Frontiers in Pharmacology
·
2023
·
IF 5.6
Sujuan Wang,Wenqing Li,Wenxiu Liu,Lei Yu,Fu Peng,Junyuan Qin,Lin Pu,Yunli Tang,Xiaofang Xie,Cheng Peng
Background: Penthorum chinense Pursh (PCP) is widely utilized in China to treat a variety of liver diseases. It has been shown that flavonoids inhibit inflammation and have the potential to attenuate tissue damage and fibrosis. However, the mechanisms underlying how total flavonoids isolated from PCP (TFPCP) exert their anti-fibrotic effects remain unclear. Methods: The chemical composition of TFPCP was determined using UHPLC–Q-Orbitrap HRMS. Subsequently, rats were randomly assigned to a control group (Control), a carbon tetrachloride (CCl 4 )-induced hepatic fibrosis model group (Model), a positive control group [0.2 mg/(kg∙day)] of Colchicine), and three TFPCP treatment groups [50, 100, and 150 mg/(kg∙day)]. All substances were administered by gavage and treatments lasted for 9 weeks. Simultaneously, rats were intraperitoneally injected with 10%–20% CCl 4 for 9 weeks to induce liver fibrosis. At the end of the experiment, the liver ultrasound, liver histomorphological, biochemical indicators, and inflammatory cytokine levels were tested respectively. The underlying mechanisms were assessed using Western blot, immunohistochemistry, immunofluorescence, RT-qPCR, and metabolomics. Results: Fourteen flavonoids were identified in TFPCP. Compared with control animals, CCl 4 -treated rats demonstrated obvious liver injury and fibrosis, manifested as increases in gray values, distal diameter of portal vein (DDPV) and a decrease in blood flow velocity (VPV) in the ultrasound analysis; increased biochemical index values (serum levels of ALT, AST, TBIL, and ALP); marked increases in the contents of fibrotic markers (PC III, COL4, LN, HA) and inflammatory factors (serum TNF-α, IL-6, and IL-1β); and significant pathological changes. However, compared with the Model group, the ultrasound parameters were significantly improved and the serum levels of inflammatory cytokines were reduced in the TFPCP group. In contrast, the expression of TGF-β 1 , TLR4, and MyD88, as well as the p-P65/P65 and p-IκBα/IκBα ratios, were considerably reduced following TFPCP treatment. In addition, we identified 32 metabolites exhibiting differential abundance in the Model group. Interestingly, TFPCP treatment resulted in the restoration of the levels of 20 of these metabolites. Conclusion: Our findings indicated that TFPCP can ameliorate hepatic fibrosis by improving liver function and morphology via the inactivation of the TLR4/MyD88-mediated NF-κB pathway and the regulation of liver metabolism.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2017
·
IF 4.519
Peihong Qiu,Shanshan Zhang,Yangyang Zhou,Min Zhu,Yanting Kang,Dahui Chen,Jiabing Wang,Peng Zhou,Wulan Li,Qing Xu,Rong Jin,Jianzhang Wu,Guang Liang
NF-κB is a critical target for cancer treatment due to its central role in facilitating cancer progression and desensitizing cancer cells to chemotherapeutic drugs . In this study, a series of chemically modified asymmetric curcuminoid analogs named S01–S15 were synthesized and evaluated for NF-κB inhibitory activity in gastric cancer cell lines. Cell growth inhibition assays revealed that most of these analogs effectively inhibited the growth of BGC-823, SGC-7901, and MFC cells. S06 was selected for further research. MTT assay , clonogenic assay, Hoechst 33258 staining assay, and western blotting revealed that S06 could exert anti-gastric cancer effects by downregulating NF-κB activity. Moreover, via its effects on NF-κB, S06 effectively enhanced the sensitivity of the gastric cancer cells to irinotecan . Together, this study provide a series of new curcuminoid analogs as promising cancer therapeutic agents.
