INTERNATIONAL IMMUNOPHARMACOLOGY
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2017
·
IF 2.956
Ye Tian,Zheng Li,Bingyu Shen,Qiaoling Zhang,Haihua Feng
Morin , a bioactive flavonoid extracted from the bark of Moraceae plants and many medicinal herbs, has anti-inflammatory and antioxidative effects. In this research, we explored the protective effects of morin against lipopolysaccharide (LPS) and d -galactosamine (D-GalN) induced acute liver injury in mice. Mice were given an intraperitoneal injection of morin before LPS and D-GalN treatment and the HepG2 cells were only given morin to investigate its effects. The results showed that morin markedly inhibited the production of serum alanine transaminase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and hepatic TNF-α, IL-6, and myeloperoxidase (MPO) induced by LPS/D-GalN. In order to evaluate morin effect in the future, we investigated the expression of nuclear factor E2 related factor 2 (Nrf2), nuclear factor-kappaB (NF-κB), toll like receptor 4 (TLR4) on liver injury. Taken together, these results suggested that morin could exert the anti-inflammatory and anti-oxidative effects against LPS/D-GalN-induced acute liver injury by activating Nrf2 signal pathways and inhibiting NF-κB activation.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2017
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IF 3.154
Jiarui Nie,Yaning Chang,Yujia Li,Yingjun Zhou,Jiawen Qin,Zhen Sun,Haibin Li
Caffeic acid phenethyl ester (CAPE), extracted from propolis, was evaluated for the ameliorative effects on insulin resistance and the mechanisms were identified, using non-insulin-dependent diabetes mellitus (NIDDM) model mice and insulin resistance (IR) model cells. After 5 weeks of CAPE supplementation, insulin sensitivity, hyperlipidemia, and peroxisome proliferator-activated receptor-α (PPAR-α) levels were improved in mice. Proinflammatory cytokines in serum and the expressions of tumor necrosis factor-alpha (TNF-α) mRNA in tissues were markedly downregulated from CAPE-treated mice. In vitro, CAPE supplement significantly improved glucose consumption, glucose uptake, glycogen content, and oxidative stress and decreased expression of glucose-6-phosphatase (G6Pase) mRNA in cells. Both in vivo and in vitro, CAPE enhanced p-Akt (Ser473) and p-insulin receptor substrate (IRS)-1 (Tyr612), but inhibited p-JNK (Thr183/Tyr185), p-NF-κB p65 (Ser536), and nuclear translocation of p-NF-κB p65 (Ser536). In summary, CAPE can ameliorate insulin resistance through modulation of JNK and NF-κB signaling pathway in mice and HepG2 cells.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Yanan Zhao,Bin Li,Jiang Liu,Lei Chen,Hui Teng
The potential of natural phytochemicals in addressing ethanol-related public safety concerns has been garnering attention. Galangin, a potent flavonoid renowned for its antioxidative and anti-inflammatory characteristics, is derived from the galanga plant, and propolis is derived from bees. Here, we documented the effects of galangin on ethanol-stimulated intestinal tight junction damage and investigated its potential protective mechanism in both in vivo and in vitro models, which has not been extensively investigated. Our results revealed that galangin efficaciously mitigated ethanol-induced intestine injury and dysfunction of the intestinal barrier. Concurrently, galangin significantly counteracted the ethanol-induced upregulation of NLRP3 inflammasome-associated proteins and activated the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in both the mouse colon and Caco-2 cells. Interestingly, similar to galangin, inhibitors of MAPKs and the NF-κB p65 reduced ethanol-induced NLRP3 inflammasome activation and intestinal tight junction damage. To sum up, our results showed that galangin blocks the ethanol-induced perturbation of the intestinal barrier and activation of the NLRP3 inflammasome via the NF-κB/MAPK signaling pathways.
