JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Qianru Gao,Weiyi Tian,Huabing Yang,Haiming Hu,Junping Zheng,Xiaowei Yao,Baifei Hu,Hongtao Liu
Ethnopharmacological relevance Shen-Ling-Bai-Zhu-San (SLBZS) is a classic formula for strengthening the spleen and dispelling dampness, which has shown excellent efficacy in inflammatory bowel disease (IBD) in traditional Chinese medicine clinical studies. However, its exact pharmacological mechanism needs to be further elucidated. Aim of the study This study aims to investigate the restorative effect and mechanism of SLBZS on disturbed intestinal homeostasis in DSS-induced colitis mice. Materials and methods A colitis model was induced by 3% dextran sulfate sodium (DSS) for seven days, and SLBZS was administered by gavage. The influence of SLBZS on DSS-induced clinical symptoms and disease activity index (DAI) was monitored and analyzed. Alcian blue and fluorescein isothiocyanate-conjugated wheat germ agglutinin (FITC-WGA) staining were used to assess intestinal mucus changes. The expression of intestinal barrier function indexes and immune-associated indexes were determined by H&E staining, real-time quantitative PCR (RT-qPCR), and Western blot. And gut microbiota changes were detected by 16 S rDNA sequencing technology. The antibiotic experiment was used to explore the role of gut microbiota in SLBZS treatment. Results The results showed that SLBZS significantly improved the physiological indexes including body weight, DAI score, and colon length of colitis mice. We focused on the effects of SLBZS on intestinal homeostasis in colitis mice. First, SLBZS could enhance the secretion of intestinal mucin and the expression levels of tight junctions and adhesive junctions. Second, SLBZS inhibited the expression level of inflammatory factors and reduced the protein expression level of NLRP3 inflammasome. Third, 16 S rDNA sequencing analysis revealed that SLBZS repaired the dysfunctional gut microbiota of colitis mice, such as enhancing the abundance of short-chain fatty acid-producing bacteria including Faecalibaculum , Colidextribacter , and Coprococcus . Further, by gut microbiota-depleted mice, we found that SLBZS could not exert an anti-colitis effect when gut microbiota was absent. Conclusions SLBZS restored intestinal environmental homeostasis by enhancing intestinal barrier function, inhibiting NLRP3 inflammasome, and restoring disturbed gut microbiota. And SLBZS could not ameliorate colitis mice with depleted gut microbiota. Our finding provided a theoretical basis for the clinical application of SLBZS in IBD.
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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.
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Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Xinxing Li,Wenxin Ding,Yan Lu,Haiyan Zhu,Weilian Bao,Yang Liu,Jiaren Lyu,Lishuang Zhou,Hong Li,Jiyang Li,Daofeng Chen
The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD 50 ) and methicillin-resistant Staphylococcus aureus (MRSA, 10 7 CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut–lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut–lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral–bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Jingjing Wang,Pingping Qu,Fuhan Wang,Man Qian,Ziyi Li,Mengyao Guo,Xuejiao Gao
Zearalenone is an estrogen-like mycotoxin produced by Fusarium fungi. Growing evidence shows that ZEA causes multisystem damage via oxidative stress. Glycyrrhizic acid (GA), from Glycyrrhiza glabra, has anti-inflammatory/antioxidant properties. The mechanisms of GA and ZEA in chicken pulmonary oxidative stress and inflammation remain elusive. Therefore, we established zearalenone-exposed chicken lung and CP-II cells models. ZEA exposure triggers an inflammatory cascade via the ROS-NF-κB axis, activating NLRP3 inflammasomes and promoting the release of proinflammatory factors. It also increased the apoptosis-related factors and fibrosis-related factors. GA treatment reduced oxidative stress, inflammation, and apoptosis, while suppressing fibrosis. This study reveals that GA reverses lung tissue injury by suppressing oxidative stress, inflammation, and the apoptosis-necrosis network through regulating the NF-κB/NLRP3 signaling axis by scavenging ZEA-induced reactive oxygen species (ROS). These results elucidate the antioxidant mechanism of GA and provide insights into the toxicology of ZEA.
