NEUROCHEMICAL RESEARCH
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2018
·Vol. 43
·期 5
·1058-1066
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IF 2.772
Nong Xiaolian,Lan Yuyan
Reactive astrocyte-mediated neuroinflammatory responses in the spinal dorsal horn have been reported to play a pivotal role in pathological pain. Chronic constriction injury (CCI) enhances the activation of nuclear factor kappa B (NF-κB), which is involved in neuropathic pain (NP). Picroside II (PII), a major active component of Picrorhiza scrophulariiflora, has been investigated for its anti-oxidative, anti-inflammatory, and anti-apoptotic activities. Here, we explored the analgesic effects of PII on a model of CCI-induced NP and investigated the levels of the GFAP protein and the mRNA and protein levels of pro-inflammatory cytokines in the spinal cord, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). CCI significantly induced mechanical allodynia and thermal hyperalgesia. Intraperitoneal administration of PII remarkably reversed the CCI-induced mechanical allodynia and thermal hyperalgesia and reduced the mRNA and protein levels of IL-1β, IL-6, and TNF-α in the spinal cord. Additionally, according to the in vitro data, the PII treatment inhibited LPS-induced increases in the mRNA and protein levels of IL-1β, IL-6, and TNF-α and suppressed the NF-κB pathway by inhibiting the phosphorylation of NF-κB/p65 and the degradation of inhibitor of NF-κB (IκB) in astrocytes without toxicity to astrocytes. Overall, the analgesic effect of PII correlated with the inhibition of spinal reactive astrocyte-mediated neuroinflammation through the NF-κB pathway in rats with NP.
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Open Life Sciences
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2024
·Vol. 19
·期 1
·
IF 1.7
Jingxin Cui,Liwei Xu,Yimeng Sun,Lingfei Dai,Yuxiu Mo,Keli Yun,Yifei Chen,Linglin Chen
Neuroinflammation, characterized by microglial activation and the subsequent secretion of inflammatory cytokines, plays a pivotal role in neurodegenerative diseases and brain injuries, often leading to neuronal damage and death. Alleviating neuroinflammation has thus emerged as a promising strategy to protect neurons and ameliorate neurodegenerative disorders. While peroxisome proliferator-activated receptor gamma (PPARγ) agonists have demonstrated potential therapeutic actions on neuroinflammation, their prolonged use, such as with rosiglitazone, can lead to cardiac risks and lipid differentiation disorders. In this study, we investigated the effects of a newly synthesized PPARγ agonist, VSP-2, on secretion of inflammatory cytokines in BV2 cells. Treatment with VSP-2 significantly reduced the mRNA and protein levels of proinflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Furthermore, VSP-2 attenuated the phosphorylation of nuclear factor kappa B (NF-κB) (65 kD) and IκBα, as well as the nuclear translocation of NF-κB (65 kD). Additionally, the use of PPARγ small interfering RNA was able to attenuate the effects of VSP-2 on proinflammatory cytokines and the NF-κB pathway. In conclusion, our findings suggest that VSP-2 effectively suppressed the expressions of IL-1β, IL-6, and TNF-α via the PPARγ/NF-κB signaling pathway. Given its potential therapeutic benefits, VSP-2 may emerge as a promising candidate for the treatment of neurodegenerative diseases or brain injuries associated with neuroinflammation.
