Scientific Reports
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2019
·Vol. 9
·期 1
·1-10
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IF 4.011
Liu Jiakuan,Fang Tian,Li Meiqian,Song Yuting,Li Junzun,Xue Zesheng,Li Jiaxuan,Bu Dandan,Liu Wei,Zeng Qinghe,Zhang Yidan,Yun Shifeng,Huang Ruimin,Yan Jun
Benign prostatic hyperplasia (BPH) is one of the most common diseases in the urinary system of elderly men. Pao extract is an herbal preparation of the bark of the Amazon rainforest tree Pao Pereira ( Geissospermum vellosii ), which was reported to inhibit prostate cancer cell proliferation. Herein we investigated the therapeutic potential of Pao extract against BPH development in a testosterone-induced BPH rat model. The administration of testosterone induced the prostate enlargement, compared with the sham operated group with vehicle treatment. The BPH/Pao group showed reduced prostate weight comparable with BPH/finasteride group. Notably, Pao treatment did not significantly reduce body weights and sperm number of rats, compared with the control group. Furthermore, Pao extract treatment reduced the proliferative index in prostate glands and testosterone-induced expression levels of AR, as well as androgen-associated proteins such as SRD5A1 and PSA. Moreover, Pao extract and its active component, flavopereirine, induced cytotoxicity on human prostate epithelial RWPE-1 cells in a dose- and time- dependent manner with G2/M arrest. Consistently, Pao extract and flavopereirine suppressed the expression levels of SRD5A1, AR and PSA, respectively. Together, these data demonstrated that Pao extract suppresses testosterone-induced BPH development through inhibiting AR activity and expression, and suggested that Pao extract may be a promising and relative safe agent for BPH.
研究领域:
药理学
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泌尿外科
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植物化学
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Ying Wang,Yiwen Guo,Zhu Zhu,Chengyu Zhang,Ziwei Yu,Ming Chang,Ruijie Liu
Prolonged consumption of high fat diet (HFD) contributes to skin inflammation, leading to receding hairline and thinning hair, impacting appearance and psychological well-being. This study aimed to investigate ameliorative effect of wood sterol (WS) on mice with weakened hair follicles due to HFD and to unravel underlying mechanism. The WS (96.38%) was obtained through solvent crystallization using methanol aqueous solution and 2-butanone mixed solvent, with 20 h of crystallization time, 25°C of crystallization temperature, 1:3.5 of solid-liquid ratio, 50% of concentration of methanol-water and 50% of proportion of 2-butanone. The high-fat-induced alopecia model was established by feeding mice on a HFD for three months. The mice were treated with different doses of WS, with 10 mg/d and 5 mg/d, respectively. After intervention, mice regained hair growth, with the hair follicle number reaching 26.75 and terminal hair/vellus hair ratio recovering to 4.89. With inter-sex differences, male mice showed more significant decrease in testosterone levels and more significant improvement in estradiol levels with high-dose WS, but in female mice it was low-dose WS. In summary, wood sterol facilitated the recovery of weakened hair follicles and promoted hair growth. The potential mechanisms involved regulating hair follicle growth by reducing synthetic precursor cholesterol and acting as 5α-reductase inhibitor, contributing to a balance between androgen and estrogen. It provides a potential preventive improvement option for alopecia problems caused by high-fat diet.
研究领域:
皮肤科
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营养学
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药理学
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脂质代谢
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
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2025
·
IF 2.5
Binbin Lu,Qian Zhang,Hang Lin,Shaowei Wang,Yang Zhu,Ren-shan Ge,Xingwang Li
We investigated the inhibitory effects of dithiocarbamates (DTCs) on human steroid 5α-reductase 1 (SRD5A1), an enzyme crucial for the conversion of testosterone or pregnenolone into neuroactive steroids. Utilizing a comprehensive approach that included enzyme assays, molecular docking simulations, and both structure-activity relationship (SAR) and 3D quantitative SAR (3D-QSAR) analyses, we assessed the potency and interaction mechanisms of DTCs with SRD5A1 in human SF126 cells. Our results demonstrated that zinc dibutyldithiocarbamate, disulfiram, ferbam, thiram, and ziram displayed significant inhibitory activity against SRD5A1, with IC 50 values of 1.10, 1.62, 2.31, 1.74, and 1.84 μM, respectively. Kinetic studies indicated that these compounds function as mixed inhibitors, suggesting a multifaceted interaction with the enzyme's active site. These DTCs effectively penetrated the cell membrane of SF126 cells to inhibit SRD5A1 at ≥ 5 μM. Molecular docking analyses revealed that these compounds interacted with a distinct domain located between the NADPH and testosterone binding sites of SRD5A1, primarily through sulfur bonds, which are a fundamental component of the DTC structure. Experimental validation of the inhibitory mechanism was achieved by demonstrating that the co-incubation of dithiothreitol, a sulfhydryl-reducing agent, significantly reversed the inhibitory effects of zinc dibutyldithiocarbamate and thiram. SAR analysis revealed a negative correlation between LogP, molecular weight, and IC 50 values, and a positive correlation between LogS, lowest binding energy, and IC 50 values. The 3D-QSAR analysis further indicated that hydrogen bond acceptor and hydrophobic region capabilities significantly contribute to the primary inhibition. In conclusion, this research significantly advances our understanding of the SAR of sulfur-containing DTCs as inhibitors of human SRD5A1, providing valuable insights for identifying toxicity of DTCs targeting this enzyme.
