Abstract
Yindan Xinnaotong soft capsule (YDXNT), a traditional Chinese medicine preparation, has shown a promising effect in the treatment of acute ischemic stroke (AIS). The goal of this study was to investigate the therapeutic effects and pharmacological mechanisms of YDXNT on AIS. Randomized controlled trials were searched and screened. Review Manager 5.4 was used for a meta-analysis. Active ingredients and targets of YDXNT were extracted from the Traditional Chinese Medicine Systems Pharmacology Database, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, and Encyclopaedia of Traditional Chinese Medicine. AIS-related targets were retrieved from GeneCards, OMIM, and DrugBank databases. We constructed PPI and ingredient-target networks, performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and conducted molecular docking. The YDXNT group had a higher total effective rate and a higher Barthel Index score. YDXNT reduced the low-density lipoprotein cholesterol and the whole blood viscosity at high and shear rates. Our study identified 313 ingredients and 1196 common targets. The key ingredients were mainly quercetin, neocryptotanshinone II, miltionone I, neotanshinone C, and tanshiquinone B, and the key targets were mainly SRC, MAPK3, AKT1, MAPK1, and JUN. GO analysis showed that the core targets mainly involved in atherosclerosis and neural apoptosis. The core pathways were lipid and atherosclerosis, PI3K-Akt, MAPK, and other pathways. Key ingredients exhibited robust binding interactions with core targets. YDXNT could effectively improve the total effective rate, ability of daily life, blood lipids, and blood viscosity. Antiatherosclerotic and neuroprotective effects are the main pharmacological mechanisms.
Registration number: CRD42023400127.
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References
Abulizi A, Simayi J, Nuermaimaiti M et al (2023) Quince extract resists Atherosclerosis in rats by down-regulating the EGFR/PI3K/Akt/GSK-3β pathway. Biomed Pharmacother 160:114330. https://doi.org/10.1016/j.biopha.2023.114330
Azman KF, Zakaria R (2022) Recent advances on the role of brain-derived neurotrophic factor (BDNF) in neurodegenerative diseases. Int J Mol Sci 23(12):6827. https://doi.org/10.3390/ijms23126827
Bender A, Heulin S, Röhrer S et al (2013) Early cranioplasty may improve outcome in neurological patients with decompressive craniectomy. Brain Inj 27(9):1073–1079. https://doi.org/10.3109/02699052.2013.794972
Bi C, Fu Y, Li B (2020) Brain-derived neurotrophic factor alleviates diabetes mellitus-accelerated Atherosclerosis by promoting M2 polarization of macrophages through repressing the STAT3 pathway. Cell Signal 70:109569. https://doi.org/10.1016/j.cellsig.2020.109569
Bohmwald K, Andrade CA, Mora VP et al (2022) Neurotrophin signaling impairment by viral infections in the central nervous system. Int J Mol Sci 23(10):5817. https://doi.org/10.3390/ijms23105817
Cao X, Kambe F, Yamauchi M et al (2009) Thyroid-hormone-dependent activation of the phosphoinositide 3-kinase/Akt cascade requires Src and enhances neuronal survival. Biochem J 424(2):201–209. https://doi.org/10.1042/bj20090643
Cao R, Li L, Ying Z et al (2019) A small molecule protects mitochondrial integrity by inhibiting mTOR activity. Proc Natl Acad Sci U S A 116(46):23332–23338. https://doi.org/10.1073/pnas.1911246116
