Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2016, Vol. 7 Issue (4) : 502-513     DOI: 10.14336/AD.2015.1220
Review Article |
Danggui-Shaoyao-San: New Hope for Alzheimer's Disease
Fu Xin1, Wang QiuHong1, Wang ZhiBin1, Kuang HaiXue1,*, Jiang Pinghui2
1School of Pharmacy, Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.
2College of Electrical and Information Engineering, Heilongjiang Institute of Technology, Harbin 150050, China.
Download: PDF(985 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    

Danggui-Shaoyao-San (DSS), also called Toki-shakuyaku-san (TJ-23) or Dangguijakyak-san (DJS), is a well-known herbal formula (Angelica sinensis (Oliv.) Diels., Ligusticum chuanxiong Hort., Paeonia lactiflora pall., Poria cocos (Schw.) Wolf, Alisma orientalis (Sam.) Juzep., Atractylodes macrocephala Koidz.), which has been widely used in oriental countries for the treatment of various gynecological diseases. Recent studies show that DSS has an effect on free radical-mediated neurological diseases and exhibits anti-inflammatory and antioxidant activities and reduces cell apoptosis in the hippocampus. In addition, DSS mediates the modulation of central monoamine neurotransmitter systems and ameliorates dysfunction of the central cholinergic nervous system and scopolamine-induced decrease in ACh levels. DSS improves the function of the dopaminergic, adrenergic, and serotonergic nervous systems. Interestingly, DSS can alleviate cognitive dysfunction of Alzheimer's disease (AD) patients, suggesting that it is a useful therapeutic agent for AD. This paper reviews the mechanism of DSS for the treatment of AD.

Keywords Danggui-Shaoyao-San      Alzheimer's disease      anti-inflammation      antioxidant activity      cell apoptosis     
Corresponding Authors: Kuang HaiXue   
About author:

These authors had equal contribution and are designated as co-first authors.

Issue Date: 01 August 2016
E-mail this article
E-mail Alert
Articles by authors
Fu Xin
Wang QiuHong
Wang ZhiBin
Kuang HaiXue
Jiang Pinghui
Cite this article:   
Fu Xin,Wang QiuHong,Wang ZhiBin, et al. Danggui-Shaoyao-San: New Hope for Alzheimer's Disease[J]. Aging and disease, 2016, 7(4): 502-513.
URL:     OR
Increases expressions of nuclear factor-κB and transforming growth factor-β[2]
Suppresses activities of SOD and GSH-PX[2]
Attenuates progressive accumulation of type IV collagen[2]
Decreases concentrations of the metabolites of monoamines, glutamate, and glutamine[3]
Increased the SOD activity of the mitochondrial fraction in the cortex, hippocampus, and striatum[3]
Suppresses TBARS formation[3]
Reduces the expression of the IL-1β, IL-6, TNF-α mRNA[4]
Restores the abnormal activities NOS and levels of CP, MDA, GSH and NO induced by D-gal[5]
Attenuates CUS-induced decreases in noradrenaline and dopamine[6]
Reverses CUS-induced increase MDA content[6]
Suppresses the downregulation of Bcl-2, upregulation of Bax, the release of mitochondrial cytochrome c into cytosol[7]
and sequential activation of caspase-9 and caspase-3[7]
Reduces 6-OHDA-induced intracellular ROS production and GSH depletion[8]
Inhibits mitochondrial membrane instability[8]
Protects TH-immunoreactive cells and fibers in the nigrostriatal region from MPTP toxicity[9]
Table 1  Mechanisms of protection from neuronal damage and cell apoptosis by DSS
Main componentMechanismReference
Ferulic acidAttenuated impairment induced by MECA and SCOP plus MECA and central acetylcholinergic neurotoxin ethylcholine mustard aziridinium ion (AF64A).[10]
Scavenging free radicals and enhancing the cell stress.[11]
Reverse morphological defects induced by Aβ oligomers and neutralizing reactive oxygen species.[12]
Attenuating phosphorylation of ERK1/2 activated by Abeta oligomers and modulating the expression of an anti-oxidative protein Peroxiredoxin.[13]
Protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems.[14]
