FOOD AND CHEMICAL TOXICOLOGY
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2026
·
IF 3.2
Lili Liu,Zhengyao Li,Xinlei Peng,Hongli Zhang,Yuying Yang,Jun Liu,Min Liu
TPs reduced oxidative stress in PFOA-exposed mice. • TPs reduced intestinal permeability and ERK/NF-κB pathway in the ileal tissue. • TPs reduced harmful bacteria and increased beneficial bacteria in PFOA-exposed mice. • TPs as a potential dietary intervention alleviate pollutant-induced enterotoxicity. Perfluorooctanoic acid (PFOA), a persistent environmental contaminant, has been found to induce intestinal damage. Dietary tea polyphenols (TPs) have been reported to alleviate gastrointestinal diseases, however, the underlying mechanism through which TPs alleviate PFOA-induced ileal barrier injury remains unclear. Here, the effects of TPs on oxidative stress, intestinal permeability, extracellular signal-regulated kinase (ERK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway, and gut microbiota in mice were evaluated. The results showed that TPs alleviated oxidative stress by elevating the serum GSH and CAT activities, and reducing MDA levels. Moreover, TPs decreased intestinal permeability by reducing serum DAO and LPS levels, upregulating the expression of claudin-1 and occludin, and inhibiting the phosphorylation of ERK and NF-κB in the ileum. Additionally, 16S rRNA gene sequence analysis revealed that TPs reversed PFOA-induced gut dysbiosis by decreasing harmful bacteria of Desulfovibrio and Ileibacterium , and increasing beneficial bacteria of Lachnospiraceae_NK4A136_grou p and Ligilactobacillus . This study reveals positive effects of TPs as a potential dietary intervention against pollutant-induced enterotoxicity. Download: Download high-res image (250KB) Download: Download full-size image
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高影响因子
Animals
·
2026
·Vol. 16
·期 9
·1310
·
IF 3.2
Binwen Zhang,Zheng Wei,Mei Yang,Xin Wang,Qiang Shan,Zheng Cao
Simple SummaryMastitis is a common disease in dairy cows, with major pathogens includingStaphylococcus aureusandEscherichia coli. Although berberine has antibacterial and anti-inflammatory properties, it is poorly absorbed after oral administration. We developed a novel berberine-loaded hydrogel that can be applied to the udder, delivering the drug directly to the mammary tissue. Experimental results showed that this hydrogel is stable, safe, and capable of sustained drug release. Tests in a mouse model demonstrated that it effectively reduces bacteria-induced inflammation, protects the mammary barrier, and minimizes cell damage. Its mechanism of action is related to the regulation of intracellular NF-κB and PI3K/Akt signaling pathways. This study suggests that the hydrogel offers a new topical strategy for treating mastitis, solving the problem of poor oral absorption through local application. It holds promise for providing dairy cows with a more convenient and effective treatment option in the future.Mastitis is a common disease in dairy cows, mainly caused by Staphylococcus aureus and Escherichia coli. Berberine (BBR) has antibacterial and anti-inflammatory potential, but its application is limited due to poor oral absorption and difficulty in reaching mammary tissue. To address this, this study developed a BBR-loaded composite ethosome hydrogel (BBR-CEH) to achieve targeted mammary delivery through local transdermal administration. The experimental results showed that BBR-CEH has good chemical stability and biosafety. Subsequently, a mouse mastitis model was established by intraductal injection of 50 µL of bacterial mixture (E. coli:S. aureus= 1:1, each at 1 × 107CFU/mL). The results showed that after BBR-CEH treatment, the mRNA expression ofTNF-α(tumor necrosis factor-alpha),IL-6(interleukin-6), andIL-1β(interleukin-1 beta) was significantly decreased, the mRNA expression ofZO-1(zonula occludens-1),Occludin, andClaudin-4was significantly increased, andBax/Bcl-2(Bcl-2-associated X protein/B-cell lymphoma 2) was significantly reduced (p< 0.01), indicating alleviation of mastitis by reducing inflammation, improving tight junctions, and inhibiting apoptosis. Finally, network pharmacology and in vivo experiments confirmed that its mechanism involves the NF-κB (nuclear factor kappa-B) and PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) pathways. Thus, topical BBR-CEH may represent a promising new strategy for mastitis treatment.
