Novel insight into the therapeutical potential of flavonoids from traditional Chinese medicine against cerebral ischemia/reperfusion injury.

Cerebral ischemia/reperfusion injury (CIRI) is a major contributor to poor prognosis of ischemic stroke. Flavonoids are a broad family of plant polyphenols which are abundant in traditional Chinese medicine (TCM) and have beneficial effects on several diseases including ischemic stroke. Accumulating studies have indicated that flavonoids derived from herbal TCM are effective in alleviating CIRI after ischemic stroke in vitro or in vivo, and exhibit favourable therapeutical potential. Herein, we systematically review the classification, metabolic absorption, neuroprotective efficacy, and mechanisms of TCM flavonoids against CIRI. The literature suggest that flavonoids exert potential medicinal functions including suppressing excitotoxicity, Ca2+ overloading, oxidative stress, inflammation, thrombin's cellular toxicity, different types of programmed cell deaths, and protecting the blood-brain barrier, as well as promoting neurogenesis in the recovery stage following ischemic stroke. Furthermore, we identified certain matters that should be taken into account in future research, as well as proposed difficulties and opportunities in transforming TCM-derived flavonoids into medications or functional foods for the treatment or prevention of CIRI. Overall, in this review we aim to provide novel ideas for the identification of new prospective medication candidates for the therapeutic strategy against ischemic stroke.

Reporting quality and risk of bias assessment of animal research on Chaihu-Shugan-San for depression: A systematic review.

Objective: Chaihu-Shugan-San (CSS) is a traditional Chinese medicine formula employed to treat depression. We aim to conduct a reporting quality assessment and risk of bias evaluation of animal research on CSS for depression. Methods: To acquire eligible studies, two reviewers searched plentiful databases from inception to October 23rd, 2021. Reporting quality assessment and risk of bias assessment of the included animal studies were evaluated by using Animal Research: Reporting In Vivo Experiments (ARRIVE) guidelines and the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool, respectively. Results: The initial search identified 720 records, while only 30 studies were included. The result of the reporting quality assessment was inferior, items 17 and 19 were not reported at all. The details of five items (items 3, 6, 7, 10, and 18) were not reported. The outcome of the risk of bias assessment suggested that half of the entries (5/10) displayed an unclear risk of bias and a high risk of bias. Blinding with regard to performance bias and detection bias revealed an unclear risk of bias (100%), followed by baseline characteristics (76.67%) and sequence generation (60%). Random outcome assessment showed a high risk of bias (100%). Conclusion: The included animal studies exhibited methodological defects and imprecise reporting. Hence, the ARRIVE guidelines and SYRCLE's RoB tool should be disseminated among basic medical researchers examining CSS for depression to publish studies with low risk of bias and sufficient reporting so that the animal research can promptly be transformed into clinical research.

Benefit-risk assessment of traditional Chinese medicine preparations of sinomenine using multicriteria decision analysis (MCDA) for patients with rheumatoid arthritis.

OBJECTIVE: A multicriteria decision analysis (MCDA) model was used to evaluate the benefits and risks of traditional Chinese medicine preparations of sinomenine alone or in combination with conventional drugs in the treatment of rheumatoid arthritis (RA) and to provide a basis for the rational clinical application of sinomenine. METHODS: A study search was performed using six major databases, and Review Manager 5.3 was used for data analysis. Then, an MCDA model evaluation system was established for the treatment of RA with sinomenine preparations, and the benefit values, risk values, and total benefit-risk values of sinomenine preparations alone or in combination with conventional drugs were calculated using Hiview 3.2 software. Finally, Monte Carlo simulations were performed using Crystal Ball embedded in Excel software to calculate the 95% confidence intervals (95% CI), and the probability of the differences between the 2 drug regimens was determined to optimize the evaluation results. RESULTS: Forty-four randomized controlled trials (RCTs) were included. Quantitative assessment of the MCDA model showed that the sinomenine preparation alone offered less benefits than when combined with conventional drugs with a benefit difference of 20 (95% CI 3.06, 35.71). However, the risk of the combination was significantly lower with a risk difference of 13(95% CI -10.26, 27.52). The total value of the benefit-risk of sinomenine alone and in combination with conventional drugs was 46 and 53 at 60% and 40% of the benefit-risk ratio of the two dosing regimens, respectively, with a difference of 7 (95% CI -4.26, 22.12). The probability that the comprehensive score of the combined regimen is greater than that of sinomenine alone is 90.1%, and the evaluation was steady. CONCLUSION: The benefit-risk of the combined application regimen of sinomenine is greater than that of sinomenine alone.