PaeoniflorinIncreasing GSH content, suppressing of NOS activity and NO level[15]
Decreasing of CP and MDA levels[15]
Rely on reversal of the muscarinic M1-receptor-mediated inhibition of LTP[16]
Blocking L-type Ca2+ channels in NG108-15 cells[17]
Inhibiting sodium current in mouse hippocampal CA1 neurons[18]
Modulating ASICs activity and protein expression and producing protective effects for PC12 cells against MPP(+) and acidosis-induced cytotoxicity[19]
Protecting effect on dopaminergic neurodegeneration and attenuating the MPTP-induced toxicity[20]
Preventing CA1 neurondamage and suppressing the expression of NF-kappaB in hippocampus[21]
Inhibiting Bax/Bcl-2 ratio, cytochrome c release and decreasing mitochondrial membrane potential and activity of caspase-3 and caspase-9[22]
Upregulating significantly anti-inflammatory cytokines and downregulating proinflammatory cytokines[23]
Reversing neuroinflammtory-induced activation of NF-κB signaling pathways and inhibiting the activation ofNALP3 inflammasome, caspase-1, and IL-1β[23]
Inhibiting up-regulations of pro-inflamamtory mediators (TNFα, IL-1β, iNOS, COX-2 and 5-LOX)[24]
Protecting against hypoxia-induced factor-1α (HIF-1α) accumulation[25]
Inhibiting up-regulation of p53 and Bcl-2/adenovirus E1B 19kDa interacting protein 3 (BNIP3)[25]
PaeoniflorinAmeliorating effect on the 6-OHDA-induced neurological damage[26]
Activating A1R to produce the neuroprotection in cerebral ischemia[27]
Ligustilide or Z-ligustilideReducing the expression of upregulation of TLR4 mRNA Lipopolysaccharide-induced[28]
Reducing the level of MDA as well as increasing the activity of Na(+)-K(+)-ATPase[29]
Raising the expression of GAP-43 and reducing cleaved caspase-3 and GFAP levels[29]
Decreasing Akt and Forkhead box class O1 phosphorylation and upregulating Klotho expression[30]
Increasing BDNF and phosphorylated cAMP-responsive element binding protein (p-CREB) levels and γ-aminobutyric acid (GABA) expression[31]
Improving Nrf2 nuclear translocation and increasing Nrf2 and HO-1 protein expression[32]
Up-regulating erythropoietin and inhibiting RTP801 expression[33]
Increasing SOD activity and reducing malondialdehyde levels[34]
Increasing the Bcl-2 expression and decreasing in Bax and caspase-3 immunoreactivities[35]
Increasing the activities of the antioxidant enzyme GSH-PX[35]
TMPZInhibiting the expressions of nitrotyrosine and iNOS to mediate the free radical-scavenging activity[36]
Suppressing prostaglandin E(2) production and lipopolysaccharide/interferon-gamma-induced inflammation in cultured glial cells[37]
Reducing proinflammatory mediator production and cerebral ischemia/reperfusion-induced inflammatory cell activation[37]
Reducing cerebral I/R-induced internucleosomal DNA fragmentation, caspase-3, caspase-8 and caspase-9activation, and cytochrome c release[38]
Suppressing the consequent production of monocyte chemoattractant protein 1 (MCP-1)[38]
Table 2  Mechanisms underlying neural protection by individual DSS ingredients
Figure 1.  DSS-mediated resolution of Aβ in Alzheimer’s Disease
[1] Chen L, Qi J, Chang YX, Zhu D, Yu B (2009). Identification and determination of the major constituents in Traditional Chinese Medicinal formula Danggui-Shaoyao-San by HPLC-DAD-ESI-MS/MS. J Pharm Biomed Anal, 50:127-137.
[2] Liu IM, Tzeng TF, Liou SS, Chang CJ (2012). Beneficial effect of traditional Chinese medicinal formula danggui-shaoyao-san on advanced glycation end-product-mediated renal injury in streptozotocin-diabetic rats. Evid Based Complement Alternat Med, 2012:140103.
[3] Ueda Y, Kamasu M, Hiramatsu M (1996). Free radical scavenging activity of the Japanese herbal medicine toki-shakuyaku-san (TJ-23) and its effect on superoxide dismutase activity, lipid peroxides, glutamate, and monoaminemetabolites in agedratbrain. Neurochem Res, 21:909-914.
