ReferenceID 2510

Nodakenin attenuates cartilage degradation and inflammatory responses in a mice model of knee osteoarthritis by regulating mitochondrial Drp1/ROS/NLRP3 axis

Int Immunopharmacol

Osteoarthritis (OA) is a common degenerative disease with few treatments. In traditional Chinese medicine (TCM), Radix Angelicae biseratae (RAB) is commonly used to treat OA. Nodakenin (Nod) is one main coumarin active c

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Reference Id
2510
Evidence Id
19100
Core Evidence Id
19100
Source Reference Id
5019
Herb2 Reference Id
HBREF005816
Subject Paper Key
HBIN037195_36302323
Pubmed Id
36302323
Doi
10.1016/j.intimp.2022.109349
Paper Title
Nodakenin attenuates cartilage degradation and inflammatory responses in a mice model of knee osteoarthritis by regulating mitochondrial Drp1/ROS/NLRP3 axis
Paper Abstract
Osteoarthritis (OA) is a common degenerative disease with few treatments. In traditional Chinese medicine (TCM), Radix Angelicae biseratae (RAB) is commonly used to treat OA. Nodakenin (Nod) is one main coumarin active component in RAB and exhibits anti-inflammatory, anti-oxidative, and anti-apoptotic effects. Reactive oxygen species (ROS) produced by mitochondria play a vital role in the pathogenesis of OA. We hypothesized that Nod might ameliorate cartilage degradation and inflammatory responses by regulating the mitochondrial Drp1/ROS/NLRP3 axis. With this, the effects of Nod on a mouse model of knee OA and activated primary chondrocytes were assessed. The results showed that Nod intervention improved bone volume, lowered trabecular separation, and increased trabecular number in the subchondral bone. Nod decreased the Osteoarthritis Research Society International (OARSI) scores and increased collagen II-positive areas in the articular cartilage of the tibial plateau. Compared with OA mice, Nod-treated animals exhibited lower levels of inflammatory factors in the serum and synovitis of the knee joint. In vitro results indicated that Nod suppressed dynamin-related protein 1 (Drp1) phosphorylation and massive ROS production by Drp1-dependent mitochondrial fission in lipopolysaccharide-stimulated chondrocytes. Moreover, Nod inhibited the mRNA levels of inflammatory cytokines (COX 2, IL-1β, and TNF-α), nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, and matrix metalloproteinase 13 expression in activated chondrocytes. In conclusion, Nod attenuates cartilage degradation and inflammatory responses in mice with OA by regulating the mitochondrial Drp1/ROS/NLRP3 axis, suggesting its potential for OA therapy.
Journal
Int Immunopharmacol
Publish Year
2022
Experiment Subject
mouse; lipopolysaccharide-stimulated chondrocytes; radix
Experiment Type
Animal Experiment
Phenotype Related
Knee Oa; Synovitis Of The Knee Joint; Degenerative Disease; Osteoarthritis
Paper Title Cn
Paper Title En
Nodakenin attenuates cartilage degradation and inflammatory responses in a mice model of knee osteoarthritis by regulating mitochondrial Drp1/ROS/NLRP3 axis
Bilingual Status
semi_complete