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.

Anti-inflammatory and osteoprotective effects of Chikusetsusaponin â £a on rheumatoid arthritis via the JAK/STAT signaling pathway.

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease, for which no economical and safe target drug treatment is available. Chikusetsusaponin Ⅳa (CS-IVa), an active compound in Panax japonicus C.A. Mey, has a good anti-inflammatory effect, but whether this compound can serve as a targeted drug for RA and the corresponding therapeutic mechanism remain unclear. PURPOSE: To investigate the anti-inflammatory and bone-protecting effects of CS-IVa on RA and the possible corresponding mechanisms of action. METHODS: Biomarkers and underlying pathological mechanisms were examined by performing a bioinformatics analysis of RA synovial gene expression data profiles, and the feasibility of CS-IVa treatment for RA was predicted using molecular docking and molecular dynamics simulation techniques. Histomorphological and molecular biology techniques were used to verify the feasibility and molecular mechanism of CS-IVa treatment for RA in vivo using a collagen-induced arthritis (CIA) model. RESULTS: CS-IVa alleviated symptoms and reduced the immune organ index, arthritis index, hind paw thickness, and number of swollen joints in the foot for CIA mice. Bioinformatics analysis suggested that interferon-gamma (IFN-γ), interleukin-1 ß (IL-1ß), and the Janus kinase/signal transduction and activator of transcription (JAK/STAT) pathway played important roles in the pathogenesis of RA. The results of molecular docking and molecular dynamics simulations showed that CS-IVa bound effectively to IFN-γ and IL-1ß and that the combined pose has good stability and flexibility. The histomorphological results showed that CS-IVa reduced joint histopathology scores, OARSI scores, and TRAP-positive cell counts. Molecular biology analysis indicated that CS-IVa reduced the concentration of inflammatory factors in the peripheral serum of CIA mice and suppressed the mRNA expression of these factors in the spleen in a dose-dependent manner. The protein expression level of the JAK/STAT pathway was also inhibited by CS-IVa. CONCLUSION: The results of the current study demonstrate a novel inhibitory effect of CS-IVa on inflammation and bone destruction in CIA mice, and the mechanism may be related to the JAK/STAT signaling pathway, which provides new insights into the development of CS-IVa as a therapeutic agent for RA.

Efficacy and safety of abdominal acupuncture for insomnia: A protocol of systematic review and meta-analysis.

BACKGROUND: Insomnia is characterized by high incidence, easy recurrence, and difficulty in curing. Serious insomnia not only seriously affects the body organ function, but psychological patients also cause great damage. Abdominal acupuncture (AA) has fewer side effects and is increasingly used to treat insomnia. This study aimed to systematically review the effectiveness and safety of abdominal acupuncture in the treatment of insomnia. METHODS: Literature on abdominal acupuncture for insomnia in the PubMed, Excerpt Medica Database(Embase), Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure Database, China Biomedical Literature Database, Chinese Scientific Journal Database, and Wan Fang databases were searched from the creation of these databases to October 3, 2021. In addition, the reference lists of studies meeting the inclusion criteria will also be searched to achieve a comprehensive retrieval of the maximum. All randomized controlled trials of AA for treating insomnia were included. Two reviewers will conduct literature screening, data extraction, and quality evaluation respectively. The main outcome was the Pittsburgh Sleep Quality Index, and the secondary outcomes included clinical efficacy and safety. RevMan 5.4.1 software was used for mate analysis. RESULTS: This study aimed to evaluate the current status of AA treatment for insomnia, with the aim of illustrating the effectiveness and safety of abdominal acupuncture. CONCLUSION: This study will provide high-quality evidence to evaluate the effectiveness and safety of AA in treating insomnia.Registration: INPLASY2021100088.

