Bioengineered
·
2020
·
IF 2.205
Aimin Liu,Buxin Zhang,Wei Zhao,Yuanhui Tu,Qingxing Wang,Jing Li
Psoriasis is a chronic inflammatory skin disease that affects approximately 2% of worldwide population, and causing long-term troubles to the patients. Therefore, it is urgent to develop safe and effective therapeutic drugs. Catalpol is a natural iridoid glucoside, that has several remarkable pharmacological effects, however, whether catalpol can alleviated psoriasis has not been explored. The goal of the present work is to study the role of catalpol in psoriasis in vivo and in vitro. Imiquimod-induced psoriasis-like mice were applied with different concentrations of catalpol for 8 consecutive days. The severity degree of psoriasis was estimated and the skin pathological changes were detected by H&E staining. Also, TNF-α-stimulated keratinocytes were treated with different concentrations of catalpol, then the oxidative stress and inflammation factors, as well as the expression of SIRT1 and activation of NF-kB and MAPK pathways were measured. The results showed that catalpol reduced the erythema, scaling, ear thickness, and changed pathological phenotypes in the lesioned skin region in mice. Treatment with catalpol significantly suppressed the oxidative stress and inflammatory reactions in vivo and in vitro, as reflected by the decreased secretion or expression of oxidative stress indicators and proinflammatory factors. Furthermore, the SIRT1 was up-regulated and the NF-κB and MAPKs signaling pathways were suppressed by the treatment of catalpol in vivo and in vitro. In summary, our data suggested that catalpol may have a therapeutic property of psoriasis by ameliorating oxidative stress and inflammation partly through SIRT1 mediated suppression of NF-κB and MAPKs pathways.Abbreviation: CAT: catalase; ELISA: enzyme-linked immunosorbent assay; GSH: glutathione; HRP: horseradish peroxidase; IMQ: imiquimod; JNK: c-Jun NH 2-terminal kinases; MAPKs: mitogen-activated protein kinases; MDA: malondialdehyde; NC: negative control group; NF-kB: nuclear factor kappa B; PASI: psoriasis area and severity index; PVDF: polyvinylidene difluoride membranes; qRT-PCR: quantitative real time polymerase chain reaction; ROS: reactive oxygen species; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel; SIRT1: silent information regulator 1; SOD: Cu/Zn superoxide dismutase
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高影响因子
PULMONARY PHARMACOLOGY & THERAPEUTICS
·
2020
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IF 2.681
Min Chen,Cuifen Chen,Yun Gao,Dongming Li,Dan Huang,Ziyu Chen,Xuanna Zhao,Qiu Huang,Dong Wu,Tianwen Lai,Guomei Su,Bin Wu,Beixian Zhou
Background Bergenin , a type of polyphenol compound, exhibits antiulcerogenic, anti-inflammatory, antitussive , and burn wound-healing properties. However, its therapeutic effect on tumor necrosis factor α (TNF-α)-induced proinflammatory responses in the airway and potential mechanisms of actions are still unclear. This study aimed to investigate the anti-inflammatory effects and mechanism of bergenin in TNF-α-stimulated human bronchial epithelial (16-HBE) cells. Methods Cell Counting Kit-8 was used to evaluate cytotoxicity. Cytokine expression was analyzed by reverse transcription-quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay. Immunofluorescence, western blot , and sirtuin-1 (SIRT1) activity assays were employed to investigate potential molecular mechanisms. Results Bergenin obviously decreased both mRNA and protein expression levels of interleukins 6 and 8 (IL-6 and IL-8) in TNF-α-stimulated 16-HBE cells. Bergenin blocked TNF-α-mediated activation of nuclear factor κB (NF-κB) signaling and NF-κB nuclear translocation. Interestingly, RT-qPCR and western blotting results revealed that bergenin did not affect SIRT1 expression, but significantly increased its activity. Bergenin-mediated SIRT1 activation was further confirmed by results indicating decreased acetylation levels of NF-κB-p65 and p53. Moreover, the inhibitory effects of bergenin on mRNA and protein expression levels of IL-6 and IL-8 were reversed by a SIRT1 inhibitor. In addition, combining bergenin and dexamethasone (DEX) yielded additive effects on the reduction of IL-6 and IL-8 expression. Conclusions These findings demonstrate that bergenin could suppress TNF-α-induced proinflammatory responses by augmenting SIRT1 activity to block the NF-κB signaling pathway , which may provide beneficial effects for the treatment of airway inflammation associated with asthma.
