BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2024
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IF 2.5
Menglong Gao,Lishun Dong,Yulong Yang,Jinjin Yan,Yuning Liang,Xiaolin Ma,Min Zhou,Hongfei Wu,Yarong Liu,Min Dai
Atherosclerosis (AS) is the underlying cause of many severe vascular diseases and is primarily characterized by abnormal lipid metabolism. Paeonol (Pae), a bioactive compound derived from Paeonia Suffruticosa Andr., is recognized for its significant role in reducing lipid accumulation. Our research objective is to explore the link between lipid buildup in foam cells originating from macrophages and the process of ferroptosis, and explore the effect and mechanism of Pae on inhibiting AS by regulating ferroptosis. In our animal model, ApoE-deficient mice, which were provided with a high-fat regimen to provoke atherosclerosis, were administered Pae. The treatment was benchmarked against simvastatin and ferrostatin-1. The results showed that Pae significantly reduced aortic ferroptosis and lipid accumulation in the mice. In vitro experiments further demonstrated that Pae could decrease lipid accumulation in foam cells induced by oxidized low-density lipoprotein (LDL) and challenged with the ferroptosis inducer erastin. Crucially, the protective effect of Pae against lipid accumulation was dependent on the SIRT1/NRF2/GPX4 pathway, as SIRT1 knockdown abolished this effect. Our findings suggest that Pae may offer a novel therapeutic approach for AS by inhibiting lipid accumulation through the suppression of ferroptosis, mediated by the SIRT1/NRF2/GPX4 pathway. Such knowledge has the potential to inform the creation of novel therapeutic strategies aimed at regulating ferroptosis within the context of atherosclerosis.
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International Journal of Chronic Obstructive Pulmonary Disease
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2022
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IF 2.893
Xiao Sun,Zhonghua Dong,Nan Li,Xiuli Feng,Yan Liu,Ang Li,Xiaosong Zhu,Chunyan Li,Zhongxi Zhao
Background Ophiocordyceps sinensis (C. sinensis) extracts have been found to have a therapeutic effect on patients with chronic obstructive pulmonary disease (COPD). Silent information regulator 1 (SIRT1) plays an important role in the regulation of inflammatory mediators and correlates with lung function and COPD exacerbations. The objective of this work was to explore the anti-inflammatory effect and preliminary pathways of nucleosides from cultured C. sinensis on RAW264.7 macrophages and COPD mice.Materials and methods The nucleosides were extracted from cultured C. sinensis powder and further purified by macroporous resin D101 and glucan G10 columns. Inflammation and oxidative stress models in RAW264.7 macrophages and in mice were established by injection of cigarette smoke extract (CSE). We then examined how the isolated nucleosides regulated the production of the associated inflammatory mediators in vitro and in vivo by enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and Western blot.Results The nucleosides inhibited inflammatory mediator expression of tumor necrosis factor-α, interleukin-6, interleukin-1β, and nitric oxide in both the CSE-stimulated RAW264.7 macrophages and mice. Moreover, the nucleosides elevated SIRT1 activation and suppressed nuclear factor-κB (NF-κB)/p65 activation in vitro and in vivo. Nucleoside treatment significantly decreased the levels of the inflammatory mediators in the bronchoalveolar lavage fluid (BALF) and serum of the CSE-induced mice. The nucleosides also altered the recruitment of inflammatory cells in BALF and improved characteristic features of the lungs in the CSE-induced mice.Conclusion These results show that the nucleosides suppressed COPD inflammation through the SIRT1–NF-κB/p65 pathway, suggesting that the nucleosides may be partly responsible for the therapeutic effects of cultured C. sinensis on COPD patients.
