- Six-step synthesis of Leonurine and toxicity study on zebrafish
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Leonurine (1), an important ingredient in leonurus sibiricus L., can be used for some gynecological disease. We have developed a concise and efficient synthetic route of Leonurine, which can be optimized for mass production. Commercially available compound 6 and 2,3-dihydrofuran (7) were used as starting materials. And the toxicity study on zebrafish shows that Leonurine would promote the hatching of zebrafish embryos at low concentration and result in acute death or chronic lethal toxicity at high concentration.
- Zhao, Hui,Hu, Xiang-Guo,Xu, Min-Jie,Cai, Qun-Xing,Liu, Yu-Jun,Su, Duo-Meng,Chen, Shi-Jin,Wang, Kai,Gong, Zhu-Nan
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- Leonurine hydrochloride-a new drug for the treatment of menopausal syndrome: Synthesis, estrogen-like effects and pharmacokinetics
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This research aimed to investigate the estrogen-like effects of Leonurine hydrochloride (Leo). First, we developed a total synthesis of Leo from 3,4,5-trimethoxy-benzoic acid and the structure was confirmed through 1H NMR and mass spectrometry (MS). Then the estrogenic activity of Leo in vitro and in vivo was studied. The proliferation and proliferation inhibitory effects of Leo on MCF-7 cells and MDA-MB-231 cells indicate that Leo exerts estrogen-like effects through estrogen receptor α (ERα) and estrogen receptor β((ERβ) in vitro. Uterotrophic assay in juvenile mice showed that Leo has an estrogen-like effect in vivo, as it can promote the development of the uterus of juvenile mice, increase its uterine coefficient and the size of the uterine cavity, as well as the increased number of uterine glands and the thickened uterine wall. For further research, cyclophosphamide (CTX) was used to establish a mouse model of ovarian function decline. Through this model, we found that Leo can restore the estrous cycle of mice, increase the number of primordial and primary follicles in the ovaries of mice, and regulate the disordered hypothalamic-pituitary-ovarian (HPOA) axis of mice. Finally, the pharmacokinetics of Leo was studied and oral bioavailability of Leo was calculated to be 2.21%. Leo was synthesized and the estrogen-like effect in vitro and in vivo was confirmed as well as its pharmacokinetics.
- Chen, Guoguang,Ren, Lili,Wang, Jin,Wei, Jie,Zhou, Yaxin
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