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Evidence-based Complementary and Alternative Medicine
·
2021
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IF 2.63
Fei Zheng,Hai Xue,Bi-Xiang Wang,Man-Yu Wu,Dong-Xia Chen,Hao Yue,Lian-Kui Wen,Yang He
Vitis amurensis Rupr. “Beibinghong” is abundant in anthocyanins, including malvidin (Mv), malvidin-3-glucoside (Mv3G), and malvidin-3,5-diglucoside (Mv35 G). Anthocyanins offer nutritional and pharmacological effects, but their stability is poor. Interaction of malvid anthocyanins with caffeic acid through ultrahigh pressure technology produces stable anthocyanin derivatives. This study aims to identify the structure of stable mallow-like anthocyanins and to determine the effect of these stable anthocyanins on human umbilical vein endothelial cells (HUVECs) with H2O2-induced oxidative damage and the signaling pathway involved. The products of malvid anthocyanins and caffeic acid bonding were identified and analyzed using ultra-high performance liquid chromatography-quadrupole-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS/MS). The bonding products were malvidin-3-O-guaiacol (Mv3C), malvidin-3-O-(6″-O-caffeoyl)-glucoside (Mv3CG), and malvidin-3-O-(6″-O-caffeoyl)-5-diglucoside (Mv3C5G). An oxidative stress injury model in HUVECs was established using H2O2 and treated with Mv, Mv3G, Mv35 G, Mv3C, Mv3CG, and Mv3C5G at different concentrations (10, 50, and 100 μmol/L). Results showed that the above compound concentrations can significantly increase cell proliferation rate and reduce intracellular reactive oxygen species at 100 μmol/L. The effects of the most active products Mv and Mv3C on the AMP-activated protein (AMPK)/silencing information regulator-1 (SIRT1) pathway were analyzed. Results showed that Mv and Mv3C significantly increased SOD activity in the cells and significantly upregulated the expression of SIRT1 mRNA, SIRT1, and p-AMPK protein. However, they did not significantly change the expression of AMPK protein. After the silent intervention of siRNA in SIRT1 gene expression, the upregulation of SIRT1 and p-AMPK protein by Mv and Mv3C was significantly inhibited. These results indicate that stabilization malvid anthocyanins exerts an antioxidant activity via the AMPK/SIRT1 signaling pathway.
