JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2026
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IF 5.2
Yuting Dong,Xiaodan Wang,Shize Wang,Kang Yang,Tong Xu,Hongjin Lin
DEHP induces thymus injury in chickens by activating the NF-κB/TNF-α pathway, triggering oxidative stress and PANoptosis. • QUE can alleviate the activation of the NF-κB/TNF-α pathway, oxidative stress and PANoptosis induced by DEHP in chickens. • QUE exerts a targeted effect on NF-κB, thereby mitigating DEHP-induced thymus injury in chickens. Quercetin (Que), a natural dietary flavonoid, possesses significant antioxidative and immunoregulatory properties. Di(2-ethylhexyl) phthalate (DEHP), a pervasive environmental endocrine-disrupting chemical, triggers oxidative stress (OS) and elicits immunotoxic effects in various species. However, whether Que can target NF-κB to alleviate DEHP-induced OS and PANoptosis in the chicken thymus remains unclear to date. To investigate the mechanism of thymus damage induced by DEHP and the intervention effect of Que, we established an in vivo chicken model treated with DEHP and/or Que. Based on the results of network pharmacology, molecular docking, molecular dynamics simulations, and Cell Thermal Shift Assay (CETSA), we predicted that NF-κB is the key target for the protective effect of Que. Subsequently, through H&E staining, CCK-8, immunofluorescence, Western blot and other techniques, we verified the effects of DEHP and/or Que on OS, the assembly of PANoptosome, and cellular PANoptosis in chicken thymus tissue and chicken lymphocyte cell line (MSB-1). Meanwhile, to clarify the key role of NF-κB in the above regulatory process, we conducted reverse validation experiments by introducing the NF-κB activator Act1 in cellular experiments. The results demonstrated that DEHP exposure markedly induces the upregulation of NF-κB and TNF-α(P<0.05), leading to a pronounced burst of reactive oxygen species (ROS) and consequent OS within the chicken thymus. This process further activates the ZBP1-mediated PANoptosis pathway, ultimately causing damage to chicken thymus tissue. Que intervention effectively suppresses NF-κB activation, blocking the transmission of the NF-κB/TNF-α/ROS signaling axis, thereby reversing DEHP-induced ZBP1-mediated PANoptosis in chicken thymus. Download: Download high-res image (290KB) Download: Download full-size image
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BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Wenjia Guo,Haifeng Huang,Hong Wang,Xiaodan Tan,Yujun Tu,Chao Gu,Pu Xiang,Lin Chen,Zhe Peng,Yang Yang,Dongzhi Ran,Yin Luo,Junqing Yang
The objective of this study was to explore the effects and underlying mechanisms of miR-690 on hepatic steatosis in db/db mice. Our findings revealed that miR-690 was downregulated in the liver of db/db mice and high-glucose (HG)-treated NCTC1469 cells. In vivo, miR-690 overexpression alleviated hyperglycemia, hyperlipidemia, and hyperinsulinemia, improved liver function, and mitigated steatosis and pathological damage. In vitro , miR-690 enhanced cell viability and glucose uptake while reducing lipid deposition. Mechanistically, bioinformatics analysis identified 15-LOX and NF-KappaB P65 as potential miR-690 targets, with their expression levels inversely correlated with miR-690. Furthermore, treatment with miR-690 agomir downregulated 15-LOX and NF-KappaB P65, although dual-luciferase reporter assays confirmed that 15-LOX is indirectly targeted by miR-690. Additionally, miR-690 agomir increased LC3BII/I and Beclin1 levels while decreased P62 and p-mTOR (Ser2448)/mTOR and induced autophagosome formation. Moreover, overexpression of 15-LOX or NF-KappaB P65 reversed the protective effects of miR-690 on autophagy. Collectively, these results suggest that miR-690 exerts hepatoprotective effects against diabetic hepatic steatosis by activating autophagy via modulating 15-LOX and NF-KappaB P65, providing experimental evidence for its potential use in the treatment of hepatic steatosis in diabetes, and new insight into diabetes drug development for targeting miR-690.
