Effect of niosomes containing saponin on hippocampus tissue damage in animal model of stroke

Document Type : Reasearch Paper

Authors

1 PhD student in animal physiology, Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

2 Professor, Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

3 Associate Professor, Department of Animal Sciences and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.

4 Associate Professor, Department of Veterinary, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Abstract

Cerebral ischemia is one reason for death and loss of movement ability of people, which imposes a large and significant cost on the global health system. Niosomes, as useful tools, can increase drug delivery to the brain. The purpose of this research is to investigate the effect of niosomes containing saponin (NS) on stroke- induced damage in the hippocampus of an animal model. The physicochemical characteristics of nanocarriers, such as zeta potential, size, and release test were investigated after the fabrication of thin film method. In this study, Wistar rats were divided into five experimental groups including sham group, stroke group, stroke group with empty niosome injection, stroke group with saponin injection, and stroke group with niosome saponin injection. The study examined various aspects of ischemia including stroke volume, blood-brain barrier (BBB) damage, neurological defects, levels of inflammatory cytokines, and cellular damage in the hippocampus. The findings indicate that NS, with a size of 85.92nm, zeta potential of -34.7 mv, and an entrapment efficiency (EE%) of  85.70% effectively reduced stroke volume, cerebral edema, BBB damage, expression level of TNF-α, and NF-kB genes and inflammation in hippocampal cells. Additionally, NS improved sensory and motor performance in rats. These results demonstrate that NS can mitigate stroke-induced damage in the hippocampus of the rat model by effectively crossing the BBB.

Highlights

 

Keywords

Main Subjects

 

