• 제목/요약/키워드: CYP3A subfamily

검색결과 14건 처리시간 0.023초

미세먼지에 의해 유발되는 인간각질형성세포 손상에 대한 신규 트리펩타이드의 보호 효과 (Protective Effects of Novel Tripeptide Against Particulate Matter-induced Damage in HaCaT Keratinocytes)

  • 이응지;강한아;황보별;이영민;정용지;김은미
    • 대한화장품학회지
    • /
    • 제47권1호
    • /
    • pp.75-84
    • /
    • 2021
  • 본 연구에서는 3 개의 아미노산으로 이루어진 트리펩타이드의 미세먼지에 의한 인간각질형성세포의 손상 억제 효과에 대해 확인하였다. 실험 결과 트리펩타이드 처리 시 미세먼지에 의한 세포 사멸이 억제되어 생존율 증가가 관찰되었으며, aryl hydrocarbon receptor (AhR) 기전 활성이 억제 되어 독성 대사체 생성과 염증반응에 관여하는 하위 인자인 cytochrome P450 family 1 subfamily A member 1 (CYP1A1) 및 cyclooxygenase-2 (COX-2)의 발현이 저해되었다. 또한 미세먼지에 의한 산화적 스트레스 억제 효과를 나타내어 염증성 사이토카인의 발현을 저해하였고, 피부 구성 단백질의 분해를 유도하는 matrix metalloproteinase-1 (MMP-1)의 발현을 저해하였으며, 세포 사멸 인자의 수준을 저해하였다. 이 결과를 종합해 볼 때, 본 연구의 트리펩타이드는 미세먼지에 의한 인간각질형성세포의 사멸 및 주변 피부 조직의 손상을 유도할 수 있는 기전들을 억제하여 보호 효과를 나타내는 것으로 보인다. 트리펩타이드의 이러한 안티폴루션 효과는 신규 기능성 화장품 소재로 응용될 수 있을 것으로 기대된다.

miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone

  • Lee, Su-Yeon;Kang, Youn-Jung;Kwon, Jinie;Nishi, Yoshihiro;Yanase, Toshihiko;Lee, Kyung-Ah;Koong, Mi Kyoung
    • Clinical and Experimental Reproductive Medicine
    • /
    • 제47권3호
    • /
    • pp.194-206
    • /
    • 2020
  • Objective: The aim of this study was to investigate microRNAs (miRNAs) related to follicle-stimulating hormone (FSH) responsiveness using miRNA microarrays and to identify their target genes to determine the molecular regulatory pathways involved in FSH signaling in KGN cells. Methods: To change the cellular responsiveness to FSH, KGN cells were treated with FSH receptor (FSHR)-specific small interfering RNA (siRNA) followed by FSH. miRNA expression profiles were determined through miRNA microarray analysis. Potential target genes of selected miRNAs were predicted using bioinformatics tools, and their regulatory function was confirmed in KGN cells. Results: We found that six miRNAs (miR-1261, miR-130a-3p, miR-329-3p, miR-185-5p, miR-144-5p and miR-4463) were differentially expressed after FSHR siRNA treatment in KGN cells. Through a bioinformatics analysis, we showed that these miRNAs were predicted to regulate a large number of genes, which we narrowed down to cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and estrogen receptor alpha (ESR1) as the main targets for miR-4463. Functional analysis revealed that miR-4463 is a regulatory factor for aromatase expression and function in KGN cells. Conclusion: In this study, we identified differentially expressed miRNAs related to FSH responsiveness. In particular, upregulation of miR-4463 expression by FSHR deficiency in human granulosa cells impaired 17β-estradiol synthesis by targeting CYP19A1 and ESR1. Therefore, our data might provide novel candidates for molecular biomarkers for use in research into poor responders.

