AMERICAN JOURNAL OF CHINESE MEDICINE
·
2025
·Vol. 53
·期 03
·909-930
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IF 5.5
Ke Li,Ya-Jun Wang,Kun Wei,Wen-Lin Li,Yong-Bo Liu,Jun-Nan Hu,Wen-Guang Chang,Wen-Xuan Zhang,Long Chen,Wei Li
Diabetes mellitus (DM) is considered to be the most widespread epidemic worldwide, and diabetic nephropathy (DN) is one of the most serious diabetic complications. Its complex pathogenesis makes treatment of DN an ongoing medical challenge. Ginseng ( Panax ginseng . C. A Meyer) is a valuable medicinal herb with a long medicinal and culinary history. Ginsenoside Rg2 (Rg2), an important active component in ginseng, has effective inhibitory effects on lipogenesis and hepatic glucose production. However, the potential effect and mechanism of Rg2 on DN remain unclear. In this study, we investigated the effect of Rg2 on DN in high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic mice and high glucose (HG)-induced human kidney 2 (HK-2) cells. The results demonstrated that Rg2 significantly improved the levels of FBG, dyslipidemia and impaired kidney function in DN mice. Additionally, Rg2 decreased the phosphorylation levels of IKKβ, IκBα, and NF-κB p65, inhibited the activation of NLRP3 inflammasomes (NLRP3, ASC, and Caspase 1), and restrained release of inflammatory factors (IL-18 and IL-1 β ) . In HG-induced HK-2 cells, Rg2 showed similar inhibitory effects on pyroptosis via NF-κB/NLRP3 signaling pathways. Moreover, the effect of Rg2 on inhibiting the activation of NF-κB/NLRP3 signaling pathways may have a relationship to reducing the overproduction of reactive oxygen species (ROS), which is further supported by the ROS inhibitor N-acetylcysteine (NAC). In conclusion, our findings clearly indicated that Rg2 could prevent the progress of DN by inhibiting the activation of pyroptosis-related NF-κB/NLRP3 signaling pathways in vivo and in vitro , suggesting that Rg2 may be a novel and promising therapeutic agent in the treatment of DN.
研究领域:
药理学
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分子生物学
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糖尿病研究
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DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2019
·Vol. 40
·期 8
·1019-1028
·
IF 4.01
Yi Quan,Tan Fang-hui,Tan Jia-an,Chen Xiu-hui,Xiao Qing,Liu Ying-hua,Zhang Gui-ping,Luo Jian-dong
Minocycline is a tetracycline antibiotic and has been shown to play a protective role in cerebral and myocardial ischemia/reperfusion (I/R). However, the underlying mechanism remains unclear. Herein, we investigated whether monocyte chemotactic protein-induced protein-1 (MCPIP1), a negative regulator of inflammation, was involved in the minocycline-induced cardioprotection in myocardial I/R in vivo and in vitro models. Myocardial ischemia was induced in rats by left anterior descending coronary artery occlusion for 1 h and followed by 48 h reperfusion. Minocycline was administered prior to ischemia (45 mg/kg, ip, BID, for 1 d) and over the course of reperfusion (22.5 mg/kg, ip, BID, for 2 d). Cardiac function and infarct sizes were assessed. Administration of minocycline significantly decreased the infarct size, alleviated myocardial cell damage, elevated left ventricle ejection fraction, and left ventricle fractional shortening following I/R injury along with significantly decreased pro-inflammatory cytokine IL-1β and monocyte chemoattractant protein-1 (MCP-1) levels in heart tissue. H9c2 cardiomyocytes were subjected to oxygen glucose deprivation (OGD) followed by reoxygenation (OGD/R). Pretreatment with minocycline (1−50 μmol/L) dose-dependently increased the cell viability and inhibited OGD/R-induced expression of MCP-1 and IL-6. Furthermore, minocycline dose-dependently inhibited nuclear translocation of NF-κB p65 in H9c2 cells subjected to OGD/R. In both the in vivo and in vitro models, minocycline significantly increased MCPIP1 protein expression; knockdown of MCPIP1 with siRNA in H9c2 cells abolished all the protective effects of minocycline against OGD/R-induced injury. Our results demonstrate that minocycline alleviates myocardial I/R injury via upregulating MCPIP1, then subsequently inhibiting NF-κB activation and pro-inflammatory cytokine secretion.
