Neuroprotective potentials of ferulic acid against intracerebral hemorrhage COVID-19 through using network pharmacology approach and molecular docking analysis.

Intracerebral hemorrhage (ICH) refers to severe stroke subtype that may be life-threatening or even cause death. It is clinically observed that coronavirus disease 2019 (COVID-19) may be associated with the high mortality in ICH patients. Ferulic acid, one of the functional bioactive ingredients from medicinal herbs, has been preclinically proven with beneficial activities, including neuroprotection and anti-inflammation actions. Based on current findings, we assumed that ferulic acid may play the potentials against COVID-19 when ICH. In this study, preclinical approach including network pharmacology and molecular docking was applied to detect and identify the core targets and pharmacological mechanisms involved in ferulic acid on COVID-19 and ICH. The network pharmacology analysis identified total eleven core targets in ferulic acid and COVID-19/ICH. The molecular mechanisms of ferulic acid against COVID-19 and ICH were mostly involved in induction of antiviral activity, modulation of inflammatory reaction. Molecular docking model revealed that ferulic acid might effectively bind to epidermal growth factor receptor (EGFR) protein based on strong binding capability. Current findings reflected the preclinical pharmacological activities of ferulic acid that might use for management of COVID-19 and ICH. Although there are the limitations that are absence of experimental validation, these bioinformatic results underline that ferulic acid may exert simultaneous potentials against COVID-19 and ICH through modulating integrative mechanisms and key biotargets.

The Effects of Electroacupuncture as an Adjunct Therapy on Poststroke Aphasia: A Systematic Review and Meta-Analysis.

Background: To systematically collate, appraise, and synthesize evidence of electroacupuncture (EA) as an adjunct therapy for poststroke aphasia (PSA) from randomized controlled trials (RCTs) through a systematic review and meta-analysis. Methods: An electronic search was conducted in eight databases to identify RCTs evaluating EA adjuvant therapy versus speech and language therapy (SLT). Methodological quality of the included trails was assessed by the Cochrane risk of bias. The software Review Manager 5.4 was used for data analysis. Results: Nineteen RCTs enrolling a total of 1263 subjects were identified. The use of EA combined with speech and language therapy (SLT) showed significant improvements in effective rate (RR 1.31, 95% CI [1.21, 1.41]), oral expression score (SMD 1.34, 95% CI [1.13, 1.56]), comprehension score (SMD 1.95, 95% CI [0.88, 3.03]), repetition score (SMD 1.84, 95% CI [0.75, 2.93]), naming score (SMD 1.97, 95% CI [0.81, 3.13]), and reading score (SMD 1.55, 95% CI [1.07, 2.04]) compared to the use of SLT alone. Conclusions: The pooled data indicate that EA combined with SLT for the treatment of PSA may improve clinical effectiveness, compared with SLT alone. Future high quality RCTs with large samples are still needed to confirm and expand our findings.

Effects of Tai Chi Exercise on Balance Function in Stroke Patients: An Overview of Systematic Review.

Background: Tai chi (TC) has received increased attention in stroke rehabilitation, yet services are greatly underutilized. An increasing number of systematic reviews and meta-analyses (SRs/MAs) have begun to investigate the effects of TC on balance function in stroke patients. The aim of this current study was to systematically collate, appraise, and synthesize the results of these SRs/MAs using a systematic overview. Methods: Eight databases were searched: PubMed, Cochrane Library, Embase, Web of Science, CNKI, SinoMed, Chongqing VIP, and Wanfang Data. SRs/MAs of TC on balance function in stroke patients were included. Literature selection, data extraction, and assessment of the review quality were performed by two independent reviewers. Methodological quality was assessed by the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), reporting quality by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and evidence quality by Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results: Nine SRs/MAs were included in this study. For methodological quality, what resulted in unsatisfactory methodological quality was noncompliance with critical item 4 (using a comprehensive literature search strategy) and critical item 7 (providing the list of excluded research literature). For reporting quality, what resulted in unsatisfactory reporting quality was inadequate reporting of Q1 (protocol and registration), Q8 (search), Q15 (risk of bias across studies), Q16 (additional analyses), Q22 (risk of bias across studies), Q23 (additional analysis), and Q27 (funding). For GRADE, the evidence quality was high in 0, moderate in 3, low in 11, and very low in 6. Risk of bias was the most common factor leading to downgrading of evidence, followed by inconsistency, imprecision, publication bias, and indirectness. Conclusions: TC may have beneficial effects on balance function in stroke survivors; however, this finding is limited by the generally low methodology, reporting quality, and evidence quality for published SRs/MAs.

