摘要
Alzheimer’s disease(AD)is a neurodegenerative disorder associated with brain aging,and the accumulation ofβ-amyloid(Aβ)and hyperphosphorylated Tau proteins are key pathological features.Currently,drugs for the treatment of AD are mainly single-targeted,but the complex pathogenesis of AD makes it difficult to achieve the desired results.Therefore,the development of multitargeted therapies is crucial for future interventions.Rice bran oil(RBO)has been recognized as an edible oil with several health benefits,but its effects on AD caused by brain aging remain underexplored.In this study,the effects of RBO on memory dysfunction in D-galactose(D-gal)mice and its molecular mechanisms were investigated via in vivo and in silico methods from the perspective of AD pathologies.Our results suggested that compounds in RBO could modulate the activities of Aβprecursor protein cleaving enzyme 1(BACE1),mitogen-activated protein kinase 3(MAPK3),matrix metalloproteinase 3(MMP3),and intercellular adhesion molecule 1(ICAM1),leading to inhibition of Aβaccumulation and Tau protein hyperphosphorylation.Moreover,RBO reduced Aβ-induced oxidative stress by inhibiting the activity of mouse double minute 2 homolog(MDM2)and cyclic adenosine monophosphate(cAMP)response element binding protein binding protein(CREBBP),and attenuated neuroinflammation by inhibiting the activity of nitric oxide synthase 2(NOS2)and reducing Aβaccumulation and Tau protein hyperphosphorylation.Additionally,α-linolenic acid in RBO exhibited inhibitory effects on D-gal-induced apoptosis in PC12 cells through modulation of NOS2,MDM2,ICAM1,and phospho-extracellular signal-regulated kinase 1/2(p-ERK1/2).Similarly,stigmastanol inhibited apoptosis in D-gal-induced PC12 cells through the regulation of NOS2.Thus,RBO can be considered as a potential functional food to attenuate AD owing to its multicomponent and multitarget effects.
基金
supported by the Science and Technology Innovation Program of Hunan Province(2022RC1148)
the Natural Science Foundation of Hunan Province(2022JJ31009,2022JJ50260)
the Program for Science and Technology of Changsha,China(kh2301028)
the Science and Technology Innovation Plan Project of Hunan Province(2023NK2033)
the Innovation Leading Plan Project of Hunan Province(2021GK4022)
the“Kemen Food”Graduate Science and Technology Innovation Project of Central South University of Forestry and Technology(2023KMCX02)
the Graduate Science and Technology Innovation Fund Project of Hunan Province(QL20220182).