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EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Yufang Ma,Zhenming Ma,Yiyuan Zhang,Chunyun Luo,Puxin Huang,Jing Tong,Hong Ding,Honghui Liu
Apigenin and baicalein are structurally related flavonoids that have been reported to have multiple pharmacological activities. The aim of this study was to investigate the protective effects and potential mechanisms of apigenin and baicalein in D-galactose-induced aging rats. First, apigenin and baicalein showed remarkable antioxidant activity and anti-glycation activity in vitro. Secondly, the protective effects of apigenin and baicalein on aging rats were investigated. We found that apigenin and baicalein supplementation significantly ameliorated aging-related changes such as declines in the spatial learning and memory and histopathological damage of the hippocampus and thoracic aorta. In addition, our data showed that apigenin and baicalein alleviated oxidative stress as illustrated by decreasing MDA level, increasing SOD activity and GSH level. Further data showed that they significantly reduced the accumulation of advanced glycation end products (AGEs), inhibited the expression of RAGE, down-regulated phosphorylated nuclear factor (p–NF–κB (p65)). Our results suggested that the protective effects of apigenin and baicalein on aging rats were at least partially related to the inhibition of AGEs/RAGE/NF-κB pathway and the improvement of oxidative damage. Overall, apigenin and baicalein showed almost equal anti-aging efficacy. Our results provided an experimental basis for the application of apigenin and baicalein to delay the aging process.
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Journal of Advanced Research
·
2025
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IF 13
Lin-Tao Xu,Qing-Tong Han,Zhen-Peng Xu,Xiao-Ning Wang,Hua Zhang,Tao Shen
Introduction Chronic obstructive pulmonary disease (COPD) represents a significant global health challenge, characterized by substantial morbidity and mortality rates. In traditional Chinese medicine (TCM), Farfarae Flos (FF) has been widely utilized as a therapeutic agent for COPD. However, its specific bioactive compounds and the underlying mechanisms are unclear. Objectives This study aims to identify bioactive constituent of FF against COPD and illustrate its therapeutic target and mechanism. Methods and Results In this research, a high-throughput screening on constituents of FF was conducted, leading to the identification of a potent anti-COPD lead, tussilagone (TUS). Utilizing biotin-labeling approach, Kelch-like ECH-associated protein 1 (KEAP1), the ubiquitin E3 ligase of nuclear factor erythroid 2-related factor 2 (Nrf2), was identified to be the direct target of TUS. Mechanistically, TUS activated KEAP1-Nrf2 axis by covalent modification of cysteine 434 (Cys434), a novel high-reactivity cysteine of KEAP1. TUS-mediated Nrf2 activation further suppressed the activation of nuclear factor kappa-B (NF-κB) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, consequently attenuating lung inflammation in COPD. Conclusion TUS was identified as the bioactive constituent of FF against COPD, which directly targeted Cys434 of KEAP1. KEAP1 was proven to be a pharmacological target for the treatment of COPD, and Cys434 was identified to be the first highly reactive cysteine in Kelch domain of KEAP1. TUS inhibits lung inflammation by regulating Nrf2 and NF-κB/NLRP3, which is the mechanism of FF against COPD
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Heliyon
·
2024
·Vol. 10
·期 2
·e24339
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IF 3.4
Suqin Yang,Gang Liu,Xiankun Xia,Dali Gan,Shijian Xiang,Meixian Xiang
α-Mangostin is a natural xanthone derivative isolated from Camellia atrophy (CA), commonly known as Lichuan black tea (LBT). The present study investigated the ameliorating effect and mechanism of α-mangostin on alcoholic gastric ulcers (GU) in rats. In vivo , α-mangostin relieved pathological symptoms. Moreover, α-mangostin regulated the activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) and nuclear factor κB (NF-κB)/NLR family pyrin domain containing 3 (NLRP3)/caspase-1 pathways. Reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were significantly decreased and IL-10 were increased, the microtubule-associated protein light chain 3 (LC3)-II/LC3-I ratio was increased, p62 protein expression was decreased, and inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expression was down-regulated. The relevant mechanisms were validated using GSE-1 and RAW264.7 cells in an in vitro model. Furthermore, α-mangostin increased Ligilactobacillus and Muribaculum abundance as well as propionic acid and butyric acid contents. Therefore, α-mangostin possesses antioxidant and anti-inflammatory properties, and remodels intestinal flora dysbiosis through mechanisms that may involve regulation of the Nrf2/HO-1 pathway and NF-κB/NLRP3/caspase-1 pathway. It also increases propionic acid and butyric acid contents. This study provides novel evidence regarding the use of α-mangostin for treating GU.
