title: Therapeutic effect of Cryptotanshinone on collagen-induced arthritis in rats via inhibiting nuclear factor kappa B signaling pathway.
abstract: The discovery of new therapeutic drugs with the ability of preventing inflammation and joint destruction with less adverse effects is extremely urgent for rheumatoid arthritis (RA). Cryptotanshinone (CTS), an active component isolated from the root of Salvia miltiorrhiza Bunge, has been reported to have antibacterial and antitumor effects. However, its effects on RA have not been clearly elucidated. Here, we investigated the therapeutic effect of CTS on type II collagen-induced arthritis (CIA) in rats and explored the underlying mechanisms. Our results revealed that CTS treatment efficaciously ameliorated inflammation and joint destruction of rats with CIA. Both in vivo and in vitro studies showed that CTS suppressed the production of proinflammatory cytokines including interleukin 1β, tumor necrosis factor alpha, and interleukin 17α production and downregulated the production and activity of matrix metalloproteinase 9. By receptor activator of nuclear factor kappa B (NF-κB) ligand-induced bone marrow macrophages, we observed that CTS could inhibit osteoclast differentiation, which is critic for joint destruction. Further studies on inflammatory signaling revealed that CTS could inhibit the degradation of inhibitor of NF-κB (IκB) α in vivo and in vitro, prevent the nuclear translocation of NF-κB p65 induced by lipopolysaccharide in a time- and dose-dependent manner. By electrophoretic mobility shift assay and luciferase reporter assay, we found that CTS distinctively inhibited the NF-κB DNA binding activity and NF-κB-dependent luciferase activity. These results indicate that the therapeutic effect of CTS on CIA is accomplished mainly through the inhibition of NF-κB signaling. Our findings provide the evidence to develop CTS as a potential therapeutic agent for patients with RA.
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Shaogui
authors.initials: S
authors.lastname: Wang
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: JianMin
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Cuixian
authors.initials: C
authors.lastname: Li
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Lu
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China; Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China. Electronic address: 1247380682@qq.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Shen
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D001483:Base Sequence; D003094:Collagen / Q000009:adverse effects*; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016207:Cytokines; D017931:DNA Primers; D018836:Inflammation Mediators; D016328:NF-kappa B; D010616:Phenanthrenes; C037886:cryptotanshinone; D003094:Collagen