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JOURNAL OF HAZARDOUS MATERIALS
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2025
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IF 11.3
Nan Zhao,Wei Song,Tianshu Sun,Weiwei Wu,Yongliang Feng,Ning Ma,Suping Wang
Prenatal exposure to Benzo[ a ]pyrene (BaP) has been shown to increase the risk of adverse birth outcomes, potentially through disruption of maternal metabolic homeostasis. However, the underlying pathways and mechanisms remain unclear. To address this knowledge gap, we employed a multi-omics approach combining experimental and epidemiological investigations. In the mouse model, untargeted metabolomics profiling revealed niacinamide (NAM) metabolism as the most significantly altered pathway in both maternal serum and placenta following BaP exposure. Mechanistically, BaP exposure reduced nicotinamide adenine dinucleotide (NAD+) synthesis while increasing its catabolism through activation of poly (ADP-ribose) polymerase 1 (PARP1) in placental tissue. Subsequent transcriptomic analysis showed that BaP-induced NAD+ depletion led to sirtuin 1 (SIRT1) suppression and consequent exacerbation of the NF-κB-mediated inflammatory response. These experimental findings were substantiated in human populations through targeted metabolomic analysis of a Chinese birth cohort, where significant NAM metabolic disturbances were observed in women with high BaP exposure experiencing preterm delivery. Our study provides novel mechanistic evidence that BaP-induced dysregulation of NAM metabolism mediates adverse birth outcomes through NAD+ deficiency and subsequent inflammatory response. These findings not only identify potential therapeutic targets but also highlight the urgent need for evidence-based environmental policy interventions and nutritional supplementation strategies to protect maternal-fetal health in high-risk populations.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2015
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IF 3.705
Lina Gu,Xufeng Tao,Youwei Xu,Xu Han,Yan Qi,Lina Xu,Lianhong Yin,Jinyong Peng
Oxidative stress is involved in hepatic stellate cells (HSCs) activation and extracellular matrix overproduction. We previously reported the promising effects of dioscin against CCl 4 -induced liver fibrosis, but its effects and mechanisms on BDL- and DMN-induced liver fibrosis remain unknown. The results in the present study indicated that dioscin significantly inhibited HSCs activation and attenuated hepatic fibrosis in rats. Furthermore, dioscin markedly up-regulated the levels of sirtuin 1 (Sirt1), HO-1, GST , GCLC and GCLM via increasing the nuclear translocation of nuclear erythroid factor 2-related factor 2 (Nrf2), which in turn inhibited mitogen-activated protein kinase 14 (p38 MAPK) phosphorylation and reduced the levels of COL1A1, COL3A1, α-SMA and fibronectin . These results were further validated by knockdown of Sirt1 and Nrf2 using siRNAs silencing, and abrogation of p38 MAPK using SB-203580 (a p38 MAPK inhibitor) in HSC-T6 and LX-2 cells. Collectively, our findings confirmed the potent effects of dioscin against liver fibrosis and also provided novel insights into the mechanisms of this compound as a candidate for the prevention of liver fibrosis in the future.
研究领域:
药理学
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肝病学
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细胞生物学
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分子生物学
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BRAIN RESEARCH BULLETIN
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2022
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IF 3.715
Bihui Song,Wenhao Zhou
Amarogentin (AMA), a secoiridoid glycoside that is mainly derived from SwertiaandGentiana roots, has been confirmed to exhibit antioxidative, tumor-suppressive and anti-diabetic properties. This research intends to investigate the protective effect of AMA against sepsis-induced brain injury and its mechanism. NSC-34 and HT22 cells were treated with lipopolysaccharide (LPS) to induce an in-vitro sepsis model and then treated with varying concentrations (1, 5, 10 µM) of AMA. Cell proliferation and apoptosis were evaluated. The intensity of inflammation and oxidative stress were assessed by different methods. The AMPK/SIRT1/NF-κB pathway expression was determined by WB . An in-vitro sepsis model was set up with cecal ligation and puncture (CLP) in adult C57/BL6J mice, and different concentrations (25, 50, 100 mg/kg) of AMA were applied for treatment. Neurological function was evaluated using the modified neurological severity scores (mNSS), and the brain tissue damage was measured using hematoxylin-eosin (H&E) staining and Nissl staining. Tissue apoptosis was tested using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Then, the AMPK inhibitor Compound C (CC) was administered to confirm AMA-mediated mechanism. Our finding illustrated that AMA mitigated LPS-induced neuronal damage, inflammation and oxidative stress, activated the AMPK/SIRT1 pathway and choked NF-κB phosphorylation. Furthermore, AMA improved neurological functions of sepsis mice by reliving neuroinflammation and oxidative stress. Inhibition of AMPK attenuated the protective effect of AMA on neurons or the mice’s brain tissues. In conclusion, AMA protected against sepsis-induced brain injury by modulating the AMPK/SIRT1/NF-κB pathway.