✓ 已验证
DOI
PubMed
高影响因子
Journal of Natural Medicines
·
2020
·Vol. 75
·期 1
·37-47
·
IF 2.055
Han Jieru,Shi Guangyu,Li Wenhao,Xie Ying,Li Fuzhen,Jiang Deyou
Monosodium urate (MSU)-mediated inflammation is closely related to gouty arthritis (GA). Dioscin, an active ingredient, has been reported to possess anti-inflammatory property. Nevertheless, the role of dioscin in GA and the underlying mechanism have not been fully understood. In the present study, we investigated the anti-inflammatory effect of dioscin on MSU-induced GA through in vivo and in vitro experiments. Histopathological analysis showed that dioscin alleviated the severity of GA concomitant with the lowered uric acid and creatinine levels. Moreover, the increasing IL-1β, IL-6, and TNF-α levels induced by MSU were decreased via administration of dioscin in mice and human synoviocytes. Western blotting results suggested that dioscin inhibited the activation of NLRP3 through down-regulating the protein expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved-caspase-1, as well as IL-1β. In addition, TLR4, myeloid differentiation primary response gene 88 (MyD88), p-IKKβ, p-p65, and NF-κB p65 in nuclei levels were significantly reduced by dioscin. Importantly, dioscin remarkably lowered the NF-κB p65-DNA activity in MSU-treated mice utilizing electrophoretic mobility shift assay (EMSA) analysis. Taken together, dioscin had a protective effect against MSU-initiated inflammatory response via repressing the production of inflammatory cytokines and the activation of inflammasome NLRP3 and TLR4/NF-κB signaling pathway. The above findings revealed that dioscin could be a potential drug for the treatment of GA.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2019
·
IF 8.063
Lili Wei,Chenyuan Wang,Xianjue Chen,Bing Yang,Kun Shi,Leah R. Benington,Lee Yong Lim,Sanjun Shi,Jingxin Mo
Gestational trophoblastic neoplasia (GTN), the most aggressive form of which is choriocarcinoma, can result from over-proliferation of trophoblasts. Treating choriocarcinoma requires high doses of systemic chemotherapeutic agents, which result in nonspecific drug distribution and severe toxicity. To overcome these disadvantages and enhance chemotherapeutic efficacy, we synthesized redox- and pH-sensitive, self-assembling, ascorbic acid-derived (PEG-ss-aAPP) micelles to deliver the drug methotrexate (MTX). Methods : We developed and tested self-assembling PEG-ss-aAPP micelles, which release their drug cargo in response to an intracellular reducing environment and the acidity of the early lysosome or tumoral microenvironment. Uptake into JEG3 choriocarcinoma cancer cells was examined using confocal microscopy and transmission electron microscopy. We examined the ability of MTX-loaded PEG-ss-aAPP micelles to inhibit metastasis in an orthotopic mouse model of human choriocarcinoma. Results : Drug-loaded micelles had encapsulation efficiency above 95%. Particles were spherical based on transmission electron microscopy, with diameters of approximately 229.0 nm based on dynamic light scattering. The drug carrier responded sensitively to redox and pH changes, releasing its cargo in specific environments. PEG-ss-aAPP/MTX micelles efficiently escaped from lysosome/endosomes, and they were effective at producing reactive oxygen species, strongly inducing apoptosis and inhibiting invasion and migration. These effects correlated with the ability of PEG-ss-aAPP/MTX micelles to protect IκBα from degradation, which in turn inhibited translocation of NF-κB p65 to the nucleus. In an orthotopic mouse model of human choriocarcinoma, PEG-ss-aAPP/MTX micelles strongly inhibited primary tumor growth and significantly suppressed metastasis without obvious side effects. Conclusions : Our results highlight the potential of PEG-ss-aAPP micelles for targeted delivery of chemotherapeutic agents against choriocarcinoma.
✓ 已验证
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2022
·
IF 4.46
Zeyu Li,Kanglin Wu,Yi Zou,Wei Gong,Peng Wang,Hong Wang
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases worldwide. Oxidative stress has been considered a key factor in the pathogenesis of NAFLD. Phosphatidylinositol (3,4,5)-trisphosphate-dependent Rac exchanger 1 (PREX1), a guanine nucleotide exchange factor for Rac, has been associated with inflammation and oxidative stress. This study aimed to investigate the biological function of PREX1 in the progression of NAFLD. Male C57BL/6 mice were fed a high-fat diet for 12 weeks to induce NAFLD in vivo. Adeno-associated virus type 8-mediated liver-specific PREX1 depletion was employed to investigate the role of PREX1 in the progression of high-fat diet-induced NAFLD. Murine hepatocyte cell line AML-12 was stimulated with palmitic acid for 24 h to induce steatosis in vitro. PREX1 depletion was carried out by transfection with PREX1 small interfering RNA . Results showed that PREX1 depletion exerted protective effects against lipid accumulation, oxidative stress and inflammation and inhibited activation of the nuclear factor-κB (NF-κB) signaling pathway in vivo and in vitro. Subsequently, NF-κB inhibitor BAY11–7082 was applied to investigate the role of the NF-κB signaling pathway in the protective effect of PREX1 inhibition against NAFLD. We confirmed that PREX1 inhibition mitigated palmitic acid-induced hepatocellular inflammation mainly via the NF-κB signaling pathway and lipid accumulation and oxidative stress at least partly via the NF-κB signaling pathway. This study highlights the biological function of PREX1 in the pathogenesis of NAFLD.