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MOLECULAR NEUROBIOLOGY
·
2026
·Vol. 63
·期 1
·374
·
IF 4.3
Zhao Chen-di,Liu Nan-feng,Samad Abdus,Tian Zhen,Xu Hong-mei,Tian Jiao
Depression is a widespread neuropsychiatric disorder with the current therapeutic approaches achieving only suboptimal efficacy. Neferine is the main bioactive component of Nelumbinis plumula with multiple pharmacological functions. This study sought to investigate the antidepressant activity of neferine and elucidate its underlying mechanisms. Network pharmacology analysis was performed to uncover the molecular targets and pathways involved in neferine’s antidepressant effects. The interaction of neferine with the core target was demonstrated by molecular docking and molecular dynamics simulation. The mouse model of depression triggered by chronic corticosterone (CORT) administration was utilized to validate the impact of neferine on core targets and pathways. We found that neferine remarkably attenuated CORT-induced depressive-like behaviors in mice. A total of 178 overlapping targets were acquired through the intersection of neferine and depression-related genes. The protein–protein interaction (PPI) network analysis revealed nine pivotal hub genes, namely AKT1, TNF, ESR1, PPARG, JUN, HIF1A, CASP3, NFKB1, and MMP9. Functional enrichment analysis indicated that these targets predominantly mapped to the TNF signaling pathway in depression. Molecular docking and molecular dynamics simulation showed that neferine has strong binding stability with PPARγ, a key molecule involved in regulating the TNF pathway. The results of animal experiments found that a PPARγ antagonist abolished neferine-induced alleviation of depressive-like behaviors. Moreover, neferine suppressed TNF/NF-κB pathway activation and attenuated neuronal loss in the hippocampus, potentially through activating PPARγ. Collectively, our study suggested that neferine produced antidepressant effects by suppressing hippocampal inflammation and neuronal loss through inhibiting the TNF/NF-κB signaling pathway. These preclinical evidence laid a foundation for further exploring the role of neferine in treating depression. Graphical
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
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IF 4.7
Xuejian Zhang,Xiaoke Shi,Hong Xu,Yao Wang,Dikai Zhu,Jianan Liu,Tingting Zhang,Hongqian Shentu,Wei Ding,Jun Lu,Feiyan Tao
Antibiotics remain the conventional mainstay for acute local inflammation, such as pharyngitis, but concerns over bacterial resistance, superinfections, and hepatorenal toxicity have driven research toward natural alternatives. Methyl salicylate (SAM) and L-menthol (MENT), derived from medicinal plants, exhibit anti-inflammatory, analgesic, and antimicrobial properties. However, their clinical translation is hampered by inadequate synergy, rapid metabolism, and low bioavailability in existing formulations. To overcome these issues, we synthesized an ROS-responsive prodrug, SSM, by conjugating SAM and MENT via a sulfide bond, and further encapsulated it within hydroxypropyl-β-cyclodextrin (HP-β-CD) to form HP-β-CD@SSM. This complex enabled targeted drug release in high-ROS inflammatory microenvironments, enhancing local bioavailability and reducing systemic exposure. The use of HP-β-CD not only enhanced the water solubility and stability of SSM but also masked the unpleasant odor of the drugs, thereby improving patient compliance. In vitro and in vivo studies demonstrated that HP-β-CD@SSM effectively disrupts the vicious cycle of inflammation and oxidative stress through synergistic inhibition of the NF-κB pathway and activation of the Nrf2 pathway, resulting in significantly enhanced anti-inflammatory and analgesic effects in both pharyngitis and paw edema models, with no observable systemic toxicity. This work presents not only a promising therapeutic candidate for pharyngitis but also a robust localized drug delivery strategy for natural products with considerable translational value.
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INORGANIC CHEMISTRY COMMUNICATIONS
·
2026
·
IF 5.9
Qianmei Chen,Leyang Yu,Houcheng He,Qian Li,Rui Huang,Jianfeng Wen,Ming Li,Li Jiang,Anqi Zhang,Guanghui Hu,Fengming Hou,Shuilin Li
Developing high-performance transition metal-based electrocatalysts remains a critical challenge in water electrolysis for green hydrogen production. Herein, a dual-pronged modification approach is proposed, aimed at fine-tuning the local electronic structure and optimizing the 3D morphology of NiFe-layered double hydroxide (NiFe-LDH). By coupling Mn/Cr co-doping with subsequent sulfurization on NF, a self-supported S-MnCr-NiFe/NF catalyst was successfully fabricated. In 1.0 M KOH, the as-prepared catalyst exhibits remarkable bifunctional electrocatalytic activity, with ultra-low overpotential values of 141 mV for hydrogen evolution reaction (HER) and 151 mV for oxygen evolution reaction (OER) at 10 mA cm −2 . Moreover, the S-MnCr-NiFe/NF catalyst retains excellent stability even after 2500 cyclic tests and 100 h of continuous operation. Furthermore, when S-MnCr-NiFe/NF catalysts are employed as a bifunctional electrode in a two-electrode water-splitting device, the assembled electrolyzer delivers 10 mA cm −2 at 1.42 V. This study demonstrates a scalable and cost-effective paradigm for designing high-efficiency transition metal-based catalysts, offering significant potential for industrial-scale green hydrogen production.