References

  1. Strong K., Mathers C., Bonita R., (2007), Preventing stroke: Saving lives around the world. Lancet Neurol. 6: 182-187. https://doi.org/10.1016/S1474-4422(07)70031-5
  2. Büttner F., Cordes C., Gerlach F., Heimann A., Alessandri B., Luxemburger U., (2009), Genomic response of the rat brain to global ischemia and reperfusion. Brain Research. 1252: 1-14. https://doi.org/10.1016/j.brainres.2008.10.045
  3. Yang J., Li J., Lu J., Zhang Y., Zhu Z., Wan H., (2012), Synergistic protective effect of astragaloside IV-tetramethylpyrazine against cerebral ischemic-reperfusion injury induced by transient focal ischemia. J. Ethnopharmacol. 140: 64-72. https://doi.org/10.1016/j.jep.2011.12.023
  4. Xing B., Chen H., Zhang M., Zhao D., Jiang R., Liu X., (2008), Ischemic postconditioning inhibits apoptosis after focal cerebral ischemia/reperfusion injury in the rat. Stroke. 39: 2362-2369. https://doi.org/10.1161/STROKEAHA.107.507939
  5. Rodrigues H. G., Diniz Y. S., Faine L. A., Galhardi C. M., Burneiko R. C., Almeida J. A., (2005), Antioxidant effect of saponin: potential action of a soybean flavonoid on glucose tolerance and risk factors for atherosclerosis. Int. J. Food Sci. Nutr. 56: 79-85. https://doi.org/10.1080/09637480500081738
  6. Patel M., Souto E. B., Singh K. K., (2013), Advances in brain drug targeting and delivery: Limitations and challenges of solid lipid nanoparticles. Expert Opin Drug Deliv. 10: 889-905. https://doi.org/10.1517/17425247.2013.784742
  7. Blasi P., Schoubben A., Traina G., Manfroni G., Barberini L., Alberti P. F., (2013), Lipid nanoparticles for brain targeting III. Long-term stability and in vivo toxicity. Int. J. Pharm. 454: 316-323. https://doi.org/10.1016/j.ijpharm.2013.06.037
  8. Gharbavi M., Amani J., Kheiri-Manjili H., Danafar H., Sharafi A., (2018), Niosome: A promising nanocarrier for natural drug delivery through blood-brain barrier. Adv. Pharmac. Sci. 2018: 6847971. https://doi.org/10.1155/2018/6847971
  9. Dufes C., Gaillard F., Uchegbu I. F., Schätzlein A. G., Olivier J. C., Muller J. M., (2004), Glucose-targeted niosomes deliver vasoactive intestinal peptide (VIP) to the brain. Int. J. Pharm. 285: 77-85. https://doi.org/10.1016/j.ijpharm.2004.07.020
  10. Zhou J., Wu X., Zhao Z., Wang Z., Li S., Chen C., (2020), Preparation of a novel ginkgolide B niosomal composite drug. Open Chem. 18: 1064-1074. https://doi.org/10.1515/chem-2020-0089
  11. Sita V. G., Jadhav D., Vavia P., (2020), Niosomes for nose-to-brain delivery of bromocriptine: Formulation development, efficacy evaluation and toxicity profiling. J. Drug Deliv. Sci. Technol. 58: 101791. https://doi.org/10.1016/j.jddst.2020.101791
  12. Varshosaz J., Taymouri S., Pardakhty A., Asadi-Shekaari M., Babaee A., (2014), Niosomes of ascorbic acid and α-tocopherol in the cerebral ischemia-reperfusion model in male rats. BioMed. Res. Int. 2014: 816103.https://doi.org/10.1155/2014/816103
  13. Berger N., Sachse A., Bender J., Schubert R., Brandl M., (2001), Filter extrusion of liposomes using different devices: Comparison of liposome size, encapsulation efficiency, and process characteristics. Int. J. Pharm. 223: 55-68. https://doi.org/10.1016/s0378-5173(01)00721-9
  14. Mashal M., Attia N., Soto-Sánchez C., Martínez-Navarrete G., Fernández E., Puras G., (2018), Non-viral vectors based on cationic niosomes as efficient gene delivery vehicles to central nervous system cells into the brain. Int. J. Pharm. 552: 48-55. https://doi.org/10.1016/j.ijpharm.2018.09.038
  15. Barot T., Rawtani D., Kulkarni P., (2021), Development, characterization and in vitro-in vivo evaluation of Farnesol loaded niosomal gel for applications in oral candidiasis treatment. Heliyon. 7: e07968. https://doi.org/10.1016/j.heliyon.2021.e07968
  16. Zylberberg C., Matosevic S., (2016), Pharmaceutical liposomal drug delivery: A review of new delivery systems and a look at the regulatory landscape. Drug Delivery. 23: 3319-3329. https://doi.org/10.1080/10717544.2016.1177136
  17. Fraser O. N., Bugnyar T., (2011), Ravens reconcile after aggressive conflicts with valuable partners. PLoS One. 6: 18118. doi:https://doi.org/10.1371/journal.pone.0018118
  18. Wang Y., Guo W., Liu Y., Wang J., Fan M., Zhao H., (2019), Investigating the protective effect of gross saponins of tribulus terrestris fruit against ischemic stroke in rat using metabolomics and network pharmacology. Metabolites. 9: 240. https://doi.org/10.3390/metabo9100240
  19. Longa E. Z., Weinstein P. R., Carlson S., Cummins R., (1989), Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 20: 84-91. https://doi.org/10.1161/01.str.20.1.84
  20. Long J., Cai L., Li J., Zhang L., Yang H., Wang T., (2013), JNK3 involvement in nerve cell apoptosis and neurofunctional recovery after traumatic brain injury. Neural Regen Res. 8: 1491-1499. https://doi.org/10.3969/j.issn.1673-5374.2013.16.006
  21. Bigdeli M. R., Hajizadeh S., Froozandeh M., Heidarianpour A., Rasoulian B., Asgari A. R., (2008), Normobaric hyperoxia induces ischemic tolerance and upregulation of glutamate transporters in the rat brain and serum TNF-α level. Exp. Neurology. 212: 298-306. https://doi.org/10.1016/j.expneurol.2008.03.029