研究领域:
药理学
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心脏病学
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分子生物学
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PubMed
高影响因子
MOLECULAR REPRODUCTION AND DEVELOPMENT
·
2025
·Vol. 92
·期 5
·e70029
·
IF 3
Junmei Fan,Junkun Zhang,Xingyu Bi,Pengfei Zhu,Jinbao Wang,Dan Su,Wenjing Shi,Yanling Liu,Huiping Liu,Xueqing Wu
Recurrent pregnancy loss (RPL) is one of obstetrical diseases with no effective therapy methods. Trophoblast cell dysfunction and inflammation induce embryo implantation insufficiency, thereby resulting in RPL. OTU deubiquitinase with linear linkage specificity (OTULIN) plays a role in regulating the immune response and cell death. However, the role of OTULIN in RPL remains unclear. Spontaneous abortion mouse model and lipopolysaccharide-treated HTR-8/SVneo cells were used to investigate the role of OTULIN in RPL. OTULIN expression was downregulated in the labyrinth trophoblast of RPL mice and LPS-treated trophoblast cells. The embryonic reabsorption rate was decreased in OTULIN-overexpressed spontaneous abortion mice, accompanied with the increase in placental/fetus weight ratio. OTULIN overexpression significantly inhibited apoptosis in vivo and in vitro, as evidenced by the decrease in the activity of caspase 3. The expression of pro-inflammatory cytokines was decreased with OTULIN overexpression. Moreover, OTULIN overexpression decreased p-IκBα/IκBα and p-p65/p65 ratio. The nuclear translocation of NF-κB was suppressed via OTULIN overexpression both in vivo and in vitro. Our study suggested that OTULIN deficiency might cause inflammation and trophoblast abnormalities in RPL. The supplementation with OTULIN might alleviate the development of RPL via inhibiting NF-κB mediated inflammation response.
研究领域:
生殖医学
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免疫学
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分子生物学
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PubMed
高影响因子
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
·
2024
·Vol. 76
·期 2
·139
·
IF 2
Tongrong Xu,Jiahui Han,Nan Wang,Zhirong Huan,Hao Yao,Xin Ge
Sepsis, a systemic inflammatory response often triggered by infection, can lead to multi-organ failure, with the intestine being one of the most vulnerable organs. The nuclear factor kappa-B (NF-κB) pathway plays a crucial role in immune responses, inflammation, and cell survival, making it central to sepsis-induced intestinal damage. Kakkalide (KA), a bioactive compound known for its anti-inflammatory, cardiovascular, neuroprotective, and anti-diabetic properties, has potential therapeutic effects. However, its impact on sepsis-induced intestinal injury remains unclear. In this study, murine sepsis models were used both in vivo and in vitro to evaluate the protective effects of KA on intestinal histopathology, apoptosis, and inflammation. Results showed that KA significantly reduced intestinal damage and apoptosis, as evidenced by hematoxylin-eosin and TUNEL staining. KA also improved intestinal barrier integrity, as indicated by reduced diamine oxidase activity, d -lactic acid content, and fluorescein isothiocyanate intensity, along with increased expression of zonula occludens-1. Furthermore, KA alleviates inflammation by reducing the levels of tumor necrosis factor-α, interleukin-1β, prostaglandin E2, inducible nitric oxide synthase, and cyclooxygenase-2. Immunofluorescence and Western blot analysis revealed that KA inhibited the sepsis-induced phosphorylation of inhibitor-kappaBα and RelA (P65) and prevented P65’s translocation to the nucleus. These findings were confirmed in lipopolysaccharide-induced Caco-2 cells, suggesting that KA protected the intestinal barrier during sepsis by suppressing the NF-κB pathway.