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HISTOLOGY AND HISTOPATHOLOGY
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2024
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IF 2.5
Jinfeng Xie,Yonggui Liao,Dile Wang
Background: Deep vein thrombosis (DVT) is the third most prevalent vascular disease worldwide, seriously threatening human health. Baicalin, a flavonoid isolated from the roots of Scutellaria baicalensis , has been identified to play a crucial role in various vascular diseases. The study aimed to explore the efficacy and underlying mechanisms of baicalin in DVT. Methods: Endothelial progenitor cells (EPCs) were differentiated from peripheral blood mononuclear cells isolated from rat bone marrow. Dil-ac-LDL/FITC-UEA-1 double staining and flow cytometry analysis were conducted for the identification of EPCs. The angiogenesis and migration of EPCs in vitro were tested by a tube formation assay and Transwell assay, respectively. DVT rat models were established by stenosis of the inferior vena cava (IVC). After the euthanasia of rats, thrombi in the IVC were collected and weighed, and histological alterations in IVC tissue were measured by H&E staining. The protein levels of SIRT1, p-P65, and p65 in rat IVC tissues were quantified via western blotting. Results: EPCs used in this study displayed a spindle-like shape and were positive for endothelial cell-specific markers, suggesting the phenotypic characteristics of EPCs. Baicalin enhanced the migratory and angiogenetic abilities of EPCs in vitro . For in vivo experiments, baicalin reduced thrombus weight and mitigated DVT formation in model rats. Moreover, baicalin activated SIRT but repressed NF-κB signaling in IVC tissues of DVT rats. Conclusion: Baicalin facilitates migration and angiogenesis of EPCs but impedes thrombus formation via regulation of SIRT1/NF-κB signaling in DVT model rats.
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JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2025
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IF 4.9
Heng Zhou,Yueming Long,Fangmei Yu,Chenhui Ji,Li Gui,Yunxia Lu
Resveratrol (RSV) ameliorates endothelial dysfunction (ED) primarily through sirtuin 1 (SIRT1). Increasing evidence shows pyroptosis as a novel mechanism in palmitic acid (PA)-induced ED. p66Shc is an adaptor protein involved in oxidative stress. However, whether RSV attenuates the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome via p66Shc remains elusive. This study aims to evaluate whether the anti-pyroptotic effect of RSV and the SIRT1 inhibitor EX527 are related to p66Shc. High-fat diet (HFD) induced obesity in mice, and RSV was administered intragastrically with 400mg/kg/d for 22 successive weeks. The serum levels of interleukin-1β (IL-1β) and IL-18 were analyzed, and the expression of related proteins were assayed with immunohistochemistry in the thoracic aorta. human umbilical vein endothelial cells (HUVECs) were induced by PA, then treated with RSV and EX527 respectively, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP) and expression of p66Shc, NLRP3, GSDMD and pyroptosis-related genes were assayed. RSV administration ameliorated endothelial cell pyroptosis by decreasing serum IL-1β and IL-18, the expression of NLRP3, p66Shc, and gasdermin D (GSDMD), and increasing the expression of SIRT1 in the HFD-treated thoracic aorta. PA promoted GSDMD-mediated endothelial cell pyroptosis by ROS production, LDH release, decreased MMP and SIRT1 expression, increased expression of p66Shc and activation of the NLRP3 inflammasome in a dose-dependent manner. RSV attenuated PA-induced pyroptosis, whereas EX527 reversed the antipyroptotic effect of RSV in PA-treated HUVECs. Our results suggested a new mechanism that RSV improves PA-induced pyroptosis in endothelial cells via the SIRT1-p66Shc-NLRP3 pathway.
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BIOCHEMICAL PHARMACOLOGY
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2018
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IF 4.235
Zhihua Wang,Sheng Yuan,Yanbing Li,Zhe Zhang,Wei Xiao,Dan Tang,Kaihe Ye,Zhijun Liu,Congcong Wang,Yixiong Zheng,Hong Nie,Heru Chen
( R , E )- N -(3-(2-acetamido-3-(benzyloxy) propanamido)propyl)-2-cyano-3-(4-hydroxy phenyl)acrylamide ( hr5F ) was design-synthesized based on bioactivity focus strategy as a potential agent to treat diabetic complicates. With in vitro enzyme assay, it is confirmed that hr5F is an effective ALR2 inhibitor with IC 50 value of 2.60 ± 0.15 nM, and selectivity index of 86.0 over ALR1, which is a little bit better than the reference Epalrestat (Epa). hr5F inhibits the increase of ALR2 enzyme activity and expression in human lens epithelial cells (HLECs) induced by high glucose. By applying western blot , it was found that hr5F alleviates the high glucose-induced superoxide overproduction insults by regulating SIRT1-PGC-1α/Nrf2 pathway, together with regulating NRF-1, mtTFA , Bax/Bcl-2 to ameliorate cell apoptosis . The in vivo effects of hr5F on short term streptozocin (STZ)-induced diabetic mice confirm the same functions disclosed in vitro . All the evidences support that hr5F may serve as a promising agent in the treatment of diabetic complications with close efficacy and broader indication than the reference Epa.
