Jing Jing Liang1, Hao Ran Li2, Yong Chen3, Chen Zhang4, Da Gui Chen5, Zhi Chao Liang6, Ye Qing Shi2, Lan Ling Zhang2, Lei Xin2, Dong Bao Zhao7. 1. Department of Rheumatology and Immunology, Changhai Hospital, The Second Military Medical University/Naval Medical University, Shanghai, China; Department of Endocrinology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. 2. Department of Rheumatology and Immunology, Changhai Hospital, The Second Military Medical University/Naval Medical University, Shanghai, China. 3. Department of Plastic and Reconstructive Surgery, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China. 4. Department of Joint Bone Disease Surgery, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China. 5. Second Military Medical University/Naval Medical University, Shanghai, China. 6. Department of Joint Bone Disease Surgery, Guanghua Hospital, Shanghai, China. 7. Department of Rheumatology and Immunology, Changhai Hospital, The Second Military Medical University/Naval Medical University, Shanghai, China. Electronic address: dongbaozhao@163.com.
Abstract
BACKGROUND: Diallyl Trisulfide (DATS) is an organosulfur compound extracted from garlic bulb, and exerts cardioprotective, anti-inflammatory, antioxidant, antimicrobial and anticancer effects. But its role in the pathogenesis of rheumatoid arthritis (RA) is unknown. Here we explored the influence of DATS on human fibroblast-like synoviocytes (FLS) isolated from RA patients and a mouse model of collagen-induced arthritis (CIA) and the underlying mechanism. METHODS: RA-FLS were cultured and treated with different concentrations of DATS. The CCK8 assay was used to assess cell proliferation while cell apoptosis was detected by flow cytometry and western blot. The IL-8, IL-6 and IL-1β levels were determined using RT-qPCR and ELISA assay. The expression of proteins of the NF-κB and Wnt pathways were measured using western blot. Furthermore, the effect of DATS was also explored in vivo using the collagen-induced arthritis mouse model. The Th17/Treg pattern obtain from cells of spleen of collagen-induced arthritis mouse model was detected by flow cytometry. RESULTS: Our results showed that DATS could decrease cell viability and introduce apoptosis in RA-FLS. Furthermore, DATS significantly attenuated the production of key inflammatory cytokines induced by RA-FLS cells following treatment with tumor necrosis α (TNF-α) at a concentration of 100 μM or higher. This was due to its inhibitory effect on the NF-κB and Wnt pathway signaling in RA-FLS. Additionally, DATS decreased the production of inflammatory cytokines and regulated the immune function by restoring the balance between Th17 and Treg in CIA mouse model. CONCLUSIONS: In conclusion, DATS may serve as a potential curative agent for RA.
BACKGROUND:Diallyl Trisulfide (DATS) is an organosulfur compound extracted from garlic bulb, and exerts cardioprotective, anti-inflammatory, antioxidant, antimicrobial and anticancer effects. But its role in the pathogenesis of rheumatoid arthritis (RA) is unknown. Here we explored the influence of DATS on human fibroblast-like synoviocytes (FLS) isolated from RA patients and a mouse model of collagen-induced arthritis (CIA) and the underlying mechanism. METHODS: RA-FLS were cultured and treated with different concentrations of DATS. The CCK8 assay was used to assess cell proliferation while cell apoptosis was detected by flow cytometry and western blot. The IL-8, IL-6 and IL-1β levels were determined using RT-qPCR and ELISA assay. The expression of proteins of the NF-κB and Wnt pathways were measured using western blot. Furthermore, the effect of DATS was also explored in vivo using the collagen-induced arthritismouse model. The Th17/Treg pattern obtain from cells of spleen of collagen-induced arthritismouse model was detected by flow cytometry. RESULTS: Our results showed that DATS could decrease cell viability and introduce apoptosis in RA-FLS. Furthermore, DATS significantly attenuated the production of key inflammatory cytokines induced by RA-FLS cells following treatment with tumor necrosis α (TNF-α) at a concentration of 100 μM or higher. This was due to its inhibitory effect on the NF-κB and Wnt pathway signaling in RA-FLS. Additionally, DATS decreased the production of inflammatory cytokines and regulated the immune function by restoring the balance between Th17 and Treg in CIA mouse model. CONCLUSIONS: In conclusion, DATS may serve as a potential curative agent for RA.
Authors: István Z Bátai; Ágnes Dombi; Éva Borbély; Ádám Fehér; Ferenc Papp; Zoltan Varga; Attila Mócsai; Zsuzsanna Helyes; Erika Pintér; Gábor Pozsgai Journal: Pharmaceuticals (Basel) Date: 2022-05-27
Authors: Hao Geng; Wenhao Guo; Lei Feng; Dongdong Xie; Liangkuan Bi; Yi Wang; Tao Zhang; Zhaofeng Liang; Dexin Yu Journal: J Int Med Res Date: 2021-03 Impact factor: 1.671