The efficacy and safety of diterpene ginkgolides meglumine injection for cerebral infarction: A meta-analysis of randomized controlled trials.

OBJECTIVE: To systemically evaluate the efficacy and safety of diterpene ginkgolides meglumine injection (DGMI) on cerebral infarction (CI). METHODS: Comprehensively collect randomized controlled trials of DGMI in the treatment of CI in 7 databases including Embase, PubMed, the Cochrane Library, the China National Knowledge Infrastructure Database, the WanFang Database, the China Science and Technology Journal Database, and the China Biology Medicinedisc as of January 2023. The studies were screened according to the inclusion and exclusion criteria and evaluated according to the criteria recommended by the Cochrane Handbook, then RevMan 5.3, Stata 12.0 software were used for Meta-analysis. RESULTS: A total of 22 randomized controlled trials with 2194 patients were included. Meta analysis showed that: the total effective rate of treatment (relative risk = 1.29, 95% confidence interval (1.21, 1.38), P < .001), National Institute of Health stroke scale score, Barthel index and Modified Rankin Scale were better in DGMI group than in Conventional Western Medicine Treatment group. The included studies reported 42 adverse events, 25 of which belonged to DGMI groups. CONCLUSION: Available evidence suggested that DGMI can significantly improve the clinical efficiency in the treatment of CI. DGMI is an ideal treatment for CI, which has high clinical application value.

Kaempferol-3-O-(2″-O-galloyl-ß-D-glucopyranoside): a novel neuroprotective agent from Diospryros kaki against cerebral ischemia-induced brain injury.

Our previous study demonstrated neuroprotective and therapeutic effects of a standardized flavonoid extract from leaves of Diospyros kaki L.f. (DK) on middle cerebral artery occlusion-and-reperfusion (MCAO/R)-induced brain injury and its underlying mechanisms. This study aimed to clarify flavonoid components responsible for the effects of DK using in vitro and in vivo transient brain ischemic models. Organotypic hippocampal slice cultures (OHSCs) subjected to oxygen- and glucose-deprivation (OGD) were performed to evaluate in vitro neuroprotective activity of DK extract and nine isolated flavonoid components. MCAO/R mice were employed to elucidate in vivo neuroprotective effects of the flavonoid component that exhibited the most potent neuroprotective effect in OHSCs. DK extract and seven flavonoids [quercetin, isoquercetin, hyperoside, quercetin-3-O-(2″-O-galloyl-ß-D-galactopyranoside), kaempferol, astragalin, and kaempferol-3-O-(2″-O-galloyl-ß-D-glucopyranoside) compound (9)] attenuated OGD-induced neuronal cell damage and compound (9) possessed the most potent neuroprotective activity in OHSCs. The MCAO/R mice showed cerebral infarction, massive weight loss, characteristic neurological symptoms, and deterioration of neuronal cells in the brain. Compound (9) and a reference drugs, edaravone, significantly attenuated these physical and neurological impairments. Compound (9) mitigated the blood-brain barrier dysfunction and the change of glutathione and malondialdehyde content in the MCAO mouse brain. Edaravone suppressed the oxidative stress but did not significantly affect the blood-brain barrier permeability. The present results indicated that compound (9) is a flavonoid constituent of DK with a potent neuroprotective activity against transient ischemia-induced brain damage and this action, at least in part, via preservation of blood-brain barrier integrity and suppression of oxidative stress caused by ischemic insult.

Correlation Study of Chronic Renal Insufficiency and Long-Term Prognosis of Patients with Acute Ischemic Cerebral Apoplexy After Intravenous rt-PA Thrombolysis.

Objective: To investigate the correlation between chronic renal insufficiency and the long-term prognosis of patients with acute ischemic cerebral apoplexy after intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis. Methods: 290 patients (194 males and 96 females) with acute cerebral infarction who received intravenous rt-PA thrombolysis were admitted to Ningbo Medical Center Lihuili Hospital from May 2018 to December 2020. Their clinical baseline data were recorded. According to the estimated glomerular filtration rate (eGFR) level, patients were divided into the control group (252 cases) and the chronic kidney disease (CKD) group (38 cases). The prognosis of patients was evaluated by a modified Rankin Scale (mRS) 90 days after cerebral apoplexy by telephone interview or outpatient following-up (mRS ≤ 2 reflected good prognosis, mRS >2 reflected unfavorable prognosis). Multivariate logistic regression was used to analyze the prognosis risk relationship of acute ischemic cerebral apoplexy patients with intravenous rt-PA thrombolysis with CKD. Results: Acute ischemic cerebral apoplexy patients with intravenous rt-PA thrombolysis with CKD were older ((79.08 ± 8.96) years vs (65.84 ± 13.31) years, P = .00052, 95% CI = 0.00031-0.00072) than who without CKD, and were more likely to be suffering from hypertension (94.7% (36/38) and 66.3% (167/252), P = .00023, 95% CI = 0.00011-0.00033), atrial fibrillation (50.0% (19/38) and 26.6% (67/252), P = .007, 95% CI = 0.001-0.009), high Uric acidemia (68.4% (26/38) and 17.9% (45/252), P = .00044, 95% CI = 0.00027-0.00061), hyperhomocysteinemia (47.4% (18/38) and 13.1% (33/252), P = .00032, 95% CI=0.00022-0.00053), history of malignant tumor (13.2% (5/38) and 4.4% (11/252), P = .044, 95% CI = 0.0023-0.0053), cardiogenic embolism (Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification of cerebral infarction) (47.4% (18/38) and 29.0% (73/252), P = .038, 95% CI = 0.029-0.055). The mortality rate of the CKD group was higher than the control group (13.2% (5/38) and 4.0% (10/252), P = .033, 95% CI = 0.021-0.053), and the good prognosis rate in the CKD group was significantly lower than in the control group (42.1% (16/38) and 73.8% (186/252), P = .00032, 95% CI = 0.00012-0.00043). Multivariate logistic regression analysis showed that CKD was an independent risk factor for acute ischemic cerebral apoplexy patients undergoing intravenous rt-PA thrombolysis (OR = 4.606, 95%CI 1.176~18.041, P = .028, 95% CI = 0.022-0.043). Conclusion: CKD is an independent risk factor for acute ischemic cerebral apoplexy patients with intravenous rt-PA thrombolysis.

