DOI QR코드

DOI QR Code

An alpha-lipoic acid-decursinol hybrid compound attenuates lipopolysaccharide-mediated inflammation in BV2 and RAW264.7 cells

  • Kwon, Mi-Youn (Department of Physiology and Biophysics, College of Medicine, Inha University) ;
  • Park, Jiwon (Department of Physiology and Biophysics, College of Medicine, Inha University) ;
  • Kim, Sang-Min (Department of Physiology and Biophysics, College of Medicine, Inha University) ;
  • Lee, Jooweon (Department of Physiology and Biophysics, College of Medicine, Inha University) ;
  • Cho, Hyeongjin (Department of Chemistry, Inha University) ;
  • Park, Jeong-Ho (Department of Chemical & Biological Engineering, Hanbat National University) ;
  • Han, Inn-Oc (Department of Physiology and Biophysics, College of Medicine, Inha University)
  • Received : 2019.05.20
  • Accepted : 2019.06.13
  • Published : 2019.08.31

Abstract

In this study, the anti-inflammatory effects of ${\alpha}-lipoic$ acid (LA) and decursinol (Dec) hybrid compound LA-Dec were evaluated and compared with its prodrugs, LA and Dec. LA-Dec dose-dependently inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) generation in BV2 mouse microglial cells. On the other hand, no or mild inhibitory effect was shown by the Dec and LA, respectively. LA-Dec demonstrated dose-dependent protection from activation-induced cell death in BV2 cells. LA-Dec, but not LA or Dec individually, inhibited LPS-induced increased expressions of induced NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in a dose-dependent manner in both BV2 and mouse macrophage, RAW264.7 cells. Furthermore, LA-Dec inhibited LPS-induced expressions of iNOS, COX-2, interleukin-6, tumor necrosis $factor-{\alpha}$, and $interleukin-1{\beta}$ mRNA in BV2 cells, whereas the same concentration of LA or Dec was ineffective. Signaling studies demonstrated that LA-Dec inhibited LPS-activated signal transducer and activator of transcription 3 and protein kinase B activation, but not nuclear factor-kappa B or mitogen-activated protein kinase signaling. The data implicate LA-Dec hybrid compound as a potential therapeutic agent for inflammatory diseases of the peripheral and central nervous systems.

