Pharmaceuticals
·
2025
·Vol. 18
·期 8
·1109
·
IF 4.8
Lingxin Zhuo,Mingxuan Ma,Jiayi Zhang,Jiayu Zhou,Yuqi Zheng,Aiyin Liang,Qingqing Sun,Jia Liu,Wenting Liao
Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC.Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models.Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2.Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment.
研究领域:
心脏病学
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药理学
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中医学
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分子生物学
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免疫学
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代谢组学
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网络药理学
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产品关联
DOI
PubMed
高影响因子
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2021
·Vol. 85
·期 7
·1665-1674
·
IF 2.043
Feng Wei
This study aims to explore the effect of Tectorigenin in chronic cerebral ischemia (CCI)-induced cognitive impairment mice model. Cognitive impairment, hippocampal tissue histopathology, and myelin density in CCI mice were detected. HT22 cells were used to induce oxygen–glucose deprivation/reperfusion (OGD/R) injury. Cell viability and apoptosis of transfected HT22 cells and toll-like receptor-4 (TLR4)/nuclear factor-kappaB (NF-κB) pathway–related factor levels in hippocampal tissue and OGD/R models were detected. CCI caused cognitive impairment, hippocampal damage, and decreased myelin density in mice while promoting interleukin-1β, tumor necrosis factor-alpha, TLR4, myeloid differentiation primary response gene 88, p-p65, NLRP3, and ASC levels. Tectorigenin reversed the effects of CCI in mice and reversed the promoting effects of OGD/R on apoptosis and TLR4/NF-κB pathway–related factors levels, while overexpressed TLR4 reversed the effects of Tectorigenin in OGD/R-induced HT-22 cells. Tectorigenin alleviated cognitive impairment in CCI mice by inhibiting the TLR4/NF-κB signaling pathway.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ALZHEIMERS DISEASE
·
2025
·
IF 3.1
Yanyu Zhai,Kaili Lu,Yuan Yuan,Ziyao Zhang,Lixia Xue,Fei Zhao,Xiaofeng Xu,Hongmei Wang
BackgroundAlzheimer's disease (AD) causes cognitive function disorder and has become the preeminent cause of dementia. Glucagon-like peptide-1 (GLP-1) receptor agonists, semaglutide, have shown positive effects on promoting the cognitive function. However, research about the mechanism of semaglutide as a therapeutic intervention in AD is sparse.ObjectiveThis study was to investigate the therapeutic efficacy of semaglutide in a transgenic mouse model of AD pathology and explored the detailed mechanism by semaglutide modulated neuroinflammatory processes.MethodsMale amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice were treated with semaglutide or vehicle for 8 weeks. Morris water maze test was used to assess the therapeutic efficacy of semaglutide on recognition function. Pathology analysis was performed to detect the deposition of amyloid plaques. High-throughput sequencing analysis was applied to specify the mechanism. Microglia and astrocyte activation were assessed with immunofluorescent staining. Inflammation cytokine levels were evaluated with enzyme-linked immunosorbent assay (ELISA). Related proteins and pathway were evaluated with western blot.ResultsSemaglutide treatment attenuated Aβ accumulation and enhanced cognitive function in APP/PS1 transgenic mice. Through transcriptomic profiling, immunohistochemical staining, and ELISA, semaglutide was substantiated to inhibit the overactivation of microglia and astrocytes, as well as to curtail the secretion of inflammatory mediators. Furthermore, semaglutide robustly activated AMP-activated protein kinase (AMPK) and suppressed the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling cascade, thus reducing the Aβ deposition and dampening the inflammatory cascade.ConclusionsThe results demonstrated that semaglutide mitigated neuroinflammation and decelerated the advance of AD in APP/PS1 transgenic mice.