✓ 已验证
DOI
PubMed
高影响因子
PLoS One
·
2013
·Vol. 8
·期 8
·e71071
·
IF 3.73
Bo-xin Zhao,Ya-bin Sun,Sheng-qi Wang,Lian Duan,Qi-lu Huo,Fei Ren,Guo-feng Li
The expression and function of P-glycoprotein (P-gp) is associated with the phenotype of multi-drug resistance (MDR), leading chemotherapy failure of patients suffered with cancer. Grape seed procyanidin(GSP) is a natural polyphenol supplement with anti-inflammatory effect. Present study assessed a new use of GSP on the MDR reversal activity and its possible molecular mechanisms in MDR1-overpressing paclitaxel resistant ovarian cancer cells. Our results showed GSP significantly enhanced the cytotoxicity of paclitaxel and adriamycin in paclitaxel resistant A2780/T cells but its parental A2780 cells. Furthermore, GSP strongly inhibited P-gp expression by blocking MDR1 gene transcription, as well as, increased the intracellular accumulation of the P-gp substrate rhodamine-123 in A2780/T cells. Nuclear factor-κB(NF-κB) activity, IκB degradation level and NF-κB/p65 nuclear translocation induced by lipopolysaccharide (LPS) and receptor activator for nuclear factor-κB ligand (RANKL) were markedly inhibited by pre-treatment with GSP. Meanwhile, GSP inhibited MAPK/ERK pathway by decreasing the phosphorylation of ERK1/2, resulting in reduced the Y-box binding protein 1 (YB-1) activation with blocking its nuclear translocation. Moreover, the up-regulation of P-gp expression, the activation of AKT/NF-κB and MAPK/ERK pathway induced by LPS was attenuated by GSP administration. Compared with PDTC and U1026, inhibitor of NF-κB and MAPK/ERK respectively, GSP showed the same tendency of down-regulating NF-κB and MAPK/ERK mediated YB-1 activities. Thus, GSP reverses P-gp associated MDR by inhibiting the function and expression of P-gp through down-regulation of NF-κB activity and MAPK/ERK pathway mediated YB-1 nuclear translocation, offering insight into the mechanism of reversing MDR by natural polyphenol supplement compounds. GSP could be a new potential MDR reversal agent used for combination therapy with chemotherapeutics in clinic.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
·
2025
·
IF 1.8
Jiaojiao Ren,Jun Ying,Haijian Liu,Shanshan Hu,Jiangdong Li,Danfei Zhou
Background: This study was designed to explore the action mechanism of stimulator of interferon genes (STING) on the differentiation of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment of lung cancer.Methods: Bioinformatics analysis yielded a potential pathway for STING to regulate MDSC differentiation, the interferon regulatory factor 3 (IRF3)/NF-κB axis. The transfection efficiency of STING overexpression plasmid and small interfering RNA against IRF3 (siIRF3) was examined by quantitative real-time polymerase chain reaction (qRT-PCR). After transfection, A9 cells were co-cultured with extracted bone marrow cells (BMCs). MDSC differentiation, protein expression of the IRF3/NF-κB pathway, and changes in nuclear translocation of NF-κB were analyzed by flow cytometry, Western blot, and immunofluorescence staining experiments. A transplanted tumor mouse model was used for in vivo experiments. After cyclic diadenyl monophosphate (CDA; STING agonist) treatment, changes in MDSC differentiation and protein expression of the IRF3/NF-κB axis in transplanted tumors were verified by immunohistochemical staining, qRT-PCR, and Western blot.Results: Coculture of A9 cells and BMCs promoted MDSC differentiation, inhibited activation of IRF3/NF-κB signal in A9 cells, and boosted nuclear translocation of NF-κB. However, after the upregulation of STING, IRF3/NF-κB signal was activated, while MDSC differentiation and nuclear translocation of NF-κB were inhibited. SiIRF3 reversed the effects of STING overexpression. In vivo, CDA dampened MDSC differentiation and promoted protein expression of the IRF3/NF-κB axis.Conclusion: STING signal in lung cancer cells inhibits MDSC differentiation through activation of the IRF3/NF-κB pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2026
