Artesunate improves osteoarthritis pain and chondrocyte inflammation in mice by regulating the JAK/STAT pathway

Ge Zeng^1#, RuoLan Wu^2#, Changtao Wan^*

¹Department of Anesthesiology, Wuhan Central Hospital Affiliated to Tongji Medical College of Huazhong University of science and technology, Wuhan 430014, Hubei Province, China - ²Department of Orthopedics, TheThird People's Hospitalof Hubei Province, Jianghan University, Wuhan 430033, Hubei Province, China

Objective: To explore the effect and mechanism of artesunate on pain associated with osteoarthritis (OA) and the inflammatory response of chondrocytes in mice through regulating protein tyrosine kinase (JAK) signal transduction and activating the transcription (STAT) pathway. 

Methods: A total of 48 mice were selected, with 16 mice were randomly selected for the sham control group. The other 32 mice were randomly divided into an OA group and an artesunate group, with 16 mice in each group. The artesunate group was injected intraperitoneally with artesunate 100mg/kg after operation, and the OA group was injected intraperitoneally with 5% NaHCO3 of the same volume after operation. The pain hypersensitivity behaviour and the degree of cartilage damage of the mice in each group were observed, and the OA histological score and inflammatory factors (IL-6, IL-1, TNF-α) of the mice in each group were compared (tumour necrosis factor α, TNF- α). The expression of JAK/STAT3 pathway–related proteins (STAT3, p-STAT3) was detected. 

Results: The ipsilateral contact area on the right hind paws in the OA group was significantly smaller than in the sham group. The ipsilateral contact area on the right hind paws in the artesunate group was significantly larger than in the OA group (P < 0.05). There was no significant pathological change in the articular cartilage of the sham group. In the OA group, proteoglycan decreased significantly, chondrocytes arranged disorderly, and cell hypertrophy appeared. 

In the artesunate group, proteoglycan increased, and the degree of damage was significantly improved compared with the OA group. See Figure 1. The histological score of the OA group was significantly higher than that of the sham group (P < 0.05). The OA histological score of the artesunate group was significantly lower than that of the OA group (P < 0.05). In the OA group, IL-6, IL-1, and TNF-α expression levels were significantly higher than in the sham group. In the artesunate group, IL-6, IL-1, and TNF-α expression levels were significantly decreased (P < 0.05) compared to the OA group. The expression of p-STAT3 in the OA group was significantly higher than in the sham group. The expression of p-STAT3 in the artesunate group was significantly lower than that in the OA group (P < 0.05). 

Conclusion: Artesunate can improve the inflammatory response of OA pain chondrocytes in mice by blocking the JAK/STAT pathway.