MOLECULES
·
2026
·Vol. 31
·期 10
·1560
·
IF 5.1
Sisi Huang,Wei Cai,Yan Wang,Xiaoliang Xing,Zaiqi Zhang
Objective:This study aimed to investigate whether pomolic acid (PA), a predicted bioactive metabolite of the Dong botanical drug Madeng’ai (MDA), suppresses inflammatory cytokine expression by inhibiting nuclear factor-κB (NF-κB) pathway activation in a tumor necrosis factor-α (TNF-α)-induced human rheumatoid arthritis fibroblast-like synoviocyte (RA-HFLS) model.Methods:PA content in MDA from different regions and harvest years was quantified via High-Performance Liquid Chromatography (HPLC). Network analysis was employed as a hypothesis-generating tool to predict potential targets and pathways, followed by molecular docking to validate the binding affinity of PA to core targets of the NF-κB pathway, and ADMET prediction to evaluate its pharmacokinetic properties and safety profile. The RA-HFLS inflammatory model was induced by TNF-α. Cell viability and inflammatory cytokine secretion were assessed using Cell Counting Kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA). NF-κB signaling pathway activation and downstream gene expression were examined by Western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively.Results:HPLC analysis revealed that MDA samples from Guizhou harvested in 2019 contained the highest PA content (0.1117 mg/g). Network analysis predicted the NF-κB signaling pathway as a candidate mechanism underlying PA’s potential anti-inflammatory effects. Molecular docking showed that PA stably bound to IKKβ, p65, and IκBα, while ADMET prediction indicated favorable intestinal absorption, low drug–drug interaction risk, and good genetic safety, albeit with potential hepatotoxicity and reproductive toxicity risks. In the TNF-α-induced RA-HFLS model, PA dose-dependently inhibited abnormal cell proliferation and significantly reduced the secretion of pro-inflammatory cytokines TNF-α and interleukin-6 (IL-6). Mechanistic studies indicated that PA suppressed the activation of the NF-κB signaling pathway, thereby downregulating the mRNA expression of inflammatory genes such as IL-6, TNF-α, and interleukin-1β (IL-1β).Conclusions:PA, a bioactive metabolite of the Dong botanical drug MDA, may inhibit NF-κB signaling pathway activation, thereby downregulating TNF-α-induced inflammatory cytokine expression in RA-HFLS, demonstrating its in vitro anti-inflammatory potential.
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Zhen-Min Zhang,Lian Zhu,Ru-Yue Zhang,Han-Xiu Deng,Shun-Li Xiao,Zi-Xuan Liu,Jia-Yu Zhang,Wei Cai
Background Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe respiratory diseases with high global incidence and mortality. Current therapeutic approaches remain limited, necessitating urgent development of novel treatments. Supramolecular complexes have gained attention in biomedicine due to their unique structural and functional properties. Purpose This study aimed to evaluate the therapeutic potential of neochlorogenic acid-copper supramolecular complexes (NA-Cu) against ALI/ARDS, building on prior evidence of its anti-inflammatory effects in vitro, and to elucidate its underlying metabolic mechanisms. Study design In vivo experimental investigation using an ALI model to assess NA-Cu's effects on lung pathology, inflammatory markers, and metabolic pathways. Mechanistic insights were validated through integrated metabolomics and molecular pathway analysis. Methods The therapeutic efficacy of neochlorogenic acid-copper supramolecular complexes (NA-Cu) was assessed by quantifying its effects on lung edema severity and pro-inflammatory cytokine expression levels (IL-1β, IL-6, TNF-α) in an ALI model. Mechanistic profiling was performed using an integrated analytical approach combining air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) with untargeted metabolomics to map spatial metabolic alterations. Subsequently, we screened dysregulated metabolic pathways and signaling cascades, with emphasis on the PI3K/NF-κB/iNOS axis. Validation studies established correlations between NA-Cu-induced metabolic shifts and key therapeutic outcomes, including anti-inflammatory efficacy and histological protection of lung tissue. Results This study further found that neochlorogenic acid-copper supramolecular complexes can improve edema in lung tissue by inhibiting the expression of IL-1β, IL-6, and TNF-α. The anti-ALI metabolism mechanism of NA-Cu is revealed through AFADESI-MSI combined with metabolomics. It was found that supramolecular complexes mainly affects sphingolipid metabolism, linoleic acid metabolism, α linolenic acid metabolism, ether lipid metabolism, glycerol phospholipid metabolism, arachidonic acid metabolism and PI3K/NF-κB/iNOS pathway to improve protection of lung tissue. Conclusion NA-Cu demonstrates robust anti-ALI/ARDS efficacy by synergistically suppressing inflammation and reprogramming lipid metabolism. This study validates the therapeutic promise of supramolecular complexes for ALI treatment and provides novel mechanistic insights into their mode of action.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 6.5
