EXPERIMENTAL EYE RESEARCH
·
2025
·
IF 2.7
Yarong Yan,Shulei Xing,Jinghua Liu,Xinlin Yan,Yi Guan,Zhixin Jiang,Wei Zhang,Xuan Li
Lycium barbarum glycopeptide (LbGp), derived from the Chinese medicinal plant Lycium barbarum, has demonstrated anti-inflammatory properties; however, its precise role and mechanism in corneal repair following injury remain elusive. The present research investigated the mechanisms and effects of LbGp on corneal repair following alkali burn injury using in vivo mouse models of corneal alkali burn and in vitro human keratocyte fibrosis models. Corneal inflammation, opacity, and epithelial defects were assessed via a slit lamp microscope. Results showed that LbGp-treated mice exhibited reduced edema, accelerated re-epithelialization, and decreased corneal opacity compared to the phosphate-buffered saline (PBS)-treated controls. Proteomic analysis revealed altered proteins enriched in the extracellular matrix among the control, injury, and LbGp treatment groups. Moreover, LbGp significantly attenuated TGFβ-1-induced myofibroblasts transdifferentiation from keratocytes. Consistently, LbGp treatment inhibited the upregulation of fibrosis markers (αSMA, fibronectin, and collagen III) at both the protein and mRNA levels after corneal alkali burns. LbGp also effectively suppressed the activation of the NF-κB/NLRP3/IL-1β signaling pathway and neutrophil infiltration following corneal alkali burn injury. Additionally, miR-21 was upregulated in TGFβ-1-stimulated keratocytes and in the alkali-burned mouse cornea. LbGp decreased miR-21 expression, while increasing expression of its target, Smad7, thereby dampening the TGFβ/Smad2/3 signaling pathway. This research demonstrates that LbGp promotes corneal healing by inhibiting inflammation and fibrosis after alkali burns, suggesting its potential as a supplementary therapy for corneal injury repair.
研究领域:
药理学
·
眼科
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Shengchen Ding,Jun Chen,Guangming Chen,Weiyi Tian,Junping Zheng,Haiming Hu,Lu Cao,Xiaowei Yao,Baifei Hu,Hongtao Liu
This study aimed to isolate oligosaccharides from P. sibiricum , analyze its structure, and elucidate the pharmacological mechanism for colitis improvement. First, a homogeneous oligosaccharide PSO-A was isolated and its structure was characterized. Then, the colitis model was induced with 3 % dextran sulfate sodium (DSS) and intervened with PSO-A. The results show that PSO-A was an agavin-type acetylated fructooligosaccharide with a molecular weight of 2.12 kDa. PSO-A consisted of (2 → 6)-β-D-Fru f residue backbone with an internal α-D-Glc p residue and (2 → 1)-β-D-Fru f residue side chains. Further, PSO-A increased mucin content, protected intestinal barrier integrity of colitis mice, and significantly inhibited the levels of inflammatory factors. Moreover, the protein expressions of NLRP3, ASC, and Caspase-1 in colitis mice was statistically inhibited by PSO-A. In summary, PSO-A could alleviate colitis by inhibiting NLRP3 inflammasome pathway, which provides a basis for the development and application of P. sibiricum oligosaccharides as drug or functional food to relieve colitis.
