#75 : Mechanisms and Active Ingredients of Chinese Herbal Medicine on Ameliorating Endometriosis-Associated Pain

Abstract

Background and Aims: Chinese herbal medicines (CHMs) have been effectively used to treat the endometriosis-associated pain (EAP), but its pharmacological and molecular mechanism remains unclear. In this study, we aim to use a network pharmacology-based approach to identify the potential therapeutic targets and active ingredients of CHM for EAP, and to verify their pharmaceutical actions on an experimental mouse model. Method: Pharmacological networks of 3 common CHM formulae for endometriosis (HXXYF, SFZYT and GXZYT) were built by targets collated from public databases, and the enrichment molecular pathway analysis was applied to select the potential pharmacological targets and CHM active ingredients. Pain assessments on the experimental mouse model were performed to evaluate efficacy of the CHM formulae and potential active ingredients. RT-PCR and immunostaining in endometriotic lesions were used to confirm the expression of the potential targets after treatment. Results: ‘Inflammatory mediator regulation of TRP channels’ was a major molecular pathway with highest significance in pharmacological network and enrichment analysis. In mouse, 2 CHM formulae, HXXYF and SFZYT, significantly reduced pain responses, while pain-related inflammatory mediators, IL1[Formula: see text] and PGE2, were significantly decreased after treatment. Meanwhile, densities of nerve fibers in lesions were significantly lower as well, with significantly lower expressions of TRPA1 and TRPV1. 3 CHM ingredients (baicalein, paeoniflorin and quercetin) with highest degree in pharmacological network were then selected for in-depth investigation. However, only paeoniflorin significantly reduced stimuli-evoked and non-stimuli-evoked pain in mice, along with effective reduction in all above parameters. Conclusion: Our study demonstrated multi-targets effects of CHM on EAP relief through inflammatory and neuropathic pathways, which supports CHM as alternative or complementary therapy for EAP. The active ingredients from CHM may provide a novel drug development and approach for EAP treatment.