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
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IF 4.2
Congna Zi,Xian Ma,Maodong Zheng,Ying Zhu
Myocardial injury triggers intense inflammatory reactions and oxidative stress responses. S100 calcium-binding protein A16 (S100A16), a multi-functional calcium (Ca 2+ )-binding protein, participates in inflammatory responses and contributes to ischemia/reperfusion (I/R) injury. Nevertheless, the precise mechanism by which S100A16 operates in myocardial I/R injury remains uncertain. Cardiac I/R injury was produced by ligation/release of the left anterior descending artery, and mouse cardiac cells were subjected to hypoxia/reoxygenation (H/R) to determine the biological effects in vitro . We demonstrated that S100A16 was upregulated in the ischemic hearts and cardiac cells after I/R and H/R injury. Adenovirus-mediated S100A16 inhibition led to a considerable improvement in cardiac function with a reduced infarct size, accompanied by a reduction in cardiomyocyte apoptosis. Similar effects of S100A16 inhibition on inflammation and reactive oxygen species (ROS) production were observed in cultured cardiomyocytes. Importantly, we showed that I/R and H/R treatment upregulated the expression of voltage-dependent anion channel 1 (VDAC1), which subsequently activated NF-κB/p65 to facilitate the binding of NF-κB/p65 to the S100A16 promoter, thereby activating the transcription and expression of S100A16. Mechanically, S100A16 responded to increasing Ca 2+ and interacted with calmodulin (CaM) to regulate the activation of calcium/calmodulin-dependent protein kinase 2 (CAMKK2)/AMPK pathway. In conclusion, VDAC1 sustained the NF-κB p65 pathway activation to elicit increased S100A16 expression, contributing to myocardial damage and heart failure post-I/R via the CaM/CaMKK2/AMPK pathway. This study revealed a crucial role of the VDAC1-S100A16 axis in the process of myocardial I/R injury, providing novel molecular targets for the treatment of cardiac conditions associated with I/R injury.
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Polymers
·
2025
·Vol. 17
·期 14
·1900
·
IF 4.9
Guoying Zhou,Yujia Yan,Linh Nguyen,Jiangkai Fan,Xiao Zhang,Li Gan,Tingzi Yan,Haitong Wan
Traumatic brain injury (TBI) leads to severe neurological dysfunction, disability, and even death. Surgical intervention and neurorehabilitation represent the current clinical management methods, yet there remains no effective treatment for recovery after TBI. Post-traumatic hyperinflammation and vascular injury are the key therapeutic challenges. Therefore, a novel-designed multifunctional HT/SAA/HSYA hydrogel based on hyaluronic acid (HA) co-loaded with salvianolic acid A (SAA) and hydroxysafflor yellow A (HSYA) was developed in order to simultaneously target inflammation and vascular injury, addressing key pathological processes in TBI. The HT hydrogel was formed through covalent cross-linking of tyramine-modified HA catalyzed by horseradish peroxidase (HRP). Results demonstrated that the HT hydrogel possesses a porous structure, sustained release capabilities of loaded drugs, suitable biodegradability, and excellent biocompatibility both in vitro and in vivo. WB, immunofluorescence staining, and PCR results revealed that SAA and HSYA significantly reduced the expression level of pro-inflammatory cytokines (IL-1β and TNF-α) and inhibited M1 macrophage polarization through the suppression of the TLR4/NF-κB inflammatory pathway. In vivo experiments confirmed that the HT/SAA/HSYA hydrogel exhibited remarkable pro-angiogenic effects, as evidenced by increased expression of CD31 and α-SMA. Finally, H&E staining showed that the HT/SAA/HSYA hydrogel effectively reduced the lesion volume in a mouse TBI model, and demonstrated more pronounced effects in promoting brain repair at the injury site, compared to the control and single-drug-loaded hydrogel groups. In conclusion, the HT hydrogel co-loaded with SAA and HSYA demonstrates excellent anti-inflammatory and pro-angiogenic effects, offering a promising therapeutic approach for brain repair following TBI.