[4] Zhong S, Ma S, Hong Z, Jin X (2011). Anti-inflammation effect of danggui shaoyao san on Alzheimer's diseases. Zhongguo Zhong Yao Za Zhi, 36:3155-3160.
[5] Lan Z, Liu J, Chen L, Fu Q, Luo J, Qu R, et al (2012). Danggui-Shaoyao-San ameliorates cognition deficits and attenuates oxidative stress-related neuronal apoptosis in d-galactose-induced senescent mice. J Ethnopharmacol, 141:386-395.
[6] Huang Z, Mao QQ, Zhong XM, Li ZY, Qiu FM, Ip SP (2012). Mechanistic Study on the Antidepressant-Like Effect of Danggui-Shaoyao-San, a Chinese Herbal Formula. Evid Based Complement Alternat Med, 2012: 173565.
[7] Qian YF, Wang H, Yao WB, Gao XD (2008). Aqueous extract of the Chinese medicine, Danggui-Shaoyao-San, inhibits apoptosis in hydrogen peroxide-induced PC12 cells by preventing cytochrome c release and inactivating of caspase cascade. Cell Biol Int, 32:304-311.
[8] Hwang DS, Kim HG, Kwon HJ, Cho JH, Lee CH, Lee JM, et al (2011). Dangguijakyak-san, a medicinal herbal formula, protects dopaminergic neurons from 6-hydroxydopamine-induced neurotoxicity. J Ethnopharmacol, 133: 934-939.
[9] Lee JM, Hwang DS, Kim HG, Lee CH, Oh MS (2012). Dangguijakyak-san protects dopamine neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity under postmenopausal conditions. J Ethnopharmacol, 139:883-888.
[10] Tsai FS, Wu LY, Yang SE, Cheng HY, Tsai CC, Wu CR, et al (2015). Ferulic acid reverses the cognitive dysfunction caused by amyloid β peptide 1-40 through anti-oxidant activity and cholinergic activation in rats. Am J Chin Med, 43:319-335.
[11] Mancuso C, Santangelo R (2014). Ferulic acid: pharmacological and toxicological aspects. Food Chem Toxicol, 65:185-195.
[12] Picone P, Nuzzo D, Di Carlo M (2013). Ferulic acid: a natural antioxidant against oxidative stress induced by oligomeric A-beta on sea urchin embryo. Biol Bull, 224: 18-28.
[13] Picone P, Bondi ML, Montana G, Bruno A, Pitarresi G, Giammona G, et al (2009). Ferulic acid inhibits oxidative stress and cell death induced by Ab oligomers: improved delivery by solid lipid nanoparticles. Free Radic Res, 43:1133-1145.
[14] Kanski J, Aksenova M, Stoyanova A, Butterfield DA (2002). Ferulic acid antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro: structure-activity studies. J Nutr Biochem, 13: 273-281.
[15] Zhong SZ, Ge QH, Li Q, Qu R, Ma SP (2009). Peoniflorin attentuates Aβ ((1-42))-mediated neurotoxicity by regulating calciumhomeostasis and ameliorating oxidative stress in hippocampus of rats. J Neurol Sci, 280: 71-78.
[16] Tabata K, Matsumoto K, Watanabe H (2000). Paeoniflorin, a major constituent of peony root, reverses muscarinic M1-receptor antagonist-induced suppression of long-term potentiation in the rat hippocampal slice. Jpn J Pharmacol, 83: 25-30.
[17] Tsai TY, Wu SN, Liu YC, Wu AZ, Tsai YC (2005). Inhibitory action of L-type Ca2+ current by paeoniflorin, a major constituent of peony root, in NG108-15 neuronal cells. Eur J Pharmacol, 523: 16-24.
[18] Zhang GQ, Hao XM, Chen SZ, Zhou PA, Cheng HP, Wu CH (2003). Blockade of paeoniflorin on sodium current in mouse hippocampal CA1 neurons. Acta Pharmacol Sin, 24: 1248-1252.
[19] Sun X, Cao YB, Hu LF, Yang YP, Li J, Wang F, et al (2011). ASICs mediate the modulatory effect by paeoniflorin on α-synuclein autophagicdegradation. Brain Res, 1396:77-87.
