PeerJ
·
2023
·
IF 2.7
Linlin Sun,Miao Ding,Fuhua Chen,Dingyu Zhu,Xinmiao Xie
Podocyte injury is a critical factor in the pathogenesis of diabeticnephropathy (DN). Emerging evidence has demonstrated that breviscapine (Bre) exerts a renoprotective effect on diabetic rats. However, the effects of Bre on regulating podocyte injury under high glucose (HG) conditions remain unclear. In this study, an experimental mouse model of DN was induced by intraperitoneal injections of streptozotocin (STZ) in vivo . The effects of Bre on podocyte injury were assessed using cell counting kit-8 (CCK-8) assay, TdT-mediated dUTPnick-endlabelling (TUNEL) staining, quantitative real-time PCR (qRT‒PCR) and western blot analysis. We found that renal function was significantly decreased in diabetic mice, and this effect was blocked by Bre treatment. Bre effectively increased podocyte viability and inhibited HG-induced cell apoptosis. Furthermore, Bre ameliorated HG-induced podocyte injury, as evidenced by decreased α-smooth muscle actin (α-SMA) expression and increased podocin and synaptopodin expression. Mechanistically, Bre inhibited HG-induced nuclear factorkappaB (NF-κB) signalling activation and subsequently decreased NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, resulting in a decrease in pyroptosis. Pharmacological inhibition of NLRP3 decreased HG-induced podocyte injury, whereas the NLRP3 agonist abrogated the effects of Bre on inhibiting podocyte injury. In summary, these results demonstrate that Bre alleviates HG-induced podocyte injury and improves renal function in diabetic mice, at least in part by inhibiting NF-κB/NLRP3-mediated pyroptosis.
研究领域:
药理学
·
肾病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL BIOLOGY AND MEDICINE
·
2024
·
IF 2.8
Run Ma,Na Xie,Yuanhui Shu,Yafeng Wu,Ping He,Yining Xiang,Yan Zhou,Yuping Wang
Liver fibrosis has become a serious public health problem that can develop into liver cirrhosis and hepatocellular carcinoma and even lead to death. Cannabidiol (CBD), which is an abundant nonpsychoactive component in the cannabis plant, exerts cytoprotective effects in many diseases and under pathological conditions. In our previous studies, CBD significantly attenuated liver injury induced by chronic and binge alcohol in a mouse model and oxidative bursts in human neutrophils. However, the effects of CBD on liver fibrosis and the underlying mechanisms still need to be further explored. A mouse liver fibrosis model was induced by carbon tetrachloride (CCl 4 ) for 10 weeks and used to explore the protective properties of CBD and related molecular mechanisms. After the injection protocol, serum samples and livers were used for molecular biology, biochemical and pathological analyses. The results showed that CBD could effectively improve liver function and reduce liver damage and liver fibrosis progression in mice; the expression levels of transaminase and fibrotic markers were reduced, and histopathological characteristics were improved. Moreover, CBD inhibited the levels of inflammatory cytokines and reduced the protein expression levels of p-NF-κB, NF-κB, p-IκBα, p-p38 MAPK, and COX-2 but increased the expression level of PPAR-α. We found that CBD-mediated protection involves inhibiting NF-κB and activating PPAR-α. In conclusion, these results suggest that the hepatoprotective effects of CBD may be due to suppressing the inflammatory response in CCl 4 -induced mice and that the NF-κB and PPAR-α signaling pathways might be involved in this process.