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高影响因子
Chinese Journal of Natural Medicines
·
2026
·Vol. 24
·期 7
·832-848
·
IF 7.5
Jueyao Zou,Tongyao Hu,Zhengyu Zhang,Yong He,Yuxin Wang,Yixiao Zhou,Ziyan Zhu,Suyun Yu,Wei Zou,Zhonghong Wei,Yang Zhao,Yanhong Pan,Wenxing Chen,Yin Lu
Psoriasis is a chronic skin disease driven by skin inflammation and abnormal subcutaneous blood vessels. Yinxie Granules (YXKL) is a clinically effective traditional Chinese medicine (TCM) formula that has shown promise in psoriasis treatment, but its pharmacological mechanisms and material basis remain unclear, limiting its clinical application and co-administration with other drugs. In this study, we explored the mechanism and active components of YXKL in the treatment of psoriasis using patient samples, IMQ-induced psoriatic mice, zebrafish, and in vitro assays. We discovered that YXKL alleviated skin inflammation and restored the skin barrier by reducing M1 macrophage/Th17 infiltration, lowering pro-inflammatory cytokines (IL-6, IFN-β, IL-23, IL-17), and increasing loricrin expression. Mechanistically, we identified a dynamic transition in STING signaling during psoriasis progression. Both the STING/IRF3 and STING/NF-κB pathways were activated in moderate psoriasis, while only the STING/NF-κB pathway was hyperactivated in severe disease. YXKL specifically targeted the STING/NF-κB pathway to mitigate inflammation and vasculopathy but had no significant impact on the upstream regulators, including TRAF6, LKB1, AMPK, and ULK1. Quercetin and kaempferol were identified as the primary STING-modulating components in YXKL, binding to STING proteins and inhibiting downstream pathway activation. These flavonoid components mediate the anti-psoriatic effects of YXKL by simultaneously suppressing skin inflammation and angiogenesis while enhancing vascular integrity through STING inhibition in both keratinocytes and endothelial cells. Our results elucidated the molecular basis of YXKL for psoriasis treatment, highlighting STING/NF-κB as a pivotal therapeutic target in mitigating psoriasis development and providing natural candidate compounds as potential STING inhibitors.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2026
·
IF 3.6
Jingjing Chen,Bin Liu,Yuanyuan Li,Binwu Zhuang,Dong Su,Yunlong Sang,Zibo Dong,Hao Liu
Pyrazole permethrin (also known as pyraclostrobin, abbreviated as PP) is a widely used fungicide that is chemically stable and fat-soluble; however, due to its accumulation in the environment and bioaccumulation, it poses potential health risks.This study systematically elucidates PP-induced liver injury through a combination of network toxicology and in vitro/in vivo investigations. Network toxicology identified 328 potential targets and 12 core genes associated with PP-induced liver injury. GO and KEGG enrichment analyses revealed pathway enrichment emphasizing biological processes such as inflammation, oxidative stress, apoptosis, and lipid metabolism. In vivo experiments in mice revealed that after 28 days of exposure, histopathological analysis showed minor local inflammatory cell infiltration and extensive hepatocyte necrosis and vacuolation in both low- and high-dose groups. High-dose PP significantly elevated serum transaminase (AST and ALT) activity. Biochemical analysis revealed that PP treatment reduced antioxidant enzyme activity (CAT, T-AOC, GSH-Px) while increasing malondialdehyde (MDA) levels, inducing oxidative stress. Additionally, PP exposure enhanced the expression of inflammatory cytokines (IL-1β, TNF-α). This indicates activation of oxidative stress and inflammatory pathways: oxidative damage occurs via depletion of the antioxidant enzyme system, while inflammatory cascades are mediated through the PI3K/AKT/NF-κB signaling axis. This study reveals key molecular targets and pathways involved in PP-induced hepatotoxicity, suggesting that subacute exposure risks should be fully considered when establishing safety standards for agricultural chemical use.
