Bu-Shen-Tian-Jing formulas alleviate the mitochondrial damage induced by oxidative stress in ovarian granulosa cells exposed to DEHP through the HDAC3-HSP90AA pathway.
Pharm Biol
; 61(1): 1387-1400, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37655754
ABSTRACT
CONTEXT di-(2-Ethylhexyl) phthalate (DEHP) has potential reproductive toxicity. Bu-Shen-Tian-Jing formulations (BSTJFs) are beneficial for female reproductive capacity. However, BSTJF2 has much lower cytotoxicity than BSTJF1. OBJECTIVE:
To investigate the effects of BSTJFs on ovarian granulosa cells exposed to DEHP and determine the potential molecular mechanisms. METHODS AND MATERIALS Human granulosa-like tumor cell line (KGN) cells were divided into control, DEHP, BSTJF1 and BSTJF2 groups. The DEHP group were given 1 µM DEHP for 24 h. They were then given BSTJF1 at 200 µg/mL or BSTJF2 at 100 µg/mL for 24 h. The control group was treated with the same concentration of DMSO (0.1%). Oxidative stress and mitochondrial function were measured. The mRNA and protein expression levels of HDAC3 and HSP90AA were determined. Integrative network pharmacology analysis of BSTJF2 was also performed.RESULTS:
DEHP (1 µM) significantly suppressed the proliferation of KGN cells by 17%, significantly increased ROS levels by 28% and MDA levels by 47%, significantly decreased MMP levels by 22% and mtDNA copy by 30%. DEHP significantly increased protein expression of HDAC3 by 21%and HSP90AA by 64%. All these changes were significantly reversed by BSTJFs. Integrative network pharmacology analysis revealed HSP90AA was a key target (degree = 8). Both RGFP966 and BSTJF2 significantly reversed the increased expression of HDAC3 and HSP90AA, attenuated oxidative stress, and mitochondrial damage which were induced by DEHP.CONCLUSION:
BSTJFs might have therapeutic potential on oxidative stress and mitochondrial damage through the HDAC3/HSP90AA pathway which encourages further clinical trials.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dietilexilftalato
Limite:
Female
/
Humans
Idioma:
En
Revista:
Pharm Biol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China