An Analysis of the Combination Frequencies of Constituent Medicinal Herbs in Prescriptions for the Treatment of Stroke in Korean Medicine: Determination of a Group of Candidate Prescriptions for Universal Use
Table 2
Preliminary evaluation of the effects of 13 CMHTSs in stroke via analysis of the previous studies.
Name of CMHTS
Classification of the study (number)
Source database/main outcome
Angelica gigas Nakai, root
VT (2)
(1) P/attenuated Aβ(1-42)-induced neurotoxicity and tau hyperphosphorylation at multiple AD-related sites in a dose-dependent manner [16]
(2) N and R/inhibited Glu-induced neurotoxicity with IC50 [17]
VV (24)
(1) S/improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function [18]
(2) P/improved the habituation memory, decreased AChE, corticosterone, and TNF-α, and increased antioxidants [19]
(3) S/infarct volume of Angelica group was significantly decreased [20]
(4) N/the expression of Ang-2 in the APS group was higher than that in the control group [21]
(5) P, S, and N/the hyperintense signals and volume in the right cerebrum in Angelica-treated group decreased [22]
(6) N/the expression of VEGF in the Angelica sinensis group was higher than that in the other groups [23]
(7) P and N/increased the gene expression of Flt-1 and Flk-1 [24]
(8) P, S, and N/reduced cerebral infarct and neurological deficit score and suppressed superoxide radicals in the parenchyma lesion [25]
(9) P and R/prevented the decrease in the levels of phospho-Akt and phospho-GSK-3β [26]
(10) P, S, and N/prevented neuronal loss, dendrites damage, and neuronal apoptosis in both parietal cortex and hippocampus of 2VO rats [27]
(11) S and N/reduced brain swelling by 68.62% and 82.08% and significantly improved behavioral deficits [28]
(13) P, S, and N/decreased the level of malondialdehyde (MDA) and increased the activities of the antioxidant enzyme glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in the ischemic brain tissues [30]
(14) P and S/reduced malondialdehyde levels and increased superoxide dismutase activity in ischemic brain tissue [31]
(15) S/decreased the neurologic deficit score and the cerebral infarct volume rate [32]
(16) P and S/reduced mortality, neurobehavioral deficits, brain edema, BBB permeability, and cerebral vasospasm [33]
(18) N and O/GFAP, CD81, and ERK of the brain in rats with cerebral infarction after MCAO were meaningfully decreased [35]
(19) O and R/induced in infarction areas and volume [36]
(20) N and O/elevated MCAO-induced decrease in density of neurons and c-Fos immunoreactive cells [37]
(21) R/had neuroprotective effects via attenuation of COX-2 induction in hippocampus [38]
(22) N, O, and R/inhibited decreasing the cell viability in ischemia-induced cells [39]
(23) N, O, and R/reduced infarction volume in ischemic brains of rats, degradation of neuronal cell, BBB permeability, and expression of VEGF protein dose-dependently [40]
(24) N and R/decreased infarction volume in ischemic brains and inhibited the expression of iNOS, Bax, and caspase-3 [41]
(4) P and S/attenuated the hippocampal neuronal damage in the CA1 region in high dose [52]
(5) P and S/increased the levels of PDI (protein disulfide isomerase) and 1-Cys Prx (peroxiredoxin) transcription [53]
(6) P, S, and N/increased the expression of Bcl-2 and inhibited the activation of caspase-3 ultimately inhibiting apoptosis [54]
(7) P and S/expression of PDI, Nrf2, BDNF, GDNF, and MBP genes increased [55]
(8) N and R/improved the neurological symptoms, reduced infarct volume and cerebral edema, and regulated the expression of CaMKII [56]
(9) R/decreased infarct size in the brain of GEBs or 4-HBA group [57]
(10) P and S/prevented hippocampal CA1 cell death following global ischemia [58]
(11) O and R/had protective effects in the intraperitoneal injection of 1200 mg/kg and 600 mg/kg of Gastrodiae Rhizoma extracts [59]
(12) O and R/reduced infarct size partly and volume significantly in the MCAO rat brain [60]
