Serum HMGB1 Levels and Its Association With Endothelial Dysfunction in Patients With Polycystic Ovary Syndrome

Wang, Haohua; Lin, Min; Xiang, Guangda

doi:10.33549/physiolres.933831

Cited by 16 publications

(9 citation statements)

References 31 publications

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“…Several studies, including this study (Figure 8), have confirmed that the serum level of HMGB1 is higher in PCOS [18], suggesting that inhibiting HMGB1 could be a reliable therapeutic approach against PCOS. Glycyrrhizin, a drug believed to be safe for human use, can directly bind to and inhibit HMGB1 [40].…”

Section: Discussionsupporting

confidence: 64%

Glycyrrhizin ameliorates impaired glucose metabolism and ovarian dysfunction in a polycystic ovary syndrome mouse model

Yang

Ullah

et al. 2023

Biology of Reproduction

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Objective: The aim of this study was to determine the impact of glycyrrhizin, an inhibitor of high mobility group box 1 (HMGB1), on glucose metabolic disorders and ovarian dysfunction in mice with polycystic ovary syndrome (PCOS). Methods: We generated a PCOS mouse model by using dehydroepiandrosterone (DHEA) plus high fat diet (HFD). 100 mg/kg glycyrrhizin was intraperitoneally injected into the PCOS mice and the effects on body weight, glucose tolerance, insulin sensitivity, estrous cycle, hormone profiles, ovarian pathology, glucolipid metabolism and some molecular mechanisms were investigated. Results: Increased number of cystic follicles, hormonal disorders, impaired glucose tolerance and decreased insulin sensitivity in the PCOS mice were reverted by glycyrrhizin. The increased HMGB1 levels in the serum and ovarian tissues of the PCOS mice were also reduced by glycyrrhizin. Furthermore, increased expressions of toll-like receptor (TLR) 9, myeloid differentiation factor 88 (MyD88) and nuclear factor-κB (NF-κB) as well as reduced expressions of insulin receptor (INSR), phosphorylated protein kinase B (p-AKT) and glucose transporter type 4 (GLUT4) were restored by glycyrrhizin in the PCOS mice. Conclusions: Glycyrrhizin could suppress the PCOS-induced upregulation of HMGB1, several inflammatory marker genes and the TLR9/MyD88/NF-KB pathways, while inhibiting the INSR/p-AKT/GLUT4 pathways. Hence, glycyrrhizin is a promising therapeutic agent against PCOS.

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Section: Discussionsupporting

confidence: 64%

Glycyrrhizin ameliorates impaired glucose metabolism and ovarian dysfunction in a polycystic ovary syndrome mouse model

Yang

Ullah

et al. 2023

Biology of Reproduction

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“…In this study, we show that in addition to decreased AR protein abundance (this study and [48]) and increased fetal survival in pregnant PCOS‐like rats [48], treatment with the AR antagonist flutamide also decreased HMGB1, TLR2, TLR4 and NFκB p65 protein levels in the gravid uterus with viable fetuses. It has been reported that compared to women without PCOS, the levels of HMGB1 mRNA and protein are significantly increased in both ovarian granulosa cells [33–36], endometrium (in this study), follicular fluid [35] and serum [36–39] in women with PCOS. While the actions of HMGB1‐induced inflammation are mediated by binding to TLRs [22,23], we show here that uterine HMGB1 and TLR2/4 protein levels are positively correlated with each other in pregnant PCOS‐like rats.…”

Section: Discussionmentioning

confidence: 63%

Regulatory mechanisms of HMGB1 and its receptors in polycystic ovary syndrome‐driven gravid uterine inflammation

Zhang

et al. 2022

The FEBS Journal

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High‐mobility group box 1 (HMGB1) is critical for inflammatory homeostasis and successful pregnancy, and there is a strong association among elevated levels of HMGB1, polycystic ovary syndrome (PCOS), chronic inflammation and pregnancy loss. However, the mechanisms responsible for PCOS‐driven regulation of uterine HMGB1 and its candidate receptors [toll‐like receptor (TLR) 2 and 4] and inflammatory responses during pregnancy remain unclear. In this study, we found a gestational stage‐dependent decrease in uterine HMGB1 and TLR4 protein abundance in rats during normal pregnancy. We demonstrated that increased expression of HMGB1, TLR2 and TLR4 proteins was associated with activation of inflammation‐related signalling pathways in the gravid uterus exposed to 5α‐dihydrotestosterone and insulin, mimicking the clinical features (hyperandrogenism and insulin resistance) of PCOS and this elevation was completely inhibited by treatment with the androgen receptor (AR) antagonist flutamide. Interestingly, acute exposure to lipopolysaccharide suppressed HMGB1, TLR4 and inflammation‐related protein abundance but did not affect androgen levels or AR expression in the gravid uterus with viable fetuses. Furthermore, immunohistochemical analysis revealed that, in addition to being localized predominately in the nuclear compartment, HMGB1 immunoreactivity was also detected in the cytoplasm in the PCOS‐like rat uterus, PCOS endometrium and pregnant rat uterus with haemorrhagic and resorbed fetuses, possibly via activation of nuclear factor κB signalling. These results suggest that both AR‐dependent and AR‐independent mechanisms contribute to the modulation of HMGB1/TLR2/TLR4‐mediated uterine inflammation. We propose that the elevation of HMGB1 and its receptors and disruption of the pro‐/anti‐inflammatory balance in the gravid uterus may participate in the pathophysiology of PCOS‐associated pregnancy loss.

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“…FMD improved in three (27%) out of 11 study-groups; ET-1 levels did not improve in one study where this was assessed; whilst IMT improved in three (33%), but deteriorated in one out of nine study groups (Table 2). 15,35,44,57,58,63,68,77,86,87,91,96,101, Similarly, CRP levels were not reduced in all four study groups that assessed it. A meta-analysis including three randomized controlled studies that compared oral contraceptives containing oestrogen (ethinylestradiol) with progestogen drospirenone or chlormadinone acetate, showed a beneficial effect of ethinylestradiol/drospirenone over ethinylestradiol/chlormadinone acetate in reducing androstenedione levels and total testosterone after 3 months, and Ferriman-Gallwey score after 6 months.…”

Section: Oral Contraceptive Pillsmentioning

confidence: 88%

“…CRP levels were not reduced in five out of six (83%) studies, 35,63,77,86,116 not confirming the documented anti-inflammatory action of metformin on this low-grade inflammation present in this young population. 35,63,77,86,101,117 Thiazolidinediones Thiazolidinediones include three drugs: troglitazone, rosiglitazone and pioglitazone. They act by enhancing glucose uptake in adipose and muscle tissues.…”

Section: Metforminmentioning

confidence: 99%

Assessment of Early Markers of Cardiovascular Risk in Polycystic Ovary Syndrome

Alexandraki¹,

Kandaraki²,

Poulia³

et al. 2021

touchREVIEWS in Endocrinology

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Serum HMGB1 Levels and Its Association With Endothelial Dysfunction in Patients With Polycystic Ovary Syndrome

Cited by 16 publications

References 31 publications

Glycyrrhizin ameliorates impaired glucose metabolism and ovarian dysfunction in a polycystic ovary syndrome mouse model

Glycyrrhizin ameliorates impaired glucose metabolism and ovarian dysfunction in a polycystic ovary syndrome mouse model

Regulatory mechanisms of HMGB1 and its receptors in polycystic ovary syndrome‐driven gravid uterine inflammation

Assessment of Early Markers of Cardiovascular Risk in Polycystic Ovary Syndrome

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