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Scientific Reports
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2025
·Vol. 15
·期 1
·40525
·
IF 3.9
Ma Chunli,Wang Linghong,Cao Lili,Zhao Linyun,Zhang Xin,Ma Chengyou,Lian Hua,Bao Xiufang,Eerde Mutu,Buren Qiqige,Tong He,Dai Lili,Amu Guleng,Bao Yulong,Hong Mei,Wang Li
Acute liver injury (ALI) is a prevalent hepatic condition that poses significant risks to both life and overall health. Traditional Mongolian medicine utilizes Honghua Qinggan Thirteen-Flavor Pills (HHQG) as a primary formula for dispelling liver heat, illustrating both an extensive application in clinical settings and notable therapeutic effectiveness for treating liver ailments such as hepatitis and liver failure. Nevertheless, the molecular mechanisms underpinning the hepatoprotective properties of HHQG remain inadequately understood.We employed a CCl 4 -induced mouse model of liver injury alongside network pharmacology analysis, molecular docking studies, and cellular assays to dissect the effects and mechanisms of action of HHQG. Our findings demonstrated that HHQG significantly improved CCl 4 -induced liver injury in mice, reducing pathological damage and inflammatory factors. Network pharmacology identified 184 overlapping targets, 6 key genes, and 5 key active components in HHQG. Molecular docking confirmed the binding affinity of these components to RASD1. Gene expression analysis in liver tissue revealed a positive correlation between mRNA expression of RASD1 and NLRP3. Cell experiments demonstrated the role of RASD1 in regulating NLRP3 inflammasome and inflammatory factors. Pretreatment of HHQG attenuated LPS-induced inflammatory response and the activation of PKCδ-NF-κB signaling pathway. In the CCl 4 -induced liver injury model, HHQG significantly reduced NLRP3, RASD1, and PKCδ-NF-κB expression.This study revealed that HHQG effectively mitigates CCl 4 -induced liver injury by inhibiting the activation of NLRP3 inflammasome by regulating the PKCδ-NF-κB signaling pathway via RASD1. These findings provide novel theoretical support for the rational application of HHQG as a potential hepatoprotective agent.
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PHYTOTHERAPY RESEARCH
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2025
·
IF 6.3
Xian Zheng,Yuanyue Jiang,Wenbo Wang,Kekang Sun,Libin Zhou,Yanru Zhang,Jie Cui,Haiyan Yu,Wenbin Dong,Baofei Yan
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, characterized by recurrent flare-ups and limited effectiveness of available drug therapies. Asiatic acid (AA), a triterpenoid compound extracted from Centella asiatica , has shown promising pharmacological activities and therapeutic potential in several inflammation-related diseases. However, AA's efficacy in treating UC and its precise mechanisms of action remain to be fully explored. This study aimed to provide a comprehensive assessment of AA's therapeutic effects on UC and to investigate its underlying mechanisms, with a focus on gut microbiota interactions. In our study, a dextran sulfate sodium-induced UC mouse model was used to evaluate AA's therapeutic potential and explore its impact on gut microbiota composition and function. We further used an antibiotic cocktail and fecal microbiota transplantation assays to substantiate the role of gut microbiota in AA's mechanisms of action. A metabolomic analysis was also conducted to identify key metabolic pathways and gut microbiota-derived metabolites involved in AA's effects. Our findings demonstrated that AA significantly alleviates symptoms of UC, including reducing weight loss, slowing disease progression, mitigating colonic inflammation, and restoring immune balance. Mechanistically, the beneficial effects of AA were strongly linked to alterations in the gut microbiota and its metabolites, particularly γ-glutamyltyrosine. This metabolite was found to regulate the cyclic adenosine monophosphate/protein kinase A/nuclear factor kappa-B signaling pathway, which plays a crucial role in inflammatory responses. Overall, these findings strongly suggest that AA holds promise as a therapeutic agent for UC by modulating the gut microbiota and influencing critical inflammatory pathways.
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Journal of Physical Chemistry C
·
2025
·
IF 3.2
Yubing Zheng,Bo Zhao,Furong Chen,Jun Chen,Xiaoxuan Ma,Zhiqiang Sun,Yidan Liu,Lei Huang,Hongbin Zhang,Shixun Cao,Rongrong Jia
In the pursuit of sustainable energy solutions amid rising global energy demands, hydrogen production through water electrolysis has become increasingly significant. However, the oxygen evolution reaction (OER), which occurs at the anodes, frequently acts as a kinetic limitation in the overall process. This study presents a novel CeFeO3−δ/NF catalyst with oxygen vacancies, which shows exceptional OER performance with an overpotential of just 310 mV at 10 mA·cm–2. Based on density functional theory (DFT) calculations, the electronic structure of the catalyst and its influence on the OER performance are analyzed. It is revealed that the substantial enhancement in CeFeO3−δ’s catalytic efficiency can be attributed to oxygen vacancies. These vacancies optimize the electronic structure and enhance the effective adsorption of intermediates, suggesting a promising approach for the development of next-generation OER catalysts.
