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Original Research

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

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Pages 3783-3808 | Published online: 07 Sep 2021

References

  • WuSM, WuB, LiuM, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol. 2019;18(4):394–405.30878104
  • BenjaminEJ, MuntnerP, AlonsoA, et al. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56–e528.30700139
  • LiuS, LevineSR, WinnHR. Targeting ischemic penumbra part I: from pathophysiology to therapeutic strategy. J Exp Stroke Transl Med. 2010;3(1):47–55.20607107
  • RabinsteinAA. Treatment of acute ischemic stroke. Contin Lifelong Learn Neurol. 2017;23(1):62–81.
  • LahrMMH, LuijckxGJ, VroomenPCAJ, Van Der ZeeDJ, BuskensE. Proportion of patients treated with thrombolysis in a centralized versus a decentralized acute stroke care setting. Stroke. 2012;43(5):1336–1340.22426467
  • ZhouYF, YanSJ, SongXY, et al. Intravenous thrombolytic therapy for acute ischemic stroke in Hubei, China: a survey of thrombolysis rate and barriers. BMC Neurol. 2019;19(1):202.31438899
  • MeiZG, HuangYG, FengZT, et al. Electroacupuncture ameliorates cerebral ischemia/reperfusion injury by suppressing autophagy via the SIRT1-FOXO1 signaling pathway. Aging (Albany NY). 2020;12(13):13187–13205.32620714
  • DuLP, MeiZG, HuangYG, et al. 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. Biomed Pharmacother. 2020;127:110–123.
  • ZhangB, WangX, LiS. An integrative platform of TCM network pharmacology and its application on a herbal formula, Qing-Luo-Yin. Evid Based Compl Altern Med. 2013;2013:456747.
  • LiHY, ZhaoLH, ZhangB, et al. A network pharmacology approach to determine active compounds and action mechanisms of Ge-Gen-Qin-Lian decoction for treatment of type 2 diabetes. Evid Based Compl Altern Med. 2014;2014:495840.
  • ZhangYQ, BaiM, ZhangB, et al. Uncovering pharmacological mechanisms of Wu-tou decoction acting on rheumatoid arthritis through systems approaches: drug-target prediction, network analysis and experimental validation. Sci Rep. 2015;30(5):9463.
  • WangP, ShaoBZ, DengZQ, et al. Autophagy in ischemic stroke. Prog Neurobiol. 2018;163(1):98–117.29331396
  • RenCH, WangB, LiN, JinKL, JiXM. Herbal formula Danggui-Shaoyao-San promotes neurogenesis and angiogenesis in rat following middle cerebral artery occlusion. Aging Dis. 2015;6(4):245–253.26236546
  • LohKP, QiJ, TanBKH, LiuXH, WeiBG, ZhuYZ. Leonurine protects middle cerebral artery occluded rats through antioxidant effect and regulation of mitochondrial function. Stroke. 2010;41(11):2661–2668.20947850
  • WangHW, LiouKT, WangYH, et al. Deciphering the neuroprotective mechanisms of Bu-yang Huan-wu decoction by an integrative neurofunctional and genomic approach in ischemic stroke mice. J Ethnopharmacol. 2011;138(1):22–33.21784143
  • LiaoJ, XiaX, WangGZ, ShiYM, GeJW. Naotaifang extract treatment results in increased ferroportin expression in the hippocampus of rats subjected to cerebral ischemia. Mol Med Rep. 2015;11(6):4047–4052.25672910
  • HuMB, YuZJ, WangJL, et al. Traditional uses, origins, chemistry and pharmacology of bombyx batryticatus: a review. Molecules. 2017;22(10):1–24.
