APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
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2026
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IF 3.5
Li Tong,Li Ning,Li Yi,Liu Jinwen,Hao Dajie
Oxidative stress and inflammasome-driven inflammation are key contributors to atherosclerotic disease progression. Here, we report a ROS-responsive hyaluronic acid-PEGDA hydrogel designed for the sustained delivery of palmitoleic acid. In the study, catechol-functionalized hyaluronic acid was cross-linked with polyethylene glycol diacrylate to create an extracellular matrix mimic that possessed tunable mechanical strength and redox-sensitive degradability. It showed controlled release of palmitoleic acid under normal physiological conditions and a faster rate of release under oxidative conditions. In vitro studies using vascular endothelial cells and macrophages demonstrated good cytocompatibility and a marked reduction in intracellular reactive oxygen species, lipid peroxidation, and pro-inflammatory cytokine secretion. At the molecular level, treatment with the palmitoleic acid-loaded hydrogel resulted in activation of AMP-activated protein kinase, inhibition of NF-κB nuclear translocation, and suppression of NLRP3 inflammasome activation, as evidenced by decreased caspase-1 cleavage and IL-1β maturation. These findings indicate that ROS-responsive hydrogel-mediated delivery of palmitoleic acid effectively modulates oxidative and inflammatory signalling pathways relevant to atherosclerosis. Graphical
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PubMed
高影响因子
Journal of Advanced Research
·
2025
·
IF 13
Lin-Tao Xu,Qing-Tong Han,Zhen-Peng Xu,Xiao-Ning Wang,Hua Zhang,Tao Shen
Introduction Chronic obstructive pulmonary disease (COPD) represents a significant global health challenge, characterized by substantial morbidity and mortality rates. In traditional Chinese medicine (TCM), Farfarae Flos (FF) has been widely utilized as a therapeutic agent for COPD. However, its specific bioactive compounds and the underlying mechanisms are unclear. Objectives This study aims to identify bioactive constituent of FF against COPD and illustrate its therapeutic target and mechanism. Methods and Results In this research, a high-throughput screening on constituents of FF was conducted, leading to the identification of a potent anti-COPD lead, tussilagone (TUS). Utilizing biotin-labeling approach, Kelch-like ECH-associated protein 1 (KEAP1), the ubiquitin E3 ligase of nuclear factor erythroid 2-related factor 2 (Nrf2), was identified to be the direct target of TUS. Mechanistically, TUS activated KEAP1-Nrf2 axis by covalent modification of cysteine 434 (Cys434), a novel high-reactivity cysteine of KEAP1. TUS-mediated Nrf2 activation further suppressed the activation of nuclear factor kappa-B (NF-κB) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, consequently attenuating lung inflammation in COPD. Conclusion TUS was identified as the bioactive constituent of FF against COPD, which directly targeted Cys434 of KEAP1. KEAP1 was proven to be a pharmacological target for the treatment of COPD, and Cys434 was identified to be the first highly reactive cysteine in Kelch domain of KEAP1. TUS inhibits lung inflammation by regulating Nrf2 and NF-κB/NLRP3, which is the mechanism of FF against COPD
研究领域:
药理学
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分子生物学
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呼吸医学
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民族药理学
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生物化学
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免疫学
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PubMed
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Anna Gan,Haimiao Chen,Fei Lin,Ruixuan Wang,Bo Wu,Tingxu Yan,Ying Jia