研究领域:
药理学
·
生物化学
·
分子生物学
·
免疫学
·
胃肠病学
✓ 已验证
产品关联
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Xueming Xu,Yuanfeng Han,Jiali Deng,Shengfeng Wang,Shijie Zhuo,Kai Zhao,Wenhu Zhou
Drug repurposing offers a valuable strategy for identifying new therapeutic applications for existing drugs. Recently, disulfiram (DSF), a drug primarily used for alcohol addiction treatment, has emerged as a potential treatment for inflammatory diseases by inhibiting pyroptosis, a form of programmed cell death. The therapeutic activity of DSF can be further enhanced by the presence of Cu 2+ , although the underlying mechanism of this enhancement remains unclear. In this study, we investigated the mechanistic basis of Cu 2+ -induced enhancement and discovered that it is attributed to the formation of a novel copper ethylthiocarbamate (CuET) complex. CuET exhibited significantly stronger anti-pyroptotic activity compared to DSF and employed a distinct mechanism of action. However, despite its potent activity, CuET suffered from poor solubility and limited permeability, as revealed by our druggability studies. To overcome these intrinsic limitations, we developed a scalable method to prepare CuET nanocrystals (CuET NCs) using a metal coordination-driven self-assembly approach. Pharmacokinetic studies demonstrated that CuET NCs exhibited a 6-fold improvement in bioavailability. Notably, CuET NCs exhibited high biodistribution in the intestine, suggesting their potential application for the treatment of inflammatory bowel diseases (IBDs). To evaluate their therapeutic efficacy in vivo , we employed a murine model of DSS-induced colitis and observed that CuET NCs effectively attenuated inflammation and ameliorated colitis symptoms. Our findings highlight the discovery of CuET as a potent anti-pyroptotic agent, and the development of CuET NCs represents a novel approach to enhance the druggability of CuET.
研究领域:
药理学
·
纳米技术
·
炎症
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Neuroinflammation
·
2017
·Vol. 14
·期 1
·1-18
·
IF 5.102
Zhao Hengli,Pan Pengyu,Yang Yang,Ge Hongfei,Chen Weixiang,Qu Jie,Shi Jiantao,Cui Gaoyu,Liu Xin,Feng Hua,Chen Yujie
Background Emerging studies have demonstrated the important physiological and pathophysiological roles of hydrogen sulphide (H2S) as a gasotransmitter for NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-associated neuroinflammation in the central nervous system. However, the effects of H2S on neuroinflammation after intracerebral haemorrhage (ICH), especially on the NLRP3 inflammasome, remain unknown.Methods We employed a Sprague–Dawley rat of collagenase-induced ICH in the present study. The time course of H2S content and the spatial expression of cystathionine-β-synthase (CBS) after ICH, the effects of endogenous and exogenous H2S after ICH, the effects of endogenous and exogenous H2S on NLRP3 inflammasome activation under P2X7 receptor (P2X7R) overexpression after ICH, and the involvement of the P2X7R in the mechanism by which microglia-derived H2S prevented NLRP3 inflammasome activation were investigated.Results We found ICH induced significant downregulation of endogenous H2S production in the brain, which may be the result of decreasing in CBS, the predominant cerebral H2S-generating enzyme. Administration of S-adenosyl-l-methionine (SAM), a CBS-specific agonist, or sodium hydrosulfide (NaHS), a classical exogenous H2S donor, not only restored brain and plasma H2S content but also attenuated brain oedema, microglial accumulation and neurological deficits at 1 day post-ICH by inhibiting the P2X7R/NLRP3 inflammasome cascade. Endogenous H2S production, which was derived mainly by microglia and above treatments, was verified by adenovirus-overexpressed P2X7R and in vitro primary microglia studies.Conclusion sThese results indicated endogenous H2S synthesis was impaired after ICH, which plays a pivotal role in the P2X7R/NLRP3 inflammasome-associated neuroinflammatory response in the pathogenesis of secondary brain injury. Maintaining appropriate H2S concentrations in the central nervous system may represent a potential therapeutic strategy for managing post-ICH secondary brain injury and associated neurological deficits.