Keywords

References

  1. Brown GC and Bal-Price A (2003) Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria. Mol Neurobiol 27, 325-355 https://doi.org/10.1385/MN:27:3:325
  2. Korhonen R, Lahti A, Kankaanranta H and Moilanen E (2005) Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy 4, 471-479 https://doi.org/10.2174/1568010054526359
  3. MacMicking J, Xie QW and Nathan C (1997) Nitric oxide and macrophage function. Annu Rev Immunol 15, 323-350 https://doi.org/10.1146/annurev.immunol.15.1.323
  4. Packer L, Witt EH and Tritschler HJ (1995) alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med 19, 227-250 https://doi.org/10.1016/0891-5849(95)00017-R
  5. Sola S, Mir MQ, Cheema FA et al (2005) Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study. Circulation 111, 343-348 https://doi.org/10.1161/01.CIR.0000153272.48711.B9
  6. Zhang Y, Han P, Wu N et al (2011) Amelioration of lipid abnormalities by alpha-lipoic acid through antioxidative and anti-inflammatory effects. Obesity 19, 1647-1653 https://doi.org/10.1038/oby.2011.121
  7. Bilska A and Wlodek L (2005) Lipoic acid - the drug of the future? Pharmacol Rep 57, 570-577
  8. Corson TW, Aberle N and Crews CM (2008) Design and applications of bifunctional small molecules: Why two heads are better than one. ACS Chem Biol 3, 677-692 https://doi.org/10.1021/cb8001792
  9. Li L, Li W, Jung SW, Lee YW and Kim YH (2011) Protective effects of decursin and decursinol angelate against amyloid beta-protein-induced oxidative stress in the PC12 cell line: the role of Nrf2 and antioxidant enzymes. Biosci Biotechnol Biochem 75, 434-442 https://doi.org/10.1271/bbb.100606
  10. Kang SY, Lee KY, Park MJ et al (2003) Decursin from Angelica gigas mitigates amnesia induced by scopolamine in mice. Neurobiol Learn Mem 79, 11-18 https://doi.org/10.1016/S1074-7427(02)00007-2
  11. Kang SY and Kim YC (2007) Decursinol and decursin protect primary cultured rat cortical cells from glutamateinduced neurotoxicity. J Pharm Pharmacol 59, 863-870 https://doi.org/10.1211/jpp.59.6.0013
  12. Lee TH, Park JH, Kim JD et al (2012) Protective effects of a novel synthetic alpha-lipoic acid-decursinol hybrid compound in experimentally induced transient cerebral ischemia. Cell Mol Neurobiol 32, 1209-1221 https://doi.org/10.1007/s10571-012-9861-z
  13. Kim WK, Hwang SY, Oh ES, Piao HZ, Kim KW and Han IO (2004) TGF-beta1 represses activation and resultant death of microglia via inhibition of phosphatidylinositol 3-kinase activity. J Immunol 172, 7015-7023 https://doi.org/10.4049/jimmunol.172.11.7015
  14. Hwang JS, An JM, Cho H, Lee SH, Park JH and Han IO (2015) A dopamine-alpha-lipoic acid hybridization compound and its acetylated form inhibit LPS-mediated inflammation. Eur J Pharmacol 746, 41-49 https://doi.org/10.1016/j.ejphar.2014.10.052
  15. Choi KH, Park MS and Kim HS (2015) Alpha-lipoic acid treatment is neurorestorative and promotes functional recovery after stroke in rats. Mol Brain 8, 9 https://doi.org/10.1186/s13041-015-0101-6
  16. Xie QW, Kashiwabara Y and Nathan C (1994) Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase. J Biol Chem 269, 4705-4708 https://doi.org/10.1016/S0021-9258(17)37600-7
  17. Kim HY, Park SJ, Joe EH and Jou I (2006) Raft-mediated Src homology 2 domain-containing proteintyrosine phosphatase 2 (SHP-2) regulation in microglia. J Biol Chem 281, 11872-11878 https://doi.org/10.1074/jbc.M511706200
  18. Jung EH, Hwang JS, Kwon MY et al (2016) A tryptaminepaeonol hybridization compound inhibits LPS-mediated inflammation in BV2 cells. Neurochem Int 100, 35-43 https://doi.org/10.1016/j.neuint.2016.08.010
  19. Suh HS, Kim MO and Lee SC (2005) Inhibition of granulocyte-macrophage colony-stimulating factor signaling and microglial proliferation by anti-CD45RO: role of Hck tyrosine kinase and phosphatidylinositol 3-kinase/Akt. J Immunol 174, 2712-2719 https://doi.org/10.4049/jimmunol.174.5.2712
  20. Murase S and McKay RD (2014) Neuronal activitydependent STAT3 localization to nucleus is dependent on Tyr-705 and Ser-727 phosphorylation in rat hippocampal neurons. Eur J Neurosci 39, 557-565 https://doi.org/10.1111/ejn.12412
  21. Nam HY, Nam JH, Yoon G et al (2018) Ibrutinib suppresses LPS-induced neuroinflammatory responses in BV2 microglial cells and wild-type mice. J Neuroinflammation 15, 271 https://doi.org/10.1186/s12974-018-1308-0
  22. Kim BR, Cho YC and Cho S (2018) Anti-inflammatory effects of a novel compound, MPQP, through the inhibition of IRAK1 signaling pathways in LPS-stimulated RAW 264.7 macrophages. BMB Rep 51, 308-313 https://doi.org/10.5483/BMBRep.2018.51.6.064