·
IF 2.9
Rencong Wang,Peng Xu,Yindi Zhang,Xiaoli Jin,Ziyan Zhao,Liping Qu,Feifei Wang
Excessive exposure to UVB can induce inflammatory responses and oxidative stress, leading to skin damage. Peony seed oil is rich in unsaturated fatty acids and has been reported to possess anti-inflammatory and antioxidant properties. This study investigated the protective effects and underlying mechanisms of Paeonia delavayi seed oil (PDSO) against UVB-induced damage in human keratinocytes. PDSO at 30–120 μg/mL attenuated UVB-induced inflammation by reducing the mRNA expression of TNF , IL6 , CXCL8 , and PTGS2 and suppressing the secretion of IL-6 and IL-8. PDSO also inhibited UVB-induced activation of NF-κB signaling. Regarding oxidative stress, 120 μg/mL PDSO reduced intracellular ROS production, decreased MDA levels by approximately 29.4%, and increased SOD activity by approximately 122.0% compared with the UVB group. PDSO also increased the mRNA expression of antioxidant-related genes, including NFE2L2, HMOX1, SOD1, CAT, GCLC, and GCLM . In addition, PDSO alleviated the UVB-induced reduction in keratinocyte viability and attenuated photoaging-related changes. Transcriptomic analysis identified PI3K/Akt signaling as a candidate pathway associated with PDSO treatment, and western blotting further showed that PDSO inhibited UVB-induced PI3K/Akt signaling. Pharmacological intervention with the PI3K activator 740Y P partially reversed the anti-inflammatory effects of PDSO, whereas LY294002 exerted anti-inflammatory effects and further enhanced those of PDSO. Moreover, oleic acid and linolenic acid alleviated UVB-induced inflammation and oxidative stress. Collectively, PDSO protects keratinocytes against UVB-induced damage, with PI3K/Akt and NF-κB signaling contributing to its protective effects. Download: Download high-res image (117KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2023
·
IF 5
Lei Li,Guojun He,Mingyu Shi,Juehua Zhu,Yongqing Cheng,Yang Chen,Jin Chen,Qun Xue
Cerebral small vessel disease (CSVD) is one of the most important causes of stroke and vascular dementia , so exploring effective treatment modalities for CSVD is warranted. This study aimed to explore the anti-inflammatory effects of Edaravone dexborneol (C.EDA) in a CSVD model. Mice with CSVD showed distinct cognitive decline, as assessed by the Morris water maze (MWM). Pathological staining verified leakage across the blood‒brain barrier (BBB), microglial proliferation, neuronal loss and demyelination . Western blot analysis demonstrated that M1 microglia dominated prophase and released proinflammatory molecules; the aryl hydrocarbon receptor (AHR) was found to participate in modulating nuclear factor-kappa B (NF-κB) signalling activation through tumour necrosis factor receptor-associated factor-6 (TRAF6). C.EDA treatment resulted in the polarization of microglia from the M1 to the M2 phenotype. Mice sequentially treated with C.EDA exhibited a significant improvement in cognitive function; expression of the anti-inflammatory cytokines and modulatory proteins AHR and TRAF6 was upregulated, while the levels of pNF-κBp65 and pIΚBα were downregulated. C.EDA promoted microglial activation towards the M2 phenotype by upregulating AHR expression, which prevented TRAF6 ubiquitination , promoted NF-κB RelA/p65 protein degradation and inhibited subsequent NF-κB phosphorylation. Mechanistically, the anti-inflammatory effect of C.EDA alleviated neuronal loss and myelin damage, while at the functional level, C.EDA improved cognitive function and thus showed good application prospects.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2025
·Vol. 52
·期 3
·e70025
·
IF 2.5
Suqin Sun,Rong Fan,Li Chang,Lei Gao,Chunting Liu,Dongying Liu,Shiyu Niu