研究领域:
神经科学
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药理学
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分子生物学
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神经退行性疾病
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炎症研究
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Guohui Xue,Huifang Xiong,Shixiu Wang,Yingjun Fu,Yong Xie
Objective Tripterygium glycoside (TG) is a fat-soluble extract of Tripterygium wilfordii, with anti-inflammatory properties associated with TLR signaling pathways. This study constructed a targeted delivery system for experimental colitis, namely, eudragit (EuL)-coated chitosan (Ch)-TG conjugate microspheres (Ch-TG-MS/EuL), and evaluated its therapeutic efficacy and underlying mechanisms. Methods Ch-TG-MS was fabricated using emulsification cross-linking technique and then coated with EuL to create Ch-TG-MS/EuL. Drug release properties were assessed using a dialysis model. Additionally, the therapeutic benefits of Ch-TG-MS/EuL on colonic inflammation and its specific effect on TLR4/NF-κB signaling in intestinal mucosa were evaluated in vivo using a DSS-induced murine colitis model. Results The Ch-TG-MS/EuL microspheres appeared as yellow powders with a slightly enlarged shape, rough surface, and adhesions. The Ch-TG-MS/EuL formulations also exhibited high entrapment efficiency and drug loading rate. High-performance liquid chromatography revealed that Ch-TG-MS/EuL exhibited a less intense peak than free TG, confirming that the drug is contained within the formulation. Free TG displayed explosive release within the first 5 h of administration, while Ch-TG-MS/EuL prevented the pre-mature release of TG and exhibited controllable release up to 24 h. In vivo, noticeable amelioration of intestinal mucosal tissue destruction was achieved with Ch-TG-MS/EuL compared to free TG. Additionally, immunohistochemical and western blotting results revealed that Ch-TG-MS/EuL markedly down-regulated the expression of intestinal mucosal TLR4, MyD88, and NF-κB p65. Hence, Ch-TG-MS/EuL may ameliorate the colon inflammatory response by inhibiting the hyperactivation of TLR4/NF-κB signaling. Conclusion Novel Ch-TG-MS/EuL preparation may represent a colonic delivery system for UC therapeutics by inhibiting TLR4/NF-κB hyperactivation. Data availability All experimental data supporting the conclusions of this study are available from the corresponding author on reasonable request.
研究领域:
药学
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药理学
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免疫学
·
药物递送系统
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炎症性肠病
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ANIMAL PHYSIOLOGY AND ANIMAL NUTRITION
·
2024
·
IF 2.2
Wenyue Qiu,Wenxin Jiang,Yiman Su,Hui Huang,Jiali Ye,Rongmei Wang,Zhaoxin Tang,Rongsheng Su
Lipopolysaccharides (LPS) is the major compoent of Gram-negative bacteria and an important factor in inducing inflammation, which usually leads to multiple organ failure in broilers, seriously affecting the growth performance of broilers and hindering the development of poultry farming. Under the policy of prohibiting antibiotics in feed, it has become more urgent to find natural drugs to prevent liver damage caused by LPS in broilers. Asiatic acid (AA) is a pentacyclic triterpene that has been proven to have anti-inflammatory and antioxidant effects. However, the protective effects of AA in LPS-induced liver damage in broilers still need to be clarified. This study aims to explore the complete mechanism of AA against LPS-induced acute liver injury (ALI) in broilers. A total of 60 broilers (1 day old) were randomly divided into the control group, LPS group, LPS+AA (15, 30 and 60 mg/kg) group and control+AA (60 mg/kg) group. At 16, 18 and 20 days of age, the broilers were attacked with LPS (0.5 mg/kg) to construct liver injury model. H&E staining assessed liver pathological changes. The mRNA and protein expression levels related to the HMGB1/TLR4/NF-κB pathway, pyroptosis, and ERS-mediated apoptosis in the liver tissue were detected. Our results founded that intraperitoneal injection of LPS in broilers increased the activities of AST and ALT, as well as raising the related gene and protein expression of the HMGB1/TLR4/NF-κB pathway, pyroptosis, and ERS-mediated apoptosis. Interestingly, AA improved LPS-induced liver damage and decreased the activities of AST and ALT in broilers. Additionally, AA mitigated LPS-induced ALI by reducing the mRNA levels and protein expressions of the HMGB1/TLR4/NF-κB pathway, pyroptosis and ERS-mediated apoptosis. In conclusion, the present study investigated that AA mitigated LPS-induced ALI in broilers by reducing pyroptosis and ERS-mediated apoptosis via inhibition of the HMGB1/TLR4/NF-κB pathway. Therefore, AA may serve as a potential feed additive for the prevention of LPS-induced ALI in broilers.