研究领域:
药理学
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神经科学
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炎症研究
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分子生物学
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高影响因子
MEDIATORS OF INFLAMMATION
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2023
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IF 4.6
Zhousheng Yang,Tianyu Li,Chunyan Wang,Mingyu Meng,Shenglan Tan,Lei Chen
Dihydromyricetin (DMY), a natural flavonoid compound extracted from the stems and leaves of Ampelopsis grossedentata, has been found as a potential therapeutic chemical for treating atherosclerosis. This study explores the underlying mechanism of DMY repressing M1 macrophage polarization in atherosclerosis. We showed that DMY treatment markedly decreased M1 macrophage markers (e.g., Tnf-α and IL-1β) and p65-positive macrophage numbers in the vessel wall of Apoe-deficient (Apoe–/–) mice. Overexpression of miR-9 or knockdown of SIRT1 in macrophages reversed the effect of DMY on M1 macrophage polarization. The data we presented in the study indicate that the miR-9-mediated SIRT1/NF-κB pathway plays a pivotal role in M1 macrophage polarization and is one of the molecular mechanisms underlying the anti-atherosclerosis effects of DMY. We provide new solid evidence that DMY may be explored as a potential therapeutic adjuvant for treating atherosclerosis.
研究领域:
药理学
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免疫学
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心血管疾病
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2021
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IF 6.291
Lin Bai,Rundong Liu,Ruike Wang,Yongjuan Xin,Zuntao Wu,Yue Ba,Huizhen Zhang,Xuemin Cheng,Guoyu Zhou,Hui Huang
This study examined the neuroprotective properties of resveratrol (Res) and its target sirtuin1 (SIRT1) against lead (Pb)-mediated toxicity and discovered that both resveratrol treatment and SIRT1 overexpression restored blocked autophagic flux as well as reduced β-amyloid (Aβ) contents. Four-week-old male C57BL/6 mice were employed to consumed 0.2% Pb(Ac) 2 solution or deionized water for 3 months followed by 12 months of Res (50 mg/kg BW) or vehicle gavage. In in vitro study, SH-SY5Y cells were pretreated with the SIRT1 activator SRT1720 (2 μM) or the inhibitor EX527 (2 μM) for 2 h, then 25 μM of Pb(Ac) 2 was added and incubated for 48 h. Western blotting, RT-qPCR, enzyme-linked immunosorbent assay (ELISA), and Lyso-Tracker Red Staining were next used to estimate the potential alterations of the autophagic pathway as well as BACE1-mediated amyloid processing in response to Pb exposure, respectively. Our data revealed that Res treatment or SIRT1 activation resisted the induction of autophagy by Pb exposure through inhibition of LC3 and Beclin-1 expression and promoted the degradation of Aβ and Tau phosphorylation. Besides, the SIRT1 activator (SRT1720) downregulated the expression of BACE1, the rate-limiting enzyme for Aβ production, by inhibiting the activation of nuclear factor-κB (NF-κB) in Pb-treated SH-SY5Y cells, which resulted in reduced Aβ production. Collectively, we verified the role of Res-SIRT1-autophagy as well as the SIRT1-NF-κB-BACE1 pathway in Pb-induced neuronal cell injury by in vivo or in vitro models. Our findings further elucidate the important role of SIRT1 and Res in counteracting Pb neurotoxicity, which may provide new interventions and targets for the subsequent treatment of neurodegenerative diseases.
