Alzheimer’s Disease Curing Effect Of V11

Co-evolution of symbionts with hosts may increase their productivity of natural products with novel structures and significant bioactivities, from which the lead compound may be discovered.The incidence of Alzheimer’s disease are rising rapidly, due to its complex and diverse etiology,conventional acetylcholinesterase inhibitors can only be alleviated to some extent, the mild symptoms of Alzheimer’s patients, and can not terminate and reverse the progression of Alzheimer’s disease. Therefore, the search for newand effective anti-Alzehimer’s drug is imperative to improve health and living quality of the patients.This thesis deals with the Alzheimer’s disease curing effect of V11,a new diterpenoid isolated from the culture of Phomopsis sp. S12, residing in the apparently normal seed of Illigera rhodantha(Hernandiaceae).The first chapter is a mini-review concerning progress of treatment of Alzheimer’s disease pathogenesis and drug.The second chapter presents AChE inhibiting activity of V11. By Ellman assay, V11 showed significant inhibitory activity of AChE with its ICsovalue close to positive control huprezine. Thediterpene-basedstructureof V11 allows a good solubility, permeability across the blood brain barrier, and a prolonged stayin the brain, as evidenced from the LC-MS analysis which addressed the distribution-efficacy relationshipof V11. IntheAβ1-42 injected mice, V11 was shownto improve learning and memory in the animal model.The 3rd chapter describes the immunosuppressive activity of V11.Using DCFH-DA as a fluorescent probe, theAβ1-42-induced increment in reactive oxygen species(ROS) was reduced by the VI1 exposure. The inflammatoty cytokines(IL-6, TNF-α and IL-1α) induced by Aβ1-42 was indicated by real time PCR to be suppressed by V11 in a dose-dependent manner. The Western blot demonstrated that V11 inhibited the expressions of Toll-like receptor 4,activation of NF-κB, and Bax protein level to inhibit apoptosis, and it also increased the CREB-phosphorylation levels to promote the long-term memory.