An Integrated Analysis of Network Pharmacology and Experimental Validation to Reveal the Mechanism of Chinese Medicine Formula Naotaifang in Treating Cerebral Ischemia-Reperfusion Injury.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is a crucial factor leading to a poor prognosis for ischemic stroke patients. As a novel Chinese medicine formula, Naotaifang (NTF) was proven to exhibit a neuroprotective effect against ischemic stroke, clinically, and to alleviate CIRI in animals. However, the mechanisms underlying the beneficial effect have not been fully elucidated. METHODS: In this study, we combined a network pharmacology approach and an in vivo experiment to explore the specific effects and underlying mechanisms of NTF in the treatment of ischemia-reperfusion injury. A research strategy based on network pharmacology, combining target prediction, network construction, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking was used to predict the targets of NTF in treating the ischemic stroke and CIRI. On the other hand, we used HPLC and HRMS to identify biologically active components of NTF. Middle cerebral artery occlusion models in rats were utilized to evaluate the effect and the underlying mechanisms of NTF against CIRI after ischemic stroke. RESULTS: Network pharmacology analysis revealed 43 potential targets and 14 signaling pathways for the treatment of NTF against CIRI after ischemic stroke. Functional enrichment analysis showed that a STAT3/PI3K/AKT signaling pathway serves as the target for in vivo experimental study validation. The results of animal experiments showed that NTF significantly alleviated CIRI by decreasing neurological score, infarct volume, numbers of apoptotic neuronal cells, increasing density of dendritic spines and survival of neurons. Furthermore, NTF could increase the expression of p-STAT3, PI3K, p-AKT. In addition, the detection of apoptosis-related factors showed that the NTF could raise the expression of Bcl-2 and reduce the expression of Bax. CONCLUSION: This network pharmacological and experimental study indicated that NTF, as a therapeutic candidate for the management of CIRI following ischemic stroke, may exert a protective effect through the STAT3/PI3K/AKT signaling pathway.

Acupuncture for experimental cerebral ischemia/reperfusion injury: a systematic review of methodology and reporting quality.

OBJECTIVES: Preclinical research is essential to the advancement of science but susceptible to insufficient reporting and methodological shortcomings, which compromise internal validity. We aimed to systematically assess the methodological and reporting quality of studies conducted on acupuncture for experimental cerebral ischemia/reperfusion injury (CIRI). METHODS: A comprehensive search in six databases was performed for animal research concerning acupuncture for CIRI. Two authors independently selected articles, extracted data, and assessed the methodological and reporting quality of identified articles using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool, and Animal Research: Reporting In Vivo Experiments (ARRIVE) guideline, respectively. RESULTS: A total of 24 studies were identified. Only 1 article (4%) achieved a decent overall rating in using SYRCLE (percentage of items with "low risk" ⩾50%). Of the 22 items on the SYRCLE tool, only 8 items (37%) were rated as "low risk" of bias in more than 50% of the included studies. Of the 39 items of ARRIVE, 20 (51%) items were rated as "low risk" in more than 50% of the included studies. CONCLUSIONS: The methodological and reporting quality of included studies was generally low, which demands further improvement. These findings should inform the development of evidence-based guidelines for future preclinical research assessing the effect of acupuncture on CIRI.

Umbilical acupuncture for insomnia: A protocol for systematic review and meta-analysis.

