BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Heng Tang,Ke Ning,Boji Wu,Xuhong Wang,Jingyu He,Pingping Li,Lina Pan,Jiawen Zhang,Yi He,Shizhu Bian,Xingyu Ma,Jihang Zhang,Chuan Liu,Zhexue Qin,Houyuan Hu
Scutellarein (Sc), a natural flavonoid, holds potential for treating pulmonary arterial hypertension (PAH), yet its mechanisms remain unexplored. This study investigated Sc’s therapeutic effects and underlying pathways in PAH. In vivo experiments demonstrated that Sc significantly attenuated right ventricular hypertension, pulmonary arterial remodeling, αSMA expression, and vascular inflammation in PAH models. In vitro, Sc suppressed hypoxia-induced proliferation, migration, inflammation, and pyroptosis in human pulmonary artery smooth muscle cells (HPASMCs). Mechanistically, Sc activated the SIRT1/NAD + axis to restore mitochondrial homeostasis: it upregulated SIRT1 expression and elevated NAD + levels by promoting SIRT1-mediated deacetylation of nicotinamide nucleotide transhydrogenase (NNT), thereby enhancing NNT activity. Elevated NAD + further activated SIRT1, forming a self-reinforcing SIRT1/NNT/NAD + feedback loop that mitigated hypoxia-induced mitochondrial dysfunction. This study identifies Sc as a novel regulator of the SIRT1-dependent NNT deacetylation pathway, which stabilizes NAD + homeostasis to counteract HPASMCs dysregulation in PAH. These findings highlight Sc’s potential as a therapeutic candidate for PAH, offering insights into targeting mitochondrial-metabolic pathways for vascular remodeling diseases.
研究领域:
药理学
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心血管疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Cosmetic Dermatology
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2025
·Vol. 24
·期 12
·e70606
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IF 2.5
Kejie Peng,Jian Mu,Yumeng Li,Zhangtie Wang,Yansong Peng,Tian Zhao,Yixuan Wang,Jing Wang,Baiyi Lu
Background Excessive ultraviolet exposure triggers skin pigment deposition, potentially leading to conditions such as melasma, freckles, and post‐inflammatory hyperpigmentation. The skin of individuals with these dermatological conditions exhibits reduced levels of nicotinamide nucleotide transhydrogenase (NNT). While many seek skin‐whitening products to address pigmentation, existing options often fail to achieve optimal efficacy. To accomplish a synergistic whitening effect, we developed PPV, a composite formulation incorporating three depigmenting agents: Pterocarpus marsupium bark extract (PMBE), Pinus strobus bark extract (PSBE), and ascorbyl tetraisopalmitate (VC‐IP). Aims This study aimed to investigate the effects of PPV on skin whitening and elucidate its mechanisms. Methods After administering PPV to B16F10 melanoma cells, we measured melanin content and gene expression of TYR , TRP‐1 , and TRP‐2 using a microplate reader and qPCR. Western blotting was used to assess p‐CREB, CREB, MITF, and NNT expression. The Jin's formula was used to evaluate the combined effect of the three components of PPV on NNT at the genetic level. Oxidative stress levels were evaluated with ROS, GSH/GSSG, and NADP + /NADPH assay kits, along with confocal microscopy. Transmission electron microscopy and ELISA were employed to quantify the eumelanin/pheomelanin ratio and melanosome maturation. Finally, immunodetection was performed to assess epidermal basal pigmentation, tyrosinase, and NNT expression in a human ex vivo skin model. Results PPV significantly influenced melanin production in melanocytes and human ex vivo skin. This effect was due to the inhibitory effect of PPV on the CREB‐MITF signaling pathway and the synergistic activation effect of PMBE, PSBE, and VC‐IP on the NNT gene expression in B16F10 cells. Activation of NNT led to a reduction in ROS levels and the NADP + /NADPH ratio, ultimately inhibiting melanogenesis, tyrosinase activity, and melanosome maturation in B16F10 cells. Furthermore, PPV treatment reduced pigmentation and increased NNT expression in the aged ex vivo skin model. Conclusion PPV, synthesized from PMBE, PSBE, and VC‐IP, exhibited an anti‐melanogenic effect. This effect was attributed to the inhibition of CREB‐MITF‐mediated melanogenesis and the regulation of oxidative stress by NNT. The findings suggest PPV as a potential therapeutic agent for skin pigmentation disorders.
研究领域:
皮肤病学
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药理学
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分子生物学
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化妆品科学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）