  22. Lin T. N., He Y. Y., Wu G., Khan M., Hsu C. Y., (1993), Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats. Stroke. 24: 117-121. https://doi.org/10.1161/01.str.24.1.117
  23. Gilat E., Kadar T., Levy A., Rabinovitz I., Cohen G., Kapon Y., (2005), Anticonvulsant treatment of sarin-induced seizures with nasal midazolam: an electrographic, behavioral, and histological study in freely moving rats. Toxicol. Appl. Pharmacol. 209: 74-85. https://doi.org/10.1016/j.taap.2005.03.007
  24. Pfaffl M. W., (2001), A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29: e45. https://doi.org/10.1093/nar/29.9.e45
  25. Detoni C. B., Cabral-Albuquerque E. C., Hohlemweger S. V., Sampaio C., Barros T. F., Velozo E. S., (2009), Essential oil from Zanthoxylum tingoassuiba loaded into multilamellar liposomes useful as antimicrobial agents. J. Microencapsul. 26: 684-691. https://doi.org/10.1080/02652040802661887
  26. Fang J. Y., Hong C. T., Chiu W. T., Wang Y. Y., (2001), Effect of liposomes and niosomes on skin permeation of enoxacin. Int. J. Pharm. 219: 61-72. https://doi.org/10.1016/s0378-5173(01)00627-5
  27. Markova E., Taneska L., Kostovska M., Shalabalija D., Mihailova L., Glavas Dodov M., (2022), Design and evaluation of nanostructured lipid carriers loaded with Salvia officinalis extract for Alzheimer's disease treatment. J. Biomed. Mater. Res. B. Appl. Biomater. 110: 1368-1390. https://doi.org/10.1002/jbm.b.35006
  28. Sadeghi Ghadi Z., Dinarvand R., Asemi N., Talebpour Amiri F., Ebrahimnejad P., (2019), Preparation, characterization and in vivo evaluation of novel hyaluronan containing niosomes tailored by Box-Behnken design to co-encapsulate curcumin and quercetin. Eur. J. Pharm. Sci. 130: 234-246. https://doi.org/10.1016/j.ejps.2019.01.035
  29. Ag Seleci D., Maurer V., Stahl F., Scheper T., Garnweitner G., (2019), Rapid microfluidic preparation of niosomes for targeted drug delivery. Int. J. Mol. Sci. 20: 4696-5001. https://doi.org/10.3390/ijms20194696
  30. Lu B., Huang Y., Chen Z., Ye J., Xu H., Chen W., (2019), Niosomal nanocarriers for enhanced skin delivery of quercetin with functions of anti-tyrosinase and antioxidant. Molecules. 24: 2322-2327. https://doi.org/10.3390/molecules24122322
  31. Mukherjee B., Patra B., Layek B., Mukherjee A., (2007), Sustained release of acyclovir from nano-liposomes and nano-niosomes: an in vitro study. Int. J. Nanomedicine. 2: 213-225. https://pubmed.ncbi.nlm.nih.gov/17722549/
  32. Kiefer D., Pantuso T., (2003), Panax ginseng. Am. Fam. Physician. 68: 1539-1542. https://pubmed.ncbi.nlm.nih.gov/14596440/
  33. Lin M., Sun W., Gong W., Ding Y., Zhuang Y., Hou Q., (2015), Ginsenoside Rg1 protects against transient focal cerebral ischemic injury and suppresses its systemic metabolic changes in cerabral injury rats. Acta Pharm. Sin. B. 5: 277-284. https://doi.org/10.1016/j.apsb.2015.02.001
  34. Duan J., Cui J., Zheng H., Xi M., Guo C., Weng Y., (2019), Aralia taibaiensis Protects against I/R-Induced Brain Cell Injury through the Akt/SIRT1/FOXO3 a Pathway. Oxid. Med. Cell Longev. 2019: 7609765. https://doi.org/10.1155/2019/7609765
  35. Stanimirovic D., Satoh K., (2000), Inflammatory mediators of cerebral endothelium: A role in ischemic brain inflammation. Brain Pathol. 10: 113-126. https://doi.org/10.1111/j.1750-3639.2000.tb00248.x
  36. Nagahiro S., Uno M., Sato K., Goto S., Morioka M., Ushio Y., (1998), Pathophysiology and treatment of cerebral ischemia. J. Med. Invest. 45: 57-70. doi:https://pubmed.ncbi.nlm.nih.gov/9864965/
  37. Buttini M., Appel K., Sauter A., Gebicke-Haerter P. J., Boddeke H. W. G. M., (1996), Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat. Neuroscience. 71: 1-16. https://doi.org/10.1016/0306-4522(95)00414-9
  38. Liang Z. Q., Li Y. L., Zhao X. L., Han R., Wang X. X., Wang Y., (2007), NF-kappaB contributes to 6-hydroxydopamine-induced apoptosis of nigral dopaminergic neurons through p53. Brain Res. 1145: 190-203. https://doi.org/10.1016/j.brainres.2007.01.130
  39. Zhang Y., Sun M., Han Y., Zhai K., Tang Y., Qin X., (2015), The saponin DT-13 attenuates tumor necrosis factor-α-induced vascular inflammation associated with Src/NF-кB/MAPK pathway modulation. Int. J. Biol. Sci. 11: 970-981. https://doi.org/10.7150/ijbs.11635
  40. Jang K. J., Kim H. K., Han M. H., Oh Y. N., Yoon H. M., Chung Y. H., (2013), Anti-inflammatory effects of saponins derived from the roots of Platycodon grandiflorus in lipopolysaccharidestimulated BV2 microglial cells. Int. J. Mol. Med. 31: 1357-1366. https://doi.org/10.3892/ijmm.2013.1330
  41. Liu Z., Sun R., Lü W., Dang C., Song Y., Wang C., (2012), The -938A/A genotype of BCL2 gene is associated with esophageal cancer. Med. Oncol. 29: 2677-2683. https://doi.org/10.1007/s12032-011-0135-2
  42. Tan Z. W., Hu H. Y., Chen X., (2012), Effect of qingxin kaiqiao recipe saponin on the expressions of Bax, Bcl-2, Abeta, and betaAPP in the cortex and hippocampus of Alzheimer's disease rats. Zhongguo. Zhong. Xi. Yi. Jie He Za Zhi. 32: 1258-1263. https://pubmed.ncbi.nlm.nih.gov/23185771/

 

International Journal of Nano Dimension
Volume 15, Issue 1
January 2024
Pages 23-34

Files

Share

How to cite

Statistics