A Traditional Chinese Medicine for the Treatment of Endometrial Hyperplasia via Regulating the HPO Axis in Rats

Abstract

Dysfunctional uterine bleeding, accompanied by endometrial hyperplasia (EH), is a common gynecological disease that seriously affects female physical and mental health. Some drugs have been prompted to cure the disease, but most medications have certain side effects and limitations. In the present study, we demonstrated an unexploited Chinese traditional medicine, a combination of Saururus chinensis, Celosia cristata, and Spatholobus suberectus (SCS), which could be used for the treatment of EH and associated complications in rats. We identified the active components from the three Chinese herbs via thin-layer chromatography and high-performance liquid chromatography methods. In addition, serum biochemical indexes and histologic section results found that acute high-dose SCS exerted no adverse impacts on the rats. We then showed that SCS shortened coagulation time (p=0.018) and degree of swelling (p=0.021) on rats at 30 min compared to blank control. Further studies proved that recovered endometrial thickness was associated with the modulation of four hormones (follicle-stimulating hormone, luteinizing hormone, estrogen, and progesterone). Specifically, follicle-stimulating hormone and progesterone contents increased gradually with time, and estrogen was decreased, whereas luteinizing hormone content was returned to normal after a short-term elevation (p < 0.05). Besides, SCS increased uterine endometrium's mRNA expression levels of matrix metalloproteinase-1 (p < 0.001) and tissue inhibitor of matrix metalloproteinase-1 (p < 0.001), promoting the repair of proliferating endometrium in the rats. Collectively, our study indicates that SCS harbors a profoundly curative effect on the treatment of EH and relative complications and uncovers the mechanism at molecular and gene expression levels.

Figure 1

Thin-layer chromatography (TLC) images of three herbs. (a) TLC chromatogram of S. chinensis (1: S. chinensis, 2: control herb, 3: leaf, 4: root, 5: stem). (b) TLC chromatogram of C. cristata (1: control herb, 2: C. cristata). (c) TLC chromatogram of S. suberectus (1 and 3: control herb, 2: S. suberectus).

Figure 2

High-performance liquid chromatography (HPLC) images of S. chinensis and S. suberectus. (a) HPLC chromatogram of control herb (sauchinone). (b) HPLC chromatogram of S. chinensis. Arrow refers to the sauchinone. (c) HPLC chromatogram of control herb (formononetin). (d) HPLC chromatogram of S. suberectus. Arrow refers to the formononetin.

Figure 3

The effects of acute high-dose SCS drug on the SD rats. (a) Histogram of body mass alterations in high-dose SCS treated rats. (b) Effects of acute medication on the organ coefficients in rats. The organ coefficient is expressed by dividing the organ weight by body mass. (c–i) The alterations of blood biochemical parameters under the gavage of acute SCS. (j) Histologic section images of the rat kidney after 3 and 7 d of gavage. (k) Histologic section images of the rat liver after 3 and 7 d of gavage. ^∗Asterisk (^∗) indicates the significant difference (p < 0.05, n = 4). Abbreviations: GM, glomeruli; KT, kidney tubes; HC, hepatocyte; TP, total protein; ALB, albumin; TC, total cholesterol; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactic dehydrogenase; ALP, alkaline phosphatase.

Figure 4

The effects of SCS drug on the coagulation, hemostasis, and anti-inflammation of SD rats. (a, b) Effects of different medical treatments on coagulation time and hemostatic time. (c) The changes of paw detumescence. Relative toe edema expressed by (toe volume after swelling-toe volume before swelling)/toe volume before swelling. Different superscripts (^ab) or ^∗asterisk (^∗) indicates the significant difference in the different or same comparisons (p < 0.05) (n = 4).

Figure 5

Scanning electron microscope (SEM) images of rat endometrium. (a) SEM image of CK rat endometrium. (b) SEM image of estradiol benzoate treated rat endometrium. (c–e) SEM images of rat endometrium after 3 d of gavage (c: EH, d: GXN, and e: SCS). (f–h) SEM images of rat endometrium after 7 d of gavage (f: EH, g: GXN, h: SCS). The white arrow indicates pinopode.

Figure 6

The effects of SCS drug on the thickness of endometrium in the endometrial hyperplasia rats. Values are means ± SEM. Different superscripts (^abc) indicate the significant difference (p < 0.05, n = 4).

Figure 7

Effects of SCS drug on the hormone expression in the endometrial hyperplasia rats. The concentration of follicle-stimulating hormone (a), luteotropic hormone (b), estrogen (c), and progesterone (d) in the serum of rats. Values are means ± SEM. Different superscripts (^abc) indicate the significant difference (p < 0.05, n = 4).

Figure 8

Effects of SCS on the MMP-1 and TIMP-1 expression in the endometrial hyperplasia rats. (a) mRNA expression levels of MMP-1 in endometrium; (b) mRNA expression levels of TIMP-1 in the endometrium. Values are means ± SEM. Different superscripts (^abcde) indicate the significant difference (p < 0.05, n = 4).