MOLECULAR AND CELLULAR BIOCHEMISTRY
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2022
·Vol. 478
·期 2
·241-247
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IF 3.842
Zhou Quan,Cai Xu,Huang Ying,Zhou Youliang
Curcumin (CUR) is an extract of Curcuma longa Linn., which has various pharmacological activities. The instability, low water solubility and bioavailability of CUR greatly limit its clinical application. This work prepared Pluronic F127-liposome-encapsulated curcumin (CUR-LIP-F127) and explored its functional role in wound healing. Liposome-encapsulated curcumin (CUR-LIP) and CUR-LIP-F127 were prepared. Human keratinocyte cell line (HaCaT) was treated with CUR, Pluronic F127-liposome (LIP-F127) and CUR-LIP-F127, or combined with ML385 (Nrf2 inhibitor). The expression of mRNAs and proteins was detected by quantitative real-time PCR and western blotting. MTT and wound healing assays were performed to detect cell viability and migration. CUR, LIP-F127 and CUR-LIP-F127 all had no influence on cell viability of HaCaT cells. CUR-LIP-F127 treatment significantly accelerated cell migration and enhanced the expression of nuclear factor erythroid-related factor 2 (Nrf2) and kelch-like erythroid cell-derived protein 1 (Keap1) in HaCaT cells with respect to CUR or LIP-F127 treatment. ML385 treatment impaired CUR-LIP-F127-mediated promotion of migration and up-regulation of Nrf2 and Keap1 in HaCaT cells. This work demonstrated that CUR-LIP-F127 activated Nrf2/Keap1 signaling pathway to promote migration of HaCaT cells, suggesting that CUR-LIP-F127 may contribute to wound healing.
研究领域:
药理学
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细胞生物学
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材料科学
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生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 3
·1252
·
IF 6.208
Jing Yang,Xujiao Tang,Xue Ke,Yutong Dai,Jinsong Shi
Triptolide (TP), the main active ingredient ofTripterygium wilfordii Hook.f., displays potent anti-inflammatory, antioxidant, and antiproliferative activities. In the present study, the effect of TP on acute pancreatitis and the underlying mechanisms of the disease were investigated using a caerulein-induced animal model of acute pancreatitis (AP) and an in vitro cell model. In vivo, pretreatment with TP notably ameliorated pancreatic damage, shown as the improvement in serum amylase and lipase levels and pancreatic morphology. Meanwhile, TP modulated the infiltration of neutrophils and macrophages (Ly6G staining and CD68 staining) and decreased the levels of proinflammatory factors (TNF-α and IL-6) through inhibiting the transactivation of nuclear factor-κB (NF-κB) in caerulein-treated mice. Furthermore, TP reverted changes in oxidative stress markers, including pancreatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), in acute pancreatitis mice. Additionally, TP pretreatment inhibited intracellular reactive oxygen species (ROS) levels via upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and Nrf2-regulated redox genes expression (HO-1, SOD1, GPx1 and NQO1) in vitro. Taken together, our data suggest that TP exert protection against pancreatic inflammation and tissue damage by inhibiting NF-κB transactivation, modulating immune cell responses and activating the Nrf2-mediated antioxidative system, thereby alleviating acute pancreatitis.Keywords:acute pancreatitis;triptolide;inflammatory responses;oxidative stress
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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DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2025
·Vol. 86
·期 7
·e70174
·
IF 4.2
Zhenfei Yu,Xiaoling Qian,Weihua Wu,Meiqi Zhang,Ying Li
Intracerebral hemorrhage (ICH) is a serious acute cerebrovascular disease with a high death and disability rate. Baicalin plays a neuroprotective role in various diseases, but its regulatory mechanism on ICH remains unclear. In this study, we investigated the protective effects and mechanisms of baicalin in ICH using an ICH mouse model. ICH mouse model was established by injection of collagenase type IV into intracranial in C57BL/6 mice. Neurological function was evaluated by neurological severity scores and the rotarod test. Hemorrhagic foci of brain was evaluated by TTC and hematoxylin−eosin staining. Iron ion deposition in brain was detected by Prussian blue staining. Ferroptosis was evaluated by measuring expression of FTH-1, SLC7A11, GPX4, and TFRC, as well as detecting iron content and levels of glutathione (GSH) and malondialdehyde (MDA). GPX4 expression and apoptosis of brain were detected by immunofluorescence staining and TUNEL assay. Results showed that baicalin improved neurological function and reduced the area of hemorrhagic foci of brain in ICH mouse model. Baicalin decreased iron ion deposition, inhibited ferroptosis and apoptosis, and upregulated GPX4 in brain of ICH mouse model. Moreover, baicalin increased AKT1 phosphorylation and the protein level of Nrf2 in brain of ICH mouse model. Notably, AKT1 inhibitor LY294002 and Nrf2 inhibitor reversed the effects of baicalin on the activation of AKT1/Nrf2/GPX4 axis and the inhibition of ferroptosis in brain of ICH mouse model. Collectively, we demonstrated that baicalin promotes ICH recovery by inhibiting ferroptosis in brain tissue through activation of AKT/Nrf2/GPX4 axis. These results may provide new insights for the study of baicalin in the treatment of ICH.