研究领域:
神经科学
·
药理学
·
炎症
·
神经病学
✓ 已验证
DOI
PubMed
高影响因子
Chinese Medicine
·
2023
·Vol. 18
·期 1
·1-16
·
IF 4.9
Wang Xiaohu,Shen Chaozhuang,Wang Xingwen,Tang Jin,Wu Zijing,Huang Yunzhe,Shao Wenxin,Geng Kuo,Xie Haitang,Pu Zhichen
Background According to the Chinese Pharmacopoeia, the fruit of Schisandra chinensis (Turcz.) Baill. (SC) is an important traditional Chinese medicine that can be used to treat diarrhea. Despite the increasing research on the anti-inflammatory and anti-oxidant aspects of SC, the studies on the anti-ulcerative colitis of Schisandrin (SCH), the main constituent of SC, are relatively few.Methods The mice used in the study were randomly distributed into 6 groups: control, model, 5-ASA, and SCH (20, 40, 80 mg/kg/d). The mice in the model group were administered 3% (w/v) dextran sulfate sodium (DSS) through drinking water for 7 days, and the various parameters of disease activity index (DAI) such as body weight loss, stool consistency, and gross blood were measured. ELISA was used to detect inflammatory factors, and bioinformatics combined with transcriptome analysis was done to screen and verify relevant targets. 16S rDNA high-throughput sequencing was used to analyze the composition of the gut microbiota(GM), while mass spectrometry was done to analyze the changes in the content of bile acids (BAs) in the intestine.Results Mice treated with SCH experienced significant weight gain, effectively alleviating the severity of colitis, and decreasing the levels of inflammatory factors such as TNF-α, IL-1β, IL-18, IL-6, and other related proteins (NLRP3, Caspase-1, SGK1) in UC mice. Furthermore, the analysis of GM and BAs in mice revealed that SCH increased the relative abundance of Lactobacilli spp, reduced the relative abundance of Bacteroides, and promoted the conversion of primary BAs to secondary BAs. These effects contributed to a significant improvement in the DSS-induced GM imbalance and the maintenance of intestinal homeostasis.Conclusion It seems that there is a close relationship between the SCH mechanism and the regulation of SGK1/NLRP3 pathway and the restoration of GM balance. Therefore, it can be concluded that SCH could be a potential drug for the treatment of UC.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 7
·3946-3956
·
IF 6.317
Zhe Wang,Chunhai Li,Xi He,Kang Xu,Zhipeng Xue,Ting Wang,Zhenshang Xu,Xinli Liu
The effect of Platycodon grandiflorum (PG) on colitis and its underlying mechanism were rarely studied. In this study, Lactobacillus rhamnosus 217-1 was used to ferment PG roots, and the concentrations of platycodin-D, flavonoids, and polyphenols and the DPPH free radical scavenging rate were significantly increased. Treatment with a PG root fermentation broth (PGRFB) could reduce dextran sulfate sodium (DSS) induced ulcerative colitis (UC) in mice. Meanwhile, the PGRFB significantly reduced the content of inflammatory factors in mouse serum and the expression of inflammatory factor mRNA in the intestinal tract, regulated the polarization of M1/M2 macrophages, and increased the expression of tight junction protein mRNA in intestinal epithelial cells. In summary, it was proved that the PGRFB could inhibit the nuclear factor kappa B (NF-κB) signaling pathway and the expression of Nod-like receptor protein 3 (NLRP3) inflammasomes by activating AMP-activated protein kinase (AMPK) and lowering the release of pro-inflammatory cytokines.