研究领域:
药理学
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生物化学
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计算生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2022
·
IF 6.064
Xiangru Chen,Peiyu Yan,Wenqiang Zhang,Xin He,Rihua Jiang,Yulin Li,Jing Sun,Jinlan Jiang
Androgenic alopecia (AGA) is a common disease that negatively affects patients’ physical and mental health. AGA can be treated with drugs that improve the perifollicular microenvironment, such as 5α-reductase inhibitors (e.g., dutasteride [DUT]), androgen receptor blockers, and minoxidil. However, the efficacy of these treatments is limited. Therefore, this study aimed to show that nanoparticles are effective as stable carriers with high curative benefits and little adverse effects. The in vitro study showed that PLGA-DUT/siAR@DPCM NPs could deliver both DUT and siAR to dermal papilla cells. They could successfully suppress 5α-reductase and knock down androgen receptor, respectively, and thereby promote cell proliferation. In the in vivo study, PLGA-DUT/siAR@DPCM NPs showed a significant therapeutic effect in an AGA mouse model. They successfully penetrated the stratum corneum and showed a clear targeting effect on hair follicles and surrounding tissues. PLGA-DUT/siAR@DPCM NPs could enable the targeted delivery of DUT and siAR through percutaneous penetration, enhancing phagocytosis and decreasing adverse effects. Thus, they have great potential in the clinical treatment of AGA.
研究领域:
药学
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纳米技术
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皮肤科
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
·
IF 4.8
Hong Xiang,Yu Zhang,Jiaming Li,Li Li,Ziwei Li,Rui Ni,Dan Peng,Lining Jiang,Jianhong Chen,Yao Liu
Ethnopharmacological relevance Terminalia bellirica (Gaertn.) Roxb. (TBR) , a popular herbal remedy in India and Southeast Asia, has been demonstrated to possess multiple pharmacological activities. However, systematic studies on the medicinal effects and mechanism of TBR for the androgenetic alopecia (AGA) treatment are deficient. Materials and methods Human Umbilical Vein Endothelial Cells (HUVECs) and testosterone-induced AGA mice were used to evaluate the hair regrowth activity of TBR extracts. Chemical constituents and potential active components of TBR extracts were analyed by UPLC-Q-TOF-MS in vitro / vivo . The hair regrowth mechanisms of TBR were elucidated through network pharmacology and experimental validation. Results Totally 28 chemical constituents in TBR were identified, of which 15 were predicted as potential active components for AGA therapy. TBR could significantly scavenge ROS, promote VEGF level/cell migration of HUVECs, and inhibiting type II 5α-reductase activity (the inhibit rate: 82.35 ± 1.02 %). Pharmacodynamic evaluation suggested that TBR effectively led to hair regrowth in C57BL6 mice compared to minoxidil. TBR promoted the hair follicle (HF) transition from the telogen phase to anagen phase by decreasing MDA levels, increasing VEFG expression and up-regulating phosphorylated P38/ERK protein levels in the MAPK signalling pathway. Conclusions TBR reversed AGA via inhibiting SRD5A2 activity and stimulating the MAPK pathway. Meantime, TBR could remodel the follicle microenvironment by reducing oxidative stress and increasing angiogenesis.
