The ameliorating effects of Guizhi Fuling Wan combined with rosiglitazone in a rat ovarian model of polycystic ovary syndrome by the PI3K/AKT/NF-κB and Nrf2/HO-1 pathways.

Abstract

OBJECTIVE:

GuizhiFulingWan (GFW) has been reported to be effective against polycystic ovary syndrome (PCOS) by possessing oxidative stress and inflammation which related to PI3K/AKT/NF-κB, Nrf2/HO-1 pathway. This study aims to probe the effects and mechanisms of GFW combined with rosiglitazone on PCOS via PI3K/AKT/NF-κB and Nrf2/HO-1 pathways.

METHODS:

A rat PCOS model established by dehydroepiandrosterone (DHEA) injection. The experiment was allocated to control, DHEA, GFW, rosiglitazone, GFW + rosiglitazone groups. Treatment for 30 days, we monitored weight and ovarian weight of rats. Fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), lipid metabolism indexes, estrous cycle and sex hormone-, inflammation-, oxidative stress-related factors were examined. Hematoxylin&eosin staining assessed ovarian tissue pathological changes. Western blot determined PI3K/AKT/NF-κB, Nrf2/HO-1 pathways-related markers.

RESULTS:

GFW and rosiglitazone treatment suppressed body weight and ovarian weight in PCOS rats. They also decreased FBG, FINS, HOMA-IR while inhibited total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and enhanced high-density lipoprotein (HDL). They ameliorated estrous cycle, ovarian histological changes and follicular development. They restrained testosterone (T), luteinizing hormone (LH) and accelerated estradiol (E2), progesterone (P), follicle stimulating hormone (FSH). They inhibited glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD) in serum while increased GSH-Px, SOD and decrease MDA in ovarian tissues. They reduced C-reactive protein, interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), IL-6, IL-1β levels. GFW and rosiglitazone co-intervention regulated PI3K/AKT/NF-κB and Nrf2/HO-1 pathways in PCOS rats.

CONCLUSION:

GFW alleviated ovarian dysfunction in PCOS rats, which may be related to the PI3K/AKT/NF-κB, Nrf2/HO-1 pathways.

• Authors: Yongju Ye, Weimei Zhou, Yuefang Ren, Jiali Lu, Aixue Chen, Ruiying Jin, Feilan Xuan
• Journal: Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology (Gynecol Endocrinol) Vol. 39 Issue 1 Pg. 2254848 (Dec 2023) ISSN: 1473-0766 [Electronic] England
• PMID: 37706434 (Publication Type: Journal Article)

Chemical References

• NF-kappa B
• keishibukuryogan
• NF-E2-Related Factor 2
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Rosiglitazone
• Dehydroepiandrosterone

Topics

• Female
• Humans
• Animals
• Rats
• NF-kappa B
• Polycystic Ovary Syndrome (drug therapy)
• NF-E2-Related Factor 2
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Rosiglitazone (pharmacology, therapeutic use)
• Dehydroepiandrosterone