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Treatment with MQA, a Derivative of Caffeoylquinic Acid, Provides Neuroprotective Effects against Cerebral Ischemia Through Suppression of the p38 Pathway and Oxidative Stress in Rats

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Abstract

1,5-O-dicaffeoyl-3-O-(4-malic acid methylester)–quinic acid (MQA), extracted from Arctium lappa L., has been observed to exert neuroprotective effects in vitro. The aim of this study was to investigate whether MQA is an effective therapeutic method for cerebral ischemic injury in vivo. In this study, adult male rats were randomly divided into four groups: a normal group, a model group subjected to middle cerebral artery occlusion (MCAO) for 24 h, a model + MQA group (which received intragastric MQA for the 7 days prior to MCAO), and a model + positive drug group. MQA appeared to induce effects in cerebral ischemic injury in rats, by downregulating malondialdehyde, glutathione peroxidase, and nitric oxide synthase levels. Treatment with MQA significantly reduced infarcted sections. In addition, caspase-3 and Iba1 protein expression were evaluated with immunohistochemistry, and cortical cell apoptosis was assessed with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays. Expression of AKT and Bax, ERK1/2, P38 and Bcl-2, NFkB1, PARP, and caspase-3 was assessed with Western blotting. We found Bcl-2 and NFkB1 (p50) expressions were upregulated, whereas the expression of PARP, caspase-3, NFkB1 (p105), ERK1/2, P38, AKT, and Bax was downregulated. In conclusion, we observed MQA was an effective treatment for cerebral ischemic injury in rats.

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References

  • Abas F, Alkan T, Goren B, Taskapilioglu O, Sarandol E, Tolunay S (2010) Neuroprotective effects of postconditioning on lipid peroxidation and apoptosis after focal cerebral ischemia/reperfusion injury in rats. Turk Neurosurg 20:1–8

    PubMed  Google Scholar 

  • Atochin DN, Chernysheva GA, Aliev OI (2017) An improved three-vessel occlusion model of global cerebral ischemia in rats. Brain Res Bull 132:213–221

    Article  PubMed  Google Scholar 

  • Brahmbhatt H, Oppermann S, Osterlund EJ, Leber B, Andrews DW (2015) Molecular pathways: leveraging the BCL-2 Interactome to kill cancer cells--mitochondrial outer membrane permeabilization and beyond. Clin Cancer Res 21:2671–2676

    Article  CAS  PubMed  Google Scholar 

  • Cao J, Chen Z, Zhu Y, Li Y, Guo C, Gao K, Chen L, Shi X, Zhang X, Yang Z, Wen A (2014) Huangqi−Honghua combination and its main components ameliorate cerebral infarction with Qi deficiency and blood stasis syndrome by antioxidant action in rats. J Ethnopharmacol 155:1053–1060

    Article  PubMed  Google Scholar 

  • Duan S, Wang T, Zhang J, Li M, Lu C, Wang L, Zou Y, Fu F (2017) Huatuo zaizao pill promotes functional recovery and neurogenesis after cerebral ischemia-reperfusion in rats. BMC Complement Altern Med 17:19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edelmayer RM, Brederson JD, Jarvis MF, Bitner RS (2014) Biochemical and pharmacological assessment of MAP-kinase signaling along pain pathways in experimental rodent models: a potential tool for the discovery of novel antinociceptive therapeutics. Biochem Pharmacol 87:390–398

    Article  CAS  PubMed  Google Scholar 

  • Fierascu RC, Georgiev MI, Fierascu I, Ungureanu C, Avramescu SM, Ortan A, Georgescu MI, Sutan AN, Zanfirescu A, Dinu-Pirvu CE, Velescu BS, Anuta V (2018) Mitodepressive, antioxidant, antifungal and anti-inflammatory effects of wild-growing Romanian native Arctium lappa L. (Asteraceae) and Veronica persica Poiret (Plantaginaceae). Food Chem Toxicol 111:44–52

    Article  CAS  PubMed  Google Scholar 

  • Goyal M, Demchuk AM, Menon BK et al (2015) Randomized assessment of rapid endovascular treatment of ischemic stroke. J Emerg Med 49:258–259

    Google Scholar 

  • Guo JF, Zhou JM, Zhang Y et al (2008) Rhabdastrellic acid-a inhibited PI3K/Akt pathway and induced apoptosis in human leukemia HL-60 cells. Cell Biol Int 32:48–54

    Article  CAS  PubMed  Google Scholar 

  • Huang HM, Guo ZJ, Luo PZ (2011) Effects of aqueous extract of cinnamon on •OH and GSH-Px in the whole cerebral ischemia reperfusion injury rats. Chin J Gerontol 31:3083–3085

    CAS  Google Scholar 

  • Jiang Z, Wang Y, Zhang X, Peng T, Lu Y, Leng J, **e Q (2013) Preventive and therapeutic effects of ginsenoside Rb1 for neural injury during cerebral infarction in rats. Am J Chin Med 41:341–352

    Article  CAS  PubMed  Google Scholar 

  • Kernan WN, Viscoli CM, Furie KL (2016) Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 64:1321–1331

    Article  CAS  Google Scholar 

  • Koul HK, Pal M, Koul S (2013) Role of p38 MAP kinase signal transduction in solid tumors. Genes Cancer 4:342–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leila MN, Beitollah A, Reza A et al (2016) Effects of Arctium lappa L. (Burdock) root tea on inflammatory status and oxidative stress in patients with knee osteoarthritis. Int J Rheum Dis 19:255–261