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INFLAMMATION
·
2024
·
IF 4.5
Jin Guang-Nan,Wang Yu,Liu Yi-Ming,Lu Yu-Nan,Lu Jing-Mei,Wang Jing-He,Ma Jing-Wen,Quan Yan-Zhu,Gao Hong-Yan,Cui Yue-Xian,Xu Xiang,Piao Lian-Xun
Depression, recognized globally as a primary cause of disability, has its pathogenesis closely related to neuroinflammation and neuronal damage. Arctiin (ARC), the major bioactive component of Fructus arctii , has various pharmacological activities, such as anti-inflammatory and neuroprotective effects. Building on previous findings that highlighted ARC's capability to mitigate depression by dampening microglial hyperactivation and thereby reducing neuroinflammatory responses and cortical neuronal damage in mice, the current study delves deeper into ARC's therapeutic potential by examining its impact on hippocampal neuronal damage in depression. Utilizing both chronic unpredictable mild stress (CUMS)-induced depression model in mice and corticosterone (CORT)-stimulated PC12 cell model of neuronal damage, the techniques including Nissl staining, immunohistochemistry, western blotting, ELISA, lactate dehydrogenase assays, colony formation assays, immunofluorescence staining and molecular docking were employed to unravel the mechanisms behind ARC's neuroprotective effects. The findings revealed that ARC not only mitigates hippocampal neuropathological damage and reduces serum CORT levels in CUMS-exposed mice but also enhances cell activity while reducing lactate dehydrogenase release in CORT-stimulated PC12 cells. ARC attenuated neuroinflammatory responses and neuronal apoptosis by inhibiting the overactivation of the P2X7 receptor (P2X7R)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling pathway, similar to the effect of A438079 (P2X7R antagonist). Interestingly, pretreatment with A438079 blocked the neuroprotective effect of ARC. Computer modeling predicted that both ARC and A438079 have strong binding with P2X7R and they have the same binding site. These results suggested that ARC may exert a neuroprotective role by binding to P2X7R, thereby inhibiting the P2X7R/NLRP3 inflammasome 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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神经免疫学
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JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
·
2024
·Vol. 75
·期 3
·
IF 2
Q Y Zhang,Y Feng,H Cai
Bronchopulmonary dysplasia (BPD) is a common serious complication of premature babies. No effective means control it. Hyperoxia damage is one of the important mechanisms of BPD. The reaserach confirmed pyroptosis existed in BPD. Dexmedetomidine is a new, high-specific α2 receptor agonist. Previous research foundation found that dexmedetomidine has a protective effect on BPD. To investigate how dexmedetomidine improves hyperoxic lung injury in neonatal mice by regulating pyroptosis. Neonatal rats were randomly divided into four groups: normal control group, hyperoxic injury group, air plus dexmedetomidine group, and hyperoxia plus dexmedetomidine group. After seven days the lungs of rats in each group were extracted, and the wet-to-dry weight ratio of the lung was measured. The lung injury in rats was observed using hematoxylin-eosin staining. Additionally, the expression and localization of nucleotide-binding oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and gasdermin D (GSDMD) proteins were examined in the lungs of rats using immunofluorescence staining. The mRNA levels of NLRP3, ASC, caspase-1, and interleukin 18 (IL-18) in the lungs of rats were determined using real-time PCR. Moreover, the protein levels of NLRP3, ASC, caspase-1/cleaved caspase-1, interleukin 1beta (IL-1β), IL-18, and tunor necrosis factor alpha (TNF-α) were detected in lungs of rats using Western blot. The extent of mitochondrial damage in lung tissues of each group was observed by transmission electron microscopy. The lung tissue injury of the neonatal rats was significantly improved in the hyperoxia plus dexmedetomidine group compared to the hyperoxic injury group. Furthermore, the expressions of pyroptosis-related proteins such as NLRP3, ASC, cleaved-caspase-1, and GSDMD were significantly decreased, along with the expressions of inflammatory factors in lung tissues. By inhibiting the NLRP3/caspase-1/GSDMD pyroptosis pathway, dexmedetomidine reduces the activation and release of inflammatory factors and provides a protective effect against hyperoxic lung injury in neonatal mice.
