Securidaca inappendiculata-Derived Xanthones Protected Joints from Degradation in Male Rats with Collagen-Induced Arthritis by Regulating PPAR-γ Signaling
Jian Zuo,1– 3,* Meng-Qing Tao,1,3,* Xin-Yue Wu,4 Tian-Tian Jiang,1 Opeyemi Joshua Olatunji,5 Jiyang Dong,4 Jun Han,6 Cong-Lan Ji7 1Department of Traditional Chinese Medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, 241000, People’s Repub...
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Dove Medical Press
2021
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peroxisome proliferators-activated receptor gamma (ppar-γ) energy metabolism rheumatoid arthritis metabolomics macrophage inflammation Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
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peroxisome proliferators-activated receptor gamma (ppar-γ) energy metabolism rheumatoid arthritis metabolomics macrophage inflammation Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Zuo J Tao MQ Wu XY Jiang TT Olatunji OJ Dong J Han J Ji CL Securidaca inappendiculata-Derived Xanthones Protected Joints from Degradation in Male Rats with Collagen-Induced Arthritis by Regulating PPAR-γ Signaling |
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Jian Zuo,1– 3,* Meng-Qing Tao,1,3,* Xin-Yue Wu,4 Tian-Tian Jiang,1 Opeyemi Joshua Olatunji,5 Jiyang Dong,4 Jun Han,6 Cong-Lan Ji7 1Department of Traditional Chinese Medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, 241000, People’s Republic of China; 2Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, 241000, People’s Republic of China; 3Research Center of Integration of Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu, 241000, People’s Republic of China; 4Department of Electronic Science, Xiamen University, Xiamen, 361005, People’s Republic of China; 5Faculty of Traditional Thai Medicine, Prince of Songkla University, Hat Yai, 90112, Thailand; 6Drug Research and Development Center, School of Pharmacy, Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of China; 7School of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, 241000, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun HanDrug Research and Development Center, School of Pharmacy, Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of ChinaEmail hanjun@wnmc.edu.cnCong-Lan JiSchool of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, 241000, Anhui, People’s Republic of ChinaEmail 37709103@qq.comBackground: The bark of Securidaca inappendiculata Hassk. is traditionally used for treating inflammatory diseases and bone fractures in China. We have previously validated the xanthone-enriched fraction (XRF) of S. inappendiculata with anti-rheumatic potentials, but mechanism underlying the joints protective effects is still largely unknown.Materials and Methods: The male rats with collagen-induced arthritis (CIA) were treated with XRF. The therapeutic efficacy of XRF was evaluated by arthritis score changes, morphological observation of paws, histological examinations and serological analyses. Protein expression in tissues and cells was investigated by either immunohistochemical or immunoblotting methods, while levels of mRNA expression were investigated by RT-qPCR. Metabolites in serum were detected by LC-MS approach. The joints homogenates were used for analyzing possible targeted genes by genome microarray analyses.Results: Treatment with XRF and methotrexate (MTX) led to significant decrease in arthritis scores, and alleviated deformation of paws in CIA rats. In addition, XRF and MTX reduced circulating TNF-α, IL-1β and IL-17α in the serum and down-regulated TLR4/NF-κB and JNK pathways in joints of CIA rats. Compared to MTX, XRF-loading microemulsion significantly protected joints, which was accompanied by dramatic decrease in MMP3. Differential genes-based KEGG enrichment and metabolomics analysis suggested that XRF reduced fatty acids biosynthesis by regulating PPAR-γ signaling. S inappendiculata-derived 1,7-dihydroxy-3,4-dimethoxyxanthone (XAN) up-regulated PPAR-γ expression in macrophages, but suppressed it in pre-adipocytes in vitro, which was synchronized with SIRT1 changes. Adiponectin production and SCD-1 expression in pre-adipocytes were also decreased. Aside the direct inhibition on MMP3 expression in synovioblast, the presence of XAN in macrophages-pre-adipocytes co-culture system further reinforced this effect.Conclusion: This study revealed the joint protective advantages of the bioactive fraction from S. inappendiculata in CIA rats over MTX, and demonstrated that S. inappendiculata-derived xanthones suppressed the erosive nature of synovioblast acquired under inflammatory circumstances by regulating PPAR-γ signaling-controlled metabolism-immunity feedback.Keywords: peroxisome proliferators-activated receptor gamma, PPAR-γ, energy metabolism, rheumatoid arthritis, metabolomics, macrophage, inflammation |
| format |
article |
| author |
Zuo J Tao MQ Wu XY Jiang TT Olatunji OJ Dong J Han J Ji CL |
| author_facet |
Zuo J Tao MQ Wu XY Jiang TT Olatunji OJ Dong J Han J Ji CL |
| author_sort |
Zuo J |
| title |
Securidaca inappendiculata-Derived Xanthones Protected Joints from Degradation in Male Rats with Collagen-Induced Arthritis by Regulating PPAR-γ Signaling |
| title_short |