The Role of Traditional Chinese Medicine Nursing for Stroke: An Umbrella Review.

BACKGROUND: An increasing number of systematic reviews/meta-analyses (SRs/MAs) of clinical trials have begun to investigate the effects of traditional Chinese medicine (TCM) nursing in patients with stroke. To systematically appraise and synthesize these results, we conducted an overview of SRs/MAs. METHODS: Eight databases from their inception to April 2020 were searched to include all SRs/MAs on TCM nursing for stroke. Methodological quality assessment was performed using Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) and evidence quality assessment was performed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS: Eleven SRs/MAs regarding TCM nursing for stroke were included. The assessments with AMSTAR-2 indicated that the methodological quality of all included SRs/MAs was critically low. According to the evaluation results of GRADE, 10 (40%) outcomes were rated as critically low-quality evidence, 7 (28%) low-quality evidence, and 8 (32%) moderate-quality evidence. Descriptive analysis results showed that TCM nursing was effective for stroke. CONCLUSIONS: All included SRs/MAs suggested positive findings of TCM nursing for stroke, but the credibility of the results is limited. Studies with methodologically rigorous and adequately powered are still needed in this field.

The Effects of Tai Chi Exercise Among Adults With Chronic Heart Failure: An Overview of Systematic Review and Meta-Analysis.

Background: Tai chi (TC) is a popular form of exercise among adults with chronic heart failure (CHF), yet services are greatly underutilized. The aim of the current study was to identify and summarize the existing evidence and to systematically determine the clinical effectiveness of Tai Chi in the management of CHF using a systematic overview. Methods: Both English and Chinese databases were searched for systematic reviews (SRs)/meta-analyses (MAs) on TC for CHF from their inception to June 2020. The methodological quality, reporting quality, and risk of bias of SRs/MAs were assessed using Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, and Risk of Bias in Systematic reviews (ROBIS), respectively. The evidence quality of outcome measures was assessed by the Grades of Recommendations, Assessment, Development and Evaluation (GRADE). Results: Six SRs/MAs using a quantitative synthesis to assess various outcomes of TC in CHF were included in this overview. The methodological quality, reporting quality and risk of bias of the SRs/MAs and the evidence quality of the outcome measures are generally unsatisfactory. The limitations of the past SRs/MAs included the lack of either the protocol or registration, the list of excluded studies, and the computational details of meta-analysis were inadequately reported. The critical problems were that qualitative data synthesis relied on trials with small sample sizes and critical low quality. Conclusions: TC may be a promising complementary treatment for CHF. However, further rigorous and comprehensive SRs/MAs and RCTs are required to provide robust evidence for definitive conclusions.

A Critical Overview of Systematic Reviews of Shenfu Injection for Heart Failure.

OBJECTIVES: Shenfu Injection (SFI) was widely used in the treatment of heart failure (HF) in China. A plethora of systematic reviews/meta-analyses (SRs/MAs) has been conducted in this research area, although with scattered results. The purpose of this overview was to conduct a comprehensive review to summarize and critically evaluate the existing evidence. METHODS: Digital databases were searched for SRs/MAs up to January 28, 2021. Two authors independently screened the reviews and assessed the methodological quality of included SRs/MAs using Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2). Quality of evidence for outcomes evaluated within the reviews was appraised with the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE). RESULTS: Thirteen SRs/MAs met the inclusion criteria. Based on AMSTAR-2, the quality of all SRs/MAs was critically low, because all of them have more than one critical domains that were unmet. Based on GRADE, the evidence quality of 24 outcome measures was low or very low, 27 outcome measures was moderate, and none outcome measure was high. Descriptive analysis showed that SFI was an effective and safe method for HF. CONCLUSIONS: The use of SFI for the treatment of HF may be clinically effective and safe. However, this conclusion must be interpreted cautiously due to the generally low methodological quality and low evidence quality of the included SRs/MAs. More rigorously designed SRs/MAs and RCTs with high methodological quality are necessary for further proof.

