In:
Phytotherapy Research, Wiley
Abstract:
Atractylenolide‐III (AT‐III) is well known as its role in antioxidant and anti‐inflammatory. Present study was aimed to figure out its effects on osteoarthritis and potential mechanisms. Rat model, human osteoarthritis cartilage explants as well as rat/human chondrocyte cultures were prepared to test AT‐III's effects on osteoarthritis progression and chondrocyte senescence. Potential targeted molecules of AT‐III were predicted using network pharmacology and molecular docking, assessed by Western blotting and then verified with rescue experiments. AT‐III treatment alleviated osteoarthritis severity (shown by OARSI grading score and micro‐CT) and chondrocyte senescence (indexed by levels of SA‐β‐gal, P16, P53, MMP13, ROS and ratio of healthy/collapsed mitochondrial membrane potentials). Network pharmacology and molecular docking suggested that AT‐III might play role through NF‐κB pathway. Further experiments revealed that AT‐III reduced phosphorylation of IKKα/β, IκBα and P65 in NF‐κB pathway. As well as nuclear translocation of p65. Both in vivo and in vitro experiments indicated that AT‐III's effects on osteoarthritis and anti‐senescence were reversed by an NF‐κB agonist. AT‐III could alleviate osteoarthritis by inhibiting chondrocyte senescence through NF‐κB pathway, which indicated that AT‐III is a prospective drug for osteoarthritis treatment.
Type of Medium:
Online Resource
ISSN:
0951-418X
,
1099-1573
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
1493490-5
SSG:
15,3
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