Longevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer's disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panax ginseng extract improves AD symptoms in patients with AD, and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid β-protein (Aβ) formation by inhibiting β- and γ-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and Aβ-induced neurotoxicity, and decrease Aβ-induced production of reactive oxygen species and neuroinflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates Aβ-induced cholinergic deficits in AD models. Similarly, gintonin inhibits Aβ-induced neurotoxicity and activates the nonamyloidogenic pathway to reduce Aβ formation and to increase acetylcholine and choline acetyltransferase expression in the brain through lysophosphatidic acid receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems and neurogenesis, thereby ameliorating learning and memory impairments. It also improves cognitive functions in patients with AD. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses research demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.
Keywords: AChE, acetylcholinesterase; AD, Alzheimer's disease; APP, amyloid precursor protein; Adjuvant; Alzheimer's disease; Aβ, amyloid β-protein; BDNF, brain-derived neurotrophic factor; EGF, Epidermal growth factor; GLP151, ginseng major latex-like protein 151; Ginsenoside; Gintonin; LPA, Lysophosphatidic acid; NGF, nerve growth factor; NMDA, n-methyl-d-aspartic acid; PI3K, phosphoinositide-3 kinase; PPARγ, peroxisome proliferator-activated receptor-γ; Panax ginseng; ROS, reactive oxygen species; sAPPα, soluble amyloid precursor protein α.