Bushen Jieyu Tiaochong Formula reduces apoptosis of granulosa cells via the PERK-ATF4-CHOP signaling pathway in a rat model of polycystic ovary syndrome with chronic stress

Pan, Xue; Liu, Yanfeng; Liu, Liuqing; Pang, Bo; Sun, Zhidi; Guan, Siqi; Yan, Qingya; Mo, Tingting; Chen, Ran; Xu, Mengbai; Chang, Zhuo; Zhou, Xiaoliang

doi:10.1016/j.jep.2021.114923

Cited by 22 publications

(12 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Scan duration is 100 ms, interscan time is 50 ms, and the scan range is 70-1050 m/z. Data was analyzed using Compound Discoverer 3.1 software (Thermo Fisher Scientific,USA), normalized, and converted into a two-dimensional matrix using Excel 2010 software, containing retention time, compound molecular weight, observations (samples), and peak intensity ( 39 , 40 ).…”

Section: Methodsmentioning

confidence: 99%

Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome

Wang

Yang

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

BackgroundPolycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Gut microbiota dysbiosis and metabolite are associated with PCOS clinical parameters. Yulin Tong Bu formula (YLTB), a traditional Chinese medicine formula, has been recently indicated to be capable of ameliorating polycystic ovary symptoms and correcting abnormal glucose metabolism. However, the therapeutic mechanism of YLTB on PCOS has not been fully elucidated.MethodsA pseudo sterile mouse model was established during this four-day acclimatization phase by giving the animals an antibiotic cocktail to remove the gut microbiota. Here, the therapeutic effects of YLTB on PCOS were investigated using dehydroepiandrosterone plus high-fat diet-induced PCOS mice model. Female prepuberal mice were randomly divided into three groups; namely, the control group, PCOS group and YLTB (38.68 g·kg-1·day-1) group. To test whether this effect is associated with the gut microbiota, we performed 16S rRNA sequencing studies to analyze the fecal microbiota of mice. The relationships among metabolites, gut microbiota, and PCOS phenotypes were further explored by using Spearman correlation analysis. Then, the effect of metabolite ferulic acid was then validated in PCOS mice.ResultsOur results showed that YLTB treatment ameliorated PCOS features (ovarian dysfunction, delayed glucose clearance, decreased insulin sensitivity, deregulation of glucolipid metabolism and hormones, etc.) and significantly attenuated PCOS gut microbiota dysbiosis. Spearman correlation analysis showed that metabolites such as ferulic acid and folic acid are negatively correlated with PCOS clinical parameters. The effect of ferulic acid was similar to that of YLTB. In addition, the bacterial species such as Bacteroides dorei and Bacteroides fragilis were found to be positively related to PCOS clinical parameters, using the association study analysis.ConclusionThese results suggest that YLTB treatment systematically regulates the interaction between the gut microbiota and the associated metabolites to ameliorate PCOS, providing a solid theoretical basis for further validation of YLTB effect on human PCOS trials.

show abstract

Section: Methodsmentioning

confidence: 99%

Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome

Wang

Yang

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…These 15 articles [ 14 , 15 , 23 – 35 ] investigated 13 formulas and 35 treatment arms according to dose and herb composition. The main characteristics are summarized in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…As the most effective formula to reduce high testosterone, BGC decreased the expression of P450c17 α and increased the expression of P450arom to improve hyperandrogenism [ 30 ]. There were also studies on the effect of CHM on ovarian granule cell apoptosis through the PKR-like Reticulum Kinase (PERK)-ATK4- C/EBP homologous protein (CHOP) signaling pathway, PI3K/AKT/mTOR pathway, and P13K/AKT/Forkhead Box Protein O1A (FOXO1A) pathway [ 15 , 23 , 24 , 31 ]. Furthermore, studies on the mechanism of CHM improving PCOS insulin resistance generally explored the glucose transporter 4 (GLU4) related pathways [ 27 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of Chinese Herbal Medicine in Animal Models of Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Zhang