Study on the Difference of Protective Efficacy and Mechanism of Radix Aconiti Coreani and Rhizoma Typhonii in Gerbils with Ischemic Stroke.

Ischemic stroke is a common type of stroke, but effective treatment methods are still imperfect and new effective therapies need to be explored. Radix Aconiti Coreani and Rhizoma Typhonii used as Baifuzi in the treatment of stroke or symptoms associated with stroke have been recorded in ancient Chinese books and are widely used. Modern pharmacological studies have demonstrated that both of them have antioxidant and anti-inflammatory effects. The purpose of this study is to investigate whether Radix Aconiti Coreani and Rhizoma Typhonii have therapeutical effects on gerbils with ischemic stroke, to investigate their potential mechanisms of action, and to provide a reference for rational clinical application by comparing the differences between them. In this manuscript, the right unilateral ligation of the carotid artery of gerbils was used to cause an ischemic stroke model. The neurological deficits of gerbils in each group were scored by Longa scale. The area of cerebral infarction was detected by 2,3,5-tribenzotetrazolchloride staining. The levels of inflammatory factors, oxidative stress indexes, and vascular endothelial function indexes in brain homogenate and serum were determined by ELISA. The expression levels of P-Akt PI3K, HO-1, and KEAP1 proteins in brain tissue were determined by Western blot. Immunofluorescence staining was used to observe the recovery of neuronal cells in the hippocampal CA1 region of the gerbil brain tissue and the expression of proteins related to PI3K/Akt and KEAP1/Nrf2 signaling pathways in neuronal cells in the hippocampal CA1 region. It was found that Radix Aconiti Coreani and Rhizoma Typhonii could improve neurological deficits and reduce cerebral infarction rate in gerbils. The results showed that Radix Aconiti Coreani and Rhizoma Typhonii could significantly decrease the expression of inflammatory factors, increase the expression of antioxidative stress indexes and vascular endothelial function factors, activate the PI3K/Akt, KEAP1/Nrf2 signaling pathway, reduce the inflammatory response, inhibit the oxidative stress, enhance the vascular endothelial cell function, and thus protect against ischemic brain injury. From the experimental results, both Radix Aconiti Coreani and Rhizoma Typhonii had neuroprotective effects on ischemic brain injury. Compared with Rhizoma Typhonii, the effects of Radix Aconiti Coreani on anti-inflammatory and antioxidative stress were more significant, while Rhizoma Typhonii had showed more significant effects in promoting angiogenesis after ischemic stroke by increasing the level of NO.

The efficacy of different nimodipine administration route for treating subarachnoid hemorrhage: A network meta-analysis.

BACKGROUND: A systematic review and network meta-analysis (NMA) were conducted to explore the optimal administration route of nimodipine for treatment subarachnoid hemorrhage. METHODS: Electronic databases (Pubmed, Embase, Web of Science and Cochrane databases) were systematically searched to identify randomized controlled trials evaluating different administration route of nimodipine (intravenous and enteral) versus placebo for treatment subarachnoid hemorrhage. Outcomes included case fatality at 3 months, poor outcome measured at 3 months (defined as death, vegetative state, or severe disability), incidence of delayed cerebral ischemia (DCI), delayed ischemic neurological deficit. A random-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as odds ratios (ORs) and 95% credible intervals. The NMA was performed using R Software with a GeMTC package. A Bayesian NMA was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. RESULTS: Nine randomized controlled trials met criteria for inclusion and finally included in this NMA. There was no statistically significant between intravenous and enteral in terms of case fatality, the occurrence of DCI, delayed ischemic neurologic deficit and poor outcomes (P > .05). Both intravenous and enteral could reduce case fatality, the occurrence of DCI, delayed ischemic neurologic deficit and poor outcomes (P < .05). The SUCRA shows that enteral ranked first, intravenous ranked second and placebo ranked the last for case fatality, the occurrence of DCI and poor outcomes. The SUCRA shows that intravenous ranked first, enteral ranked second and placebo ranked the last for delayed ischemic neurologic deficit. CONCLUSIONS: It is possible that both enteral and intravenous nimodipine have comparable effectiveness in preventing poor outcomes, DCI, and delayed ischemic neurological deficits. However, further investigation may be necessary to determine the exact role of intravenous nimodipine in current clinical practice.

