•  
  •  
 

Abstract

In the paper, the protective effect of maslinic acid (MA) on LPS-induced inflammatory response in RAW264.7 cells was investigated, and its inhibition of transcription 3 (STAT3) phosphorylation, a signal transducer and activator, was also explored. NO generation was measured by Griess method. The levels of IL-6, IL-1β and IL-10 were detected by ELISA. The relative expression of iNOS, p-STAT3, p-JAK2 and SOCS3 were determined by Western blot. The release of reactive oxygen (ROS) was evaluated using DCFH-DA fluorescence. Results showed that MA could significantly inhibit the NO generation and the production of ROS. MA also decreased the releases of IL-6 and IL-1β, increased the content of IL-10. The expression of iNOS in LPS-induced RAW264.7 cells was inhibited by MA. In addition, the phosphorylation and the nuclear translocation of STAT3 could be suppressed by MA in dose and time-dependent manner. The phosphorylation of JAK2 was also inhibited by MA, while the expression of SOCS3 could be activated. These results suggested that MA protected against LPS-induced inflammatory response in RAW264.7 cells, and its mechanism was probably associated with the inhibition of the phosphorylation of STAT3.

Publication Date

6-28-2021

First Page

36

Last Page

42

DOI

10.13652/j.issn.1003-5788.2021.06.007

References

[1] LI C H, YANG Z F, LI Z X, et al. Maslinic acid suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss by regulating RANKL-mediated NF-κB and MAPK Signaling pathways[J]. Journal of Bone and Mineral Research, 2011, 26(3): 644-656.
[2] ALVAREZ M E, ROTELLI A E, PELZER L E, et al. Phytochemical study and anti-inflammatory properties of Lampaya hieronymi Schum. ex Moldenke[J]. Farmaco, 2000, 55(6/7): 502-505.
[3] MRQUEZ MARTN A, DE LA PUERTA VZQUEZ R, FERNNDEZ-ARCHE A, et al. Supressive effect of maslinic acid from pomace olive oil on oxidative stress and cytokine production in stimulated murine macrophages[J]. Free Radical Research, 2006, 40(3): 295-302.
[4] MKHWANAZI B N, SERUMULA M R, MYBURG R B, et al. Antioxidant effects of maslinic acid in livers, hearts and kidneys of streptozotocin-induced diabetic rats: Effects on kidney function[J]. Renal Failure, 2014, 36(3): 419-431.
[5] 李桂兰, 郑开丰, 秦韶刚, 等. 山楂酸对H2O2诱导的BRL-3A细胞氧化损伤及p38和Nrf2/HO-1通路的影响[J]. 中国细胞生物学学报, 2020, 42(3): 453-460.
[6] LIU J, SUN H B, DUAN W G, et al. Maslinic acid reduces blood glucose in KK-Ay mice[J]. Biol Pharm Bull, 2007, 30(11): 2 075-2 078.
[7] 王乐旬, 吴惠娟, 张盛昔, 等. 山楂酸对 LPS诱导RAW264.7细胞炎症反应的作用及机制[J]. 广东药科大学学报, 2020, 36(2): 219-224.
[8] MACMICKING J, XIE Q W, NATHAN C. Nitric oxide and macrophage function[J]. Annu Rev Immunol, 1997, 15: 323-350.
[9] CHESROWN S E, MONNIER J, VISNER G, et al. Regulation of inducible nitric oxide synthase mRNA levels by LPS, INF-gamma, TGF-beta, and IL-10 in murine macrophage cell lines and rat peritoneal macrophages[J]. Biochem Biophys Res Commun, 1994, 200(1): 126-134.
[10] SHUAI K, LIU B. Regulation of JAK-STAT signalling in the immune system[J]. Nat Rev Immunol, 2003, 3(11): 900-911.
[11] HU Y S, HAN X, LIU X H. STAT3: A potential drug target for tumor and inflammation[J]. Curr Top Med Chem, 2019, 19(15): 1 305-1 317.
[12] WANG Y Y, DIAO B Z, ZHONG L H, et al. Maslinic acid protects against lipopolysaccharide/d-galactosamine-induced acute liver injury in mice[J]. Microb Pathog, 2018, 119: 49-53.
[13] 陈磊. 山楂酸对LPS诱导的RAW264.7细胞的抗炎作用及其机制研究[D]. 太谷: 山西农业大学, 2019: 12-17.
[14] ANNE F McGettrick, LUKE A J O'Neill. How metabolism generates signals during innate immunity and inflammation[J]. J Biol Chem, 2013, 288(32): 22 893-22 898.
[15] GABRYSOVA L, HOWES A, SARAIVA M, et al. The regulation of IL-10 expression[J]. Curr Top Microbiol Immunol, 2014, 380: 157-190.
[16] MARTN M C, MARTINEZ A, MENDOZA J L, et al. Influence of the inducible nitric oxide synthase gene (NOS2A) on inflammatory bowel disease susceptibility[J]. Immuno Genetics, 2007, 59(11): 833-837.
[17] BI X X, WANG P, MA Q J, et al. Anti-inflammatory activities and liver protection of alisol F and 25-anhydroalisol F through the inhibition of MAPK, STAT3, and NF-κB activation in vitro and in vivo[J]. Molecules, 2017, 22(6): 951.
[18] AGGARWAL B B, KUNNUMAKKARA A B, HARIKUMAR K B, et al. Signal transducer and activator of transcription-3, inflammation, and cancer: How intimate is the relationship? [J]. Ann N Y Acad Sci, 2009, 1 171: 59-76.
[19] SONG L X, TURKSON J, KARRAS J G, et al. Activation of Stat3 by receptor tyrosine kinases and cytokines regulates survival in human non-small cell carcinoma cells[J]. Oncogene, 2003, 22(27): 4 150-4 165.
[20] MA Y F, TANG T, SHENG L L, et al. Aloin suppresses lipopolysaccharide induced inflammation by inhibiting JAK1 STAT1/3 activation and ROS production in RAW264.7 cells[J]. Int J Mol Med, 2018, 42(4): 1 925-1 934.
[21] KOU X J, QI S M, DAI W X, et al. Arctigenin inhibits lipopolysaccharide-induced iNOS expression in RAW264.7 cells through suppressing JAK-STAT signal pathway[J]. Int Immunopharmacol, 2011, 11(8): 1 095-1 102.
[22] LINOSSI E M, CALLEJA D J, NICHOLSON S E. Understanding SOCS protein specificity[J]. Growth Factors, 2018, 36(3/4): 104-117.
[23] D'AUTRAUX B, TOLEDANO M B. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis[J]. Nature Reviews Molecular Cell Biology, 2007, 8(10): 813-824.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.