PHYTOMEDICINE
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2026
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IF 11.3
Hongdan Chu,Yichen Li,Zheng Liang,Yanwei Wang,Yuqi Luo,Jing Gan,Gang Li,Zhenhua Wang,Bo Xu
The decrease of bone mineral density in zebrafish larvae caused by continuous light is closely related to circadian rhythm gene disorder. • LG improved the circadian rhythm gene disorder of zebrafish larvae caused by continuous light. • LG alleviated the decrease of bone mineral density in zebrafish larvae caused by continuous light. • LG reversed the inhibition of osteogenic differentiation of MC3T3-E1 cells caused by circadian rhythm gene disorder. • Circadian rhythm genes play a key role in LG intervention in osteogenic differentiation. Circadian rhythm disorders can destroy the balance of bone metabolism and hence closely related to bone metabolic diseases. To further explore the relationship between circadian rhythm and bone metabolism, the sleep deprivation model of zebrafish induced by continuous light and the MC3T3-EI cell model induced by Nr1d1-specific agonist STL1267 (STL1267) were used to study the intervention mechanism of liquiritigenin on bone metabolism imbalance mediated by circadian rhythm. Molecular docking, behavioral studies, calcein staining, alizarin red staining, alkaline phosphatase and osteocalcin activity, qRT-PCR, Western blotting, and other methods were adopted to screen and study the effects of licorice flavonoids on circadian rhythm disorder and its induced decrease of bone mineral density in zebrafish, osteogenic differentiation, and mineralization inhibition of MC3T3-EI cells. The results showed that liquiritigenin significantly alleviated the expression disorders of zebrafish circadian rhythm genes brain and muscle ARNT-like 1 (Bmal1), circadian locomotor output cycles kaput (Clock), period (Per), cryptochrome (Cry), retinoic acid receptor-related orphan receptor α (Rorα), and nuclear receptor subfamily 1 group D member (Nr1d1) induced by continuous light and caused zebrafish behavioral defects, decreased alkaline phosphatase and osteocalcin activity, and bone mineral density as well. Similarly, liquiritigenin effectively improved the expression of circadian rhythm-related genes at mRNA and protein levels in MC3T3-EI cells induced by STL1267 and enhanced cell viability, alkaline phosphatase and osteocalcin activity, and bone matrix mineralization. Therefore, this work reveals the key role of circadian rhythm in bone metabolism homeostasis, and proves that liquiritigenin can effectively alleviate the imbalance of bone homeostasis caused by circadian rhythm disorders, providing research basis for the application of natural small molecule components to improve circadian rhythm disorders and bone metabolism imbalance. Download: Download high-res image (338KB) Download: Download full-size image
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DOI
PubMed
高影响因子
WORLD JOURNAL OF GASTROENTEROLOGY
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2026
·Vol. 32
·期 10
·115334
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IF 7.7
Si-Wei Xia,Huan Liu,Kai-Yao Yang,Yi-Jie Gao,Meng-Ru Zhang,Jing-Wen Zhou,De-Song Kong,Hong-Yan Wu,Feng Zhang,Li Chen
BACKGROUND Reversal of hepatic fibrosis (HF) represents a potential cure for chronic liver pathologies; however, clinically approved agents targeting this process remain scarce. Emerging evidence from traditional Chinese medicine (TCM) suggests that Hedyotis diffusa (HD), a botanical agent related to TCM principles of liver pathogenesis, may exert therapeutic effects against fibrotic liver damage. Despite its historical use, the molecular mechanisms underlying its antifibrotic properties and regulatory pathways require systematic elucidation. AIM To elucidate the efficacy and potential mechanism of HD against HF and to explore potential therapeutic targets. METHODS Liquid chromatograph mass spectrometer revealed six bioactive components of HD injection (HDI) that enter the blood and liver. Network pharmacology using these components predicted related signaling pathways. A HF mouse model was induced by administration of 10% carbon tetrachloride for 8 weeks to validate the efficacy of HDI. Integrated Gene Expression Omnibus (GEO) mining and liver proteomics revealed the antifibrotic mechanism of HD, which was confirmed via target gene interference to elucidate upstream-downstream regulatory relationships. RESULTS Network pharmacology analysis suggests that HDI may ameliorate HF through the modulation of circadian rhythm, urea metabolism, and hypoxia inducible factor-1 (HIF-1) signaling. GEO data mining and hepatic proteomic profiling in a fibrotic mouse model confirmed the close associations between disease progression and dysregulation of these pathways. HDI intervention significantly restored expression of the circadian regulator NR1D1 . Further mechanistic investigations revealed NR1D1 as an upstream regulator of HIF-1 signaling, urea cycle function, and ammonia metabolism. In vitro experiments demonstrated that ammonium chloride-induced ammonia accumulation promoted LX2 cell activation, which is potentially associated with mitochondrial dysfunction. CONCLUSION HD demonstrates unequivocal efficacy in combating HF, potentially by modulating HIF-1 and the urea cycle through its influence on circadian rhythm genes, with NR1D1 as a prominent representative target.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
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IF 6.8
Guanqing Jiang,Xu Song,Jiaying Xie,Tongxing Shi,Qiaoyuan Yang
Polycyclic aromatic hydrocarbons (PAHs) in PM 2.5 pose potentially serious threats to human health. In this study, the distribution characteristics of 16 priority controlled, fine PM (PM 2.5 )-bound PAHs in the ambient air of Guangzhou city were analysed from 2016 to 2019. Four high-molecular-weight PAHs with the highest annual average concentrations were benzo[ghi]perylene (BghiP; 0.757 ng/m 3 ), indeno(1,2,3-cd)pyrene (IcdP; 0.627 ng/m 3 ), benzo[ b ]fluoranthene (BbF, 0.519 ng/m 3 ) and 3,4-benzopyrene (BaP; 0.426 ng/m 3 ). Increasing concentrations of BghiP, IcdP, BbF and BaP were associated with increasing numbers of outpatient visits for respiratory diseases, indicating that exposure to these PAHs potentially causes acute respiratory injury in residents. Acute exposure of the human bronchial epithelial cell line BEAS-2B cells to BghiP, IcdP, BbF and BaP in vitro resulted in acute inflammation, DNA damage and apoptosis. Further bioinformatic analysis indicated that nuclear receptor subfamily 1 group D member 1 ( NR1D1 ) may be a key target gene involved in mediating the toxic effects of BghiP. Collectively, our results suggest that BghiP and the other PAHs represented by it can damage the respiratory system and induce lung cancer. This study provides valuable evidence regarding the potential health risks posed by local ambient PAHs pollution.
研究领域:
环境科学
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公共卫生
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毒理学
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Advanced Science
·
2026
·
IF 14.1
Lang Chen,Wenyi Lin,Lang Jiang,Xuehui Gao,Chenyan Yu,Jili Han,Zhenping Liu,Xuefeng Li,Mei He,Chang Li,Qilan Li,Chaoying Song,Jiqian Xu,You Shang
Patients with sepsis exhibit circadian disruption and persistent immunosuppression. However, the molecular mechanisms linking them remain unclear. Integration of multi‐cohort transcriptomic and single‐cell datasets shows that circadian gene dysregulation in patients with sepsis and septic mice correlates with disease severity and immunosuppressive states, with monocytes/macrophages emerging as a principal affected population. Sustained endotoxin stimulation elevates the core clock repressor NR1D1 in macrophages, which occupies the Igf2bp2 promoter and suppresses its transcription. Loss of IGF2BP2 destabilizes the V‐ATPase subunit transcripts Atp6v1b2 and Atp6v0c through an m 6 A‐dependent mechanism, disrupting phagolysosomal acidification rhythms and pathogen clearance. siRNA‐mediated NR1D1 knockdown restores IGF2BP2 expression, circadian oscillations, and phagolysosomal function during the development of endotoxin tolerance. To achieve therapeutic delivery, we engineer hybrid membrane nanovesicles (siNR1D1@HM‐LNP) that reverse circadian and immune dysregulation in septic mice, enhance bacterial clearance, and markedly improve survival. These findings establish an NR1D1‐mediated circadian‐immune coupling mechanism and provide a therapeutic strategy for targeting sepsis‐induced immunosuppression. Sepsis disrupts immune‐cell rhythms and weakens bacterial clearance. Biomimetic nanovesicles combining erythrocyte and inflammation‐activated macrophage membranes deliver siNR1D1 to dysfunctional macrophages, restoring the NR1D1–IGF2BP2–V‐ATPase pathway, circadian regulation, phagolysosomal acidification, and antimicrobial defense. In mouse models of polymicrobial sepsis and secondary pneumonia, treatment improves immune balance and bacterial control, reduces organ injury, and increases survival.
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高影响因子
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