The protective effect of an extract of Salvia miltiorrhiza Bunge (Danshen) on cerebral ischemic injury in animal models: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia is a common disease that seriously threatens the health of human beings. Tanshinone IIA (TSA) is a fat-soluble compound isolated from the traditional Chinese medicine Danshen. Recent studies have shown that TSA plays a significant protective role in the animal models of cerebral ischemic injury. AIM OF THE STUDY: The meta-analysis was to evaluate the protective effect of Danshen (Salvia miltiorrhiza Bunge) extract (TSA) in cerebral ischemic injury, aiming at providing scientific evidence for clinical application of TSA in the treatment of cerebral ischemia in patients. MATERIALS AND METHODS: All relevant studies published in PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Scientific Journals Database (VIP) and Chinese Biomedicine Database (CBM) before Jan 2023 were systematically retrieved. The methodological quality was assessed by SYRCLE's risk of bias tool for the animal studies. Data was analyzed using Rev Man 5.3 software. RESULTS: A total of 13 studies were included. Compared with the control group, TSA significantly reduced the expression of glial fibrillary acidic protein (GFAP) (mean difference [MD], -1.78; 95% CI, [-2.13, -1.44]; P < 0.00001) and high mobility group protein B1 (HMGB1) (MD, -0.69; 95% CI, [-0.87, -0.52]; P < 0.00001). TSA also inhibited the activation of brain nuclear factor κB (NF-κB) (MD, - 0.36; 95% CI, [-0.41, -0.32]; P < 0.00001), malondialdehyde (MDA) (MD, -0.90; 95% CI, [-1.66, -0.13]; P = 0.02), cysteine protease-3 (Caspase-3) (MD, -1.39; 95% CI, [-1.98, -0.81]; P < 0.00001), and reduced cerebral infarction volume(MD, -16.26; 95% CI, [-20.76, -11.77]; P < 0.00001), brain water content (MD, -4.89; 95% CI, [-7.06, -2.71]; P < 0.0001) and neurological deficit scores (MD, -1.19; 95% CI, [-1.48, -0.89]; P < 0.00001). Additionally, TSA increased the brain content of superoxide dismutase (SOD) (MD, 68.31; 95% CI, [10.41, 126.22]; P = 0.02). CONCLUSIONS: The result of this study showed that TSA had a protective effect on cerebral ischemic injury in animal models, and the mechanism is associated with the reduction of inflammation and oxidative stress, and the inhibition of cell apoptosis. However, the quality of included studies may affect the accuracy of positive results. Therefore, more high-quality randomized controlled animal experiments are need for meta-analysis in the future.

Clinical Efficacy of the Huo Xue Hua Yu Method Combined with Aspirin in the Treatment of Acute Cerebral Infarction: A Systematic Evaluation and Meta-analysis.

OBJECTIVE: The study aimed to evaluate the clinical efficacy of the Huo Xue Hua Yu method combined with aspirin in the treatment of patients with acute cerebral infarction (ACI). METHODS: By searching electronic databases, such as the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure Database (CNKI), the China Science and Technology Journal Database, Wanfang, PubMed, Embase, and the Cochrane Library, all randomized controlled trials (RCTs) published before 14 July, 2022, and published in Chinese or English languages were selected. Statistical analysis was performed using Review Manager 5.4 calculation software to calculate the odds ratio (OR), mean difference (MD), 95% confidence interval (CI), and p values. RESULTS: 13 articles that included 1,243 patients were identified; in 646 of them, the Huo Xue Hua Yu method combined with aspirin has been administered, while 597 have only been administered aspirin therapy. The combined treatment significantly improved clinical efficacy (OR: 4.41, 95% CI: 2.90 to 5.84, p < 0.001, I2 = 0), as assessed by the National Institutes of Health Stroke Scale score (MD = -4.18, 95% CI: -5.69 to -2.67, p < 0.001, I2 = 94%), Barthel score (MD = -2.23, 95% CI: -2.66 to -1.81, p < 0.001, I2 = 82%), the China Stroke Scale score (MD = 6.74, 95% CI: -3.49 to 16.96, P = 0.20, I2 = 99%), packed cell volume (MD = -8.45, 95% CI: -8.81 to -8.09, p < 0.001, I2 = 98%), fibrinogen levels (MD = -0.93, 95% CI: -1.23 to -0.63, p < 0.001, I2 = 78%) and plasma viscosity (MD = -0.51, 95% CI: -0.72 to -0.30, p < 0.001, I2 = 62%). CONCLUSION: The combination of the Huo Xue Hua Yu method and aspirin represents a beneficial adjunctive therapy for ACI.

Neuroprotective Effect of Dexmedetomidine on Cerebral Ischemia-Reperfusion Injury in Rats.