  • ZhangJ, ZouHY, ZhangQX, et al. Effects of Xiaoshuan enteric-coated capsule on neurovascular functions assessed by quantitative multiparametric MRI in a rat model of permanent cerebral ischemia. BMC Complement Altern Med. 2016;16(1):1–14.26729470
  • LanB, GeJW, ChengSW, et al. Extract of Naotaifang, a compound Chinese herbal medicine, protects neuron ferroptosis induced by acute cerebral ischemia in rats. J Integr Med. 2020;18(4):344–350.32107172
  • HeYH, HaoXY, GeJW. Clinical study of naotai formula in treating cerebral infarction with Qi deficiency and blood stasis syndrome. Zhong Guo Zhong Yi Ji Zheng. 2001;10(6):1–4.
  • ZhongQ, TongJ, ZhongXC, WuDS, ZhuD, GeJW. Effects of Naotaifang extracts on nerve regeneration after cerebral ischemia reperfusion in rats and influence on Notch 1 protein expression. Zhong Hua Zhong Yi Yao Xue Kan. 2016;34(8):3–6.
  • ChenY, ZhuHB, LiaoJ, et al. Regulation effect of Naotai formula on HIF-1α/ VEGF in rats with cerebral ischemia reperfusion. Zhong Guo Zhong Xi Yi Jie He. 2014;34:1225.
  • HuangJ, LiaoJ, PengXW, et al. Effect of Naotai formula on the expression of Nrf2, HO-1 and membrane iron transport helper protein in hippocampus of rats with cerebral ischemia/reperfusion. Zhong Guo Yao Li Xue Tong Bao. 2017;33(10):1467–1472.
  • BoezioB, AudouzeK, DucrotP, TaboureauO. Network-based approaches in pharmacology. Mol Inform. 2017;36(10):1–10.
  • SzklarczykD, MorrisJH, CookH, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2017;45(1):362–368.
  • SmootME, OnoK, RuscheinskiJ, WangPL, IdekerT. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2011;27(3):431–432.21149340
  • TangY, LiM, WangJ, PanY, WuFX. CytoNCA: a cytoscape plugin for centrality analysis and evaluation of protein interaction networks. BioSystems. 2015;127:67–72.25451770
  • WanYX, XuL, LiuZY, et al. Utilising network pharmacology to explore the underlying mechanism of Wumei Pill in treating pancreatic neoplasms. BMC Complement Altern Med. 2019;19(1):1–12.30606178
  • EswariJS, DhagatS, KaserS. Homology modeling and molecular docking studies of Bacillomycin and Iturin synthetases with novel ligands for the production of therapeutic lipopeptides. Curr Drug Discov Technol. 2018;15(2):132–141.28814239
  • HalgrenT. New method for fast and accurate binding-site identification and analysis. Chem Biol Drug Des. 2007;69(2):146–148.17381729
  • HalgrenTA. Identifying and characterizing binding sites and assessing druggability. J Chem Inf Model. 2009;49(2):377–389.19434839
  • LiXH, HouY, WangXB, et al. To elucidate the inhibition of excessive autophagy of rhodiola crenulata on exhaustive exercise-induced skeletal muscle injury by combined network pharmacology and molecular docking. Biol Pharm Bull. 2020;43(2):296–305.31787729
  • ÖzçelikAB, ÖzdemirZ, SariS, UtkuS, UysalM. A new series of pyridazinone derivatives as cholinesterases inhibitors: synthesis, in vitro activity and molecular modeling studies. Pharmacol Rep. 2019;71(6):1253–1263.31675671
  • ChenL, ZhangYH, WangS, ZhangY, HuangT, CaiYD. Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways. PLoS One. 2017;12(9):1–22.
  • OuBJ, TaoW, YangSB, et al. The antiapoptosis effect of Geum japonicum thunb. var. chinense extracts on cerebral ischemia reperfusion injury via PI3K/Akt pathway. Evidence-Based Complement Altern Med. 2018;11:1–13.
  • LongaEZ, WeinsteinPR, CarlsonS, CumminsR. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20(1):84–91.2643202
  • GibbR, KolbB. A method for vibratome sectioning of Golgi-Cox stained whole rat brain. J Neurosci Methods. 1998;79(1):1–4.9531453
  • SunMS, HangJ, SunX, et al. Free radical damage in ischemia-reperfusion injury: an obstacle in acute ischemic stroke after revascularization therapy. Oxid Med Cell Longev. 2018;1(31):1–17.