研究领域:
神经病学
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分子医学
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药理学
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自由基生物学
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脑血管病
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神经保护机制
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2016
·Vol. 7
·期 11
·4683-4692
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IF 2.686
Fan Yuan-jing,Wei Wei,Luo Jian-ping,Jin Yu-xia,Dai Zi-ling
This study aimed to explore the effects of genistein on regulating the activation of UGTs via the Nrf2/Keap1 pathway and to elucidate the underlying mechanisms of detoxification and hepatic protection. Experiments monitoring genistein-induced protection against acetaminophen-induced cell damage were performed in L-02, HepG2 and Hep3b cells. The results of the MTT, AST, ALT, LDH, GSH and GSSG assays showed that genistein evidently protected the cells from acetaminophen-induced injury in a dose-dependent manner. The control cells were treated with 10 mM acetaminophen without genistein to compare with the effects of the combination of acetaminophen and genistein on the expression of UGT1A1, 1A6 and 1A9, Nrf2 and Keap1 mRNAs, as well as the expression of Nrf2 and Keap1 proteins, which were tested by western blotting. The results showed that the expression of the Nrf2 mRNA and protein increased; in contrast, the expression levels of the Keap1 mRNA and protein were obviously reduced by genistein in a dose-dependent manner. Meanwhile, the expression of the UGT mRNA was increased, and UGT1A9 exhibited the highest expression among the three UGTs. Accordingly, the residual acetaminophen content was obviously reduced and acetaminophen glucuronidation increased after 24 hours of treatment with genistein in a dose-dependent manner.
研究领域:
药理学
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毒理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Genes & Genomics
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2024
·
IF 1.6
Lv Junqi,Ma Shengmao,Wang Xiaowen,Dang Jifang,Ma Fuchun
Background Non-small cell lung cancer (NSCLC) contributes to the vast majority of cancer-related deaths. Proteasome 26S subunit, non-ATPase 12 (PSMD12), a subunit of 26S proteasome complex, is known to play the tumor-promoting role in several types of cancer but its function in NSCLC remains elusive. Objective To explore the role and underlying mechanisms of PSMD12 in NSCLC. Methods The PSMD12 expression in human normal lung epithelial cell line (BEAS-2B) and four NSCLC cell lines (A549, NCI-H1299, NCI-H1975, Calu-1) were determined by qRT-PCR and western blot. Malignant phenotypes of NSCLC cells were detected by CCK-8, EdU staining, immunofluorescence staining for E-cadherin, flow cytometry, and Transwell assays to assess cell viability, proliferation, epithelial-mesenchymal transition (EMT), apoptosis, migration and invasion. Dual luciferase assay was used to verify the regulatory role of transcription factor on the promoter. Results We identified the upregulation of PSMD12 in NSCLC tissues based on the GEO datasets, which further verified in NSCLC and BEAS-2B cell lines. PSMD12 knockdown significantly suppressed malignant behaviors of NSCLC cells, including cell growth, invasion, and migration, while PSMD12 overexpression presented the opposite effects. Interestingly, we found that PSMD12 upregulated the tumor-promoting factor TrxR1 mRNA expression. For its potential mechanisms, we demonstrated that PSMD12 elevated transcription factor Nrf2 protein level and promoted Nrf2 nuclear translocation. And Nrf2 further increased TrxR1 promoter activity and enhanced TrxR1 transcription. Meanwhile, we proved that TrxR1 overexpression erased the inhibitory effect of PSMD12 knockdown. Conclusion PSMD12 promotes NSCLC progression by activating the Nrf2/TrxR1 pathway, providing a novel prognostic and therapeutic target for NSCLC treatment.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Sheng Mingyue,Chen Xun,Yu Yan,Wu Qi,Kou Junping,Chen Gangling
