Betulin suppresses TNF-α and IL-1β production in osteoarthritis synovial fibroblasts by inhibiting the MEK/ERK/NF-κB pathway
Osteoarthritis (OA) is characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. Betulin is a natural analogue of betulinic acid, a lupane-type pentacyclic triterpene that displays many important biological activities, including anti-inflammatory act...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-11-01
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| Series: | Journal of Functional Foods |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464621003789 |
| _version_ | 1818907628416270336 |
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| author | Chin-Horng Su Chih-Yang Lin Chun-Hao Tsai Hsiang-Ping Lee Lun-Chien Lo Wei-Chien Huang Yang-Chang Wu Ching-Liang Hsieh Chih-Hsin Tang |
| author_facet | Chin-Horng Su Chih-Yang Lin Chun-Hao Tsai Hsiang-Ping Lee Lun-Chien Lo Wei-Chien Huang Yang-Chang Wu Ching-Liang Hsieh Chih-Hsin Tang |
| author_sort | Chin-Horng Su |
| collection | DOAJ |
| description | Osteoarthritis (OA) is characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. Betulin is a natural analogue of betulinic acid, a lupane-type pentacyclic triterpene that displays many important biological activities, including anti-inflammatory activity, although the effects on inflammatory cytokine production in OA are unknown. Analyses of samples from the Gene Expression Omnibus (GEO) dataset and our own clinical samples revealed higher levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) in OA synovial tissue compared with normal healthy tissue. This was also the case in synovial tissue from normal healthy rats and rats subjected to anterior cruciate ligament transaction (ACLT)-induced OA. High-throughput screening of inflammatory cytokines in betulin-treated OA synovial fibroblasts (OASFs) identified TNF-α and IL-1β as potential targets of betulin. Further analyses found that betulin suppresses TNF-α and IL-1β production in OASFs by inhibiting mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK) and nuclear factor kappa B (NF-κB) signaling cascades. Betulin shows promise for the treatment of OA. |
| first_indexed | 2024-12-19T21:58:09Z |
| format | Article |
| id | doaj.art-d7ebd0b07e8649e8880434660f030d82 |
| institution | Directory Open Access Journal |
| issn | 1756-4646 |
| language | English |
| last_indexed | 2024-12-19T21:58:09Z |
| publishDate | 2021-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Functional Foods |
| spelling | doaj.art-d7ebd0b07e8649e8880434660f030d822022-12-21T20:04:13ZengElsevierJournal of Functional Foods1756-46462021-11-0186104729Betulin suppresses TNF-α and IL-1β production in osteoarthritis synovial fibroblasts by inhibiting the MEK/ERK/NF-κB pathwayChin-Horng Su0Chih-Yang Lin1Chun-Hao Tsai2Hsiang-Ping Lee3Lun-Chien Lo4Wei-Chien Huang5Yang-Chang Wu6Ching-Liang Hsieh7Chih-Hsin Tang8Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Orthopedics, Yuan-Lin Christian Hospital, Changhua, TaiwanDepartment of Pharmacology, School of Medicine, China Medical University, Taichung, TaiwanDepartment of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, TaiwanGraduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Chinese Medicine, China Medical University Hospital, Taichung, TaiwanDepartment of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan; Drug Development Center, Research Center for Cancer Biology, China Medical University, Taichung, Taiwan; The Biotechnology Department, College of Medical and Health Science, Asia University, Taichung, TaiwanThe Biotechnology Department, College of Medical and Health Science, Asia University, Taichung, Taiwan; Chinese Medicine Research and Development Center, China Medical University Hospital, China Medical University, Taichung, Taiwan; Graduate Institute of Chinese Medicine, China Medical University, Taichung, TaiwanDepartment of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung, Taiwan; Corresponding authors at: Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan (C. Hseih). Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan (C. Tang).Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan; The Biotechnology Department, College of Medical and Health Science, Asia University, Taichung, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung, Taiwan; Corresponding authors at: Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan (C. Hseih). Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan (C. Tang).Osteoarthritis (OA) is characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. Betulin is a natural analogue of betulinic acid, a lupane-type pentacyclic triterpene that displays many important biological activities, including anti-inflammatory activity, although the effects on inflammatory cytokine production in OA are unknown. Analyses of samples from the Gene Expression Omnibus (GEO) dataset and our own clinical samples revealed higher levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) in OA synovial tissue compared with normal healthy tissue. This was also the case in synovial tissue from normal healthy rats and rats subjected to anterior cruciate ligament transaction (ACLT)-induced OA. High-throughput screening of inflammatory cytokines in betulin-treated OA synovial fibroblasts (OASFs) identified TNF-α and IL-1β as potential targets of betulin. Further analyses found that betulin suppresses TNF-α and IL-1β production in OASFs by inhibiting mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK) and nuclear factor kappa B (NF-κB) signaling cascades. Betulin shows promise for the treatment of OA.http://www.sciencedirect.com/science/article/pii/S1756464621003789BetulinOsteoarthritisTNF-αIL-1βACLTProinflammatory cytokines |
| spellingShingle | Chin-Horng Su Chih-Yang Lin Chun-Hao Tsai Hsiang-Ping Lee Lun-Chien Lo Wei-Chien Huang Yang-Chang Wu Ching-Liang Hsieh Chih-Hsin Tang Betulin suppresses TNF-α and IL-1β production in osteoarthritis synovial fibroblasts by inhibiting the MEK/ERK/NF-κB pathway Journal of Functional Foods Betulin Osteoarthritis TNF-α IL-1β ACLT Proinflammatory cytokines |
| title | Betulin suppresses TNF-α and IL-1β production in osteoarthritis synovial fibroblasts by inhibiting the MEK/ERK/NF-κB pathway |
| title_full | Betulin suppresses TNF-α and IL-1β production in osteoarthritis synovial fibroblasts by inhibiting the MEK/ERK/NF-κB pathway |
| title_fullStr | Betulin suppresses TNF-α and IL-1β production in osteoarthritis synovial fibroblasts by inhibiting the MEK/ERK/NF-κB pathway |
| title_full_unstemmed | Betulin suppresses TNF-α and IL-1β production in osteoarthritis synovial fibroblasts by inhibiting the MEK/ERK/NF-κB pathway |
| title_short | Betulin suppresses TNF-α and IL-1β production in osteoarthritis synovial fibroblasts by inhibiting the MEK/ERK/NF-κB pathway |
| title_sort | betulin suppresses tnf α and il 1β production in osteoarthritis synovial fibroblasts by inhibiting the mek erk nf κb pathway |
| topic | Betulin Osteoarthritis TNF-α IL-1β ACLT Proinflammatory cytokines |
| url | http://www.sciencedirect.com/science/article/pii/S1756464621003789 |
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