BACKGROUND AND PURPOSE Primary dysmenorrhea is the most common gynaecologic problem in menstruating women and is characterized by spasmodic uterine contraction and pain symptoms associated with inflammatory disturbances. Paeonol is an active phytochemical component that has shown anti-inflammatory and analgesic effects in several animal models. The aim of this study was to explore whether paeonol is effective against dysmenorrhea and to investigate the potential mechanism of cannabinoid receptor signalling. EXPERIMENTAL APPROACH Dysmenorrhea was established by injecting oestradiol benzoate into female mice. The effects of paeonol on writhing time and latency, uterine pathology and inflammatory mediators were explored. Isolated uterine smooth muscle was used to evaluate the direct effect of paeonol on uterine contraction. KEY RESULTS The oral administration of paeonol reduced dysmenorrhea pain and PGE2 and TNF-α expression in the uterine tissues of mice, and paeonol was found to be distributed in lesions of the uterus. Paeonol almost completely inhibited oxytocin-, high potassium- and Ca2+-induced contractions in isolated uteri. Antagonists of CB2R (AM630) and the MAPK pathway (U0126), but not of CB1R (AM251), reversed the inhibitory effect of paeonol on uterine contraction. Paeonol significantly blocked L-type Ca2+ channels and calcium influx in uterine smooth muscle cells via CB2R. Molecular docking results showed that paeonol fits well with the binding site of CB2R. CONCLUSIONS AND IMPLICATIONS Paeonol partially acts through CB2R to restrain calcium influx and uterine contraction to alleviate dysmenorrhea in mice. These results suggest that paeonol has therapeutic potential for the treatment of dysmenorrhea.

中文翻译：

---

丹皮酚通过激活子宫中的CB2R减轻小鼠的原发性痛经。

背景和目的原发性痛经是经期女性中最常见的妇科问题，其特征是痉挛性子宫收缩和与炎症性疾病相关的疼痛症状。丹皮酚是一种活性植物化学成分，在几种动物模型中均显示出抗炎和止痛作用。这项研究的目的是探讨丹皮酚是否对痛经有效，并研究大麻素受体信号转导的潜在机制。实验方法痛经是通过将雌二醇苯甲酸酯注射入雌性小鼠体内而建立的。探讨了丹皮酚对扭体时间和潜伏期，子宫病理学和炎性介质的影响。使用离体子宫平滑肌评估丹皮酚对子宫收缩的直接作用。关键结果口服丹皮酚可减轻小鼠子宫组织中的痛经痛以及PGE2和TNF-α的表达，并且发现丹皮酚分布在子宫病变中。丹皮酚几乎完全抑制了催产素，高钾和钙离子诱导的离体子宫收缩。CB2R（AM630）和MAPK途径（U0126）的拮抗剂而不是CB1R（AM251）的拮抗剂逆转了丹皮酚对子宫收缩的抑制作用。丹皮酚通过CB2R显着阻断子宫平滑肌细胞的L型Ca2 +通道和钙流入。分子对接结果表明丹皮酚与CB2R的结合位点非常吻合。结论和意义丹皮酚部分通过CB2R发挥作用，以抑制钙的流入和子宫收缩，从而减轻小鼠的痛经。