Background: The number of patients having ischemic stroke is increasing year on year. The anesthetic adjuvant dexmedetomidine is neuroprotective in rats and has potential for use in the treatment of ischemic stroke. Objective: The neuroprotective mechanism of dexmedetomidine in cerebral ischemia-reperfusion injury was studied in relation to its regulation of the oxidative stress response, astrocyte response, microglia overactivation, and apoptosis-related protein expression. Methods: We randomly and equally divided 25 male Sprague-Dawley rats into 5 groups: a sham-operation group, an ischemia-reperfusion injury group, and low-, medium-, and high-dose dexmedetomidine groups. A rat model of focal cerebral ischemia-reperfusion injury was established by embolization of the right middle cerebral artery for 60 minutes and reperfusion for 2 hours. The volume of cerebral infarction was calculated by triphenyl tetrazolium chloride staining. The protein expression levels of caspase-3, methionyl aminopeptidase 2 (MetAP2 or MAP2), glial fibrillary acidic protein, and allograft inflammatory factor 1 (AIF-1) in the cerebral cortex were determined by Western blot and immunohistochemistry. Results: The volume of cerebral infarction in rats decreased with increasing dose of dexmedetomidine (P = .039, 95% CI = .027 to .044). The expression levels of caspase-3, glial fibrillary acidic protein, and allograft inflammatory factor 1 and the amount of 4-hydroxynonenal decreased with increasing doses of dexmedetomidine (P = .033, 95% CI = .021 to .037). Methionyl aminopeptidase 2 (MetAP2 or MAP2) expression increased with increasing doses of dexmedetomidine (P = .023, 95% CI = .011 to .028). Conclusion: Dexmedetomidine has a dose-dependent protective effect on cerebral ischemic injury in rats. The neuroprotective effects of dexmedetomidine are achieved, in part, by reducing the oxidative stress response, inhibiting glial overactivation, and inhibiting expression levels of apoptosis-related proteins.

[CiteSpace knowledge map analysis of Angong Niuhuang Pills in recent twenty years].

Angong Niuhuang Pills, a classical formula in traditional Chinese medicine, are lauded as one of the "three treasures of febrile diseases" and have been widely used in the treatment of diverse disorders with definite efficacy. However, there is still a lack of bibliometric analysis of research progress and development trend regarding Angong Niuhuang Pills. Research articles on Angong Niuhuang Pills in China and abroad(2000-2022) were retrieved from CNKI and Web of Science. CiteSpace 6.1 was used to visualize the key contents of the research articles. In addition, the research status of Angong Niuhuang Pills was analyzed by information extraction to allow insight into the research trends and hotspots about Angong Niuhuang Pills. A total of 460 Chinese articles and 41 English articles were included. Beijing University of Chinese Medicine and Sun Yat-Sen University were the research institutions that have published the largest amount of research articles in Chinese and English. The keyword analysis showed that the Chinese articles focused on cerebral hemorrhage, stroke, neurological function, coma, cerebral infarction, craniocerebral injury, and clinical application, while the English articles focused on the mechanisms of cerebral ischemia, stroke, heavy metal, blood-brain barrier, and oxidative stress. Stroke, blood-brain barrier, and oxidative stress were presumably the research hotspots in the future. At present, the research on Angong Niuhuang Pills is still in the developing stage. It is necessary to highlight the in-depth research on the active components and mechanism of action and carry out large-scale randomized controlled clinical trials to provide references for the further development and application of Angong Niuhuang Pills.

Edaravone combined with Shuxuening versus edaravone alone in the treatment of acute cerebral infarction: A systematic review and meta-analysis.

BACKGROUND: Shuxuening injection (SXN) is a traditional Chinese medicine used in the treatment of cardiovascular diseases. Whether it can provide better outcomes when combined with edaravone injection (ERI) for the treatment of acute cerebral infarction is not well determined. Therefore, we evaluated the efficacy of ERI combined with SXN versus that of ERI alone in patients with acute cerebral infarction. METHODS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang electronic databases were searched up to July 2022. Randomized controlled trials comparing the outcomes of efficacy rate, neurologic impairment, inflammatory factors, and hemorheology were included. Odds ratio or standard mean difference (SMD) with corresponding 95% confidence intervals (CIs) were used to present the overall estimates. The quality of the included trials was evaluated by the Cochrane risk of bias tool. The study was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses. RESULTS: Seventeen randomized controlled trials were included consisting of 1607 patients. Compared to ERI alone, treatment with ERI plus SXN had a greater effective rate than ER alone (odds ratio = 3.94; 95% CI: 2.85, 5.44; I2 = 0%, P < .00001), a lower National Institute of Health Stroke Scale (SMD= -1.39; 95% CI: -1.73, -1.05; I2 = 71%, P < .00001), lower neural function defect score (SMD= -0.75; 95% CI: -1.06,-0.43; I2 = 67%, P < .00001), and lower level of neuron-specific enolase (SMD= -2.10; 95% CI: -2.85, -1.35; I2 = 85%, P < .00001). ERI plus SXN treatment provided significant improvements in whole blood high shear viscosity (SMD = -0.87; 95% CI: -1.17, -0.57; I2 = 0%, P < .00001), and whole blood low shear viscosity (SMD = -1.50; 95% CI: -1.65, -1.36; I2 = 0%, P < .00001) compared to ERI alone. CONCLUSION: ERI plus SXN showed better efficacy than ERI alone for patients with acute cerebral infarction. Our study provides evidence supporting the application of ERI plus SXN for acute cerebral infarction.