Chao SM, Huang YH, Luo P (2019) Effect of Yindan Xinnaotong soft capsule on carotid plaque, hypersensitive C-reactive protein and hemorheology in patients with ischemic stroke. Chin J Integr Med Cardio-Cerebrovasc Dis 17(04):615–617. https://doi.org/10.12102/j.issn.1672-1349.2019.04.040
Chen G, Xu H, Wu Y et al (2021) Myricetin suppresses the proliferation and migration of vascular smooth muscle cells and inhibits neointimal hyperplasia via suppressing TGFBR1 signaling pathways. Phytomedicine 92:153719. https://doi.org/10.1016/j.phymed.2021.153719
Cowan AQ, Cho DJ, Rosenson RS (2012) Importance of blood rheology in the pathophysiology of atherothrombosis. Cardiovasc Drugs Ther 26(4):339–348. https://doi.org/10.1007/s10557-012-6402-4
Dai C, Zhang Q, Shen L et al (2022) Quercetin attenuates quinocetone-induced cell apoptosis in vitro by activating the P38/Nrf2/HO-1 pathway and inhibiting the ROS/Mitochondrial apoptotic pathway. Antioxidants (Basel) 11(8):1498. https://doi.org/10.3390/antiox11081498
Duan HD, Qiu YH, Chang BY et al (2013) Clinical observation on YindanXinnaotong soft capsule in treatment of acute cerebral infarction. Chin J Integr Med Cardio-Cerebrovasc Dis 11(11):1287–1288. https://doi.org/10.3969/j.issn.1672-1349.2013.11.005
Ejiri J, Inoue N, Kobayashi S et al (2005) Possible role of brain-derived neurotrophic factor in the pathogenesis of coronary artery disease. Circulation 112(14):2114–2120. https://doi.org/10.1161/circulationaha.104.476903
Fernández-Hernando C, Ackah E, Yu J et al (2007) Loss of Akt1 leads to severe Atherosclerosis and occlusive coronary artery disease. Cell Metab 6(6):446–457. https://doi.org/10.1016/j.cmet.2007.10.007
Fu C, Zheng Y, Lin K et al (2021) Neuroprotective effect of apigenin against hypoxic-ischemic brain injury in neonatal rats via activation of the PI3K/Akt/Nrf2 signaling pathway. Food Funct 12(5):2270–2281. https://doi.org/10.1039/d0fo02555k
Genovese T, Impellizzeri D, Ahmad A et al (2013) Post-ischaemic thyroid hormone treatment in a rat model of acute stroke. Brain Res 1513:92–102. https://doi.org/10.1016/j.brainres.2013.03.001
Godínez-Rubí M, Rojas-Mayorquín AE, Ortuño-Sahagún D (2013) Nitric oxide donors as neuroprotective agents after an ischemic stroke-related inflammatory reaction. Oxid Med Cell Longev 2013:297357. https://doi.org/10.1155/2013/297357
Gorelick PB (2019) The global burden of stroke: persistent and disabling. Lancet Neurol 18(5):417–418. https://doi.org/10.1016/s1474-4422(19)30030-4
Guo L, Huang Z, Huang L et al (2021) Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons. J Nanobiotechnol 19(1):141. https://doi.org/10.1186/s12951-021-00879-4
Habib P, Jung J, Wilms GM et al (2021) Posthypoxic behavioral impairment and mortality of Drosophila melanogaster are associated with high temperatures, enhanced predeath activity and oxidative stress. Exp Mol Med 53(2):264–280. https://doi.org/10.1038/s12276-021-00565-3
Ham PB 3rd, Raju R (2017) Mitochondrial function in hypoxic ischemic injury and influence of aging. Prog Neurobiol 157:92–116. https://doi.org/10.1016/j.pneurobio.2016.06.006
Higgins JP, Altman DG, Gøtzsche PC et al (2011) The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928. https://doi.org/10.1136/bmj.d5928
Hu YJ, Zhang JC, Wang F et al (2011) Regulation of lipid metabolism and vascular endothelial function by soft capsule of Yindan Xinnaotong in hyperlipidemia rat. Chin J Exper Tradit Med Formulae 17(21):162–164. https://doi.org/10.3969/j.issn.1005-9903.2011.21.045