  • SoaresROS, LosadaDM, JordaniMC, ÉvoraP, Castro-E-SilvaO. Ischemia/reperfusion injury revisited: an overview of the latest pharmacological strategies. Int J Mol Sci. 2019;20(20):5034.
  • WuMY, YiangGT, LiaoWT, et al. Current mechanistic concepts in ischemia and reperfusion injury. Cell Physiol Biochem. 2018;46(4):1650–1667.29694958
  • OrnellasFM, OrnellasDS, MartiniSV, et al. Bone marrow-derived mononuclear cell therapy accelerates renal ischemia-reperfusion injury recovery by modulating inflammatory, antioxidant and apoptotic related molecules. Cell Physiol Biochem. 2017;41(5):1736–1752.28365681
  • ZhangY, ZhangY, JinXF, et al. The role of Astragaloside IV against cerebral ischemia/reperfusion injury: suppression of apoptosis via promotion of P62-LC3-autophagy. Molecules. 2019;24(9):1838.
  • DaiYY, ZhangHJ, ZhangJP, YanMG. Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-κB pathway. Chem Biol Interact. 2018;284:32–40.29454613
  • KhandelwalP, YavagalDR, SaccoRL. Acute ischemic stroke intervention. J Am Coll Cardiol. 2016;67(22):2631–2644.27256835
  • HanJY, LiQ, MaZZ, FanJY. Effects and mechanisms of compound Chinese medicine and major ingredients on microcirculatory dysfunction and organ injury induced by ischemia/reperfusion. Pharmacol Ther. 2017;177:146–173.28322971
  • LiLT, QiuHY, LiuMM, CaiYM. A network pharmacology-based study of the molecular mechanisms of shaoyao-gancao decoction in treating Parkinson’s disease. Interdiscip Sci. 2020;12(2):131–144.32006382
  • YanXL, YuAM, ZhengHZ, WangSX, HeYY, WangLS. Calycosin-7-O-β-D-glucoside attenuates OGD/R-induced damage by preventing oxidative stress and neuronal apoptosis via the SIRT1/FOXO1/PGC-1α pathway in HT22 cells. Neural Plast. 2019;2019:8798069.31885537
  • WangHL, ZhouQH, XuMB, ZhouXL, ZhengGQ. Astragaloside IV for experimental focal cerebral ischemia: preclinical evidence and possible mechanisms. Oxid Med Cell Longev. 2017;2017:8424326.28303172
  • KohPO. Ferulic acid attenuates focal cerebral ischemia-induced decreases in p70S6 kinase and S6 phosphorylation. Neurosci Lett. 2013;555:7–11.24036263
  • DingY, DuJ, CuiF, ChenL, LiK. The protective effect of ligustrazine on rats with cerebral ischemia–reperfusion injury via activating PI3K/Akt pathway. Hum Exp Toxicol. 2019;38(10):1168–1177.31250662
  • HuangCQ, LiW, ZhangQF, et al. Anti-inflammatory activities of Guang-Pheretima extract in lipopolysaccharide-stimulated RAW 264.7 murine macrophages. BMC Complement Altern Med. 2018;18(1):1–11.29295712
  • WuYL, HuSN, MaYN, et al. Novel Pheretima guillelmi-derived antithrombotic protein DPf3: identification, characterization, in vitro evaluation and antithrombotic mechanisms investigation. Int J Biol Macromol. 2020;154:545–556.32173431
  • KwonHC, LeeKC, ChoOR, et al. Sphingolipids from Bombycis Corpus 101A and their neurotrophic effects. J Nat Prod. 2003;66(4):466–469.12713394
  • BlakeJA, ChristieKR, DolanME, et al. Gene ontology consortium: going forward. Nucleic Acids Res. 2015;43(1):1049–1056.
  • KanehisaM, SatoY, KawashimaM, FurumichiM, TanabeM. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 2016;44(1):457–462.