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INFLAMMATION
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2021
·Vol. 44
·期 5
·1993-2005
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IF 4.092
Wu Yuqin,Fan Lin,Wang Yun,Ding Jing,Wang Rongfu
This study is aimed at exploring the potential of isorhamnetin in protection against diabetes-exacerbated ischemia/reperfusion-induced brain injury and elucidating its action mechanism. After establishment of the model of high glucose (HG)-aggravated oxygen-glucose deprivation and reoxygenation (OGD/R), HT22 cell viability was detected by CCK-8. Lactate dehydrogenase (LDH) activity, casapase-3 activity, and oxidative stress-related markers in HT22 cells were detected by corresponding commercial kits. The apoptosis of HG-treated HT22 cells following OGD/R was observed with TUNEL staining. The level of pro-inflammatory cytokines was examined by ELISA. The expression of Akt/SIRT1/Nrf2/HO-1 signaling-related proteins was assayed by Western blot. The results showed that HG noticeably worsened the OGD/R-induced apoptosis of HT22 cells. Isorhamnetin relieved the HG-aggravated OGD/R-induced apoptosis, inflammatory response, and oxidative stress of HT22 cells. Isorhamnetin alleviated the HG-aggravated OGD/R injury in HT22 cells through Akt/SIRT1/Nrf2/HO-1 signaling pathway. Meanwhile, treatment with Akt inhibitor LY294002 reversed the protective effects of isorhamnetin against HG-aggravated OGD/R injury in HT22 cells. In a conclusion, Isorhamnetin alleviates HG-aggravated OGD/R in HT22 hippocampal neurons through Akt/SIRT1/Nrf2/HO-1 signaling pathway.
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Dake Huang,Ke Shen,Li Gui,Qiongqiong Cao,Fangmei Yu,Yunxia Lu
Given resveratrol's (RES) potential as an anti-aging agent, this study explored its ability to inhibit the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome through the miR-217/SIRT1 axis in senescent endothelial cells. Male C57BL/6 mice were administered a customized regular diet supplemented with 0.04 % RES for 64 consecutive weeks. Subsequently, the effects of RES on senescent human umbilical vein endothelial cells (HUVECs) induced by H 2 O 2 were evaluated. Gene expression analyses were conducted following SIRT1 knockdown in HUVECs treated with H 2 O 2 and RES, or transfected with miR-217 mimics and inhibitors. The study found that RES reduced body weight, improved endothelial function, enhanced SIRT1 expression, and suppressed the expression of miR-217, NADPH oxidase 4 (NOX4), and NLRP3 in the senescent thoracic aorta. Additionally, RES significantly reduced the expression of NOX4, X-box binding protein 1 spliced (XBP1s), and reactive oxygen species (ROS) production in a dose-dependent manner in senescent HUVECs. SIRT1 knockdown resulted in the activation of the NLRP3 inflammasome by upregulating NOX4 and XBP1s expression, an effect that was partially attenuated by RES pretreatment. RES also suppressed the expression of miR-217 induced by H 2 O 2 . The miR-217 mimic facilitated cellular senescence; however, RES mitigated this effect, which was further amplified by the miR-217 inhibitor.
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FOOD AND CHEMICAL TOXICOLOGY
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2020
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IF 4.679
Rili Hao,Xinyu Song,Feng Li,Xintong Tan,Dongxiao Sun-Waterhouse,Dapeng Li
Exposure to nonbiodegradable cadmium (Cd) causes many health problems including the damage to the nervous system. This study aimed to increase knowledge about its neurotoxic effects and the neuroprotective potential of caffeic acid phenethyl ester (CAPE, a polyphenol abundant in honeybee propolis). In mice, CAPE (10 μmol/kg/day body weight) attenuated significantly learning and memory deficits induced by CdCl 2 (1.5 mg/kg/day body weight). For the CdCl 2 -treated mice, CAPE increased crossing number in open field test, decreased the alternation in Y-maze test, and increased the latency time and error number in step down test. CAPE also inhibited CdCl 2 -initiated Aβ accumulation and activation of pro-inflammatory factors and microglia in the brains. Therefore, CAPE could be a food-derived neuroprotective agent against Cd-induced neurotoxicity and neurodegenerative disorders, through attenuating neuronal apoptosis and neuroinflammation via the AMPK/SIRT1 pathway and amyloid-tau-neuroinflammation axis.