研究领域:
医学
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免疫学
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药理学
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DOI
PubMed
高影响因子
Colloid and Interface Science Communications
·
2023
·
IF 4.5
Tongtong Li,Wan Wan,Yali Cao,Jialing Xu,Hui Chai
Electrocatalysts comprising MoO 3 coated by Co 2 P 2 O 7 nanocrystals were grown on a nickel foam (NF) substrate. The applicability of the nanocomposite material (Co 2 P 2 O 7 @MoO 3 /NF) as an electrode for the oxygen evolution reaction (OER) and overall water splitting was verified. The as-synthesized product showed the overpotentials of 227 and 377 mV to drive the OER at current densities of 50 and 100 mA cm −2 , respectively. Furthermore, the voltage of Co 2 P 2 O 7 @MoO 3 /NF as a bifunctional overall water splitting catalyst was 1.55 V at 10 mA cm −2 . Co 2 P 2 O 7 @MoO 3 /NF@NF (+)//Co 2 P 2 O 7 @MoO 3 /NF (−) can maintain >80% of its initial current density after 30 h at 15 mA cm −2 . The Co 2 P 2 O 7 @MoO 3 /NF electrode also showed a low hydrogen evolution reaction overpotential of 58.7 mV at 10 mA cm −2 . The excellent oxygen evolution and electrochemical water decomposition stability of the catalyst have broad application prospects.
研究领域:
材料科学
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电化学
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DOI
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Yuhang Gong,Da Wo,Canran Wang,Ruokun Huang,En Ma,Celiang Wu,Jun Peng,Weidong Zhu,Dan-ni Ren
Background: Angiotensin II (Ang II) type 1 receptor (AT1R) signaling pathway is a key component of the renin-angiotensin-aldosterone system (RAAS) that is involved in the development of hypertension. Chronic Ang II overactivation results in pathological cardiac hypertrophy that progresses into decompensated cardiac dysfunction and impairment. Qingda granule (QDG) is a Traditional Chinese formula that has been used clinically in treating hypertension and its complications.Purpose: This study aimed to elucidate the role and underlying mechanisms of QDG in preventing Ang II-induced cardiac hypertrophy.Methods: We used chronic Ang II infusion via minipumps in mice and administered QDG daily to examine the effects of QDG on preventing hypertension and various parameters of cardiac impairment.Results: QDG treatment significantly reduced Ang II-induced elevation in blood pressure. Furthermore, QDG exerted a robust cardioprotective effect on chronic Ang II-induced cardiac hypertrophy and decompensated cardiac dysfunction. QDG also inhibited Ang II-induced adverse NF-κB signaling activation and downstream pro-inflammatory targets, which were prevented via administration with SC75741, a specific NF-κB inhibitor.Conclusion: Our findings provide further insight into the robust ability of QDG in preventing Ang II-induced cardiac hypertrophy via preventing NF-κB signaling activation and implicate its use in the clinical treatment of hypertension and cardiac hypertrophy.
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高影响因子
HUMAN & EXPERIMENTAL TOXICOLOGY
·
2022
·
IF 3.247
Shengwei Li,Guangqing Feng,Min Zhang,Xing Zhang,Jihong Lu,Chenyahui Feng,Fangshi Zhu
Objective: Due to its well-known anti-inflammatory property, oxymatrine (OMT) has received more attention on the aspect of treating ulcerative colitis. Although efforts have been undertaken to understand the therapeutic mechanism of OMT on ulcerative colitis (UC), the remedial principle is still ambiguous. Numerous studies have shown that TLR9/Myd88/NF-κB signal pathway played a key role in the pathogenesis of UC. Moreover, TLR9/Myd88/NF-κB signal pathway is a part of the most important pathways for regulating the immune response.Methods: We explored the influence of OMT with different dosages on UC by establishing a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Moreover, the participation of TLR9/Myd88/NF-κB signal pathway and whether OMT protects against UC though targeting this pathway are further studied.Results: Our data revealed that OMT could significantly relieve the symptom of TNBS-induced colitis in rats by reactivating the tight junction protein and, more important, by inhibiting the activation of TLR9/Myd88/NF-κB pathway and protein expression levels of its downstream inflammatory factors.Conclusion: OMT could relieve colitis in rat models by impacting tight junction proteins’ TLR9/Myd88/NF-κB signal pathways and activity.