BACKGROUND: Insomnia is characterized by high incidence, easy recurrence, and difficulty in curing. Serious insomnia not only seriously affects the body organ function but also causes great damage psychological.Umbilical acupuncture (UA) has fewer side effects and is increasingly used to treat insomnia. This study aimed to systematically review the effectiveness and safety of UA in the treatment of insomnia. METHODS: Literature on UA for insomnia in PubMed, Excerpt Medica Database, the Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure Database, China Biomedical Literature Database, Chinese Scientific Journal Database, and Wan Fang Database were searched from the creation of these databases to October 3, 2021. In addition, the reference lists of studies meeting the inclusion criteria will also be searched to achieve a comprehensive retrieval of the maximum. All randomized controlled trials of UA for treating insomnia were included. Two reviewers will conduct literature screening, data extraction, and quality evaluation respectively. The main outcome was the Pittsburgh Sleep Quality Index, and the secondary outcomes included clinical efficacy, and safety. RevMan 5.4.1 software was used for mate analysis. RESULTS: This study aimed to evaluate the current status of UA treatment for insomnia, with the aim of illustrating the effectiveness and safety of UA. CONCLUSION: This study will provides a high-quality evidence to evaluate the effectiveness and safety of UA in treating insomnia. REGISTRATION: PROSPERO CRD42021283036.

Antidepressant-Like Effects of Chaihu Shugan Powder () on Rats Exposed to Chronic Unpredictable Mild Stress through Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis.

OBJECTIVE: To investigate the antidepressant-like effects of Chaihu Shugan Powder (CSP, ) and to explore its underlying mechanisms. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into control (CON), chronic unpredictable mild stress (CUMS), fluoxetine (FLU), and CSP groups, 8 rats in each group. All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model. The open field test (OFT), forced swimming test (FST), and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP. Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues. The mRNA and protein levels of glucose-regulated protein (GRP) 78, spliced X-box-binding protein (XBP)-1, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and c-Jun N-terminal kinase (JNK) in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis, respectively. RESULTS: Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats, as revealed by enhanced time and distance in the center of the OFT (P<0.05), an increased preference for sucrose, and longer swimming time and shorter immobility time during the FST (all P<0.05). In addition, CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons (P<0.05). The mRNA and protein expression levels of GRP78, spliced XBP-1, and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins (all P<0.05), whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats. CONCLUSION: CSP can improve depression-like behavior in rats exposed to CUMS, possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.

Total glucosides of paeony for the treatment of rheumatoid arthritis: A methodological and reporting quality evaluation of systematic reviews and meta-analyses.

OBJECTIVE: To assess the methodological, reporting and evidence quality of systematic reviews and meta-analyses of total glucosides of paeony (TGP) for rheumatoid arthritis (RA). METHODS: We comprehensively searched the literature in numerous databases from inception to July 29th, 2020. Two appraisers collected data and assessed the methodological and reporting quality of the included reviews by revised A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) tool and the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA), respectively. The level of evidence quality was evaluated by employing the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) scale. RESULTS: Eleven relevant articles were collected. The results from AMSTAR-2 showed that the methodological quality of all included reviews was critically low; no authors met the standard of those critical domains (0%), particularly in item 2, item 4 and item 7. The PRISMA scores ranged from 16.5 to 25, and one meta-analysis almost conformed to the PRISMA structure. According to GRADE, the 11 studies included 59 outcomes: 27 had very low quality, 22 had low quality, 10 had moderate quality, and none had high quality evidence. The most prominent downgrading factors were risk of bias, followed by publication bias, inconsistency, imprecision, and indirectness. CONCLUSIONS: Although included studies summarized that TGP was effective and safe in the treatment of RA, the methodological and reporting quality and the quality of evidence was poor overall; decision-makers should be prudent when using TGP in treating RA patients. High-quality and multicenter studies investigating TGP for RA are urgently needed.

Electroacupuncture ameliorates cerebral ischemia/reperfusion injury by suppressing autophagy via the SIRT1-FOXO1 signaling pathway.