[20] Liu HQ, Zhang WY, Luo XT, Ye Y, Zhu XZ (2006). Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of the Parkinson's disease by activation of a denosine A1 receptor. Br J Pharmacol, 148: 314-325.
[21] Liu J, Jin DZ, Xiao L, Zhu XZ (2006). Paeoniflorin attenuates chronic cerebral hypoperfusion-induced learning dysfunctionand brain damage in rats. Brain Res, 1089: 162-170.
[22] Wang K, Zhu L, Zhu X, Zhang K, Huang B, Zhang J, et al (2014). Protective effect of paeoniflorin on Aβ25-35-induced SH-SY5Y cell injury by preventing mitochondrial dysfunction. Cell Mol Neurobiol, 34: 227-234.
[23] Zhang HR, Peng JH, Cheng XB, Shi BZ, Zhang MY, Xu RX (2015). Paeoniflorin Atttenuates Amyloidogenesis and the Inflammatory Responses in a Transgenic Mouse Model of Alzheimer's Disease. Neurochem Res, 40: 1583-1592.
[24] Guo RB, Wang GF, Zhao AP, Gu J, Sun XL, Hu G (2012). Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses. PLoS One, 7: e49701.
[25] Ji Q, Yang L, Zhou J, Lin R, Zhang J, Lin Q, et al (2012). Protective effects of paeoniflorin against cobalt chloride-induced apoptosis of endothelial cells via HIF-1α pathway. Toxicol In Vitro, 26: 455-461.
[26] Liu DZ, Zhu J, Jin DZ, Zhang LM, Ji XQ, Ye Y, et al (2007). Behavioral recovery following sub-chronic paeoniflorin administration in the striatal 6-OHDA lesion rodent model of Parkinson's disease. J Ethnopharmacol, 112: 327-332.
[27] Liu DZ, Xie KQ, Ji XQ, Ye Y, Jiang CL, Zhu XZ, et al (2005). Neuroprotective effect of paeoniflorin on cerebral ischemic rat by activating adenosine A1 receptor in a manner different from its classical agonists, 146: 604-611.
[28] Qian B, Li F, Zhao LX, Dong YL, Gao YJ, Zhang ZJ (2015). Ligustilide Ameliorates Inflammatory Pain and Inhibits TLR4 Upregulation in Spinal Astrocytes Following Complete Freund's Adjuvant Peripheral Injection. Cell Mol Neurobiol, First online: 27 June 2015
[29] Li JJ, Zhu Q, Lu YP, Zhao P, Feng ZB, Qian ZM, et al (2015). Ligustilide prevents cognitive impairment and attenuates neurotoxicity in D-galactose induced aging mice brain. Brain Res, 1595:19-28.
[30] Kuang X, Chen YS, Wang LF, Li YJ, Liu K, Zhang MX, et al (2014). Klotho upregulation contributes to the neuroprotection of ligustilide in an Alzheimer's disease mouse model. Neurobiol Aging, 35: 169-178.
[31] Xin J, Zhang J, Yang Y, Deng M, Xie X (2013). Radix Angelica Sinensis that contains the component Z-ligustilide promotes adult neurogenesis to mediate recovery from cognitive impairment. Curr Neurovasc Res, 10: 304-315.
[32] Peng B, Zhao P, Lu YP, Chen MM, Sun H, Wu XM, et al (2013). Z-ligustilide actviates the Nrf2/HO-1 pathway and protects against cerebral ischemia-reperfusion injury in vivo and in vitro. Brain Res, 1520: 168-177.
[33] Wu XM, Qian ZM, Zhu L, Du F, Yung WH, Gong Q, et al (2011). Neuroprotective effect of ligustilide against ischaemia-reperfusion injury via up-regulation of erythropoietin and down-regulation of RTP801. Br J Pharmacol. 164: 332-343.
[34] Kuang X, Du JR, Liu YX, Zhang GY, Peng HY (2008). Postischemic administration of Z-Ligustilide ameliorates cognitive dysfunction and brain damage induced by permanent forebrain ischemia in rats. Pharmacol Biochem Behav. 88: 213-221.
