Journal of Jilin University(Medicine Edition) ›› 2022, Vol. 48 ›› Issue (1): 129-135.doi: 10.13481/j.1671-587X.20220116

• Research in basic medicine • Previous Articles     Next Articles

Therapeutic effect of alpinetin in letrozole-induced polycystic ovary syndrome model rats and its mechanism

Yanmin SUN,Junpan HU,Bingyu WANG,Jinying FU()   

  1. Department of Obstetrics and Gynecology,Henan Province Hospital of Traditional Chinese Medicine,Second Affiliated Hospital,Henan University of Chinese Medicine,Zhengzhou 450002,China
  • Received:2021-03-19 Online:2022-01-28 Published:2022-01-17
  • Contact: Jinying FU E-mail:fujinying2003@163.com

Abstract: Objective

To investigate the effect of alpinetin (ALP) in the letrozole-induced polycystic ovary syndrome (PCOS) model rats, and to elucidate its potential mechanism.

Methods

The SD rats were randomly divided into control group, model group, low dose of ALP group and high dose of ALP group.The PCOS rat models were constructed by oral administration of 1 mg·kg-1·d-1 letrozole for 21 d, and the rats in low and high doses of ALP groups were orally administrated with 50 and 100 mg·kg-1 ALP once a day for 14 consecutive days after modeling. The body weights, ovary weight/body weight ratios and oestrous cycle of the rats in various groups were detected. The levels of testosterone and 17β-estradiol in serum of the rats were detected by ELISA. The pathomorphology of ovary tissue of the rats in various groups was observed by HE staining. The expression intensities and distribution of Cleaved cysteine-containing aspartate-specific protease-3 (Cleaved caspase-3) protein in ovary tissue of the rats in various groups were observed by immunohistochemical staining.The expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein (Bax), and microtubule associated protein 1 light chain 3 (LC3)-Ⅱ(LC3-Ⅱ)and LC3-Ⅰ proteins in granulosa cells of the rats in various groups were detected by Western blotting method.The Bax/Bcl-2 and LC3-Ⅱ/LC3-Ⅰ ratios were calculated.

Results

Compared with control group, the body weight, the ovary weight/body weight ratio, and the percentage of diestrous phase of the rats in model group were increased(P<0.01),and the levels of testosterone and 17β-estradiol in serum were increased (P<0.01); compared with model group, the body weights, the ovary weight/body weight ratios, the percentage of diestrous phase and the serum testosterone level in low and high doses of ALP groups were significantly decreased(P<0.05 or P<0.01), and the serum 17β-estradiol levels in high dose of ALP group were significantly decreased(P<0.05). The structure of granulosa cell layer in ovary of the rats in control group was normal; the ovary of the rats in model group showed polycystic changes, the fluid-filled large cystic follicles and atretic follicles were found, and the granulosa cell layer was disordered and the number of layers was reduced; the number of cystic follicles and atretic follicles in ovary of the rats in low and high doses of ALP groups was decreased, the structure of granulosa cell layer tended to be normal.The expression of Cleaved caspase-3 in the granulosa cell layer of the rats in control group;the expression of Cleaved caspase-3 in granulose cell layer of the rats in model group was posititive,and the expression intensities of Cleaved caspase-3 in granulosa cell layer in low and high doses of ALP groups were decreased compared with model group.Compared with control group, the ratios of Bax/Bcl-2 and LC3-Ⅱ/LC3-Ⅰ in granulosa cells of the rats in model group were significantly increased (P<0.01); compared with model group, the ratios of Bax/Bcl-2 and LC3-Ⅱ/LC3-Ⅰ in granulosa cells of the rats in low and high doses of ALP groups were significantly decreased (P<0.05 or P<0.01).

Conclusion

ALP exerts the therapeutical effects in the letrozole-induced PCOS model rats which might be due to its ability to decrease the levels of testosterone and 17β-oestradiol in the peripheral blood and the levels of autophagic death-related proteins in granulosa cells.

Key words: Alpinetin, Polycystic ovary syndrome, Hormone regulation, Autophagy, Granulosa cells

CLC Number: 

  • R285.5