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二氢睾酮 (DHT)
Food Bioscience · 2024 · IF 4.8

The metabolites of Bifidobacterium longum BB536 alleviate DHT-damaged human dermal papilla cells by activating WNT/β-catenin signaling

Yiming Ren,Liang Li

Probiotics have numerous biological functions and clinical studies have reported that consuming probiotic foods could promote hair growth and hair follicle health. Bifidobacterium longum BB536 was selected to investigate the possibility of treating hair loss with Cell-Free Supernatant (CFS) of B. longum BB536 and the alleviation mechanism of CFS on dihydrotestosterone (DHT)-damaged human dermal papilla cells (HDPCs). The results showed that HDPCs treated with 10% CFS of B. longum BB536 for 24 h could significantly promote cell proliferation, repair cell damage, accelerate the process of cell cycle and increase the secretion of VEGF. The CFS of B. longum BB536 reduced the apoptosis rate of DHT-damaged HDPCs. In addition, it could reduce the level of pro-inflammatory factors and improve the alkaline phosphatase (ALP) activity. Metabolites of B. longum BB536 may increase the protein expression of Wnt10b, β-catenin and LEF-1 by activating Wnt/β-catenin signaling pathway and inhibit the expression of DHT-induced negative feedback factors DKK1 and GSK-3β, which alleviates the damage of DHT on HDPCs, some protein expression levels such as LEF-1 are close to minoxidil (common drugs for hair loss). So, metabolites of B. longum BB536 can be used as new treatment for hair loss due to its safety. This study provides theoretical basis for probiotics to prevent androgenic alopecia.

研究领域: 微生物学 · 细胞生物学 · 药理学 · 皮肤病学
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Journal of Ovarian Research · 2025 ·Vol. 18 ·期 1 ·1-14 · IF 4.2

Targeting UGT2B15 and NR1H4 interaction: a novel therapeutic strategy for polycystic ovary syndrome using naftopidil enantiomers

Zheng Xiufen,Chen Zikai,Liang Miao,Zhou Liting,Wang Miaoru,Zhang Silin,Zhang Shuyun,Ma Lei,Yi Wei,Liu Xiawen

Background Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age. It is characterized by hyperandrogenism, ovulatory dysfunction, and the presence of polycystic ovarian morphology (PCOM) on ultrasound, often accompanied by metabolic disturbances such as insulin resistance and obesity. Current treatments, including oral contraceptives and anti-androgen medications, often yield limited efficacy and undesirable side effects. This study investigates the role of UGT2B15, an essential enzyme for androgen metabolism, in PCOS pathogenesis and its potential as a therapeutic target.Methods We used RNA sequencing to examine the effects of UGT2B15 knockdown in KGN cells. To modulate UGT2B15 expression, we employed siRNA and (R)/(S)-NAF (naftopidil), a chemical inducer of UGT2B15 identified in our previous studies on a prostate hyperplasia model. The effects of siRNA and (R)/(S)-NAF on dihydrotestosterone (DHT) levels, cell apoptosis, and the expression of apoptosis-related proteins in KGN cells were evaluated. In a PCOS mouse model, we assessed the effects of (R)-NAF and (S)-NAF on serum androgen levels, menstrual cycles, ovarian morphology, and UGT2Bs expression. Additionally, luciferase reporter and ChIP assays were utilized to study UGT2B15 regulation by NR1H4.Results Elevated androgens were found to suppress UGT2B15 expression in ovarian granulosa cells, leading to DHT accumulation and apoptosis. (R)-NAF and (S)-NAF treatments reversed these effects, alleviating PCOS symptoms in mice such as hyperandrogenism, irregular menstrual cycles, and the presence of ovarian cysts. NR1H4 negatively regulated the transcription of UGT2B15 in KGN cells. (R)-NAF and (S)-NAF disrupted NR1H4 binding to the UGT2B15 promoter without affecting its protein levels, indicating direct interference with its regulation.Conclusion sUGT2B15 represents a promising target for novel PCOS therapies by modulating androgen metabolism and protecting ovarian granulosa cells from apoptosis. (R)-NAF and (S)-NAF regulate UGT2B15 by disrupting NR1H4's binding to its promoter, implying potential therapeutic compounds for PCOS treatment.

CAS / MDL: 112809-51-5
研究领域: 内分泌学 · 生殖医学 · 药理学 · 分子生物学
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MOLECULES · 2019 ·Vol. 24 ·期 12 ·2266 · IF 3.06

Mechanism Investigation of Tagetes patula L. against Chronic Nonbacterial Prostatitis by Metabolomics and Network Pharmacology

Xueying Liu,Xiaoku Ran,Muhammad Riaz,Haixue Kuang,Deqiang Dou,Decheng Cai

The major objective of this study was to investigate the anti-chronic nonbacterial prostatitis (CNP) mechanism ofT. patulaby metabolomics and network pharmacology. The study demonstrated that the flavonoids and polysaccharides ofT. patulacould alleviate prostatitis by improving the level of DHT, reducing the secretion of PSA and TNF-α. Besides, both could enhance Na+/K+-ATPase activity, decrease the O2consumption, CO2production, heat production, energy expenditure of rats and promote respiratory exchange ratio of rats. Up to 28 potential biomarkers and 8 key metabolic pathways related to the treatment of CNP were elucidated by the metabolomics analysis, including phenylalanine metabolism, taurine and hypotaurine metabolism, tryptophan metabolism etc. Network pharmacology prediction also reflected the potential mechanism was associated with tryptophan metabolism and energy pathway. Generally, the potential anti-CNP mechanism of flavonoids and polysaccharides ofT. patulamight be through reducing the expression of inflammation factors, adjusting the level of hormone and regulating the amino acid metabolism, energy metabolism and glucose and lipid metabolism.Keywords:Tagetes patulaL.;chronic nonbacterial prostatitis;metabolomics;energy metabolism;network pharmacology

研究领域: 药理学 · 代谢组学 · 传统医学 · 前列腺疾病
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