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
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Shanbo Ma,Rui Zhang,Long Li,Jin Wang,Meiling Zheng,Xiaodi Guo,Shan Miao,Wei Quan,Wenjuan Liu,Xiaopeng Shi
The current study isolated a homogeneous polysaccharide (AP) with a molecular weight of 7.9 kDa from the pomace of Fuji apples. AP was found to consists of rhamnose, galactose, arabinose, glucose, and galacturonic acid in a ratio of 4.3:5.2:2.6:1.0:11.9. Ten sugar residues in AP, including T-Ara f , 1,5-Ara f , 1,2-Rha p , 1,3-Rha p , T-Gal p , 1,3,5-Ara f, 1,4-Gal p , 1,4-Gal p A, 1,6-Glc p , and 1,3,6-Glc p were identified using methylation and GC–MS. Combined with 1D and 2D NMR, it was further revealed that AP possesses a backbone of α-Gal p- (1 → [3)-α-Rha p -(1 → 2)-α-Rha p -(1] 2 → [4)-α-Gal p A-(1] 10 → 3,6)-β-Glc p -(1 → 6)-β-Glc p -(1 → 4)-β-Gal p -(1 → 4)-β-Gal p -(1→, with two branches: α-Ara f -(1 → 5)-α-Ara f -(1 → 5)-α-Ara f -(1 → 3,5)-α-Ara f -(1 → 6)-β-Glc p -(1→ and →3)-α-Rha p -(1 → 5)-α-Ara f -(1 → 3,6)-β-Glc p -(1→ bonded to the C-3 of β-1,3,6-Glc p . AP significantly inhibited the release of cytokines and inflammatory mediators, such as TNF-α, IL-1β, IL-6, reactive oxygen species (ROS) and nitric oxide (NO). Western blotting results indicated that AP treatment markedly downregulated iNOS and NF-κB protein expression in LPS-induced RAW264.7 cells, leading to decreased levels of phosphorylated proteins (p-NF-κB and p-ΙκΒα) and preventing the degradation of ΙκΒα. Furthermore, in LPS-induced RAW264.7 macrophages, AP inhibited the expression of TLR4 protein, which in turn inhibited the activity of the NF-κB pathway. The findings demonstrated that AP exhibits anti-inflammatory properties in vitro by targeting the TLR4/NF-κB signaling pathway, thus impeding the nuclear translocation of NF-κBp65, suppressing the expression of related pro-inflammatory factors.
研究领域:
食品科学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2020
·
IF 1.813
Yang Zheng,Jiahui Wang,Jiaru Wang,Haiyuan Xie,Tiejian Zhao
Objective. To study the effect of curcumol on liver sinusoidal endothelial cells (LSECs) and to analyze the mechanism of antihepatic fibrosis. Methods. The effects of drug intervention on cell proliferation rates were detected by MTT assay. The expression of NF-κB was detected by RT-PCR and WB. The NF-κB expression and entry into the nucleus were detected by immunofluorescence; scanning electron microscopy was used to observe the changes of LSECs fenestrae. Results. MTT results showed that the interference of cell proliferation in each group was small. RT-PCR showed that the expression of NF-κB in the curcumol intervention group was significantly lower than that in the positive control group (). The WB detection found that, in the curcumol intervention group, the expression of pNF-κB in the NF-κB signaling pathway was significantly lower than that in the positive control group (). Scanning electron microscopy showed that the LSEC fenestrae were significantly improved compared with the positive control group. Conclusion. Curcumol may be one of the mechanisms of antihepatic fibrosis by inhibiting the activity of the NF-κB signaling pathway and increasing the fenestrae of LSECs.
