Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route in osteoarthritis
1. Abstract: Objective: Osteoarthritis (OA), the most prevalent form of arthritis, impacts approximately 10% of men and 18% of women aged above 60 years. Currently, a complete cure for OA remains elusive, making clinical management challenging. The traditional Chinese herb Notopterygium incisum, in...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024041252 |
| _version_ | 1797224157608411136 |
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| author | Ko-Ta Chen Chi-Tai Yeh Vijesh Kumar Yadav Narpati Wesa Pikatan Iat-Hang Fong Wei-Hwa Lee Yen-Shuo Chiu |
| author_facet | Ko-Ta Chen Chi-Tai Yeh Vijesh Kumar Yadav Narpati Wesa Pikatan Iat-Hang Fong Wei-Hwa Lee Yen-Shuo Chiu |
| author_sort | Ko-Ta Chen |
| collection | DOAJ |
| description | 1. Abstract: Objective: Osteoarthritis (OA), the most prevalent form of arthritis, impacts approximately 10% of men and 18% of women aged above 60 years. Currently, a complete cure for OA remains elusive, making clinical management challenging. The traditional Chinese herb Notopterygium incisum, integral to the Juanbi pill for rheumatism, shows promise in safeguarding chondrocytes through its strong anti-inflammatory effects. Methods: To explore the protective effect of notopterol and miRNA (has-miR-4248) against inflammation, we simulated an inflammatory environment in chondrocytes cell lines C20A4 and C28/12, focusing on inflammasome formation and pyroptosis. Results: Our finding indicates notopterol significantly reduced interleukin (IL)-18 and tumor necrosis factor (TNF)-alpha levels in inflamed cells, curtailed reactive oxygen species (ROS) production post-inflammation, and inhibited the JAK2/STAT3 signaling pathway, thus offering chondrocytes protection from inflammation. Importantly, notopterol also hindered inflammasome assembly and pyroptosis by blocking the NF-κB/NLRP3 pathway through hsa-miR-4282 modulation. In vivo experiments showed that notopterol treatment markedly decreased Osteoarthritis Research Society International (OARSI) scores in OA mice and boosted hsa-miR-4282 expression compared to control groups. Conclusions: This study underscores notopterol's potential as a therapeutic agent in OA treatment, highlighting its capacity to shield cartilage from inflammation-induced damage, particularly by preventing pyroptosis. |
| first_indexed | 2024-04-24T13:48:39Z |
| format | Article |
| id | doaj.art-cc2ef0d17d614a4095f3913ae5d3da08 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T13:48:39Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-cc2ef0d17d614a4095f3913ae5d3da082024-04-04T05:06:49ZengElsevierHeliyon2405-84402024-03-01106e28094Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route in osteoarthritisKo-Ta Chen0Chi-Tai Yeh1Vijesh Kumar Yadav2Narpati Wesa Pikatan3Iat-Hang Fong4Wei-Hwa Lee5Yen-Shuo Chiu6Department of Orthopedics, Taipei Medical University Hospital, Taipei, 11031, TaiwanDepartment of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan; Continuing Education Program of Food Biotechnology Applications, College of Science and Engineering, National Taitung University, Taitung, 95092, TaiwanDepartment of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, TaiwanDepartment of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, TaiwanDepartment of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, TaiwanDepartment of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, TaiwanDepartment of Orthopaedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan; Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan; School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan; Research Center of Geriatric Nutrition, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan; Corresponding author. Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, Taipei, 23561, Taiwan.1. Abstract: Objective: Osteoarthritis (OA), the most prevalent form of arthritis, impacts approximately 10% of men and 18% of women aged above 60 years. Currently, a complete cure for OA remains elusive, making clinical management challenging. The traditional Chinese herb Notopterygium incisum, integral to the Juanbi pill for rheumatism, shows promise in safeguarding chondrocytes through its strong anti-inflammatory effects. Methods: To explore the protective effect of notopterol and miRNA (has-miR-4248) against inflammation, we simulated an inflammatory environment in chondrocytes cell lines C20A4 and C28/12, focusing on inflammasome formation and pyroptosis. Results: Our finding indicates notopterol significantly reduced interleukin (IL)-18 and tumor necrosis factor (TNF)-alpha levels in inflamed cells, curtailed reactive oxygen species (ROS) production post-inflammation, and inhibited the JAK2/STAT3 signaling pathway, thus offering chondrocytes protection from inflammation. Importantly, notopterol also hindered inflammasome assembly and pyroptosis by blocking the NF-κB/NLRP3 pathway through hsa-miR-4282 modulation. In vivo experiments showed that notopterol treatment markedly decreased Osteoarthritis Research Society International (OARSI) scores in OA mice and boosted hsa-miR-4282 expression compared to control groups. Conclusions: This study underscores notopterol's potential as a therapeutic agent in OA treatment, highlighting its capacity to shield cartilage from inflammation-induced damage, particularly by preventing pyroptosis.http://www.sciencedirect.com/science/article/pii/S2405844024041252OsteoarthritisNotopterolInterleukin 1 betaPyroptosisNLRP3 inflammasomeJAK2/NF-κB/hsa-miR-4282 pathway |
| spellingShingle | Ko-Ta Chen Chi-Tai Yeh Vijesh Kumar Yadav Narpati Wesa Pikatan Iat-Hang Fong Wei-Hwa Lee Yen-Shuo Chiu Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route in osteoarthritis Heliyon Osteoarthritis Notopterol Interleukin 1 beta Pyroptosis NLRP3 inflammasome JAK2/NF-κB/hsa-miR-4282 pathway |
| title | Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route in osteoarthritis |
| title_full | Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route in osteoarthritis |
| title_fullStr | Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route in osteoarthritis |
| title_full_unstemmed | Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route in osteoarthritis |
| title_short | Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route in osteoarthritis |
| title_sort | notopterol mitigates il 1β triggered pyroptosis by blocking nlrp3 inflammasome via the jak2 nf kb hsa mir 4282 route in osteoarthritis |
| topic | Osteoarthritis Notopterol Interleukin 1 beta Pyroptosis NLRP3 inflammasome JAK2/NF-κB/hsa-miR-4282 pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024041252 |
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