Background Acute lung injury (ALI) is a serious respiratory ailment marked by dysregulation of the immune dysregulation and an inflammatory reaction.Currently, effective treatment options for ALI are limited. Sanzi Yangqin Decoction (SZYQ) is a traditional formula used clinically to treat respiratory diseases, although its effects on ALI have not yet been fully elucidated. Purpose This research seeks to elucidate the pharmacodynamic material basis of SZYQ within the context of lipopolysaccharide (LPS)-induced ALI, thereby establishing a robust foundation for considering SZYQ as a possible intervention for improving ALI. Methods The chemical constituents of SZYQ were identified by UHPLC-QTOF-MS. The pharmacological mechanism of SZYQ on ALI was preliminarily investigated through network pharmacology. An ALI model induced by LPS was employed to evaluate the efficacy of SZYQ via histopathological analysis and other methodologies. Transcriptomic analysis of lung tissue from ALI mice was conducted to uncover the potential mechanisms underlying SZYQ's effects. Additionally, LPS was used to induce murine alveolar macrophages (MH-S), creating an in vitro ALI model; siRNA was introduced to further validate the pharmacological mechanisms of SZYQ's protective effects on ALI. Results This study identified a total of 37 chemical components within SZYQ, and network pharmacology results indicated that these components exert their effects via the Toll-like receptor pathway. The protective effects of SZYQ on ALI are manifested by the modulation of the immune response and the reduction of lung epithelial barrier damage. Transcriptomics, western blot, flow cytometry, and siRNA experiments demonstrated that SZYQ can inhibit levels of TLR2, p-NF-κB/NF-κB, p-IκB/IκB, p-IKKα/IKKα, MyD88, NLRP3, Caspase-1 and ASC. Furthermore, SZYQ was observed to reduce the release of reactive oxygen species (ROS), suppresses inflammasome activation, as well as decrease the incidence of cell pyroptosis. Conclusions This article demonstrated for the first time that SZYQ can enhance ALI through immune regulation. The proposed mechanism of action involved the TLR2-mediated NF-κB/NLRP3 signaling pathway and the inhibition of NLRP3 inflammasome activation.
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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传统中医
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Dan Wang,Yimeng Zou,Tianqi Zhao,Weiyue Cao,Jiachi Han,Qing Wu,Zhitong Li,Xinyu Li,Peijing Liu,Lin Bai,Guiping Ren
Background The blood FGF21 expression has been previously suggested to increase in patients developing atopic dermatitis (AD) and asthma. However, its impact on atopic march is rarely analyzed. The present work focused on investigating the role of Fibroblast Growth Factor 21(FGF21) in atopic march mice and its underlying mechanisms. Methods The models were induced with Diisononyl phthalate (DINP) and OVA in wild-type C57BL/6 and FGF21 −/− mice. RAW264.7 cells were induced by LPS with/without FGF21 or KLB-SiRNA for in vitro analyses. Results The data indicated that there were more severe allergic reactions including IgE levels and the proportion of mast cells in the blood of FGF21 −/− mice in relative to WT model mice during the progression from AD to asthma. However, exogenous administration of FGF21 inhibited allergies. In this study, we reported that FGF21 mitigated AD-like lesions and Th1/2 or Th17/Treg cell imbalance in AD mice, and significantly decreased TSLP, IL-33, IL-4, IL-5, IL-13 and IL-17A expression on skin. During the asthma phase, FGF21 improved airway remodeling by downgrading inflammatory factors IL-4, IL-5, IL-13 and IL-17A; fibrotic markers α-SMA and Collagen I; and oxidative products MDA and ROS in wild-type model mice. Compared with WT model mice, the adverse consequences were aggravated in FGF21 −/− asthmatic mice. From the mechanistic perspective, FGF21 suppressed NF-κB/NLRP3, TGF-β1/Smad3 and JNK signaling pathways and increased Nrf2 expression in vivo and in vitro. In addition, β-Klotho knockdown attenuated the ameliorative impact of FGF21 on cellular damage. Blocking AMPKα in the LPS-treated RAW264.7 cells inhibited the reduction of FGF21 and the phosphorylation of JNK. Conclusions To conclude, FGF21 alleviated atopic march by inhibiting Th2/17 immune response, and reduced airway remodeling by regulating NF-κB/NLRP3, TGF-β1/Smad3 and AMPKα/JNK pathways. Moreover, this study provides a rationale and novel ideas for applying FGF21 in treating AD and asthma.