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2026
·
IF 4.6
Qidi Zhai,Zhisheng Guo,Chenbo Ni,Qingsheng Tang,Jie Li
Low-dose BPA enhances proliferation and migration in RCC cells. • BPA shifts redox balance: higher GSH/GSSG, lower ROS, preserved mitochondrial membrane potential. • SLC7A11 is upregulated by BPA. • BPA attenuates responses to erastin, a system xc− inhibitor. Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical, yet its influence on renal cell carcinoma (RCC) remains unclear. We examined whether low-dose BPA alters redox regulation linked to ferroptosis susceptibility in 786-O and ACHN cells. After concentration screening, 100 nM BPA was used for mechanistic experiments. BPA enhanced proliferation and migration, increased the glutathione redox ratio (GSH/GSSG), reduced reactive oxygen species (ROS) signals, and preserved mitochondrial membrane potential. Public cancer dataset analyses prioritized SLC7A11, which was upregulated by BPA at mRNA and protein levels. Under inhibition of the cystine/glutamate antiporter system xc− with erastin, BPA co-treatment partially attenuated cytotoxicity and functional suppression. BPA increased NF-κB p65 phosphorylation, and pyrrolidine dithiocarbamate reduced p-p65 and SLC7A11 expression. These findings suggest that environmentally relevant BPA exposure may promote stress-tolerant phenotypes in RCC cells via an NF-κB–SLC7A11–associated antioxidant response.
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NEW JOURNAL OF CHEMISTRY
·
2025
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IF 2.5
Jiaxuan Wei,Yue Hou,Zhaodi Zhang,Shuangshuang He,Yufei Li,Yuanzhen Zhou,Kangkang Wang,Zhen Wang,Yuan Dang
The combination of photoelectrocatalysis and persulfate-based advanced oxidation processes (AOPs) offers a promising strategy for in-situ ROS generation in environmental remediation. In this study, a light-assisted electrocatalytic system using Co3O4-SnO2/NF as the cathode was developed. Applying a low current suppressed the recombination of photogenerated charges, facilitating continuous hole (h+) generation to activate PMS and produce ROS, enabling efficient degradation of tetracycline (TC). Under optimized conditions, the system exhibited excellent pH tolerance, maintaining a high degradation efficiency (92%-100%) across a wide pH range from 3 to 11, significantly outperforming traditional Fenton-like systems limited to acidic conditions. Furthermore, the light irradiation introduction increased the TOC removal rate of TC by 20% compared to the single electrocatalytic activation system. It enhanced TOC removal rated addressed the importance of the external light radiation during the mineralization of TC. Quenching and EPR analysis confirmed that 1O2, SO4·-, and h+ were the dominant ROS. Their efficient production was attributed to the Co3O4-SnO2 heterojunction, which promoted charge separation and accelerated electron transfer in the Co redox cycle. This research holds significant importance in the field of light-assisted electrocatalytic activation of PMS to enhance the generation of ROS for efficient pollutant degradation.
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TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
·
2023
·Vol. 22
·期 1
·15-22
·
IF 0.6
Jingwen Gong,Yu Xie,Yinfen Tan,Hailong Li,Junqing Zhang
Purpose: To investigate the mechanism of action of galangin (GAL) against indomethacin (Indo)-induced gastric injury.
Methods: Ten micromolar GAL with 2 mM Indo or 0.5 mM L-NAME or 2 mM propargylglycine were co-administered to human gastric mucosal epithelial cells GES-1 for 24 h. Cell viability assay and reactive oxygen species (ROS) test were conducted with commercial kits. Protein expressions of constitutive and inducible nitric oxide synthase (cNOS and iNOS, respectively), and cystathionine-γ-lyase (CSE) in GSE-1 cells were investigated by western blot. After 100 - 300 mg/kg, GAL was daily administered to rats for 5 days, and 30 mg/kg Indo was administered to induce gastric injury. Protein expressions of endothelial NOS (eNOS), iNOS, CSE, nuclear factor (NF)-κB, PKC, Akt, phospho-eNOS (Ser-1177), and phospho-eNOS (Thr-495) were investigated by western blot.
Results: Galangin ameliorated the proliferative inhibitions of Indo, propargylglycine, and L-NAME on GSE-1 cells (p < 0.05), rapidly scavenged ROS, and increased cNOS protein expressions (p < 0.05). Galangin (300 mg/kg) inhibited protein expressions of iNOS (p < 0.01), NF-κB, Akt, and PKC (p < 0.05), inhibited the Ser-1177 and Thr 495 phosphorylation of eNOS, elevated eNOS and CSE protein expressions (p < 0.001).