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JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Ruyue Wang,Chunping Yu,Xin Wang,Minfei Yang,Yang Gao,Hailong Zhang
Ethnopharmacological relevance Lonicera caerulea var. edulis is an Oroqen medicine with fever relief, detoxification, and anti-inflammatory activities. However, pharmacological and chemical research on its leaves is limited. Aim of the study Focusing on L. caerulea var. edulis leaves, the research involved identification of active constituents, examination of anti-inflammatory effects in mice, and analysis of mechanisms. Materials and methods Based on activity-guided fractionation, the phytochemicals were separated via various chromatographic and spectroscopic techniques. The anti-inflammatory effects were evaluated in mice with LPS-stimulated acute lung injury. Antioxidant capacity was determined through DPPH • and OH • scavenging, ferric-reducing and lipid peroxidation assay. The active compounds were screened in LPS-treated RAW 264.7 macrophage cells. Then, the anti-inflammatory mechanisms were investigated via RT-qPCR, western blot analysis, and molecular docking experiments. Results The EtOAc fraction (EF) displayed the strongest anti-inflammatory activity, with a pronounced inhibitory effect on cellular NO production, markedly decreasing the levels of inflammatory factors, effectively improving acute lung injury, and alleviating pulmonary edema in mice. Meanwhile, EF was also the strongest antioxidant layer which could effectively scavenge free radicals. Phytochemical investigation of EF resulted in the isolation of one new diterpenoid and 19 known constituents, of which ten compounds are lignans. Among them, a lignan ( 8 ) significantly reduced NO production, inhibited the IL-1β, IL-6, iNOS, and COX-2 gene expression, and decreased the phosphorylation levels of p65 and IκBα in RAW 264.7 macrophages. Additionally, 8 could tightly interact with the p65 and IκBα proteins of NF-κB. Conclusion The leaves of L . caerulea var. edulis have significant anti-inflammatory properties, and lignans are the main active components, whose anti-inflammatory mechanisms are mainly through inhibiting the NF-κB signaling pathway.
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NEUROCHEMICAL RESEARCH
·
2024
·Vol. 50
·期 1
·1-12
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IF 3.7
Chen Hao,Zhao Haosen
Spinal cord injury (SCI) represents a severe trauma to the central nervous system, resulting in significant disability and imposing heavy burdens on families and society. Pathophysiological changes following SCI often trigger secondary injuries that complicate treatment. Bone marrow mesenchymal stem cells (BM-MSCs) have become a focal point of research due to their multifunctionality and self-renewal capabilities; however, their survival and neuroprotective functions are compromised in inflammatory environments. Resveratrol, known for its anti-inflammatory, anti-aging, and anti-oxidative stress properties, has been extensively studied. This research focuses on the anti-inflammatory effects of resveratrol post-SCI and its combined application with BM-MSCs to treat rat spinal cord injuries, exploring both efficacy and mechanisms. In vivo experiments investigated changes in the Sirt-1 signaling pathway post-SCI, while in vitro studies examined the effects of resveratrol on BM-MSCs under inflammatory conditions. The assessment included recovery of motor function, neuronal survival, and apoptosis in SCI rats treated with resveratrol alone or in combination with BM-MSCs. Findings reveal a correlation between Sirt-1 and inflammation signaling pathways post-injury. Resveratrol significantly enhanced the survival and efficacy of BM-MSCs in inflammatory environments by upregulating Sirt-1 and downregulating NF-κB and other inflammatory markers, thereby reducing apoptosis. Combined treatment with resveratrol and BM-MSCs showed superior outcomes in motor function recovery and neuronal survival compared to treatment with BM-MSCs alone. This study offers a novel therapeutic strategy for SCI, enhancing stem cell survival and function through modulation of the Sirt-1/NF-κB pathway, providing a theoretical and experimental foundation for clinical applications.
