<p>Primary dysmenorrhea (PD) refers to menstrual pain that occurs in the absence of obvious pelvic disease. By inhibiting the increase of prostaglandins in the endometrium, inhibiting excessive contraction of the uterus can relieve pain. Motherwort is mainly used to treat menstrual irregularities in women with leonurine as its major active alkaloid compound. The effects and mechanism of leonurine on PD remain unclear.PD model rats were induced, and blood and uterine tissues were collected. The concentration of prostaglandin F2α (PGF2α), prostaglandin E2 (PGE2), and beta-endorphin (β-EP) levels in blood samples were evaluated by enzyme linked immunosorbent assay (ELISA). IL-6, TNF-α and IL-1β in uterine tissues were also measured by ELISA. After intraperitoneal injection of oxytocin, number of writhing times and incubation period within 30 min were recorded. Structural and morphological changes of uterine tissues were observed by Hematoxylin-eosin (H&amp;E) staining method. The proteome profiler rat phospho-kinase array kit was used to reveal possible phosphorylated kinases and signaling nodes that leonurine treatment affected. Western blot method was used to verify the results of phospho-kinase array.Compared with the model group, the twisting times of both ibuprofen and leonurine intervention group were significantly reduced, the latency of twisting body was significantly prolonged. Ibuprofen and leonurine treatment significantly down-regulated PGF2α levels and up-regulated PGE2 and β-EP levels. Leonurine treatment inhibited phosphorylation of the JNK/p38 signaling pathway, and JNK inhibitor SP600125 enhanced the effects of leonurine while JNK agonist Anisomycin exerted the opposite function.In conclusion, our data illustrated that the pain relief effect of leonurine for PD is similar to that of ibuprofen, and this may be related to the inhibition of JNK/p38 signaling pathway.</p>

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Leonurine Exerts an Anti-Primary Dysmenorrhea Effect in Rats by Inactivating the JNK/p38 Pathway

  • Lili Jiang,
  • Yu Jiang,
  • Lijuan Lin,
  • Xiaoyu Ren,
  • Zhe Ding,
  • Shu Luan,
  • Lina Xu,
  • Shengjin Yu,
  • Linlin Zheng

摘要

Primary dysmenorrhea (PD) refers to menstrual pain that occurs in the absence of obvious pelvic disease. By inhibiting the increase of prostaglandins in the endometrium, inhibiting excessive contraction of the uterus can relieve pain. Motherwort is mainly used to treat menstrual irregularities in women with leonurine as its major active alkaloid compound. The effects and mechanism of leonurine on PD remain unclear.PD model rats were induced, and blood and uterine tissues were collected. The concentration of prostaglandin F2α (PGF2α), prostaglandin E2 (PGE2), and beta-endorphin (β-EP) levels in blood samples were evaluated by enzyme linked immunosorbent assay (ELISA). IL-6, TNF-α and IL-1β in uterine tissues were also measured by ELISA. After intraperitoneal injection of oxytocin, number of writhing times and incubation period within 30 min were recorded. Structural and morphological changes of uterine tissues were observed by Hematoxylin-eosin (H&E) staining method. The proteome profiler rat phospho-kinase array kit was used to reveal possible phosphorylated kinases and signaling nodes that leonurine treatment affected. Western blot method was used to verify the results of phospho-kinase array.Compared with the model group, the twisting times of both ibuprofen and leonurine intervention group were significantly reduced, the latency of twisting body was significantly prolonged. Ibuprofen and leonurine treatment significantly down-regulated PGF2α levels and up-regulated PGE2 and β-EP levels. Leonurine treatment inhibited phosphorylation of the JNK/p38 signaling pathway, and JNK inhibitor SP600125 enhanced the effects of leonurine while JNK agonist Anisomycin exerted the opposite function.In conclusion, our data illustrated that the pain relief effect of leonurine for PD is similar to that of ibuprofen, and this may be related to the inhibition of JNK/p38 signaling pathway.