研究领域:
免疫学
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药理学
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分子生物学
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PubMed
高影响因子
JOURNAL OF DAIRY SCIENCE
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2026
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IF 4.7
Yi Ma,Jiatao Zhang,Cheng Chen,Mengzhi Wang,Haifei Li,Yunfei Deng,Xingru Zhou,Jianhui Hu,Hao Zhang,Guohui Li,Jin Wang,Zhongjian Guo
Subacute ruminal acidosis, induced by high-concentrate diets, can trigger systemic inflammation and mastitis, a pathology linked to ruminal dysbiosis and disruption of the host's circadian rhythm. In this study, 32 mid-lactating Saanen goats (41.5 ± 1.79 kg BW) were randomly allocated to 4 treatment groups (n = 8/group): a low-concentrate diet (LC; 30:70 concentrate:forage ratio), a high-concentrate diet (HC; 70:30), and their respective counterparts supplemented with 200 mg/kg of DM thiamine (LCT and HCT). Results demonstrated that the HC diet decreased ruminal pH, induced microbial dysbiosis, and increased plasma LPS concentrations. This resulted in systemic and mammary inflammation, characterized by elevated cytokine expression and a significant decline in milk yield and quality. Thiamine supplementation in the high-concentrate diet (HCT group) effectively reversed these changes. It stabilized ruminal pH, modulated the microbiota by enriching beneficial taxa such as f_Ruminococcaceae , reduced inflammatory cytokine levels, and restored milk production. At the molecular level, goats receiving thiamine supplementation exhibited reduced activation of the NF-κB and NLRP3 inflammasome pathways and higher expression of core clock proteins (CLOCK, BMAL1) in the mammary tissue. In conclusion, thiamine alleviates SARA-induced mastitis by stabilizing the rumen microbiota and mitigating inflammation, and these protective effects are associated with concurrent changes in the NF-κB/NLRP3/CLOCK signaling axis in the mammary gland.
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高影响因子
BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Suiqing Mai,Jiale Ke,Shiqin Lin,Rongrong Huang,Fengxin Zheng,He Jiao,Hong Wang,Shuqin Zhang,Mengying Mao,Qiuping Li,Zean Zhao,Jianxin Pang,Qun Zhang
A high-purine diet is an important factor in the development of hyperuricemia (HUA), in which the intestinal tract is the main site of dietary purine absorption. Inhibition of intestinal concentrative nucleoside transporter 2 (CNT2) can inhibit dietary purine-induced elevation of serum uric acid (sUA) levels. However, there is a lack of research on CNT2 inhibitors for the treatment of HUA. By using high throughput virtual screening from an in-house natural product database, the natural active component 5-methylvisammioside (MeV) in Saposhnikovia divaricata (Turcz.) Schischk was predicted to be an effective CNT2 inhibitor with the highest docking score. In vitro , MeV showed the strongest inhibitory activity against CNT2, with IC 50 value of 11.22 ± 2.18 μM. Moreover, MeV showed little or almost no inhibitory effect on other nucleoside transporters CNT3 and equilibrative nucleoside transporters (ENTs), as well as on uric acid (UA) transporter-related targets. In vivo , MeV significantly reduced sUA, inhibited adenosine uptake, and had an ameliorative effect on pathological changes in the liver, kidney, and intestinal tract. Moreover, MeV improved serum and intestinal indices related to inflammation and oxidative stress in mice, reduced intestinal permeability. Through our further study, we found that MeV inhibited the activation of reactive oxygen species (ROS) and NF-κB P65, reduced the production of the NOD-like receptor protein 3 (NLRP3) inflammasome, and improved intestinal injury in a high UA environment. The study suggests that MeV is a potent CNT2 inhibitor for the treatment of HUA and also protects intestinal function by inhibiting the ROS/NF-κB/NLRP3 pathway.