Cerebral ischemia/reperfusion (CIR) injury occurs when blood flow is restored in the brain, causing secondary damage to the ischemic tissues. Previous studies have shown that electroacupuncture (EA) treatment contributes to brain protection against CIR injury through modulating autophagy. Studies indicated that SIRT1-FOXO1 plays a crucial role in regulating autophagy. Here we investigated the mechanisms underlying the neuroprotective effect of EA and its role in modulating autophagy via the SIRT1-FOXO1 signaling pathway in rats with CIR injury. EA pretreatment at "Baihui", "Quchi" and "Zusanli" acupoints (2/15Hz, 1mA, 30 min/day) was performed for 5 days before the rats were subjected to middle cerebral artery occlusion, and the results indicated that EA pretreatment substantially reduced the Longa score and infarct volume, increased the dendritic spine density and lessened autophagosomes in the peri-ischemic cortex of rats. Additionally, EA pretreatment also reduced the ratio of LC3-II/LC3-I, the levels of Ac-FOXO1 and Atg7, and the interaction of Ac-FOXO1 and Atg7, but increased the levels of p62, SIRT1, and FOXO1. The above effects were abrogated by the SIRT1 inhibitor EX527. Thus, we presume that EA pretreatment elicits a neuroprotective effect against CIR injury, potentially by suppressing autophagy via activating the SIRT1-FOXO1 signaling pathway.

Methodological and reporting quality evaluation of meta-analyses on the Chinese herbal preparation Zheng Qing Feng Tong Ning for the treatment of rheumatoid arthritis.

BACKGROUND: Zheng Qing Feng Tong Ning (ZQFTN) is a sinomenine (SIN) preparation that has been used in clinical practice. Our study aimed to assess the methodological and reporting quality of meta-analyses on the Chinese herbal formula ZQFTN for the treatment of rheumatoid arthritis (RA). METHODS: Systematic searches were carried out with the 5 following electronic databases from inception to July 2019: China National Knowledge Infrastructure (CNKI), Wanfang, VIP database for Chinese technical periodicals (VIP), Cochrane Library and PubMed. The quality of the methodology and reporting was measured with the assessment of multiple systematic reviews 2 (AMSTAR 2) scale, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: Eight studies were identified. Among the 16 items of the AMSTAR 2 scale, four items were optimally reported ("Y" =100% of the items), and another four items were poorly reported ("Y" =0% of the items). Only 2 studies received a good overall score ("Y" ≥50% of the items). Regarding the PRISMA statement, the scores of 5 studies were lower than the average score (17.69), indicating that the quality of the reports was very low. In terms of the GRADE, none of the 61 results were of high quality (0.0%). Fifteen results were of medium quality (25%), 34 were of low quality (55%), and 12 were of very low quality (20%). Among the five downgrading factors, deviation risk (n = 61, 100%) was the most common downgrading factor, followed by inconsistency (n = 30, 50%), publication bias (n = 17, 28%), inaccuracy (n = 11, 18%) and indirectness (n = 0, 0%). CONCLUSIONS: The methodological and reporting quality of the meta-analyses and systematic reviews in the included studies are less than optimal, and researchers should undergo additional training and follow the AMSTAR 2 scale, PRISMA statement and GRADE to design high-quality studies in the future.

Efficacy and safety of the classic Chinese herbal prescription Sanpian decoction on migraine: A meta-analysis.

OBJECTIVES: To evaluate the efficacy and safety of the classic Chinese herbal prescription Sanpian decoction for curing migraine. METHODS: Scopus, PubMed, EMBASE, SPRINGER LINK, China National Knowledge Infrastructure (CNKI), Weipu Database and WanFang Database were searched from inception through January 2019 to identify randomized controlled trials (RCTs) that evaluated the efficacy and safety of Sanpian decoction. RESULTS: Fifteen RCTs with a total of 1377 participants were identified. Compared with the control drugs, Sanpian decoction and Sanpian decoction combined with Sibelium significantly improved the clinical efficacy separately (relative risk [RR] 4.19, 95% confidence intervals [CI] 2.91 to 6.04, P < 0.00001; RR 1.29, 95% CI 1.09 to 1.54, P = 0.003 separately); the Sanpian decoction significantly improved the visual analogue scale score (VAS) (mean differences [MD] -1.83, 95% CI -2.69 to -0.97, P < 0.0001), headache score (MD -3.77, 95% CI -7.20 to -0.34, P = 0.03) and reduced the frequency of headache attacks (MD -1.61, 95% CI -2.07 to -1.14, P < 0.00001) and the concentration of endothelin (ET) (MD -11.90, 95% CI -23.22 to -0.58, P = 0.04) when compared with control drugs. There were minor side effects related to Sanpian decoction which were well tolerated. CONCLUSIONS: Sanpian decoction is of significant benefits and relative safety in treating migraine. However, more rigorous studies with larger sample sizes are needed due to methodological flaws and low quality of the included trials in this meta-analysis.