Effects of NBP injection on the inflammatory response, oxidative stress response and vascular endothelial function in patients with ACI: A systematic review and meta-analysis.

BACKGROUND: Acute cerebral infarction (ACI) is a common medical emergency. This study is the first systematic review of the use of Dl-3-n-butylphthalide (NBP) injection in the treatment of ACI. The purpose of this study was to systematically evaluate the effects of NBP injection on the inflammatory response, oxidative stress response and vascular endothelial function in patients with acute ACI. The objective is to provide reference for clinical application. METHODS: From the establishment of the database until August 2022, we systematically searched EMbase, PubMed, Cochrane Library, Web of Science, CNKI, VIP, and Wanfang Database. RCTs and retrospective studies were included in this study, and the results that qualified for inclusion were screened by 2 researchers and cross-checked. After the relevant data were extracted, a meta-analysis was performed using RevMan5.3 software. RESULTS: A total of 3307 patients with ACI from 34 studies were analyzed. The meta-analysis showed that the C-reactive protein levels in the NBP combined group were effectively reduced compared with those in the control group (MD = -3.75, 95% confidence intervals [95% CI] [-4.95, -2.56], P < .00001). Based on comparison with the control group, it is evident that combination treatment with NBP is more effective than control group in reducing the oxidative stress response of ACI (MD[superoxide dismutase levels] = 22.16, 95% CI [14.20,30.11], P < .00001; MD[malondialdehyde levels] = -1.97, 95% CI [-2.62, -1.32], P < .00001). Comparison with the control group shows that combination treatment with NBP is more effective in improving vascular endothelial function in ACI patients (MD[vascular endothelial growth factor levels] = 71.44, 95% CI [41.22, 101.66], P < .00001; MD[endothelin-1 levels] = -11.47, 95% CI [-17.39, -5.55], P = .0001; MD[nitric oxide levels] = 9.54, 95% CI [8.39, 10.68], P < .00001) than control group. The NBP combined group also showed a greater reduction in cerebral infarct volume (CIV) and cerebral infarct size (CIS) of ACI (MD[CIV] = -1.52, 95% CI [-2.23, -0.81], P < .0001; MD[CIS] = -2.79, 95% CI [-3.65, -1.94], P < .00001). The NBP combined group did not show an increase in the incidence of adverse reactions compared with the control group (odds ratio = 1.06, 95% CI [0.73, 1.53], P = .77). CONCLUSION: In summary, the use of NBP in combination with control group for ACI can reduce the degree of nerve damage, reduce inflammation and oxidative stress, improve vascular endothelial function, and reduce CIS and CIV in ACI patients, without increasing the incidence of clinical adverse events.

Delayed administration of Trichilia catigua A. Juss. Ethyl-acetate fraction after cerebral ischemia prevents spatial memory deficits, decreases oxidative stress, and impacts neural plasticity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Trichilia catigua A. Juss (Meliaceae) is used in Brazilian folk medicine to alleviate fatigue and emotional stress and improve memory. Previous studies from our laboratory reported that an ethyl-acetate fraction (EAF) of T. catigua that was given before cerebral ischemia in vivo prevented memory loss and reduced oxidative stress and neuroinflammation. Despite the value of these findings of a neuroprotective effect of T. catigua, treatment that was given immediately before or immediately after ischemia limits its clinical relevance. Thus, unknown is whether T. catigua possesses a specific time window of efficacy (TWE) when administered postischemia. AIM OF THE STUDY: Given continuity to previous studies, we investigated whether an EAF of T. catigua maintains its neuroprotective properties if treatment begins at different time windows of efficacy after ischemia. We also evaluated, for the first time, whether T. catigua possesses neuroplasticity/neurotrophic properties. MATERIAL AND METHODS: Rats were subjected to transient global brain ischemia (TGCI) and then given a single dose of the EAF (400 mg/kg) or vehicle (1 ml/kg) orally 1, 4, or 6 h postischemia. The levels of protein PCG, GSH, and GSSG, and activity of SOD and CAT were assayed as markers of oxidative stress on the day after ischemia. In another experiment, naive rats underwent spatial learning training in a radial maze task and then subjected to TGCI. Delayed treatment with the EAF began 4 or 6 h later and continued for 7 days. Retrograde memory performance was assessed 10, 17, and 24 days postischemia. Afterward, brains were examined for neurodegeneration and neuronal dendritic morphology in the hippocampus and cerebral cortex. Another group received the EAF at 4 h of reperfusion, and 4 days later their brains were examined for GFAP and Iba-1 immunoreactivity. Lastly, ischemic rats received the EAF 4 h after ischemia and neural plasticity-related proteins, BDNF, SYN, PSD 95, and NeuN were measured in the hippocampus 7 and 14 days after ischemia. RESULTS: A single EAF administration 1, 4, or 6 h postischemia alleviated oxidative stress that was caused by ischemia, expressed as a reduction of the amount of the PCG and GSSG, normalization of the GSH/GSSG ratio, and the restoration of SOD activity. Ischemia caused the persistent loss of memory (i.e., amnesia), an outcome that was consistently ameliorated by treatment with the EAF that was initiated 4 or 6 h postischemia. The 4 h delay in EAF treatment positively impacted dendritic morphology in neurons that survived ischemia. TGCI reduced BDNF, SYN, PSD-95, and NeuN protein levels in the hippocampus and cerebral cortex. The EAF normalized SYN and PSD-95 protein levels. Ischemia-induced neurodegeneration and glial cell activation were not prevented by EAF treatment. CONCLUSION: The present study corroborates prior data that demonstrated the neuroprotective potential of T. catigua and extends these data by showing that the delayed administration of EAF postischemia effectively prevented memory impairment and decreased oxidative stress, dendritic deterioration, and synaptic protein loss within a TWE that ranged from 1 to 6 h. This specific TWE in preclinical research may have clinical relevance by suggesting the possible utility of this plant for the development of neuroprotective strategies in the setting of ischemic brain diseases. Another innovative finding of the present study was the possible neurotrophic/neuroplastic properties of T. catigua.