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高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2026
·
IF 3.6
Peng Wan,Fuyuan Cao,Gai Li,Xiaohui Hao,Yu Mu,Jian Sun,Ling Xue,Nan Liu
Indium lung disease is characterized by interstitial pneumonia, pulmonary alveolar proteinosis (PAP), pulmonary fibrosis, and lung cancer. However, this is insofar irreversible. The disease is believed to be caused by inhalation of indium and its compounds. We constructed a rat model of indium lung disease to explore the possible role of the NF-κB/Nrf2 pathway in indium‑tin oxide nanoparticle (Nano-ITO)-induced pulmonary injury and to reveal the regulatory mechanism. To integrate computational network toxicology and molecular docking with a rat model to identify core molecular targets and pathways underpinning ITO toxicity, and evaluate whether modulation of the NF-κB/Nrf2 axis by sulforaphane or all-trans retinoic acid mitigates Nano-ITO-induced lung injury. Toxicity prediction, target mining and integration with oxidative stress and vascular remodeling gene sets identified intersection targets that were analyzed by PPI, GO/KEGG/Reactome enrichment and topological analysis to select core nodes. Molecular docking probed interactions between ITO components and proteins in NF-κB/Nrf2 pathways. Next, we evaluated the NF-κB/Nrf2 signaling pathway to elucidate the molecular mechanism of sulforaphane in regulating inflammation, oxidative stress, vascular remodeling, vascular hyperplasia, PAP, cholesterol accumulation, and interstitial fibrosis in indium lung disease induced by Nano-ITO. Findings show that the NF-κB/Nrf2 signaling pathway is involved in Nano-ITO-induced vascular remodeling, cholesterol crystal formation, alveolar protein deposition, collagen hyperplasia, and interstitial fibrosis in rats. Sulforaphane can effectively attenuate Nano-ITO-induced inflammation, oxidative stress and vascular remodeling, as manifested by decreased expression of CD31, α-SMA, Collagen I, SP-A, SP-D, and inflammatory cytokine, via activating Nrf2 and inhibiting the NF-κB signaling pathway.
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CNS Neuroscience & Therapeutics
·
2026
·Vol. 32
·期 2
·e70787
·
IF 6.6
Shengnan Xiao,Lianmei Liu,Xuemei Qin,Lei Xu,Zhenyu Li,Zhi Chai
Cycloastragenol derivatives regulate the TLR4/NF‐κB/TERT signaling pathway and tyrosine metabolism, breaking the vicious cycle of “inflammation‐aging” and improving symptoms of Parkinson's disease. This study provides direction for the application of natural products in the development of PD drugs.
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高影响因子
Food Frontiers
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2026
·Vol. 7
·期 1
·e70225
·
IF 6.9
Qiaoyu Sun,Qingqing Zhou,Sitong Ge,Danli Wu,Ping Li,Qing Gu
Impairment of intestinal barrier function is intricately linked to intestinal inflammation. Emerging evidence highlights that tryptophan-derived metabolites from the intestinal microbiota play a crucial role in maintaining the homeostasis of intestinal barrier function. In this study, a Caco-2/HT29 co-culture model was applied to evaluate the effects of indole-3-acetic acid (IAA) on the intestinal barrier and explore its underlying mechanism of action. Results demonstrated that lipopolysaccharide (LPS) caused the transepithelial resistance to drop to 387.5 ± 30.41 Ω·cm 2 , while IAA was able to increase it to 542 ± 31.11 Ω·cm 2 . At the same time, it reduced the paracellular permeability and restored the FITC-Dextran 4 (FD-4) permeability to 108.01%. This phenomenon was accompanied by an upregulation in the expression of tight junction (TJ) proteins. Concurrently, after IAA intervention, aryl hydrocarbon receptor (AHR) pathway was activated, while nuclear factor kappa-B (NF-κB) pathway was significantly inhibited. Furthermore, IAA exerted an inhibitory effect on the LPS-triggered upregulation of inflammatory factors (TNF-α, IL-6, IL-8) in RAW264.7 cells. These findings provide novel insights into the enhancement of intestinal barrier function and the in vitro anti-inflammatory properties of gut microbiota-derived metabolites.