研究领域:
药理学
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免疫学
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胃肠病学
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2021
·Vol. 35
·期 7
·e21497
·
IF 5.192
Sha Tu,Yanzhi Jiang,Haihua Cheng,Xiangning Yuan,Ying He,Yu Peng,Xiongqun Peng,Zhangzhe Peng,Lijian Tao,Huixiang Yang
Despite the increasing understanding of the pathophysiology of hepatic fibrosis, the therapies to combat it remain inadequate. Fluorofenidone (AKF-PD) is a novel pyridone agent able to ameliorate hepatic fibrosis in an experimental hepatic fibrosis model induced by dimethylnitrosamine. However, the underlying mechanism remains to be further elucidated. In light of the critical role of the NF-κB pathway in inflammation and hepatic fibrosis, together with the preliminary finding that AKF-PD decreases the release of proinflammatory cytokines in the endotoxemia and unilateral ureteral occlusion model, the aim of this study was to explore whether AKF-PD exerts an antifibrotic effect in hepatic fibrosis by inhibiting inflammation and suppressing the activation of the NF-κB pathway in vivo and in vitro. To test this possibility, the effect of AKF-PD on hepatic fibrosis models induced by both carbon tetrachloride (CCL 4 ) and porcine serum (PS) was investigated. Our results showed that AKF-PD treatment ameliorated hepatic injury and fibrosis in both models. Furthermore, the administration of AKF-PD induced a robust anti-inflammatory reaction revealed by the downregulation of the proinflammatory cytokines as well as the suppression of the infiltration of inflammatory cells in the fibrotic liver. The analysis of the mechanism of action demonstrated that the attenuation of the production of proinflammatory cytokines and chemokines mediated by AKF-PD in vivo and in vitro were accompanied by the suppression in the activation of the NF-κB signaling pathway. In conclusion, AKF-PD might be considered as an antifibrotic agent attenuating hepatic inflammation and fibrosis potentially through the suppression of the NF-κB pathway.
研究领域:
药理学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2019
·Vol. 24
·期 5
·833-848
·
IF 2.214
Gui-xin Zhang,Chen Zhan,Kai Wang,Jian Han,Dong Shang,Hai-long Chen
Acute biliary pancreatitis (ABP) is a potentially life-threatening disease that is induced by the common bile duct (CBD) sludge or stones. This study aimed to investigate protective effects of Qingyi Decoction (QYT) on deoxycholic-acid-sodium salt (DCA) induced ABP in rats. Gpbar1 is a G-protein coupled receptor that can be activated by DCA. Both Gpbar1 overexpression vector and Gpbar1 RNAi were constructed and transfected into ABP cell models. Functional assays reveal that DCA significantly induced AR42J apoptosis and triggered Gpbar1 expression. Gpbar1 significantly activated caspase 8 and caspase 9 as compared to LV5-NC and LV3-NC (p<0.05). Gpbar1 significantly triggered apoptosis associated inflammatory factors as compared to LV5-NC and LV3-NC (p<0.05). Gpbar1 significantly induced calcium flux as compared to LV5-NC and LV3-NC (p<0.05). Gpbar1 up-regulated caspases and inflammatory factors in DCA treated pancreatic acinar cells. QYT reversed DCA induced apoptosis and inflammatory response. QYT significantly reduced Gpbar1 levels compared to no-QTY treated cells (p<0.05). In conclusion, QYT protects against DCA induced pancreatic acinar cell damage in ABP by inhibiting Gpbar1/NF-kB/p-RIP signaling pathway.
研究领域:
药理学
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胃肠病学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2025
·
IF 5.9
Huan Xu,Kaixuan Ma,Ziting Ma,Tianyu Zhuang,Ling Lin
Introduction: Pulmonary fibrosis (PF) is a fatal pathological subtype of interstitial lung disease, frequently manifests as a pulmonary complication of connective tissue disease. Iguratimod (IGU) is a new class of anti-rheumatic drugs used in the treatment of rheumatoid arthritis (RA). Studies have reported that RA patients treated with IGU have better lung function, and IGU effectively ameliorates PF. However, the mechanism by which IGU improves PF is still unclear. This study aims to elucidate the therapeutic efficacy and mechanisms of IGU in PF through in vivo and in vitro investigations, so as to provide a new treatment method for PF.Methods: In our research, bleomycin (BLM)-induced PF of mice were used to observe the therapeutic effect of different concentrations of IGU. And the effects of IGU on macrophage polarization and activation pathway TLR4/NF-κB in lung tissue were analyzed. In addition, Raw264.7 macrophages were induced to M1 and M2 polarization in vitro, and the effects of IGU on Raw264.7 macrophage polarization and related pathways were observed.Results: In our study, database analysis suggested that macrophage polarization-relative genes and pathways as well as TLR4 activation played important roles in BLM-induced PF in mice. Besides, we found that IGU effectively ameliorated BLM-induced PF and epithelial-mesenchymal transition in mice, and inhibited the polarization of M1/M2 macrophages at different stages of PF. Moreover, In vitro studies further demonstrated that IGU suppressed M1 polarization of Raw264.7 and its activation pathway TLR4/NF-κB.Discussion: In summary, IGU inhibits the activation of macrophages and M1 polarization through inhibiting the TLR4/NF-κB pathway, thereby improving BLM-induced pulmonary inflammation and fibrosis in mice. It is suggested that IGU may be a new therapeutic option for interstitial pulmonary fibrosis.
