Fig 1.
The roles of the MAPK and NFκB pathways in the onset and progression of osteoarthritis.
Molecular docking is a powerful computational technique used to simulate the interaction between a compound and a protein to evaluate their binding potential. As a strong competitor to high-throughput omics, this technique has been widely used in drug discovery [10]. However, to our knowledge, no studies focused on screening anti-osteoarthritis compounds using molecular docking. This study aimed to screen potential anti-osteoarthritis compounds by docking with core human proteins in the MAPK and NFκB pathways, analyze their drug-likeness, pharmacokinetics, bioactivity, and toxicity, and test their cytotoxicity and anti-osteoarthritis effect on mouse chondrocytes.
Fig 2.
Study design.
Fig 3.
Distribution of phi and psi of residues.
A, B, and L indicate most favored regions. a, b, l, and p indicate additional allowed regions. ~ a, ~ b, ~ l, and ~ p indicate generously allowed regions. Triangles indicate glycine residues.
Fig 4.
Bonding energies (kcal/mol) of molecular dockings between compounds and proteins.
Compounds were ranked from lowest to highest based on the first binding energy score formula.
Fig 5.
Positional relationships between compounds and ERK2 and interactions between compounds and residues.
Fig 6.
Positional relationships between compounds and JNK2 and interactions between compounds and residues.
Fig 7.
Positional relationships between compounds and p38 and interactions between compounds and residues.
Fig 8.
Positional relationships between compounds and p65 and interactions between compounds and residues.
Fig 9.
Positional relationships between compounds and I
κBα and interactions between compounds and residues.
Fig 10.
Interactions between compounds and residues.
The top 10 compounds ranked based on the second binding energy score formula are Sesamolin, Rutaecarpine, Corilagin, Apigetrin, Gamabufotalin, Protopine, Viaminate, 5-methoxyflavone, 7,3’,4’-Trihydroxyisoflavone, and Savinin (S6 Table).
Fig 11.
Type II collagen and DAPI immunofluorescence staining images of mouse chondrocytes.
Table 1.
Drug-likeness analysis of selected compounds based on Lipinski’s rule of 5.
Table 2.
Pharmacokinetic prediction of selected compounds.
Table 3.
Molinspiration bioactivity score of selected compounds.
Table 4.
Toxicity prediction of selected compounds.
Fig 12.
Cell viability of mouse chondrocytes at 24 h after treatment with compounds.
Fig 13.
NO concentration in the mouse chondrocyte culture medium at 24 h after treatment with compounds.
“*” indicates P < 0.05. “**” indicates P < 0.01. “***” indicates P < 0.001. “****” indicates P < 0.0001.