Securidaca inappendiculata-Derived Xanthones Protected Joints from Degradation in Male Rats with Collagen-Induced Arthritis by Regulating PPAR-γ Signaling |
| title_full |
Securidaca inappendiculata-Derived Xanthones Protected Joints from Degradation in Male Rats with Collagen-Induced Arthritis by Regulating PPAR-γ Signaling |
| title_fullStr |
Securidaca inappendiculata-Derived Xanthones Protected Joints from Degradation in Male Rats with Collagen-Induced Arthritis by Regulating PPAR-γ Signaling |
| title_full_unstemmed |
Securidaca inappendiculata-Derived Xanthones Protected Joints from Degradation in Male Rats with Collagen-Induced Arthritis by Regulating PPAR-γ Signaling |
| title_sort |
securidaca inappendiculata-derived xanthones protected joints from degradation in male rats with collagen-induced arthritis by regulating ppar-γ signaling |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/e033dac93f3442e39cbafb7da2546823 |
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oai:doaj.org-article:e033dac93f3442e39cbafb7da25468232021-12-02T14:12:25ZSecuridaca inappendiculata-Derived Xanthones Protected Joints from Degradation in Male Rats with Collagen-Induced Arthritis by Regulating PPAR-γ Signaling1178-7031https://doaj.org/article/e033dac93f3442e39cbafb7da25468232021-02-01T00:00:00Zhttps://www.dovepress.com/securidaca-inappendiculata-derived-xanthones-protected-joints-from-deg-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Jian Zuo,1– 3,* Meng-Qing Tao,1,3,* Xin-Yue Wu,4 Tian-Tian Jiang,1 Opeyemi Joshua Olatunji,5 Jiyang Dong,4 Jun Han,6 Cong-Lan Ji7 1Department of Traditional Chinese Medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, 241000, People’s Republic of China; 2Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, 241000, People’s Republic of China; 3Research Center of Integration of Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu, 241000, People’s Republic of China; 4Department of Electronic Science, Xiamen University, Xiamen, 361005, People’s Republic of China; 5Faculty of Traditional Thai Medicine, Prince of Songkla University, Hat Yai, 90112, Thailand; 6Drug Research and Development Center, School of Pharmacy, Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of China; 7School of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, 241000, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun HanDrug Research and Development Center, School of Pharmacy, Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of ChinaEmail hanjun@wnmc.edu.cnCong-Lan JiSchool of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, 241000, Anhui, People’s Republic of ChinaEmail 37709103@qq.comBackground: The bark of Securidaca inappendiculata Hassk. is traditionally used for treating inflammatory diseases and bone fractures in China. We have previously validated the xanthone-enriched fraction (XRF) of S. inappendiculata with anti-rheumatic potentials, but mechanism underlying the joints protective effects is still largely unknown.Materials and Methods: The male rats with collagen-induced arthritis (CIA) were treated with XRF. The therapeutic efficacy of XRF was evaluated by arthritis score changes, morphological observation of paws, histological examinations and serological analyses. Protein expression in tissues and cells was investigated by either immunohistochemical or immunoblotting methods, while levels of mRNA expression were investigated by RT-qPCR. Metabolites in serum were detected by LC-MS approach. The joints homogenates were used for analyzing possible targeted genes by genome microarray analyses.Results: Treatment with XRF and methotrexate (MTX) led to significant decrease in arthritis scores, and alleviated deformation of paws in CIA rats. In addition, XRF and MTX reduced circulating TNF-α, IL-1β and IL-17α in the serum and down-regulated TLR4/NF-κB and JNK pathways in joints of CIA rats. Compared to MTX, XRF-loading microemulsion significantly protected joints, which was accompanied by dramatic decrease in MMP3. Differential genes-based KEGG enrichment and metabolomics analysis suggested that XRF reduced fatty acids biosynthesis by regulating PPAR-γ signaling. S inappendiculata-derived 1,7-dihydroxy-3,4-dimethoxyxanthone (XAN) up-regulated PPAR-γ expression in macrophages, but suppressed it in pre-adipocytes in vitro, which was synchronized with SIRT1 changes. Adiponectin production and SCD-1 expression in pre-adipocytes were also decreased. Aside the direct inhibition on MMP3 expression in synovioblast, the presence of XAN in macrophages-pre-adipocytes co-culture system further reinforced this effect.Conclusion: This study revealed the joint protective advantages of the bioactive fraction from S. inappendiculata in CIA rats over MTX, and demonstrated that S. inappendiculata-derived xanthones suppressed the erosive nature of synovioblast acquired under inflammatory circumstances by regulating PPAR-γ signaling-controlled metabolism-immunity feedback.Keywords: peroxisome proliferators-activated receptor gamma, PPAR-γ, energy metabolism, rheumatoid arthritis, metabolomics, macrophage, inflammationZuo JTao MQWu XYJiang TTOlatunji OJDong JHan JJi CLDove Medical Pressarticleperoxisome proliferators-activated receptor gamma (ppar-γ)energy metabolismrheumatoid arthritismetabolomicsmacrophageinflammationPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 395-411 (2021) |