Methodological and reporting quality evaluation of Buyang Huanwu decoction for experimental cerebral ischemia-reperfusion injury: a systematic review.

Buyang Huanwu decoction, a classic traditional Chinese prescription, has been used to prevent and treat stroke for hundreds of years. An increasing number of the laboratory research on Buyang Huanwu decoction used in treating cerebral ischemia-reperfusion injury have been published recently. However, the problem of methodological and reporting quality of some studies is lack of assessment. This study aims to evaluate the methodological and reporting quality of the research on Buyang Huanwu decoction against experimental cerebral ischemia-reperfusion injury. A comprehensive search on six databases was performed. Two researchers independently screened the literature considering the eligibility criteria. Methodological and reporting quality of the included studies were evaluated by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tool and Animal Research: Reporting of In Vivo Experiments (ARRIVE) guideline. Forty-five studies met the inclusion criteria. No study achieved a decent overall rating in using the SYRCLE tool (percentage of items with "low risk" ≥ 50%). Of the 22 items on the SYRCLE tool, only 7 items (31.82%) were rated as "low risk" in more than 50% of the included studies. Of the 39 items of ARRIVE guideline, 14 (35.9%) items were rated as "yes" in more than 50% of the included studies. The methodological and reporting quality of Buyang Huanwu decoction for experimental cerebral ischemia-reperfusion injury was substandard, which needed to be further improved. The limitations should be addressed when planning similar studies in the future. Additionally, these findings provided evidence-based guidance for future preclinical studies evaluating the efficacy of Buyang Huanwu decoction in the treatment of cerebral ischemia-reperfusion injury.

The study of chemical components in Qishiwei Zhenzhu pills and its anti-apoptotic mechanism in cerebral ischemic based on LC-MS and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Qishiwei Zhenzhu pills are one of the most representative precious treasure proprietary medicines and have been used for nearly 500 years in clinical practice in Chinese. This medicine can prevent diseases and play a certain role in fighting altitude sickness with cerebral ischemia. AIM OF THE STUDY: This study used LC-MS to analyse the chemical constituents of Qishiwei Zhenzhu pills, which laid a foundation for the improvement of the quality standard and the basic research of pharmacodynamics substances. This study aims to reveal the mechanism of Qishiwei Zhenzhu pills on cerebral ischemia from the perspective of the inflammatory and apoptotic pathway. MATERIALS AND METHOD: UPLC-Q-TOF-MS was used to analyse the chemical constituents of Qishiwei Zhenzhu pills qualitatively. HPLC-QQQ-MS was used to analyse the contents of Qishiwei Zhenzhu pills quantitatively. The therapeutic target and pathway of Qishiwei Zhenzhu pills in the treatment of ischemic stroke were predicted on the basis of network pharmacology. On the basis of the MCAO rat model, the cerebral infarction rate (TTC staining) and the number of Nissl bodies (toluidine blue staining) were measured, the pathological morphologies of cortex and hippocampus were observed (HE staining), and the mRNA levels were determined by RT-PCR. The protein expressions of Bax, Bcl-2, and Caspase3 in the ischemic brain tissue of rats were determined using the WB method. RESULTS: A total of 42 chemical constituents, including 11 triterpenoids, 10 flavonoids, 8 organic acids and their derivatives, 4 diterpenoids, 4 tannins, 2 steroids, and 3 other components, were identified from Qishiwei Zhenzhu pills by UPLC-Q-TOF-MS. HPLC-QQQ-MS results found that among the 16 different batches, the content difference between the two batches of preparations with the national drug approval number was small and that the quality was stable. However, significant differences were observed among the preparations of nine medical institutions. Network pharmacology study found that the effect of Qishiwei Zhenzhu pills might be related to the AGE-rage and tumour necrosis factor signalling pathways. Qishiwei Zhenzhu pills could improve the neurobehavioral abnormalities of MCAO rats, reduce the rate of cerebral infarction, improve the pathological changes in the hippocampal area of brain tissue, and increase the number of Nissl body in the brain tissue. Qishiwei Zhenzhu pills tended to reduce the mRNA transcription levels of Bax, Caspase-3, p65, c-fos and VEGF-A and increase the expression of Bcl-2 and MAPK8 mRNA. Moreover, the Bax protein expression tended to decrease, and the bcl-2 protein expression tended to increase. CONCLUSIONS: A total of 42 chemical components were qualitatively identified from Qishiwei Zhenzhu pills, and 16 chemical components from 16 batches were determined. These components improved the quality standard level of Qishiwei Zhenzhu pills and provided reference for the later exploration of its pharmacodynamics substance basis. The protective mechanism of Qishiwei Zhenzhu pills against ischemic stroke might be related to the downregulation of the apoptosis factor caspase-3.