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Food Science & Nutrition
·
2026
·Vol. 14
·期 1
·e71438
·
IF 3.8
Ziyue Wang,Jianxiong Hao,Junye Yin,Huan Rao,Xia Zhao,Lulu Yu,Dandan Zhao
Acute lung injury (ALI) is a life‐threatening condition characterized by acute inflammatory damage to the alveolar epithelium and capillary endothelium, triggered by various pathological factors. Our previous study demonstrated the anti‐inflammatory and anti‐oxidative effects of Lycium barbarum polysaccharide (LBP) and chlorogenic acid (CA) against lipopolysaccharides (LPS)‐induced inflammatory response of NR8383 cells, while the current study further investigated the alleviating effect of LBP and CA against ALI through in‐depth experiments. In vitro experiments identified potential targets ( CASP3 , KDR ) and related pathways, while in mice with ALI induced by 5 mg/kg LPS, CA‐LBP (CA:LBP = 1:7, L/M/H dose: 25/50/100 mg/kg) was administered for 14 consecutive days, which reversed weight loss, alleviated lung injury, suppressed MPO activity, reduced TNF‐α, IL‐1β, IL‐6 and MDA levels, enhanced SOD and GSH‐Px activities, and mitigated NF‐κB activation significantly. Data of molecular docking further confirmed that the CA‐LBP complex can exert alleviating effects through suppressing the NF‐κB signaling pathway. Taken together, the present work sheds light on the multi‐target regulatory mechanism of CA‐LBP against ALI. Lycium barbarum polysaccharide (LBP) and chlorogenic acid (CA) ameliorate LPS‐induced acute lung injury (ALI) through a multi‐target regulatory mechanism, which involves suppression of the NF‐κB signaling pathway.
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高影响因子
Nature Communications
·
2026
·
IF 18.1
Ye Shiju,Zhao Yanbo,Tu Hanxiao,Han Xue,Liu Tong,Gong Yingchao,Lu Jiangting,Jin Tingting,Luo Wu,Qu Xuefeng,Lai Dongwu,Fu Guosheng,Liang Guang
Hypertensive heart failure highlights an urgent need for effective therapeutic strategies. Protein kinases regulate multiple pathways in cardiac pathophysiology and may provide promising therapeutic targets. Here, we identified a Cyclin-dependent kinase, CDK9, promoting inflammation and cardiac remodeling in terminally differentiated cardiomyocytes. Firstly, kinase enrichment analysis and experimental evidence revealed CDK9 phosphorylation at Thr-186 in both human and mouse hypertrophic heart tissues. CDK9 loss of function via T186A mutation in cardiomyocytes attenuated Ang II-induced heart remodeling and NF-κB-mediated inflammation, whereas CDK9 overactivation by T186E mutation induces. This regulatory function of CDK9 in cardiac remodeling is cell cycle-independent. Further studies demonstrate that the kinase domain of CDK9 directly binds to NF-κB P65 protein, which leads to the CDK9/P65 complex nuclear translocation, P65 phosphorylation, and transcription of inflammatory and hypertrophic genes in cardiomyocytes. This process requires CDK9 Thr-186 phosphorylation and Cyclin T1 presence, but is independent on IKKβ and CDK9-RNAPII pathways. Pharmacological inhibition of CDK9 phosphorylation significantly attenuated Ang II-induced cardiac inflammation, remodeling, and dysfunction in mice. Collectively, Ang II-activated CDK9 directly binds to and phosphorylates P65 to drive cardiac inflammation and remodeling. This study identifies CDK9 as a potential target in heart failure therapeutics.
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Frontiers in Immunology
·
2026
·
IF 7
Jiquan Shen,Changjian Zhou,Xinggao Wang,Yuxuan Chen,Run Liu,Liang Hong,Weiping Ji,Bo Wang
BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by severe synovial inflammation, joint deformities, and progressive tissue destruction. Celastrol (Cel), a natural triterpenoid with anti-inflammatory and antioxidant activity, is a promising therapeutic candidate for RA; however, its application is limited by poor aqueous solubility, low bioavailability, and systemic toxicity.PurposeThis study aimed to develop folate-modified liposomes encapsulating Cel (FA-Cel-LPs) to improve its solubility, stability, and joint accumulation, and to evaluate their anti-inflammatory efficacy and associated molecular changes in LPS-activated RAW264.7 macrophages and collagen-induced arthritis (CIA) rats.MethodsFA-Cel-LPs were prepared by thin-film hydration followed by extrusion and characterized for particle size, morphology, polydispersity index (PDI), encapsulation efficiency (EE), and in vitro release behavior. In LPS-activated RAW264.7 cells, cellular uptake, intracellular ROS levels, NF-κB nuclear translocation, COX-2/iNOS expression, and cytokine secretion were evaluated. In CIA rats, therapeutic efficacy was assessed by paw