Protection of the Geum japonicum Thunb. var. chinense extracts against oxygen-glucose deprivation and re-oxygenation induced astrocytes injury via BDNF/PI3K/Akt/CREB pathway.

Geum japonicum Tunb. var. chinense (GJ) is a traditional Chinese medicine usually used for the alleviation of dizziness and headache. Previous studies have reported that the GJ extracts could alleviate cerebral I/R injury by reducing apoptosis in vivo. To further elucidate the positive role and underlying mechanism of the GJ extracts in cerebral I/R injury, the current study investigated the effects of the GJ extracts on oxygen-glucose deprivation and re-oxygenation (OGD/R)-induced astrocytes injury in light of BDNF/PI3K/Akt/CREB signaling pathway with seropharmacological method. In the present study, the LC-MS profiling of the GJ extracts, obtain by reflux extraction, led to the identification of three possible active components were 5-desgalloylstachyurin, tellimagrandin II (TG II) and 3,4,5-Trihydroxybenzaldehyde (THBA). Drug-containing serum was collected from rats given different doses of the GJ extracts (0, 1.75 g/kg, 7 g/kg). Data indicated that the GJ extracts could increase the cell viability and decrease apoptosis and the expression of glial fibrillary acidic protein (GFAP) in OGD/R-induced astrocytes. In addition, the detection of apoptosis-related factors showed that the GJ extracts could obviously increase the expression of Bcl-2 and reduce the expression of Bax, Caspase-3 and cleaved-Caspase-3. Furthermore, the GJ extracts markedly increased the expression of BDNF, TrkB, PI3K, p-Akt and p-CREB. All these effects of the GJ extracts could be significantly reversed by LY294002, an inhibitor of PI3K. These data indicated that the GJ extracts could protect astrocytes against OGD/R-induced injury by inhibiting astrocytes reactivity and apoptosis, owing to the activation of the BDNF/PI3K/Akt/CREB pathway. The results support the application of the GJ extracts in the treatment of ischemic stroke and other ischemic encephalopathy.

Efficacy of herbal medicine (Gegen Qinlian Decoction) on ulcerative colitis: A systematic review of randomized controlled trials.