研究领域:
神经科学
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药理学
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毒理学
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高影响因子
Frontiers in Physiology
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2017
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IF 4.134
Zhang Lijie,Tu Runqi,Wang Yawei,Hu Yazhen,Li Xing,Cheng Xuemin,Yin Yanyan,Li Wenjie,Huang Hui
Pb is a potential risk factor for cognition, mainly mediated by enhanced oxidative stress. Resveratrol, a natural polyphenol with crucial anti-oxidative property, is recently implicated in preventing cognitive deficits in normal aging and neurodegenerative disorders. Its beneficial effects have been linked to sirtuin 1(SIRT1) activation. The aim of this work is to investigate the possible linkage between alterations in Pb-induced oxidative damage and cognitive impairment by prolonged treatment of resveratrol. Male C57BL/6 mice were given Pb(Ac)2 treatment or deionized H2O for 12 weeks, and subjected to resveratrol gavage at the dose of 50 mg/kgBw•d or vehicle after Pb exposure. Results from biochemical analysis and immunohistofluorescence showed that Pb induced oxidative DNA damage and decreased cortical antioxidant biomarker. As expected, these abnormalities were improved by resveratrol treatment. Morris water maze test, Western blotting, immunohistofluorescence staining and RT-qPCR indicated that resveratrol ameliorated spatial learning and memory deficits with alterations in hippocampal BDNF-TrkB signaling, promoted nuclear localization and phosphorylation of hippocampal SIRT1, partly increased protein levels of AMPK and PGC-1α involving in modulation of antioxidant response in Pb-exposed mice. Our results support the hypothesis that resveratrol could attenuate Pb-induced cognitive impairment which was associated with activating SIRT1 via modulation of oxidative stress. Additionally, resveratrol also repressed the Pb-induce amyloidogenic processing with resultant decline in cortical Aβ1−−40. Noteworthy, such effects were not mediated by resveratrol treatment alone. These findings emphasize the potential of SIRT1 activator as an efficacious dietary intervention to downgrade the Pb-induced neurotoxic lesion.
研究领域:
神经科学
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药理学
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毒理学
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分子生物学
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高影响因子
Oxidative Medicine and Cellular Longevity
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2021
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IF 6.543
Fangzhou Jiao,Yao Wang,Qian Chen,Pan Cao,Chunxia Shi,Maohua Pei,Luwen Wang,Zuojiong Gong
Hepatic encephalopathy (HE) is a neuropsychiatric disorder resulting from acute or chronic liver failure. This study is aimed at investigating the therapeutic effects and mechanisms of SIRT1 in thioacetamide- (TAA-) induced rat HE models. A selective activator (CAY10602) and inhibitor (EX527) of SIRT1 were used in this study. All male rats were separated into control, TAA, CAY10602+TAA, and EX527+TAA groups. Histological damage, liver function, serum ammonia, behavioral changes, and brain oxidative stress were measured in each group. Western blotting was used to measure SIRT1, NLRP3, ASC, and IL-1β protein expression. The results showed that CAY10602 alleviated liver injury, improved neurological decline, reduced microglial activation and brain oxidative stress, and improved the survival rates of HE rats. Moreover, CAY10602 inhibited activation of the NLRP3 inflammasome in microglia of the brain cortex in HE rats. Next, cell experiments confirmed that CAY10602 inhibited activation of the NLRP3 inflammasome in BV2 microglial cells. However, inhibition of SIRT1 by EX527 or lentivirus could enhance activation of the NLRP3 inflammasome in this process. Finally, CAY10602 reduced the neurotoxicity induced by high levels of ammonia in HT22 cells. Taken together, CAY10602 alleviates TAA-induced HE by suppressing microglial activation and the NLRP3 inflammasome and reducing the neurotoxicity of NH4Cl in HT22 cells. A pharmacologic activator of SIRT1 may be a promising approach for the treatment of HE.