Huang X, Mu Z, Xu F et al (2020) Mechanism of anti-inflammatory effects of volatile compounds of Ai Pian based on network pharmacology, in vivo animal experiments, and GC-MS. J Pharm Biomed Anal 186:113287. https://doi.org/10.1016/j.jpba.2020.113287
Huang BF, Wang W, Fu YC et al (2009) The effect of quercetin on neointima formation in a rat artery balloon injury model. Pathol Res Pract 205(8):515–523. https://doi.org/10.1016/j.prp.2009.01.007
Kang JJ (2011) 45 cases of atherosclerotic cerebral infarction treated with Yindan Xinnaotong soft capsule combined with atorvastatin. Chin J Integr Med Cardio-Cerebrovasc Dis 9(08):948–949. https://doi.org/10.3969/j.issn.1672-1349.2011.08.029
Kwon H, Choi YH, Lee JM (2019) A physarum centrality measure of the human brain network. Sci Rep 9(1):5907. https://doi.org/10.1038/s41598-019-42322-7
Lee BK, Jung YS (2016) Allium cepa extract and quercetin protect neuronal cells from oxidative stress via PKC-ε Inactivation/ERK1/2 Activation. Oxid Med Cell Longev 2016:2495624. https://doi.org/10.1155/2016/2495624
Lee YJ, Bernstock JD, Nagaraja N et al (2016) Global SUMOylation facilitates the multimodal neuroprotection afforded by quercetin against the deleterious effects of oxygen/glucose deprivation and the restoration of oxygen/glucose. J Neurochem 138(1):101–116. https://doi.org/10.1111/jnc.13643
Lei X, Chao H, Zhang Z et al (2015) Neuroprotective effects of quercetin in a mouse model of brain ischemic/reperfusion injury via anti-apoptotic mechanisms based on the akt pathway. Mol Med Rep 12(3):3688–3696. https://doi.org/10.3892/mmr.2015.3857
Li WH (1996) All types of cerebrovascular disease diagnosis. Chin J Neurol 29(6):379–380. https://doi.org/10.3760/j.issn:1006-7876.1996.06.006
Li JJ, Shen M, Li X et al (2013) Influence of chemical compositions of Salvia Miltiorrhiza Bunge and Salvia Root P.E on proteins expression of P38 and NF-κB signaling pathway in Kupffer cells induced by Lipopolysaccharide in rats. Med Pharm J Chin People’s Lib Army 25(8):6–914. https://doi.org/10.3969/j.issn.2095-140X.2013.08.002
Li C, Zhang WJ, Frei B (2016) Quercetin inhibits LPS-induced adhesion molecule expression and oxidant production in human aortic endothelial cells by p38-mediated Nrf2 activation and antioxidant enzyme induction. Redox Biol 9:104–113. https://doi.org/10.1016/j.redox.2016.06.006
Li J, Long ZX, Li Q (2018a) Clinical efficacy of Yindan Xinnaotong soft capsule combined with edaravone in the treatment of acute ischemic stroke. Chin J Integr Med Cardio-Cerebrovasc Dis 16(18):2717–2719. https://doi.org/10.12102/j.issn.1672-1349.2018.18.037
Li S, Wang N, Hong M et al (2018b) Hepatoprotective effects of a functional formula of three Chinese medicinal herbs: experimental evidence and network pharmacology-based identification of mechanism of action and potential bioactive components. Molecules 23(2):352. https://doi.org/10.3390/molecules23020352
Li XF, Mou Z, Wang XP et al (2019) Geographic analysis of the cultivation region of Ai pian derived from Blumea balsamifera through the determination of volatiles in the medicinal product and blood of treated mice by gas chromatography - mass spectrometry (GC-MS). Instrum Sci Technol 47(6):597–610. https://doi.org/10.1080/10739149.2019.1614613
Li J, Xu L, Zuo YX et al (2022) Potential intervention target of atherosclerosis: ferroptosis (review). Mol Med Rep 26(5):343. https://doi.org/10.3892/mmr.2022.12859