Backgrounds: The circadian clock protein Rev-erbα is a crucial regulator of circadian rhythms that affects multiple molecular, cellular, and physiology pathways that control susceptibility, injury, and recovery in the neurological disorders. Emerging evidence suggest that Rev-erbα plays a key role in the inflammation and oxidative stress, two pivotal mechanisms in the pathogenesis, progression, and recovery process of ischemic stroke. However, it remains inconclusive whether Rev-erbα activation is protective against ischemic brain damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a master regulator of inflammatory and oxidative responses. Our study aimed to determine whether pharmacological activation of Rev-erbα by SR9009 protects against acute ischemic brain damage partly via Nrf2 pathway.Methods: Adult mice were pretreated with SR9009 or Nrf2 inhibitor all-trans-retinoic acid (ATRA) for 3 days prior to Sham or middle cerebral artery occlusion (MCAO) operation. After ischemia for 1 h and reperfusion for 24 h, the neurological function and cerebral infarction volume were determined, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and glutathione peroxidase (GSH-PX) activity in serum were detected by kit. The mRNA and/or protein level of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), Period (Per)1, Brain and muscle arnt-like1 (Bmal1), Circadian locomotor output cycles kaput (Clock), Rev-erbα, Nrf2, heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1) in cerebral cortex were detected by q-PCR and Western blot.Results: We confirmed that SR9009 activated Rev-erbα gene in the cerebral cortex under basal condition. At 24 h after reperfusion, SR9009 ameliorated acute neurological deficits, reduced infarct volume. Meanwhile, the inflammatory TNF-α, IL-1β, iNOS and MDA content levels were significant decreased, SOD and GSH-PX activity were obviously increased, which were markedly blunted (or abolished) by ATRA. SR9009 enhanced the induction of Nrf2 and its downstream target genes HO-1 and NQO1 after ischemic insult. In addition, we found that SR9009 restored Rev-erbα, Bmal1, Clock, Per1 genes expression in the cerebral cortex under ischemic condition.Conclusion: Taken together, Rev-erbα activation by SR9009 protects against ischemic stroke damage, at least, partly through Nrf2 pathway.
研究领域:
神经科学
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药理学
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分子生物学
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生物钟
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2015
·
IF 2.912
Chuanyang Su,Xiaomin Xia,Qiong Shi,Xiufang Song,Juanli Fu,Congxue Xiao,Hongjun Chen,Bin Lu,Zhiyin Sun,Shanmei Wu,Siyu Yang,Xuegang Li,Xiaoli Ye,Erqun Song,Yang Song
Neohesperidin dihydrochalcone (NHDC), a sweetener derived from citrus, belongs to the family of bycyclic flavonoids dihydrochalcones. NHDC has been reported to act against CCl4-induced hepatic injury, but its mechanism is still unclear. We first discovered that NHDC showed a strong ability to scavenge free radicals. In addition, NHDC induces the phase II antioxidant enzymes heme oxygenase 1 (HO-1) and NAD(P)H/quinone oxidoreductase 1 (NQO1) through the activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) signaling. Further assays demonstrated that NHDC induces accumulation of Nrf2 in the nucleus and augmented Nrf2-ARE binding activity. Moreover, NHDC inhibits the ubiquitination of Nrf2 and suggests the modification of Kelch-like ECH-associated protein 1 (Keap1) and the disruption of the Keap1/Nrf2 complex. c-Jun N-terminal kinase (JNK) and p38 but not extracellular signal-regulated protein kinase (ERK) phosphorylations were up-regulated by NHDC treatment. Taken together, NHDC showed its protective antioxidant effect against CCl4-induced oxidative damage via the direct free radical scavenging and indirect Nrf2/ARE signaling pathway.