Tianyue Guan,Audrey Dela,Yichen Jin,Juqin Song,Tingyan Wang,Yu Zhu,Jingquan Dong,Panpan Zhao
Sepsis-induced acute lung injury (ALI) remains a critical factor contributing to mortality in intensive care units, and effective therapeutic strategies are still lacking. The present research explores the defensive impacts and associated mechanisms of Tubuloside A (TA), an active phenanthrenoid glycoside extracted from Cistanche deserticola, in sepsis-induced ALI. Utilizing both a cecal ligation and puncture (CLP) mouse model and LPS-stimulated MLE-12 alveolar epithelial cells, we found that TA markedly attenuated lung injury, as indicated by improved histopathological features, reduced pulmonary edema, and maintenance of alveolar structure. Mechanistically, TA provided multifaceted protection by concurrently inhibiting oxidative stress, ferroptosis, and inflammatory signaling—critical drivers of sepsis-induced ALI. Treatment with TA diminished lipid peroxidation, restored GPX4 expression, and inhibited pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). Network pharmacology identified NFKB1 as a therapeutic target of TA against ALI. Molecular docking predicted and SPR analysis verified that TA binds to NF-κB p50. Notably, functional validation via NF-κB p50 overexpression abolished TA-mediated protection and re-sensitized cells to ferroptosis, confirming NF-κB p50 as a central regulatory node. Furthermore, TA activated Nrf2 signaling in an NF-κBp50–dependent manner, as demonstrated by nuclear translocation assays and rescue experiments. Calcein AM imaging and iron chelation studies confirmed that TA’s anti-ferroptotic effect requires functional NF-κB/Nrf2/GPX4 crosstalk. Collectively, our findings reveal that TA ameliorates sepsis-ALI by targeting the NF-κBp50–Nrf2/GPX4 axis to coordinately inhibit inflammation, oxidative stress, and ferroptosis, highlighting its potential as a multi-target phytotherapeutic agent for acute respiratory disorders
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2026
·
IF 2.9
Qian Sun,Shi-Liu Xu,Shuang-Ning Liu,De-Jian Chen,Zheng-Jun Li,Xiao-Jun Qiu,Xia Yang,Feng-Xiang Zhang,Jian-Xin Chen
SWLDH was firstly confirmed to treat bacterial infection-induced ALI. • PI3K-AKT/NF- κ B and MAPK signaling pathways were confirmed as the core mechanism for SWLDH to treat ALI. • Five potential anti-ALI compounds in SWLDH were identified. Shi-Wei-Long-Dan-Hua capsule (SWLDH) is clinically used to alleviate bacterial or viral infection induced bronchitis. Recent studies have reported its effects on viral infection induced acute lung injury, broadening our understanding of its clinical applications. However, its effects against bacterial infection-induced ALI were still unclear, along with not fully elucidated chemical profile, significantly limiting its clinical application and product improvement. In this work, we aimed to systematically characterize the chemical components in SWLDH and explore its effects and mechanisms against bacterial infection-induced ALI. Results showed that SWLDH (2 g/kg/day) significantly reduced lung index, alleviated pathological injury and depressed cytokine expression in LPS-challenged mice. SWLDH also inhibited LPS-induced over-expression of iNOS and pro-inflammatory cytokines (TNF- α , IL-1 β , IL-6) in RAW264.7 cells. Moreover, 128 chemical components in SWLDH and its 32 prototypes in rats were identified by using UPLC-Q/TOF MS. Network pharmacology and Western blot were used to confirm that SWLDH can alleviate LPS- induced ALI by suppressing pulmonary inflammation and the PI3K-Akt-NF- κ B/MAPK axis. Further, five potential anti-ALI substances in SWLDH were found. This is the first time to comprehensively profile the chemical components in SWLDH and reveal its effects and mechanisms against bacterial infection-induced ALI, providing the potential substances and pharmacological data for further quality improvement and product development. Download: Download high-res image (166KB) Download: Download full-size image
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2026
·
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2026
·
IF 7.3
Hongwei Li,Huiying Zhuang,Dianxi Zhang,Tingting Qiu,Lu Liu,Ziyi Sunyang,Yuqiang Han,Rilei Yu,Guanzhao Wu,Ruijuan Yin,Tao Jiang