Lin HC, Chang WL (2000) Diterpenoids from Salvia miltiorrhiza. Phytochemistry 53(8):951–953. https://doi.org/10.1016/s0031-9422(99)00433-1
Long C, Pan GF, Zhang XD et al (2015) Yindanxinnaotong, a Chinese compound medicine, synergistically attenuates Atherosclerosis progress. Sci Rep 5:12333. https://doi.org/10.1038/srep12333
Lu ZG, Chen B, Lv ZH (2012) Effect of Yindan Xinnaotong soft capsule on MCP-1, IL-1β and VEGF in patients with acute ischemic stroke. Chin J Integr Med Cardio-Cerebrovasc Dis 10(11):1336–1337. https://doi.org/10.3969/j.issn.1672-1349.2012.11.030
Lu J, Xu F, Zhang J (2019) Inhibition of angiotensin II-induced cerebrovascular smooth muscle cell proliferation by LRRC8A downregulation through suppressing PI3K/AKT activation. Hum Cell 32(3):316–325. https://doi.org/10.1007/s13577-019-00260-6
Luo S, Li H, Mo Z et al (2019) Connectivity map identifies luteolin as a treatment option of ischemic Stroke by inhibiting MMP9 and activation of the PI3K/Akt signaling pathway. Exp Mol Med 51(3):1–11. https://doi.org/10.1038/s12276-019-0229-z
Luo TT, Lu Y, Yan SK et al (2020) Network pharmacology in research of Chinese medicine formula: methodology, application and prospective. Chin J Integr Med 26(1):72–80. https://doi.org/10.1007/s11655-019-3064-0
Mendes-de-Aguiar CB, Alchini R, Decker H et al (2008) Thyroid hormone increases astrocytic glutamate uptake and protects astrocytes and neurons against glutamate toxicity. J Neurosci Res 86(14):3117–3125. https://doi.org/10.1002/jnr.21755
Mongkolpobsin K, Sillapachaiyaporn C, Nilkhet S et al (2023) Stigmasterol isolated from Azadirachta indica flowers attenuated glutamate-induced neurotoxicity via downregulation of the Cdk5/p35/p25 signaling pathway in the HT-22 cells. Phytomedicine 113:154728. https://doi.org/10.1016/j.phymed.2023.154728
Mostajeran M, Edvinsson L, Warfvinge K et al (2017) Inhibition of mitogen-activated protein kinase 1/2 in the acute phase of stroke improves long-term neurological outcome and promotes recovery processes in rats. Acta Physiol (Oxf) 219(4):814–824. https://doi.org/10.1111/apha.12632
Murolo M, Vincenzo OD, Cicatiello AG et al (2022) Cardiovascular and neuronal consequences of thyroid hormones alterations in the ischemic stroke. Metabolites 13(1):22. https://doi.org/10.3390/metabo13010022
Pan Y (2012) Clinical observation of the Yindanxinnaotong capsule to acute cerebral infarction. Proc Clin Med 21(1):12–1325. https://doi.org/10.3969/j.issn.1671-8631.2012.01.006
Pan Z, Ma G, Kong L et al (2021) Hypoxia-inducible factor-1: Regulatory mechanisms and drug development in stroke. Pharmacol Res 170:105742. https://doi.org/10.1016/j.phrs.2021.105742
Pang HQ, An HM, Yang H et al (2019) Comprehensive chemical profiling of Yindan Xinnaotong soft capsule and its neuroprotective activity evaluation in vitro. J Chromatogr A 1601:288–299. https://doi.org/10.1016/j.chroma.2019.05.023
Park HJ, Kim HN, Kim CY et al (2021) Synergistic protection by Isoquercitrin and Quercetin against Glutamate-Induced oxidative cell death in HT22 cells via activating Nrf2 and HO-1 signaling pathway: neuroprotective principles and mechanisms of Dendropanax morbifera leaves. Antioxidants (Basel) 10(4):554. https://doi.org/10.3390/antiox10040554
Paul R, Zhang ZG, Eliceiri BP et al (2001) Src deficiency or blockade of src activity in mice provides cerebral protection following stroke. Nat Med 7(2):222–227. https://doi.org/10.1038/84675