研究领域:
免疫学
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呼吸病学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF ENVIRONMENTAL MANAGEMENT
·
2024
·
IF 8
Meichen Liu,Meichen Gao,Xu Shi,Yilin Yin,Huanyi Liu,Ruirui Xie,Chenxi Huang,Wenwen Zhang,Shiwen Xu
With the increasing development of the society, silicon dioxide (SiO 2 ) has been used in various fields, such as agriculture, food industry, etc., and its residues can pose a potential health threat to organisms. Quercetin (Que) is a potent free radical scavenger commonly found in plants. C57BL/6 mice were chosen to established a mouse model of SiO 2 exposure and Que antagonism to investigate the mechanism of action of Que in rescuing the toxic damage of SiO 2 on mouse cerebellum tissue. The results showed that cytoplasmic vacuolization, and inflammatory cell infiltration caused by SiO 2 were alleviated by the addition of Que, and reduced oxidative stress in mouse cerebellum, alleviated the activation of TLR4 pathway induced by SiO 2 , and substantially reduced the occurrence of ZBP-1-mediated PANoptosis induced by SiO 2 exposure in mouse cerebellum. In NS20Y cells, the oxidative stress activator (Elesclomol) and inhibitor N-acetyl cysteine (NAC), and the NF-κB activator 2 (NA2) were added. Elesclomol and NAC confirm the involvement of ROS in regulating the TLR4/NF-κB pathway, the TLR4/NF-κB pathway regulated ZBP-1-mediated PANoptosis in cerebellum and NS20Y cells induced by SiO 2 exposure. In conclusion, the present experimental data suggest that Que mitigates the onset of ZBP-1-mediated PANoptosis in neuronal cells induced by SiO 2 through the ROS/TLR4/NF-κB pathway. The present experimental findings help to understand the detoxification effect of Que in more tissues and provide an important reference for the rescue of organisms in long-term SiO 2 environment.
研究领域:
神经生物学
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毒理学
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细胞信号传导
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DOI
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2017
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IF 3.148
Lei Liu,Xiao Tu,Yu-Feng Shen,Wei-Chao Chen,Bin Zhu,Gao-Xue Wang
Different viruses could induced ROS generation to alter intracellular redox state in the host cells, and unbalanced redox state was suggested to have various effects on viral replication. In this study, we investigated the influence of reactive oxygen species (ROS) on replication of spring viraemia of carp virus (SVCV) in fish cells. After SVCV infection, there existed a time-dependent increase in ROS generation. The present results revealed that antioxidant N-acetyl- l -cysteine (NAC) resulted in a lower ROS levels and increased SVCV replication in EPC cell. In contrast, a GSH synthesis inhibitor buthionine sulfoximine (BSO) induced ROS generation and decreased SVCV replication. In addition, activation of NF-κB suppressed SVCV replication by using two inhibitors of cytokine-induced IκBα phosphorylation. More importantly, enhancement of the activity of NF-κB was found in BSO treatment, which indicated that dropped SVCV replication likely occurred via ROS activation of NF-κB. Overall, our results revealed that the SVCV infection and replication could generate ROS and be affected by the redox state, where this progression was associated with the alteration in NF-κB pathway induced by oxidative stress .
研究领域:
病毒学
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细胞生物学
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DOI
PubMed
高影响因子
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