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Effect of Huluan Decoction on SIRT1/NF-κB/p53/p21 Pathway in Model Mice with Premature Ovarian Insufficiency / 中国实验方剂学杂志
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 36-42, 2021.
Article in Chinese | WPRIM | ID: wpr-906360
ABSTRACT

Objective:

To observe the effects of Huluan decoction on the expression of apoptosis-related protein silence information regulator 1 (SIRT1), tumor suppressor gene (p53), acetylated p53 (Ac-p53), cyclin-dependent kinase inhibitor (p21), and nuclear factor-<italic>κ</italic>B (NF-<italic>κ</italic>B) p65 and changes in ovarian tissue structure of a mouse model with premature ovarian insufficiency (POI) induced by tripterygium glycosides.

Method:

Fifty female C57BL/6J mice were randomly divided into the blank group, model group, low- and high-dose Huluan decoction groups, and western medicine (estradiol valerate) group. After intragastric administration of tripterygium glycosides at 80 mg·kg<sup>-1</sup>·d<sup>-1</sup> for 14 successive days, mice in the low- and high-dose Huluan decoction groups and western medicine group were treated with Huluan decoction at 1.6 g·kg<sup>-1</sup>·d<sup>-1</sup> and 6.2 g·kg<sup>-1</sup>·d<sup>-1</sup> and estradiol valerate at 0.13 mg·kg<sup>-1</sup>·d<sup>-1</sup>, respectively, by gavage since the 15<sup>th</sup> day, while those in the blank group were provided with an equal amount of distilled water for 21 consecutive days. Following the last administration, the blood was sampled for detecting the levels of serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) by ELISA and the ovary was harvested for observing the morphological changes by HE staining. The mRNA expression levels of p53 and p21 were measured by Real-time polymerase chain reactionReal-time PCR), and the protein expression levels of SIRT1, p53, p21, Ac-p53, NF-<italic>κ</italic>B were assayed by Western blot.

Result:

Compared with the blank group, the model group exhibited a disordered estrous cycle, diminished ovarian volume, decreased number of follicles at various developmental stages, reduced AMH, and elevated FSH and LH, and elevated p53,p21,Ac-p53,NF-<italic>κ</italic>B protein expression and p53,p21 mRNA, reduced SIRT1 protein expression(<italic>P</italic><0.01). As revealed by the comparison with the model group, each medication group displayed an increased number of follicles, elevated AMH, reduced FSH and LH (<italic>P</italic><0.01), up-regulated SIRT1 protein expression (<italic>P</italic><0.01), and significantly down-regulated mRNA and protein expression of aging-related genes p53, p21, and down-regulated Ac-p53,NF-<italic>κ</italic>B protein expression (<italic>P</italic><0.01).

Conclusion:

Huluan decoction significantly reverses the aging process and improves ovarian function possibly by boosting the activity of SIRT1/NF-<italic>κ</italic>B/p53/p21 pathway in ovarian cells, changing the apoptotic state, increasing the growing and mature follicles, and reducing the atretic follicles.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article