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MOLECULAR NEUROBIOLOGY
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2025
·
IF 4.3
Wan Yu-hui,Cheng Zeng-jing,Fan Ling-xiang,Yang De-hong,Chen Bing-lin,Chen Xiang-xin,Zhu Qing
Subarachnoid hemorrhage (SAH) is associated with high mortality and morbidity rates. In its early stages, a substantial influx of blood into the subarachnoid space triggers excessive activation of microglia, which markedly contributes to early brain injury (EBI), a pivotal determinant of poor prognosis. Tremella fuciformis polysaccharides (TFPSs), as acidic heteropolysaccharides from the fruiting bodies of Tremella, exhibit robust anti-inflammatory characteristics and many biological properties. Nonetheless, the impact of TFPSs on EBI after SAH has yet to be reported, and the molecular mechanisms underlying these effects remain elusive. We used in vivo and in vitro models to study the effects of TFPSs on microglia post-SAH. Network pharmacology analysis was used to predict the targets of TFPSs and the pathways through which it exerts its therapeutic effects. These predictions were subsequently corroborated through flow cytometry, Western blotting, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), and quantitative real‑time polymerase chain reaction, both in vivo and in vitro. After 24 h post-SAH, TFPS-treated mice presented improved neurological function and reduced cerebral edema. TFPSs reversed microglial activation, enhanced phagocytic ability, and reduced neuronal apoptosis. Network pharmacology identified KDR as a potential target of TFPSs, with the P38 MAPK pathway as the downstream pathway. TFPSs attenuated KDR expression, inhibited the P38 MAPK/NF-κB pathway, reduced inflammatory cytokine expression, and increased microglial phagocytic capacity post-SAH. This investigation revealed that TFPSs may ameliorate EBI after SAH, potentially via the regulation of the KDR-mediated P38 MAPK/NF-κB pathway and phagocytic function.
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Catalysts
·
2024
·Vol. 14
·期 11
·752
·
IF 3.8
Mengjie Lu,Run Cheng,Li Wang,Dandan Liang,Meng Qin,Bili Wang,Rui Song,Duo Chen
The elaborate design of inexpensive, high-performance electrocatalysts from earth-abundant elements toward oxygen evolution reaction (OER) is critical in various (electro)chemical processes. Herein, a novel binder-free catalyst of Ce-coupled Ni3S2/NiS supported on Ni foam (Ce-Ni3S2/NiS@NF) is successfully synthesized via a facile one-step hydrothermal method that enables practical feasibility with a significant enhancement of OER activity through anchoring Ce dopants on an Ni3S2/NiS nanobud host. Ce species coupling can modulate electronic structure, which reduces the reaction energy barrier and optimizes OER catalytic activity. More profoundly, the superhydrophilic and superaerophobic properties of the Ce-Ni3S2/NiS@NF electrode further promote mass transfer. As a result, the Ce-Ni3S2/NiS@NF electrode exhibits excellent OER activity with a low overpotential of 236 and 350 mV to achieve current densities of 10 and 100 mA cm−2, respectively, and long-term durability for 24 h in alkaline medium. These results could supply valuable guidelines for the design of other OER catalysts and beyond.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
·
IF 8.5
Kexin Liu,Yanling He,Shasha Li,Han Tao,Liang Wei,Jianqin Huang,Chenyu Jiang,Mohamed A. Farag,Lili Song,Fei Gao
Neuroinflammation, a critical innate immune response in the central nervous system (CNS), is closely associated with dysregulated inflammatory pathways. Targeting key mediators such as inducible nitric oxide synthase (iNOS) and the NF-κB/MAPK signaling axis offers a promising strategy for mitigating inflammatory cascades. In this study, three novel peptides derived from Carya cathayensis (DFR, GAR, NAK) were computationally screened via molecular docking and dynamics simulations for their iNOS inhibitory potential. DFR demonstrated superior binding affinity and stability, validated through in vitro assays where it significantly suppressed LPS-induced nitric oxide (NO) and pro-inflammatory cytokine (IL-1β, TNF-α, IL-6) production in BV2 microglia. To enhance therapeutic efficacy, DFR was engineered into a nanostructured delivery system (pADFR) through conjugation with a targeting ligand and PEGylation. In vivo evaluations revealed that pADFR alleviated LPS-induced behavioral deficits and reduced inflammatory mediators in mice, with mechanistic studies highlighting its suppression of NF-κB/MAPK pathway activation. This study underscores the potential of peptide-based nanostructures for targeted modulation of neuroinflammatory pathways, offering a platform for precision therapeutic development.
