MOLECULAR NEUROBIOLOGY
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2026
·Vol. 63
·期 1
·374
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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
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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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Biomedicines
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2026
·Vol. 14
·期 7
·1586
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IF 4.5
Xiaofei Tong,Meina Sun,Xin Gan,Xin Chen,Shiyang Liu,Ieong Sun,Lin Zhang,Weihong Zheng
Background: Capsular contracture is driven by self-amplifying foreign body response (FBR) where inflammatory and fibrotic signals from fibroblasts and macrophages reinforce each other. We hypothesized that cogradient simultaneous blockade of NF-κB as an inflammatory node and TGF-β/Smad as fibrotic node could attenuate the FBR. Emodin has dual inhibitory activity but suffers from poor delivery.Methods: Emodin liposomes (Emo-Lip) were characterized and tested on TGF-β1-stimulated NIH/3T3 fibroblasts and LPS-stimulated RAW264.7 macrophages. In a rat silicone implant model, periprosthetic injections were given for four weeks. Fibrous capsule formation was evaluated by histology, immunofluorescence, and FAPI-PET/CT. Transcriptomic analyses were performed to verify and predict relevant pathways.Results: Emo-Lip had uniform size and high encapsulation efficiency. In vitro, Emo-Lip inhibited fibroblast migration, ROS production, myofibroblast differentiation (α-SMA+) as well asCtgfexpression, while suppressing M1 polarization and reduced IL-12/IL-6 secretion in macrophages. In vivo, Emo-Lip reduced capsule thickness, collagen area, and α-SMA/Col I expression, comparable to dexamethasone. Transcriptomics showed coordinated downregulation of inflammatory/fibrotic genes, and Western blot confirmed suppressed phosphorylation of Smad3.Conclusions: Coordinated two-node blockade of NF-κB and TGF-β/Smad by liposomal emodin reprograms the FBR and effectively prevents capsular contracture in rats, offering a translational strategy for implant-associated fibrosis.
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Brain and Behavior
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2026
·Vol. 16
·期 10
·e71773
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IF 2.8
Xin-ying Cai,Wen-jun Li,Cai-xia Chen,Lu Peng,Li-chao Yang,Xiao-ning Lin,Hong-tao Liu,Jian-bo Jia,Yan-chao Jiao,Ying Li
Background Glycyrrhizic acid (Gly-A) exhibits anti-inflammatory and antioxidant effects in various central nervous system disorders. Acute fatigue and chronic fatigue (CF) are associated with serious physical and psychological effects. However, the underlying pathophysiology and effective therapeutic strategies for these conditions remain poorly understood. Purpose This study aims to evaluate the therapeutic potential of Gly-A against fatigue, and to elucidate the underlying mechanisms of its action. Methods We established a mouse model of acute exercise-induced fatigue and evaluated fatigue-related indices. To identify specific pathways involved in Gly-A's therapeutic effects, we employed RNA sequencing, network pharmacology, and in vitro oxygen-deficit models, aiming to clarify the mechanisms. Additionally, we established a mouse model of CF to compare the therapeutic efficacy of Gly-A with positive control drugs by assessing identical parameters. Results Gly-A significantly improved fatigue-related indices without affecting body weight. RNA sequencing and network pharmacology analyses showed that Gly-A modulates oxidative stress responses and targets the NF-κB (nuclear factor-kappa B)/NLRP3 (NOD-like receptor thermal protein domain associated protein 3) signaling and apoptotic pathways. In the CF mouse model, oral administration of Gly-A significantly increased motor activity, alleviated anxiety and depression, and improved neurocognitive function compared to model mice, exhibiting superior efficacy to positive control drugs. These findings suggest that Gly-A exerts anti-inflammatory effects by targeting the NF-κB/NLRP3 signaling pathway, thereby reducing neuronal apoptosis in CF. Conclusions Gly-A exhibits therapeutic potential against acute exercise-fatigue and CF, primarily by attenuating apoptosis through the inhibition of the NF-κB/NLRP3 signaling pathway.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2026
