Introduction:
LY294002 has been validated as a PI3K pan-inhibitor in the pathogenesis of airway inflammation, which attenuated IL-25-induced asthma-like AHR. Liriodendrin was proved to play essential roles in attenuating endometriosis-associated pain. This work aimed to gain a mechanical insight into the therapeutic efficiency of Liriodendrin administration on attenuating endometriosis-associated pain.

Material and methods:
Von Frey filament test and thermal hyperalgesia test were carried out to evaluate the acute and daily efficiency of drug administration. Western blot was used to analyze the expression of substance P, PI3K/AKT/mTOR, p-PI3K/p-AKT/p-mTOR, and CGRP. ELISA was performed to examine interleukin-1, interleukin-2, interleukin-6, TNF-α and PGE2 levels.

Results:
As a result, Liriodendrin significantly attenuated pain in endometriosis rats and restored the up-regulation of p-PI3K/p-AKT/p-mTOR in the endometriosis rats. The increased interleukin-1, interleukin-2, interleukin-6, TNF-α, and PGE2 levels were remarkably restored by Liriodendrin in endometriosis rats. Moreover, the activated expression of substance P in the ventral horn of the spinal cord of endometriosis rats was notably restored by Liriodendrin in addition to CGRP. Furthermore, Liriodendrin effectively restored the LPS induced up-regulation of p-PI3K/p-AKT/p-mTOR protein as well as the LPS activated IL-6, TNF-α, and IL-1β mRNA and protein expression in 12Z cells.

Conclusions:
We found that compared with LY294200, Liriodendrin exerted a more evident therapeutic effect in the treatment of endometriosis-associated pain by suppressing the secretion of pro-inflammatory cytokines.