Shanghai Institute of Geriatrics and Gerontology, Shanghai Key Laboratory of Clinical Geriatrics, Huadong Hospital, and Research Center of Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai 200040, China.
Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Pharmacol Res. 2018 Feb;128:345-358. doi: 10.1016/j.phrs.2017.08.010. Epub 2017 Aug 25.
Flavonoids are efficacious candidates as pharmaceuticals or nutraceuticals in the treatment of Alzheimer's disease (AD), aging and other age-related chronic inflammatory diseases. Natural flavonoids reduce pathological hallmarks, extracellular amyloid deposits and neurofibrillary tangles by mediating amyloid precursor protein (APP) processing, Aβ accumulation and tau pathology. The antioxidant and anti-inflammatory actions as well as modulation of sirtuins and telomeres are also involved in the amelioration of aging, neurodegeneration and other age-related diseases. Recently, some flavonoids were shown to inhibit poly (ADP-ribose) polymerases (PARPs) and cyclic ADP-ribose (cADP) synthases (CD38 and CD157), elevate intracellular nicotinamide adenine dinucleotide (NAD) levels and activate NAD dependent sirtuin -mediated signaling pathways. We summarized how flavonoids reduce the degradation of NAD with an emphasis on the mechanisms through which flavonoids affect the NAD-sirtuin axis to protect against AD. Aging and age-related diseases as well as a decline in the physiological reserve are the risk factors for cognitive frailty. Flavonoids with multiple therapeutic targets may also be potential candidates for the prevention and treatment of cognitive frailty.
类黄酮是治疗阿尔茨海默病（AD）、衰老和其他与年龄相关的慢性炎症性疾病的有效药物或营养药物候选物。天然类黄酮通过调节淀粉样前体蛋白（APP）处理、Aβ 积累和 tau 病理学，减少病理标志物、细胞外淀粉样沉积物和神经原纤维缠结。抗氧化和抗炎作用以及对沉默调节蛋白和端粒的调节也参与了衰老、神经退行性变和其他与年龄相关疾病的改善。最近，一些类黄酮被证明可以抑制聚（ADP-核糖）聚合酶（PARPs）和环 ADP-核糖（cADP）合酶（CD38 和 CD157），提高细胞内烟酰胺腺嘌呤二核苷酸（NAD）水平，并激活 NAD 依赖性沉默调节蛋白介导的信号通路。我们总结了类黄酮如何减少 NAD 的降解，并重点介绍了类黄酮影响 NAD-沉默调节蛋白轴以预防 AD 的机制。衰老和与年龄相关的疾病以及生理储备的下降是认知脆弱的危险因素。具有多种治疗靶点的类黄酮也可能是预防和治疗认知脆弱的潜在候选药物。
