Xuelian injection ameliorates complete Freund's adjuvant-induced acute arthritis in rats via inhibiting TLR4 signaling
Background: Xuelian injection (XI), a classic preparation extracted from Saussureae Involucratae Herba, has been clinically used to manage rheumatoid arthritis (RA) for nearly twenty years in China. However, the underlying anti-RA mechanism of XI remains unclear. In this study, complete Freund'...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023088436 |
| _version_ | 1827615924941750272 |
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| author | Li-Shan Yan Brian Chi-Yan Cheng Yi-Wei Wang Shuo-Feng Zhang Xin-Yu Qiu Jian-Ying Kang Chao Zhang Zhan-Hong Jia Gan Luo Yi Zhang |
| author_facet | Li-Shan Yan Brian Chi-Yan Cheng Yi-Wei Wang Shuo-Feng Zhang Xin-Yu Qiu Jian-Ying Kang Chao Zhang Zhan-Hong Jia Gan Luo Yi Zhang |
| author_sort | Li-Shan Yan |
| collection | DOAJ |
| description | Background: Xuelian injection (XI), a classic preparation extracted from Saussureae Involucratae Herba, has been clinically used to manage rheumatoid arthritis (RA) for nearly twenty years in China. However, the underlying anti-RA mechanism of XI remains unclear. In this study, complete Freund's adjuvant (CFA)-induced acute arthritic model was used to examine the anti-RA effects of XI in vivo. The molecular mechanisms of this action were further investigated using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods: XI and XI freeze dried powder were characterized by UPLC analysis. CD68 and TLR4 expression in the ankle joints was measured by immunohistochemistry. The secretion of inflammatory mediators was detected by ELISA. The expression levels of TLR4 involved components were measured by Western blotting. The localization of transcription factors was measured by immunofluorescence assay. Results: XI treatment ameliorated arthritic symptoms induced by CFA in the ankle joints of rats. The serum levels of inflammatory mediators, including TNF-α, MCP-1, and Rantes were decreased by XI treatment. The elevation of CD68 and TLR4 levels in ankle joints caused by CFA was suppressed by XI treatment. Moreover, XI treatment inhibited the secretion of nitric oxide and prostaglandin E2 in LPS-treated RAW264.7 macrophages. The expression of their enzymes iNOS and COX-2 was also decreased after XI treatment. The production of inflammatory mediators, including TNF-α, IL-6, IL-1β, MCP-1, MIP-1α, and Rantes was reduced by XI treatment in LPS-stimulated RAW264.7 cells. The phosphorylation of p38, JNK, ERK, TBK1, IKKα/β, IκB, p65, c-Jun, and IRF3 was reduced after XI treatment. Additionally, the expression levels of nuclear proteins of p65, c-Jun, and IRF3 were inhibited by XI treatment. Conclusions: Taken together, XI possesses potential anti-RA effect and the underlying mechanism may be closely associated with the inhibition of TLR4 signaling. Our findings provide further pharmacological justifications for the clinical use of XI in RA treatment. |
| first_indexed | 2024-03-09T09:18:34Z |
| format | Article |
| id | doaj.art-25da0cb2774f4e11962f813f66b52b9d |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-09T09:18:34Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-25da0cb2774f4e11962f813f66b52b9d2023-12-02T07:03:32ZengElsevierHeliyon2405-84402023-11-01911e21635Xuelian injection ameliorates complete Freund's adjuvant-induced acute arthritis in rats via inhibiting TLR4 signalingLi-Shan Yan0Brian Chi-Yan Cheng1Yi-Wei Wang2Shuo-Feng Zhang3Xin-Yu Qiu4Jian-Ying Kang5Chao Zhang6Zhan-Hong Jia7Gan Luo8Yi Zhang9School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR ChinaHong Kong Productivity Council, Hong Kong, PR ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR China; Corresponding author.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR China; Corresponding author.Background: Xuelian injection (XI), a classic preparation extracted from Saussureae Involucratae Herba, has been clinically used to manage rheumatoid arthritis (RA) for nearly twenty years in China. However, the underlying anti-RA mechanism of XI remains unclear. In this study, complete Freund's adjuvant (CFA)-induced acute arthritic model was used to examine the anti-RA effects of XI in vivo. The molecular mechanisms of this action were further investigated using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods: XI and XI freeze dried powder were characterized by UPLC analysis. CD68 and TLR4 expression in the ankle joints was measured by immunohistochemistry. The secretion of inflammatory mediators was detected by ELISA. The expression levels of TLR4 involved components were measured by Western blotting. The localization of transcription factors was measured by immunofluorescence assay. Results: XI treatment ameliorated arthritic symptoms induced by CFA in the ankle joints of rats. The serum levels of inflammatory mediators, including TNF-α, MCP-1, and Rantes were decreased by XI treatment. The elevation of CD68 and TLR4 levels in ankle joints caused by CFA was suppressed by XI treatment. Moreover, XI treatment inhibited the secretion of nitric oxide and prostaglandin E2 in LPS-treated RAW264.7 macrophages. The expression of their enzymes iNOS and COX-2 was also decreased after XI treatment. The production of inflammatory mediators, including TNF-α, IL-6, IL-1β, MCP-1, MIP-1α, and Rantes was reduced by XI treatment in LPS-stimulated RAW264.7 cells. The phosphorylation of p38, JNK, ERK, TBK1, IKKα/β, IκB, p65, c-Jun, and IRF3 was reduced after XI treatment. Additionally, the expression levels of nuclear proteins of p65, c-Jun, and IRF3 were inhibited by XI treatment. Conclusions: Taken together, XI possesses potential anti-RA effect and the underlying mechanism may be closely associated with the inhibition of TLR4 signaling. Our findings provide further pharmacological justifications for the clinical use of XI in RA treatment.http://www.sciencedirect.com/science/article/pii/S2405844023088436Xuelian injectionRheumatoid arthritisRAW264.7 macrophagesTLR4 signaling pathways |
| spellingShingle | Li-Shan Yan Brian Chi-Yan Cheng Yi-Wei Wang Shuo-Feng Zhang Xin-Yu Qiu Jian-Ying Kang Chao Zhang Zhan-Hong Jia Gan Luo Yi Zhang Xuelian injection ameliorates complete Freund's adjuvant-induced acute arthritis in rats via inhibiting TLR4 signaling Heliyon Xuelian injection Rheumatoid arthritis RAW264.7 macrophages TLR4 signaling pathways |
| title | Xuelian injection ameliorates complete Freund's adjuvant-induced acute arthritis in rats via inhibiting TLR4 signaling |
| title_full | Xuelian injection ameliorates complete Freund's adjuvant-induced acute arthritis in rats via inhibiting TLR4 signaling |
| title_fullStr | Xuelian injection ameliorates complete Freund's adjuvant-induced acute arthritis in rats via inhibiting TLR4 signaling |
| title_full_unstemmed | Xuelian injection ameliorates complete Freund's adjuvant-induced acute arthritis in rats via inhibiting TLR4 signaling |
| title_short | Xuelian injection ameliorates complete Freund's adjuvant-induced acute arthritis in rats via inhibiting TLR4 signaling |
| title_sort | xuelian injection ameliorates complete freund s adjuvant induced acute arthritis in rats via inhibiting tlr4 signaling |
| topic | Xuelian injection Rheumatoid arthritis RAW264.7 macrophages TLR4 signaling pathways |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023088436 |
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