Acupuncture for the Treatment of Alzheimer's Disease: An Overview of Systematic Reviews.

Background: Acupuncture may be an effective complementary treatment for Alzheimer's disease (AD). The aim of this study was to summarize the evidence provided by systematic reviews (SRs)/meta-analyses (MAs) on the effect of acupuncture on AD. Methods: Eight electronic databases were searched from their inception until October 19, 2020. The methodological quality, reporting quality, and risk of bias of the included SRs were assessed by the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Reviews (ROBIS) tool, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Moreover, the evidence quality of the outcome measures was assessed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results: Eleven SRs/MAs met all inclusion criteria. According to the results of the AMSTAR-2, all included reviews were rated critically as being of low quality. With PRISMA, the reporting checklist was relatively complete, but some reporting weaknesses remained in the topics of the protocol and registration, search strategy, risk of bias, additional analyses, and funding. Based on the ROBIS tool, only two SRs/MAs had a low risk of bias. With the GRADE system, no high-quality evidence was found, and only seven outcomes provided moderate-quality evidence. Among the downgraded factors, the risk of bias within the original trials was ranked first, followed by inconsistency, imprecision, and publication bias. Conclusions: Acupuncture is a promising complementary treatment for AD. However, due to the low quality of the SRs/MAs supporting these results, high-quality studies with rigorous study designs and larger samples are needed before widespread recommendations can be made.

A Critical Overview of Systematic Reviews and Meta-Analyses on Acupuncture for Poststroke Insomnia.

OBJECTIVES: Acupuncture has increasingly been used for insomnia relief after stroke. We aimed to evaluate the methodological quality and summarize the evidence regarding the effectiveness of acupuncture for poststroke insomnia (PSI) from systematic reviews/meta-analyses (SRs/MAs). METHODS: Eight databases were searched from inception through August 23, 2020. SRs/MAs on acupuncture treatment for PSI were included. Methodological quality assessment was performed using Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), and evidence quality assessment was performed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS: Six SRs/MAs on acupuncture treatment for PSI were included. The AMSTAR-2 showed that the methodological quality of all included SRs/MAs was rated as critically low. According to the evaluation results of GRADE, 38.9% (7/18) of outcomes were rated as very low-quality evidence, 22.2% (4/18) were low-quality evidence, and 8.9% (7/18) were moderate-quality evidence. Descriptive analysis results showed that acupuncture was an effective treatment modality for PSI. CONCLUSIONS: All included reviews indicated that acupuncture was more effective than the control group for the treatment of PSI, but the credibility of the results is limited owing to the generally low methodological and evidence quality of the included SRs/MAs. More high-quality evidence is needed to determine whether acupuncture is more effective than other treatments.

Clinical Effects and Safety of Electroacupuncture for the Treatment of Poststroke Dysphagia: A Comprehensive Systematic Review and Meta-Analysis.

OBJECTIVES: Electroacupuncture (EA), an extension of acupuncture, which is based on traditional acupuncture combined with modern electrotherapy, is commonly used for poststroke dysphagia (PSD) in clinical treatment and research. However, there is still a lack of sufficient evidence to recommend the routine use of EA for PSD. The aim of this study was to assess the efficacy and safety of EA in the treatment of PSD. METHODS: Randomized controlled trials (RCTs) evaluating the effects of EA on PSD were identified through a comprehensive literature search of the PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, and VIP databases from their inception to July 2020. The quality assessment of the included trials was performed based on the guidance of the Cochrane Reviewers' Handbook, and meta-analysis (MA) was performed by using the RevMan 5.3 software. RESULTS: Sixteen trials were identified, and these included 1,216 patients with PSD. The results demonstrated that EA in combination with swallowing rehabilitation training (SRT) was significantly superior to SRT alone with regard to effective rate (OR 5.40, 95% CI [3.78, 7.72], P < 0.00001, water swallow test (WST) (MD -0.78, 95% CI [-1.07, -0.50], P < 0.00001), the video fluoroscopic swallowing study (VFSS) (MD 1.47, 95% CI [1.11, 1.84], P < 0.00001), the Ichiro Fujishima Rating Scale (IFRS) (MD 1.94, 95% CI [1.67, 2.22], P < 0.00001), and the incidence of aspiration pneumonia (IAP) (OR 0.20, 95% CI [0.06, 0.61], P=0.005). CONCLUSIONS: The results showed that EA was better than the control treatment in terms of the effective rate, WST, VFSS, IFRS, and IAP of dysphagia after stroke. Strict evaluation standards and high-quality RCT designs are necessary for further exploration.