研究领域:
药理学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHIMIE
·
2018
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IF 3.188
Ji Li,Yanping Li,Shuang Pan,Lin Zhang,Lina He,Yumei Niu
Paeonol is a natural phenolic compound in Moutan Cortex with multiple biological functions, such as anti-inflammatory and anti-oxidant activity. Recent evidence has proven that persistent inflammation, oxidative stress , along with nuclear factor E2-related factor 2 (Nrf2) signaling dysfunction in periodontium are the possible causes of alveolar bone resorption , and ultimately lead to periodontitis. The present study was designed to explore the protective effects of paeonol on ligation-induced periodontitis in rats, and investigate the possible mechanism. We found that treatment with paeonol (40, 80 mg/kg, intraperitoneal injection) for 7 days remarkably decreased the expression of receptor activator of nuclear factor kappa-B ligand increased the expression of osteoprotegrin and inhibited the formation of osteoclasts . This function of paeonol might be correlated with its ability to reduce inflammatory factors (IL-1β, IL-6 and TNF-α) and alleviate oxidative stress (SOD, MDA, GSH and ROS) in gingival tissues. Besides, paeonol increased Nrf2 activity. Silence of Nrf2 using specific siRNA diminished the inhibitory effect of paeonol on NF-κB p65 activation and downstream expression, suggesting that Nrf2 was essential for protective effect of paeonol. These results showed that paeonol protected against periodontitis-aggravated osteoclastogenesis and alveolar bone lesion via regulating Nrf2/NF-κB/NFATc1 signaling pathway .
研究领域:
药理学
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牙医学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Neuroscience
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2019
·
IF 3.648
Chen Xiao,Xi Zhiyu,Liang Huaibin,Sun Yuhao,Zhong Zhihong,Wang Baofeng,Bian Liuguan,Sun Qingfang
Secondary injuries mediated by oxidative stress lead to deterioration of neurological functions after intracerebral hemorrhage (ICH). Cortical astrocytes are among the most important cells in the central nervous system (CNS), and play key roles in maintaining redox homeostasis by providing oxidative stress defense. Hemin is a product of hemoglobin degradation, which has strong toxicity and can induce reactive oxygen species (ROS). Melatonin (Mel) and its metabolites are well tolerated without toxicity, prevent tissue damage as well as effectively assist in scavenging free radicals. We evaluated the hemin neurotoxicity to astrocytes and the resistance of Mel-treated astrocytes to hemin neurotoxicity. And we found Mel induced PKCα phosphorylation (p-PKC), nuclear translocation of Nrf2 in astrocytes, and upregulation of HO-1, which contributed to the reduction of ROS accumulation and cell apoptosis. Nrf2 and HO1 protein expression upregulated by Mel were decreased after administration of PKC inhibitor, Ro 31-8220 (Ro 31). Luzindole (Luz), a melatonin receptor inhibitor, suppressed p-PKCα, HO-1, and Nrf2 expression upregulated by Mel and increased cell apoptosis rate. The upregulation of HO-1 induced by Mel was depressed by knocking down Nrf2 expression by siRNA, which also decreased the resistance of astrocytes to toxicity of hemin. Mel activates astrocytes through PKCα/Nrf2/HO-1 signaling pathway to acquire resistance to toxicity of hemin and resist from oxidative stress and apoptosis. The positive effect of Mel on PKCα/Nrf2/HO-1 signaling pathway may become a new target for neuroprotection after intracerebral hemorrhage.
研究领域:
神经科学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Hepatology Communications
·
2025
·Vol. 9
·期 3
·e0658
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IF 4.6
Cai Fangfang,Zhou Kaiqian,Wang Peipei,Zhang Wen,Liu Lei,Yang Yunwen
Background: Acetaminophen-induced acute liver injury (AILI) is one of the common causes of abrupt liver failure in numerous nations. Several previous studies revealed that tiliroside, a glycoside flavonoid, exerts neuroprotective and renal protective effects. However, whether it has hepatoprotective effects is not known. The objective of this research is to examine whether tiliroside can protect against AILI. Methods: AILI mouse and cell models were performed to evaluate the protective effects of tiliroside. Molecular docking, cellular thermal shift assay, immunoprecipitation, and RNA-seq were performed to analyze the possible mechanisms of tiliroside. Results: In vivo, tiliroside attenuated AILI in mice significantly, as evidenced by lower ALT and AST levels. Molecular docking, cellular thermal shift assay, and RNA-seq analysis revealed that tiliroside promoted the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and the expression of its downstream genes through disruption of the NRF2-KEAP1 protein-protein interaction to inhibit KEAP1-mediated ubiquitination and degradation of NRF2, thereby inhibiting oxidative stress in the livers of AILI mice. Furthermore, hepatocyte-specific knockout of NRF2 greatly attenuated the hepatic-protective effects of tiliroside in mice. In vitro, tiliroside protected against acetaminophen-induced oxidative stress on cultured hepatocytes through activation of NRF2. In addition, NRF2 knockout markedly blunted the protection effects of tiliroside, suggesting that NRF2 mediates the hepatic-protective effects of tiliroside. Conclusions: Our study demonstrated that tiliroside could protect against AILI by activating the KEAP1/NRF2 pathway, which primarily inhibits the processing of oxidative stress and cell death. Our results suggest that tiliroside could serve as a potential agent for the clinical treatment of AILI.