Powers WJ, Rabinstein AA, Ackerson T et al (2019) Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 50(12):e344–e418. https://doi.org/10.1161/str.0000000000000211
Qiao H, Zhang X, Zhu C et al (2012) Luteolin downregulates TLR4, TLR5, NF-κB and p-p38MAPK expression, upregulates the p-ERK expression, and protects rat brains against focal ischemia. Brain Res 1448:71–81. https://doi.org/10.1016/j.brainres.2012.02.003
Rahman TA, Hassim NF, Zulkafli N et al (2016) Atheroprotective effects of pure tocotrienol supplementation in the treatment of rabbits with experimentally induced early and established Atherosclerosis. Food Nutr Res 60:31525. https://doi.org/10.3402/fnr.v60.31525
Sacco RL, Kasner SE, Broderick JP et al (2013) An updated definition of Stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 44(7):2064–2089. https://doi.org/10.1161/str.0b013e318296aeca
Sawe N, Steinberg G, Zhao H (2008) Dual roles of the MAPK/ERK1/2 cell signaling pathway after Stroke. J Neurosci Res 86(8):1659–1669. https://doi.org/10.1002/jnr.21604
Shamseer L, Moher D, Clarke M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 350:g7647. https://doi.org/10.1136/bmj.g7647
Shapiro MD, Fazio S (2016) From lipids to inflammation: new approaches to reducing atherosclerotic risk. Circ Res 118(4):732–749. https://doi.org/10.1161/circresaha.115.306471
Simion V, Zhou H, Pierce JB et al (2020) LncRNA VINAS regulates Atherosclerosis by modulating NF-κB and MAPK signaling. JCI Insight 5:e140627. https://doi.org/10.1172/jci.insight.140627
Sousa FTG, Nunes C, Romano CM et al (2020) Anti-zika virus activity of several abietane-type ferruginol analogues. Rev Inst Med Trop Sao Paulo 62:e97. https://doi.org/10.1590/s1678-9946202062097
Sun J, Nan G (2016) The Mitogen-Activated Protein Kinase (MAPK) signaling pathway as a discovery target in stroke. J Mol Neurosci 59(1):90–98. https://doi.org/10.1007/s12031-016-0717-8
Tian HP, Huang BS, Zhao J et al (2009) Non-receptor tyrosine kinase src is required for ischemia-stimulated neuronal cell proliferation via Raf/ERK/CREB activation in the dentate gyrus. BMC Neurosci 10:139. https://doi.org/10.1186/1471-2202-10-139
Trinh TA, Seo YH, Choi S et al (2021) Protective effect of Osmundacetone against neurological cell death caused by oxidative glutamate toxicity. Biomolecules 11(2):328. https://doi.org/10.3390/biom11020328
Trochon V, Blot E, Cymbalista F et al (2000) Apigenin inhibits endothelial-cell proliferation in G(2)/M phase whereas it stimulates smooth-muscle cells by inhibiting P21 and P27 expression. Int J Cancer 85(5):691–696. https://doi.org/10.1002/(sici)1097-0215(20000301)85:5%3C691::aid-ijc15%3E3.0.co;2-q
Tu XK, Zhang HB, Shi SS et al (2016) 5-LOX inhibitor Zileuton reduces inflammatory reaction and ischemic brain damage through the activation of PI3K/Akt signaling pathway. Neurochem Res 41(10):2779–2787. https://doi.org/10.1007/s11064-016-1994-x
Verma M, Lizama BN, Chu CT (2022) Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration. Transl Neurodegener 11(1):3. https://doi.org/10.1186/s40035-021-00278-7
Wang HT (2019) Clinical observation of Yindan Xinnaotong soft capsule combined with edaravone injection on acute ischemic stroke. Chin J Integr Med Cardio-Cerebrovasc Dis 17(13):2051–2053. https://doi.org/10.12102/j.issn.1672-1349.2019.13.043
Wang D, Ali F, Liu H et al (2022a) Quercetin inhibits angiotensin II-induced vascular smooth muscle cell proliferation and activation of JAK2/STAT3 pathway: a target based networking pharmacology approach. Front Pharmacol 13:1002363. https://doi.org/10.3389/fphar.2022.1002363