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IF 6.6
Yangwei Xiang,Qin Wang,Ke Zhou,Weili Han
Phthalate esters (PAEs), widely used as plastic additives in consumer products such as food packaging, can be metabolized to phthalic acid (PTA) in vivo . However, the potential contribution of PTA to respiratory fibrotic processes remains poorly understood. In this study, we investigated the effects and underlying mechanisms of PTA on pulmonary fibrogenesis using human lung fibroblast IMR-90 cells chronically exposed to environmentally relevant concentrations of PTA (0–60 μg/L) for 14 days. PTA exposure promoted pro-fibrotic responses and cellular senescence, as evidenced by increased expression of fibrosis-associated markers, enhanced senescence-associated β-galactosidase activity, and upregulation of CDKN2A . Proteomic profiling and functional perturbation experiments further implicated the IL-1α/NF-κB/SASP signaling axis in these responses. PTA-induced senescence and pro-fibrotic effects were attenuated by inhibition of NF-κB signaling and IL-1 signaling, supporting the functional involvement of this pathway. In a bleomycin-induced progressive pulmonary fibrosis model, subsequent PTA exposure further aggravated collagen deposition and increased the pulmonary expression of fibrosis-, senescence-, and Il-1a/Nf-κb -associated genes, providing in vivo support for the biological relevance of the pathway identified in vitro . Molecular docking additionally predicted a potential interaction between PTA and IL-1α. Therefore, these findings offer novel mechanistic insights into environmental pollutant-induced fibrogenesis. Download: Download high-res image (131KB) Download: Download full-size image
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
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2026
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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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Scientific Reports
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2026
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IF 4.9
Li Ruifang,Sun Yan,Feng Mingzhi,Kelsang Drolma,Cai Hanhui,Zhang Jun
Ulcerative colitis (UC) is a chronic disease characterized by intestinal inflammation, mucosal damage, and immune dysregulation. Current treatments are often inadequate, driving the search for alternatives with fewer side effects. Isoliquiritigenin (ISL), a flavonoid from licorice, has demonstrated anti-inflammatory effects, but its efficacy in UC remains uncertain. Male C57BL/6 mice were divided into six groups: Control, DSS model, low-, medium-, and high-dose ISL (25, 50, 100 mg/kg), and 5-aminosalicylic acid (5-ASA, 100 mg/kg). UC was induced by administering 3% DSS, followed by ISL or 5-ASA treatment. Disease activity index (DAI), histopathology, real-time PCR, Western blotting, immunohistochemistry, and 16 S rRNA sequencing were used to assess inflammation, intestinal barrier integrity, and gut microbiota (GM) composition. a Caco-2 cell-based model of UC was developed. After transfection to induce the overexpression of TLR4 and its adaptor protein MyD88, the cells were incubated with ISL. The effects of this intervention were evaluated by measuring the expression of inflammatory cytokines, tight junction-associated proteins, and components of the TLR4/MyD88 signaling pathway. ISL significantly alleviated DSS-induced UC symptoms, such as weight loss and colonic shortening. ISL reduced colonic mucosal damage and inflammatory cell infiltration, downregulated TLR4, MyD88, and phosphorylated NF-κB expression, and lowered TNF-α, IL-1β, and IL-6 levels. It also improved intestinal barrier function by upregulating ZO-1, Claudin-1, and Occludin expression. ISL modulated GM by increasing beneficial bacteria (Muribaculaceae) and reducing pathogenic bacteria (Escherichia-Shigella). Overexpression of TLR4 and MyD88 in the Caco-2 cell line abrogated the protective effects of ISL, as evidenced by increased expression of inflammatory cytokines and downregulated expression of tight junction proteins. Overall, these findings suggest ISL may protects against DSS-induced UC by suppressing the TLR4/MyD88/NF-κB pathway, enhancing intestinal barrier function, and modulating GM, supporting its potential as a therapeutic supplement for UC.