  • ShengLL, MaoXY, YuQX, YuD. Effect of the PI3K/AKT signaling pathway on hypoxia-induced proliferation and differentiation of bone marrow-derived mesenchymal stem cells. Exp Ther Med. 2017;13(1):55–62.28123468
  • PanBS, WangYK, LaiMS, MuYF, HuangBM. Cordycepin induced MA-10 mouse Leydig tumor cell apoptosis by regulating p38 MAPKs and PI3K/AKT signaling pathways. Sci Rep. 2015;5:13372.26303320
  • TianYS, ZhongD, LiuQQ, et al. Upregulation of miR-216a exerts neuroprotective effects against ischemic injury through negatively regulating JAK2/STAT3-involved apoptosis and inflammatory pathways. J Neurosurg. 2018;130(3):977–988.29521586
  • HouYY, WangK, WanWJ, ChengY, PuX, YeXF. Resveratrol provides neuroprotection by regulating the JAK2/STAT3/PI3K/AKT/mTOR pathway after stroke in rats. Genes Dis. 2018;5(3):245–255.30320189
  • JiaoSJ, ZhuHC, HeP, TengJF. Betulinic acid protects against cerebral ischemia/reperfusion injury by activating the PI3K/Akt signaling pathway. Biomed Pharmacother. 2016;84:1533–1537.27876208
  • ZhangHF, XiongXX, LiuJ, et al. Emulsified isoflurane protects against transient focal cerebral ischemia injury in rats via the PI3K/Akt signaling pathway. Anesth Analg. 2016;122(5):1377–1384.26859875
  • ZhangYH, LiuJX, YangB, et al. Ginkgo biloba extract inhibits astrocytic lipocalin-2 expression and alleviates neuroinflammatory injury via the JAK2/STAT3 pathway after ischemic brain stroke. Front Pharmacol. 2018;9:518.29867513
  • PalaretiG, LegnaniC, CosmiB, et al. Comparison between different D-Dimer cutoff values to assess the individual risk of recurrent venous thromboembolism: analysis of results obtained in the DULCIS study. Int J Lab Hematol. 2016;38(1):42–49.26362346
  • LiL, SunLL, QiuY, ZhuWJ, HuKY, MaoJQ. Protective effect of stachydrine against cerebral ischemia-reperfusion injury by reducing inflammation and apoptosis through P65 and JAK2/STAT3 signaling pathway. Front Pharmacol. 2020;11:1–14.32116689
  • ToddL, SquiresN, SuarezL, FischerAJ. Jak/Stat signaling regulates the proliferation and neurogenic potential of Müller glia-derived progenitor cells in the avian retina. Sci Rep. 2016;6:35703.27759082
  • MüllerS, ChakrapaniBPS, SchweglerH, HofmannHD, KirschM. Neurogenesis in the dentate gyrus depends on ciliary neurotrophic factor and signal transducer and activator of transcription 3 signaling. Stem Cells. 2009;27(2):431–441.19023034
  • HuaY, PardollD, JoveR. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9(11):798–809.19851315
  • XinP, XuXY, DengCJ, et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases. Int Immunopharmacol. 2020;80:106210.31972425
  • MorrisR, KershawNJ, BabonJJ. The molecular details of cytokine signaling via the JAK/STAT pathway. Protein Sci. 2018;27(12):1984–2009.30267440
  • TakagiY, HaradaJ, ChiarugiA, MoskowitzMA. STAT1 is activated in neurons after ischemia and contributes to ischemic brain injury. J Cereb Blood Flow Metab. 2002;22(11):1311–1318.12439288
  • CaiW, DaiXJ, ChenJ, et al. STAT6/Arg1 promotes microglia/ macrophage efferocytosis and inflammation resolution in stroke mice. JCI Insight. 2019;4(20):1–20.