[35] Kuang X, Yao Y, Du JR, Liu YX, Wang CY, Qian ZM (2006). Neuroprotective role of Z-ligustilide against forebrain ischemic injury in ICR mice. Brain Res. 1102: 145-153.
[36] Hsiao G, Chen YC, Lin JH, Lin KH, Chou DS, Lin CH, et al (2006). Inhibitory mechanisms of tetramethyl-pyrazine in middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats. Planta Med, 72: 411-417.
[37] Liao SL, Kao TK, Chen WY, Lin YS, Chen SY, Raung SL, et al (2004). Tetramethylpyrazine reduces ischemic brain injury in rats. Neurosci Lett, 372: 40-45.
[38] Kao TK, Ou YC, Kuo JS, et al (2006). Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats. Neurochem Int. 48: 166-176.
[39] Hu WX, Xiang Q, Wen Z, He D, Wu XM, Hu GZ, et al (2014). Neuroprotective effect of Atractylodes macrocephalaon polysaccharides in vitro on neuronal apoptosis induced by hypoxia. Mol Med Rep, 9: 2573-2581.
[40] Zengyong Q, Jiangwei M, Huajin L (2011). Effect of Ligusticum wallichii aqueous extract on oxidative injury and immunity activity in myocardial ischemic reperfusion rats. Int J Mol Sci, 12: 1991-2006.
[41] Kou J, Zhu D, Yan Y (2005). Neuroprotective effects of the aqueous extract of the Chinese medicine Danggui-Shaoyao-san on aged mice. J Ethnopharmacol, 97: 313-318.
[42] Xu F, Peng D, Tao C, Yin D, Kou J, Zhu D, et al (2011). Anti-depression effects of Danggui-Shaoyao-San, a fixed combination of Traditional Chinese Medicine, on depression model in mice and rats. Phytomedicine, 18: 1130-1136.
[43] Arendt T, Allen Y, Sinden J, Schugens MM, Marchbanks RM, Lantos PL, et al (1988). Cholinergic-rich brain transplants reverse alcohol-induced memory deficits. Nature, 332:448.
[44] Itoh T, Murai S, Saito H, et al (1998). Effects of single and repeated administrations of Toki-shakuyaku-san on the concentrations of brain neurotransmitters in mice. Methods Find Exp Clin Pharmacol. 20(1):11-17.
[45] Itoh T, Michijiri S, Murai S, Saito H, Nakamura K, Itsukaichi O, et al (1996). Regulatory effect of danggui-shaoyao-san on central cholinergic nervous system dysfunction in mice. Am J Chin Med, 24: 205-217.
[46] Song QH, Toriizuka K, Jin GB, Yabe T, Cyong JC (2001). Long term effects of Toki-shakuyaku-san on brain dopamine and nerve growth factor in olfactory-bulb-lesioned mice. Jpn J Pharmacol, 86: 183-188.
[47] Toriizuka K, Hou P, Yabe T, Iijima K, Hanawa T, Cyong JC (2000). Effects of Kampo medicine, Toki-shakuyaku-san (Tang-Kuei-Shao-Yao-San), on choline acetyltransferase activity and norepinephrine contents in brain regions, and mitogenic activity of splenic lymphocytes in ovariectomized mice. J Ethnopharmacol, 71: 133-143.
[48] Kou J, Zhu D, Yan Y (2005). Neuroprotective effects of the aqueous extract of the Chinese medicine Danggui-Shaoyao-san on aged mice. J Ethnopharmacol, 97:313-318.
[49] Hatip-Al-Khatib I, Hatip FB, Yoshimitsu Y, Iwasaki K, Egashira N, Liu AX, et al (2007). Effect of Toki-shakuyaku-san on acetylcholine level and blood flow in dorsal hippocampus of intact and twice-repeated ischemic rats. Phytother Res, 21:291-294.
[50] Komatsu M, Ueda Y, Hiramatsu M (1999). Different changes in concentrations of monoamines and their metabolites and amino acids in various brain regions by the herbal medicine/Toki-Shakuyaku-San between female and male senescence-accelerated mice (SAMP8). Neurochem Res, 24:825-831.
[51] Usuki S (1991). Blended effects of herbal components of tokishakuyakusan on somatomedin C/insulin-like growth factor 1 level in rat corpus luteum. Am J Chin Med, 19: 61-64.