研究领域:
兽医学
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药理学
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免疫学
·
动物科学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Canchao Jia,Minjuan Yang,Guanlin Xiao,Zhihao Zeng,Lingjie Li,Yangxue Li,Jieyi Jiang,Aili Xu,Jinyan Qiu,Ruiyin Tang,Dongmei Li,Dezheng Jia,Canhui Xie,Guangying Wu,Dake Cai,Xiaoli Bi
Backgrounds Idiopathic pulmonary fibrosis (IPF) is a persistent and advanced pulmonary ailment. The roles of innate immunity and adaptive immunity are pivotal in the evolution of IPF. An ill-adjusted interaction between epithelial cells and immune cells is responsible for initiating the epithelial–mesenchymal transition (EMT) process and sustaining chronic inflammation, thereby fostering fibrosis progression. The intricacy of IPF pathogenesis has hindered the availability of efficacious agents. Elephantopus scaber Linn. (ESL) is a canonical Chinese medicine with significant immunoregulatory effects, and its aqueous extract has been proven to attenuate IPF symptoms in bleomycin (BLM)-induced mice. However, the underlying mechanism through which ESL relieves IPF remains unclear. Aim To validate whether ESL reverses IPF by mediating the immune response and EMT. Methods : Ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and UPLC were used to identify the components and determine the concentrations of the specific compounds in the ESL. Network pharmacology and molecular docking were applied to predict the potential mechanism underlying the anti-IPF effect of ESL. BLM-induced IPF mice were used to validate the anti-IPF effect of ESL, and lung tissue was collected to test putative pathways involved in inflammation and EMT via immunohistochemistry (ICH), real-time quantitative polymerase chain reaction (RT–qPCR) and Western blotting. Results Sixty-one compounds were identified, and thirteen main ingredients were quantified in the ESL. In silico experiments predicted that the IPF-mediated reversal of adverse effects by ESL would be related to interruption of the Toll-like receptor 4 (TLR4)/nuclear factor-k-gene binding (NF- ĸ B) inflammatory pathway and the transforming growth factor-beta l (TGF-β1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O3 (FOXO3a) fibrosis pathway. In vivo experiments showed that ESL alleviates BLM-induced lung inflammation and fibrosis by reducing neutrophil aggregation and fibroblast foci, similar to the effects of the positive control drug pirfenidone (PFD). ESL markedly inhibited the transcription of TNF-α, IL-1 β, and IL-6, which are downstream genes of the NF-κB signaling pathway. Furthermore, the protein levels of TLR4 and p-NF- κ B were correspondingly inhibited in response to ESL treatment. Additionally, ESL reverses BLM-induced changes in the expression of EMT-related biological characteristic indicators (collagen I [COLIA1], E-cadherin, and alpha smooth muscle actin [ α -SMA]) at the messenger ribonucleic acid (mRNA) level and markedly inhibits the expression of EMT-related upstream proteins (TGF- β 1, p-PI3K, p-Akt, and p-FOXO3a). Conclusion Our research suggested that ESL attenuates BLM-induced IPF through mediating the EMT process via the TGF-β1/PI3K/Akt/FOXO3a signaling pathway and inhibiting inflammation through the TLR4/NF-κB signaling pathway, highlighting that ESL can serve as an immunoregulator for relieving the abnormal immune response and reversing the EMT in IPF.
研究领域:
药理学
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免疫学
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呼吸医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 14
·6678-6689
·
IF 6.1
Ziqian He,Na Deng,Bisheng Zheng,Yingjie Gu,Jian Chen,Tong Li,Rui Hai Liu,Ling Yuan,Wenzhi Li
The intestine and its flora have established a strong link with each other and co-evolved to become a micro-ecological system that plays an important role in human health. Plant polyphenols have attracted a great deal of attention as potential interventions to regulate the intestinal microecology. In this study, we investigated the effects of apple peel polyphenol (APP) on the intestinal ecology by establishing an intestinal ecological dysregulation model using lincomycin hydrochloride-induced Balb/c mice. The results showed that APP enhanced the mechanical barrier function of mice by upregulating the expression of the tight junction proteins at the transcriptional and translational levels. In terms of the immune barrier, APP downregulated the protein and mRNA expression of TLR4 and NF-κB. As for the biological barrier, APP promoted the growth of beneficial bacteria as well as increasing the diversity of intestinal flora. In addition, APP treatment significantly increased the contents of short-chain fatty acids in mice. In conclusion, APP can alleviate intestinal inflammation and epithelial damage as well as inducing potentially beneficial changes in the intestinal microbiota, which helps to reveal the potential mechanisms of host–microbial interactions and polyphenol regulation of intestinal ecology.
