BRAIN RESEARCH BULLETIN
·
2024
·
IF 3.5
Zhijuan Cheng,Jianglong Tu,Kai Wang,Fang Li,Yuan He,Wei Wu
Cerebral ischemia-reperfusion (IR) is the main pathophysiological process after stroke and can seriously impair neurological function. Wogonin, a natural flavonoid extracted from the roots of Scutellaria baicalensis, has potent anti-inflammatory properties. In this study, we investigated the protective mechanism of wogonin against middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) model-induced cerebral IR injury through adenosine 5‘-monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome axis. Our results showed that wogonin (20 mg/kg, intraperitoneal injection) effectively reduced infarct size, attenuated brain edema, improved neurological deficits, and alleviated histopathological damage. In addition, wogonin reduced microglial cell activation and inflammatory factors, including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10, in brain tissue and serum after cerebral IR injury. Wogonin also effectively activated the AMPK/SIRT1 signaling pathway and inhibited NLPR3 inflammasome-related molecules upregulation in cerebral IR injury as well as in OGD/R-stimulated HT-22 cells. Furthermore, inhibition of the AMPK/SIRT1 signaling pathway by Compound C, an AMPK inhibitor, significantly reversed the protective effect of wogonin on OGD/R-induced NLRP3 inflammasome. Meanwhile, the protective effect of wogonin against brain IR injury was also reversed in the presence of compound C. These results suggest that wogonin ameliorates cerebral IR injruy-induced inflammation by inhibiting NLRP3 inflammasome through the AMPK/SIRT1 signaling pathway.
研究领域:
神经科学
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药理学
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炎症研究
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Ya Zhang,Qifang Wu,Jian Liu,Zhongshan Zhang,Xiaojing Ma,Yaoyue Zhang,Jiawen Zhu,Ronald W. Thring,Mingjiang Wu,Yitian Gao,Haibin Tong
Insulin resistance is a characteristic feature of type 2 diabetes. Sulforaphane (SFN) is a natural antioxidant extracted from the cruciferous vegetables. Recent study reported that SFN exhibits excellent anti-diabetic effects, however, the underlying mechanism is still unclear. This study aimed to investigate the therapeutic effects of SFN on a high-fat diet (HFD)-induced insulin resistance and potential mechanism. SFN was found to effectively reduce body weight, fasting blood glucose and hyperlipidemia, and improve liver function in HFD-fed mice. Furthermore, SFN effectively increased glucose uptake and improved insulin signaling in palmitic acid (PA)-induced HepG2 cells. SFN also led to increased expression of antioxidant genes downstream of Nrf2 and decreased accumulation of lipid peroxides MDA and 4-HNE, both in vivo and in vitro. Further studies revealed that SFN significantly reduced glutathione peroxidase 4 (GPx4) inactivation-mediated oxidative stress by activating the AMPK and Nrf2 signaling pathways. In PA-induced HepG2 cells and flies , the alleviation of insulin resistance by SFN was diminished by GPx4 inhibitor. Taken together, SFN ameliorated HFD-induced insulin resistance by activating the AMPK-Nrf2-GPx4 pathway, providing new insights into SFN as a therapeutic compound for the alleviation of insulin resistance.
研究领域:
药理学
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内分泌学
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分子生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
PHARMAZIE
·
2018
·Vol. 73
·期 10
·594-597
·
IF 1.016
Wu Bo,Chen Xi,Zhou Ying,Hu Pingjun,Wu Dan,Zheng Guodong,Cai Yi
Background: Andrographolide (Andro) belongs to the main bioactive ingredients of Andrographis paniculata. Many studies have shown that andro has a variety of pharmacological activities such as anti-inflammatory, anti-bacterial, anti-virus, anti-oxidant, immune regulation
and liver protective effects. Moreover andro has been reported to have anticancer activity in multiple types of cancer, including gastric cancer, breast cancer, lung cancer and so on. However, there is no report about the effect of andro on the human NPC cell line C666-1 and the molecular
mechanisms of andro-mediated apoptosis in C666-1 cells remain to be clarified. Methods: Cell proliferation was measured by a CCK8 assay, cell apoptosis rate was evaluated by flow cytometric analysis, and the protein expression of LKB1/AMPK signaling pathways was detected by Western
blotting. Results: Treatment with andro inhibited cell proliferation and induced apoptosis of C666-1 cells. Moreover, andro could activate LKB1-AMPK signaling. We also demonstrated that Ca2+/calmodulin-dependent protein kinase kinaseβ (CaMKKβ) was not involved in
the regulation of andro on AMPK activation in C666-1 Cells. Conclusions: Andro suppressed proliferation and induced apoptosis of C666-1 cells through regulating the LKB1/AMPK/mTOR signal pathway.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Yuan Liu,Xiaohui Jin,Caiyin Li,Jingjing Bu,Baoying Wang,Ming Bai,Pan Su,Erping Xu,Yucheng Li