[52] Koyama T, Hagino N, Cothron AW, Saito M (1989). Neuroendocrine effect of toki-shakuyaku-san on ovulation in rats. Am J Chin Med, 17: 29-33.
[53] Kitabayashi Y, Shibata K, Nakamae T, Narumoto J, Fukui K (2007). Effect of traditional Japanese herbal medicine toki-shakuyakusan for mild cognitive impairment: SPECT study. Psychiatry Clin Neurosci, 61: 447-448.
[54] Enomoto K, Higashida H, Maeno T (1992). Effects of toki-shakuyaku-san (Tsumura TJ-23) on electrical activity in neuroblastoma cells and frog neuromuscular junctions. Neurosci Res, 15: 81-89.
[55] Lu MC (2001). Danggui shaoyao san improve colchichine-induced learning acquisition impairment in rats. Acta Pharmacol Sin, 22:1149-1153.
[56] Iizuka S, Ishige A, Komatsu Y, Matsumiya T, Inazu M, Takeda H (1998). Effects of Toki-shakuyaku-san on electric footshock stress in ovariectomized mice. Methods Find Exp Clin Pharmacol, 20: 39-46.
[57] Rudy CC, Hunsberger HC, Weitzner DS, Reed MN2 (2015). The Role of the Tripartite Glutamatergic Synapse in the Pathophysiology of Alzheimer’s Disease. Aging and Disease, 6: 131-148.
[58] Curtis DR, Phillis JW, Watkins JC (1960). The chemical excitation of spinal neurones by certain acidic amino acids. The Journal of physiology, 150: 656-682.
[59] Sheldon AL, Robinson MB (2007). The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention. Neurochem Int, 51:333-355.
[60] Lu MC (2001). Danggui shaoyao san improve colchichine-induced learning acquisition impairment in rats. Acta Pharmacol Sin, 22: 1149-1153.
[61] Matsuoka T, Narumoto J, Shibata K, Okamura A, Taniguchi S, Kitabayashi Y, et al (2012). Effect of toki-shakuyaku-san on regional cerebral blood flow in patients with mild cognitive impairment and Alzheimer's disease. Evid Based Complement Alternat Med, 2012:245091.
[62] Akase T, Hihara E, Shimada T, Kojima K, Akase T, Tashiro S, Aburada M (2007). Efficacy of Tokishakuyakusan on the anemia in the iron-deficient pregnant rats. Biol Pharm Bull, 30: 1523-1528.
[63] Egashira N, Iwasaki K, Akiyoshi Y, Takagaki Y, Hatip-Al-Khatib I, Mishima K, et al (2005). Protective effect of Toki-shakuyaku-san on amyloid beta25-35-induced neuronal damage in cultured rat cortical neurons. Phytother Res, 19:450-453.
[64] Pu F, Mishima K, Egashira N, et al (2005). Post-ischemic treatment with toki-shakuyaku-san (tang-gui-shao-yao-san) prevents the impairment of spatial memory induced by repeated cerebral ischemia in rats. Am J Chin Med, 33:475-489.
[65] Hatip-Al-Khatib I, Egashira N, Mishima K, Iwasaki K, Iwasaki K, Kurauchi K, et al (2004). Determination of the effectiveness of components of the herbal medicine Toki-Shakuyaku-San and fractions of Angelica acutiloba in improving the scopolamine-induced impairment of rat's spatial cognition in eight-armed radial maze test. J Pharmacol Sci, 96: 33-41.
[66] Hardingham GE, Bading H (2010). Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat Rev Neurosci, 11: 682-696.
[67] Mizushima Y, Kan S, Yoshida S, Irie Y, Urata Y (2003). Effect of Choto-san, a Kampo medicine, on impairment of passive avoidance performance in senescence accelerated mouse (SAM). Phytother Res, 17:542-545.
[68] Hu ZY, Liu G, Yuan H, Yang S, Zhou WX, Zhang YX, et al (2010). Danggui-Shaoyao-San and its active fraction JD-30 improve Aβ-induced spatial recognition deficits in mice. J Ethnopharmacol, 128: 365-372.