研究领域:
药理学
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民族药理学
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分子生物学
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细胞生物学
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皮肤科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Integrative Medicine-JIM
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2020
·
IF 2.446
Tian Fang,Ze-sheng Xue,Jia-xuan Li,Jia-kuan Liu,Di Wu,Mei-qian Li,Yu-ting Song,Shi-feng Yun,Jun Yan
Objective Herbal medicine is an important therapeutic option for benign prostatic hyperplasia (BPH), a common disease in older men that can seriously affect their quality of life. Currently, it is crucial to develop agents with strong efficacy and few side effects. Herein we investigated the effects of the extract of Rauwolfia vomitoria , a shrub grown in West Africa, on BPH. Methods Rats with testosterone-induced BPH were treated with R. vomitoria . Prostates were histologically analyzed by Hematoxylin and eosin staining. Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting. Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction. The sperm count and body weight of rats were also measured. Results The oral administration of R. vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats, supported by the decreased thickness of the prostate epithelial layer and increased lumen size. Similar effects were observed in the BPH rats treated with the reference drug, finasteride. R. vomitoria extract significantly reduced the testosterone-induced proliferation markers, including proliferating cell nuclear antigen and cyclin D1 , in the prostate glands of BPH rats; it also reduced levels of androgen receptor, its associated protein steroid 5α-reductase 1 and its downstream target genes ( FK506-binding protein 5 and matrix metalloproteinase 2 ). Notably, compared with the finasteride group, R. vomitoria extract did not significantly reduce sperm count. Conclusion R. vomitoria suppresses testosterone-induced BPH development. Due to its milder side effects, R. vomitoria could be a promising therapeutic agent for BPH.
研究领域:
药理学
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泌尿学
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草药医学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
·
IF 8.5
Yudie Lv,Yongjia Zhang,Xiaoli Zhou,Weili Yang,Ting Zhang,Han Zhang,Yao Li,Ruibo Zhao,Xiangdong Kong
Androgenetic alopecia (AGA)-induced progressive hair loss is a worldwide phenomenon primarily attributed to excessive dihydrotestosterone (DHT) and reactive oxygen species (ROS) within hair follicles. This leads to follicle atrophy and eventual loss, posing a significant challenge for hair regeneration in affected individuals. Herein, we designed a bifunctional sodium hyaluronate microneedle patch as an in situ medical intervention, incorporating glycyrrhizin-loaded dutasteride (GL-DUT) micelles as the 5α-reductase inhibitor to reduce DHT levels and mesoporous polydopamine nanoparticles (MPDA NPs) as ROS scavenger. Dermal papilla cells (DPCs) were used as a representative model to evaluate the dual regulatory effects of GL-DUT micelles and MPDA NPs. The GL-DUT micelles effectively inhibited type 2 5α-reductase activity within hair follicle cells. At the same time, MPDA NPs efficiently reduced excessive ROS, thereby mitigating the conversion of testosterone to DHT and preventing hair follicle miniaturization. Furthermore, the bifunctional microneedle patch (D/M-MNs) demonstrated successful DHT inhibition and ROS elimination in vitro and in vivo , enhancing DPCs activity and significantly accelerating hair growth with good biocompatibility. These findings introduce a novel strategy for promoting rapid hair regeneration by inhibiting DHT in situ and eliminating ROS, offering a promising translational treatment for hair regeneration.
研究领域:
生物医学工程
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药剂学
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皮肤科学
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纳米技术
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
·
IF 12.2
He Zhu,Chentao Ding,Yunbing Tang,Jingyi Zheng,Shaowei Wang,Zhongyao Ji,Yang Zhu,Ren-shan Ge,Huitao Li
Parabens are preservatives used in personal care products, cosmetics, and pharmaceuticals. Steroid 5α-reductase 1 (SRD5A1) catalyzes the conversion of testosterone to dihydrotestosterone and is present in the brain, contributing to neurosteroid production. This study aimed to assess the effects of nine paraben preservatives on SRD5A1 in human SF126 glioblastoma cell and rat brain microsomes, particularly focusing on dihydrotestosterone production in SF126 cells. The results showed that methyl, ethyl, propyl, butyl, hexyl, heptyl, nonyl, phenyl, and benzyl paraben inhibited human SRD5A1, with nonylparaben having the strongest effect (7.59 μM). Additionally, kinetic analysis indicated that parabens acted as mixed/noncompetitive inhibitors, leading to a significant decrease in dihydrotestosterone production in SF126 cells. While rat SRD5A1 exhibited lower sensitivity to parabens, docking analysis revealed that parabens bind to the NADPH-binding site of both human and rat SRD5A1. In conclusion, these results highlight the inhibitory effects of paraben preservatives on SRD5A1 and elucidate their binding mechanisms, underscoring their role in hormone production.
研究领域:
药理学
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毒理学
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生物化学
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分子生物学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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