研究领域:
药理学
·
肝脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2021
·Vol. 10
·期 12
·2019
·
IF 6.313
Zebin Huang,Lingna Xie,Yongyu Xu,Kai Zhao,Xuetong Li,Jiaben Zhong,Yujing Lu,Xuetao Xu,Susan Goodin,Kun Zhang,Lanyue Zhang,Chunlian Li,Xi Zheng
Zingiber striolatumDiels (Z. striolatum), a widely popular vegetable in China, is famous for its medicinal and nutritional values. However, the anti-inflammatory effects of essential oil fromZ. striolatum(EOZS) remain unclear. In this study, EOZS from seven regions in China were extracted and analyzed by GC–MS. LPS-induced RAW264.7 cells and 12-O-Tetradecanoylphorbol 13-acetate (TPA)-stimulated mice were used to evaluate the anti-inflammatory effects of EOZS. Results show that 116 compounds were identified in EOZS from seven locations. Samples 2, 4 and 5 showed the best capability on DPPH radical scavenging and NO inhibition. They also significantly reduced the production of ROS, pro-inflammatory cytokines, macrophage morphological changes, migration and phagocytic capability. Transcriptomics revealed MAPK and NF-κB signaling pathways may be involved in the anti-inflammatory mechanism, and the predictions were proven by Western blotting. In TPA-induced mice, EOZS reduced the degree of ear swelling and local immune cell infiltration by blocking the activation of MAPK and NF-κB signaling pathways, which was consistent with the in vitro experimental results. Our research unveils the antioxidant capability and potential molecular mechanism of EOZS in regulating inflammatory response, and suggests the application of EOZS as a natural antioxidant and anti-inflammatory agent in the pharmaceutical and functional food industries.Keywords:Zingiber striolatumDiels;essential oil;oxidant stress;anti-inflammatory activity;MAPK;NF-κB
研究领域:
药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CARDIOVASCULAR DRUGS AND THERAPY
·
2024
·
IF 3.1
Ye Bozhi,Cai Xueli,Liang Xiaohe,Chen Yunxuan,Dai Shanshan,Huang Zhuqi,Huang Weijian,Zhang Lei,Wang Zixuan,Xing Jincheng,Lai Xianhui,Huang Zhouqing,Jia Zhuyin
Purpose Inflammatory responses induced by NLRP3 inflammasome contribute to the progression of atherosclerosis. This study seeks to investigate the effect of emodin on the NLRP3 inflammasome in atherogenesis and to probe the underlying mechanism. Methods ApoE-knockout (ApoE −/− ) mice were treated with a high-fat diet (HFD) for 12 weeks and intragastrically with emodin for 6 weeks. Human mononuclear cell line THP-1 was pretreated with emodin or signaling pathway inhibitors and induced into macrophages using phorbol 12-myristate 13-acetate (PMA) for 48 h. The NLRP3-mediated inflammatory response was studied both in vivo and in vitro. The level of the inflammation was detected by western blot, real-time PCR analysis, and ELISA. Results Emodin attenuated atherosclerotic lesions in HFD-treated ApoE −/− mice. Emodin dramatically decreased the expression of NLRP3, GSDMD, IL-1β, and IL-18 in HFD-treated ApoE −/− mice and PMA-induced macrophages. Moreover, emodin significantly hindered the activation of nuclear factor kappa-B (NF-κB) by inhibiting the formation of the TLR4/MyD88 complex in PMA-induced macrophages. Conclusion Our data demonstrate that emodin can inhibit the development of atherosclerotic plaques by alleviating NLRP3/GSDMD-induced inflammation through repressing the TLR4/MyD88/NF-κB signaling pathway in macrophages. This finding suggests that emodin can be a potential candidate for the treatment of atherosclerosis.
研究领域:
免疫学
·
心血管疾病
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Aging-US
·
2020
·
IF 4.831
Ke Lin,Wu Luo,Jueqian Yan,Siyuan Shen,Qirui Shen,Jun Wang,Xinfu Guan,Gaojun Wu,Weijian Huang,Guang Liang
Excessive vascular remodeling has been shown in hypertensive patients. In experimental models of hypertensive vascular injury, such as angiotensin II (Ang II) challenged mice, toll like receptor 2 (TLR2) initiates inflammatory responses. More recently, studies have reported atypical endothelial to mesenchymal transition (EndMT) in vascular injuries and inflammatory conditions. Here, we aimed to investigate whether TLR2 mediates Ang II-induced vascular inflammation and initiates EndMT. In a mouse model of angiotensin II-induced hypertension, we show that aortas exhibit increased medial thickening, fibrosis, and features of EndMT. These alterations were not observed in TLR2 knockout mice in response to Ang II. TLR2 silencing in cultured endothelial cells confirmed the essential role of TLR2 in Ang II-induced inflammatory factor induction, and EndMT-associated phenotypic change. Mechanistically, we found Ang II activates nuclear factor-κB signaling, inducing pro-inflammatory cytokine production, and mediates EndMT in both cultured endothelial cells and in mice. These studies illustrate a novel role of TLR2 in regulating Ang II-induced deleterious vascular remodeling through the induction of EndMT. The studies also suggest that TLR2 may be targeted to alleviate hypertension-associated vascular injury.
