Mario A. Tan | Seong Soo A. An
Alzheimer's disease (AD) is a dominant neurological disorder characterized by cognitive impairments and synaptic dysfunctions affecting mostly the elderly. There are only five drugs approved to minimize the progression of symptoms related to AD. Hence, the challenge of finding an alternative treatment or therapy from natural products is warranted. The purified oxindole alkaloids, isomitraphylline, and mitraphylline from Uncaria perrottetii (locally known as "sungay kalabaw"), revealed their ability to break amyloid aggregates in vitro suggesting their therapeutic potentials in Alzheimer's disease (AD). Thioflavin-T assay for assessing amyloid-beta (Abeta) aggregation of these alkaloids exhibited inhibitions at 60.32% +/- 2.61 (50 uM) for isomitraphylline and 43.17% +/- 3.48 (50 uM) for mitraphylline. Neuroprotective effects were elaborated against Abeta-induced SH-SY5Y cells at 20 uM and 10 uM for isomitraphylline, and 20 uM for mitraphylline. In addition, both alkaloids attenuated and protected the H2O2-induced SH-SY5Y cell cytotoxicity at 20 uM. The intracellular ROS levels of SH-SY5Y cells from H2O2-induced oxidative stress were reduced at 20 uM and 10 uM, and the mitochondrial membrane potentials of Abeta-induced SH-SY5Y cells were protected at 20 uM. The overall results suggested the potentials of both alkaloids to target certain pathological biomarkers of AD and could be further investigated as therapeutic or preventive drug leads against AD.