Alzheimer’s disease (AD) causes progressive memory loss and cognitive dysfunction. It is triggered by multifaceted burdens such as cholinergic toxicity, insulin resistance, neuroinflammation, and oxidative stress. Syzygium plants are ethnomedicinally used in treating inflammation, diabetes, as well as memory impairment. They are rich in antioxidant phenolic compounds, which can be multi-target neuroprotective agents against AD. This review attempts to review the pharmacological importance of the Syzygium genus in neuroprotection, focusing on anti-cholinesterase, anti-diabetic, anti-inflammatory, and antioxidant properties. Articles published in bibliographic databases within recent years relevant to neuroprotection were reviewed. About 10 species were examined for their anti-cholinesterase capacity. Most studies were conducted in the form of extracts rather than compounds. Syzygium aromaticum (particularly its essential oil and eugenol component) represents the most studied species owing to its economic significance in food and therapy. The molecular mechanisms of Syzygium species in neuroprotection include the inhibition of AChE to correct cholinergic transmission, suppression of pro-inflammatory mediators, oxidative stress markers, RIS production, enhancement of antioxidant enzymes, the restoration of brain ions homeostasis, the inhibition of microglial invasion, the modulation of ß-cell insulin release, the enhancement of lipid accumulation, glucose uptake, and adiponectin secretion via the activation of the insulin signaling pathway. Additional efforts are warranted to explore less studied species, including the Australian and Western Syzygium species. The effectiveness of the Syzygium genus in neuroprotective responses is markedly established, but further compound isolation, in silico, and clinical studies are demanded.
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