A metabolic exploration of the protective effect of Ligusticum wallichii on IL-1β-injured mouse chondrocytes.

Osteoarthritis (OA) is a metabolic disorder and able to be relieved by traditional Chinese medicines. However, the effect of Ligusticum wallichii on OA is unknown.

Cytokine IL-1β and L. wallichii extracts were used to stimulate the primary mouse chondrocytes. MTT assay was used to measure the cell viability. The mRNA and protein level of each gene were test by qRT-PCR and western blotting, respectively. The rate of apoptotic cell was measured by flow cytometry. GC/MS-based metabolomics was utilized to characterize the variation of metabolome.

Here, we found that L. wallichii attenuated the IL-1β-induced apoptosis, inflammatory response, and extracellular matrix (ECM) degradation in mouse chondrocytes. Then we used GC/MS-based metabolomics to characterize the variation of metabolomes. The established metabolic profile of mouse chondrocytes showed that the abundance of most metabolites (n = 40) altered by IL-1β stimulation could be repressed by L. wallichii treatment. Multivariate data analysis identified that cholesterol, linoleic acid, hexadecandioic acid, proline, l-valine, l-leucine, pyruvate, palmitic acid, and proline are the most key biomarkers for understanding the metabolic role of L. wallichii in IL-1β-treated chondrocytes. Further pathway analysis using these metabolites enriched fourteen metabolic pathways, which were dramatically changed in IL-1β-treated chondrocytes and capable of being reprogrammed by L. wallichii incubation. These enriched pathways were involved in carbon metabolisms, fatty acid biosynthesis, and amino acid metabolisms.

These findings provide potential clues that metabolic strategies are linked to protective mechanisms of L. wallichii treatment in IL-1β-stimulated chondrocytes and emphasize the importance of metabolic strategies against inflammatory responses in OA development.