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References

Kim HJ, Kim P, Shin CY. A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system. J Ginseng Res. 2013 Mar;37(1):8-29.

Chu S, Gu J, Feng L, Liu J, Zhang M, Jia X, Liu M, Yao D. Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses. Int Immunopharmacol. 2014 Apr;19(2):317-26.

Cai M, Yang EJ. Ginsenoside Re Attenuates Neuroinflammation in a Symptomatic ALS Animal Model. Am J Chin Med. 2016;44(2):401-13

Vinoth Kumar R, Oh TW, Park YK. Anti-Inflammatory Effects of Ginsenoside-Rh2 Inhibits LPS- Induced Activation of Microglia and Overproduction of Inflammatory Mediators Via Modulation of TGF-β1/Smad Pathway. Neurochem Res. 2016 May;41(5):951-7.

Ardah MT, Paleologou KE, Lv G, Menon SA, Abul Khair SB, Lu JH, Safieh-Garabedian B, Al-Hayani AA, Eliezer D, Li M, El-Agnaf OM. Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils. Neurobiol Dis. 2015 Feb;74:89-101.

Li Z, Li H, Zhao C, Lv C, Zhong C, Xin W, Zhang W. Protective Effect of Notoginsenoside R1 on an APP/PS1 Mouse Model of Alzheimer's Disease by Up-Regulating Insulin Degrading Enzyme and Inhibiting Aβ Accumulation. CNS Neurol Disord Drug Targets. 2015;14(3):360-9.

Chu S, Gu J, Feng L, Liu J, Zhang M, Jia X, Liu M, Yao D. Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses. Int Immunopharmacol. 2014 Apr;19(2):317-26.

Heng Y, Zhang QS, Mu Z, Hu JF, Yuan YH, Chen NH. Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecid-induced parkinsonism mouse model by targeting α-synuclein abnormalities in the substantia nigra. Toxicol Lett. 2016 Jan 22;243:7-21.

Liu XY, Zhou XY, Hou JC, Zhu H, Wang Z, Liu JX, Zheng YQ. Ginsenoside Rd promotes neurogenesis in rat brain after transient focal cerebral ischemia via activation of PI3K/Akt pathway. Acta Pharmacol Sin. 2015 Apr;36(4):421-8.

Wu SD, Xia F, Lin XM, Duan KL, Wang F, Lu QL, Cao H, Qian YH, Shi M. Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways. Int J Mol Sci. 2016 Jan 29;17(2). pii: E177.

Wan Q, Ma X, Zhang ZJ, Sun T, Xia F, Zhao G, Wu YM. Ginsenoside Reduces Cognitive Impairment During Chronic Cerebral Hypoperfusion Through Brain-Derived Neurotrophic Factor Regulated by Epigenetic Modulation. Mol Neurobiol. 2016 Mar 28.

Zhu G, Wang Y, Li J, Wang J.Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice. Neuroscience. 2015 Apr 30;292:81-9.

Liang W1, Ge S, Yang L, Yang M, Ye Z, Yan M, Du J, Luo Z. Ginsenosides Rb1 and Rg1 promote proliferation and expression of neurotrophic factors in primary Schwann cell cultures. Brain Res. 2010 Oct 21;1357:19-25.

Salim KN, McEwen BS, Chao HM. Ginsenoside Rb1 regulates ChAT, NGF and trkA mRNA expression in the rat brain. Brain Res Mol Brain Res. 1997 Jul;47(1-2):177-82.


1. Antioxidant activity /Preservation of Mitochondrial function

Oxidative stress causes molecular damage that can lead to critical failure of biological functions and ultimately cell death. Severe oxidative stress can eventually lead to mitochondrial dysfunction. Studies have demonstrated that oxidative stress and mitochondrial dysfunction often precedes Aβ plaque formation in AD, suggesting their importance in the early pathology of the disease. These factors are also important in the pathology of other neurodegenerative disorders such as Parkinson’s. Studies have demonstrated that neuroprotection provided by ginsenosides is at least partially attributed to their antioxidant activity as well as their ability to preserve mitochondrial function.


References:

D.D. Kitts, A.N. Wijewickreme, C. Hu Antioxidant properties of a North American ginseng extract. Mol. Cell. Biochem., 203 (2000), pp. 1–10)

Zhao H, Li Q, Zhang Z, Pei X, Wang J, Li Y. Long-term ginsenoside consumption prevents memory loss in aged SAMP8 mice by decreasing oxidative stress and up-regulating the plasticity-related proteins in hippocampus. Brain Res. 2009 Feb 23;1256:111-22.

Liu Y, Zhang RY, Zhao J, Dong Z, Feng DY, Wu R, Shi M, Zhao G. Ginsenoside Rd Protects SH-SY5Y Cells against 1-Methyl-4-phenylpyridinium Induced Injury. Int J Mol Sci. 2015 Jun 24;16(7):14395- 408.


2. Enhancement of cholinergic activity

Central cholinergic systems have been implicated in mediating learning and memory processes and AD is characterized by decreased cholinergic activity. Ginsenosides have been shown to increase the uptake of choline in the central cholinergic nerve endings and to facilitate the release of acetylcholine, effects that may counter the symptoms and progress of AD


References:

Kim MS, Yu JM, Kim HJ, Kim HB, Kim ST, Jang SK, Choi YW, Lee DI, Joo SS. Ginsenoside Re and Rd enhance the expression of cholinergic markers and neuronal differentiation in Neuro-2a cells. Biol Pharm Bull. 2014;37(5):826-33.

Benishin CG, Lee R, Wang LC, Liu HJ. Effects of ginsenoside Rb1 on central cholinergic metabolism. Pharmacology. 1991;42(4):223-9.


3. Reduction of apoptosis

It is generally accepted that massive neuronal death due to apoptosis is a common characteristic in the brains of patients suffering from neurodegenerative diseases, and apoptotic cell death has been found in neurons and glial cells in AD. Ginsenosides can attenuate this apoptosis.


References: Liu JF, Yan XD, Qi LS, Li L, Hu GY, Li P, Zhao G. Ginsenoside Rd attenuates Aβ25-35-induced oxidative stress and apoptosis in primary cultured hippocampal neurons. Chem Biol Interact. 2015 Sep 5;239:12-8.

Huang XP, Tan H, Chen BY, Deng CQ. Chin J. Combination of total astragalus extract and total Panax notoginseng saponins strengthened the protective effects on brain damage through improving energy metabolism and inhibiting apoptosis after cerebral ischemia-reperfusion in mice. Integr Med. 2015 Mar 24.

Shimohama S. Apoptosis in Alzheimer's disease--an update. Apoptosis. 2000 Feb;5(1):9-16. Review.

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