POLYDATIN, A HERBAL BIOFLAVONOID, IS PROTECTIVE AGAINST CEREBRAL ISCHEMIA-REPERFUSION INJURY: MOLECULAR, BIOCHEMICAL AND HISTOLOGICAL DATA
Year 2023,
Issue: 052, 247 - 265, 29.03.2023
Saadet Çeliközlü
,
Said Altıkat
,
Filiz Özyiğit
,
Sibel Köktürk
,
Halit Çeliközlü
Abstract
This study aims to research the protective effects Polydatin have against cerebral ischemia/reperfusion damage. Polydatin is a natural polyphenic phytoalexin and which has strong antioxidant properties.
In the present study, 5 groups were prepared as control, sham, ischemia/reperfusion (IR), Polydatin 30 (Pol 30), and Polydatin 60 (Pol 60). The four-vessel occlusion model was used to induce ischemia. Polydatin was injected intraperitoneally 30 minutes before ischemia. Hematoxylin Eosin staining were applied for histopathological study, SOD, CAT, and MDA levels determined, and TNF-α mRNA expression levels were measured by the RT-qPCR technique in brain tissue. According to the results, a serious loss of neurons in the CA 1 region of the hippocampus was observed in the IR group. Neuronal damage in the hippocampus decreased and the number of neurons increased significantly in the Pol 60 group compared to the IR group. CAT and SOD levels were reduced, and the MDA level rose in the IR group. In Pol 60 and Pol 30 groups, an increase was observed in the CAT and SOD levels, a decrease was observed in the MDA and total protein levels compared to the IR group. The amount of TNF-α mRNA expression in the brain tissues of the IR group was significantly higher compared to the control group. In the Pol 60 group, mRNA expression level decreased significantly compared to the IR group. In conclusion, the increase in MDA, decrease in SOD and CAT values, increase in TNF-α gene mRNA expression, and histological damage in the brain because of cerebral ischemia/reperfusion in rats were restored to normal levels with 30 and 60 mg/kg polydatin administration as protective before ischemia. Especially at 60 mg/kg polydatin supplementation with antioxidant properties has a neuroprotective effect against oxidative stress damage caused by cerebral ischemia/reperfusion.
Supporting Institution
Kütahya Dumlupınar Üniversitesi BAP Birimi
Thanks
This work was supported by the Scientific Research Project Unit of Kütahya Dumlupınar University (No: 2018-07). This study was presented as oral presentation 1. International Health Sciences And Biomedical Congress on January 23-24 2021, Ankara, Turkey.
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Year 2023,
Issue: 052, 247 - 265, 29.03.2023
Saadet Çeliközlü
,
Said Altıkat
,
Filiz Özyiğit
,
Sibel Köktürk
,
Halit Çeliközlü
References
- [1] Yang, W., Chen, X., Pan, J., Ge, H., Yin, K., Wu, Z., Li, X., Sha, D., and Xu, Y., (2015), Malibatol A protects against brain injury through reversing mitochondrial dysfunction in experimental stroke, Neurochemistry International, 80, 33-40.
- [2] Tang, K.S. and Tan, J.S., (2019), The protective mechanisms of polydatin in cerebral ischemia, European Journal of Pharmacology, 842, 133-138.
- [3] Gao, Y., Chen, T., Lei, X., Li, Y., Dai, X., Cao, Y., Ding, Q., Lei, X., Li, T., and Lin, X., (2016), Neuroprotective effects of polydatin against mitochondrial-dependent apoptosis in the rat cerebral cortex following ischemia/reperfusion injury. Molecular Medicine Reports, 14(6), 5481-5488.
- [4] Wicha, P., Tocharus, J., Janyou, A., Jittiwat, J., Changtam, C., Suksanrarn, A., and Tocharus, C., (2017), Hexahydrocurcumin protects against cerebral ischemia/reperfusion injury, attenuates inflammation, and improves antioxidant defenses in a rat stroke model, Plos One, 12(12), e0189211.
- [5] Bonnefont-Rousselot, D., (2016), Resveratrol and cardiovascular diseases, Nutrients, 8(5), 250.
- [6] Du, Q. H., Peng, C., and Zhang, H., (2013), Polydatin: a review of pharmacology and pharmacokinetics, Pharmaceutical Biology, 51(11), 1347-1354.
- [7] Kakoti, B.B., Hernandez-Ontiveros, D.G., Kataki, M.S., Shah, K., Pathak, Y., and Panguluri, S.K., (2015), Resveratrol and omega-3 fatty acid: its implications in cardiovascular diseases, Frontiers in Cardiovascular Medicine, 2, 38.
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- [10] Wang, J., Feng, J., Xu, L., Ma, J., Li, J., Ma, R., Sun, K., Wang, Z., and Zhang, H., (2019), Ionic liquid-based salt-induced liquid-liquid extraction of polyphenols and anthraquinones in Polygonum cuspidatum, Journal of Pharmaceutical and Biomedical Analysis, 163, 95-104.
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- [16] Chen, Z., Wei, Q., Hong, G., Chen, D., Liang, J., He, W., and Chen, M. H., (2016), Polydatin induces bone marrow stromal cells migration by activation of ERK1/2, Biomedicine and Pharmacotherapy, 82, 49-53.
- [17] Su, D., Cheng, Y., Liu, M., Liu, D., Cui, H., Zhang, B., Zhou, S., Yang, T., and Mei, Q., (2013), Comparison of piceid and resveratrol in antioxidation and antiproliferation activities in vitro, PloS One, 8(1), e54505.
