Experimental Study of Yuxuebi Tablets by Inhibiting Peripheral Inflammation to Relieve Hyperalgesia and Foot Swelling in Mice with Chronic Inflammatory Pain / 中国实验方剂学杂志

ABSTRACT

Objective:To observe the effect of Yuxuebi tablets on hyperalgesia and foot swelling in mice with chronic inflammatory pain， and to explore the preliminary mechanism of action. Method:A mouse model of chronic inflammatory pain was established with left plantar injection of complete Freund's adjuvant （CFA）. The mice were divided into model group， positive drug ibuprofen group （91 mg·kg^-1）， Yuxuebi tablets low， medium and high dose groups （55， 110， 220 mg·kg^-1），with the sham operation group as the control. After successful modeling， the daily dose was divided into two doses in the morning and evening by gavage to give Yuxuebi tablets or ibuprofen to the stomach for a total of 19 days. On the 18^th day after the administration， the thermal pain threshold was detected by the hot plate method. On the 19^th day， the standard Von Frey fiber needle was used to detect the mechanical pain threshold of the mice， and the degree of foot swelling was scored and photographed. The liquid-phase suspension chip technology was used to quantitatively analyze 36 classic broad-spectrum inflammation-related factors like inflammatory factors and receptors. Bioinformatics were used to screen core targets and perform enzymelinked immunosorbent assay （ELISA） detection. Result:Compared with the sham operation group， the mechanical pain threshold and foot swelling score of the model froup significantly increased （<italic>P</italic><0.01）， the latent time of heat sensitivity significantly decreased（<italic>P</italic><0.01）， the expressions of 30 inflammatory factors in the foot increased（<italic>P</italic><0.05）. Compared with the model group， the high dose of Yuxuebi tablets significantly reduced the mechanical pain threshold and foot swelling score of mice with chronic inflammatory pain（<italic>P</italic><0.01）， significantly increased the latent time of heat sensitivity（<italic>P</italic><0.05）， and reduced the expressions of 30 inflammatory factors in the foot（<italic>P</italic><0.05）， among which tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and C-C chemokine ligand 2 （CCL2） were the core targets screened out， and the expressions of TNF-<italic>α</italic>， IL-17A， and CCL2 significantly decreased （<italic>P</italic><0.01）. Conclusion:Yuxuebi tablets can relieve hyperalgesia and foot swelling in mice with chronic inflammatory pain， and its mechanism may be related to the inhibition of the expressions of peripheral inflammatory factors such as TNF-<italic>α</italic>， IL-17A， and CCL2 .