In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and In Vivo Analysis of Its Therapeutic Potential in Osteoarthritis
Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory an...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-05-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/9/6/615 |
| _version_ | 1797532180543438848 |
|---|---|
| author | Shang-En Huang Erna Sulistyowati Yu-Ying Chao Bin-Nan Wu Zen-Kong Dai Jong-Hau Hsu Jwu-Lai Yeh |
| author_facet | Shang-En Huang Erna Sulistyowati Yu-Ying Chao Bin-Nan Wu Zen-Kong Dai Jong-Hau Hsu Jwu-Lai Yeh |
| author_sort | Shang-En Huang |
| collection | DOAJ |
| description | Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA. |
| first_indexed | 2024-03-10T10:55:28Z |
| format | Article |
| id | doaj.art-4797bc1175c24bf3874cc73c409ceba3 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T10:55:28Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-4797bc1175c24bf3874cc73c409ceba32023-11-21T21:53:43ZengMDPI AGBiomedicines2227-90592021-05-019661510.3390/biomedicines9060615In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and In Vivo Analysis of Its Therapeutic Potential in OsteoarthritisShang-En Huang0Erna Sulistyowati1Yu-Ying Chao2Bin-Nan Wu3Zen-Kong Dai4Jong-Hau Hsu5Jwu-Lai Yeh6Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanOsteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.https://www.mdpi.com/2227-9059/9/6/615xanthine-derived KMUP-1anti-inflammationNF-κBSIRT1osteoarthritis |
| spellingShingle | Shang-En Huang Erna Sulistyowati Yu-Ying Chao Bin-Nan Wu Zen-Kong Dai Jong-Hau Hsu Jwu-Lai Yeh In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and In Vivo Analysis of Its Therapeutic Potential in Osteoarthritis Biomedicines xanthine-derived KMUP-1 anti-inflammation NF-κB SIRT1 osteoarthritis |
| title | In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and In Vivo Analysis of Its Therapeutic Potential in Osteoarthritis |
| title_full | In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and In Vivo Analysis of Its Therapeutic Potential in Osteoarthritis |
| title_fullStr | In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and In Vivo Analysis of Its Therapeutic Potential in Osteoarthritis |
| title_full_unstemmed | In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and In Vivo Analysis of Its Therapeutic Potential in Osteoarthritis |
| title_short | In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and In Vivo Analysis of Its Therapeutic Potential in Osteoarthritis |
| title_sort | in vitro evaluation of the anti inflammatory effect of kmup 1 and in vivo analysis of its therapeutic potential in osteoarthritis |
| topic | xanthine-derived KMUP-1 anti-inflammation NF-κB SIRT1 osteoarthritis |
| url | https://www.mdpi.com/2227-9059/9/6/615 |
| work_keys_str_mv | AT shangenhuang invitroevaluationoftheantiinflammatoryeffectofkmup1andinvivoanalysisofitstherapeuticpotentialinosteoarthritis AT ernasulistyowati invitroevaluationoftheantiinflammatoryeffectofkmup1andinvivoanalysisofitstherapeuticpotentialinosteoarthritis AT yuyingchao invitroevaluationoftheantiinflammatoryeffectofkmup1andinvivoanalysisofitstherapeuticpotentialinosteoarthritis AT binnanwu invitroevaluationoftheantiinflammatoryeffectofkmup1andinvivoanalysisofitstherapeuticpotentialinosteoarthritis AT zenkongdai invitroevaluationoftheantiinflammatoryeffectofkmup1andinvivoanalysisofitstherapeuticpotentialinosteoarthritis AT jonghauhsu invitroevaluationoftheantiinflammatoryeffectofkmup1andinvivoanalysisofitstherapeuticpotentialinosteoarthritis AT jwulaiyeh invitroevaluationoftheantiinflammatoryeffectofkmup1andinvivoanalysisofitstherapeuticpotentialinosteoarthritis |