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ACS Applied Materials & Interfaces
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2026
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IF 8.2
Mingjing Wang,Kang Liu,Peng She,Tianci Gao,Zhansen Shi,Yunlai Wang,Xiaoya Ding,Ye Yang,Dengke Yin,Wei Shen,Hanmeng Liu
Rheumatoid arthritis (RA) tissues exhibit high levels of reactive oxygen species (ROS) and free Ca2+, which contribute to a vicious cycle of sustained inflammatory responses. This study developed an in situ Ca2+-reinforced injectable full-active HPAP hydrogel. The full-active hydrogel is formed by cross-linking phenylboronic acid-functionalized hyaluronic acid (HA-PBA) with sodium alginate (ALG) and paeoniflorin (PF) through boronate ester bonds, all of which play significant roles in RA treatment. HPAP hydrogel exhibits relatively low strength in vitro, allowing for easy injection into the joint cavity. Then, ALG can trigger secondary cross-linking in the RA joint cavity using Ca2+, forming the HPAP/Ca2+ hydrogel in situ and enhancing drug retention (with significant signals detectable in vivo even 17 days postinjection). Furthermore, a decrease in the free Ca2+ concentration can inhibit the activation of the NLRP3 inflammasome pathway. HA-PBA participates in the formation of ROS-responsive boronate ester bonds in hydrogel, thereby reducing ROS levels in RA tissues. Additionally, the released PF inhibits the activation of the NF-κB pathway, mitigating the inflammatory response. In vitro and in vivo experiments demonstrate that the HPAP hydrogel can effectively scavenge ROS, inhibit the NF-κB and NLRP3 pathways, reprogram macrophages, and reduce osteoclast differentiation and cartilage matrix degradation. In the RA animal models, HPAP hydrogel significantly improved arthritis scores, bone erosion, and inflammation levels, showing better treatment efficacy compared to commercial dexamethasone. Given the simplicity of the components of this full-active hydrogel, all of which are natural and safe compounds, it exhibits promising clinical translation potential in RA treatment.
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2026
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IF 2.5
Zhen Yang,Huiying Li,Wei Zhao,Yingxia Yu,Yanling Lin,Jianxuan Liu,Xinghu Fan,Moyan Wang,Xin Teng,Zhikai Qiu
Objective Evaluation of the therapeutic effect of Tongfu Zhike Formula (TFZKF) on mice with cough variant asthma (CVA) and exploration of its mechanism of action in improving CVA. Methods The main chemical components of TFZKF were detected and analyzed using UHPLC-MS/MS. Network pharmacology was employed to investigate the potential targets of TFZKF in CVA. After grouping and drug administration, the number of coughs and cough latency were observed in CVA mice. White blood cell differential counts in BALF, serum levels of IgE, IL-4, IL-5, IL-13 and IFN-γ, as well as pathological changes in lung tissue were assessed. Western blot and RT-qPCR were used to analyze the protein expression levels and mRNA changes of TLR4, MyD88, and NF-κB in the lung tissue of CVA mice. Results A total of 495 chemical components were detected in TFZKF under both positive and negative ion modes. Network pharmacology analysis identified 199 potential targets related to TFZKF and CVA, and found close associations with the TLR4 and NF-κB signaling pathways. Animal experiments showed that, compared to the Model group, TFZKF significantly reduced the number of coughs, prolonged cough latency, decreased serum levels of IgE, IL-4, IL-5, and IL-13, reduced the total number of white blood cells, neutrophils, and eosinophils in BALF, alleviated inflammatory cell infiltration and fibrosis in lung tissue, and downregulated the protein and mRNA expression of TLR4, MyD88, and NF-κB. Conclusion The interaction within the TLR4/MyD88/NF-κB signaling pathway may be a potential key target for the treatment of cough variant asthma.
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YONSEI MEDICAL JOURNAL
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2021
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IF 2.759
Chunting Hu,Chen Li,Qiaoya Ma,Ruili Wang,Ya He,Hui Wang,Guogang Luo
Purpose Ischemic brain injury results in high mortality and serious neurologic morbidity. Here, we explored the role of SNHG15 in modulating neuronal damage and microglial inflammation after ischemia stroke. Materials and Methods The hypoxia/ischemia models were induced by middle cerebral artery occlusion in mice and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Quantitative real-time PCR (qRT-PCR) and Western blot were conducted to determine the levels of SNHG15, miR-302a-3p, and STAT1/NF-κB. Moreover, gain- or loss-of functional assays of SNHG15 and miR-302a-3p were conducted. MTT assay was used to evaluate the viability of HT22 cells, and the apoptotic level was determined by flow cytometry. Furthermore, enzyme-linked immunosorbent assay was performed to detect oxidative stress and inflammatory mediators in the ischemia cortex and OGD/R-treated BV2 microglia. Results The SNHG15 and STAT1/NF-κB pathways were both distinctly up-regulated, while miR-302a-3p was notably down-regulated in the ischemia cortex. Additionally, overexpressing SNHG15 dramatically enhanced OGD/R-mediated neuronal apoptosis as well as the expression of oxidative stress and inflammation factors from microglia. In contrast, knocking down SNHG15 or overexpressing miR-302a-3p relieved OGD/R-mediated neuronal apoptosis and microglial activation. Moreover, the rescue experiment testified that overexpressing miR-302a-3p also attenuated SNHG15 up-regulation-induced effects. In terms of the mechanisms, SNHG15 sponged miR-302a-3p and activated STAT1/NF-κB as a competitive endogenous RNA, while miR-302a-3p targeted STAT1 and negatively regulated the STAT1/NF-κB pathway. Conclusion SNHG15 was up-regulated in the hypoxia/ischemia mouse or cell model. The inhibition of SNHG15 ameliorates ischemia/hypoxia-induced neuronal damage and microglial inflammation by regulating the miR-302a-3p/STAT1/NF-κB pathway.