[69] Hu ZY, Liu G, Cheng XR, Huang Y, Yang S, Qiao SY, et al (2012). JD-30, an active fraction extracted from Danggui-Shaoyao-San, decreases β-amyloid content and deposition, improves LTP reduction and prevents spatial cognition impairment in SAMP8 mice. Exp Gerontol, 47: 14-22.
[70] Borroni B, Colciaghi F, Lenzi GL, Caimi L, Cattabeni F, Di Luca M, et al (2003). High cholesterol affects platelet APP processing in controls and in AD patients. Neurobiol Aging, 24: 631-636.
[71] Huang Y, Hu ZY, Yuan H, Shu L, Liu G, Qiao SY, et al (2014). Danggui-Shaoyao-San Improves Learning and Memory in Female SAMP8 via Modulation of Estradiol. Evid Based Complement Alternat Med, 2014:327294.
[72] Qu HG, Cheng SW, Tian RB, Li ZL, Lei WL, Wang HQ, et al (2008). Effects of the aqueous extract of the Chinese medicine Danggui-Shaoyao-San on rat pineal melatonin synthesis. Neuro Endocrinol Lett, 29: 366-372.
[73] Birge SJ (1997). The role of estrogen in the treatment of Alzheimer’s disease. Neurology, 48:S36.
[74] Usuki S (1990). Effects of tokishakuyakusan and keishibukuryogan on steroidogenesis by rat preovulatory follicles in vivo. Am J Chin Med, 18: 149-156.
[75] He WQ, Lv WS, Zhang Y, Qu Z, Wei RR, Zhang L, et al (2015). Study on Pharmacokinetics of Three Preparations from Levistolide A by LC-MS-MS. J Chromatogr Sci, 53: 1265-1273.
[76] Bramanti E, Fulgentini L, Bizzarri R, Lenci F, Sgarbossa A (2013). β-Amyloid amorphous aggregates induced by the small natural molecule ferulic acid. J Phys Chem B. 117: 13816-13821.
[77] Mori T, Koyama N, Guillot-Sestier MV, Tan J, Town T (2013). Ferulic acid is a nutraceutical β-secretase modulator that improves behavioral impairment and alzheimer-like pathology in transgenic mice. PLoS One, 8: e55774.
[78] Yan JJ, Jung JS, Kim TK, Hasan A, Hong CW, Nam JS, et al (2013). Protective effects of ferulic acid in amyloid precursor protein plus presenilin-1 transgenic mouse model of Alzheimer disease. Biol Pharm Bull, 36: 140-143.
[79] Cho JY, Kim HS, Kim DH, Yan JJ, Suh HW, Song DK (2005). Inhibitory effects of long-term administration of ferulic acid on astrocyte activation induced by intracerebroventricular injection of beta-amyloid peptide (1-42) in mice. Prog Neuropsychopharmacol Biol Psychiatry, 29: 901-907.
[80] Cui L, Zhang Y, Cao H, Wang Y, Teng T, Ma G, et al (2013). Ferulic Acid Inhibits the Transition of Amyloid-β42 Monomers to Oligomers but Accelerates the Transition from Oligomers to Fibrils. J Alzheimers Dis, 37: 19-28.
[81] Mori T, Koyama N, Guillot-Sestier MV, Tan J, Town T (2013). Ferulic acid is a nutraceutical β-secretase modulator that improves behavioral impairment and Alzheimer-like pathology in transgenic mice. PLoS One, 8:e55774.
[82] Li J, Ji X, Zhang J, Shi G, Zhu X, Wang K (2014). Paeoniflorin attenuates Aβ25-35-induced neurotoxicity in PC12 cells by preventing mitochondrial dysfunction. Folia Neuropathol, 52: 285-290.
[83] Kuang X, Du JR, Chen YS, Wang J, Wang YN (2009). Protective effect of Z-ligustilide against amyloid beta-induced neurotoxicity is associated with decreased pro-inflammatory markers in rat brains. Pharmacol Biochem Behav, 92: 635-641.
[84] Kim MJ, Seong AR, Yoo JY, Jin CH, Lee YH, Kim YJ, et al (2011). Gallic acid, a histone acetyltransferase inhibitor, suppresses β-amyloid neurotoxicity by inhibiting microglial-mediated neuroinflammation. Mol Nutr Food Res, 55: 1798-1808.