研究领域:
儿科
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呼吸医学
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药理学
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分子生物学
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免疫学
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ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Wenjia Xie,Yuxuan Wang,Jicenyuan Wu,Xu Wang,Jiaxin Wu,Bin Cheng,Hao Feng,Xinxu Huang,Xinting Cheng,Junyu Chen,Qianbing Wan,Jian Wang,Xibo Pei
Diabetic periodontitis is characterized by persistent and aggravated inflammation, largely driven by a reactive oxygen species (ROS) vicious loop in M1 macrophages driven by mitochondrial dysfunction. To disrupt this pathogenic cascade, we developed hierarchically targeted polymeric nanoparticles (MPPT NPs) by conjugating the tuftsin peptide for selective uptake by M1 macrophages and loading mitoquinone mesylate (MitoQ) to restore mitochondrial function after mitochondrial localization. For local retention and responsive drug release, MPPT NPs were incorporated into a ROS-responsive hydrogel (MTP hydrogel) constructed by cross-linking poly(vinyl alcohol) (PVA) with a ROS-cleavable linker (N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diaminium (TSPBA)). This constructed platform not only enabled the on-demand release of MPPT NPs but also provided additional ROS-scavenging ability. In vitro studies demonstrated that MTTP NPs effectively repaired oxidatively damaged mitochondria and suppressed NLRP3 inflammasome priming and activation. MTP hydrogel platform reduced pro-inflammatory cytokine release and rescued inflammation-induced osteogenic impairment. In a diabetic periodontitis rat model, local administration of the MTP hydrogel significantly attenuated periodontal tissue destruction and promoted alveolar bone regeneration, achieving BV/TV 1.5 times that of previous reports. Collectively, this hierarchically targeted and ROS-responsive platform disrupts the ROS vicious loop in M1 macrophages by repairing damaged mitochondria, offering a promising therapeutic strategy for the management of diabetic periodontitis.
研究领域:
纳米医学
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牙科
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免疫学
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活性氧信号通路
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生物材料
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炎症性疾病
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EUROPEAN JOURNAL OF CELL BIOLOGY
·
2021
·
IF 4.492
Jian Zhao,Zhaoyu Liu,Zhihui Chang
Endothelial cell pyroptosis is a novel cause of endothelial dysfunction in sepsis. Reticulocalbin-2 (RCN2) is involved in regulating vascular inflammation and plays an important role in the cardiovascular system. However, the role of RCN2 in inflammation-induced endothelial cell pyroptosis remains to be explored. Here, we found that RCN2 was upregulated after lipopolysaccharide (LPS) treatment in a concentration‐ and time-dependent manner. RCN2 knockdown resulted in a significant decrease in pyroptosis, reduced LDH and IL-1β release and ROS production and inhibited the expression of pyroptosis‐related proteins (NLRP3, cleaved caspase-1, and cleaved GSDMD) (all p < 0.05). N‐acetyl‐L‐cysteine (NAC) counteracted the effects of RCN2 on pyroptosis (all p < 0.01). The silencing of RCN2 antagonized the inhibitory effect of LPS on the phosphorylation of eNOS (p < 0.05). We predicted and confirmed that specificity protein-1(SP1) could directly bind to the RCN2 promoter and regulate RCN2. RCN2 overexpression rescued the inhibitory effect of SP1 inhibitor on HUVEC pyroptosis induced by LPS (all p < 0.05). These findings suggested that the activation of the SP1/RCN2/ROS signaling pathway could promote LPS-induced endothelial cell pyroptosis.
研究领域:
免疫学
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心血管生物学
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细胞信号传导
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炎症
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CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Xiaohua Dong,Jing Zhao,Dongya Jiang,Ziyi Lu,Xingdan Liu,Kaijia Tan,Kelvin W.K. Yeung,Xuanyong Liu,Liping Ouyang
Spinal cord injury is hard to repair due to the aggregated injury to neighbor cells caused by neuro-inflammation, which always results in severe outcomes. In this work, Tc peptide, which served as the antagonist of CXCR4 and the agonist of CXCR7, was loaded in a self-healing hydrogel. The hydrogel containing Tc was found to possess superior spinal cord injury repair abilities, including motor neuron regeneration, axon bridging repair and motor functions recovery, due to the inflammation inhibition. The mechanism analysis by RNA-sequencing and in vitro experiments found that the elevated ANT1 accelerates OPTN recruitment, which subsequently recognized by LC3 to form phagophore around dysfunctional mitochondria, resulting in a regressive NLRP3 expression. However, this regression was abolished after inhibiting OPTN. Beneficial from the mitophagy process, ROS was reduced and type 1 microglia activation was diminished. This positive feedback loop accelerated spinal cord injury repair. In summary, the hydrogel containing Tc could promote spinal cord injury repair through reducing neuro-inflammation via enhanced ANT1/OPTN axis mediated mitophagy, which may provide a new peptide containing hydrogel for repairing spinal cord injury.
