Anti-inflammatory Effects of Oroxylin A on RAW 264.7 Mouse Macrophages Induced with Polyinosinic-polycytidylic Acid

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2016 Jun 28

PMID 27347031

Citations 15

Authors

Ji Young Lee

Wansu Park

Affiliations

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Abstract

Oroxylin A (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; Baicalein 6-methyl ether) is an active flavonoid compound originally isolated from Scutellaria radix, which has been used to treat pulmonary infection in Korea, China, and Japan. Oroxylin A is known to possess dopamine reuptake inhibitor activity. However, the effects of oroxylin A on virus-induced macrophages has not been fully elucidated. In the present study, the anti-inflammatory effects of oroxylin A on double-stranded RNA-induced macrophages were examined. Production of nitric oxide (NO), various cytokines, as well as calcium release and the mRNA expression of signal transducer and activator of transcription 1 (STAT1) in dsRNA polyinosinic-polycytidylic acid (PIC)-induced RAW 264.7 mouse macrophages were evaluated. Oroxylin A restored the cell viability in PIC-induced RAW 264.7 mouse macrophages at concentrations of up to 50 µM. Additionally, oroxylin A significantly inhibited the production of nitric oxide (NO), interleukin (IL)-1α, IL-1β, IL-6, IL-10, interferon gamma-induced protein 10, granulocyte-colony stimulating factor (CSF), granulocyte macrophage-CSF, leukemia inhibitory factor (IL-6 class cytokine), lipopolysaccharide-induced CXC chemokine (LIX), monocyte chemoattractant protein 1, macrophage inflammatory protein (MIP)-1α, MIP-1β, MIP-2, Regulated on Activation, Normal T Expressed and Secreted, tumor necrosis factor-α, and vascular endothelial growth factor as well as calcium release and the mRNA expression of STAT1 in PIC-induced RAW 264.7 cells (P<0.05). Thus, the present results suggest that oroxylin A has anti-inflammatory properties, associated with its inhibition of NO, cytokines, chemokines and growth factors in PIC-induced macrophages via the calcium-STAT pathway.

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References

Yoon S, Lee Y, Park S, Kim H, Bae H, Kim H . Anti-inflammatory effects of Scutellaria baicalensis water extract on LPS-activated RAW 264.7 macrophages. J Ethnopharmacol. 2009; 125(2):286-90. DOI: 10.1016/j.jep.2009.06.027. View

Canna S, de Jesus A, Gouni S, Brooks S, Marrero B, Liu Y . An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet. 2014; 46(10):1140-6. PMC: 4177369. DOI: 10.1038/ng.3089. View

Lee J, Park W . Anti-inflammatory effect of myristicin on RAW 264.7 macrophages stimulated with polyinosinic-polycytidylic acid. Molecules. 2011; 16(8):7132-42. PMC: 6264243. DOI: 10.3390/molecules16087132. View

Riedemann N, Neff T, Guo R, Bernacki K, Laudes I, Sarma J . Protective effects of IL-6 blockade in sepsis are linked to reduced C5a receptor expression. J Immunol. 2002; 170(1):503-7. DOI: 10.4049/jimmunol.170.1.503. View

Wareing M, Lyon A, Lu B, Gerard C, Sarawar S . Chemokine expression during the development and resolution of a pulmonary leukocyte response to influenza A virus infection in mice. J Leukoc Biol. 2004; 76(4):886-95. DOI: 10.1189/jlb.1203644. View

Hui H, Yang H, Dai Q, Wang Q, Yao J, Zhao K . Oroxylin A inhibits ATRA-induced IL-6 expression involved in retinoic acid syndrome by down-regulating CHOP. Gene. 2014; 551(2):230-5. DOI: 10.1016/j.gene.2014.08.061. View

Srivastava M, Jung S, Wilhelm J, Fink L, Buhling F, Welte T . The inflammatory versus constitutive trafficking of mononuclear phagocytes into the alveolar space of mice is associated with drastic changes in their gene expression profiles. J Immunol. 2005; 175(3):1884-93. DOI: 10.4049/jimmunol.175.3.1884. View

Yuk S, Lim E, Lee J, Lee Y, Kim Y, Lee T . Antiinflammatory effects of Epimedium brevicornum water extract on lipopolysaccharide-activated RAW264.7 macrophages. Phytother Res. 2010; 24(12):1781-7. DOI: 10.1002/ptr.3161. View

Carrithers M . Innate immune viral recognition: relevance to CNS infections. Handb Clin Neurol. 2014; 123:215-23. DOI: 10.1016/B978-0-444-53488-0.00009-2. View

10.

Gao H, Hong J . Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol. 2008; 29(8):357-65. PMC: 4794280. DOI: 10.1016/j.it.2008.05.002. View

11.

Zhou D, Diao B, Zhou W, Feng J . Oroxylin A Inhibits Allergic Airway Inflammation in Ovalbumin (OVA)-Induced Asthma Murine Model. Inflammation. 2016; 39(2):867-72. DOI: 10.1007/s10753-016-0317-3. View

12.

Sakaguchi S, Wing K . Immunology. Damping by depletion. Science. 2011; 332(6029):542-3. DOI: 10.1126/science.1206122. View

13.

Li H, Nie F, Liu W, Dai Q, Lu N, Qi Q . Apoptosis induction of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo. Toxicology. 2009; 257(1-2):80-5. DOI: 10.1016/j.tox.2008.12.011. View

14.

Ruddy M, Shen F, Smith J, Sharma A, Gaffen S . Interleukin-17 regulates expression of the CXC chemokine LIX/CXCL5 in osteoblasts: implications for inflammation and neutrophil recruitment. J Leukoc Biol. 2004; 76(1):135-44. DOI: 10.1189/jlb.0204065. View

15.

Kim D, Kim S, Jeon S, Son K, Lee S, Yoon B . The effects of acute and repeated oroxylin A treatments on Abeta(25-35)-induced memory impairment in mice. Neuropharmacology. 2008; 55(5):639-47. DOI: 10.1016/j.neuropharm.2008.05.019. View

16.

Zong Y, Sun L, Liu B, Deng Y, Zhan D, Chen Y . Resveratrol inhibits LPS-induced MAPKs activation via activation of the phosphatidylinositol 3-kinase pathway in murine RAW 264.7 macrophage cells. PLoS One. 2012; 7(8):e44107. PMC: 3432093. DOI: 10.1371/journal.pone.0044107. View

17.

Timmins J, Ozcan L, Seimon T, Li G, Malagelada C, Backs J . Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways. J Clin Invest. 2009; 119(10):2925-41. PMC: 2752072. DOI: 10.1172/JCI38857. View

18.

Spite M, Norling L, Summers L, Yang R, Cooper D, Petasis N . Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature. 2009; 461(7268):1287-91. PMC: 2779525. DOI: 10.1038/nature08541. View

19.

Ye M, Wang Q, Zhang W, Li Z, Wang Y, Hu R . Oroxylin A exerts anti-inflammatory activity on lipopolysaccharide-induced mouse macrophage via Nrf2/ARE activation. Biochem Cell Biol. 2014; 92(5):337-48. DOI: 10.1139/bcb-2014-0030. View

20.

Qiao C, Wei L, Dai Q, Zhou Y, Yin Q, Li Z . UCP2-related mitochondrial pathway participates in oroxylin A-induced apoptosis in human colon cancer cells. J Cell Physiol. 2014; 230(5):1054-63. DOI: 10.1002/jcp.24833. View