Defective mitophagy is closely related to the neuronal dysfunction and major depressive disorder (MDD). Our previous study found that baicalin could enhance nip-like protein (NIX)-mediated mitophagy and exhibit antidepressant effects, and predicted that AMPK may be the pharmacological target of baicalin. However, validated experiments are lacking. In the present study, we first demonstrated the effect of baicalin on hippocampal NIX-mediated mitophagy in CORT-induced depressive mice. Secondly, we transfected siRNA to knockdown AMPK, PGC-1α, and NIX respectively in HT22 cells, and detected the effects of baicalin on mitochondrial function, AMPK/PGC-1α/NIX pathway protein expression and mitophagy levels. Finally, AAV-shAMPKα was injected into hippocampal CA3 to knockdown AMPK in mice to validate the antidepressant effects of baicalin in vivo. The results showed that CORT induced depressive-like behaviors, accompanied with neuronal damage, mitochondrial injury, and inhibited mitophagy in the hippocampus, which were prevented by baicalin (20 mg/kg) treatment. In HT22 cells, baicalin remarkably ameliorated mitochondrial dysfunction and mitophagy disturbance induced by CORT, and these protective effects of baicalin were blocked by knockdown of AMPK, PGC-1α and NIX. Moreover, the beneficial effects of baicalin on depressive-like behaviors and NIX-mediated mitophagy were suppressed by knockdown of AMPKα in mice. Our present results further demonstrated that baicalin promotes NIX-mediated mitophagy and improves depression in an AMPK-dependent manner.
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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抑郁症
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Lijiao Zhao,Heyun Zhu,Haoye Li,Shuaihao Guo,Jingchun Wang,Zhaoxin Tang,Jianzhao Liao,Jianying Guo
Nano-copper (nanoCu), a nanoscale form of copper (Cu), has been widely applied in the animal husbandry industry. However, it is of great concern that the Cu exposure to humans and animals can cause toxic damage to multiple organs. Hesperidin (Hes), a flavonoid found in citrus fruits, has shown mitigating effects on various organ damages. In our study, we aimed to investigate the toxic effects of nanoCu exposure on the kidneys of chickens and the therapeutic efficacy of Hes in nanoCu-induced renal injury. Our results indicated that Hes could alleviate endoplasmic reticulum stress (ERS) caused by nanoCu exposure. Intriguingly, nanoCu significantly disrupted endoplasmic reticulum (ER) homeostasis, which manifested as increased levels of key proteins such as GRP78, PERK, and CHOP, as well as elevated H 2 O 2 levels. But Hes treatment exhibited an opposite trend. Furthermore, nanoCu significantly induced autophagy in renal cells, which was accompanied by the activation of the AMPK-AKT/mTOR pathway and a concurrent increase in the protein levels of ATG5, Beclin 1, LC3 Ⅱ/LC3 Ⅰ, and ULK1, along with a decrease in the level of p62. However, it can be reversed by Hes treatment. These findings suggest that Hes could mitigate ER homeostasis disruption and autophagy caused by nanoCu exposure, providing new insights into the pharmacological treatment of Hes in related health issues.
研究领域:
动物医学
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毒理学
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药理学
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产品关联
DOI
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2021
·
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.
研究领域:
药理学
·
生物化学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Bo Yu,Dongna Liu,Hongli Zhang,Di Xie,Wei Nie,Kaiyao Shi,Ping Yang
Left ventricular hypertrophy (LVH) is a pathological characteristic shared by distinct heart disorders. Atorvastatin is employed as a lipid lowering agent and its heart protection effect has been recently reported as well. Thus, the current study attempted to validate the anti-hypertrophy effect of atorvastatin as well as the associated mechanism. Hypertrophic feature was induced in rats using transverse aortic constriction (TAC) method and in cardiomyocytes using angiotensin II (Ang II). Then the animals and cells were treated with atorvastatin and the effect on cardiac weight and structure as well as cell viability, surface area, and apoptosis was assessed. The mechanism associated with the anti-hypertrophy effect of atorvastatin was further explored by focusing on the AMPK/Foxo1/miR-143-3p axis. The results showed that the administration of atorvastatin significantly suppressed TAC-induced heart weight increase and attenuated cardiac structure deteriorations in rats. In in vitro assays, atorvastatin increased cell viability, and reduced cell surface area and apoptosis in Ang II-treated H9c2 cells. At molecular level, atorvastatin activated AMPK, which further promoted Foxo1 activation and suppressed miR-143-3p level. The key role of AMPK during atorvastatin treatment was further validated by subjecting Ang II-treated H9c2 cells to co-incubation of atorvastatin and Compound C, which blocked the pro-survival and anti-hypertrophy effect of atorvastatin on H9c2 cells. The findings outlined in the current study confirmed the anti-hypertrophy effect of atorvastatin and provided a preliminary explanation on the mechanism associated with the treatment: the protective effect of atorvastatin on myocardium against hypertrophy depended on miR-143-3p inhibition via AMPK and Foxo1 activation.