swelling, arthritis scores, in vivo fluorescence imaging, MRI, histological analysis, and micro-CT-based bone parameters. Safety was evaluated using hemolysis, serum biochemical analysis, and organ histology.ResultsFA-Cel-LPs showed a mean particle size of 110.65 ± 1.24 nm, an EE of 84.67 ± 2.55%, a PDI of 0.230 ± 0.018, and a sustained release profile with pH-dependent differences in vitro. In RAW264.7 cells, folate-modified liposomes showed greater cellular uptake and were associated with reduced ROS levels, attenuated NF-κB activation, and decreased COX-2, iNOS, and pro-inflammatory cytokine expression, with low cytotoxicity. In CIA rats, in vivo imaging suggested greater accumulation of FA-Cel-LPs in inflamed joints. Compared with free Cel and Cel-LPs, FA-Cel-LPs more effectively reduced paw swelling and joint inflammation while attenuating bone erosion and preserving joint architecture. Serum ALT and AST levels in the FA-Cel-LPs group remained within physiological ranges and were significantly lower than those in the free Cel group. Organ histology showed no obvious treatment-related injury, suggesting acceptable preliminary safety.ConclusionFA-Cel-LPs improved the solubility, formulation stability, and apparent joint accumulation of Cel and enhanced its anti-inflammatory and bone-protective effects in experimental RA. These effects were associated with reduced ROS/NF-κB/COX-2-related inflammatory changes, suggesting FA-Cel-LPs may represent a promising liposomal strategy for RA.
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高影响因子
MOLECULES
·
2023
·Vol. 28
·期 8
·3395
·
IF 4.6
Yi Ou,Zonglin You,Min Yao,Yingfan Cao,Xiu Xue,Min Chen,Rihui Wu,Lishe Gan,Dongli Li,Panpan Wu,Xuetao Xu,Wingleung Wong,Vincent Kam Wai Wong,Wenfeng Liu,Jiming Ye,Jingwei Jin
Naproxen is widely used for anti-inflammatory treatment but it can lead to serious side effects. To improve the anti-inflammatory activity and safety, a novel naproxen derivative containing cinnamic acid (NDC) was synthesized and used in combination with resveratrol. The results showed that the combination of NDC and resveratrol at different ratios have a synergistic anti-inflammatory efficacy in RAW264.7 macrophage cells. It was indicated that the combination of NDC and resveratrol at a ratio of 2:1 significantly inhibited the expression of carbon monoxide (NO), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), induced nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and reactive oxygen species (ROS) without detectable side effects on cell viability. Further studies revealed that these anti-inflammatory effects were mediated by the activation of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt) signaling pathways, respectively. Taken together, these results highlighted the synergistic NDC and resveratrol anti-inflammatory activity that could be further explored as a strategy for the treatment of inflammatory disease with an improved safety profile.Keywords:naproxen derivative;resveratrol;synergistic;anti-inflammatory;mechanism
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高影响因子
Foods
·
2023
·Vol. 12
·期 11
·2120
·
IF 5.2
Jie Li,Bingyong Mao,Xin Tang,Qiuxiang Zhang,Jianxin Zhao,Hao Zhang,Shumao Cui
Naringenin and apigenin are common flavonoids derived from edible plants with the potential to alleviate inflammation and improve skin antioxidation. This study aimed to evaluate the effects of naringenin and apigenin on oleic acid-induced skin damage in mice and compare their underlying mechanisms of action. Triglycerides and non-esterified fatty acids were significantly decreased by naringenin and apigenin, while apigenin intervention resulted in a better recovery of skin lesions. Naringenin and apigenin improved the antioxidative abilities of the skin by increasing catalase and total antioxidant capacity levels and decreasing malondialdehyde and lipid peroxide levels. The release of skin proinflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor α, was inhibited after naringenin and apigenin pretreatments, but naringenin only promoted the excretion of IL-10. Additionally, naringenin and apigenin regulated antioxidant defense and inflammatory response by activating nuclear factor erythroid-2 related factor 2-dependent mechanisms and suppressing the expression of nuclear factor-kappa B. In summary, naringenin and apigenin are prospective ingredients that contribute to the amelioration of skin damage by activating anti-inflammatory and antioxidative responses.Keywords:naringenin;apigenin;antioxidative system;inflammation;signaling pathway
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高影响因子
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