研究领域:
药理学
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分子生物学
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肝脏病学
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
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2022
·Vol. 15
·期 12
·1548
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IF 5.215
Fei Yang,Cuizhen Shen
On the basis of the mice pressure ulcers (PU) model, the protective effect and potential mechanism of sodium Danshensu (SDSS) cream against PU were investigated. The mice were randomly divided into three groups: the negative control group (cream without 0.5 g SDSS), the SDSS group (cream containing 0.5 g SDSS), and the positive group (0.5 g Hirudoid®). After 7 and 14 days of ointment application, the wound-healing rate of the SDSS and positive groups was significantly higher than that of the control group (p< 0.05). The results of hematoxylin–eosin staining also indicated that SDSS has the potential to promote the healing of PU. In addition, the serum IL-6, IL-1β, TNF-α, and MDA levels decreased significantly (p< 0.01) after 14 days of SDSS treatment, while the SOD, CAT, and GSH-Px activities increased significantly (p< 0.01). In addition, SDSS cream was able to significantly increase the expression of Nrf2, HO-1, GCLM, NQO1, NF-κB p65, NF-κB p50, IKKα, and IKKβ while decreasing the expression of Keap1 and IκBαin the Nrf2/HO-1 and NF-κB pathways. Our research will provide a foundation for the future clinical prevention and treatment of PU with SDSS cream.Keywords:pressure ulcers;sodium Danshensu cream;ischemia/reperfusion injury;Nrf2/HO-1 pathway;NF-κB pathway
研究领域:
药理学
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伤口愈合
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炎症
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氧化应激
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产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
·
2023
·
IF 2.6
Lei Huang,Mengxuan Bian,Shunyi Lu,Jiayi Wang,Jieqin Yu,Libo Jiang,Jian Zhang
Ferroptosis is a novel form of cell death, which is a unique modality of cell death and closely associated with iron concentrations, generation of reactive oxygen species (ROS), and accumulation of the lipid reactive oxygen species. In the present study, the anti-ferroptosis effects of Engeletin was studied in erastin-induced bone marrow mesenchymal stem cells (BMSCs). After treatment with Engeletin, cell viability was determined by CCK-8 assay. The production of ROS, malonaldehyde (MDA), Superoxide dismutase (SOD) activities and glutathione peroxidase (GSH) were detected by using commercially-available kits. Ferroptosis-related proteins (GPX4, SLC7A11, TFR1, FPN1, Nrf2, Keap1) were evaluated by Western blotting. Osteogenic capacity was evaluated by ALP staining and ARS staining. The expression of osteogenic-related proteins (OPN, Runx2, OCN) were evaluated by Western blotting and changes in mRNA (ALP, BMP-2, COL-1, Osterix) were evaluated by RT-PCR. Consistent improvements in angiogenesis are observed with Engeletin in the presence of erastin. Engeletin significantly alleviated erastin-induced oxidative damage and protected against ferroptosis in BMSCs. Ferroptosis was inhibited by Engeletin, leading to decreasing reducing accumulation of ROS and lipid peroxidation products. Moreover, Engeletin promoted osteogenic differentiation in BMSCs and angiogenesis in human umbilical vein endothelial cells (HUVECs). Taken together, these findings indicate that Engeletin can protect BMSCs from erastin-induced ferroptosis through the Nrf2/Keap1 antioxidant pathway and identify Engeletin as a novel ferroptosis inhibitor, suggesting that Engeletin may promote resistance to ferroptosis and enable osteogenic function of BMSCs.
研究领域:
细胞生物学
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药理学
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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）