研究领域:
心脏病学
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分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2024
·
IF 4.5
Kelin Li,Victoria A. Uyanga,Xiaojuan Wang,Hongchao Jiao,Jingpeng Zhao,Yunlei Zhou,Haifang Li,Hai Lin
Scope Allicin, a product of enzymatic reaction when garlic is injured, plays an important role in maintaining glucose homeostasis in mammals. However, the effect of allicin on glucose homeostasis in the state of insulin resistance remains to be elucidated. This study investigates the effect of allicin on glucose metabolism using different muscle fibers in a chicken model. Methods and results Day-old male Arbor Acres broilers are randomly divided into three groups and fed a basal diet supplemented with 0, 150, or 300 mg kg −1 allicin for 42 days. Results show that allicin improves the zootechnical performance of broilers at the finishing stage. The glucose loading test (2 g kg −1 body mass) indicates the regulatory role of allicin on glucose homeostasis. In vitro results demonstrate allicin increases glutathione (GSH) level and the expression of cystathionine γ lyase (CSE), leading to endogenous hydrogen sulfide (H 2 S) production in M. pectoralis major (PM) muscle-derived myotubes. Allicin stimulates adenosine monophosphate-activated protein kinase (AMPK) S-sulfhydration and AMPK phosphorylation to promote glucose uptake, which is suppressed in the presence of d , l -propargylglycine (PAG, a CSE inhibitor). Conclusion This study demonstrates that allicin induces AMPK S-sulfhydration and AMPK phosphorylation to promote glucose uptake via the CSE/H 2 S system in a muscle fiber-dependent manner.
研究领域:
动物科学
·
营养学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AFFECTIVE DISORDERS
·
2025
·
IF 4.9
Siqi Sun,Jingtong Rong,Chao Wang,Ruiling Li,Honghan Zhang,Wei Wang,Hao Duan,Zhaowen Nie,Dan Xiang,Zhongchun Liu
Background Major depressive disorder (MDD) is a severe, and often treatment-resistant, psychiatric disorder. Mesenchymal stem cell-derived exosomes have been shown to be neuroprotective. Here we employed adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) as a novel therapeutic approach for depressive-like behavior in mice and explored the underlying mechanisms. Methods ADSC-Exos were administered intranasally to mice subjected to chronic restraint stress to assess behavioral changes and neuroprotection in terms of apoptosis, AMPK-mTOR signaling, and NLRP3 pathway activation by western blotting, microglial activation by immunofluorescence, and changes in serum inflammatory factors by ELISA. The effects of ADSC-Exos were also studied in vitro in HT22 cells. Results ADSC-Exos significantly improved depressive-like behavior, anxiety-like behavior, and cognitive function in mice. ADSC-Exos had significant neuroprotective effects, including reducing neuronal apoptosis and promoting autophagy by activating AMPK-mTOR signaling, ultimately reducing neuroinflammation. In vitro, ADSC-Exos inhibited corticosterone-induced apoptosis, activated autophagy in an AMPK pathway-dependent manner, and inhibited NLRP3 inflammasome activation. Conclusion ADSC-Exos may be a potential treatment for MDD by alleviating depressive-like behaviors and protecting against tissue injury, possibly through activation of AMPK-mTOR signaling and inhibition of NLRP3 inflammasome-mediated neuroinflammation.