Xin

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Objective. This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) on ovarian mass, weight, sex hormone disorders, and insulin resistance in animal models of polycystic ovary syndrome (PCOS). Methods. This systematic review and meta-analysis was conducted through a comprehensive search in three databases to find studies testing CHM in animal models of PCOS. Two researchers independently reviewed the retrieval, extraction, and quality assessment of the dataset. The pooled effects were calculated using random-effect models; heterogeneity was explored through subgroup analysis; and stability was assessed through sensitivity analysis. In addition, publication bias was assessed using the Egger’s bias test. Results. Fifteen studies with twelve mice and 463 rats published from 2016 to 2021 met the inclusion criteria. The results of primary outcomes revealed that CHM therapy was significantly different with control animals in ovarian mass and testosterone (SMD, −1.01 (95% CI, −1.58, −1.45); SMD, −1.62 (95% CI, −2.07, −1.16), respectively). The secondary outcomes as well showed an overall positive effect of CHM compared with control animals in weight (SMD, −1.02 (95% CI, −1.39, −0.65)), follicle-stimulating hormone (FSH) (SMD, 0.58 (95% CI, 0.19, 0.97)), luteinizing hormone (LH) (SMD, −0.94 [95% CI, −1.25, −0.64)), homeostasis model assessment-insulin resistance (HOMA-IR) (SMD, −1.24 (95% CI, −1.57, −0.92)). Subgroup analyses indicated that PCOS induction drug, formula composition, random allocation, and assessment of model establishment were relevant factors that influenced the effects of interventions. The stability of the meta-analysis was showed robust through sensitivity analysis. The publication bias was substantial. Conclusions. Administration with CHM revealed a statistically positive effect on ovarian mass, weight, sex hormone disorders, and insulin resistance. Moreover, these data call for further high-quality studies investigating the underlying mechanism in more depth.

show abstract

“…Furthermore, the administration of TUDCA to mice with PCOS reduces the apoptosis of GCs in antral follicles, and this is associated with a concomitant decrease in the expression of CHOP and DR5, which implies that ER stress activated by HA in PCOS promotes the apoptosis of GCs via CHOP followed by caspase cascade and follicular growth arrest ( 27 ). Similarly, treatment with curcumin, a polyphenol extracted from turmeric rhizomes, or traditional Chinese medicines abrogates androgen-induced ER stress and the apoptosis of GCs, both in vivo and in vitro ( 43 – 46 ). In addition, the high levels of oxidative stress that is founded in patients with PCOS cause the activation of the UPR in both the ER and mitochondria, resulting in the apoptosis of GCs ( 47 ).…”

Section: Pathophysiological Role Of Er Stress In Pcosmentioning

confidence: 99%

Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome

Koike

Harada²,

Kusamoto³

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, affecting up to 15% of women in this group, and the most common cause of anovulatory infertility. Although its etiology remains unclear, recent research has revealed the critical role of endoplasmic reticulum (ER) stress in the pathophysiology of PCOS. ER stress is defined as a condition in which unfolded or misfolded proteins accumulate in the ER because of an imbalance in the demand for protein folding and the protein-folding capacity of the ER. ER stress results in the activation of several signal transduction cascades, collectively termed the unfolded protein response (UPR), which regulates various cellular activities. In principle, the UPR restores homeostasis and keeps the cell alive. However, if the ER stress cannot be resolved, it induces programmed cell death. ER stress has recently been recognized to play diverse roles in both physiological and pathological conditions of the ovary. In this review, we summarize current knowledge of the roles of ER stress in the pathogenesis of PCOS. ER stress pathways are activated in the ovaries of both a mouse model of PCOS and in humans, and local hyperandrogenism in the follicular microenvironment associated with PCOS is responsible for activating these. The activation of ER stress contributes to the pathophysiology of PCOS through multiple effects in granulosa cells. Finally, we discuss the potential for ER stress to serve as a novel therapeutic target for PCOS.

show abstract

Bushen Jieyu Tiaochong Formula reduces apoptosis of granulosa cells via the PERK-ATF4-CHOP signaling pathway in a rat model of polycystic ovary syndrome with chronic stress

Cited by 22 publications

References 48 publications

Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome

Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome

The Efficacy of Chinese Herbal Medicine in Animal Models of Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome

Contact Info

Product

Resources

About