Septic acute lung injury (Septic-ALI, SA) is a severe complication of sepsis with limited clinical treatment options. Ethyl Caffeate (EC) is a phenolic compound isolated from Ilex latifolia Thunb (I. latifolia) of the Aquifoliaceae family.

PURPOSE:

This study aimed to investigate the potential mechanisms of EC in treating SA by integrating network pharmacology and transcriptomics.

METHODS:

We used network pharmacology to predict the potential pathways and targets of EC and validated these predictions using the GEO database, molecular docking and MDS. Subsequently, LPS-induced inflammation models in RAW cells and a mouse model of SA were established to evaluate the therapeutic effects of EC. Cell transcriptomic sequencing, along with ELISA, qRT-PCR, and Western blot analyses, were performed on both cellular and animal models to validate the key pathways and targets.

RESULTS:

EC targeted TNF-α and MMP9, significantly alleviating LPS-induced SA through the TNF-α/NF-κB/MMP9 axis. Specifically, network pharmacology and molecular docking suggested that EC may target TNF, MMP9, EGFR, PRKACA, and MAPK3. Transcriptomic analyses, MDS and in vitro and in vivo experiments showed that EC primarily reduced the expression of p-p65 and p-IκBα in the TNF pathway by inhibiting TNF-α, thereby downregulating the expression of downstream effector molecules MMP9 and MMP14, and improving lung tissue damage, cell apoptosis, and inflammation levels in mice.

CONCLUSION:

This study was the first to integrate network pharmacology and transcriptomic results, revealing the mechanism by which EC ameliorated SA through the TNF-α/NF-κB/MMP9 axis. Furthermore, experimental validation identified TNF-α and MMP9 as two core targets of EC, providing a valuable reference for the clinical treatment of SA.

2025-06-01·BIOORGANIC CHEMISTRY

Phenylpropanoids of Eleutherococcus senticosus (Rupr. & maxim.) maxim. Alleviate oxidative stress in Alzheimer's disease in vitro and in vivo models by regulating Mst1 and affecting the Nrf2/Sirt3 pathway

Article

作者: Meng, Xin ; Xu, Shi-Qi ; Li, Hua ; Chen, Qing-Shan ; Yang, Bing-You ; Zhao, Wei ; Guan, Wei ; Kuang, Hai-Xue ; Zhang, Li-Li ; Liu, Yan ; Yang, Rui ; Wang, Si-Yi ; Li, Meng-Meng

Alzheimer's disease (AD) is a common neurodegenerative disorder, and oxidative stress plays a significant role in its progression. Owing to its nourishing effects, Eleutherococcus senticosus (Rupr. & maxim.) maxim. (ES) has gained widespread popularity globally as a functional food and long-term consumption has been shown to enhance memory. The phenylpropanoid components extracted from Eleutherococcus senticosus (Rupr. & maxim.) maxim. (ESP) exhibit a diverse array of bioactivities and are commonly employed in the treatment of central nervous system (CNS) disorders. Nonetheless, the exact mechanisms by which ESP alleviates oxidative stress in AD models require further investigation. Therefore, this study utilized SAMP8 mice as models for AD and employed L-glutamate (L-Glu)-induced HT22 cells to establish an in vitro AD model. The effects of ESP on cognitive function were evaluated using the Morris water maze (MWM) test. Additionally, various techniques such as pathology, immunofluorescence staining (IF), ROS staining, cellular thermal shift assay (CETSA), Mst1 inhibitor analysis, and western blotting (WB) were conducted to further investigate the pharmacological efficacy and potential molecular mechanisms of ESP. In vivo, ESP was found to improve cognitive function in SAMP8 mice and alleviate AD-like pathological features. In vitro, ESP reduced intracellular ROS levels. Mechanistically, CETSA analysis confirmed the binding affinity between ESP and Mst1, demonstrated that ESP modulated the Mst1 signaling pathway to mitigate oxidative stress and decrease ROS levels. These findings suggested that ESP holded significant potential for developing therapeutic strategies for AD.

2025-05-01·POULTRY SCIENCE

Network pharmacology and molecular docking reveal the mechanism of Chinese herb ultrafine powder improving meat nutritional value in aged laying hens

Article

作者: Meng, Chengwen ; Azad, M A K ; Lan, Wei ; He, Jianhua ; Gui, Jue ; Kong, Xiangfeng ; Lin, Wenchao ; Cui, Yadong

This study investigated the effects of dietary Chinese herb ultrafine powder (CHUP) supplementation on meat quality, plasma biochemical parameters, and fatty acid and amino acid composition in pectoral muscles of aged laying hens. A total of 576 Xinyang black-feather laying hens (300-d-old) were randomly allocated to eight groups, including the control group (fed a basal diet) and different CHUP groups (details in 'Materials and methods' section). The trial lasted 120 d. The findings showed that L-LF and L-LF-T supplementation increased the contents of polyunsaturated fatty acids and unsaturated fatty acids (P < 0.05), while CHUP supplementation increased (P < 0.05) the total essential amino acid content in pectoral muscles. Network pharmacology analysis predicted that L-LF-T supplementation mainly influenced the PPAR signaling pathway, which is associated with meat quality. These findings suggest that CHUP supplementation can enhance the nutritional value of pectoral muscles, potentially through its association with the PPAR signaling pathway in aged laying hens.

100 项与 Ethyl caffeate 相关的药物交易

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