(13) R/showed a significant decrease in infarct size in the ipsilateral brain with the extracts [61]
R (3)
(1) S/had the greatest neuronal survival after ischemia insult with vanillin-treated animals [62]
(2) S/protected against neuronal cell damage after transient global ischemia in gerbils [63]
(3) S/had correlation with stroke by statistics and association analysis [64]
Glycyrrhiza uralensis Fisch., root
VV (5)
(1) P, S, and N/had robust neuroprotection in the postischemic brain via anti-inflammatory effect by inhibiting HMGB1 phosphorylation and secretion [65]
(2) P, S, and N/decreased the focal infarct volume, cerebral histological damage, and apoptosis in MCAO rats [66]
(3) P, S, and N/the neurological deficits, infarct volume, and the levels of MDA and carbonyl decreased [67]
(4) P/reduced LDH release from PC12 cells exposed to hypoxic chamber [68]
(5) P, S, and N/inhibited the increases of brain MDA content and prevented the activities of brain superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) from decline caused by cerebral ischemia-reperfusion [69]
Ligusticum chuanxiong Hort., rhizome
VT (6)
(1) N/the levels of tumor necrosis factor-α (TNF-α), endothelin (ET), and intercellular adhesion molecule-1 (ICAM-1) were lower significantly in the groups treated with volatile oil [70]
(2) P, S, and N/reduced cerebral infarct and neurological deficit score [25]
(3) P and R/prevented the decrease in the levels of phospho-Akt and phospho-GSK-3β proteins [26]
(4) P, S, N, and R/decreased the infarct size and behavior deficits score [71]
(5) N/scores of neurological deficit and infarct volume were lower significantly in the groups treated with volatile oil, and the nitric oxide (NO) and malondialdehyde (MDA) levels were found to be decreased [72]
(6) O and R/reduced the infarction areas and volume [73]
C (3)
(1) N/results are healing in 19 cases, obvious effect in 13 cases, availability in 5 cases, and invalidation in 3 cases; healing and obvious effect rate: 80.0% [74] (2) P/the effect of L. chuanxiong on the treatment of acute cerebral infarction was superior to low molecular weight dextran [75] (3) P, C, S, and N/improved brain microcirculation through inhibiting thrombus formation and platelet aggregation as well as blood viscosity [76]
Paeonia lactiflora Pallas, root
VV (14)
(1) P/ischemia-reperfusion significantly increased AUC values, decreased CL values, and prolonged the terminal half-life of paeoniflorin [77]
(2) P/prevented reduction of Na(+)-K(+)-ATPase activity, increased NO level, and enhanced NOS activity [78]
(3) P and S/reduced the infarct volume and alleviated related tongue protrusion (TP) [79]
(4) S, N, and R/the injuries of ischemia-reperfusion could play an important role in pharmacokinetic process of paeoniflorin in the cortex after intravenous administration of Paeoniae Radix extract [80]
(5) P/displaced the binding of 3HNECA to the membrane preparation of rat cerebral cortex in a manner different from its classical agonists [81]
(6) P and S/reduced protein levels of Ras, MEK, p-MEK, and p-ERK [82]
(7) P and S/produced delayed protection in the ischemia-injured rats via inhibiting MAPKs/NF-κB mediated peripheral and cerebral inflammatory response [83]
(8) P/increased cell survival rate and reduced the binding activity of NMDA receptors [84]
(10) P and S/reduced the cerebral infarction area and the neurodeficit score and reduced lucigenin-CL counts at 2 h period of reperfusion [86]
(11) P/reduced the decrease of superoxide dismutase (SOD), inhibited the increase of nitric oxide (NO), and lessened the level of malondialdehyde (MDA) and reduced the decrease of lactate dehydrogenase (LDH) in cerebrum remarkably [87]
(12) P/relieved brain edema, enhanced SOD activity, and lowered MDA concentration in the gerbils and had milder injury of the cells in the hippocampal CA1 region [88]
