪ Induction of HO-1 expression; ▪ Suppression of ROS; ▪ Increasing of intracellular calcium influx. Zeatin showed an potential neuroprotective effect via activation of the A2A-R signaling.
Anti-inflammatory and immunomodulatory [128,129,139,140]	Zeatin riboside modulated mammalian T lymphocyte and immune system activity via an A2AR-dependent mechanism by -Stimulation of the production of cAMP by T lymphocytes; -Suppression of the production of IFN-c, IL-2, TNF-a, IL-4 and IL-13, by CD31CD41 T cells; -Production of IFN-c, IL-2 and TNF-a by CD31CD81 T cells. Kinetin improves familial dysautonomia by increasing exon 20 inclusion in RNA and increasing IKBKAP mRNA and IKAP protein to normal levels.