Research on the Material Basis and Mechanism of Kudzu Root in Preventing and Treating Cerebral Ischemia based on Network Pharmacology.

BACKGROUND: It has been shown that Kudzu root has significant pharmacological effects such as improving microcirculation, dilating coronary arteries, and increasing cerebral and coronary blood flow, but its material basis and mechanism of action are not clear. OBJECTIVE: The aim of this study was to investigate the mechanism of action of Kudzu root in the prevention and treatment of cerebral ischemia (CI) through network pharmacology combined with animal experiments. METHODS: The components of kudzu root were screened by using the Chemistry Database, Chinese Academy of Science. Linpinski's five rules were used to perform pharmacophore-like analysis to obtain the active ingredients of Kudzu root. The Swiss Target Prediction Service database was used to predict the potential protein targets of kudzu root components associated with CI. An active ingredient-target network was constructed by using Cytoscape 3.6.0. A rat model of middle cerebral artery occlusion (MCAO) was established, then the main targets and signaling pathways predicted were verified by observing the area of cerebral infarction and Western blot experiments. RESULTS: In total, 84 major active compounds and 34 targets included gerberoside, belonging to the isoflavone class, gallic acid, amino acid class, 4-Methylphenol, phenolic class, and quercetin, and flavonoid class (Flavonoids). The targets covered were proteins related to excitatory amino acids and calcium overload, including Excitatory amino acid transporter 2 (SLC1A2), Glutamate receptor ionotropic, kainate 1 (GRIK1), Glutamate receptor ionotropic, NMDA 1 (GRIN1), Glutamate receptor 2(GRIA2), Calcium/calmodulin-dependent protein kinase II (CaMKII), Neuronal nitric oxide synthase(nNOS). Glutamatergic energy is prominent, and calcium transport across the membrane is central to the network and occupies an important position. CONCLUSION: Kudzu root can significantly reduce neurological damage in rats with CI, and also significantly reduce the rate of cerebral infarction. It is worth noting that Kudzu root can prevent and treat CI by reducing excitatory amino acid toxicity and improving calcium overload.

CiteSpace knowledge map analysis of Angong Niuhuang Pills in recent twenty years / 中国中药杂志

Angong Niuhuang Pills, a classical formula in traditional Chinese medicine, are lauded as one of the "three treasures of febrile diseases" and have been widely used in the treatment of diverse disorders with definite efficacy. However, there is still a lack of bibliometric analysis of research progress and development trend regarding Angong Niuhuang Pills. Research articles on Angong Niuhuang Pills in China and abroad(2000-2022) were retrieved from CNKI and Web of Science. CiteSpace 6.1 was used to visualize the key contents of the research articles. In addition, the research status of Angong Niuhuang Pills was analyzed by information extraction to allow insight into the research trends and hotspots about Angong Niuhuang Pills. A total of 460 Chinese articles and 41 English articles were included. Beijing University of Chinese Medicine and Sun Yat-Sen University were the research institutions that have published the largest amount of research articles in Chinese and English. The keyword analysis showed that the Chinese articles focused on cerebral hemorrhage, stroke, neurological function, coma, cerebral infarction, craniocerebral injury, and clinical application, while the English articles focused on the mechanisms of cerebral ischemia, stroke, heavy metal, blood-brain barrier, and oxidative stress. Stroke, blood-brain barrier, and oxidative stress were presumably the research hotspots in the future. At present, the research on Angong Niuhuang Pills is still in the developing stage. It is necessary to highlight the in-depth research on the active components and mechanism of action and carry out large-scale randomized controlled clinical trials to provide references for the further development and application of Angong Niuhuang Pills.

Network pharmacology study on the potential effect mechanism of Chuanzhi Tongluo Capsule in the treatment of cerebral infarction.

BACKGROUND: Chuanxiong Tongluo capsules have been widely used to treat recovered stroke and cerebral infarction, but their specific therapeutic mechanism is not well understood. METHODS: This study aims to investigate the mechanism of action for Chuanzhi Tongluo capsule on cerebral infarction based on a network pharmacology approach. The TCMSP platform collected the chemical composition of Chuanzhi Tongluo capsules. Its potential targets were predicted by Swiss target prediction and standardized using the Uniprot database for gene normalization. Meanwhile, the OMIM, Genecards, and TTD databases were used to obtain the targets related to cerebral infarction. The standard targets of Chuanzhi Tongluo capsule and cerebral infarction were uploaded to the STRING database to construct protein-protein interaction networks. Topological methods analyzed the key targets and components in the drug-component-disease-target network. Gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the shared targets were performed using the DAVID database. RESULTS: A total of 105 active ingredients and 427 targets were associated with Chuanzhi Tongluo capsule, and there were 3055 targets related to cerebral infarction disease and 240 common targets between the two keywords. The key targets included INS, ALB, IL-6, VEGFA, TNF, and TP53. The conduction pathways involved include the calcium signaling pathway, cAMP signaling pathway, cGMP-PKG signaling pathway, and TNF signaling pathway. CONCLUSION: The active ingredients in Chuanzhi Tongluo capsule may participate in the therapeutic process of cerebral infarction by regulating the calcium, cAMP, cGMP-PKG, and TNF signaling pathway through critical targets such as INS, ALB, IL-6, VEGFA, TNF, and TP53.