Mitogen-activated protein kinase-interacting kinase (MNK), a pivotal kinase downstream of MAPK signaling, is currently the only enzyme reported to be capable of phosphorylating eIF4E. This study first confirmed that MNK silencing in LPS-stimulated macrophages inhibits eIF4E phosphorylation, inflammatory polarization, and cytokine release. Based on the prior discovery that the imidazo[2,1-b][1,3,4]thiadiazole skeleton can effectively inhibit the MNK kinases, this study further designed and synthesized a series of imidazo[2,1-b][1,3,4]thiadiazole derivatives modified with sulfonyl or phosphoryl groups. Among these derivatives, compound 13 potently and selectively inhibited MNK1/2 (IC50 = 10.84/12.81 nM), exerted dose-dependent anti-inflammatory effects in LPS-induced RAW 264.7 cells, and alleviated kidney and spleen damage in the mouse model of LPS-induced inflammation. Mechanistically, 13 suppressed eIF4E phosphorylation, NF-κB signaling, and macrophage polarization, thereby reducing pro-inflammatory cytokines and oxidative stress. These results suggest that MNK inhibition is a promising strategy for treating inflammatory diseases by targeting both inflammation and oxidative stress.
✓ 已验证
DOI
PubMed
高影响因子
Food Chemistry-X
·
2026
·
IF 9.2
Chunlei Li,Yanxiao Xiang,Tao Jiang,Jiyuan Zhang,Xuekui Xia,Anchang Liu
Inflammation is a natural host defense response to injury or infection, and seafood-derived polypeptides exhibit prominent anti-inflammatory potential with promising therapeutic applications. Here, we report the screening, characterization and anti-inflammatory evaluation of a novel cupin-like polypeptide OGP1-1 from Ostrea gigas . OGP1-1 exerted significant anti-inflammatory effects in RAW264.7 macrophages in vitro and in a transgenic zebrafish model in vivo. Chemical proteomics identified transforming growth factor-β-activated kinase 1 (TAK1) as the direct molecular target, and molecular docking and dynamics simulations confirmed stable binding within TAK1's activation loop. Mechanistic studies demonstrated that OGP1-1 exerts its anti-inflammatory effects by suppressing the TAK1-mediated NF-κB signaling pathway. Collectively, these findings position OGP1-1 as a novel cupin-like polypeptide with potent anti-inflammatory activity and high potential for development as a functional food ingredient in inflammation management.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
METABOLIC BRAIN DISEASE
·
2026
·Vol. 41
·期 1
·104
·
IF 3.8
Zhong Guangcheng,Shi Jiahui,Jiang Yue,Li Shiyin,Wang Xuejing,Zhang Ting,Chen Zhuo,Wang Qi,Liu Shan
Alzheimer’s disease (AD) is a prevalent neurodegenerative condition distinguished by intricate pathological mechanisms. Cinnamaldehyde, a natural active chemical sourced from the bark of Cinnamomum species, exhibits remarkable neuroprotective properties that have been validated in various neurological disorders. In this study, network pharmacology alongside zebrafish experiments was employed to investigate the molecular mechanisms and signaling pathways through which cinnamaldehyde ameliorates AD. Potential targets of cinnamaldehyde were found using the SuperPred, TargetNet, SwissTargetPrediction, and SEA databases, whilst AD-related targets were obtained from TTD, OMIM, GeneCards, and DrugBank databases. Subsequently, protein-protein interaction analysis was performed using the STRING database, followed by GO and KEGG enrichment studies via the DAVID platform. Finally, molecular docking validation was conducted using CB-Dock2. The network pharmacology results indicated that cinnamaldehyde might impact its beneficial effects on AD via regulating the toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-κB) signaling pathway. To further validate this mechanism, an AD model was established in zebrafish induced by aluminum chloride (AlCl₃). Behavioral assays demonstrated that cinnamaldehyde significantly improved AlCl₃-induced cognitive impairment. Hematoxylin-eosin and Nissl staining revealed that cinnamaldehyde attenuated neuropathological damage. Biochemical analyses indicated that cinnamaldehyde alleviated oxidative stress and restored cholinergic dysfunction. Furthermore, RT-qPCR findings indicated that cinnamaldehyde reduced inflammatory mediator expression and diminished TLR4 and NF-κB p65 mRNA levels, while western blotting confirmed reduced TLR4 and phosphorylated NF-κB p65 protein expression. In summary, cinnamaldehyde may mitigate neuroinflammation through suppressing the TLR4/NF-κB signaling pathway, thereby ameliorating AlCl₃-induced cognitive impairment, neuropathological injury, oxidative stress imbalance, and cholinergic system dysfunction in zebrafish. Graphical The alternative text for this image may have been generated using AI.