    Article  CAS  Google Scholar 

  • Li Q, Guo YL, Li Z et al (2010) The interference of picroside II on the expressions of caspase-3 and PARP following cerebral ischemia reperfusion injury in rats. Chin Pharmacol Bull 26:342–345

    CAS  Google Scholar 

  • Liang K, Ye Y, Wang Y, Zhang J, Li C (2014) Formononetin mediates neuroprotection against cerebral ischemia/reperfusion in rats via downregulation of the Bax/Bcl-2 ratio and upregulation PI3K/Akt signaling pathway. J Neurol Sci 344:100–104

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Zhang XJ, Yang CH, Fan HG (2009) Oxymatrine protects rat brains against permanent focal ischemia and downregulates NF-κB expression. Brain Res 1268:174–180

    Article  CAS  PubMed  Google Scholar 

  • Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91

    Article  CAS  PubMed  Google Scholar 

  • Mei L, Fan R, Li X, Wang Y, Han B, Gu Y, Zhou L, Zheng Y, Tong A, Guo G (2017) Nanofibers for improving the wound repair process: the combination of a grafted chitosan and an antioxidant agent. Polym Chem 8:1664–1671

    Article  CAS  Google Scholar 

  • Nai Y, Liu H, Bi X et al (2017) Protective effect of astaxanthin on acute cerebral infarction in rats. Hum Exp Toxicol 9:929–936

    Google Scholar 

  • Predes FS, Ruiz AL, Carvalho JE, Foglio MA, Dolder H (2011) Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts. BMC Complement Altern Med 11:25

    Article  PubMed  PubMed Central  Google Scholar 

  • Santos ACD, Baggio CH, Freitas CS et al (2008) Gastroprotective activity of the chloroform extract of the roots from Arctium lappa L. J Pharm Pharmacol 60:795–801

    Article  CAS  PubMed  Google Scholar 

  • Silva LMD, Allemand A, Mendes DAGB et al (2013) Ethanolic extract of roots from Arctium lappa, L. accelerates the healing of acetic acid-induced gastric ulcer in rats: involvement of the antioxidant system. Food Chem Toxicol 51:179–187

    Article  CAS  PubMed  Google Scholar 

  • Solá S, Morgado AL, Rodrigues CM (2013) Death receptors and mitochondria: two prime triggers of neural apoptosis and differentiation. Biochim Biophys Acta 1830:2160–2166

    Article  CAS  PubMed  Google Scholar 

  • Tian X, An L, Gao LY, Bai JP, Wang J, Meng WH, Ren TS, Zhao QC (2015a) Compound MQA, a caffeoylquinic acid derivative, protects against NMDA-induced neurotoxicity and potential mechanisms in vitro. CNS Neurosci Ther 21:575–584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tian X, Guo L-P, Hu X-L, Huang J, Fan Y-H, Ren T-S, Zhao Q-C (2015b) Protective effects of Arctium lappa L. root against hydrogen peroxide-induced cell injury and potential mechanisms in SH-SY5Y cells. Cell Mol Neurobiol 35:335–344

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Dai P, Bao H, Liang P, Wang W, **ng A, Sun J (2017) Anti-inflammatory and neuroprotective effects of sanguinarine following cerebral ischemia in rats. Exp Ther Med 13:263–268

    Article  CAS  PubMed  Google Scholar 

  • **ao-Hong BA, Cai LP, Han W (2014) Effect of cilostazol pretreatment on the PARP/AIF-mediated apoptotic pathway in rat cerebral ischemia-reperfusion models. Exp Ther Med 7:1209–1214

    Article  CAS  Google Scholar 

  • Yaidikar L, Byna B, Thakur SR (2014) Neuroprotective effect of punicalagin against cerebral ischemia-reperfusion induced oxidative brain injury in rats. J Stroke Cerebrovasc Dis 23:2869–2878

    Article  PubMed  Google Scholar 

  • Yao FZ, Xue RL, Wang N (2008) The relationship of apoptosis and p38 after whole cerebral ischemia-reperfusion in rats. J Clin Anesth 24:892–894

    CAS  Google Scholar 

  • Zhao, Lian-dong, ** GR et al (2006) Effects of edaravone on content of cerebra and serum SOD, NO, MDA in rats with focal cerebral ischemia and reperfusion. J Clin Neurol 1:57–59

    Google Scholar 

  • Zhao P, Zhou R, Zhu XY et al (2015) Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice. Int J Mol Med 36:633–644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao H, Chen Z, **e LJ et al (2017) Suppression of Tlr4/nf-κb signaling pathway improves cerebral ischemia–reperfusion injury in rats. Mol Neurobiol 4:1–9

    CAS  Google Scholar 

  • Zhu P, Zhan L, Zhu T, Liang D, Hu J, Sun W, Hou Q, Zhou H, Wu B, Wang Y, Xu E (2014) The roles of p38 MAPK/MSK1 signaling pathway in the neuroprotection of hypoxic postconditioning against transient global cerebral ischemia in adult rats. Mol Neurobiol 49:1338–1349

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by grants from The Applied Basic Research Program of **, Jilin, China

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    Correspondence to Ke Zhang, **ng Tian or Hang-yu Wang.

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    All experimental procedures were in line with the National Institutes of Health guidelines for animal care and use experiments.

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    The authors declare that they have no conflicts of interest.

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    Chen, L., Liu, Dn., Wang, Y. et al. Treatment with MQA, a Derivative of Caffeoylquinic Acid, Provides Neuroprotective Effects against Cerebral Ischemia Through Suppression of the p38 Pathway and Oxidative Stress in Rats. J Mol Neurosci 67, 604–612 (2019). https://doi.org/10.1007/s12031-019-01268-1

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