Alisol A 24‐acetate ameliorates osteoarthritis progression by inhibiting reactive oxygen species and inflammatory response through the AMPK/mTOR pathway
Abstract Introduction Osteoarthritis is a degenerative knee joint disease featured with articular cartilage degeneration and inflammation. Alisol A 24‐acetate (ALA‐24A) is an active triterpene that has antioxidant and anti‐inflammatory pharmacological properties. However, its effect and molecular me...
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| Format: | Article |
| Language: | English |
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Wiley
2023-05-01
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| Series: | Immunity, Inflammation and Disease |
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| Online Access: | https://doi.org/10.1002/iid3.848 |
| _version_ | 1797816584985640960 |
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| author | Guosong Xu Zhensen He Yinping Liu |
| author_facet | Guosong Xu Zhensen He Yinping Liu |
| author_sort | Guosong Xu |
| collection | DOAJ |
| description | Abstract Introduction Osteoarthritis is a degenerative knee joint disease featured with articular cartilage degeneration and inflammation. Alisol A 24‐acetate (ALA‐24A) is an active triterpene that has antioxidant and anti‐inflammatory pharmacological properties. However, its effect and molecular mechanism on osteoarthritis progression have not been reported. Methods IL‐1β‐induced chondrocyte injury model and monosodium iodoacetate (MIA)‐induced rat osteoarthritis model were used. The protective effects of ALA‐24A on osteoarthritis were evaluated by determining cell viability, extracellular matrix (ECM) degradation, inflammatory response and oxidative stress using CCK‐8 assay, Western blot, ELISA, and DCFH‐DA fluorescent probe. The severity and matrix degradation of articular cartilage were assessed by histopathological and immunohistochemical examination. Results We found that ALA‐24A attenuated IL‐1β‐induced cell viability inhibition Moreover, ALA‐24A suppressed expression levels of ECM degradation‐related genes ADAMTS5 and MMP13, and promoted expression levels of ECM synthesis‐related genes Aggrecan and Collagen II. In addition, ALA‐24A treatment decreased reactive oxygen species (ROS) production and increased antioxidant enzymes (SOD, CAT, and GSH‐px) activities, while increased MDA levels. The inflammatory levels of NO, PGE2, TNF‐α, and IL‐6 were also reduced following treatment with ALA‐24A. Our data also revealed that ALA‐24A treatment triggered p‐AMPK upregulation and p‐mTOR downregulation. In rat osteoarthritis model, ALA‐24A treatment significantly alleviated the severity and matrix degradation of articular cartilage comparted with model group. Conclusions Our findings suggested a protective role of ALA‐24A against osteoarthritis by inhibiting ROS and inflammatory response. Furthermore, ALA‐24A might be a promising therapeutic option for osteoarthritis treatment. |
| first_indexed | 2024-03-13T08:39:49Z |
| format | Article |
| id | doaj.art-344cd9165f244e0099442ef8823db6fa |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-03-13T08:39:49Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-344cd9165f244e0099442ef8823db6fa2023-05-30T12:34:31ZengWileyImmunity, Inflammation and Disease2050-45272023-05-01115n/an/a10.1002/iid3.848Alisol A 24‐acetate ameliorates osteoarthritis progression by inhibiting reactive oxygen species and inflammatory response through the AMPK/mTOR pathwayGuosong Xu0Zhensen He1Yinping Liu2Department of Orthopedics The First Hospital of Putian City Putian ChinaDepartment of Orthopedics The First Hospital of Putian City Putian ChinaDepartment of Orthopedics The First Hospital of Putian City Putian ChinaAbstract Introduction Osteoarthritis is a degenerative knee joint disease featured with articular cartilage degeneration and inflammation. Alisol A 24‐acetate (ALA‐24A) is an active triterpene that has antioxidant and anti‐inflammatory pharmacological properties. However, its effect and molecular mechanism on osteoarthritis progression have not been reported. Methods IL‐1β‐induced chondrocyte injury model and monosodium iodoacetate (MIA)‐induced rat osteoarthritis model were used. The protective effects of ALA‐24A on osteoarthritis were evaluated by determining cell viability, extracellular matrix (ECM) degradation, inflammatory response and oxidative stress using CCK‐8 assay, Western blot, ELISA, and DCFH‐DA fluorescent probe. The severity and matrix degradation of articular cartilage were assessed by histopathological and immunohistochemical examination. Results We found that ALA‐24A attenuated IL‐1β‐induced cell viability inhibition Moreover, ALA‐24A suppressed expression levels of ECM degradation‐related genes ADAMTS5 and MMP13, and promoted expression levels of ECM synthesis‐related genes Aggrecan and Collagen II. In addition, ALA‐24A treatment decreased reactive oxygen species (ROS) production and increased antioxidant enzymes (SOD, CAT, and GSH‐px) activities, while increased MDA levels. The inflammatory levels of NO, PGE2, TNF‐α, and IL‐6 were also reduced following treatment with ALA‐24A. Our data also revealed that ALA‐24A treatment triggered p‐AMPK upregulation and p‐mTOR downregulation. In rat osteoarthritis model, ALA‐24A treatment significantly alleviated the severity and matrix degradation of articular cartilage comparted with model group. Conclusions Our findings suggested a protective role of ALA‐24A against osteoarthritis by inhibiting ROS and inflammatory response. Furthermore, ALA‐24A might be a promising therapeutic option for osteoarthritis treatment.https://doi.org/10.1002/iid3.848alisol A 24‐acetateinflammationosteoarthritisoxidative stressreactive oxygen species |
| spellingShingle | Guosong Xu Zhensen He Yinping Liu Alisol A 24‐acetate ameliorates osteoarthritis progression by inhibiting reactive oxygen species and inflammatory response through the AMPK/mTOR pathway Immunity, Inflammation and Disease alisol A 24‐acetate inflammation osteoarthritis oxidative stress reactive oxygen species |
| title | Alisol A 24‐acetate ameliorates osteoarthritis progression by inhibiting reactive oxygen species and inflammatory response through the AMPK/mTOR pathway |
| title_full | Alisol A 24‐acetate ameliorates osteoarthritis progression by inhibiting reactive oxygen species and inflammatory response through the AMPK/mTOR pathway |
| title_fullStr | Alisol A 24‐acetate ameliorates osteoarthritis progression by inhibiting reactive oxygen species and inflammatory response through the AMPK/mTOR pathway |
| title_full_unstemmed | Alisol A 24‐acetate ameliorates osteoarthritis progression by inhibiting reactive oxygen species and inflammatory response through the AMPK/mTOR pathway |
| title_short | Alisol A 24‐acetate ameliorates osteoarthritis progression by inhibiting reactive oxygen species and inflammatory response through the AMPK/mTOR pathway |
| title_sort | alisol a 24 acetate ameliorates osteoarthritis progression by inhibiting reactive oxygen species and inflammatory response through the ampk mtor pathway |
| topic | alisol A 24‐acetate inflammation osteoarthritis oxidative stress reactive oxygen species |
| url | https://doi.org/10.1002/iid3.848 |
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