✓ 已验证
DOI
PubMed
高影响因子
BIOGERONTOLOGY
·
2026
·Vol. 27
·期 2
·72
·
IF 5.3
Zhang Xiaoli,Wang Chengniu,Chen Weiguan
Aging is a major risk factor for the onset and progression of many neurodegenerative diseases. Inflammation is the body’s natural defense mechanism against harmful stimuli . A growing body of research has highlighted the intricate relationship between aging and inflammation, with chronic low - grade inflammation, often referred to as “inflammaging,” being a hallmark of the aging process. Cycloneolitsol (CL) is a C-32 cycloartane-type triterpene from Taxodium ascendens which has been reported to possess the anticancer, neuroprotection and antibacterial activities. Its specific role and the underlying molecular mechanisms in modulating the aging process remain unclear. Our study aimed to explore the possible anti-aging effect and mechanisms of CL. Network pharmacology predicted core targets and several potential pathways, which are associated with the anti-aging effect of CL. RAW264.7 macrophages and Caenorhabditis elegans were selected for evaluating its anti-aging and anti-inflammation activity. The results showed that CL exerted obvious anti-inflammatory effects against LPS-induced M1-type polarization of RAW264.7 cells via NF-κB signaling pathway. In C. elegans , CL improved Biological Characteristics and prolonged the lifespan without reproductive toxicity. Furthermore, experiments on different mutant C. elegans strains and the nuclear translocation of SKN-1 confirmed that CL activates autophagy and enhances the antioxidant stress response ability through the SEK-1/PMK-1/SKN-1 signaling pathway. This study provides novel insights into the biological activities of CL, highlighting its potential as a natural product for treating inflammation-related diseases and delay aging.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
·
2026
·
IF 2.2
XinQun Xu,QuanLan Wang,Long Wang,WenQiang Cheng,Fei Li,HuanBing Liu,YuangBing Guo
Objective To investigate the regulatory mechanism of IDO1 on brain tissue damage in Alzheimer’s disease (AD) mice. Methods APP/PS1 mice (AD model mice) and C57BL/6J mice were treated with IDO1 inhibitor 1-MT. Behavioral changes were assessed using the open field test, and histopathological changes were analyzed using HE staining, Nissl staining, and transmission electron microscopy. TUNEL staining and immunofluorescence were used to detect cell apoptosis and the expression of IDO1 and GFAP, respectively. Metabolomics was analyzed using liquid chromatography-mass spectrometry. An in vitro AD cell model was established, and inflammatory factor levels were measured using ELISA/qPCR, while NF-κB pathway activation was assessed using WB. Results In vivo experiments showed that compared with the model group mice, 1-MT intervention improved behavioral abnormalities in AD mice, reduced hippocampal tissue damage, decreased neuronal apoptosis, and downregulated the expression of IDO1 and GFAP. In vitro experiments demonstrated that interfering with IDO1 could decrease the levels of IL-1β, TNF-α, and IL-6, reduce GFAP expression, and inhibit p65 phosphorylation. Conclusion Interfering with IDO1 can inhibit the NF-κB pathway, reduce the release of inflammatory factors, and improve brain tissue damage in AD mice.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Lei Lei,Guoguo Wan,Xiaoyu Geng,Jianguo Sun,Yi Zhang,Jianwei Wang,Congwen Yang,Zheng Pan
