JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2026
·
IF 6.7
Yao Wang,Yongxiao Chai,Qisheng Qian,Yue Liang,Xin-xin Chen,Guangxu Xing,Liutao Zhao,Songlin Qiao,Rui Li,Gaiping Zhang
Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious swine disease and poses a severe economic burden to the global swine industry. Owing to the inadequacy of current prevention and control measures, developing effective antiviral strategies for preventing PRRS epidemics is imperative. Honokiol (HNK) is a bioactive component of the dietary supplement magnolia extract. Here, we demonstrated that HNK exhibited potent antiviral effects against different PRRSV strains in vitro. Mechanistically, HNK was shown to interfere with PRRSV replication rather than attachment, internalization, or release. HNK was further determined to target PRRSV RNA-dependent RNA polymerase to impair viral genomic RNA synthesis. In addition, HNK was found to decrease PRRSV-triggered inflammatory responses. More importantly, HNK was revealed to reduce viral loads and alleviate lung damage in vivo. This study highlights the potential of HNK as an inhibitor of PRRSV and provides novel insights into its antiviral properties.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Yu Su,Haobo Wen,Ke Hu,Cuiping Wen,Ping Wang,Lulu Zhao,Gang Zou,Wei Jiang,Yaxi Chen,Yunfei Zhao,Qiu Li
The multifaceted pathogenesis and multi-cellular involvement of diabetic nephropathy (DN) stand in stark contrast to the inadequacy of conventional single-target therapeutic strategies. This disparity underscores the urgent need for novel drugs with comprehensive targeting capabilities. Herein, the SREBP cleavage-activating protein/sterol regulatory element-binding proteins (SCAP/SREBPs) pathway was identified as a central driver in DN, where its activation in key renal parenchymal cells promotes lipid metabolic disorders and inflammation, thereby exacerbating renal injury. Guided by this discovery, we screened a 245-member nanoparticle library comprising SCAP inhibitors self-assembled with chitosan, and identified chitosan-lycorine nanoparticles (CLNPs) as the optimal candidate. Owing to its efficient intestinal absorption and significant accumulation in mesangial and proximal tubular epithelial cells, oral CLNPs strongly alleviated renal injury in a murine model of DN by counteracting lipid accumulation and inflammation, consistent with SCAP/SREBPs pathway inhibition. Critically, CLNPs prevented hepatotoxicity from free lycorine, which reduced mortality and enabled safer prolonged therapy. Together, our findings demonstrate the viability of CLNPs for DN, thereby offering a generalizable strategy for combating complex diseases through a single combinatorial agent that counters multiple co-existing pathological injuries.
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高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Chao Meng,Lingye Zhou,Lin Huang,Qi Gu,Xinyue Du,Cheng Wang,Fanglan Liu,Chunhua Xia
Background Hypercholesterolemia is widely implicated in the etiology of coronary heart disease , stroke, and dementia. Evidence suggests that chlorogenic acid (CA) reduces the risk of cardiovascular disease. Purpose The current study aims to explore the underlying molecular mechanism of CA in lowering cholesterol based on pregnane X receptor (PXR) and sterol regulatory element-binding protein 2 (SREBP2) regulatory pathways and their interactions with heat shock protein 90 (HSP90). Methods A hypercholesterolemic mouse model, HepG2 and Caco2 cell models, metabolomics analysis, and co-immunoprecipitation (COIP) were used to study the mechanism of CA lowering cholesterol. Results Treatment of the hypercholesterolemic mice with CA for 12 weeks significantly reduced body weight, blood lipid, hepatic lipid accumulation , and increased lipid excretion. The nuclear aggregation of PXR and SREBP2 was inhibited simultaneously. In addition, the expression of downstream target genes, including Niemann-pick C1-like 1 (NPC1L1) and 3‑hydroxy-3-methylglutaryl-CoA reductase (HMGCR), was downregulated after CA administration. Furthermore, in HepG2 and Caco2 cell models, CA reduced intracellular cholesterol levels by inhibiting the nuclear translocation of PXR and SREBP2 and the expression of NPC1L1 and HMGCR. SREBP2 interacts with PXR through HSP90, and CA reduces the binding stability of SREBP2 and HSP90 and enhances the binding of PXR and HSP90, thus reducing the nuclear accumulation of SREBP2 and PXR simultaneously. Moreover, CA promoted the phosphorylation of AMP-activated protein kinase (AMPK) and its binding to SREBP2. This was not conducive to the binding of HSP90 and SREBP2 but enhanced the binding of HSP90 and PXR, thereby inhibiting the nuclear translocation of SREBP2 and PXR and reducing intracellular cholesterol levels. However, no noticeable direct binding between AMPK and PXR was observed. Conclusion CA downregulates NPC1L1 and HMGCR expression by acting on the AMPK/SREBP2 direct pathway and the AMPK/SREBP2/HSP90/PXR indirect pathway, thus retaining cholesterol homeostasis.
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高影响因子
Advanced Science
·
2022
·Vol. 9
·期 28
·2200750
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IF 17.521
Shaoqin Zheng,Jiahui Lin,Zhongqiu Pang,Hui Zhang,Yinuo Wang,Lanjing Ma,Haijiao Zhang,Xi Zhang,Maorong Chen,Xinjun Zhang,Chao Zhao,Jun Qi,Liu Cao,Min Wang,Xi He,Ren Sheng
Frizzled (Fzd) proteins are Wnt receptors and play essential roles in development, homeostasis, and oncogenesis. How Wnt/Fzd signaling is coupled to physiological regulation remains unknown. Cholesterol is reported as a signaling molecule regulating morphogen such as Hedgehog signaling. Despite the elusiveness of the in-depth mechanism, it is well-established that pancreatic cancer specially requires abnormal cholesterol metabolism levels for growth. In this study, it is unexpectedly found that among ten Fzds, Fzd5 has a unique capacity to bind cholesterol specifically through its conserved extracellular linker region. Cholesterol-binding enables Fzd5 palmitoylation, which is indispensable for receptor maturation and trafficking to the plasma membrane. In Wnt-addicted pancreatic ductal adenocarcinoma (PDAC), cholesterol stimulates tumor growth via Fzd5-mediated Wnt/ β -catenin signaling. A natural oxysterol, 25-hydroxylsterol competes with cholesterol and inhibits Fzd5 maturation and Wnt signaling, thereby alleviating PDAC growth. This cholesterol-receptor interaction and ensuing receptor lipidation uncover a novel mechanism by which Fzd5 acts as a cholesterol sensor and pivotal connection coupling lipid metabolism to morphogen signaling. These findings further suggest that cholesterol-targeting may provide new therapeutic opportunities for treating Wnt-dependent cancers.
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高影响因子
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