JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Mengze Ding,Xiaohan Wei,Changshun Liu,Xiaomei Tan
Ethnopharmacological relevance Allergic rhinitis (AR) is a prevalent nasal inflammatory disorder, and pyroptosis plays a crucial role in aggravating AR. Current medications for AR treatment still have deficiencies, and finding new agents is of great interest. Mahuang Fuzi Xixin decoction (MFXD), an ancient Chinese medicine, is now commonly used to treat AR, which has anti-inflammatory and immunomodulatory effects, but its underlying mechanism is unknown. Aim of this study This study aims to evaluate the effects of MFXD on AR and explore its potential mechanisms in view of the regulatory effect on pyroptosis. Methods MFXD, Mahuang, Fuzi, and Xixin water extracts were analyzed using ultra high performance liquid chromatography-Orbitrap-high-resolution accurate mass spectrometry. In in vivo study, the effects of MFXD on AR treatment were evaluated in an ovalbumin-induced mouse model. Mice were administered saline (control and model groups), MFXD (1.375, 2.75 g/kg), and dexamethasone (2.5 mg/kg) for 13 days. AR symptoms were evaluated by blinded observers. Immunoglobulin E (IgE) and histamine levels were measured using enzyme-linked immunosorbent assays. Expression of pyroptosis-related proteins (NLRP3, ASC, Caspase-1 p10/p20, GSDMD-N and IL-1β) in AR mouse nasal mucosa were estimated by immunohistochemistry. In in vivtro study, the effects of MFXD on pyroptosis were assessed in human nasal epithelial cells (HNEpCs) stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP), and incubated with MFXD (12.5, 25, and 50 μg/mL). Pyroptosis-related protein expression was measured by western blotting. Results Thirty-three compounds in MFXD were identified, including ephedrine, pseudoephedrine, higenamine, aconine, aconitine, benzoylmesaconitine, benzoylhypaconine and hypaconitine. In the in vivo study, oral taken of MFXD/dexamethasone significantly ameliorated AR symptoms, reduced swelling of the nasal mucosa, and decreased the levels of IgE and histamine in AR mice serum. MFXD/dexamethasone attenuated histopathological changes and reduced the expression of pyroptosis-related proteins in nasal mucosa, indicating the inhibitory effect on nasal epithelial pyroptosis. In the in vitro study, MFXD (50 μg/mL) significantly alleviated cytotoxicity, protected cells from swelling and rupture, and downregulated the expression of pyroptosis-related proteins in LPS/ATP-induced HNEpCs. Conclusion MFXD suppressed nasal epithelial pyroptosis by inhibiting the NLRP3/Caspase-1/GSDMD-N signaling pathway, which alleviates AR. Our results offer valuable insights into potential AR therapies and provide evidence for the clinical utilization of MFXD to treat AR.
研究领域:
药理学
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免疫学
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民族药理学
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炎症
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中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-24
·
IF 12.6
Tong Xin-Yi,Nong Wei-Jian,Tan Run-Min,Ouyang Jian-Ming
Objective This study aimed to compare the differences in pyroptosis and polarization of macrophages induced by different sizes of calcium oxalate monohydrate (COM) crystals and discuss the mechanism of kidney stone formation. Methods COM crystals with sizes of about 100 nm, 500 nm, 2.5 μm, and 10 μm were synthesized and characterized. THP-1 cells were induced to differentiate into macrophage-like cells. The damage of COM crystals to Mφs was evaluated by CCK-8 assay. The activation of the pyroptosis signaling pathway, cell morphology, and proportion of pyroptosis cells in Mφs induced by COM crystals were detected. Finally, the proportion of M1/M2 polarization was qualitatively and quantitatively assessed. Results COM-100 nm, COM-500 nm, COM-2.5 μm, and COM-10 μm all significantly induced the pyroptosis and polarization of Mφs. Among them, at the same cell viability, COM-10 μm induced the highest pyroptosis rate. The expression of NLRP3 and GSDMD-N induced by COM-10 μm increased by 81.43 ± 11.45% and 112.00 ± 9.87%, respectively, and the rate of caspase-1/PI double-positive pyroptosis cells was 22.2%. Meanwhile, COM-10 μm induced the highest proportion of M1 polarization (M1/M2 ratio was 209.90% ± 2.54%). Conclusion COM-10 μm significantly activates the classical caspase-1-mediated pyroptosis pathway and promotes M1 polarization in Mφs. Therefore, at the same cell viability, large-sized micro-COM is more capable of inducing inflammation than nano-COM. Graphical
