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.
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.
Increases expressions of nuclear factor-κB and transforming growth factor-β
Suppresses activities of SOD and GSH-PX
Attenuates progressive accumulation of type IV collagen
Decreases concentrations of the metabolites of monoamines, glutamate, and glutamine
Increased the SOD activity of the mitochondrial fraction in the cortex, hippocampus, and striatum
Suppresses TBARS formation
Reduces the expression of the IL-1β, IL-6, TNF-α mRNA
Restores the abnormal activities NOS and levels of CP, MDA, GSH and NO induced by D-gal
Attenuates CUS-induced decreases in noradrenaline and dopamine
Reverses CUS-induced increase MDA content
Suppresses the downregulation of Bcl-2, upregulation of Bax, the release of mitochondrial cytochrome c into cytosol
and sequential activation of caspase-9 and caspase-3
Reduces 6-OHDA-induced intracellular ROS production and GSH depletion
Inhibits mitochondrial membrane instability
Protects TH-immunoreactive cells and fibers in the nigrostriatal region from MPTP toxicity
Table 1 Mechanisms of protection from neuronal damage and cell apoptosis by DSS
Attenuated impairment induced by MECA and SCOP plus MECA and central acetylcholinergic neurotoxin ethylcholine mustard aziridinium ion (AF64A).
Scavenging free radicals and enhancing the cell stress.
Reverse morphological defects induced by Aβ oligomers and neutralizing reactive oxygen species.
Attenuating phosphorylation of ERK1/2 activated by Abeta oligomers and modulating the expression of an anti-oxidative protein Peroxiredoxin.
Protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems.
Increasing GSH content, suppressing of NOS activity and NO level
Decreasing of CP and MDA levels
Rely on reversal of the muscarinic M1-receptor-mediated inhibition of LTP
Blocking L-type Ca2+ channels in NG108-15 cells
Inhibiting sodium current in mouse hippocampal CA1 neurons
Modulating ASICs activity and protein expression and producing protective effects for PC12 cells against MPP(+) and acidosis-induced cytotoxicity
Protecting effect on dopaminergic neurodegeneration and attenuating the MPTP-induced toxicity
Preventing CA1 neurondamage and suppressing the expression of NF-kappaB in hippocampus
Inhibiting Bax/Bcl-2 ratio, cytochrome c release and decreasing mitochondrial membrane potential and activity of caspase-3 and caspase-9
Upregulating significantly anti-inflammatory cytokines and downregulating proinflammatory cytokines
Reversing neuroinflammtory-induced activation of NF-κB signaling pathways and inhibiting the activation ofNALP3 inflammasome, caspase-1, and IL-1β
Inhibiting up-regulations of pro-inflamamtory mediators (TNFα, IL-1β, iNOS, COX-2 and 5-LOX)
Protecting against hypoxia-induced factor-1α (HIF-1α) accumulation
Inhibiting up-regulation of p53 and Bcl-2/adenovirus E1B 19kDa interacting protein 3 (BNIP3)
Ameliorating effect on the 6-OHDA-induced neurological damage
Activating A1R to produce the neuroprotection in cerebral ischemia
Ligustilide or Z-ligustilide
Reducing the expression of upregulation of TLR4 mRNA Lipopolysaccharide-induced
Reducing the level of MDA as well as increasing the activity of Na(+)-K(+)-ATPase
Raising the expression of GAP-43 and reducing cleaved caspase-3 and GFAP levels
Decreasing Akt and Forkhead box class O1 phosphorylation and upregulating Klotho expression
Increasing BDNF and phosphorylated cAMP-responsive element binding protein (p-CREB) levels and γ-aminobutyric acid (GABA) expression
Improving Nrf2 nuclear translocation and increasing Nrf2 and HO-1 protein expression
Up-regulating erythropoietin and inhibiting RTP801 expression
Increasing SOD activity and reducing malondialdehyde levels
Increasing the Bcl-2 expression and decreasing in Bax and caspase-3 immunoreactivities
Increasing the activities of the antioxidant enzyme GSH-PX
Inhibiting the expressions of nitrotyrosine and iNOS to mediate the free radical-scavenging activity
Suppressing prostaglandin E(2) production and lipopolysaccharide/interferon-gamma-induced inflammation in cultured glial cells
Reducing proinflammatory mediator production and cerebral ischemia/reperfusion-induced inflammatory cell activation
Reducing cerebral I/R-induced internucleosomal DNA fragmentation, caspase-3, caspase-8 and caspase-9activation, and cytochrome c release
Suppressing the consequent production of monocyte chemoattractant protein 1 (MCP-1)
Table 2 Mechanisms underlying neural protection by individual DSS ingredients
Figure 1. DSS-mediated resolution of Aβ in Alzheimer’s Disease
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