INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Anming Zhu,Junxi Liu,Xianxian Cao,Jiahui Wu,Fengkun Xiao,Youyun Liu,Yanzhen Shen,Feifei Wang,Liping Qu
Pedunculoside as a TLR3-targeting immunomodulator for cheilitis-like inflammation treatment. • Pedunculoside has anti-skin inflammation and barrier repaire effects. • Pedunculoside inhibits the TLR3/TRIF/NF-κB signaling. • Pedunculoside provides a novel plant-assisted strategy for the treatment of cheilitis. Background Cheilitis is a lip-specific inflammatory disorder lacking safe long-term therapies. Topical glucocorticoids are limited by adverse effects, highlighting the need for plant-derived immunomodulators with dual anti-inflammatory and barrier-repairing effects. Objective To evaluate the therapeutic potential, mechanism and human efficacy of pedunculoside in cheilitis. Methods Pedunculoside was evaluated in vitro using CCK-8, scratch, ELISA, immunofluorescence, RT-qPCR, western blot, molecular docking and SPR. In human efficacy evaluation, pedunculoside formulation were assessed by VISIA-CR imaging, skin hydration and transepidermal water loss on the lips. Results Pedunculoside (≤120 μM) showed no cytotoxicity and increased scratch wound closure 4.5-fold ( N = 4). It upregulated barrier genes (AQP3: 1.7-fold, FLG: 2.3-fold, SPINK5: 11.16-fold, IVL: 7.96-fold, ZO-1: 2.26-fold, OCLN: 2.22-fold and KRT1: 4.41-fold) ( N = 4) and suppressed inflammatory cytokines (IL-6: 0.68-fold, IL-8: 0.53-fold, IL-1β: 0.65-fold, TSLP: 0.69-fold, CCL5: 0.55-fold and CCL17: 0.58-fold) ( N = 3). Mechanistically, pedunculoside directly bound with TLR3 and suppressed TLR3/TRIF/NF-κB signaling. In human efficacy, the pedunculoside formulation reduced lip redness by 0.3-fold (4 h, N = 32) and 0.23-fold (at 28 days, N = 20), decreased TEWL value by 0.22-fold (at 4 h) and 0.27-fold (at 28 days) and improved hydration by 0.22-fold (at 4 h) and 0.27-fold (at 28 days) versus baseline. Conclusion Pedunculoside is a novel TLR3-targeting immunomodulator that enhances barrier repair and suppresses inflammation in vitro, while its formulation improves cheilitis symptoms. The absence of animal studies before human testing represents a limitation; larger trials are warranted to confirm long-term safety and efficacy. Download: Download high-res image (372KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
ENVIRONMENTAL POLLUTION
·
2022
·
IF 9.988
Ying Tu,Yongyong Yang,Yue Wang,Nana Wu,Junyan Tao,Guanghong Yang,Mingdan You
Neurodevelopmental exposure to chlorpyrifos (CPF) could increase risks for neurological disorders, such as autism spectrum disorder, cognitive impairment, or attention deficit hyperactivity disorder. The potential involvement of microglia reactive to inflammatory stimuli in these neurological disorders has been generally reported. However, the concrete effects and potential mechanisms of microglia dysfunction triggered by developmental CPF exposure remain unclear. Therefore, we established mouse and human embryonic microglial cells (HMC3 cell) models of developmental CPF exposure to evaluate the effects of developmental CPF exposure on neuroinflammation and underlying mechanisms. The results showed that developmental exposure to CPF enhanced the expression of Iba1 in hippocampus. CPF treatment increased inflammatory cytokines levels and TSPO expression in hippocampus and HMC3 cells. The levels of necroptosis and necroptosis-related signaling RIPK/MLKL were increased in hippocampus and HMC3 cells following CPF exposure. Furthermore, the expression of TLR4/TRIF signaling was increased in hippocampus and HMC3 cells subjected to CPF exposure. Notably, the increased levels of TLR4/TRIF signaling, RIPK/MLKL signaling, necroptosis and pro-inflammatory cytokines induced by CPF treatment were remarkably inhibited by TAK-242 (a specific TLR4 inhibitor). Additionally, the necroptosis and pro-inflammatory cytokines production induced by CPF treatment were significantly relieved by Nec-1 (a specific RIPK1 inhibitor). In general, the above results suggested that activated microglia in hippocampus subjected to developmental CPF exposure underwent RIPK1/MLKL-mediated necroptosis regulated by TLR4/TRIF signaling.
研究领域:
神经科学
·
毒理学
·
细胞生物学
·
发育生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2015
·
IF 5.736
Xiaomin Xia,Juanli Fu,Xiufang Song,Qiong Shi,Chuanyang Su,Erqun Song,Yang Song
Fulminant hepatic failure (FHF) is a lethal clinical syndrome characterized by the activation of macrophages and the increased production of inflammatory mediators . The purpose of this study was to investigate the effects of neohesperidin dihydrochalcone (NHDC), a widely-used low caloric artificial sweetener against FHF. An FHF experimental model was established in mice by intraperitoneal injection of D-galactosamine ( d -GalN) (400 mg/kg)/lipopolysaccharides (LPS) (10 μg/kg). Mice were orally administered NHDC for 6 continuous days and at 1 h before d -GalN/LPS administration. RAW264.7 macrophages were used as an in vitro model. Cells were pre-treated with NHDC for 1 h before stimulation with LPS (10 μg/ml) for 6 h. d -GalN/LPS markedly increased the serum transaminase activities and levels of oxidative and inflammatory markers, which were significantly attenuated by NHDC. Mechanistic analysis indicated that NHDC inhibited LPS-induced myeloid differentiation factor 88 (MyD88) and TIR-containing adapter molecule (TRIF)-dependent signaling. Transient transfection of TLR4 or MyD88 siRNA inhibited the downstream inflammatory signaling. This effect could also be achieved by the pretreatment with NHDC. The fluorescence microscopy and flow cytometry results suggested that NHDC potently inhibited the binding of LPS to TLR4 in RAW264.7 macrophages. In addition, the inhibitory effect of NHDC on LPS-induced translocation of TLR4 into lipid raft domains played an important role in the amelioration of production of downstream pro-inflammatory molecules. Furthermore, the activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) by NHDC inhibited TLR4 signaling. In conclusion, our results suggest that NHDC attenuates d -GalN/LPS-induced FHF by inhibiting the TLR4-mediated inflammatory pathway, demonstrating a new application of NHDC as a hepatoprotective agent.
研究领域:
免疫学
·
肝病学
·
药理学
✓ 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）