研究领域:
纳米技术
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泌尿科学
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免疫学
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细胞生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Meitong Liu,Jing Lu,Qingbin Liu,Yuelin Chen,Guang Wang,Qian Zhang,Shuang Guan
Sodium metabisulphite (SMB) is the most used foods and drugs antioxidant among sulfites . So far, there were few studies about its harm, especially in mast cells. Our study was to investigate the effects of SMB on mitophagy and pyroptosis in mast cells. The results revealed that SMB dose-dependently promoted the expressions of NLRP3, GSDMD-N and other marker proteins of pyroptosis. Knockdown of GSDMD, NLRP3 inhibitor, mitophagy activator and mtROS inhibitor all reversed the changes in pyroptosis indicators caused by SMB. Considering the degranulation characteristics of mast cells and the sensitization of sulfite, we examined the effects of the above inhibitors on the degranulation of mast cells caused by SMB. The results showed that SMB-mediated mast cell degranulation was significantly inhibited by the above inhibitors. Meanwhile, we used immunofluorescence co-localization experiments and found that GSDMD pore-forming protein and histamine co-localized near the cell membrane. Overall, evidence suggested that SMB caused pyroptosis by inhibiting mitophagy, leading to mast cell degranulation. These findings are of great significance to the sensitization mechanism of SMB and provide a new insight into SMB toxicology and mast cell degranulation.
研究领域:
毒理学
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免疫学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
eNeuro
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2024
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IF 2.7
Yonghong Tan,Qiong Wang,Yubing Guo,Na Zhang,Yingyi Xu,Xue Bai,Jianhua Liu,Xiaobao Bi
Pyroptosis, an inflammatory Programmed cell death, has recently been found to play an important role in spinal cord injury (SCI). C-type lectin domain family 5 member A (CLEC5A), triggering receptor expressed on myeloid cells 1 (TREM1), and NLR-family CARD-containing protein 4 (NLRC4) have been reported to be associated with neuronal pyroptosis, but few studies have clarified their functions and regulatory mechanisms in SCI. In this study, CLEC5A, TREM1, and NLRC4 were highly expressed in lidocaine-induced SCI rat models, and their knockdown alleviated lidocaine-induced SCI. The elevation of proptosis related indicators LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1β levels in SCI rats was attenuated after silencing of CLEC5A, TREM1, or NLRC4. Lidocaine-induced the decrease in cell viability and the elevation in cell death were partly reversed after CLEC5A, TREM1, or NLRC4 silencing. Lidocaine-mediated effects on the levels of LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1β in lidocaine-induced PC-12 cells were weakened by downregulating CLEC5A, TREM1, or NLRC4. CLEC5A could interact with TREM1 to mediate NLRC4 expression, thus accelerating neuronal pyroptosis, ultimately leading to SCI exacerbation. In conclusions, CLEC5A interacted with TREM1 to increase NLRC4 expression, thus promoting neuronal pyroptosis in rat SCI models, providing new insights into the role of neuronal pyroptosis in SCI.Significance statement Pyroptosis has been reported to be involved in SCI. Higher levels of CLEC5A, TREM1, and NLRC4 associated with neuronal pyroptosis. However, the role and regulatory mechanism of CLEC5A, TREM1, and NLRC4 in SCI were not clear. Here, high expression of CLEC5A, TREM1, and NLRC4 was observed in lidocaine-induced SCI rat models. CLEC5A could interact with TREM1 to enhance the expression of NLRC4, thus accelerating neuronal pyroptosis in rat SCI models. These findings identify CLEC5A, TREM1, and NLRC4 as potential therapeutic targets for SCI.
研究领域:
神经科学
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细胞生物学
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炎症
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脊髓损伤
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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