(13) P/prolonged gasp time of decapitative mice, lessened cerebral water content, and decreased permeability of cerebral capillary [89]
(14) P, S, and N/reduced the counts of ED1, IL-1beta, TNF-alpha, and ICAM-1 of microvessels and MPO immunoreactive cells and apoptotic cells [90]
R (1)
(1) S/showed less potent caspase inhibitory activity [91]
Pinellia ternata (Thunb.) Breit., rhizome
Not available
Poria cocos Wolf, sclerotium
VV (1)
(1) N/showed neuroprotective effects with EC50 values of 21.6 μg/mL [92]
Rehmannia glutinosa Liboschitz, root
VT (1)
(1) P, S, and N/increased astrocyte survival significantly in a concentration-dependent manner [93]
VV (3)
(1) P and S/enhanced angiogenesis around the infarct of cortex and neurogenesis in the hippocampal dentate gyrus (DG) [94]
(2) P, S, and N/rescued neurons in hippocampal CA1 subfield and reduced working errors during behavioral testing [95]
(3) S and N/upregulated GAP-43 protein expression [96]
Scutellaria baicalensis Georgi, root
VT (1)
(1) P, S, and N/did not block NMDA-induced neuronal death [97]
VV (20)
(1) P, S, and N/activated GABAergic signaling and HSP70 and MAPKs cascades in global ischemia [98]
(2) P, S, and N/performed well in regulating proteins in energy metabolism but had a relatively weak effect in the regulation of proteins in neurogenesis and apoptosis [99]
(3) P, S, and N/the level of NF-κB p65 was decreased by 73% after baicalin treatment [100]
(4) P, S, and N/suppressed caspase-3 in ischemic gerbils hippocampus [101]
(5) P, S, and N/inhibited the formation of 3-nitrotyrosine, reduced infarct size, and attenuated apoptotic cell death, whose effects were similar to FeTMPyP [102]
(6) P, S, N, and R/inhibited microglial tumor necrosis factor-alpha (TNF-alpha) and nitric oxide production [103]
(7) P, S, N, and R/the increased contents of MDA and NO and SOD activity and the decreased activity of CAT in the hippocampus and cerebral cortex induced by cerebral ischemia were differently reversed [104]
(8) P, S, and N/the activities of lactate dehydrogenase, Na(+)-K(+)-ATPase, Ca(2+)-ATPase, and superoxide dismutase were significantly lowered [105]
(9) P/increased cell survival and inhibited cell apoptosis and excessive production of malondialdehyde [106]
(10) R/decreased the release of neuron-specific enolase and the production of TBARS [107]
(11) N/reduced the volume of infarction in the cerebral cortex as well as in the striatum [108]
(12) P, S, N, and R/reduced the infarct volume, prevented apoptosis in hippocampal cells, attenuated neuronal and blood-brain barrier damage, and upregulated Bcl-2 protein expression [109]
(13) P and S/reduced brain water content and the permeability of blood vessels, ameliorated ischemia-induced morphology changes in hippocampal microvessels, and downregulated Fas and FasL protein expression [110]
(14) P, S, N, and R/prolonged gasping time (prolonged ratio: 23.79%) and survival time after carotid artery occlusion and decreased malondialdehyde (MDA) content in damaged brain tissues [111]
(15) P and S/inhibited PKC(alpha) translocation [112]
(16) N/protected CA1 hippocampal neurons against 20 min transient forebrain ischemia [113]
(17) P, S, and N/attenuated neuronal injury and improved abnormality of energy metabolites in rats induced by global ischemia [114]
(18) P and S/inhibited MMP-9 activity in the hippocampus [115]
(19) O/CAT and GSH were activated by Scutellaria Radix extract administration [116]
(20) P, S, and N/reduced the pMCAO- (permanent occlusion of middle cerebral artery-) induced infarct areas in the cerebral cortex as well as in the striatum [117]
R (2)
(1) S/exerted neuroprotection by inhibiting TNF-α [62]
(2) P/Had antiapoptotic and antiglutamate activity which are the key processes for neuroprotection [118]
PubMed (P), Cochrane (C), Scopus (S), Ndsl (N), Oasis (O), and Riss (R) In vitro study (VT), in vivo study (VV), clinical study (C), and review (R).
