3 Biotech

, 9:211 | Cite as

Neovascular glaucoma regulation by arylsulfonyl indoline-benzamide (ASIB) through targeting NF-kB signalling pathway

  • Xiaojun LeiEmail author
  • Yongxia Zhao
Original Article


The present study investigated the effect of arylsulfonyl indoline-benzamide (ASIB) on neovascular glaucoma in the mice model in vivo. In the mice model of glaucoma, ASIB treatment significantly (P < 0.05) increased PDGF-B-positive cell count in the corneal tissues. ASIB treatment at 5, 10, 15 and 20 mg/kg doses raised the level of PDGF-B mRNA in the mice cornea by 2.3-, 3.8-, 5.4- and 5.5-fold, respectively. Pre-treatment of the glaucoma mice with ASIB leads to inhibition of TNF-α and IL-6 production. In the glaucoma mice, treatment with ASIB leads to a marked decrease in the level of NOD2 mRNA and protein. ASIB treatment caused a significant decrease in the glaucoma-induced up-regulation of NF-κB p65 activation. The phosphorylation of NF-κB p65 was almost completely inhibited in the glaucoma mice on treatment with 15 mg/kg dose of ASIB. ASIB exhibited inhibitory effect on glaucoma-induced inflammatory cytokine and oxidative factor damage in the mice. It caused up-regulation of PDGF expression and down-regulated NF-κB activation. Therefore, ASIB can be of therapeutic significance for neovascular glaucoma treatment. However, more studies need to be performed to fully understand the molecular mechanism of ASIB in glaucoma treatment.