Ethnopharmacological relevance Lamiophlomis rotata (Benth.) Kudo ( L . rotata ), a Tibetan medicinal plant , is used to treat “yellow-water diseases”, such as skin disease, jaundice and rheumatism . Our previous study showed that the iridoid glycoside extract of L. rotata (IGLR) is the major constituent of skin wound healing. However, the role of IGLR in the biological process of trauma repair and the probable mechanism of the action remain largely unknown. Aim of the study To investigate the role of IGLR in the biological process of trauma repair and the probable mechanism of the action. Materials and methods The role of IGLR in wound healing was investigated by overall skin wound in mice with Hematoxylin and Eosin (H&E) and Masson trichrome staining. The anti-inflammatory, angiogenesis-promoting and fibril formation effects of IGLR were visualized in wound skin tissue by immunofluorescence staining, and the proinflammatory factors and growth factors were assayed by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Macrophages, dermal fibroblasts, and endothelial cells were cultured to measure the direct/indirect interaction effects of IGLR on the proliferation and migration of cells, and flow cytometry was employed to assess the role of IGLR on macrophage phenotype. Network pharmacology combined with Western blot experiments were conducted to explore possible mechanisms of the actions. Results IGLR increased the expression of CD206 (M2 markers) through the RAS/p38 MAPK/NF-κB signaling pathway during wound injury in vivo and in vitro . IGLR suppressed the inflammatory cytokines iNOS, IL-1β and TNF-α in the early stage of wound healing . During the proliferation step of wound repair, IGLR promoted angiogenesis and fibril formation by increasing the expression of VEGF, CD31, TGF-β and α-SMA in wound tissue, and similar results were verified by RT-PCR and ELISA. In a paracrine mechanism, the extract promoted the proliferation of dermal fibroblasts, and endothelial cells were founded by the conditioned medium (CM). Conclusion IGLR induced M2 macrophage polarization in the early stage of wound healing; in turn, IGLR played a key role in the transition from inflammation to cell proliferation during the biological process of wound healing.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Yao Liu,Ruifang Sun,XiaoPing Lin,Lanlan Wu,Hengying Chen,Siwen Shen,Yan Li,Yuanhuan Wei,Guifang Deng
Gestational Diabetes Mellitus (GDM) has an effect on the health of pregnant women and fetuses. Procyanidins (PA) is a flavonoid with anti-diabetic activity, but its effects and mechanisms on GDM have not been defined. Herein, we studied further the functions and mechanisms of PA on insulin resistance (IR) in GDM mice, as well as on postpartum and offspring mice. GDM mice model was built by feeding a high-fat-high-sucrose diet, and PA intervention (27.8 mg/kg/d) was performed from 4 weeks before pregnancy to delivery. Intestinal flora deficient (IFD) mice model was established by broad spectrum antibiotics. PA decreased the gestational weight gain, and the levels of fasting blood glucose, insulin, homeostasis model of assessment for IR index, yet increased the levels of HOMA for insulin sensitivity index. Interestingly, in IFD mice the effect of PA on improving IR was significantly weakened. PA inhibited inflammation by decreasing the levels of IL-6, TNF-α, IL-17 and CRP, which also been blocked in the IFD mice. Moreover, PA improved glycometabolism and reduced the secretion of inflammatory factors and hepatic inflammation infiltration of mice at 4 weeks postpartum, but had no significant effect on offspring mice. Mechanistically, PA treatment suppressed the nuclear factor‐κB (NF‐κB) p65 nuclear translocation and nucleotide‐binding domain like receptor protein 3 (NLRP3) inflammasome activation. In vitro studies, 4-hydroxyphenylacetic acid and 3-(4-hydroxyphenyl) propionic acid, main intestinal flora metabolites of PA restrained NF‐κB/NLRP3 activation. In conclusions, PA improved IR via NF-κB/NLRP3 pathway in GDM and postpartum mice, which partly through its metabolites by gut microbiome.
✓ 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）