研究领域:
神经科学
·
细胞生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2017
·Vol. 38
·期 7
·998-1008
·
IF 3.223
Zhou Bing,Zhou Dan-li,Wei Xiao-hong,Zhong Rong-yu,Xu Jie,Sun Liao
Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is not completely understood, the increased influx of free fatty acids (FFAs) into the liver and the FFA-induced hepatic endoplasmic reticulum (ER) stress are two crucial pathogenic processes in the initiation and development of NAFLD. In this study we investigated the effects of astragaloside IV (AS-IV), a bioactive compound purified from Astragali Radix , on FFA-induced lipid accumulation in hepatocytes and elucidated the underlying mechanisms. Human HepG2 cells and primary murine hepatocytes were exposed to FFAs (1 mmol/L, oleate/palmitate, 2:1 ratio) with or without AS-IV for 24 h. Exposure to FFAs induced marked lipid accumulation in hepatocytes, whereas co-treatment with AS-IV (100 μg/mL) significantly attenuated this phenomenon. Notably, AS-IV (50–200 μg/mL) concentration-dependently enhanced the phosphorylation of AMPK, acetyl-CoA carboxylase (ACC) and SREBP-1c, inhibited the accumulation and nuclear translocation of mature SREBP-1 and subsequently decreased the mRNA levels of lipogenic genes including acc1 , fas and scd1 . AS-IV treatment also concentration-dependently attenuated FFA-induced hepatic ER stress evidenced by the reduction of the key markers, GRP78, CHOP and p-PERK. Pretreated the cells with the AMPK inhibitor compound C (20 μmol/L) greatly diminished these beneficial effects of AS-IV. Our results demonstrate that AS-IV attenuates FFA-induced ER stress and lipid accumulation in an AMPK-dependent manner in hepatocytes, which supports its use as promising therapeutics for hepatic steatosis.
研究领域:
药理学
·
肝病学
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细胞生物学
·
代谢疾病
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DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 14
·7560-7571
·
IF 6.317
Shuai Lu,Jinyi Zhou,Chen Yang,Xiaoxue Zhang,Yingying Shi,Jie Liu,Xintong Yan,Juanjuan Liang,Xianli Liu,Lan Luo,Da Zhou,Zhimin Yin
Aging is a natural process accompanied by inflammation and oxidative stress and is closely associated with age-related diseases. As a direct precursor of glutathione, γ-glutamylcysteine (γ-GC) possesses antioxidant and anti-inflammatory properties; however, whether γ-GC plays an important role in anti-aging remains unknown. Here, we investigated the protective effects and mechanisms of γ-GC in D-galactose (D-gal)-induced senescence in PC12 cells and aging mice. Our results showed that γ-GC treatment significantly reduced the percentage of senescence-associated-β-galactosidase (SA-β-Gal)-positive cells and inhibited D-gal-induced cell cycle arrest in PC12 cells. The results of Nissl and hematoxylin and eosin (H&E) staining in mouse brain showed that γ-GC treatment markedly reversed the damage in the hippocampus of D-gal-induced aging mice. Moreover, γ-GC increased the phosphorylation of AMP-activated protein kinase (AMPK) to promote the nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) while inhibiting the nuclear translocation of deleted in breast cancer 1 (DBC1), which leads to the activation of sirtuin 1 (SIRT1) and deacetylation of p53 in the nucleus. Therefore, γ-GC may be a potential therapeutic candidate compound for the prevention and treatment of age-related diseases.
研究领域:
药理学
·
衰老
·
神经科学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2023
·
IF 4.7
Zhiying Miao,Zhiruo Miao,Shuang Feng,Shiwen Xu
Chlorpyrifos (CPF) is a typical organophosphate insecticide known to has serious toxicological effects on aquatic animals and causes many environmental contamination problems. To assess the effects of CPF on the epithelioma papulosum cyprini (EPC) cells of the common carps from the point of calcium ion (Ca 2+ ) transport, the CPF-exposed EPC models were primarily established, and both AO/EB staining and Annexin V/PI assay with flow cytometry analysis were subsequently implemented to identify that CPF-induced EPC cell apoptosis, in consistent with the up-regulated expression of BAX, Cyt- c , CASP3 and CASP9, and down-regulated BCL-2 expression. Then, Mag-Fluo-4 AM, Fluo-4 AM and Rhod-2 AM staining probes were co-stained with ER-Tracker Red and Mito-Tracker Green applied to image cellular Ca 2+ flux, illuminating Ca 2+ depleted from ER and flux into mitochondria, resulting in ER stress and mitochondrial dysfunction. Additionally, 2-Aminoethyl Diphenylborinate (2-APB), 4-Phenylbutyric acid (4-PBA) and Dorsomorphin (Compound C) were performed as the inhibitor of Ca 2+ transition, ER stress and AMPK phosphorylation, suggesting CPF-mediated Ca 2+ overload triggered ER stress. And the over-generation of Mito-ROS intensified oxidative stress , promoting the phosphorylation of AMPK and deteriorating cell apoptotic death. The results of this study demonstrated Ca 2+ overload-dependent mitochondrial dysfunction engages in the CPF-induced apoptosis, providing a novel concept for investigating the toxicity of CPF as environmental pollution on aquatic organisms .
研究领域:
毒理学
·
环境科学
·
细胞生物学
·
水生生物学
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产品关联
DOI
PubMed
高影响因子
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