Wang F, Xie X, Xing X et al (2022b) Excitatory synaptic transmission in ischemic Stroke: a new outlet for classical neuroprotective strategies. Int J Mol Sci 23(16):9381. https://doi.org/10.3390/ijms23169381
Wang QS, Luo XY, Fu H et al (2020a) MiR-139 protects against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced nerve injury through targeting c-Jun to inhibit NLRP3 inflammasome activation. J Stroke Cerebrovasc Dis 29(9):105037. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.105037
Wang MM, Zhang M, Feng YS et al (2020b) Electroacupuncture inhibits neuronal autophagy and apoptosis via the PI3K/AKT pathway following ischemic Stroke. Front Cell Neurosci 14:134. https://doi.org/10.3389/fncel.2020.00134
Wang Y, Zhang XF, Wang JD et al (2015) The therapeutic effect of Yindan Xinnaotong soft capsule on elderly patients with acute ischemic stroke and its influence on the serum levels of brain-derived neurotrophic factor, Fibulin-5 and P-selectin. Chin J Gerontol 35(09):2408–2410. https://doi.org/10.3969/j.issn.1005-9202.2015.09.044
Wei G, Ruan BQ (2013) 80 cases of acute ischemic stroke treated with Yindan Xinnaotong soft capsule. Chin J Integr Med Cardio-Cerebrovasc Dis 11(03):326–327. https://doi.org/10.3969/j.issn.1672-1349.2013.03.039
Won KJ, Lee KP, Baek S et al (2017) Desalted Salicornia europaea extract attenuated vascular neointima formation by inhibiting the MAPK pathway-mediated migration and proliferation in vascular smooth muscle cells. Biomed Pharmacother 94:430–438. https://doi.org/10.1016/j.biopha.2017.07.108
Wu LM (2012) Effect of Yindan Xinnaotong soft capsule on hemorheology of ischemic stroke. Chin J Integr Med Cardio-Cerebrovasc Dis 10(10):1187–1188. https://doi.org/10.3969/j.issn.1672-1349.2012.10.020
Wu YT, Chen L, Tan ZB et al (2018) Luteolin inhibits vascular smooth muscle cell proliferation and migration by inhibiting TGFBR1 signaling. Front Pharmacol 9:1059. https://doi.org/10.3389/fphar.2018.01059
Wu B, Luo H, Zhou X et al (2017) Succinate-induced neuronal mitochondrial fission and hexokinase II malfunction in ischemic stroke: therapeutical effects of kaempferol. Biochim Biophys Acta Mol Basis Dis 1863(9):2307–2318. https://doi.org/10.1016/j.bbadis.2017.06.011
Wu C, Zhao W, Zhang X et al (2015) Neocryptotanshinone inhibits lipopolysaccharide-induced inflammation in RAW264.7 macrophages by suppression of NF-κB and iNOS signaling pathways. Acta Pharm Sin B 5(4):323–329. https://doi.org/10.1016/j.apsb.2015.01.010
Xie R, Cheng M, Li M et al (2013) Akt isoforms differentially protect against stroke-induced neuronal injury by regulating mTOR activities. J Cereb Blood Flow Metab 33(12):1875–1885. https://doi.org/10.1038/jcbfm.2013.132
Xu XJ, Gao HX, Zhu LC et al (2022) Identifying tumor-associated genes from Bilayer networks of DNA methylation sites and RNAs. Life (Basel) 13(1):76. https://doi.org/10.3390/life13010076
Yang SJ (2008) Observation on 60 cases of acute ischemic stroke treated by Yindan Xinnaotong soft capsule. Chin J Integr Med Cardio-Cerebrovasc Dis 6(11):1379–1380. https://doi.org/10.3969/j.issn.1672-1349.2008.11.069
Yang EJ, Kim GS, Jun M et al (2014) Kaempferol attenuates the glutamate-induced oxidative stress in mouse-derived hippocampal neuronal HT22 cells. Food Funct 5(7):1395–1402. https://doi.org/10.1039/c4fo00068d
