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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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  • Jin Wang,
  • Jie Wei,
  • Yaxin Zhou,
  • Lili Ren,
  • Guoguang Chen
Jin Wang
Nanjing Tech University

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Jie Wei
Nanjing Tech University
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Yaxin Zhou
Nanjing Tech University
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Lili Ren
Nanjing Tech University
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Guoguang Chen
Nanjing Tech University
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Abstract

The purpose of this research was to develop a new drug for the treatment of Menopausal Syndrome (MPS) caused by ovarian function decline. First, 3,4,5-trimethoxy-benzoic acid was used as a starting material to synthesize Leonurine hydrochloride (Leo). The structural was confirmed through differential calorimetry scanning (DSC), Fourier infrared spectroscopy (FTIR), 1H NMR and mass spectrometry (MS). Next, 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 the number of uterine glands and the thickened uterine wall. Then 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. Cyclophosphamide 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, strengthen ovarian function, and regulate the disordered 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 pharmacokinetic.