Nano Today
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2024
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IF 13.2
Hui Yan,Danping Wang,Chengyin Tian,Long Zhao,Yong Wang,Guoqing Long,Bingjun Sun,Jingming Jia,Anhua Wang
Darutigenol (DL) is an active diterpenoid extracted from the traditional Chinese medicine Sigesbeckia glabrescens (Makino) Makino, widely employed in the treatment of rheumatoid arthritis (RA) for centuries in China. However, the anti-inflammatory mechanism of DL requires further exploration. In this study, we discovered that DL could scavenge reactive oxygen species (ROS) and nitric oxide (NO), and reduce the secretion of proinflammatory cytokines, inducing the M1-to-M2 polarization of macrophages in vitro . In vivo , DL was demonstrated to exert an anti-inflammatory effect via the JAK1, 3/STAT3 and MAPK pathways. It also showed efficacy in repairing cartilage damage via downregulating the proteins MMP2/MMP9 and inhibiting angiogenesis through the CXCL12/CXCR7 system in synovial tissues. However, the application and therapeutic effect of DL was constrained by its poor water solubility and low bioavailability. To address these limitations, ROS-responsive prodrug nanoassemblies were employed, which could be passively transported to the joint inflammation site and decomposed in the inflammatory environment to release DL. The therapeutic effect of prodrug nanoassemblies was superior to that of DL, with negligible toxicity to organs. In summary, we clarified the anti-RA mechanism of DL and constructed an efficient and safe drug delivery system, which provided a strategy for the further application and development of active compounds in traditional Chinese medicine.
研究领域:
药理学
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纳米技术
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免疫学
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传统中药
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药物递送系统
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炎症
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Benyue Sun,Yunhui Wang,Jingjing Bai,Xuejiao Li,Long Ma,Shuli Man
Ulcerative colitis (UC) is a common chronic, relapsing inflammatory bowel condition. Procyanidins (PC) are known for their antiangiogenic, anti-inflammatory, antioxidant, and antimetastatic properties. However, there is comparatively limited information on how PC interacts with UC. In this study, 5 mg/10 mL/kg body weight of PC was administered to mice with dextran sulfate sodium (DSS)-induced colitis mice. PC treatment prolonged the survival period of mice, ameliorated UC symptoms, reduced damage to the intestinal mucosal barrier, and increased the protein expression of ZO-1 and occludin in the DSS-treated mice. Importantly, PC treatment significantly reduced gene expression related to Th17 cell differentiation, including STAT3, SMAD3, TGF-β, and JAK1. The results of the flow cytometry analysis indicated significant increase in the number of Treg cells and a concomitant decrease in the proportion of Th17 cells in the colon following PC treatment. Additionally, PC increased the abundance of gut microbiota such as Bacteroidota, Oscillospiraceae, Muribaculaceae, and Desulfovibrionaceae, as well as the concentrations of acetate acid, propionate acid, and butyrate acid in the feces. PC also activated short-chain fatty acid receptors, such as G-protein coupled receptor 43 in the colon, which promoted the proliferation of Treg cells. The depletion of gut microbiota and subsequent transplantation of fecal microbiota demonstrated that PC’s effects on gut microbiota were effective in improving UC and restoring intestinal Th17/Treg homeostasis in a microbiota-dependent manner. This suggests that PC could be a promising functional food for the prevention and treatment of UC in the future.