BACKGROUND: This systematic review aims to evaluate the efficacy of Gegen Qinlian Decoction (GQD) for ulcerative colitis (UC). METHODS: PubMed, EMBASE, Springer LINK, Cochrane Library, the China National Knowledge Infrastructure, Chongqing Weipu Database for Chinese Technical Periodicals, Wan-fang Database, and Chinese Biomedicine Database were searched from their inception to December 2018 for randomized controlled trials comparing the use of GQD alone or in combination with western medicine (WM) with that of WM therapies for UC. Outcomes on the therapy's effectiveness rate, ulcerative colitis endoscopic index of severity (UCEIS), recurrence rate, and adverse events were extracted and analyzed by Review Manager 5.3 software. Meta-analysis was combined with fixed or random-effects model, and risk ratios (RR) and 95% confidence intervals (CI) were calculated for all outcomes. Two researchers independently reviewed each trial to determine its inclusion. The Cochrane risk of bias assessment tool was used for quality assessment. RESULTS: We included 22 trials involving 2028 patients with UC. When compared with WM therapy, GQD significantly improved the clinical effectiveness (n = 591, RR = 1.21, 95% CI: 1.12-1.31, P < .00001) and recurrence rate (n = 94, RR = 0.23, 95% CI: 0.10-0.54, P = .0006). GQD plus WM was more effective in improving the clinical effectiveness (n = 1337, RR = 1.21, 95% CI: 1.16-1.27, P < .00001), and decreasing UCEIS scores (n = 384, mean difference  = -0.63, 95% CI: -1.26--0.01, P = .05), recurrence rate (n = 179, RR = 0.18, 95% CI: 0.06-0.61, P = .006). In addition, the adverse events for GQD (n = 238, RR = 0.20, 95% CI: 0.02-1.68, P = .14) and GQD plus WM (n = 427, RR = 0.37, 95% CI: 0.15-0.90, P = .03) was significantly lower than that for WM alone. Noted adverse events primarily included gastrointestinal symptoms, headache, dizziness, and leukocytopenia. CONCLUSIONS: This meta-analysis shows that GQD used alone or in combination with WM might have potential benefits in curing UC. However, there is no sufficient evidence to draw definite conclusion supporting the effect of GQD for UC due to poor methodological quality of the included trials. More rigorously designed investigations and studies with large sample sizes should be conducted to establish clinical evidence further.

[Electroacupuncture pretreatment alleviated cerebral ischemia-reperfusion injury via suppressing autophagy in cerebral cortex tissue in rats].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) preconditioning on autophagy in cerebral cortex tissues of rats with cerebral ischemia-reperfusion injury (CIRI), so as to explore its mechanisms underlying improvement of CIRI. METHODS: Thirty-three male Sprague-Dawley rats were randomly divided into sham operation, model and EA groups (n=11 in each group). EA (2 Hz/15 Hz, 1 mA) was applied to "Baihui"(GV20), "Quchi" (LI11) and "Zusanli" (ST36) for 30 min, once daily for 5 days, followed by establishment of CIRI model by occlusion of the middle cerebral artery (MCAO) for 1.5 h and reperfusion for 24 h. The neurological deficit score was assessed in reference to Longa's methods, and the infarct volume assessed by 2,3,5-triphenyltetrazolium chloride staining. The density of dendrite spines of neurons in the ischemic cerebral cortex tissue was detected by Golgi's staining, the autophagosome observed by electron microscopy, and the expression levels of microtubule-associated protein 1 light chain 3 (LC3) and p62 (a selective autophagy substrate) were detected by Western blot. RESULTS: Compared with the sham operation group, the neurological deficit score and infarct volume were significantly increased (P<0.01), the number of autophagosomes and the ratio of LC3-Ⅱ/LC3-Ⅰ also significantly increased (P<0.01), while the expression level of p62 was notably decreased in the model group (P<0.01). Following the intervention and in comparison with the model group, the neurological deficit score and infarct volume were significantly reduced (P<0.01), the number of autophagosomes and the ratio of LC3-Ⅱ/LC3-Ⅰ obviously decreased (P<0.01), and the expression of p62 was significantly up-regulated in the EA group (P<0.01). CONCLUSION: EA pretreatment is effective in improving CIRI in rats, which may be realized through suppressing autophagy in the ischemic cerebral cortex tissue.

[Progress of researches on acupuncture treatment of cerebral ischemia-reperfusion injury by regulating autophagy in the ischemic cerebral tissue].

