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. 2019 Jan 8:2019:5493714.
doi: 10.1155/2019/5493714. eCollection 2019.

Estrogenic Effect of the Extract of QingYan Formula on Reproductive Tissues in Immature Mice

Yuan Zhao  1 , Hong-Xia Zheng  2 , Ying Xu  2 , Na Lin  2
Affiliations

Estrogenic Effect of the Extract of QingYan Formula on Reproductive Tissues in Immature Mice

Yuan Zhao et al. Evid Based Complement Alternat Med. .

Abstract

A Chinese herbal preparation, QingYan formula (QYF), has been used clinically for kidney-invigorating. However, no evidence base links QYF to estrogen replacement therapy. In this study, the estrogenic effects of QingYan formula 70% ethanol extract (QYFE) were investigated in immature mice. Immature mice were treated with QYFE at doses of 1, 2, and 4g/kg for 7 days. QYFE treatments promoted vaginal cornification and prolonged the estrus status of the immature mice, promoted the growth and development of uterus and vagina, upregulated ERα and ERβ expression at protein level in uterus and vagina, increased the level of estradiol (E2), and decreased concentration of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in serum. This study demonstrated that QYFE exerts estrogenic effects by stimulating biosynthesis of estrogen and increasing estrogen receptors (ERs) in target tissues and provided an evidence base for QYFE treatment instead of estrogen replacement therapy.

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Figures

Figure 1
Figure 1
The effect of QingYan formula extract (QYFE) on the estrous cycle in immature mice (200×). Smears from control group consisted of leukocytes, confirming a state of diestrus. Smears from immature mice treated with estradiol valerate (EV) or QYFE showed a large number of keratinized epithelial cells, indicating that both EV and QYFE can promote keratinization of the superficial vaginal epithelium and advanced estrus. (I) The control group untreated; (II) treated with EV; (III) treated with QYFE (4 g/kg).
Figure 2
Figure 2
The effect of QingYan formula extract (QYFE) on uterine weight in immature mice. The uterine weights of immature mice were measured at the end of the 7-day treatment period. Immature mice treated with QYFE (1, 2, or 4 g/kg) or estradiol valerate (EV) had significantly higher uterus index compared with the untreated control group, showing that QYFE can promote uterine growth. Data are the mean ± standard deviation (SD) of samples from 10 mice. P values are for the one-way analysis of variance (ANOVA) comparing treatment group with untreated immature mice. ∗∗∗P < 0.001, ∗∗P < 0.01, and ∗P < 0.05 compared with the control group.
Figure 3
Figure 3
Effect of QingYan formula extract (QYFE) on levels of serum estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in immature mice. Serum levels of E2, LH, and FSH were measured at the end of the treatment period. Data are the mean ± standard deviation (SD) of samples from 10 mice. P values are for the one-way analysis of variance (ANOVA) comparing treatment group with untreated immature mice. ∗∗∗P < 0.001, ∗∗P < 0.01, and ∗P < 0.05 compared with the control group.
Figure 4
Figure 4
The effect of QingYan formula extract (QYFE) treatment on the histology of uterus and vagina in the immature mice. Representative photomicrographs taken at 200‐X magnification of uterine sections and 400‐X magnification of vaginal sections in immature mice; (a) and (b) are the histology of the uterus and vagina in immature mice. The unstimulated uterus from an immature mice ((a), I) shows a single layer of cuboidal or low columnar cells lining the uterine lumen. Treatment with estradiol valerate (EV) ((a), II) or QYFE ((a), III~V) shows tall columnar epithelial cells, with thickened endometrial linings, an increased number of glands, and extended glandular cavities. The vaginal epithelial cells of immature mice ((b), I) only two to four cell layers were present, and no cornification was observed. Treating with EV ((a), II) or QYFE ((b), III~V) obviously promoted keratinization of the vaginal mucosal epithelium, increased the number of stratified squamous epithelial cells and the number of layers. The treatment groups in immature mice are shown: (I) control group; (II) treated with EV; (III) treated with QYFE at 1 g/kg; (V) treated with QYFE at 2g/kg; (V) treated with QYFE at 4 g/kg.
Figure 5
Figure 5
Effect of QingYan formula extract (QYFE) on expression of estrogen receptor (ER) subtype in the uterus and vagina in immature mice. ERs expressions were assessed by immunohistochemistry. Representative photomicrographs taken at 200‐X magnification in the uterus and 400‐X magnification in the vagina. (a) ERs expression of uterus in immature mice. ERs expressed in the epithelial cells of the endometrium, interstitial cells, and smooth muscle cells in the uterus. (b) ERs expression of vagina in immature mice. ERs were expressed in the vaginal epithelium cells of squamous and smooth muscle cells in vagina. Data are the mean and standard deviation from 10 mice. P values are for the one-way analysis of variance comparing the treatment group with untreated immature mice. Treatment groups are shown: (I) control group; (II) treated with estradiol valerate (EV); (III) treated with QYFE (1 g/kg); (IV) treated with QYFE (2 g/kg); (V) treated with QYFE (4 g/kg). ∗∗∗P < 0.001, ∗∗P < 0.01, and ∗P < 0.05 compared with the control group.
Figure 6
Figure 6
Effect of QingYan formula extract (QYFE) on protein levels of estrogen receptor (ER) subtype in the uterus and vagina in immature mice. Western blot analysis of ER subtype expression in uterus and vagina was carried out as described in Materials and Methods. (a) Protein expression levels of ERs in the uterus; (b) protein expression levels of ERs in the vagina. Representative blots are shown in the above. Quantitative analysis of expression is shown in the below. P values are for one-way analysis of variance (ANOVA) comparing treatment groups with untreated immature mice. ∗∗∗P < 0.001, ∗∗P < 0.01, and ∗P < 0.05 compared with the control group.
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