研究领域:
药理学
·
免疫学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biochemistry and Biophysics Reports
·
2023
·
IF 2.7
Ke Zhang,Youyang Liu,Yunlu Zhao,Qi Guo,Shengjun An,Shuhui Wu
Many chronic inflammatory diseases, such as autoimmune inflammation, are associated with M1 macrophages, and the key to their treatment is blocking inflammation. Oxymatrine (OMT), a traditional Chinese medicine, has a marked anti-inflammatory effect. However, its anti-inflammatory target and mechanism in M1 cells remain unclear, which limits its clinical application. In this study, we investigated the anti-inflammatory effects of oxymatrine (OMT) on the M1 inflammatory response. We also determined the relationship between OMT treatment and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathway with OMT treatment. To this end, we induced the differentiation of human peripheral blood monocytes (THP-1) into M1 cells. THP-1 cells were induced with a phorbol ester (phorbol-12-myristate-13-acetate (PMA)) and differentiated into naïve M0 macrophages. M0 cells were induced into M1 cells using lipopolysaccharide (LPS). The experimental groups were divided into the M0 macrophage group (NC), M1 inflammatory response group (LPS group), and M1 group treated with different concentrations of OMT (LPS + OMT-L, LPS + OMT-M, LPS + OMT-H). The cells in the OMT-treated groups were treated with OMT for 6 h, followed by LPS for 24 h, and the LPS group was treated with LPS only. The resulting supernatants and cells were collected. The secretion levels of NO were detected by the Griess method and the secretion levels of TNF-α and IL-1β in the supernatants were detected by the ELISA method. The secretion levels of these inflammatory factors were reduced in every OMT-treated group compared to the LPS group (P < 0.01), and the most significant reductions were found in the OMT-H group (P < 0.0001). By western blotting, the protein expression levels of TLR4, NF-κB, NLRP3, and Caspase-1 were all found to be downregulated in the cells of OMT-treated groups compared to the LPS group (P < 0.0001). In situ changes in NLRP3 expression were observed using immunofluorescence. The fluorescence intensity of NLRP3 in M1 cells was weaker in all OMT intervention groups than in the LPS group (P < 0.001). In conclusion, OMT has significant anti-inflammatory effects on the M1 inflammatory responses, and the TLR4/NF-κB/NLRP3 pathway was blocked proportional to the concentration of OMT.
研究领域:
免疫学
·
药理学
·
细胞生物学
·
炎症性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2022
·
IF 7.31
Lu Bai,Jing Dai,Yuxuan Xia,Kaichuan He,Hongmei Xue,Qi Guo,Danyang Tian,Lin Xiao,Xiangjian Zhang,Xu Teng,Yuming Wu,Sheng Jin
Although it is an essential nutrient, high choline intake directly or indirectly via its metabolite is associated with increased risk of cardiovascular disease, the mechanism of which remains to be elucidated. The present study was performed to investigate whether hydrogen sulfide (H2S) was involved in high choline-induced cardiac dysfunction and explore the potential mechanisms. We found that ejection fraction (EF) and fractional shortening (FS), the indicators of cardiac function measured by echocardiography, were significantly decreased in mice fed a diet containing 1.3% choline for 4 months as compared to the control, while applying 3,3-dimethyl-1-butanol (DMB) to suppress trimethylamine N-oxide (TMAO, a metabolite of choline) generation ameliorated the cardiac function. Subsequently, we found that feeding choline or TMAO significantly increased the protein levels of cyclic GMP-AMP (cGAMP) synthase (cGAS), stimulator of interferon genes (STING), NOD-like receptor protein 3 (NLRP3), caspase-1, and interleukin-1β (IL-1β) as compared to the control, which indicated the activation of cGAS-STING-NLRP3 inflammasome axis. Moreover, the protein expression of cystathionine γ-lyase (CSE), the main enzyme for H2S production in the cardiovascular system, was significantly increased after dietary supplementation with choline, but the plasma H2S levels were significantly decreased. To observe the effect of endogenous H2S, CSE knockout (KO) mice were used, and we found that the EF, FS, and plasma H2S levels in WT mice were significantly decreased after dietary supplementation with choline, while there was no difference between CSE KO + control and CSE KO + choline group. To observe the effect of exogenous H2S, mice were intraperitoneally injected with sodium hydrosulfide (NaHS, a H2S donor) for 4 months, and we found that NaHS improved the cardiac function and reduced the protein levels of cGAS, STING, NLRP3, caspase-1, and IL-1β in mice receiving dietary choline. In conclusion, our studies revealed that high choline diet decreased plasma H2S levels and induced cardiac dysfunction via cGAS-STING-NLRP3 inflammasome axis while H2S treatment could restore the cardiac function by inhibiting cGAS-STING-NLRP3 inflammasome axis.