Yang JL, Mukda S, Chen SD (2018) Diverse roles of mitochondria in ischemic stroke. Redox Biol 16:263–275. https://doi.org/10.1016/j.redox.2018.03.002
Yao RQ, Qi DS, Yu HL et al (2012) Quercetin attenuates cell apoptosis in focal cerebral ischemia rat brain via activation of BDNF-TrkB-PI3K/Akt signaling pathway. Neurochem Res 37(12):2777–2786. https://doi.org/10.1007/s11064-012-0871-5
Yu L, Chen C, Wang LF et al (2013) Neuroprotective effect of kaempferol glycosides against brain injury and neuroinflammation by inhibiting the activation of NF-κB and STAT3 in transient focal Stroke. PLoS ONE 8(2):e55839. https://doi.org/10.1371/journal.pone.0055839
Yuan HW, Yang YN, Chen HF et al (2020) Rise in low-density lipoprotein cholesterol during hospitalization is related with poor outcome at discharge in patients with acute ischemic stroke. Cerebrovasc Dis 49(1):88–96. https://doi.org/10.1159/000505615
Zhang J (2017) Clinical observation of Yindan Xinnaotong soft capsules combined with fibrinogenase in treatment of cerebral infarction. Drugs Clin 32(02):201–204. https://doi.org/10.7501/j.issn.1674-5515.2017.02.009
Zhang Y, Ma YX (2017) Analysis on the clinical curative effect observation Yindan Xinnaotong Ruanjiaonang United Alpmstadil treatment of patients with acute cerebral infarction. China J Pharm Econ 12(03):54–56. https://doi.org/10.12010/j.issn.1673-5846.2017.03.019
Zhang JQ, Shi JS, Wang LH (2010) Experimental study on improving hyperlipidemia of Ying Dan Xin Nao Tong Capsulae Molles. J Zunyi Med Univ 33(1):4–6. https://doi.org/10.3969/j.issn.1000-2715.2010.01.002
Zhang SS, Liu M, Liu DN et al (2022a) Network pharmacology analysis and experimental validation of Kaempferol in the treatment of ischemic stroke by inhibiting apoptosis and regulating neuroinflammation involving neutrophils. Int J Mol Sci 23(20):12694. https://doi.org/10.3390/ijms232012694
Zhang Y, Yang L, Zhang L (2022b) Observation on effect of Yindan Xinnaotong soft capsule on cerebral infarction. Chin Youjiang Med J 50(6):429–433. https://doi.org/10.3969/j.issn.1003-1383.2022.06.006
Zhao YH, Gu XX, Xu DS et al (2006) Clinical study on Yindan Xinnaotong capsule in treating acute ischemic stroke. Shanghai J Tradit Chin Med 40(9):18–19. https://doi.org/10.3969/j.issn.1007-1334.2006.09.009
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This work was supported by the Henan Province Science and Technology Research Project [grant numbers 232102310466], National Natural Science Foundation of China [grant numbers 81704135] and Foundation of Henan Educational Committee [grant numbers 18A360012].
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All authors contributed to the study conception and design. Yasu Zhang, Fangjie Yang, Qian Gao, and Mengyang Pan designed the experimental methods. Xinmin Li, Junzi Long, Fangjie Yang, and Jing Wang collected and analyzed the data. Fangjie Yang and Xinmin Li wrote initial draft of the manuscript. All authors read and approved the final manuscript.
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Yang, F., Li, X., Long, J. et al. Therapeutic efficacy and pharmacological mechanism of Yindan Xinnaotong soft capsule on acute ischemic stroke: a meta-analysis and network pharmacology analysis. Metab Brain Dis 39, 523–543 (2024). https://doi.org/10.1007/s11011-023-01337-w
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DOI: https://doi.org/10.1007/s11011-023-01337-w