Journal of Inflammation Research
·
2024
·
IF 4.2
Jia-Huan He,Xiang-Jun Li,Shi-Peng Wang,Xia Guo,Hao-Xuan Chu,Han-Chi Xu,Yu-Shi Wang
Objective In this study, we investigated the effect and mechanism of action of eugenol on oxidized low-density lipoprotein (ox-LDL)-induced abnormal proliferation and migration of human vascular smooth muscle cells (HVSMCs).Methods HVSMCs were treated with 100 ug/mL ox-LDL for 24 hours to establish a cell model. After 1-hour pretreatment, eugenol at concentrations of 5, 25, and 50 uM was added. Cell viability was assessed using an MTT assay, PCNA expression was detected using Western blot, cell cycle distribution was analyzed using flow cytometry, and cell migration ability was evaluated using wound healing and Transwell migration assays. To investigate the mechanisms, Ang II receptors were inhibited by 1000 nM valsartan, MFG-E8 was knocked down by shRNA, MCP-1 was inhibited by siRNA, and MFG-E8 was overexpressed using plasmids.Results The findings from this study elucidated the stimulatory impact of ox-LDL on the proliferation and functionality of HVSMCs. Different concentrations of eugenol effectively mitigated the enhanced activity of HVSMCs induced by ox-LDL, with 50 uM eugenol exhibiting the most pronounced inhibitory effect. Flow cytometry and Western blot results showed ox-LDL reduced G1 phase cells and increased PCNA expression, while 50 uM eugenol inhibited ox-LDL-induced HVSMC proliferation. In wound healing and Transwell migration experiments, the ox-LDL group showed larger cell scratch filling and migration than the control group, both of which were inhibited by 50 uM eugenol. Inhibiting the Ang II/MFG-E8/MCP-1 signaling cascade mimicked eugenol’s effects, while MFG-E8 overexpression reversed eugenol’s inhibitory effect.Conclusion Eugenol can inhibit the proliferation and migration of ox-LDL-induced HVSMCs by inhibiting Ang II/MFG-E8/MCP-1 signaling cascade, making it a potential therapeutic drug for atherosclerosis.
研究领域:
心血管疾病
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CURRENT PHARMACEUTICAL BIOTECHNOLOGY
·
2021
·Vol. 22
·期 12
·1672-1682
·
IF 2.837
Qiu Chengjiang,Liu Kairui,Li Xuguang,Chen Weirun,Zhang Sheng,Huang Youxing
Background: The pathogenesis of Severe Acute Pancreatitis (SAP) is mediated substantially by dysfunctions in the intestinal barrier. Euphorbia kansui (EK) is a medicinal plant used widely in traditional Chinese medicine to treat inflammation; however, its efficacy and mechanism of action
in SAP treatment are not yet well understood. Objective: To investigate the role of EK in intestinal barrier tissue repair and in the pathogenesis and development of SAP. Methods: The rat SAP model was established by a retrograde injection of sodium taurocholate into the pancreatic
bile duct. The SAP model group and the SAP + EK treatment groups were divided into 6 subgroups according to timing: 2, 6, 12, 24, 48, or 72h after inducing SAP. The progression of the SAP rats and of the rats receiving the EK treatment was evaluated using the ascites volume, serum amylase
and plasma endotoxin levels, and histological grading of intestinal mucosal damage. In addition, serum inflammatory factor contents were measured using Enzyme-Linked Immunosorbent Assay (ELISA) tests and apoptotic cells in damaged ileum tissue were detected using TUNEL staining. Apoptosis
markers and other signaling proteins in intestinal mucosal cells were detected by immunohistochemical assays and then validated by combining these data with quantitative polymerase chain reactions and western blotting. Results: Compared with the results of the SAP model rats, the results
of the rats that received EK treatment demonstrated that EK could effectively reduce the ascites volume and serum amylase and plasma endotoxin levels. EK treatment also greatly reduced the abnormal intestinal morphological alterations in the rat SAP model and significantly downregulated the
serum contents of Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. EK treatment inhibited the elevation of capapse-3, inhibited the decrease of the Bcl-2 protein, and decreased the number of apoptotic cells in rat ileum tissue. Finally, EK treatment abrogated the increase
of HMGB1 and the suppression of MFG-E8 protein expression in the SAP + EK rat ileum tissue. Conclusion: EK suppresses SAP pathogenesis by restoring the intestinal barrier function and modulating the HMGB1/MFG-E8 signaling axis.
研究领域:
药理学
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病理生理学
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中医药学
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分子生物学
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DOI
PubMed
高影响因子
Neurochemical Journal
·
2026
·Vol. 20
·期 1
·97-112
·
IF 0.6
Lifang Li,He Xiaoyi,Zhang Jiaqi,Wang Xiao,Li Guoying,Yang Junhua
Mild traumatic brain injury (mTBI) originates from tensile injury of axons caused by rapid forces. ATPase phospholipid transporting 8A2 (ATP8A2) maintains membrane asymmetry, and its dysregulation leads to phosphatidylserine (PS) exposure. Neuronal injury induced by ATP8A2 mutation or knockout resembles the pathological phenotype of mTBI, indicating its involvement in the pathological process of mTBI. Given that the PS/MFG-E8/VNR pathway mediates microglial phagocytosis, this study aimed to investigate whether blocking VNR can alleviate mTBI-induced synaptic loss and cognitive impairments, and clarify the underlying mechanism. We induced traumatic brain injury (TBI) in C57BL/6J mice using a weight-drop model, assessed neurological function by neurological deficit scoring (NSS) at 4 h, 1 day and 3 days after injury, and detected brain edema, neuroinflammation, pathological changes and by brain water content measurement, ELISA, HE staining, immunofluorescence and Western blotting. Cerebral edema, neuroinflammation, pathological changes and ATP8A2, microglia and synapse-related proteins were detected by ELISA, HE staining, immunofluorescence and Western blotting. Blocking the VNR receptor altered the outcomes of synaptic loss and cognitive behavioral abnormalities, but did not change the result of increased inflammatory factor levels in the prefrontal cortex. Blocking the PS/MFG-E8/VNR pathway promotes cognitive functional recovery in mTBI model mice by inhibiting microglial phagocytosis of synapses in the prefrontal cortex.
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DOI
高影响因子
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