To discuss the mechanism of colchicine in the treatment of acute cerebral infarction based on network pharmacology.

To explore the mechanism of action of colchicine in the treatment of acute cerebral infarction (ACI) based on network pharmacology. The Swiss Target Prediction Database and CTD database were used to predict the target information of colchicine. ACI-related targets were retrieved using the GeneCards database, and the target protein interaction network (PPI) and active ingredient-target network were obtained by combining Cytoscape 3.7.1 software and R language. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and gene function analysis (GO) enrichment analysis were performed using R language to preliminarily explore the multiple pharmacological mechanisms of action of colchicine. There were 200 targets identified by network parameter analysis; 958 ACI targets were identified. Overlapping comparisons allowed the extraction of 143 overlapping targets, and the top 30 targets were screened according to the topological isomerization parameters. Component-target networks were constructed. A PPI of overlapping targets was established to identify key targets. In addition, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and GO functional enrichment analysis were performed to explore the multiple mechanisms of action of colchicine in the treatment of ACI. Colchicine treatment of ACI is characterized by multi-component, multi-target and multi-pathway, and can exert complex network regulation through the interaction between different targets, providing a new idea and new basis for further exploration of the mechanism of action of colchicine in the treatment of ACI.

[Effect of Xingnao Kaiqiao acupuncture on safety of rt-PA intravenous thrombolysis in patients with cerebral infarction: a randomized controlled trial].

OBJECTIVE: To assess the effect of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on the efficacy and safety of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with cerebral infarction. METHODS: A total number of 142 patients of cerebral infarction undergoing rt-PA intravenous thrombolysis were randomized into an acupuncture-medication group (71 cases) and a western medication group (71 cases, 1 case dropped off). In the western medication group, rt-PA intravenous thrombolysis was given. In the acupuncture-medication group, besides the intervention as the control group, Xingnao Kaiqiao acupuncture was provided at Shuigou (GV 26), Neiguan (PC 6), Sanyinjiao (SP 6), Jiquan (HT 1), etc. once daily. One treatment session contained 6 treatments and 1 session was required. Before and after treatment, the score of the National Institute of Health stroke scale (NIHSS), the levels of the relevant indexes of symptomatic intracerebral hemorrhage (sICH) (platelet [PLT], D-dimer and fibrinogen), the incidences of sICH and adverse effect were compared between groups. The efficacy was assessed in two groups. RESULTS: After treatment, NIHSS scores and the levels of D-dimer were reduced compared with those before treatment in both groups (P<0.05), and those in the acupuncture-medication group were lower than the western medication group (P<0.05). The level of fibrinogen in the acupuncture-medication group was increased in comparison with that before treatment (P<0.05), and also higher than the western medication group (P<0.05). The incidence of sICH was 0% (0/71) in the acupuncture-medication group, lower than 8.6% (6/70) in the western medication group (P<0.05). The effective rate was 97.2% (69/71) in the acupuncture-medication group, higher than 87.1% (61/70) in the western medication group (P<0.05). The incidence of adverse effect was 2.8% (2/71) in the acupuncture-medication group, lower than 12.9% (9/70) in the western medication group (P<0.05). CONCLUSION: Xingnao Kaiqiao acupuncture may improve the efficacy of rt-PA intravenous thrombolysis in the patients with cerebral infraction and decrease the incidences of sICH and adverse effect. The mechanism may be related to the regulation of fibrinogen and D-dimer levels.

New Therapeutic Approaches to and Mechanisms of Ginsenoside Rg1 against Neurological Diseases.

Neurological diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), stroke, cerebral infarction, ischemia-reperfusion injury, depression and, stress, have high incidence and morbidity and often lead to disability. However, there is no particularly effective medication against them. Therefore, finding drugs with a suitable efficacy, low toxicity and manageable effects to improve the quality of life of patients is an urgent problem. Ginsenoside Rg1 (Rg1) is the main active component of ginseng and has a variety of pharmacological effects. In this review, we focused on the therapeutic potential of Rg1 for improving neurological diseases. We introduce the mechanisms of Ginsenoside Rg1 in neurological diseases, including apoptosis, neuroinflammation, the microRNA (miRNA) family, the mitogen-activated protein kinase (MAPK) family, oxidative stress, nuclear factor-κB (NF-κB), and learning and memory of Rg1 in neurological diseases. In addition, Rg1 can also improve neurological diseases through the interaction of different signal pathways. The purpose of this review is to explore more in-depth ideas for the clinical treatment of neurological diseases (including PD, AD, HD, stroke, cerebral infarction, ischemia-reperfusion injury, depression, and stress). Therefore, Rg1 is expected to become a new therapeutic method for the clinical treatment of neurological diseases.