Conclusion: Galangin protects gastric mucosa from Indo by scavenging ROS and inhibiting protein expressions of Akt and PKC. The inhibition leads to Ser-1177 and Thr 495 dephosphorylation of eNOS, thereby prolonging eNOS activity. Besides, GAL inhibits iNOS-produced NO by inhibiting NF-κB to ameliorate the inflammatory reaction induced by Indo.
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Experimental and Therapeutic Medicine
·
2023
·Vol. 25
·期 5
·1-16
·
IF 2.7
Yijuan Wu,Zhiyu Wang,Shengmian Li,Xianliang Chen,Shengyun Zhou
Excessive proliferation, metastasis and immune escape are considered to be hallmarks of cancer contributing to tumor progression. Split hand and foot malformation 1 (SHFM1) is highly expressed in various cancers and has been reported to increase malignant behaviors. However, the biological functions of SHFM1 in esophageal squamous cell carcinomas (ESCC) progression remain to be elucidated. An integrated bioinformatics analysis was performed to identify candidate genes in ESCC progression based on GSE microarrays. SHFM1 was found to be profoundly upregulated in ESCC tissues compared with normal tissues and SHFM1 expression was positively associated with poor prognosis. The biological effects of SHFM1 on cell growth, metastasis and immune escape were investigated following depletion or overexpression of SHFM1 in vitro. A xenograft mouse model was established to investigate the effect of SHFM1 on ESCC progression in vivo. SHFM1 overexpression promoted ESCC cell proliferation and migration in vitro as well as tumorigenesis in vivo, while SHFM1 knockdown restored those phenotype changes. Additionally, the present study demonstrated that the effects of SHFM1 on malignant behaviors of ESCC cells were achieved by activating the NF‑κB signaling accompanied by increased P65 phosphorylation and nuclear translocation. Furthermore, SHFM1 was also found to regulate the sensitivity of cancer cells to natural killer (NK) cells. Specifically, inhibition of SHFM1 enhanced cell‑mediated cell apoptosis and increased NK toxicity, which might involve the downregulation of c‑Myc and programmed death‑ligand 1, key targets in cancer immunotherapy. In conclusion, these findings suggested that SHFM1 probably promoted ESCC progression by activating the NF‑κB pathway and enhancing the resistance of ESCC cells to NK cell cytotoxicity, indicating that SHFM1 may be a promising target for ESCC treatment.
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Neural Regeneration Research
·
2023
·
IF 6.1
Jingwen Jiang,Hong Pan,Fanxia Shen,Yuyan Tan,Shengdi Chen
Alzheimer’s disease is a progressive neurological disorder characterized by cognitive decline and chronic inflammation within the brain. The ketogenic diet, a widely recognized therapeutic intervention for refractory epilepsy, has recently been proposed as a potential treatment for a variety of neurological diseases, including Alzheimer’s disease. However, the efficacy of ketogenic diet in treating Alzheimer’s disease and the underlying mechanism remains unclear. The current investigation aimed to explore the effect of ketogenic diet on cognitive function and the underlying biological mechanisms in a mouse model of Alzheimer’s disease. Male amyloid precursor protein/presenilin 1 (APP/PS1) mice were randomly assigned to either a ketogenic diet or control diet group, and received their respective diets for a duration of 3 months. The findings show that ketogenic diet administration enhanced cognitive function, attenuated amyloid plaque formation and proinflammatory cytokine levels in APP/PS1 mice, and augmented the nuclear factor-erythroid 2-p45 derived factor 2/heme oxygenase-1 signaling pathway while suppressing the nuclear factor-kappa B pathway. Collectively, these data suggest that ketogenic diet may have a therapeutic potential in treating Alzheimer’s disease by ameliorating the neurotoxicity associated with Aβ-induced inflammation. This study highlights the urgent need for further research into the use of ketogenic diet as a potential therapy for Alzheimer’s disease.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Jiani Sun,Lei Gan,Siji Lv,Tao Wang,Chaoqun Dai,Jing Sun