研究领域:
药理学
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生物化学
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分子生物学
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药物化学
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营养学
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胃肠病学
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PubMed
高影响因子
LIPIDS
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2026
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IF 1.6
Xujiao Hu,Yu Fang
In atherosclerosis (AS), the conversion of vascular smooth muscle cells (VSMCs) to a macrophage-like phenotype is a key contributor to plaque instability. Although retinoic acid receptor responder 2 (RARRES2) has been identified as an adipokine implicated in inflammation and metabolism, its role in VSMC phenotypic transformation remains unknown. This study aimed to investigate whether RARRES2 regulates the macrophage-like transformation and dysfunction of VSMCs. In the in vitro AS model, RARRES2 expression was significantly upregulated. Knockdown of RARRES2 inhibited VSMC proliferation and migration, reduced the secretion of inflammatory factors, decreased lipid accumulation, and the number of CD68-positive cells, and suppressed the activation of key proteins in the NF-κB/NLRP3 pathway. In the AS model, RARRES2 expression was found to be significantly upregulated. Knockdown of RARRES2 inhibited the proliferation and migration of VSMCs, reduced the secretion of TNF-α, IL-6, IL-1β, and MMP-2, reduced lipid accumulation, decreased the number of CD68-positive cells (indicating an acquisition of partial macrophage-like features, though further lineage markers are needed to confirm full partial macrophage-like phenotype), and inhibited the activation of key proteins (p-p65, NLRP3, ASC) in the NF-κB/NLRP3 pathway. RARRES2 knockdown suppresses NF-κB/NLRP3 signaling and attenuates macrophage-like transformation, inflammatory responses, and lipid accumulation in VSMCs, suggesting that RARRES2 may represent a potential therapeutic target for AS.
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高影响因子
FOOD CHEMISTRY
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2022
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IF 9.231
Chuang Liu,Zhichang Qiu,Duanyin Gu,Fangzhou Wang,Rentang Zhang
This study explored the structural characteristics of the purified blackened polysaccharide fraction (BJP-4) and its potential to alleviate colitis. BJP-4 had a molecular weight of 1.24 × 10 5 Da and mainly consisted of → 4)- α - l -Gal p A (1→, →5)- α - l -Ara f (1 → and → 4)- β - d -Gal p (1 → residues. After the administration of BJP-4, the disease activity index of colitic mice was reduced by 40.38–50.96%, accompanied by increased colon length (30.00–62.50%) and ameliorated pathological damage. The mechanisms involved regulation of the intestinal microbiota and subsequent inhibition of the TLR4/MyD88/NF- κ B/NLRP3 pathway, balance of pro/anti-inflammatory cytokines and oxidative status, enhancement of epithelial barrier integrity and production of short-chain fatty acids. In particular, high-doses of BJP-4 significantly increased the abundance of beneficial bacteria (f_ Muribaculaceae , Lactobacillus and Lachnospiraceae _NK4A136_group, 0.78–1.04-fold) and suppressed the levels of harmful bacteria (o_ Clostridia _UCG-014, Bacteroides and Escherichia-Shigella , 32.30–90.42%). These findings revealed the anti-inflammatory effects and mechanisms of purified blackened polysaccharides, which facilitated their application in functional foods.
研究领域:
药理学
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免疫学
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微生物学
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营养学
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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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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高影响因子
Evidence-based Complementary and Alternative Medicine
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2023
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IF 2.65
Xingcai Zhang,Wei Zhang,Xianhai Chen,Yuli Cai
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease. Bilobalide (BB) is a sesquiterpene isolated from Ginkgo biloba, and its role in IPF is poorly understood. Mice were intratracheally instilled with 2.5 mg/kg bleomycin (BLM) to induce IPF and then treated with 2.5, 5, and 10 mg/kg BB daily for 21 days. Treatment with BB ameliorated pathological injury and fibrosis of lung tissues in BLM-induced mice. BB suppressed BLM-induced inflammatory response in mice as demonstrated by reduced inflammatory cells counts (leukocytes, neutrophils, macrophages, and lymphocytes) and pro-inflammatory factors (CCL2 and TNF-α), as well as increased CXCL10 levels in BALF. The expression of BLM-induced hydroxyproline, LDH, and pro-fibrotic mediators including fibronectin, collagen I, α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-2, and MMP-9 in lung tissue was inhibited by BB treatment, and the tissue inhibitor of metalloproteinase-1 (TIMP-1) expression was increased. BB blocked the phosphorylation of JNK and NF-κB, and the nuclear translocation of NF-κB in the lung tissue of mice induced by BLM. Additionally, it abated the activation of NLRP3 inflammasome in lung tissue induced by BLM, which led to the downregulation of IL-18 and IL-1β in BALF. Our present study suggested that BB might ameliorate BLM-induced pulmonary fibrosis by inhibiting the early inflammatory response, which is probably via the inhibition of the JNK/NF-κB/NLRP3 signal pathway. Thus, BB might serve as a therapeutic potential agent for pulmonary inflammation and fibrosis.
