Antioxidant mitoquinone suppresses benign prostatic hyperplasia by regulating the AR–NLRP3 pathway

Jin, Byoungho; Lim, Chae-Young; Kim, Hyojung; Lee, Minho; An, Hyo-Jin

doi:10.1016/j.redox.2023.102816

Cited by 8 publications

(5 citation statements)

References 48 publications

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“…Women are more likely to develop asthma and prone to have more severe phenotypes than man 2 , and sex hormones are considered to be associated with this gender difference 3 . The hormonal levels fluctuate in women during menstrual cycles, pregnancies, the perimenopausal and menopause periods, which are correlated to higher risk of asthma exacerbations and worsened symptoms 4 , 5 , 33 , and it's been well-characterized that reproductive factors participated in the development of asthma 34 . Different sex hormones have varied influences on asthma.…”

Section: Discussionmentioning

confidence: 99%

Combination of androgen and estrogen improves asthma by mediating Runx3 expression

He,

Wasti,

Yuan

et al. 2024

Int. J. Med. Sci.

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Objective: Asthma is a chronic heterogeneous airway disease, and imbalanced T-helper type 1 (Th1) and Th2 cell-mediated inflammation contribute to its pathogenesis. Although it has been suggested that androgen and estrogen were involved in development of asthma, the underlying mechanisms remained largely unclear. Studies have demonstrated that Runx3 could promote naive CD4 + T cells to differentiate into Th1 cells. Hence, our study aimed to explore the potential regulatory mechanism of androgen and estrogen on asthma via modulating Runx3. Methods: First, clinical assessments and pulmonary function tests were conducted on 35 asthma patients and 24 healthy controls. The concentrations of androgen, estrogen, and androgen estrogen ratios were assessed in peripheral blood samples of asthma patients and healthy controls. Then, a murine asthma model was established to explore the effects of estrogen and androgen (alone or in combination) on asthma. Third, an in vitro assay was used to explore the mechanism of combination of androgen and estrogen in asthma. Results: We observed decreased androgen and increased estrogen levels in asthma patients compared with healthy controls. In mice with experimental asthma, there were increased serum concentrations of estrogen and decreased serum concentrations of androgen, intervention with combination of androgen and estrogen alleviated airway inflammations, increased Runx3 expressions and elevated Th1 differentiation. In CD4+ T cells co-cultured with bronchial epithelial cells (BECs), treatment with androgen plus estrogen combination promoted Th1 differentiation, which was mitigated by Runx3 knockdown in BECs and enhanced by Runx3 overexpression. Conclusion: These findings suggest that androgen estrogen combination modulate the Th1/Th2 balance via regulating the expression of Runx3 in BECs, thereby providing experimental evidence supporting androgen and estrogen combination as a novel therapy for asthma.

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Section: Discussionmentioning

confidence: 99%

Combination of androgen and estrogen improves asthma by mediating Runx3 expression

He,

Wasti,

Yuan

et al. 2024

Int. J. Med. Sci.

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“…Beyond cancer, the beneficial effects of MitoQ on various diseases have been previously documented, including the inhibition of prostatic hyperplasia via androgen receptor and NOD-like receptor family pyrin domain-containing 3 inhibition [68][69][70][71][72][73][74]. Additionally, MitoQ has successfully completed phase I safety and phase II clinical trials for diverse diseases, including Parkinson's disease and hepatitis C. Numerous studies have demonstrated that MitoQ provides protection against oxidative stress-induced conditions in both cell lines and animal disease models [39].…”

Section: Discussionmentioning

confidence: 99%

Anticancer Effects of Mitoquinone via Cell Cycle Arrest and Apoptosis in Canine Mammary Gland Tumor Cells