研究领域:
免疫学
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胃肠病学
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微生物学
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药理学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
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2021
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IF 6.922
Zhen-Hua Ying,Hui-Min Li,Wen-Ying Yu,Chen-Huan Yu
Purpose Abnormal glycolysis of immune cells contributed to the development of inflammatory response. Inhibition of this Warburg phenotype could be a promising strategy for preventing various inflammatory diseases. Iridin (IRD) is a natural isoflavone, and exerts anticancer, antioxidant, and anti-inflammatory effects. However, the underlying mechanism of IRD on acute inflammation remains unknown. In this study, the protective effects of IRD against lipopolysaccharide (LPS)-induced inflammation were investigated in murine macrophage RAW264.7 cells and in mice. Methods The inhibition of IRD on NO production in culture medium was detected by Griess assay while the levels of TNF-α, IL-1β, and MCP-1 were detected by ELISA assay. The effects of IRD on OCR and ECAR levels in LPS-treated macrophages were monitored by using Seahorse Analyzer. The apoptosis rate as well as the release of ROS and NO of RAW264.7 cells were analyzed by flow cytometric assay. The protective effects of IRD were investigated on LPS-induced inflammation in mice. The expressions of PKM2 and its downstream (p-JAK1, p-STAT1, p-STAT3, p-p65, iNOS, and COX2) in cells and in lung tissues were detected by Western blotting analysis. Results IRD treatment at the concentrations of 12.5–50 μM significantly inhibited the productions of TNF-α, IL-1β, MCP-1, and ROS, and suppressed the levels of glucose uptake and lactic acid in LPS-treated RAW264.7 cells. Oral administration with IRD (20–80 mg/kg) inhibited LPS-induced acute lung injury as well as inflammatory cytokine production in mice. Moreover, IRD targeted pyruvate kinase isozyme type M2 (PKM2) and suppressed its downstream p-JAK1, p-STAT1, p-STAT3, p-p65, iNOS, and COX2, which could be abolished by PKM2 agonist DASA-58 and antioxidant N-acetyl-L-cysteine, but partly be reversed by NF-κB activator CUT129 and JAK1 activator RO8191. Conclusion IRD alleviated LPS-induced inflammation through suppressing PKM2-mediated pathways, and could be a potential candidate for the prevention of inflammatory diseases.
研究领域:
药理学
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免疫学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
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2025
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IF 26.8
Wentao Wang,Zhenyu Li,Siming Zhang,Yue Ma,Lei Yu,Qidong Zhang,Guoqing Pan,Dechun Geng,Chen Zhu,Jiaxiang Bai
The reduced initial stability of orthopedic implants in osteoporotic bone matrices, coupled with excessive M1 macrophage polarization at bone-implant interfaces, disrupt bone–immune homeostasis and vascularization, ultimately leading to implant loosening or failure. Inspired by the marine mussel Mytilus edulis foot protein (Mefp), a pH-responsive multifunctional bone glue (YDC-Gel-Zn) with broad-spectrum adhesion capabilities is developed for osteoporotic bone-implant integration. This pseudo-Mefp bioglue enables dual-interface adhesion via catechol-rich sequences that mediate stable metal-phenolic coordination with metallic implants and hydrogen-bonded/Michael addition-driven interactions with the bone matrix, thereby improving initial implant fixation. Under osteoporotic inflammatory microenvironments, sequential dissociation of borate ester bonds and metal‒phenolic coordination facilitates the controlled release of Zn 2 ⁺ and proangiogenic/osteogenic peptides (YDC). The released Zn 2 ⁺ remodels glutathione metabolism through glutathione S-transferase (GST)-mediated regulation of glutathione (GSH) levels, inhibits JAK1/STAT1/NLRP3 inflammasome activation, and suppresses the release of proinflammatory cytokines from senescent M1 macrophages, recalibrating the osteo-vascular-immune microenvironment. Due to its positive effects on bone regeneration and angiogenesis, the bioinspired bone bioglue demonstrated a 194% increase in fixation strength in osteoporotic rat models, achieving 93% healthy bone-implant stability. Overall, this study provides a clinically translatable strategy for stable implantation under osteoporotic conditions through synergistic mechanical adaptation, bioactivity regulation, and smart environmental responsiveness.
研究领域:
生物医学工程
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生物材料
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组织工程
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骨科
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免疫调节
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再生医学
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生物粘合剂
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）