Isoferulic acid (IA), a derivative of cinnamic acid, is derived from Danshen and exhibits anticancer properties by disrupting cancer cell activities. However, its role in pancreatic cancer, the “king of cancer”, was unknown. In this study, pancreatic cancer cells were subjected to treatment with IA (6.25, 12.5, 25 μM), and nude mice injected with pancreatic cancer cells were received IA at doses of 7.5 mg/kg/day or 30 mg/kg/day by oral administration. CCK8, Annexin V-FITC/propidium iodide (PI) double staining and TUNEL assay were conducted to evaluate the cell viability and apoptosis. Hoechst staining and comet assay was employed to measure DNA damage. Mitochondrial membrane potential (MMP) analysis was carried out to explain the mitochondrial damage. EdU and wound healing assay were performed for cell proliferation and migration detection. Immunofluorescence and western blot were used to explore the mechanism. We found that IA reduced cell viability and induced apoptosis, as evidenced by an increase in Annexin V-FITC + PI − and Annexin V-FITC + PI + cell populations, brighter TUNEL and Hoechst staining, and more percentage of tail DNA. Furthermore, IA decreased MMP and changed levels of apoptosis-related proteins. The cell proliferation and migration were inhibited by IA treatment. Mechanically, IA downregulated the phosphorylation of IĸBα and inhibited p65 nuclear translocation, consequently suppressing NF-κB pathway. In general, IA suppressed the cell proliferation and migration, and caused apoptosis of pancreatic cancer cells in a mitochondria-dependent manner through blocking NF-κB signalling pathway, indicating that IA may be a potential therapeutic strategy for pancreatic cancer.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2026
·
IF 7.5
Yannan Xiang,Tianyue Guan,Jun Wang,Shasha Zhang,Yusa Li,Jing Xia,Panpan Zhao,Lei Wang
This study explores the protective effects of Atraric Acid (AA) against chronic kidney disease (CKD) induced by a high-fat diet (HFD) and its underlying mechanisms. In vivo HFD-induced CKD mouse models and in vitro OA/PA-stimulated HK2 cells were treated with AA. AA improved kidney morphology, reduced fibrosis, lipid accumulation, and body weight. It also decreased serum TC, TG, HDL-C, Scr, BUN, and Cys-C levels, indicating improved renal function. AA alleviated oxidative stress, ROS accumulation, and inflammation, as confirmed by DHE staining, oxidative stress markers, and pro-inflammatory cytokine levels. Western blotting showed that AA activated Nrf2 and suppressed NF-κB signaling. AMPK inhibition experiments demonstrated that AA regulated Nrf2 and NF-κB via AMPKα phosphorylation. In conclusion, AA mitigates HFD-induced CKD by targeting AMPKα to regulate oxidative stress and inflammation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 15
·5035
·
IF 4.927
Fengmao An,Xinran Xuan,Zheng Liu,Ming Bian,Qingkun Shen,Zheshan Quan,Guowei Zhang,Chengxi Wei
Alzheimer’s disease (AD) is a major neurodegenerative disease, but so far, it can only be treated symptomatically rather than changing the process of the disease. Recently, triazoles and their derivatives have been shown to have potential for the treatment of AD. In this study, the neuroprotective effects of 4-(4-(heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (W112) against β-amyloid (Aβ)-induced AD pathology and its possible mechanism were explored both in vitro and in vivo. The results showed that W112 exhibits a neuroprotective role against Aβ-induced cytotoxicity in PC12 cells and improves the learning and memory abilities of Aβ-induced AD-like rats. In addition, the assays of the protein expression revealed that W112 reversed tau hyperphosphorylation and reduced the production of proinflammatory cytokines, tumor necrosis factor-α and interleukin-6, both in vitro and in vivo studies. Further study indicated that the regulation of mitogen-activated protein kinase/nuclear factor-κB pathways played a key role in mediating the neuroprotective effects of W112 against AD-like pathology. W112 may become a potential drug for AD intervention.Keywords:triazoles;Alzheimer’s disease;amyloid beta-peptides;neuroinflammation;mitogen-activated protein kinase/NF-kappa B signaling pathways
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）