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Cell Communication and Signaling
·
2025
·Vol. 23
·期 1
·1-17
·
IF 8.9
Xu Teng,Wang Yaning,Zhao Zechen,Wang Jinsong,Zhao Zhenyuan,Yang Yuemei,Song Xiaomeng,Lai Qingguo
Background Tumor dissemination is a life-threatening event which confers to most cancer-related deaths with limited effective therapeutic option. TNFα-induced protein 2 (TNFAIP2) reveals pro-metastasis potential in several cancers. However, its definite role and underlying mechanism in oral squamous cell carcinoma (OSCC) is largely unknown. Methods The impact of TNFAIP2 on tumor metastasis was assessed based on the conditional knockout mouse with 4-nitroquinoline-1-oxide (4NQO) induced OSCC model through feature and immunohistochemistry analysis. To explore the specific mechanism, enrichment analysis and co-immunoprecipitation were applied. Meanwhile, the nano-hydroxyapatite (nHAp) and poly-L-lysine (PLL) based RNA interference delivery system was designed to restrict tumor dissemination. Results The conditional knockout Tnfaip2 in epithelium reduced tumor initiation rate, differentiation degree and cervical lymph node metastasis (LNM) in mouse exposed to 4NQO. Enrichment analysis suggested nuclear factor-kappa B (NF-κB) signaling was associated with these effects. Western blot proved that TNFAIP2 prevented the ubiquitin proteasome degradation of inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKKβ), a classical transcriptional activator protein in NF-κB signaling. Mechanistically, TNFAIP2 was demonstrated to competitively interact with kelch-like ECH-associated protein 1 (KEAP1) to avoid IKKβ from ubiquitination at K63 and proteasomal degradation subsequently, which finally sustained NF-κB signaling and facilitated tumor metastasis by enhancing epithelial-mesenchymal transition (EMT) and lymphangiogenesis. Notably, the synthetic small interfering RNA delivery systems nHAp@PLL-siTnfaip2 showed significant effect in attenuating tumor progression of OSCC mouse. Conclusion Above results showed TNFAIP2 promoted EMT and lymphangiogenesis of OSCC by regulating NF-κB signaling, a mechanism that was dependent on the interaction with KEAP1 competitively. The nHAp based TNFAIP2 interference might serve as a novel therapeutic in limiting OSCC metastasis.
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EXPERIMENTAL AND MOLECULAR MEDICINE
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2025
·
IF 12.9
Yang Qihao,Wu Jianqun,Huang Songqiang,Zeng Jing,Jing Yihan,Wang Zhiyong,Zhang Chi,Wu Zenghui,Liu Song,Wang Zhao
Here we investigate the effects and mechanisms of eicosapentaenoic acid (EPA) in regulating chondrocyte mechanics during inflammation in the progression of osteoarthritis (OA). Primary porcine chondrocytes and human OA chondrocytes were isolated and cultured. Cell mechanical properties were measured using atomic force microscopy. RNA sequencing, immunocytochemistry, quantitative PCR and western blotting were used to elucidate associated signaling mechanisms. Porcine cartilage and human OA cartilage explants were collected. Human articular cartilage samples were obtained from ten donors. Anterior cruciate ligament transection surgery was performed to induce OA in male C57BL/6J mice. The therapeutic effects of EPA and activation of associated signaling were evaluated using histology, immunohistochemistry and micro-computed tomography. EPA reduced F-actin intensity and Young’s modulus in IL-1α-treated porcine chondrocytes and in human OA chondrocytes. Mechanistically, EPA inhibited IL-1α-induced increase in CD44 expression in porcine chondrocytes by suppressing phosphorylation of NF-κB subunits p65. In addition, EPA alleviated articular cartilage degeneration and decreased the expression of p-p65 and CD44 in IL-1α-treated porcine and human OA cartilage explants. Moreover, EPA suppressed the increase in Young’s modulus induced by CD44 ligands (A6 peptide and low-molecular-weight hyaluronic acid) in porcine chondrocytes. Finally, intraarticular injection of EPA emulsion-integrated hyaluronic acid injection attenuated OA-associated alterations in articular cartilage and subchondral bone and decreased CD44 expression in mice. Our data not only provide new insights into EPA’s chondroprotective actions and underlying mechanisms but also offer new evidence supporting the therapeutic efficacy of a novel EPA emulsion-integrated hyaluronic acid injection for OA treatment.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Guo-Dong Zhuang,Si-Min Deng,Meng-Di Chen,Chao-Fan Deng,Wen-Ting Gu,Shu-Mei Wang,Dan Tang