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- [19] Fang, J., Luo, L., Ke, Z., Liu, C., Yin, L., Yao, Y., Feng, Q., Huang, C., Zheng, P., and Fan, S., (2019), Polydatin protects against acute cholestatic liver injury in mice via the inhibition of oxidative stress and endoplasmic reticulum stress, Journal of Functional Foods, 55, 175-183.
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- [21] Xu, G., Kuang, G., Jiang, W., Jiang, R., and Jiang, D., (2016b), Polydatin promotes apoptosis through upregulation the ratio of Bax/Bcl-2 and inhibits proliferation by attenuating the β-catenin signaling in human osteosarcoma cells, American Journal of Translational Research, 8(2), 922.
- [22] Hu, T., Fei, Z., Su, H., Xie, R., and Chen, L., (2019), Polydatin inhibits proliferation and promotes apoptosis of doxorubicin-resistant osteosarcoma through LncRNA TUG1 mediated suppression of Akt signalling, Toxicology and Applied Pharmacology, 371, 55-62.
- [23] Xu, B., Lin, H.B., Zhou, H., and Xu, J.P., (2010), Protective effect of polydatin on a PC12 cell model of oxygen-glucose deprivation. Journal of Southern Medical University, 30(5), 1041-1043.
- [24] Wang, F.Y., Xu, Z.J., Zhang, X.L., Wang, W.T., Ha, M.L., and Wang, Y., (2008), Protective effects of polydatin against lung ischemia/reperfusion injury andhe initial exploration for its mechanism, Chinese Journal of Applied Physiology, 24(1), 62-65.
- [25] Zhang, L.P., Yang, C.Y., Wang, Y.P., Cui, F., and Zhang, Y., (2008), Protective effect of polydatin against ischemia/reperfusion injury in rat heart, Acta Physiologica Sinica, 60(2), 161-168.
- [26] Liu, H.B., Meng, Q.H., Huang, C., Wang, J.B., and Liu, X.W., (2015), Nephroprotective effects of polydatin against ischemia/reperfusion injury: a role for the PI3K/Akt signal pathway, Oxidative Medicine and Cellular Longevity, Article ID 362158.
- [27] Li, T., Cai, S., Zeng, Z., Zhang, J., Gao, Y., Wang, X., and Chen, Z., (2014), Protective effect of polydatin against burn-induced lung injury in rats, Respiratory Care, 59(9), 1412-1421.
- [28] Wang, W., Tang, L., Li, Y., and Wang, Y., (2015), Biochanin A protects against focal ischemia/reperfusion in rats via inhibition of p-38-mediated inflammatory responses, Journal of Neurological Science, 348(1-2), 121-125.
- [29] Li, P., Wang, X., Zhao, M., Song, R., and Zhao, K.S., (2015), Polydatin protects hepatocytes against mitochondrial injury in acute severe hemorrhagic shock via SIRT1-SOD2 pathway, Expert Opinion on Therapeutic Targets, 19(7), 997-1010.
- [30] Zeng, Z., Chen, Z., Li, T., Zhang, J., Gao, Y., Xu, S., and Zhao, K.S., (2015a), Polydatin: a new therapeutic agent against multiorgan dysfunction, Journal of Surgical Research, 198(1), 192-199.
- [31] Zeng, Z., Chen, Z., Xu, S., Song, R., Yang, H., and Zhao, K.S., (2015b), Polydatin alleviates small intestine injury during hemorrhagic shock as a SIRT1 activator, Oxidative Medicine and Cellular Longevity, Article ID 965961.
- [32] Deng, Y.H., Alex, D., Huang, H.Q., Wang, N., Yu, N., Wang, Y.T., and Lee, S.M.Y., (2011), Inhibition of TNF‐α‐mediated endothelial cell–monocyte cell adhesion and adhesion molecules expression by the resveratrol derivative, trans‐3, 5, 4′‐trimethoxystilbene, Phytotherapy Research, 25(3), 451-457.
- [33] Li, R.P., Wang, Z.Z., Sun, M.X., Hou, X.L., Sun, Y., Deng, Z.F., and Xiao, K., (2012), Polydatin protects learning and memory impairments in a rat model of vascular dementia, Phytomedicine, 19(8-9), 677-681.
- [34] White, B.C., Grossman, L.I., and Krause, G.S., Brain injury by global ischemia and reperfusion: A theoretical perspective on membrane damage and repair, Neurology. 1993, 43(9), 1656.
- [35] Islekel, H., Islekel, S., Guner, G., and Özdamar, N., (1999), Evaluation of lipid peroxidation, cathepsin L and acid phosphatase activities in experimental brain ischemia-reperfusion, Brain Research, 843(1-2), 18-24.
- [36] Roumen, R.M.H., Hendriks, T., Ven-Jongekrijg, J., Nieuwenhuijzen, G.A., Sauerwein, R.W., van der Meer, J.W., and Goris, R.J., (1993), Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Relation with subsequent adult respiratory distress syndrome and multiple organ failure, Annals of Surgery, 218(6), 769-776.
- [37] Ferran, C., Millan, M.T., Csizmadia, V., Cooper, J.T., Brostjan, C., Bach, B.F., and Wnkler, H., (1995), Inhibition of NF-kappa B by pyrrolidine dithiocarbamate blocks endothelial cell activation, Biochemical and Biophysical Research Communication, 214(1), 212–223.
- [38] Draper, H.H. and Hadley, M., (1990), Malondialdehyde determination as index of lipid peroxidation, In Methods in Enzymology, Academic Press, Cambridge, Massachusetts, ABD, 186, 421-431.
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