Evaluation of Zhilong Huoxue Tongyu capsule in the treatment of acute cerebral infarction: A systematic review and meta-analysis of randomized controlled trials

Liu, Mengnan; Pu, Yuting; Gu, Juan; He, Qi-da; Liu, Yan; Zeng, Yunhong; Li, Jingchi; Long, xingru; Yang, Sijin; Wu, Qibiao; Zhou, Hua

doi:10.1016/j.phymed.2021.153566

Cited by 16 publications

(10 citation statements)

References 32 publications

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“…In all, 207 studies were excluded due to the following reasons: samples overlap with other studies (n = 80), no necessary sample data (n = 45), other outcomes (n = 27), other stroke (n = 20), other language (n = 17), no placebo group (n = 11), mild cognitive impairment (n = 7), (Figure 1). Thus, 43 studies were included in the umbrella review: Pan et al, 2020;Pan et al, 2020); Liu et al, 2021); (Liu et al, 2011);Blann et al, 2015); (Blann et al, 2015); Emberson et al, 2014) (Emberson et al, 2014); Peng et al, 2014); (Peng et al, 2014); Zhang et al, 2019); Shang et al, 2019); Puñal-Riobóo et al, 2015;Yuan et al, 2008;(Fu et al, 2013), Fan et al, 2014), Lin et al, 2014; Xu et al, 2015); Cao and Li, (2015); Marmagkiolis et al, 2015); Zheng et al, 2017), Li et al, 2017), Zhang et al, 2017), Chong et al, 2020); (Zhao et al, 2021), Li et al (2020); (Li et al, 2020), Gao et al, 2021); Huang et al, 2020); (Huang and Xiao, 2021), Liu et al, 2022), Feng et al, 2021, Lee et al (2010); Zhou et al, 2022); Hu et al, 2021); Lee, 2015, Liu et al, 2021); (Liu et al, 2021), Xin et al, 2020);…”

Section: Resultsmentioning

confidence: 99%

The Efficacy and Safety of Ischemic Stroke Therapies: An Umbrella Review

Cui

Fan

et al. 2022

Front. Pharmacol.

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Background: Ischemic stroke is a leading cause of morbidity and mortality in neurological diseases. Numerous studies have evaluated the efficacy and safety of ischemic stroke therapies, but clinical data were largely inconsistent. Therefore, it is necessary to summarize and analyze the published clinical research data in the field.Objective: We aimed to perform an umbrella review to evaluate the efficacy and safety of ischemic stroke therapies.Methods: We conducted a search for meta-analyses and systematic reviews on PubMed, the Cochrane Library, and the Web of Science to address this issue. We examined neurological function deficit and cognitive function scores, quality of life, and activities of daily living as efficacy endpoints and the incidence of adverse events as safety profiles.Results: Forty-three eligible studies including 377 studies were included in the umbrella review. The results showed that thrombolytic therapy (tPA; alteplase, tenecteplase, and desmoteplase), mechanical thrombectomy (MTE), edaravone with tPA, stem cell-based therapies, stent retrievers, acupuncture with Western medicines, autologous bone marrow stromal cells, antiplatelet agents (aspirin, clopidogrel, and tirofiban), statins, and Western medicines with blood-activating and stasis-dispelling herbs (NaoShuanTong capsule, Ginkgo biloba, Tongqiao Huoxue Decoction, Xuesaitong injection) can improve the neurological deficits and activities of daily living, and the adverse effects were mild for the treatment of ischemic stroke. Moreover, ligustrazine, safflower yellow, statins, albumin, colchicine, MLC601, salvianolic acids, and DL-3-n-butylphthalide showed serious adverse events, intracranial hemorrhage, or mortality in ischemic stroke patients.Conclusion: Our study demonstrated that tPA, edaravone and tPA, tPA and MTE, acupuncture and Western medicines, and blood-activating and stasis-dispelling herbs with Western medicines are the optimum neurological function and activities of daily living medication for patients with ischemic stroke.Systematic Review Registration: https://inplasy.com/, identifier [INPLASY202250145].

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Section: Resultsmentioning

confidence: 99%

The Efficacy and Safety of Ischemic Stroke Therapies: An Umbrella Review

Cui

Fan

et al. 2022

Front. Pharmacol.

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“…Despite ZLH being used to dispel wind and dehumidify, relieve pain, and treat vascular headache and migraine, the molecular mechanism is largely unknown ( She et al, 2019 ). Previously, it was only reported that ZLH has a therapeutic effect on acute cerebral infarction, and its safety and effectiveness were systematically evaluated ( Liu et al, 2021 ); however, the gene network of ZLH is waiting to be explored. In this study, the gene network analysis and molecular docking between ZLH and cerebral ischemia disease were conducted ( Liang et al, 2021 ), which laid the foundation for studying the mechanism of ZLH in treating cerebral ischemia–reperfusion.…”

Section: Discussionmentioning

confidence: 99%

“…As a complex preparation, ZLH, consisting of Astragalus , Cassia twig, leech, Panax notoginseng , and chuanxiong, is effective in dispelling wind and dampness and relieving pain for vascular headache and migraine. Among of them, Astragalus can hold the surface for qi and fold sweat; cassia twig can generate muscle, warm the meridians, and pass through Yang Qi; leech can precipitate and break blood clots ( Liu et al, 2021 ). However, the molecular network mechanism of ZLH in improving brain damage is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Gene Network Mechanism of Zhilong Huoxue Tongyu Capsule in Treating Cerebral Ischemia–Reperfusion

Sun

Chen

et al. 2022

Front. Pharmacol.

