Paeonia × suffruticosa Andrews leaves improve endometriosis with anxiety/depression by regulating microglial polarization via JAK2/STAT3 pathway.

Abstract

BACKGROUND: Endometriosis (EMs) is a chronic inflammatory disease often treated with blood-activating and stasis-resolving therapies. Anxiety and depression are common mental comorbidities in patients with EMs. There are no medications available for treating EMs with anxiety/depression. Paeonia × suffruticosa Andrews leaves (PSL) has blood-activating and stasis-resolving effects, which are commonly used to treat inflammation and gynecological conditions. PURPOSE: The purpose of this study was to explore the therapeutic effect of PSL on EMs with anxiety/depression and elucidate its mechanisms. METHODS: This study evaluated the inhibitory effect of PSL on EMs through pathological assessment of EMs tissue. Behavioral experiments and pathological characteristics of the brain demonstrated that PSL improved brain damage in EMs mice. Further molecular-level detection and analysis in the hippocampus and prefrontal cortex investigated the mechanism of PSL treatment for EMs with anxiety/depression. RESULTS: PSL inhibited the growth of EMs lesions and reduced Ki67 expression of EMs lesions. PSL improved anxiety/depression-like behavior in EMs mice. Furthermore, PSL treatment contributed to restore neuronal damage in the hippocampus and prefrontal cortex of EMs mice, consistent with behavioral changes. PSL reduced the mRNA and protein expression of IL-1β, IL-6, TNF-α and iNOS in the brain tissue of EMs mice, and promoted the expression of IL-4, CD163, and Arg-1. In addition, the inflammation-related JAK2/STAT3 signaling pathway was activated in the brain of EMs mice with anxiety/depression. PSL downregulated the expression of M1-type microglia and upregulated the expression of M2-type microglia by inhibiting the activation of the JAK2/STAT3 pathway in the hippocampus and prefrontal cortex. CONCLUSIONS: PSL suppressed neuroinflammation through JAK2/STAT3 pathway to treat EMs with anxiety/depression.