研究领域:
心血管研究
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免疫学
·
分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Zhou-Wei Wu,Xing-Rong Peng,Xiao-Cui Liu,Luan Wen,Xin-Yu Tao,Abdulbaset Al-Romaima,Ming-Yi Wu,Ming-Hua Qiu
Lepidium meyenii Walp., also known as the “Peruvian national treasure”, is a popular functional food in the daily lives of Peruvian people due to its bioactive with main polysaccharides. However, studies on polysaccharides isolated from Lepidium meyenii were few. Two new highly heterogeneous polysaccharides, MCP-1a and MCP-2b, were isolated and purified from the tuber of Lepidium meyenii . The structure characterization revealed that MCP-1a primarily consisted of D-Glc and had a molecular weight of 6.6 kDa. Its backbone was composed of 1,4,6- α -D-Glc, while branches feature T- α -L-Ara, 1,5- α -L-Ara, and T- α -D-Glc attached to the O -6 positions. MCP-2b was a rare arabinogalactan with a molecular weight of 49.4 kDa. Interestingly, the backbone of MCP-2b was composed of 1,6- β -D-Gal, 1,3,6- β -D-Gal with a few 1,3- β -D-Glc p A-4-OMe units inserted. Side chains of MCP-2b were mainly composed of 1,3- β -D-Gal, T- β -D-Gal, T- α -L-Ara, 1,5- α -L-Ara, with trace amounts of 1,4- β -D-Glc and T- β -D-Glc. The bioactivity assay results revealed that MCP-1a and MCP-2b increased the release of NO, IL-1 β , TNF- α , and IL-6 from RAW 264.7 cells at concentrations ranging from 50 μg/mL to 400 μg/mL. Furthermore, MCP-1a and MCP-2b could promote the expression of key transcription factors (IκB- α , p-IκB- α , p65, and p-p65) in the NF-κB pathway, indicating that MCP-1a and MCP-2b had potential immunomodulatory activities.
研究领域:
药理学
·
免疫学
·
植物化学
✓ 已验证
DOI
PubMed
高影响因子
CELL CYCLE
·
2021
·
IF 4.534
Limei Yan,Zeping He,Wei Li,Ning Liu,Song Gao
Rhophilin Rho GTPase binding protein 2 (P76RBE) belongs to rhophilin family of Rho-GTPase-binding proteins and is found to contribute to the development of diverse cancers. Data in Oncomine and Kaplan–Meier Plotter databases showed that P76RBE was upregulated in ovarian cancer tissues compared with normal tissues, and patients with high P76RBE expression had worse overall survival, which indicated P76RBE may be associated with the pathogenesis of ovarian cancer. This study aimed to investigate the role of P76RBE in ovarian cancer and to reveal the possible underlying mechanisms. The results demonstrated that P76RBE was highly expressed in ovarian cancer tissues and ovarian cancer cell lines. Functionally, silencing of P76RBE suppressed the proliferation, induced cell cycle arrest, and inhibited migration and invasion in OVCAR-3 and OV-90 cells, while overexpression of P76RBE showed opposite effects on A2780 cells. Mechanically, P76RBE silencing resulted in downregulation of integrin β1, accompanying the reduced NF-κB p65 phosphorylation and nuclear translocation. Importantly, integrin β1 knockdown effectively rescued the effects of P76RBE overexpression on ovarian cancer cells with suppressed proliferation, migration, and invasion. Additionally, in the xenograft tumors derived from OVCAR-3 and OV-90 cell lines, P76RBE knockdown inhibited tumor growth. Meanwhile, the expression of integrin β1 and NF-κB p65 phosphorylation was decreased. In summary, our findings indicate that P76RBE contributes to the progression of ovarian cancer through regulating the integrin β1/NF-κB signaling, and it may be a promising target for ovarian cancer therapy.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2025
·Vol. 53
·期 03
·909-930
·
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
·
分子生物学
·
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
·
心脏病学
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分子生物学
✓ 已验证
产品关联
DOI
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
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）