研究领域:
神经科学
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分子生物学
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病理学
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EXPERIMENTAL AND MOLECULAR PATHOLOGY
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2020
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IF 2.28
Chunyan Tian,Fengli Gao,Xing Li,Zhuying Li
Asthma is a chronic inflammatory airway disease. Icariside II has been reported to exert anti-inflammatory effect in multiple human diseases . The present study aimed to investigate the effects and mechanisms of Icariside II on airway inflammation and remodeling in asthma. We established an asthma mouse model with ovalbumin (OVA) immunization. Histological analysis using H&E, PAS and Masson staining showed that administration of Icariside II attenuated OVA-induced airway inflammation and remodeling. Icariside II reduced the numbers of total white blood cells and eosinophils in bronchoalveolar lavage fluid (BALF). The levels of interleukin (IL)-4, IL-5, IL-13 and transforming growth factor (TGF)-β1 in peripheral blood and the expression of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), eotaxin-1, CC-chemokine receptor-3 (CCR-3), Toll-like receptor (TLR)-2 and TLR-4 were significantly down-regulated in lung tissues of OVA-induced mouse model. These results suggested that Icariside II inhibited eosinophil activation and thus decreased eosinophils-induced airway inflammation and remodeling in asthma. Moreover, Icariside II suppressed TGF-β1-induced cell proliferation , migration, and CTGF expression in airway smooth muscle cells (ASMCs). In both OVA-induced mouse model of asthma and TGF-β1-induced ASMCs, Icariside II decreased IκBα degradation, nuclear translocation of NF-κB p65 and STAT3 phophorylation, indicating an inactivation of NF-κB and STAT3 in the presence of Icariside II. Therefore, we demonstrate that Icariside II attenuates eosinophils-induced airway inflammation and remodeling in asthmatic mice and inhibits TGF-β1-induced cell proliferation and migration in ASMCs via suppressing NF-κB and STAT3 signalings.
研究领域:
免疫学
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药理学
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呼吸医学
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BIOSCIENCE REPORTS
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2021
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IF 3.84
Yao Qiuwen,Jing Guiying,Zhang Xiaowen,Li Meiling,Yao Qihuan,Wang Longhui
Background: Endometriosis is a painful disorder characterized by the growth of endometrial tissue outside the uterine cavity. Here, we investigated the effects of the cinnamic acid isolated from the Chinese medicinal plant Cinnamomum cassia Presl on primary endometrial stromal cells. Methods: Immunohistochemistry was used to examine protein expression and cell purity. Quantitative RT-PCR was conducted to assess mRNA expression, and Western blot was performed to determine protein level. Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Glycolysis and mitochondrial function were evaluated by measuring the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR) of cells, respectively. Lastly, plasmid transfection and inhibitor treatment were used for overexpression and inhibition studies. Results: Cinnamic acid inhibited cell viability and cell invasion, as well as decreased ECAR and OCR, in primary endometrial stromal cells. Cinnamic acid suppressed the effects of PKM2 overexpression, and inhibition of PKM2 using Compound 3k mimicked the effects of cinnamic acid. Treatment with Compound 3k and cinnamic acid did not lead to additive effects, but rather displayed effects similar to those of Compound 3k alone, suggesting that cinnamic acid elicits its effects on primary endometrial stromal cells by targeting PKM2. Conclusions: Our study identified cinnamic acid as a novel compound from Cinnamomum cassia Presl that displays potent effects on primary endometrial stromal cell viability, invasion, and glycolysis, suggesting its potential use for endometriosis treatment.
研究领域:
妇科学
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药理学
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细胞生物学
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分子生物学
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