Sequential anti-inflammatory and osteogenic effects of a dual drug delivery scaffold loaded with parthenolide and naringin in periodontitis

  • Rui Chen;Mengting Wang;Qiaoling Qi;Yanli Tang;Zhenzhao Guo;Shuai Wu;Qiyan Li
    • Journal of Periodontal and Implant Science
    • /
    • 제53권1호
    • /
    • pp.20-37
    • /
    • 2023
  • Purpose: Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system. Methods: The targets and pathways of parthenolide and naringin were predicted. Three cell models were used to assess the anti-inflammatory effects of parthenolide and the osteogenic effects of naringin. First, the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) and the bone mineral density (BMD) of surgical defects were measured in a rat model of periodontitis with periodontal fenestration defects. Additionally, the mRNA expression levels of matrix metallopeptidase 9 (MMP9) and alkaline phosphatase (ALP) were measured. Furthermore, the number of inflammatory cells and osteoclasts, as well as the protein expression levels of tumor necrosis factor-alpha (TNF-α) and levels of ALP were determined. Results: Target prediction suggested prostaglandin peroxidase synthase (PTGS2) as a potential target of parthenolide, while cytochrome P450 family 19 subfamily A1 (CYP19A1) and taste 2 receptor member 31 (TAS2R31) were potential targets of naringin. Parthenolide mainly targeted inflammation-related pathways, while naringin participated in steroid hormone synthesis and taste transduction. In vitro experiments revealed significant antiinflammatory effects of parthenolide on RAW264.7 cells, and significant osteogenic effects of naringin on bone marrow mesenchymal stem cells and MC3T3-E1 cells. DDDS loaded with parthenolide and naringin decreased the CEJ-ABC distance and increased BMD and ALP levels in a time-dependent manner. Inflammation was significantly alleviated after 14 days of DDDS treatment. Additionally, after 56 days, the DDDS group exhibited the highest BMD and ALP levels. Conclusions: DDDS loaded with parthenolide and naringin in a rat model achieved significant synergistic anti-inflammatory and osteogenic effects, providing powerful preclinical evidence.

Anti-Diabetic Effects of Dung Beetle Glycosaminoglycan on db Mice and Gene Expression Profiling

  • Ahn, Mi Young;Kim, Ban Ji;Yoon, Hyung Joo;Hwang, Jae Sam;Park, Kun-Koo
    • Toxicological Research
    • /
    • 제34권2호
    • /
    • pp.151-162
    • /
    • 2018
  • Anti-diabetes activity of Catharsius molossus (Ca, a type of dung beetle) glycosaminoglycan (G) was evaluated to reduce glucose, creatinine kinase, triglyceride and free fatty acid levels in db mice. Diabetic mice in six groups were administrated intraperitoneally: Db heterozygous (Normal), Db homozygous (CON), Heuchys sanguinea glycosaminoglycan (HEG, 5 mg/kg), dung beetle glycosaminoglycan (CaG, 5 mg/kg), bumblebee (Bombus ignitus) queen glycosaminoglycan (IQG, 5 mg/kg) and metformin (10 mg/kg), for 1 month. Biochemical analyses in the serum were evaluated to determine their anti-diabetic and anti-inflammatory actions in db mice after 1 month treatment with HEG, CaG or IQG treatments. Blood glucose level was decreased by treatment with CaG. CaG produced significant anti-diabetic actions by inhiting creatinine kinase and alkaline phosphatase levels. As diabetic parameters, serum glucose level, total cholesterol and triglyceride were significantly decreased in CaG5-treated group compared to the controls. Dung beetle glycosaminoglycan, compared to the control, could be a potential therapeutic agent with anti-diabetic activity in diabetic mice. CaG5-treated group, compared to the control, showed the up-regulation of 48 genes including mitochondrial yen coded tRNA lysine (mt-TK), cytochrome P450, family 8/2, subfamily b, polypeptide 1 (Cyp8b1), and down-regulation of 79 genes including S100 calcium binding protein A9 (S100a9) and immunoglobulin kappa chain complex (Igk), and 3-hydroxy-3-methylglutaryl-CoenzymeAsynthase1 (Hmgcs1). Moreover, mitochondrial thymidine kinase (mt-TK), was up-regulated, and calgranulin A (S100a9) were down-regulated by CaG5 treatment, indicating a potential therapeutic use for anti-diabetic agent.