Acute spinal cord injury: protective role of oroxylin A/neural cell regeneration

 
crossMark

doi: 10.18081/2333-5106/015-06/354-368
American Journal of BioMedicine Volume 3, Issue 6, pages 354-368
Published: June 28, 2015


Emiko Potácová, Shuolin Tsai, Qian Wang, Choi Xingquan, Liping Liu, Yongjun Lee

Abstract

Oroxylin A is a flavonoid isolated from Scutellaria baicalensis, which is one of the most important medicinal herbs in traditional Korean/Chinese/Japanese medicine. The amelioration of Abeta(25-35) peptide-induced memory impairment by oroxylin A is believed to be mediated via the GABAergic neurotransmitter system after a single administration, or by reductions in Abeta(25-35) peptide-induced astrocyte and microglia activations, iNOS expression, lipid peroxidation, and increased cholinergic neurotransmission after subchronic administration. We investigated the neuroprotective role of oroxylin A against spinal cord injury in rat. Male Sprague-Dawley rats weighing 200–250 grams at the time of surgery were used. Rats were randomized into the following four groups of ten animals each: control, sham, trauma and oroxylin A. In the control group, no surgical intervention was performed. In the sham group, only the spinal cord trauma model was created by the occlusion of the spinal cord with an aneurysm clip, while last group treated with oroxylin A. Histopathological and ultrastructural evaluations were also performed. Neurological evaluation was performed using the Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test. Oroxylin A treatment showed improved results concerning the histopathological scores, the ultrastructural score and the functional tests. Biochemical, histopathological, ultrastructural analysis and functional tests revealed that oroxylin A exhibits meaningful neuroprotective effects against spinal cord injury.

Keywords: Oroxylin A; Spinal cord injury; Neurological evaluation; Surgical intervention


Limited Access           Full Text-PDF                Feedback


References

1. Basso DM, Beattie MS, Bresnahan JC. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 1996;139:244–256. [PubMed]

2. Liu W, Mu R, Nie FF, et al. MAC-related mitochondrial pathway in oroxylin A-induced apoptosis in human hepatocellular carcinoma HepG2 cells. Cancer Lett 2009; 284:198–207. [PubMed]

3. Demediuk P, Saunders RD, Anderson DK, Means ED, Horrocks LA. Membrane lipid changes in laminectomized and traumatized cat spinal cord. Proc Natl Acad Sci U S A 1985;82:7071–7075. [PubMed]

4. Fitch MT, Doller C, Combs CK, Landreth GE, Silver J. Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. Journal of Neuroscience 1999;19:8182–8198. [PubMed]

5. Wood PL, Khan MA, Moskal JR, Todd KG, Tanay VA, Baker G. Aldehyde load in ischemia-reperfusion brain injury: neuroprotection by neutralization of reactive aldehydes with phenelzine. Brain Res 2006;1122:184–190. [PubMed]

6. Lu Z, Lu N, Li C, et al. Oroxylin A inhibits matrix metalloproteinase-2/9 expression and activation by up-regulating tissue inhibitor of metalloproteinase-2 and suppressing the ERK1/2 signaling pathway. Toxicol Lett 2012;209: 211–220. [PubMed]

7. Chen Y, Yang L, Lee TJ. Oroxylin A inhibition of lipopolysaccharide-induced iNOS and COX-2 gene expression via suppression of nuclear factor-kappaB activation. Biochem. Pharmacol 2000;59:1445–1457. [PubMed]

8. Ha J, Zhao L, Zhao Q, et al. Oroxylin A improves the sensitivity of HT-29 human colon cancer cells to 5-FU through modulation of the COX-2 signaling pathway. Biochem Cell Biol 2012; 90:521-31. [PubMed]

9. Gao Y, Lu N, Ling Y, et al. Oroxylin A inhibits angiogenesis through blocking vascular endothelial growth factor-induced KDR/Flk-1 phosphorylation. J. Cancer Res. Clin. Oncol 2010; 136(5):667-675. [PubMed]

10. Pham TA, Che H, Phan PT, Lee JW, Kim SS, Park H. Oroxylin A analogs exhibited strong inhibitory activities against iNOS-mediated nitric oxide (NO) production. Bioorganic & medicinal chemistry letters 2012; 22: 2534-2535. [PubMed]

11. Song X, Chen Y, Sun Y, et al. Oroxylin A, a classical natural product, shows a novel inhibitory effect on angiogenesis induced by lipopolysaccharide. Pharmacological reports 2012;PR 64:1189-1199. [PubMed]

12. Yoon SY, dela Peña I, Kim SM, et al. Oroxylin A improves attention deficit hyperactivity disorder-like behaviors in the spontaneously hypertensive rat and inhibits reuptake of dopamine in vitro. Archives of pharmacal research 2013;36:134-140. [PubMed]

13. Taub R. Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Biol 2014; 5: 836–847. [PubMed]

14. Masuda Y. Learning toxicology from carbon tetrachloride-induced hepatotoxicity. Yakugaku Zasshi 2006; 126:885–899. [PubMed]

15. Taniguchi M, Takeuchi T, Nakatsuka R, Watanabe T, Sato K. Molecular process in acute liver injury and regeneration induced by carbon tetrachloride. Life Sci 2004; 75:1539–1549. [PubMed]

16. Basu S. Carbon Tetrachloride-Induced Hepatotoxicity: A Classic Model of Lipid Peroxidation and Oxidative Stress. In: Basu S, Wiklund L, editors. Studies on Experimental Models: Humana Press. 467–480.

17. Novobrantseva TI, Majeau GR, Amatucci A, et al. Attenuated liver fibrosis in the absence of B cells. The Journal of Clinical Investigation 2005; 115:3072–3082. [PubMed]

18. Yoneyama H, Kai Y, Koyama J, et al. Neutralization of CXCL10 accelerates liver regeneration in carbon tetrachloride-induced acute liver injury. Medical Molecular Morphology 2007;40:191–197. [PubMed]

19. Min JK, Han KY, Kim EC, et al. Capsaicin inhibits in vitro and in vivo angiogenesis. Cancer Res 2004;64:644–651. [PubMed]

20. Gao Y, Lu N, Ling Y, et al.  Oroxylin A inhibits angiogenesis through blocking vascular endothelial growth factor-induced KDR/Flk-1 phosphorylation. J Cancer Res Clin Oncol  2010;136: 667–675. [PubMed]

21. Li HN, Nie FF, Liu W, et al. Apoptosis induction of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo. Toxicology 2009; 257: 80–85. [PubMed]

Print Friendly, PDF & Email