Ethnopharmacological relevance Cognitive dysfunction associated with diabetes, known as diabetic encephalopathy (DE), is a grave neurodegenerative condition triggered by diabetes, and persistent inflammation plays a vital role in its development. The renowned traditional Chinese medicine Huang-Lian-Jie-Du Decoction (HLJDD) is clinically proven to manage diabetes mellitus and Alzheimer's disease and is famous for its heat-clearing and detoxifying effects. However, the underlying mechanisms through which HLJDD affects DE remain to be elucidated. Aim of the study To explore the beneficial effects of HLJDD on improving cognitive dysfunction in DE mice. Study design and methods A diabetic mouse was established through a high-fat diet and subsequent administration of streptozotocin over five consecutive days. After the animals were confirmed to have diabetes, they were treated with HLJDD. After oral administration of HLJDD or metformin for 14 weeks, behavioral tests were used to assess their cognitive capacity. Biochemical analyses were then performed to detect levels of glucose metabolism, followed by histological analyses to assess pathological damage. Furthermore, AGEs/RAGE/NF-κB axis related proteins were detected by Western blot or immunofluorescence techniques. An advanced UPLC-Q-Orbitrap HRMS/MS analytical technique utilizing a chemical derivatization strategy was employed for comprehensive metabolic profiling of carbonyl compounds in the plasma of DE mice. Results Pharmacological assessment revealed that HLJDD effectively mitigated cognitive dysfunction, normalized glucose metabolic imbalances, and repaired neuronal damage in DE mice. It reduced neuroinflammation by attenuating carbonyl stress, deactivating astrocytes and microglia, and preserving dopaminergic neurons. Additionally, metabolomics analysis revealed 18 carbonyl compounds with marked disparities between DE and control mice, with 12 metabolites approaching normal levels post-HLJDD intervention. Further investigations showed that HLJDD regulated inflammation and pyroptosis through suppressing AGEs/RAGE/NF-κB pathways. Conclusion Our study indicated that HLJDD could ameliorate carbonyl stress via the regulation of carbonyl compound metabolism profiling, and inhibiting the AGEs/RAGE/NF-κB pathway, thereby alleviating inflammation and pyroptosis to exert beneficial effects on DE.
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JOURNAL OF MOLECULAR MEDICINE-JMM
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2024
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IF 4.8
Wang Pengtao,Tao Wei,Li Qiujie,Ma Wanting,Jia Wei,Kang Yuting
Indole-3-aldehyde (I3A) is an intestinal microbial metabolite that regulates inflammation in various inflammatory diseases; however, its role in chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to investigate the anti-inflammatory effects and molecular mechanisms of I3A in COPD. We constructed in vivo models using cigarette smoke (CS)-stimulated mice and in vitro models using cigarette smoke extract (CSE)-stimulated MH-S cells. The results demonstrated that I3A significantly alleviated bronchial obstruction in mice with COPD and reduced the expression of inflammatory factors such as TNF-α, IL-1β, and IL-6. Additionally, I3A decreased the levels of matrix metalloproteinases MMP2, MMP12, and inhibited the NF-κB p65/NLRP3 pathways. Further investigation revealed that I3A inhibited NF-κB activity by suppressing p65 phosphorylation and nuclear translocation in CSE-stimulated MH-S cells. The activation of the NF-κB and NLRP3 signaling pathways is mediated by histone deacetylase 5 (HDAC5) and HDAC6, both of which are inhibited by I3A. Subsequent experiments indicated that aryl hydrocarbon receptor (AHR) knockdown attenuated the inhibitory effect of I3A on pro-inflammatory cytokines and the HDACs/NF-κB/NLRP3 signaling pathways, highlighting the dependence of I3A's anti-inflammatory effects on the AHR receptor. Key messages
I3A effectively reduced lung inflammation in COPD mice by inhibiting the NF-κB pathway.
In CSE-stimulated MH-S cells, I3A suppressed p65 phosphorylation and nuclear translocation, thereby inhibiting NF-κB activity.
The activation of the NF-κB/NLRP3 pathways by HDAC5 and HDAC6 was diminished by I3A.
Through the activation of the AHR receptor, I3A suppressed the activities of HDAC5/6, leading to a decrease in inflammatory factor levels.
Graphical abstract
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