研究领域:
神经科学
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生物医学工程
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材料科学
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药理学
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高影响因子
DNA AND CELL BIOLOGY
·
2022
·Vol. 41
·期 12
·1038-1052
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IF 3.55
Qianyu Tang,Wenhui Liu,Xuefeng Yang,Yaying Tian,Jiacheng Chen,Yang Hu,Nian Fu
Despite activated autophagy ameliorating hepatocyte steatosis and metabolic associated fatty liver disease (MAFLD), mechanisms underlying the beneficial roles of autophagy in hepatic deregulation of lipid metabolism remain undefined. We explored whether autophagy can ameliorate oleic acid (OA)-induced hepatic steatosis by suppressing pyroptosis. Pyroptosis is involved in hepatocyte steatosis induced by OA. In addition, autophagy flux was blocked in OA-treated hepatocytes. Treatment with OA induced lipid accumulation in liver cell line L-02, which was attenuated by rapamycin (Rap), an autophagy agonist, while aggravated by autophagy inhibitor bafilomycin A1 (Baf A1). Inversely, treatment with pyroptotic agonist Nigericin aggravated OA-induced hepatic steatosis, while pyroptosis antagonist disulfiram ameliorated this effect. Mechanistically, treatment with Rap downregulated the expression of pyroptosis-related proteins, including NLRP3, Caspase-1, IL-18, GSDMD expression evoked by OA, thus improving pyroptosis in hepatic steatosis. Significantly, overexpression of ATG5 obviously downregulated cleaved caspase-1 expressions without altering the total caspase1 expressions in hepatic cell steatosis. Taken together, our studies strongly demonstrated that the activation of ATG5 inhibits pyroptosis to improve hepatic steatosis and suggest autophagy activation as a potential therapeutic strategy for pyroptosis-mediated MAFLD.
研究领域:
肝脏病学
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细胞生物学
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分子生物学
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药理学
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JOURNAL OF FOOD BIOCHEMISTRY
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2022
·Vol. 46
·期 7
·e14140
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IF 3.654
Dongyin Yuan,Ling Lin,Yingqi Peng,Yang Zhou,Li Li,Wenjun Xiao,Zhihua Gong
Black tea, a traditional drink, can induce urination and quench thirst. Black brick tea with fungal growth, prepared by steaming, pressing, inducing fungal growth, and drying the black tea, is a new type of black tea with different sensory qualities and is suitable for storage. However, the effects of black brick tea with fungal growth on lowering uric acid are still unexplored. Therefore, the potassium oxonate was administered for 7 consecutive days to establish the hyperuricemic mice. Then allopurinol, black tea, and black brick tea with fungal growth were orally administered with hyperuricemic mice for 14 days. Serum uric acid levels, liver xanthine oxidase (XOD) and adenosine deaminase (ADA) activities, and expression of renal urate transporters and inflammatory response were detected. Compared to the model group, both types of black tea lowered serum uric acid by decreasing the uric acid production with inhibiting the activities of XOD and ADA, and increasing uric acid excretion because of downregulating urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) expressions, and upregulating organic anion transporter 1 (OAT1), organic anion transporter 3 (OAT3), and organic cation transporter 1 (OCT1) expressions. They could also improve renal injury by suppressing the activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, and nuclear factor-κB (NF-κB) signaling, thereby reducing renal proinflammatory cytokine levels. Compared with black tea, black brick tea with fungal growth with a higher content of theabrownins had a better effect on lowering serum uric acid. Practical applications Black tea accounts for approximately 78% of the total consumed tea in the world. Black brick tea with fungal growth is a new kind of black tea product with different sensory qualities and is suitable for storage. The study found that black brick tea with fungal growth is superior to black tea in reducing serum uric acid levels, which make a significant contribution to promote people’s health and stimulate the production and consumption of black brick tea with fungal growth. In addition, it provides a clue for future research to identify the effective components of black brick tea with fungal growth lowering uric acid.
研究领域:
药理学
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生物化学
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营养学
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动物科学
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