研究领域:
心脏病学
·
营养学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
OBESITY SURGERY
·
2020
·Vol. 30
·期 9
·3435-3443
·
IF 3.412
Sun Kangyue,Wang Jing,Lan Zhixian,Li Ling,Wang Yadong,Li Aimin,Liu Side,Li Yue
Purpose Endoscopic sleeve gastroplasty (ESG) has been suggested to be effective for treating obesity and its related non-alcoholic fatty liver disease (NAFLD). A small molecule named CY-09 is the selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome. We aim to investigate whether a surgery imitating ESG combined with CY-09 is more effective for treatment of obesity and NAFLD in a mouse model. Material and Methods Forty mice were randomly divided into a control group ( n = 5) and an NAFLD group ( n = 35) fed by high-fat diet (HFD). The NAFLD mice were randomly assigned to the following groups at the timepoint of 19 weeks: (1) sham surgery; (2) surgery; (3) the combination of surgery with CY-09 injection. NAFLD activity score (NAS) was used for histological evaluation of steatosis. We also detected fasting glucose and insulin to measure the homeostasis model assessment of insulin resistance (HOMA-IR). Results HFD resulted in significant obesity and metabolic disorders, indicating successful modelling of obesity and NAFLD. The combination therapy resulted in significantly lower body weight than surgery alone at the end of the 8-week follow-up (40.4 ± 4.8 vs. 45.0 ± 2.2 g, P = 0.025). Furthermore, more dramatic improvements in HOMA-IR (5.8 ± 1.1 vs. 12.2 ± 2.1 mmol mIU L −2 , P = 0.036) and NAS (4.5 ± 1.3 vs. 8.0 ± 1.8, P = 0.006) were also observed in the combination group. Conclusions Surgery imitating ESG combined with CY-09 reduces body weight, improves insulin resistance and alleviates hepatic steatosis. The combination therapy may be a promising method for treating obesity and NAFLD.
研究领域:
医学
·
生物学
✓ 已验证
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2018
·
IF 2.064
Yinji Liang,Yupei Zhang,Yuanjun Deng,Shu Liang,Yifang He,Yanning Chen,Chan Liu,Chenli Lin,Li Han,Guifang Tu,Qinhe Yang
We evaluate the effects of the Chaihu-Shugan-San decoction on intestinal microbe dysbiosis and chronic metabolic inflammation via the NLRP3 pathway in NAFLD rats that were fed a high-fat diet. Twenty-four SD rats (male, six weeks old, 200 ± 20 g) were randomly divided into three groups: normal control group (NC group), high-fat diet-fed group (HFD group), and Chaihu-Shugan-San decoction intervention group (CH group). The NC group rats were given standard feed, the HFD group rats were all fed a high-fat diet (83% standard feed + 10% lard oil + 5% sucrose + 1.5% cholesterol + 0.5% cholate), and the CH group rats were given a HFD plus Chaihu-Shugan-San at 9.6 g•kg−1•d−1. Body composition, serum and liver lipids, inflammatory markers, intestinal microbial population, and the NLRP3 pathway-associated protein were assessed. The results showed that Chaihu-Shugan-San decoction significantly reduced body weight and total fat mass and the levels of serum LPS, TG, TNF-α, IL-1β, and IL-18, as well as liver TC, TG, TNF-α, IL-1β, and IL-18 (P < 0.05). The abundance of Enterobacteriaceae (0.375% versus 0.064%, P < 0.05), Staphylococcaceae families (0.049% versus 0.016%, P < 0.05) and Veillonella genus (0.096% versus 0.009%, P < 0.01) significantly decreased, whereas the abundance of Anaeroplasma genus (0.0005% versus 0.0178%, P < 0.01) significantly increased. The expression levels of NLRP3, ASC, and Caspase-1 were changed significantly (P < 0.05). In summary, the Chaihu-Shugan-San decoction modulated intestinal microbe dysbiosis, reduced fat accumulation, and alleviated inflammatory factor expression, which are all processes related to the NLRP3 inflammasome pathway in NAFLD rats.