研究领域:
药理学
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微生物学
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免疫学
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营养学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ANIMAL PHYSIOLOGY AND ANIMAL NUTRITION
·
2023
·
IF 2.7
Wenyue Qiu,Xinting Zhang,Xiaoyue Pang,Jianjia Huang,Shuilian Zhou,Ruixia Wu,Rongmei Wang,Zhaoxin Tang,Rongsheng Su
Inflammatory response induced by biological stress usually occurs in weaning piglets, it reduces the production performance of piglets and even causes death. Tert-butylhydroquinone (TBHQ) is a food additive that has the effect of anti-inflammation and anti-oxidation. However, there are few reports related to the protective mechanisms of TBHQ on lipopolysaccharide (LPS) induced injury in intestinal porcine epithelial (IPEC-J2) cells. Quantitative real-time polymerase chain reaction and western blot analysis, respectively, detected the mRNA levels and protein expressions related to pyroptosis, tight junction (TJ) protein and high-mobility group box 1/toll-like receptor 4/nuclear factor kappa-B (HMGB1/TLR4/NF-κB) axis. Localisation and expression of NOD-like receptor pyrin domain containing 3 (NLRP3), HMGB1 and P-NF-κB proteins detected by immunofluorescence. The results showed that TBHQ (12.5 and 25 μM) can increase cell activity and reduce intracellular lactate dehydrogenase (LDH) levels in a dose-dependent manner. LPS significantly decreases cell viability and increases the LDH level. However, pretreatment with TBHQ evidently increases cell viability and decreases the LDH level of IPEC-J2 cells. In addition, treatment with LPS decreased the mRNA level and protein expression of zonula occludens-1, occludin and claudin-1, and increased the mRNA level and protein expression of pyroptosis and HMGB1/TLR4/NF-κB axis. Interestingly, pretreatment with TBHQ increased the TJ protein expressions as well as decreased the mRNA level and protein expressions of pyroptosis and HMGB1/TLR4/NF-κB axis. Moreover, the results of immunofluorescence showed that TBHQ significantly reduced the expression of NLRP3, HMGB1 and P-NF-κB in LPS-induced injury of IPEC-J2 cells. Therefore, we come to the conclusion that TBHQ attenuates LPS-induced pyroptosis in IPEC-J2 cells through downregulation of the HMGB1/TLR4/NF-κB axis, TBHQ may become a potential feed additive for preventing inflammatory diarrhoea in piglets.
研究领域:
兽医学
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细胞生物学
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免疫学
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动物营养学
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Waimei Si,Xin Li,Bei Jing,Shiquan Chang,Yachun Zheng,Zhenni Chen,Guoping Zhao,Di Zhang
(Switching from the microglial M1 phenotype to the M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). This study aimed to investigate the potential use of stigmasterol for treating NP. In animal experiments, 32 male Sprague–Dawley rats were randomly divided into the sham operation group, chronic constriction injury (CCI) group, CCI + ibuprofen group, and CCI + stigmasterol group. We performed behavioral tests, enzyme-linked immunosorbent assay, hematoxylin-esoin staining (H&E) staining and immunohistochemistry, immunofluorescence, and Western blotting. In cell experiments, we performed flow cytometry, immunofluorescence, Western blotting, and qRT-PCR. Stigmasterol reduced thermal and mechanical hyperalgesia and serum IL-1β and IL-8 levels and increased serum IL-4 and TGF-β levels in CCI rats. Stigmasterol reduced IL-1β, COX-2, and TLR4 expression in the right sciatic nerve and IL-1β expression in the spinal cord. Stigmasterol reduced the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, COX-2, IL-1β, and CD32 in the spinal cord of CCI rats while increasing the expression of IL-10 and CD206. Stigmasterol decreased M1 polarization markers and increased M2 polarization markers in lipopolysaccharide (LPS)-induced microglia and decreased the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, iNOS, COX-2, and IL-1β in LPS-treated microglia while increasing the expression of Arg-1 and IL-10. Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF-κB pathway to alleviate NP.
研究领域:
药理学
·
神经科学
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免疫学
·
疼痛研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2023
·
IF 5
Yi Wei,Ming Qi,Chao Liu,Lujia Li
Purpose Astragalus polysaccharide (APS) is a naturally-occurring compound derived from Astragalus membranaceus with anti-inflammatory and antioxidant properties. However, its beneficial effects and mechanisms on pulmonary fibrosis are unknown. Gut microbiota impact lung diseases via the gut-lung axis. Herein, we investigated APS progression to intervene in pulmonary fibrosis via the toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway and gut microbiota homeostasis regulation. Methods We used bleomycin (BLM) to construct an idiopathic pulmonary fibrosis (IPF) mouse model and assessed the pathology with Masson, hematoxylin-eosin (HE), and Sirius red staining . Enzyme-linked immunosorbent assay (ELISA) kits were employed to evaluate the inflammatory cytokine levels. Western blot evaluated TLR4/NF-κB signaling pathway expression. TUNEL staining to detect apoptosis. Mice feces samples were gathered for 16S rRNA gene sequencing. Results Our findings revealed that APS ameliorated the extent of damage and collagen deposition in lung tissues, reduced inflammatory cytokines TNF-α, IL-6, and IL-1β levels, and decreased apoptosis. APS might attenuate the inflammatory response through TLR4/NF-κB signaling pathway inhibition. Meanwhile, the IPF mice model exhibited dysregulation of gut microbiota, and these changes were restored after APS intervention. APS may increase the proportion of probiotics , decrease that of harmful bacteria, and balance the gut microbiota via regulating metabolic pathways. Conclusion APS ameliorated lung tissue injury in the IPF mice model, inhibited TLR4/NF-κB signaling pathway, suppressed inflammatory cytokines activation, and reduced apoptosis. Moreover, APS regulated the metabolism of gut microbiota besides beneficial bacteria content elevation.