[85] Bastianetto S, Yao ZX, Papadopoulos V, Quirion R (2006). Neuroprotective effects of green and black teas and their catechin gallate esters against beta-amyloid-induced toxicity. Eur J Neurosci, 23: 55-64.
[86] Ho SL, Poon CY, Lin C, Yan T, Kwong DW, Yung KK, et al (2015). Inhibition of β-amyloid aggregation by albiflorin, aloeemodin and neohesperidin and their neuroprotective effect on primary hippocampal cells against β-amyloid induced toxicity. Curr Alzheimer Res, 12: 424-433.
[87] Kwon EY, Cho YY, Do GM, Kim HJ, Jeon SM, Park YB, et al (2009). Actions of ferulic acid and vitamin E on prevention of hypercholesterolemia and atherogenic lesion formation in apolipoprotein E-deficient mice. J Med Food, 12: 996-1003.
[88] Chao J, Huo TI, Cheng HY, Tsai JC, Liao JW, Lee MS, et al (2014). Gallic acid ameliorated impaired glucose and lipid homeostasis in high fat diet-induced NAFLD mice. PLoS One, 9: e96969.
[89] Choi R, Kim BH, Naowaboot J, Lee MY, Hyun MR, Cho EJ, et al (2011). Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes. Exp Mol Med, 43: 676-683.
[90] Chakrabarti S, Sinha M, Thakurta IG, Banerjee P, Chattopadhyay M (2013). Oxidative stress and amyloid beta toxicity in Alzheimer's disease: intervention in a complex relationship by antioxidants. Curr Med Chem, 20: 4648-4664.
[91] Santos RX, Correia SC, Wang X, Perry G, Smith MA, Moreira PI, et al. (2010). A synergistic dysfunction of mitochondrial fission/fusion dynamics and mitophagy in Alzheimer’s disease. J Alzheimers Dis, 20: S401-S412.
[92] Evans RM, Emsley CL, Gao S, Sahota A, Hall KS, Farlow MR, et al (2000). A synergistic dysfunction of mitochondrial fission/fusion dynamics and: a population-based study of African Americans. Neurology, 54: 240-242.
[93] Wolozin B (2001). A fluid connection: cholesterol and Aβ. Proc Natl Acad Sci USA, 98: 5371-5373.
[94] Puglielli L, Tanzi RE, Kovacs DM (2003). Alzheimer's disease: the cholesterol connection. Nat Neurosci. 6: 345-351.
[95] Luchsinger JA, Tang MX, Shea S, Mayeux R (2004). Hyperinsulinemia and risk of Alzheimer disease. Neurology, 63:1187-1192.
[96] Masters CL, Beyreuther K (1987). Neuronal origin of cerebral amyloidogenic proteins: their role in Alzheimer's disease and unconventional virus diseases of the nervous system. Ciba Foundation symposium, 126: 49-64.
[97] Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, et al. (1987). The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature, 325: 733-736.
[98] Glenner GG, Murphy MA (1989). Amyloidosis of the nervous system. Journal of the neurological sciences, 94: 1-28.
[99] Palmert MR, Podlisny MB, Witker DS, Oltersdorf T, Younkin LH, Selkoe DJ, et al. (1989). The betaamyloid protein precursor of Alzheimer disease has soluble derivatives found in human brain and cerebrospinal fluid. Proceedings of the National Academy of Sciences of the United States of America, 86:6338-6342.
[100] Joachim CL, Selkoe DJ (1992). The seminal role of beta-amyloid in the pathogenesis of Alzheimer disease. Alzheimer disease and associated disorders. 6:7-34
[1] Chakrabarti Sasanka, Mohanakumar Kochupurackal P.. Aging and Neurodegeneration: A Tangle of Models and Mechanisms[J]. Aging and disease, 2016, 7(2): 111-113.
[2] Sasanka Chakrabarti,Vineet Kumar Khemka,Anindita Banerjee,Gargi Chatterjee,Anirban Ganguly,Atanu Biswas. Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment[J]. A&D, 2015, 6(4): 282-299.
Full text



Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail:
Powered by Beijing Magtech Co. Ltd