Effectiveness of Acupuncture in the Treatment of Parkinson's Disease: An Overview of Systematic Reviews.

Background: The effects of acupuncture on Parkinson's disease (PD) outcomes remain unclear. The aim of this overview was to comprehensively evaluate the methodological quality and applicability of the results of systematic reviews (SRs)/meta-analyses (MAs) that examined the use of acupuncture to treat PD. Methods: Eight databases were searched to retrieve SRs/MAs on the use of acupuncture for the treatment of PD. Two reviewers independently screened and extracted the data using the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) checklist to evaluate the methodological quality and using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria to assess the evidence quality of the included reviews. Results: A total of 11 SRs/MAs were included. According to the AMSTAR-2 checklist results, all included SRs/MAs were rated as very-low-quality studies. The GRADE criteria revealed 20 studies with very-low-quality evidence, 9 with low-quality evidence, 3 with moderate-quality evidence, and 0 with high-quality evidence. Descriptive analysis showed that acupuncture appears to be a clinically effective and safe treatment for PD. Conclusions: The use of acupuncture for the treatment of PD may be clinically effective and safe. This conclusion must be interpreted cautiously due to the generally low methodological quality and low quality of evidence of the included studies.

Effectiveness of Auricular Acupuncture for Insomnia: An Overview of Systematic Reviews.

OBJECTIVES: The effectiveness of auricular acupuncture (AA) for insomnia is far from uniform. The aim of this overview was to summarize and critically evaluate the evidence from systematic reviews (SRs)/meta-analysis (MAs) and provide an overall verdict about the therapeutic value of AA for insomnia. METHODS: A search of relevant literature for SRs/MAs was performed on major medical databases. The methodological quality was assessed using the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) and the evidence quality was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: Seven SRs/MAs were deemed eligible for the present overview. According to the evaluation results of AMSTAR-2, the methodological quality of all included SRs/MAs was critically low. Consistent methodological deficiencies were item 2 (the lack of a protocol), item 4 (the lack of a specific search strategy), item 7 (the lack of a list of excluded studies), and item 15 (the lack of an assessment of publication bias). For GRADE, of the 17 outcomes, only 1 (5.9%) was rated of high-quality, 4 (23.5%) were rated of moderate-quality, and the remaining 12 (70.6%) were rated of low-or critically low-quality. Descriptive analysis of the outcomes reveals a positive effect of AA for insomnia. CONCLUSIONS: AA may be beneficial for insomnia, but the evidence is plagued by important limitations, e.g., the poor quality of SRs/MAs and primary studies.

Acupuncture for the Treatment of Tension-Type Headache: An Overview of Systematic Reviews.

OBJECTIVES: Because current evidence regarding the effectiveness of acupuncture for a tension-type headache (TTH) is controversial, we evaluated the reliability of the methodological quality and outcome measures of systematic reviews/meta-analyses (SRs/MAs) on acupuncture for TTH. METHODS: We conducted a comprehensive literature search for SRs/MAs in major databases from the database's inception to September 2019. The Methodological Quality of Systematic Reviews 2 (AMSTAR-2) and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments were used to assess the methodological quality of the included reviews and the quality of evidence, respectively. RESULTS: Eight reviews were included in the analysis. The AMSTAR-2 assessment results showed that the methodological quality of all included reviews was critically low. Thirty-six outcome measures were included in these reviews. The GRADE results showed that 25 (25/36, 69.4%) outcomes provided low- or very low-quality evidence, four (4/36, 11.1%) provided moderate-quality evidence, and seven (7/36, 19.4%) provided high-quality evidence. Descriptive analysis results showed that acupuncture treatment for TTH reduced headache frequency and severity. CONCLUSIONS: Acupuncture appears to be an effective treatment modality for TTH, but the credibility of the results is limited owing to the generally low methodological quality and evidence quality in the included SRs/MAs.

A proton-coupled organic cation antiporter is involved in the blood-brain barrier transport of Aconitum alkaloids.