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PHYTOMEDICINE
·
2025
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IF 8.3
Anna Gan,Haimiao Chen,Fei Lin,Ruixuan Wang,Bo Wu,Tingxu Yan,Ying Jia
Background Acute lung injury (ALI) is a serious respiratory ailment marked by dysregulation of the immune dysregulation and an inflammatory reaction.Currently, effective treatment options for ALI are limited. Sanzi Yangqin Decoction (SZYQ) is a traditional formula used clinically to treat respiratory diseases, although its effects on ALI have not yet been fully elucidated. Purpose This research seeks to elucidate the pharmacodynamic material basis of SZYQ within the context of lipopolysaccharide (LPS)-induced ALI, thereby establishing a robust foundation for considering SZYQ as a possible intervention for improving ALI. Methods The chemical constituents of SZYQ were identified by UHPLC-QTOF-MS. The pharmacological mechanism of SZYQ on ALI was preliminarily investigated through network pharmacology. An ALI model induced by LPS was employed to evaluate the efficacy of SZYQ via histopathological analysis and other methodologies. Transcriptomic analysis of lung tissue from ALI mice was conducted to uncover the potential mechanisms underlying SZYQ's effects. Additionally, LPS was used to induce murine alveolar macrophages (MH-S), creating an in vitro ALI model; siRNA was introduced to further validate the pharmacological mechanisms of SZYQ's protective effects on ALI. Results This study identified a total of 37 chemical components within SZYQ, and network pharmacology results indicated that these components exert their effects via the Toll-like receptor pathway. The protective effects of SZYQ on ALI are manifested by the modulation of the immune response and the reduction of lung epithelial barrier damage. Transcriptomics, western blot, flow cytometry, and siRNA experiments demonstrated that SZYQ can inhibit levels of TLR2, p-NF-κB/NF-κB, p-IκB/IκB, p-IKKα/IKKα, MyD88, NLRP3, Caspase-1 and ASC. Furthermore, SZYQ was observed to reduce the release of reactive oxygen species (ROS), suppresses inflammasome activation, as well as decrease the incidence of cell pyroptosis. Conclusions This article demonstrated for the first time that SZYQ can enhance ALI through immune regulation. The proposed mechanism of action involved the TLR2-mediated NF-κB/NLRP3 signaling pathway and the inhibition of NLRP3 inflammasome activation.
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Aging-US
·
2021
·
IF 5.682
Qin Wu,Yuhua Wang,Qingfang Li
Brain injury is a familiar complication of severe sepsis, in which excessive inflammation and oxidative stress are the main mechanisms leading to acute brain injury. Here, we focus on probing the function and mechanism of Matairesinol (Mat) in sepsis-mediated brain injury. We established a rat sepsis model by cecal ligation and perforation (CLP) and constructed an in vitro sepsis model by treating neurons and microglia with lipopolysaccharide (LPS). Rats and cells were treated with varying concentrations of Mat, and the changes of neural function, neuronal apoptosis, microglial activation, neuroinflammation and the expression of oxidative stress factors in brain tissues were examined. Additionally, the activation of the MAPK, NF-κB and AMPK pathways in brain tissues and cells was evaluated by Western blot (WB) and/or immunohistochemistry (IHC). Our findings illustrated that Mat improved neuronal apoptosis and weakened microglial activation in CLP rats. Meanwhile, Mat hampered the expression of pro-inflammatory factors (TNF-α, IL-1β, IL-6, IFN-γ, IL-8, and MCP1) and facilitated the contents of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in brain tissues and microglia. Mechanistically, Mat concentration-dependently dampened the phosphorylation of MAPK, JNK and NF-κB in CLP rats and LPS-stimulated microglia and up-regulated Nrf2 and HO-1. Besides, Mat facilitated the AMPK expression. Meanwhile, Compound C, a specific inhibitor of the AMPK pathway, substantially reduced the neuronal protection and anti-inflammatory effects mediated by Mat. Overall, Mat exerts anti-inflammatory and anti-oxidative stress effects by up-regulating AMPK, thereby ameliorating sepsis-mediated brain injury.
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