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具有不同取代基的香豆素类化合物对子宫平滑肌具有相反的作用。

Coumarins with Different Substituents from Have Opposite Effects on Uterine Smooth Muscle.

机构信息

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

出版信息

Int J Mol Sci. 2024 Sep 21;25(18):10162. doi: 10.3390/ijms251810162.

DOI:10.3390/ijms251810162
PMID:39337649
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11432705/
Abstract

Houtt is an exceptional medicinal herb used to treat obstetrical and gynecological diseases in traditional Chinese medicine, and it has significant effects on the treatment of dysmenorrhea and postpartum hemorrhage. This study investigated the effects of coumarins with diverse substituent groups from on isolated uterine smooth muscle and the preliminary mechanism of the most effective compound. Eight coumarins isolated from were assessed for their effects on the isolated uterine smooth muscle of nonpregnant rats in vitro. Coumarins and significantly promoted the contraction of rat uterine smooth muscle strips, whereas coumarins - showed remarkable relaxing effects against oxytocin (OT)-induced rat uterine smooth muscle contraction. Further mechanism investigations revealed that bergapten (coumarin ) significantly increased the level of Ca in uterine tissues by promoting extracellular Ca influx and intracellular Ca release, which were related to the activation of L-type Ca channels and α-receptors. By contrast, osthole (coumarin ), an α receptor antagonist, inhibited OT-induced uterine smooth muscle contraction by decreasing the level of Ca in uterine tissues via inhibition of extracellular Ca influx and intracellular Ca release. This study demonstrates that the coumarins from are effective substances for regulating uterine smooth muscle contraction, but different coumarins with diverse substituent groups have different, even opposite effects. It can be inferred that coumarins are closely related to the efficacy of in the treatment of dysmenorrhea and postpartum hemorrhage.

摘要

HOUTT 是一种特殊的草药，在中国传统医学中用于治疗妇产科疾病，对治疗痛经和产后出血有显著效果。本研究探讨了不同取代基的香豆素对离体子宫平滑肌的影响及最有效化合物的初步作用机制。从 HOUTT 中分离得到的 8 种香豆素，评估了它们对体外非妊娠大鼠离体子宫平滑肌的作用。香豆素 和 显著促进大鼠子宫平滑肌条的收缩，而香豆素 - 对催产素（OT）诱导的大鼠子宫平滑肌收缩具有显著的舒张作用。进一步的机制研究表明，补骨脂素（香豆素）通过促进细胞外 Ca 内流和细胞内 Ca 释放，显著增加子宫组织中 Ca 的水平，这与 L 型 Ca 通道和 α 受体的激活有关。相比之下，α 受体拮抗剂蛇床子素（香豆素）通过抑制细胞外 Ca 内流和细胞内 Ca 释放，降低子宫组织中 Ca 的水平，抑制 OT 诱导的子宫平滑肌收缩。本研究表明，HOUTT 中的香豆素是调节子宫平滑肌收缩的有效物质，但不同取代基的香豆素有不同的、甚至相反的作用。可以推断，香豆素与 HOUTT 治疗痛经和产后出血的疗效密切相关。

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