ETHNOPHARMACOLOGICAL RELEVANCE: The herbs of Aconitum are the essential Traditional Chinese medicine and have played an indispensable role in many Asian countries for thousands of years to treat critical illnesses, and chronic, stubborn diseases. However, Aconitum may induce severe neurotoxicity and even death. So far the mechanism of Aconitum penetrating the blood-brain barrier (BBB) is still unclear. AIM OF THE STUDY: To determine whether influx transporters contribute to the brain uptake of the highly toxic alkaloids in Aconitum including aconitine (AC), mesaconitine (MA) and hypaconitine (HA). MATERIALS AND METHODS: The uptake of AC, MA and HA was characterized using in vitro hCMEC/D3 model and in situ mouse brain perfusion. In hCMEC/D3 cells, the effect of incubation temperature, time, initial drug concentration, energy (NaN3), extracellular and intracellular pH (FCCP and NH4Cl), the prototypical substrates/inhibitors of known organic cation transporting carriers and trans-stimulation (pre-incubating with pyrilamine and diphenhydramine) on the cellular uptake were studied. In addition, the effect of silencing OCTN1, OCTN2 and PMAT by specific siRNA was investigated. In mice, the contribution of the proton-coupled antiporter on the brain uptake of Aconitum was investigated by chemical inhibition. RESULTS: In hCMEC/D3 cells, AC, MA and HA were each taken up in a temperature-, time- and concentration-dependent manner, which were reduced by NaN3 and FCCP. Regulation of extracellular and intracellular pH as well as trans-stimulation studies showed that AC, MA and HA were transported by a proton-coupled antiporter expressed at the plasma membrane that could also transport pyrilamine and diphenhydramine. Each uptake was markedly inhibited by various cationic drugs, but insensitive to the prototypical substrates/inhibitors of identified organic cation transporting carriers, such as OCTs, PMAT, MATEs and OCTNs. In addition, silence of OCTN1, OCTN2 and PMAT had no significant inhibitory effect on the uptake of AC, MA and HA. In mice, the brain uptake of each alkaloid measured by in situ brain perfusion was suppressed by diphenhydramine when the transport capacity of P-gp/Bcrp at the BBB was chemically inhibited. CONCLUSIONS: A novel proton-coupled organic cation antiporter plays a predominant role in the blood to brain influx of AC, MA and HA at the BBB, and thus affect the safety of Aconitum species.

Effects of electroacupuncture on functional indices and pS6 expression following acute sciatic nerve crush injury in rats.

OBJECTIVE: The aim of this study was to investigate the effect of electroacupuncture (EA) on recovery from acute sciatic nerve crush injury and the expression of pS6 in rats. METHODS: A total of 108 adult male Sprague-Dawley rats were randomly divided into control, model, EA and EA+rapamycin (EA+Rapa) groups. 28 rats were allocated to undergo measurement of sciatic functional index (SFI); one rat in the EA+Rapa group was unsuccessfully modelled and excluded because of an anaesthetic problem. The remaining 80 rats were allocated to undergo Western blot detection of S6 ribosomal protein (pS6, ser240/244). The model was created by mechanical clamping of the sciatic nerve stem. EA stimulation at GB30 and ST36 for 15 min separately was applied once daily for rats in the EA and EA+Rapa groups. For rats in the EA+Rapa group, rapamycin, a mammalian target of rapamycin (mTor) pathway inhibitor, was injected intramuscularly (1 mg/kg/day) near the site of crush injury in the sciatic nerve and an equivalent amount of dimethyl sulfoxide was injected in the other three groups every other day. After treatment for 7, 14, 28 and 42 days post-operation, the SFI of 27 rats was obtained to evaluate recovery of motor function and five rats from each group per stage were used for Western blot detection of pS6. RESULTS: The SFI values showed that EA could significantly promote recovery of the injured sciatic nerve but rapamycin hindered the therapeutic effect of EA. Moreover, immunoblotting indicated that EA improved the expression of pS6 in the area of the sciatic nerve crush injury and local injection of rapamycin near the injured sciatic nerve decreased its expression. The pS6 level correlated with the extent of recovery of the injury. CONCLUSIONS: This study indicated that EA may activate the mTOR signalling pathway to enhance expression of pS6 and facilitate recovery following sciatic nerve crush injury.