研究领域:
药理学
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肺病学
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免疫学
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病理学
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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
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2022
·Vol. 48
·期 2
·570-578
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IF 4.414
Guo Shenglong,Lei Qi,Guo Hena,Yang Qian,Xue Yanli,Chen Ruili
Ferroptosis and neuroinflammation play a crucial role in the pathogenesis of Alzheimer’s disease (AD), and Edaravone (EDA) has been demonstrated to have anti-inflammatory, antioxidant and neuroprotective effects in neurodegenerative diseases. However, the relationship between EDA and ferroptosis in AD is unidentified. This research aimed to elucidate the mechanism of EDA in AD with Aβ 1-42-induced HT22 cells as in vitro cell model. The results showed that EDA could significantly reduce Aβ 1-42 -induced apoptosis of HT22 cells and formation of pro-inflammatory factors TNF-α, IL-1β and IL-6, prevent the activation of TLR4/NF-κB /NLRP3 signaling pathway, and inhibit ferroptosis and lipid peroxidation. Taken together, EDA contributes to inhibiting neuroinflammatory injury and ferroptosis in Aβ 1-42-induced HT22 cells, and thus may be a potential candidate for the treatment of AD.
研究领域:
神经科学
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药理学
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细胞生物学
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神经退行性疾病
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PubMed
高影响因子
Theranostics
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2025
·Vol. 15
·期 16
·8587
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IF 13.3
Wei-Jia Yu,Wen-Xi Jiang,Shu-Jing Liu,Hui-Hua Li,Qiu-Yue Lin
Rationale: Infiltration of immune cells into the heart plays a crucial role in the transition from adaptive hypertrophy to heart failure (HF) following chronic pressure overload. However, the key factors in myeloid cells that regulate this process are still not well defined. Here, we studied the functional role of S100A8/A9 in myeloid cells during this transition. Methods: Cardiac hypertrophy and HF models were induced by transverse aortic constriction (TAC) for 1 to 4 weeks. The heterogeneity of CD45 + immune cells and the cellular sources of S100A8/A9 were analyzed using published single-cell RNA sequencing datasets. The effects of S100A8/A9 on TAC-induced hypertrophy and HF were verified in S100A9 knockout (KO) and bone marrow (BM)-chimeric mice and in an in vitro coculture system. Results: S100A8/A9 levels were significantly increased in HF patients and in TAC-induced HF model mice. Moreover, the TAC-induced transition from adaptive hypertrophy to HF was significantly attenuated in S100A9-KO mice and WT mice transplanted with S100A9-KO BM cells. Mechanistically, TAC-stimulated upregulation of S100A8/A9 in neutrophils induced an early inflammatory response and adaptive hypertrophy through activation of the p38 MAPK/JNK/AP-1 pathway, leading to increased production of IL-1β and chemokines (CCL2 and CCL6). These chemokines promoted the infiltration of CCR2 + macrophages to the damaged heart. Therefore, they exhibited upregulation of S100A8/A9, which led to exacerbation of inflammation, cardiac hypertrophy and fibrosis via activation of the NF-κB/NLRP3, AKT/Calcineurin A and TGF-β/Smad2 signaling pathways. Additionally, treating WT mice with the S100A9 inhibitor ABR-238901 prevented TAC-induced cardiac hypertrophy-related dysfunction. Conclusion: The present findings establish an S100A8/A9-related axis between myeloid cells and cardiac cells that drives the pressure overload-induced transition from hypertrophy to HF, suggesting that S100A8/A9 is a promising therapeutic target for this disease.
研究领域:
心脏病学
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免疫学
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分子生物学
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基因组学
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生物医学研究
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高影响因子
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