Lee,

Park

2024

IJMS

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Treating female canine mammary gland tumors is crucial owing to their propensity for rapid progression and metastasis, significantly impacting the overall health and well-being of dogs. Mitoquinone (MitoQ), an antioxidant, has shown promise in inhibiting the migration, invasion, and clonogenicity of human breast cancer cells. Thus, we investigated MitoQ’s potential anticancer properties against canine mammary gland tumor cells, CMT-U27 and CF41.Mg. MitoQ markedly suppressed the proliferation and migration of both CMT-U27 and CF41.Mg cells and induced apoptotic cell death in a dose-dependent manner. Furthermore, treatment with MitoQ led to increased levels of pro-apoptotic proteins, including cleaved-caspase3, BAX, and phospho-p53. Cell cycle analysis revealed that MitoQ hindered cell progression in the G1 and S phases in CMT-U27 and CF41.Mg cells. These findings were supported using western blot analysis, demonstrating elevated levels of cleaved caspase-3, a hallmark of apoptosis, and decreased expression of cyclin-dependent kinase (CDK) 2 and cyclin D4, pivotal regulators of the cell cycle. In conclusion, MitoQ exhibits in vitro antitumor effects by inducing apoptosis and arresting the cell cycle in canine mammary gland tumors, suggesting its potential as a preventive or therapeutic agent against canine mammary cancer.

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“…These results suggest that oxidative stress injury and release of inflammatory factors are present in the rat model of BPH induced by TP, and that SSTL can reduce collagen deposition by decreasing inflammatory factors and oxidative stress, which in turn alleviates prostate hyperplasia. In one experimental study, in a rat model of BPH, prostate inflammation was found to be mediated by NLRP3 inflammasome-induced caspase-1 release and downstream release of TNF-α and IL-1β [ 31 ]. The results of this experimental study revealed that NOX2, NOX4, NLRP3 inflammatory vesicles and the expression of Caspase-1 and IL-1β were upregulated in prostate tissues in the rat model of BPH induced by TP, suggesting that NOX4 and NOX2-mediated production of excess ROS plays an important role in the activation of NLRP3.…”

Section: Discussionmentioning

confidence: 99%

Shuangshi Tonglin Capsule treats benign prostatic hyperplasia through the ROS/NLRP3 signaling pathway

Wang,

Mao,

Yuan

et al. 2023

Int Urol Nephrol

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Objective To explore the effects of the SSTL on BPH and clarify the therapeutic mechanisms. Methods Animal model of BPH was established by castration and subcutaneous injection of TP into SD rats; rats were orally administered SSTL for 28 days while modeling. Detection of PI, LI and RI in rats, to observe histopathological changes and collagen deposition in the prostate tissue. Detects levels of sex hormones and inflammatory factors in serum and tissues of rats, the test kit detects levels of lipid peroxides and antioxidants in serum and tissues. Fluorescent staining analysis of tissue ROS; the expression of NLRP3 inflammatory vesicles was observed by immunohistochemistry; Western blotting detected the expression of NOX4, NOX2, NLRP3 inflammatory vesicles, ASC, Cleaved Caspase-1, Caspase-1, IL-1β. Results After SSTL capsule treatment, the PI and RI of the rats decrease. HE and Masson staining showed that SSTL ameliorated the pathological damage and reduced collagen deposition in the prostate tissue of BPH rats; ELISA results showed that SSTL was able to reduce T, DHT, TNF-α, IL-1β levels in BPH rats. The test kit showed that SSTL made the levels of MDA, CAT and GSH-Px in the serum and prostate tissue of rats and increased the activity of SOD. The results of ROS fluorescence showed that the ROS level was reduced in SSTL group; Western blotting showed that SSTL could cause down-regulation of NOX4, NOX2, NLRP3, ASC, Cleaved Caspase-1, IL-1β protein expression. Conclusion SSTL can reduce the PI and RI in BPH rats, it can also inhibit the level of sex hormones and inflammatory factors in BPH rats, which thereby reducing the histopathological damage of prostate gland in BPH rats, and can treat BPH in rats through ROS/NLRP3 pathway.

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Antioxidant mitoquinone suppresses benign prostatic hyperplasia by regulating the AR–NLRP3 pathway

Cited by 8 publications

References 48 publications

Combination of androgen and estrogen improves asthma by mediating Runx3 expression

Combination of androgen and estrogen improves asthma by mediating Runx3 expression

Anticancer Effects of Mitoquinone via Cell Cycle Arrest and Apoptosis in Canine Mammary Gland Tumor Cells

Shuangshi Tonglin Capsule treats benign prostatic hyperplasia through the ROS/NLRP3 signaling pathway

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