Evidence-Based Complementary and Alternative Medicine

Review Article

Neuroprotective Effects of Anthraquinones from Rhubarb in Central Nervous System Diseases

Table 1

List of the neuroprotective effects of anthraquinones in CNSD.


Disease	Anthraquinones	Outcomes	Application	Ref.

Ischemic stroke	Emodin	Improves NDS, reduces BBB permeability and decreases the infarction area via inhibiting the expression of Cx43 and AQP4	In vivo	18

	Emodin	Improves neurologic symptom evaluation score, brain water ratio and cerebral infarction area; inhibits cascade inflammatory reaction by increasing TGF-β level and depressing the levels of TNF-α/IL-1β/ICAM-1	In vivo	21

	Emodin	Enhances behavioral function, against apoptosis through increasing Bcl-2 expression and decreasing caspase-3 and BAX expression; increases BDNF expression and the phosphorylation of Akt/CREB	In vitroand In vivo	22

	Emodin	Inhibits H₂O₂-induced apoptosis in primary rat cortical neurons	In vitro	23

	Emodin	Inhibits neuronal apoptosis and alleviates the injury of PC12 nerve cells via increasing the expression of activin A	In vitro	24

	Chrysophanol	Inhibits NO-induced neuronal death through attenuating the levels of /3-NT, and decreases cleaved caspase-3 expression; increases total SOD/MnSOD activities and inhibits ROS generation	In vivo	29

	Chrysophanol	Decreases neurological deficits, infarct volume, brain edema and BBB permeability; inhibits inflammatory response via reducing the expression of IL-1β, caspase-1 as well as NALP3	In vivo	30

	Chrysophanol	Improves survival rate, reduces brain tissue loss, and improves neurological assessment and motor function; reduces the expression of TNF-α, IL-1β and NF-κB p65	In vivo	34

	Chrysophanol	Inhibits inflammatory response and neuronal apoptosis by attenuating the expression of ER stress-related factors including GRP78, CHOP, caspase-12 and IκB-α	In vivo	31

	Rhein	Improves NFSs and reduces infarction area; decreases MDA level and enhances the activities of SOD/CAT/GSH-Px; reduces the expression of BAX, caspase-9/3 and cleaved caspase-3, and increases the expression of Bcl-2	In vivo	35

	Rhubarb anthraquinones	Alleviates neurological impairment and cerebral infarction area, and inhibits neuronal apoptosis; increases the plasma levels of lipids, phosphocreatine/creatine and the urine levels of taurine, tyrosine, α-ketoglutaric acid/creatinine, and decreases the plasma levels of lactate, taurine, glutamate, glycine, methionine/glucose and the urine levels of choline, glycine, proline/glucose	In vivo	36

	Rhubarb anthraquinones	Decreases the intracranial hemorrhage ratio and mortality; reduces brain microvascular basement membrane impairment through decreasing the level of IgG and increasing the levels of CoLIV/LN	In vivo	37

	Rhubarb	Finds 287 DEPs and 76 overlapping DEPs between MG versus SG and RG versus MG; the related pathways including synaptic vesicle cycle, cGMP-PKG signaling pathway, amyotrophic lateral sclerosis, long-term potentiation, tuberculosis, and so on; increases the protein expression of Syn1 and ERK1/2	In vivo	38

	Rhubarb anthraquinones	The , t_1/2 and of aloe-emodin, rhein, emodin and chrysophanol are increased in CIS condition	In vivo	41

Intracerebral hemorrhage	Emodin	Triggers microglia cell apoptosis by increasing the activity of caspase 3/7; promotes activated microglia cell apoptosis by reducing the level of TNF-α and IL-1β, and induces the expression of TRB3 during microglial apoptosis	In vitro	42

	Rhubarb or rhubarb anthraquinones	Relieves neurological symptoms and attenuates BBB permeability by enhancing ZO-1 expression	In vivo	43

	Rhubarb	Maintains BBB integrity and reduces astrocyte end feet process swelling by inhibiting AQP-4 expression	In vivo	44

Traumatic brain injury	Emodin	Reduces brain damage, improves behavioral observation by inhibiting the expression and activity of iNOS, and attenuates the generation of NO	In vivo	48

	Emodin	Inhibits the EPSP, improves PPF of the EPSP, and inhibits glutamate excitotoxicity	In vitro	49

	Rhein and rhubarb	Reduces brain edema and BBB permeability through preventing activation of gp91phox subunit of NADPH oxidase induced ROS production; inhibits ERK/MMP-9 pathway	in vivo and in vitro	50

	Rhubarb	Down-regulates MMP-9 and up-regulates ZO-1 by inhibiting ERK signaling pathway	in vivo	51

	Rhein and rhubarb	Improves the activities of SOD and CAT, increases the level of GSH and the ratio of GSH/GSSG, and decreases the levels of MDA and GSSG	in vivo	52

	Rheum tanguticum polysaccharides	Decreases water content and the level of MDA, and improves the activities of Na+-K+ ATPase and total SOD	in vivo	53