Neovascular glaucoma Intraocular Optic nerve Pro-inflammatory 


  1. Arnalich F, Garcia-Palomero E, López J, Jiménez M, Madero R, Renart J, Vázquez JJ, Montiel C (2000) Predictive value of nuclear factor kappaB activity and plasma cytokine levels in patients with sepsis. Infect Immun 68:1942–1945CrossRefGoogle Scholar
  2. Bergsten E, Uutela M, Li X et al (2001) PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. Nat Cell Biol 3:512–516CrossRefGoogle Scholar
  3. Blackwell TS, Christman JW (1996) Sepsis and cytokines: current status. Br J Anaesth 77:110–117CrossRefGoogle Scholar
  4. Brenmoehl J, Herfarth H, Glück T, Audebert F, Barlage S, Schmitz G, Froehlich D, Schreiber S, Hampe J, Schölmerich J et al (2007) Genetic variants in the NOD2/CARD15 gene are associated with early mortality in sepsis patients. Intensive Care Med 33:1541–1548CrossRefGoogle Scholar
  5. Enge M, Wilhelmsson U, Abramsson A et al (2003) Neuron-specific ablation of PDGF-B is compatible with normal central nervous system development and astroglial response to injury. Neurochem Res 28:271–279CrossRefGoogle Scholar
  6. Feng X, Ren B, Xie W, Huang Z, Liu J, Guan R, Duan M, Xu J (2006a) Influence of hydroxyethyl starch 130/0.4 in pulmonary neutrophil recruitment and acute lung injury during polymicrobial sepsis in rats. Acta Anaesthesiol Scand 50:1081–1088CrossRefGoogle Scholar
  7. Feng X, Yan W, Liu X, Duan M, Zhang X, Xu J (2006b) Effects of hydroxyethyl starch 130/0.4 on pulmonary capillary leakage and cytokines production and NF-kappaB activation in CLP-induced sepsis in rats. J Surg Res 135:129–136CrossRefGoogle Scholar
  8. Han NR, Kim HM, Jeong HJ (2011) Inactivation of cystein-aspartic acid protease (caspase)-1 by saikosaponin A. Biol Pharm Bull 34:817–823CrossRefGoogle Scholar
  9. Hasegawa M, Fujimoto Y, Lucas PC, Nakano H, Fukase K, Núñez G, Inohara N (2008) A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation. EMBO J 27:373–383CrossRefGoogle Scholar
  10. Hayreh SS (2007) Neovascular glaucoma. Prog Retin Eye Res 26:470–485CrossRefGoogle Scholar
  11. Hotchkiss RS, Karl IE (2003) The pathophysiology and treatment of sepsis. N Engl J Med 348:138–150CrossRefGoogle Scholar
  12. Ishii Y, Oya T, Zheng L et al (2006) Mouse brains deficient in neuronal PDGF receptor-beta develop normally but are vulnerable to injury. J Neurochem 98:588–600CrossRefGoogle Scholar
  13. Janmaat ML, Heerkens JL, de Bruin AM, Klous A, de Waard V, de Vries CJ (2010) Erythropoietin accelerates smooth muscle cell-rich vascular lesion formation in mice through endothelial cell activation involving enhanced PDGF-BB release. Blood 115:1453–1460CrossRefGoogle Scholar
  14. Kim SO, Park JY, Jeon SY, Yang CH, Kim MR (2015) Saikosaponin a, an active compound of Radix Bupleuri, attenuates inflammation in hypertrophied 3T3-L1 adipocytes via ERK/NF-κB signaling pathways. Int J Mol Med 35:1126–1132CrossRefGoogle Scholar
  15. Magalhaes JG, Lee J, Geddes K, Rubino S, Philpott DJ, Girardin SE (2011) Essential role of Rip2 in the modulation of innate and adaptive immunity triggered by Nod1 and Nod2 ligands. Eur J Immunol 41:1445–1455CrossRefGoogle Scholar
  16. Parrillo JE, Parker MM, Natanson C, Suffredini AF, Danner RL, Cunnion RE, Ognibene FP (1990) Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med 113:227–242CrossRefGoogle Scholar
  17. Pinsky MR, Vincent JL, Deviere J, Alegre M, Kahn RJ, Dupont E (1993) Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. Chest 103:565–575CrossRefGoogle Scholar
  18. Sohan SH (2007) Neovascular glaucoma. Prog Ret Eye Res 26:470–485CrossRefGoogle Scholar
  19. Sun Y, Cai TT, Zhou XB, Xu Q (2009) Saikosaponin A inhibits the proliferation and activation of T cells through cell cycle arrest and induction of apoptosis. Int Immunopharmacol 9:978–983CrossRefGoogle Scholar
  20. Wong VH, Bui BV, Vingrys AJ (2011) Clinical and experimental links between diabetes and glaucoma. Clin Exp Optom 94:4–23CrossRefGoogle Scholar
  21. Worley A, Grimmer-Somers K (2011) Risk factors for glaucoma: what do they really mean? Aust J Prim Health 17:233–239CrossRefGoogle Scholar
  22. Wu SJ, Lin YH, Chu CC, Tsai YH, Chao JC (2008) Curcumin or saikosaponin A improves hepatic antioxidant capacity and protects against CCl4-induced liver injury in rats. J Med Food 11:224–229CrossRefGoogle Scholar
  23. Wu QH, Chen WS, Chen QX, Wang JH, Zhang XM (2010a) Changes in the expression of platelet-derived growth factor in astrocytes in diabetic rats with spinal cord injury. Chin Med J (Engl) 123:1577–1581Google Scholar
  24. Wu SJ, Tam KW, Tsai YH, Chang CC, Chao JC (2010b) Curcumin and saikosaponin A inhibit chemical-induced liver inflammation and fibrosis in rats. Am J Chin Med 38:99–111CrossRefGoogle Scholar
  25. Yanagi M, Kawasaki R, Wang JJ, Wong TY, Crowston J, Kiuchi Y (2011) Vascular risk factors in glaucoma: a review. Clin Exp Ophthalmol 39:252–258CrossRefGoogle Scholar
  26. Zhu J, Luo C, Wang P, He Q, Zhou J, Peng H (2013) Saikosaponin A mediates the inflammatory response by inhibiting the MAPK and NF-κB pathways in LPS-stimulated RAW 264.7 cells. Exp Ther Med 5:1345–1350CrossRefGoogle Scholar

Copyright information

© King Abdulaziz City for Science and Technology 2019

Authors and Affiliations

  1. 1.Opthalmology DepartmentFriendship Hospital of Da LianDa LianChina
  2. 2.Opthalmology DepartmentThe Third People’s Hospital of Da LianDa LianChina

Personalised recommendations