Kaempferol, a Phytoprogestin, Induces a Subset of Progesterone-Regulated Genes in the Uterus.
Kaempferol, a Phytoprogestin, Induces a Subset of Progesterone-Regulated Genes in the Uterus.
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DOI：
10.3390/nu15061407
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发表时间：
2023-03-15
期刊：
影响因子：
5.9
通讯作者：
Burdette JE
中科院分区：
文献类型：
--
作者：
Bergsten TM;Li K;Lantvit DD;Murphy BT;Burdette JE
孕酮是一种类固醇激素，与女性生殖生理有关。虽然一些生殖障碍表现出可以用黄体酮或合成孕激素治疗的症状，但最近的数据表明，女性也寻求植物补充剂来缓解这些症状。然而，植物补充剂不受美国食品和药物管理局的监管，因此，重要的是要表征和量化补充剂在细胞和动物系统中的固有活性化合物和生物靶标。在这项研究中，我们分析了两种天然产物--芹菜素和山奈酚的作用，以确定它们与体内孕酮治疗的关系。根据子宫组织的免疫组织化学分析，山奈酚和芹菜素具有一定的促孕激素活性，但作用方式与黄体酮不完全相同。更具体地说，山奈酚处理没有诱导HAND2，没有改变增殖，并诱导了ZBTB16的表达。此外，虽然芹菜素处理对转录本没有显著影响，但山奈酚处理改变了一些转录本(44%)，其方式与黄体酮处理相似，但也有一些独特的影响。山奈酚主要调节未折叠蛋白反应、雄激素反应和干扰素相关转录本，其方式与黄体酮相似。然而，黄体酮的作用更显著的是调节了数千个转录本，使山奈酚成为小鼠子宫中信号的选择性修饰物。总而言之，植物孕激素，芹菜素和山奈酚，在体内具有促孕激素活性，但也具有独特的作用。
Progesterone functions as a steroid hormone involved in female reproductive physiology. While some reproductive disorders manifest with symptoms that can be treated by progesterone or synthetic progestins, recent data suggest that women also seek botanical supplements to alleviate these symptoms. However, botanical supplements are not regulated by the U.S. Food and Drug Administration and therefore it is important to characterize and quantify the inherent active compounds and biological targets of supplements within cellular and animal systems. In this study, we analyzed the effect of two natural products, the flavonoids, apigenin and kaempferol, to determine their relationship to progesterone treatment in vivo. According to immunohistochemical analysis of uterine tissue, kaempferol and apigenin have some progestogenic activity, but do not act in exactly the same manner as progesterone. More specifically, kaempferol treatment did not induce HAND2, did not change proliferation, and induced ZBTB16 expression. Additionally, while apigenin treatment did not appear to dramatically affect transcripts, kaempferol treatment altered some transcripts (44%) in a similar manner to progesterone treatment but had some unique effects as well. Kaempferol regulated primarily unfolded protein response, androgen response, and interferon-related transcripts in a similar manner to progesterone. However, the effects of progesterone were more significant in regulating thousands of transcripts making kaempferol a selective modifier of signaling in the mouse uterus. In summary, the phytoprogestins, apigenin and kaempferol, have progestogenic activity in vivo but also act uniquely.