Endocrine-disrupting chemicals (EDCs) have been reported to affect populations by disrupting the human endocrine system. Di-(2-ethylhexyl) phthalate (DEHP) is an EDC that is present in various consumer products. Exposure to DEHP could contribute to reproductive system dysfunction, with subsequent adverse female reproductive outcomes. Granulosa cells (GCs) play essential roles in ovarian function and fertility. To further reveal the underlying mechanism by which DEHP impairs female fertility and affects the normal function of GCs, in vivo and in vitro experiments were performed. Transcript sequencing was used to identify genes that were differentially expressed in GCs after DEHP treatment. SLC39A5 was shown to be overexpressed in the DEHP group compared to the normal control group. DEHP treatment and overexpression of SLC39A5 activated NF-κB-related factors, followed by an increase in the transcript expression level of NLRP3. NLRP3 inflammasomes play crucial roles in pyroptosis by acting as sensors. Pyroptosis is a type of inflammation-related cell death associated with various diseases, including ovarian cancer and polycystic ovary syndrome. Activation of NF-κB contributed to the upregulation of pyroptosis in GCs, while pyroptosis factors were downregulated after the inhibition of NF-κB with JSH-23. The same phenomenon was also observed in a mouse model in which DEHP-treated mice had higher expression levels of NF-κB and pyroptosis markers in GCs. Moreover, this phenomenon could be partially reversed by the NF-κB inhibitor JSH-23. DEHP treatment also disrupted the normal expression of ovarian function-related genes and inhibited the proliferation of GCs. Reproductive system impairment was observed in mice exposed to DEHP. DEHP-treated mice had a lower body weight, smaller reproductive organs, fewer healthy follicles, and diminished ovarian reserve. Thus, DEHP contributes to ovarian dysfunction by inducing pyroptosis via the SLC39A5/NF-κB/NLRP3 axis in GCs.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yan Lin,Xing-Jun Chen,Jing-Jing Li,Lei He,Ya-Ru Yang,Fei Zhong,Ming-Hui He,Yi-Tong Shen,Bo Tu,Xu Zhang,Zhu Zeng
Ethnopharmacology relevance Sophora flavescens Aiton, was a crucial source of Traditional Chinese Medicine (TCM) that has benefited human health for hundreds of years. Alkaloids and flavonoids were the major bioactive constituents from S. flavescens , which had been widely used for liver disease treatment in China. However, the liver-protective components of flavonoids from S. flavescens and their mechanism of action were not clear. Aim of the study This work aimed to evaluate the in vitro hepatoprotective activities of 35 flavonoids from S. flavescens and screen active compounds. Furthermore, it was conducted to demonstrate the hepatoprotective effects of a new active compound (kurarinol A, 1 ) was isolated by authors and the ethyl acetate (EtOAc) extract form S. flavescens against carbon tetrachloride (CCl 4 )-induced hepatic injury in Kunming (KM) mice, meanwhile revealed the potential mechanism. Materials and methods The 35 flavonoids from S. flavescens were co-incubated with HepG2 cells and treated with 0.35% CCl 4 for 6 h cell viability was measured by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. Then, in vivo animal experiments, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the serum were analyzed, the degree of hepatic injury was examined using hematoxylin-eosin (H&E) staining, the mRNA expression of Superoxide Dismutase 2 (SOD2), Nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), interleukin-1β (IL-1β), and the protein levels of nuclear factor-kappa B p65/p-p65 (NF-κB p65/p-p65), toll-like receptor 2 (TLR2), IL-1β and cyclooxygenase-2 (COX2) in hepatic tissues were detected. Results The lavandulyl flavonoid (kurarinol A, 1 ) and the EtOAc extract from S. flavescens showed protective effects on CCl 4 -injured HepG2 cells, increasing cell viability from 24.5% to 61.3% and 91.8%, respectively. What’s more, we found that treatment with kurarinol A ( 1 ) and the EtOAc extract lead to a significant reduction in hepatotoxicity in response to acute CCl 4 exposure. Compared with the model group, experimental results exhibited kurarinol A (10 mg/kg, i.p.) and the EtOAc extract (300 mg/kg, i.p.) could decrease the levels of AST, ALT, ALP and tissue damage. Further mechanistic investigations revealed that up-regulated the mRNA expression of SOD2, Nrf2, OH-1 and down-regulated the IL-1β in liver tissues, respectively. Additionally, Western blot analyses elucidated that inhibition of IL-1β, TLR2, COX-2, NF-κB (p65/p-p65) via TLR2/NF-κB signaling pathway by kurarinol A and the EtOAc extract contribute to its hepatoprotective activity. Conclusion These findings demonstrated that the novel compound (kurarinol A, 1 ) possessed notable hepatoprotective activity against CCl 4 . It was confirmed that kurarinol A had a certain effect on mice with liver damage induced by CCl 4 , and its mechanism could be include inhibiting inflammation and reducing of oxidative stress reaction by regulating expression of related genes and proteins. Thus, kurarinol A could as a novel active agent that contributes to the hepatoprotective activity of S. flavescens for the treatment of live injury.
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