	Emodin	Regulates the brain intracellular Ca²⁺ level	In vitro	54

Brain tumor	Danthron	Reduces mitochondrial membrane potential level, releases cytochrome c, AIF and Endo G from mitochondria, and increases caspase-9/3 levels and ROS production	in vitro	55

	Danthron	Inhibits the invasion and migration of GBM 8401 via decreasing the expressions of FAK, MMP-7, MMP-9, uPA and ROCK-1	in vitro	56

	Danthron	Kills GBM 8401 cells and induces apoptosis by increasing the levels of ROS, cytosolic Ca²⁺, caspase-8/9 and Bax, decreasing mitochondrial membrane potential levels and pro-caspase-8/9 protein levels, and activating caspase-3/8/9	in vitro	57

	Danthron	Induces DNA damage in GBM 8401 cells via decreasing the expressions of DNA damage and repair genes such as ATM, ATR, BRCA-1, 14-3-3σ, DNA-PK and MGMT	in vitro	58

	Aloe-emodin	Inhibits U87MG human glioma cells growth and blocks U87MG in S and G2/M phase via increasing the protein level of p53/p21 and decreasing AKT phosphorylation and CDK2 expression; induces U87MG apoptosis by reducing PARP expression and activating Lamin A, reduces U87MG cell density and tumor size, and improves the levels of P53 and caspase 8/3	in vivo and in vitro	59

	Physcion	Increases the expression of hST8Sia VI through ERK and p38 MAPK pathways in SK-N-BE(2)-C human neuroblastoma cells	in vitro	63

Alzheimer’s disease	Emodin	Decreases -induced neuron death and the levels of phospho-JNK 1/2, increases the phosphorylation of Akt and Bcl-2 expression	in vitro	66

	Emodin	Inhibits cell viability and the conversion ratio of LC3-I/LC3-II, reduces the level of lactate dehydrogenase; decreases the level of LC3-II positive cells in the cortex of AβPP/PS1 mice; improves Bcl-2 expression and reduces the expressions of Beclin-1 and hVps34	in vivo and in vitro	67

	Emodin	Decreases Aβ aggregation and tau hyperphosphorylation via reducing BACE1 levels and increasing PP2A activity; increases hippocampal neuron numbers and synapse-related proteins; suppresses oxidative stress by down-regulating MDA and up-regulating SOD, decreases DNA methyltransferases 1/3β level, inhibits microglial activation by reducing 5-LO, IL-6 and TNF-α, and improves cognitive function and cerebral microvesselar integrity	in vivo	70

	Chrysophanol	Increases the viability of neuronal cells, inhibits apoptosis via increasing Bcl-2 expression and decreasing the expression of Bax and AIF; reduces ROS levels and prevents mitochondrial fission by suppressing the dephosphorylation of Drp1	in vitro	71

	Rhein lysinate	Reduces APP by improving the expression of SIRT1, decreases the expressions of TNF-α and IL-6, reduces ROS levels and increases the levels of GSH-px and SOD	in vivo	72

	Rhein-huprine hybrids	Alleviates the Aβ-induced synaptic dysfunction, increases the content of synaptic proteins and induces LTP; reduces the levels of Aβ, improves mature APP levels, suppresses the activities of AChE, BuChE and BACE-1, and reduces the aggregation of Aβ	in vivo and in vitro	73

	Rhein-huprine hybrids	Decreases memory disorders and Aβ levels, reduces tau phosphorylation and brain inflammation, and induces LTP	in vivo	75

	Rhein-huprine hybrids	Suppresses the activities of AChE and BACE-1 via reducing oxidative stress and Aβ/tau aggregation	in vitro	76

	Tacrine-rhein hybrids	Inhibits AChE-induced Aβ aggregation, and shows metal-chelating activity with less side effects	in vivo and in vitro	74

	Danthron	Inhibits neuronal injury, and suppresses oxidative damage via reducing membrane lipid peroxidation	in vitro	65

Depression	Emodin	Improves behavioral performance, reduces serum corticosterone level, increases the expressions of BDNF and GR, and improves the anhedonia symptom by increasing sucrose consumption	in vivo	81

	Chrysophanol	Alleviates inflammation via reducing the levels of IL-1β/6 and TNF-α, and attenuates the expression of P2X7/NF-κB pathway related proteins inculding P2X7, p-IKKα, p-IKKβ, p-IκBα and p-NF-κBp65	in vivo	82

Epilepsy	Emodin	Restores behavioural disorders and abnormal EEG changes by attenuating the expressions of MDR1, COX-2, NMDA receptor and P-glycoprotein	in vivo	83

Neuropathic pain	Emodin	Alleviates the hyperalgesia via reducing the expression of P2X_2/3 receptor	in vivo	88

Diabetic encephalopa-thy	Chrysophanol	Improves cognition function by decreasing the expressions of IL-1β/4/6 and TNF-α, and reduces nerve cell death via inhibiting astrocyte activity	in vivo	90

Lead poisoning	Chrysophanol	Reduces learning and memory damage, improves mitochondria and rough endoplasmic reticulum injury, raises SOD and GSH-Px activities, and decreases MDA level	in vivo	91

Encephalitis	Rheum palmatum methanol extract	kills JEV, and inhibits JEV yields and infectivity	in vitro	92