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Objective: To investigate the effect of Zhilong Huoxue Tongyu capsule (ZLH) in the treatment of cerebral ischemia–reperfusion injury and determine the underlying molecular network mechanism.Methods: The treatment effect of Zhilong Huoxue Tongyu capsule (ZLH) was evaluated for cerebral ischemia–reperfusion injury in middle cerebral artery occlusion (MACO) rat, and the underlying molecular network mechanism was explored by using molecular network analysis based on network pharmacology, bioinformatics including protein–protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), as well as molecular docking.Results: The neurological function of rats in the ZLH group was significantly improved compared to those in the NS group (p = 0.000), confirming the positive effect of ZLH for the treatment of brain ischemia. There were 126 intersecting genes screened in ischemia–reperfusion cerebrum that are associated with several important biological processes, such as lipopolysaccharide, and the most important cell component, such as raft, as well as the most important molecular function pointed as cytokine receptor binding. The most important KEGG signaling pathway was the AGE-RAGE signaling pathway in diabetic complications. Moreover, according to the STRING interaction in the PPI network, 10 hub genes including MAPK14, FOS, MAPK1, JUN, MYC, RELA, ESR1, STAT1, AKT1, and IL6 were selected and exhibited in Cytoscape and molecular docking. Lastly, the relation between PPI, GO, and KEGG was analyzed. These findings indicated that multiple hub network genes have been involved in behavior improvement in cerebral ischemia–reperfusion rats subjected to ZLH treatment.Conclusion: Zhilong Huoxue Tongyu capsule improves cerebral ischemia–reperfusion and is associated with multiple network gene expressions.

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“…Therefore, this study mainly explores new therapeutic directions besides lipid lowering and focuses on Zhilong Huoxue Tongyu capsule effectively removing cell pyrosis induced by ox-LDL. Our previous studies have demonstrated a protective role of Zhilong Huoxue Tongyu capsule in the ischemic stroke and related diseases, as well as AS [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Zhilong Huoxue Tongyu Capsule Alleviated the Pyroptosis of Vascular Endothelial Cells Induced by ox-LDL through miR-30b-5p/NLRP3

Liu

Luo

Liu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Our previous studies have demonstrated a protective role of Zhilong Huoxue Tongyu capsule in atherosclerosis (AS); however, the molecular mechanisms are unclear. Methods. Human coronary artery endothelial cells (HCAECs) were induced with oxidized low-density lipoprotein (ox-LDL) to obtain cellular AS models. Then, the medicated serum of Zhilong Huoxue Tongyu capsule was obtained and used for treatment with ox-LDL-induced HCAECs. The cell viability was detected by CCK-8 assay. Besides, the binding between miR-30b-5p and NLRP3 was determined by the dual-luciferase reporter gene system assay. Furthermore, ox-LDL-induced HCAECs were transfected with miR-30b-5p mimic or miR-30b-5p inhibitor. The pyroptosis of HCAECs was assessed by flow cytometry, LDH content detection, and qRT-PCR assays. Results. 10% medicated serum of Zhilong Huoxue Tongyu capsule was the maximum nontoxic concentration and it was used in subsequent assays. The rate of pyroptosis, LDH content, and the mRNA expression level of pyroptosis-related genes including NLRP3, ASC, Caspase 1, IL-1β, and IL-18 were prominently enhanced after HCAECs were induced by ox-LDL, which were markedly rescued with medicated serum of Zhilong Huoxue Tongyu capsule. In addition, the medicated serum of Zhilong Huoxue Tongyu capsule significantly enhanced the ox-LDL-induced reduction of miR-30b-5p level. NLRP3 could bind to miR-30b-5p and was negatively corrected with miR-30b-5p. Moreover, all the rates of pyroptosis, LDH content, and the mRNA expression levels of pyroptosis-related genes including NLRP3, ASC, Caspase 1, IL-1β, and IL-18 were further observably decreased after ox-LDL-induced HCAECs treated with medicated serum were transfected with miR-30b-5p mimic, while these were significantly rescued with transfection of miR-30b-5p inhibitor. Conclusion. Zhilong Huoxue Tongyu capsule alleviated the pyroptosis of vascular endothelial cells induced by ox-LDL through miR-30b-5p/NLRP3.

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Evaluation of Zhilong Huoxue Tongyu capsule in the treatment of acute cerebral infarction: A systematic review and meta-analysis of randomized controlled trials

Cited by 16 publications

References 32 publications

The Efficacy and Safety of Ischemic Stroke Therapies: An Umbrella Review

The Efficacy and Safety of Ischemic Stroke Therapies: An Umbrella Review

Gene Network Mechanism of Zhilong Huoxue Tongyu Capsule in Treating Cerebral Ischemia–Reperfusion

Zhilong Huoxue Tongyu Capsule Alleviated the Pyroptosis of Vascular Endothelial Cells Induced by ox-LDL through miR-30b-5p/NLRP3

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