  • JungJE, KaratasH, LiuY, et al. STAT-dependent upregulation of 12/15-lipoxygenase contributes to neuronal injury after stroke. J Cereb Blood Flow Metab. 2015;35(12):2043–2051.26174325
  • SnyderM, HuangXY, ZhangJJ. Stat3 is essential for neuronal differentiation through direct transcriptional regulation of the Sox6 gene. FEBS Lett. 2011;585(1):148–152.21094641
  • McGuckinCP, JurgaM, MillerAM, et al. Ischemic brain injury: a consortium analysis of key factors involved in mesenchymal stem cell-mediated inflammatory reduction. Arch Biochem Biophys. 2013;534(1–2):88–97.23466243
  • WhiteCW, FanXL, MaynardJC, et al. Age-related loss of neural stem cell O-GlcNAc promotes a glial fate switch through STAT3 activation. Proc Natl Acad Sci U S A. 2020;117(36):22214–22224.32848054
  • ZhuH, JianZH, ZhongY, et al. Janus kinase inhibition ameliorates ischemic stroke injury and neuroinflammation through reducing NLRP3 inflammasome activation via JAK2/STAT3 pathway inhibition. Front Immunol. 2021;22(12):1–16.
  • LinCC, ChenSY, LienHY, LinSZ, LeeTM. Targeting the PI3K/STAT3 axis modulates age-related differences in macrophage phenotype in rats with myocardial infarction. J Cell Mol Med. 2019;23(9):6378–6392.31313516
  • StarkGR, CheonH, WangY. Responses to cytokines and interferons that depend upon JAKs and STATs. Cold Spring Harb Perspect Biol. 2018;10(1):1–16.
  • ZhaoSF, FuJD, LiuXR, WangT, ZhangJL, ZhaoYL. Activation of Akt/GSK-3beta/beta-catenin signaling pathway is involved in survival of neurons after traumatic brain injury in rats. Neurol Res. 2012;34(4):400–407.22643085
  • LimW, YangC, BazerFW, SongG. Luteolin inhibits proliferation and induces apoptosis of human placental choriocarcinoma cells by blocking the PI3K/AKT pathway and regulating sterol regulatory element binding protein activity. Biol Reprod. 2016;95(4):82.27580988
  • ZhouZH, XuNB, MateiN, et al. Sodium butyrate attenuated neuronal apoptosis via GPR41/Gβγ/PI3K/Akt pathway after MCAO in rats. J Cereb Blood Flow Metab. 2021;41(2):267–281.32151222
  • RadakD, KatsikiN, ResanovicI, et al. Apoptosis and acute brain ischemia in ischemic stroke. Curr Vasc Pharmacol. 2017;15(2):115–122.27823556
  • JinXF, WangS, ShenM, et al. Effects of rehabilitation training on apoptosis of nerve cells and the recovery of neural and motor functions in rats with ischemic stroke through the PI3K/Akt and Nrf2/ARE signaling pathways. Brain Res Bull. 2017;134:236–245.28843352
  • EbnerM, LučićI, LeonardTA, YudushkinI. PI(3,4,5)P3 engagement restricts Akt activity to cellular membranes. Mol Cell. 2017;65(3):416–431.28157504
  • ZhuangZ, ZhaoXD, WuYet al. The anti-apoptotic effect of PI3K-akt signaling pathway after subarachnoid hemorrhage in rats. Ann Clin Lab Sci. 2011;41(4):364–372.22166507
  • TangH, GamdzykM, HuangL, et al. Delayed recanalization after MCAO ameliorates ischemic stroke by inhibiting apoptosis via HGF/c-Met/STAT3/Bcl-2 pathway in rats. Exp Neurol. 2020;330:113359.32428505
  • ChenBS, ShenZJ, WuDG, et al. Glutathione peroxidase 1 promotes NSCLC resistance to cisplatin via ROS-induced activation of PI3K/AKT pathway. Biomed Res Int. 2019;2019:7640547.31032363
  • KimKB, LeeS, KimJH. Neuroprotective effects of urolithin a on H2O2-induced oxidative stress-mediated apoptosis in SK-N-MC cells. Nutr Res Pract. 2020;14(1):3–11.32042368