研究领域:
药理学
·
微生物学
·
炎症研究
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Danliangmin Song,Jingqi Cheng,Kai Dong,Shiyu Liu,Chaoxin Man,Shiqian Fu,Xinyan Yang,Qianyu Zhao,Yujun Jiang
Cronobacter sakazakii is a facultative anaerobic gram-negative pathogen that has attracted widespread attention for causing necrotizing enterocolitis in infants (premature and low-weight newborns) by contaminating powdered infant formula. Several studies have found that the antibiotic tolerance of Cronobacter sakazakii isolated from food sources is increasing, thereby markedly increasing the difficulty of clinical treatment of Cronobacter sakazakii infection. At present, most studies are focused on clarifying the pathogenicity of Cronobacter sakazakii , but there is still a gap in the study of necrotizing enterocolitis in neonatal rats caused by Cronobacter sakazakii with different antibiotic tolerance. To fill this gap, we analyzed and compared the ability of Cronobacter sakazakii induced by different classes of antibiotics to induce necrotizing enterocolitis in neonatal rats by mediating TLR4-NLRP3-IL-1β pathway. In the results, Cronobacter sakazakii acquired tolerance to aminoglycosides, quinolones and cephalosporins, and caused more inflammatory damage in neonatal rats, improved the ability of mediating TLR4-NLRP3-IL-1β pathway to induce necrotizing enterocolitis. Compared with the XS001 group, the NEC scores of neonatal rats in XS001-Amp, XS001-Ami, XS001-Ofl and XS001-Ceo groups were increased by 8.3%, 58.3%, 50.0% and 58.3%. The acquisition of penicillin and tetracycline tolerance had little effect on the ability of Cronobacter sakazakii to induce necrotizing enterocolitis in neonatal rats. The ability of Cronobacter sakazakii to induce necrotizing enterocolitis in neonatal rats was significantly different due to the type and tolerance of antibiotics.
研究领域:
微生物学
·
免疫学
·
儿科
·
分子生物学
✓ 已验证
DOI
高影响因子
RENAL FAILURE
·
2023
·
IF 3
Chenlei Lv,Tianyang Cheng,Bingbing Zhang,Ke Sun,Keda Lu
Objectives: Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus. This study investigated the mechanism of triptolide (TP) in podocyte injury in DN.Methods: DN mouse models were established by feeding with a high-fat diet and injecting with streptozocin and MPC5 podocyte injury models were induced by high-glucose (HG), followed by TP treatment. Fasting blood glucose and renal function indicators, such as 24 h urine albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and kidney/body weight ratio of mice were examined. H&E and TUNEL staining were performed for evaluating pathological changes and apoptosis in renal tissue. The podocyte markers, reactive oxygen species (ROS), oxidative stress (OS), serum inflammatory cytokines, nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway-related proteins, and pyroptosis were detected by Western blotting and corresponding kits. MPC5 cell viability and pyroptosis were evaluated by MTT and Hoechst 33342/PI double-fluorescence staining. Nrf2 inhibitor ML385 was used to verify the regulation of TP on Nrf2.Results: TP improved renal function and histopathological injury of DN mice, alleviated podocytes injury, reduced OS and ROS by activating the Nrf2/heme oxygenase-1 (HO-1) pathway, and weakened pyroptosis by inhibiting the nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome pathway. In vitro experiments further verified the inhibition of TP on OS and pyroptosis by mediating the Nrf2/HO-1 and NLRP3 inflammasome pathways. Inhibition of Nrf2 reversed the protective effect of TP on MPC5 cells.Conclusions: Overall, TP alleviated podocyte injury in DN by inhibiting OS and pyroptosis via Nrf2/ROS/NLRP3 axis.
研究领域:
药理学
·
肾病学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）