研究领域:
药理学
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免疫学
·
肺科学
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微生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROREPORT
·
2024
·
IF 1.6
Bian Jing,Liu Chunxu,Li Xiang,Qin Xiaoye,Wang Feng,Xuan Lina,Zhang Weimin
This study aims to investigate how electroacupuncture regulates the learning and memory abilities of poststroke cognitive impairment (PSCI) rats through the TLR4/NF-κB/NLRP3 signaling pathway on the hippocampal microglia. Thirty male rats were randomly divided into three groups: sham surgery group, PSCI model group, and electroacupuncture group, with 10 rats in each group. Middle cerebral artery occlusion was used to establish the PSCI model. The Zea Longa method was used to score the rats’ neurological function. Electroacupuncture was utilized for 21 days to improve PSCI. The learning and memory abilities of rats were tested using the Morris water maze. Hematoxylin–eosin staining and immunofluorescence were used to find the hippocampus’ pathological changes. The concentration of interleukin-1β, interleukin-6, tumor necrosis factor-α, and interleukin-18 were detected by ELISA. The mRNA expression levels of associated inflammatory corpuscles were measured by quantitative real-time PCR. The protein expression levels of TLR4, MyD88, NF-κB, and NLRP3 were measured using western blotting. Electroacupuncture improved not only the learning and memory abilities of PSCI rats but also hippocampal morphology. Electroacupuncture inhibited the activation of microglia and the TLR4/NF-κB/NLRP3 signaling pathway. Electroacupuncture also reduced proinflammatory factors and restrained the mRNA levels of NLRP3-associated inflammatory cytokines. Its mechanism was related to inhibiting the expression of the TLR4/NF-κB/NLRP3 signaling pathway, attenuating the release of inflammatory factors, and regulating the activation of hippocampal microglia in the brain.
研究领域:
神经科学
·
针灸
·
认知障碍
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
Journal of Natural Medicines
·
2020
·Vol. 75
·期 1
·37-47
·
IF 2.055
Han Jieru,Shi Guangyu,Li Wenhao,Xie Ying,Li Fuzhen,Jiang Deyou
Monosodium urate (MSU)-mediated inflammation is closely related to gouty arthritis (GA). Dioscin, an active ingredient, has been reported to possess anti-inflammatory property. Nevertheless, the role of dioscin in GA and the underlying mechanism have not been fully understood. In the present study, we investigated the anti-inflammatory effect of dioscin on MSU-induced GA through in vivo and in vitro experiments. Histopathological analysis showed that dioscin alleviated the severity of GA concomitant with the lowered uric acid and creatinine levels. Moreover, the increasing IL-1β, IL-6, and TNF-α levels induced by MSU were decreased via administration of dioscin in mice and human synoviocytes. Western blotting results suggested that dioscin inhibited the activation of NLRP3 through down-regulating the protein expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved-caspase-1, as well as IL-1β. In addition, TLR4, myeloid differentiation primary response gene 88 (MyD88), p-IKKβ, p-p65, and NF-κB p65 in nuclei levels were significantly reduced by dioscin. Importantly, dioscin remarkably lowered the NF-κB p65-DNA activity in MSU-treated mice utilizing electrophoretic mobility shift assay (EMSA) analysis. Taken together, dioscin had a protective effect against MSU-initiated inflammatory response via repressing the production of inflammatory cytokines and the activation of inflammasome NLRP3 and TLR4/NF-κB signaling pathway. The above findings revealed that dioscin could be a potential drug for the treatment of GA.
研究领域:
药理学
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免疫学
·
风湿病学
✓ 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）