研究领域:
药理学
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神经科学
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肝病学
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分子生物学
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Hao Li,Zhenyu Guan,Wendong Li,Xiaodan Zhang,Hongwei Tang,Jianjun Yang,Wenzhi Guo,Mingjie Ding
Background Hepatic ischemia-reperfusion injury (HIRI) remains a clinical challenge during liver surgery and transplantation, largely due to the lack of effective pharmacological interventions. Isolinderalactone (ILL), a sesquiterpene lactone, exhibits potent antioxidant and anti-inflammatory properties. However, its therapeutic potential for HIRI and its precise molecular targets, particularly regarding the SIRT1/IRE1α-mediated endoplasmic reticulum stress (ERS) pathway, remain to be elucidated. Objective This study aimed to determine the hepatoprotective effects of ILL against HIRI and investigate its regulatory mechanism centered on the SIRT1/IRE1α signaling axis. Methods HIRI was modeled in mice via ischemia/reperfusion (I/R) and in AML12 cells via hypoxia/reoxygenation (H/R). Cellular injury, oxidative stress, endoplasmic reticulum stress (ERS), apoptosis, and inflammatory responses were assessed using biochemical, histological, molecular, and cellular imaging techniques. The physical and functional interaction between ILL and SIRT1 was characterized through molecular docking, dynamics simulations, surface plasmon resonance, and enzymatic activity assays. The role of SIRT1 was further validated using genetic knockdown and pharmacological inhibition (EX527). Results ILL treatment significantly attenuated liver tissue damage, restored intracellular redox homeostasis, and mitigated ERS-induced inflammation and apoptosis. Mechanistically, ILL not only upregulated SIRT1 expression but also directly bound to SIRT1 to enhance its deacetylase activity, thereby suppressing the downstream IRE1α/TRAF2/JNK signaling cascade. Notably, SIRT1 silencing or pharmacological blockade with EX527 significantly blunted, albeit did not completely abolish, the protective effects of ILL, indicating that the SIRT1/IRE1α axis serves as a primary, though not exclusive, mediator of ILL's hepatoprotective activity. Conclusion ILL attenuates HIRI by simultaneously elevating SIRT1 expression and activating its deacetylase function, thereby restraining IRE1α-dependent ERS and subsequent hepatic injury. These findings highlight ILL as a promising therapeutic candidate for the management of perioperative HIRI.
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JOURNAL OF MOLECULAR HISTOLOGY
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2025
·Vol. 56
·期 6
·1-14
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IF 2.2
Wang Pu,Sun Congcong,Shi Chao,Gao Yong,Luan Chunyu,Yan Chao
Osteoarthritis (OA) is a degenerative joint disease characterized by pathological changes such as articular cartilage degeneration and bone hyperplasia. Mitochondrial dysfunction in chondrocytes has been identified as a critical factor contributing to the progression of OA. Although Evodiamine (Evo) has been demonstrated effeicacy in inhibiting inflammatory responses and matrix degradation in OA chondrocytes, its effects and underlying mechanisms regarding mitochondrial dysfunction in these cells remain to be elucidated. IL-1β was utilized to stimulate chondrocytes in order to establish an in vitro OA model. Subsequently, the proliferation, lactate dehydrogenase (LDH) release, and apoptosis of chondrocytes were systematically evaluated. Mitochondrial function in chondrocytes was evaluated by quantifying of ATP content, ROS level, mitochondrial DNA (mtDNA) copy number, activities of mitochondrial respiratory chain Complexes I and III, as well as mitochondrial membrane potential change. Furthermore, the protein expression levels of the SIRT1/PGC-1α signaling pathway were examined, and an intervention involving the SIRT1 inhibitor EX527 was conducted to elucidate the potential mechanisms underlying the effects of Evo on chondrocytes. Evo treatment significantly elevated the proliferation activity of IL-1β-stimulated chondrocytes, inhibited LDH release and apoptosis, increased mtDNA copy number and ATP content, enhanced the enzymatic activities of Complexes I and III, and suppressed ROS production as well as mitochondrial membrane potential loss. Furthermore, Evo treatment activated the SIRT1/PGC-1α signaling pathway. However, the addition of the SIRT1 inhibitor EX-527 partially attenuated the protective effects of Evo against IL-1β-induced chondrocyte injury by exacerbating mitochondrial dysfunction. Evo promotes mitochondrial biosynthesis, reduces ROS production and improves mitochondrial function by activating SIRT1/PGC-1α pathway, thereby inhibiting IL-1β-induced chondrocyte injury.
研究领域:
药理学
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分子生物学
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细胞生物学
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风湿病学
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线粒体医学
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