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Food & Function
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2022
·Vol. 13
·期 5
·2647-2661
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IF 6.317
Yongfeng Ren,Dongxiao Sun-Waterhouse,Fangxin Ouyang,Xintong Tan,Dapeng Li,Longhua Xu,Bo Li,Yongli Wang,Feng Li
Lead can lead to neurotoxicity and cognitive impairment. In this study, for the first time, the protective effects and working mechanisms of apple phenolic extracts (APEs) against lead acetate (Pb(Ac)2)-induced cognitive impairment and depression- and anxiety-like behavior were examined in vivo. Forty male mice were administered daily (via gastric gavage; 8 weeks) with 0.9% normal saline (control), Pb(Ac)2 (20 ppm), APE (200 ppm) or Pb(Ac)2 (20 ppm) + APE (200 ppm). The APE contained five major phenolic compounds: chlorogenic acid, proanthocyanidin B2, epicatechin, phloridzin and phloretin. Behavioral tests, histopathological examinations and biochemical analyses revealed that Pb(Ac)2-treated mice exhibited cognitive and behavioral deficits (i.e. a reduced percentage of spontaneous alternation, prolonged duration of immobility and decreased open field test scores compared with the control. Pb(Ac)2 exposure significantly increased cellular oxidative damage and the levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), ionized calcium binding adaptor molecule 1 (Iba1) and pro-apoptotic proteins (caspase 3, caspase 9 and Bax), while downregulating the expression of Bcl-2 in the brain. APE administration alleviated these Pb(Ac)2-induced changes through regulating oxidative stress, neuroinflammation and apoptosis via the miR-22-3p/Sirtuin 1 (SIRT1) signaling pathway. Taken together, the APE has the potential to treat lead-induced neurotoxicity and neurodegenerative disorders via antioxidant, anti-inflammatory and anti-apoptotic actions.
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ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2026
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IF 11.3
Jinchen Jiang,Haixia Meng,Zhenhao Shu,Nannan Zhao,Xiaojun Lin,Jianglan Li,Minjun Qin,Siyu Wu,Lianglin Qiu
As an emerging alternative to perfluorooctanesulfonate (PFOS), 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFAES) is associated with male reproductive disorders, yet its testicular targets and mechanisms remain unclear. This study combined in vivo exposure of male C57BL/6J mice (0, 4, 40, and 400 μg/L for 18 weeks) and in vitro assays in primary Leydig cells to demonstrate that 6:2 Cl-PFAES dose-dependently reduced sperm count and serum/testicular testosterone, accompanied by testicular interstitial vacuolation. Transcriptomics and metabolomics demonstrated the concurrent significant enrichment of autophagy pathways and disruption of lipid metabolism. Mechanistically, 6:2 Cl-PFAES suppressed expressions of Sirtuin 1 (SIRT1), ras-related GTP binding protein 7 (RAB7), and deacetylation of forkhead box class O1 (FOXO1), thereby impairing lipophagy flux and promoting lipid droplets accumulation. Molecular docking indicated comparable binding affinity of 6:2 Cl-PFAES and PFOS to SIRT1 (−10.4 kcal/mol), and further research demonstrated that 6:2 Cl-PFAES reduced the deacetylation activity of SIRT1. Crucially, Sirt1 overexpression in transgenic mice (Sirt1TG) or pharmacological activation of SIRT1 (SRT1720) and RAB7 (ML-098) rescued testosterone synthesis and restored lipophagy flux. This study identifies the SIRT1–FOXO1–RAB7 axis as a core target for 6:2 Cl-PFAES-induced suppression of testosterone biosynthesis via lipophagy dysregulation, providing critical molecular insights for assessing the reproductive risks of PFOS alternatives.
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