Excessive autophagy is one of the crucial factors of cerebral ischemia-reperfusion injury (CIRI), which has been demonstrated to be one of the targets for acupuncture treatment of ischemic stroke. In the present paper, we make a review about the development of acupuncture intervention induced improvement of CIRI (such as reducing the infarction area, improving learning-memory ability and motor function) by regulating autophagy in animal studies. Outcomes showed that acupuncture intervention can function in 1) inhibiting CIRI-induced increase of the number of lysosomes and autophagic lysosomes, and relieving structural injury of mitochondria, and reducing the number of autophagosome in the central region of the ischemic cerebral cortex tissue; 2) down-regulating the expression of microtubule-associated protein Ⅱ light chain 3 (LC3Ⅱ) and the ratio of LC3-Ⅱ/LC3-Ⅰ in the ischemic cerebral region, and 3) regulating the expression of Beclin 1 (autophagy-related gene), promoting the expression of P62 (autophagy-related adaptor protein). In addition, acupuncture can also regulate phosphoinositide 3 kinase (PI3K)- protein kinase B (AKT)- mammalian target of rapamycin complex 1(mTOR) signaling at different time-points (down-regulation at the early stage and up-regulation at the later stage), and activating AMP-activated protein kinase (AMPK)-mTOR- UNC51-like kinase-1 signaling to relieve cerebral ischemic injury. These results reveal some mechanisms of acupuncture therapy underlying improvement of CIRI and provide experimental basis for clinical application of acupuncture therapy in the treatment of ischemic stroke.

[Effect of electrical stimulation at auricular points combined with sound masking on the expression of CREB, BDNF and TrkB in the auditory cortex of tinnitus rats].

OBJECTIVE: To explore the effect of electrical stimulation at auricular points (EAS) combined with sound masking on the expression of cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) in the auditory cortex of tinnitus rats. METHODS: A total of 27 adult male SD rats were randomly divided into a control group, a model group and an EAS group. The rats in the model group and the EAS group were intervened with intraperitoneal injection of sodium salicylate to induce tinnitus model, while the rats in the control group were intervened with injection of 0.9% NaCl solution. After the model was successfully established, the rats in the EAS group were treated with electrical stimulation at "Shenmen" (TF4) and "Yidan" (CO11), combined with sound masking; the treatment was given once a day for 15 days. The gap prepulse inhibition of acoustic startle (GPIAS) and prepulse inhibition (PPI) testing were performed using the acoustic startle reflex starter package for rats. The expression of BDNF, TrkB, CREB and p-CREB in the auditory cortex of each group were measured with Western Blot analysis. RESULTS: ① Compared with the control group, the GPIAS values in 12 kHz, 16 kHz, 20 kHz and 28 kHz were significantly decreased in the model group (all P<0.05); compared with the model group, GPIAS values in 12 kHz, 16 kHz, 20 kHz and 28 kHz were significantly increased in the EAS group (all P<0.05). ② Compared with the control group, the expression of BDNF and p-CREB in the model group was significantly increased (P<0.01), and the expression of TrkB in the model group was significantly increased (P<0.05); the differences of expression of BDNF, TrkB, CREB and p-CREB between the model group and the EAS group had no statistics significance (all P>0.05). CONCLUSION: EAS could improve the GPIAS values of high-frequency background sound in tinnitus rats, which may be related with the upregulation of the BDNF/TrkB/CREB signaling pathway in the auditory cortex, leading to the reversion of the maladaptive plasticity.

Autophagy: novel insights into therapeutic target of electroacupuncture against cerebral ischemia/ reperfusion injury.

Electroacupuncture is known as an effective adjuvant therapy in ischemic cerebrovascular disease. However, its underlying mechanisms remain unclear. Studies suggest that autophagy, which is essential for cell survival and cell death, is involved in cerebral ischemia reperfusion injury and might be modulate by electroacupuncture therapy in key ways. This paper aims to provide novel insights into a therapeutic target of electroacupuncture against cerebral ischemia/reperfusion injury from the perspective of autophagy. Here we review recent studies on electroacupuncture regulation of autophagy-related markers such as UNC-51-like kinase-1 complex, Beclin1, microtubule-associated protein-1 light chain 3, p62, and autophagosomes for treating cerebral ischemia/reperfusion injury. The results of these studies show that electroacupuncture may affect the initiation of autophagy, vesicle nucleation, expansion and maturation of autophagosomes, as well as fusion and degradation of autophagolysosomes. Moreover, studies indicate that electroacupuncture probably modulates autophagy by activating the mammalian target of the rapamycin signaling pathway. This review thus indicates that autophagy is a therapeutic target of electroacupuncture treatment against ischemic cerebrovascular diseases.