Journal of Ginseng Research
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2025
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IF 5.6
Risheng Zhao,Zhuoqun Wang,Chang Liu,Linxin Zhang,Min Zhang,Huizhu Du,Gege Yang,Haiming Sun,Wei Liu,Shuang Yan,Mengyang Wang
Background (20S)-Protopanaxatriol (PPT), a bioactive triterpenoid from Panax ginseng , has been used in Traditional Chinese Medicine (TCM) to tonify kidney yang and regulate blood pressure. The research aimed to elucidate PPT's protective effects against angiotensin II (Ang II)-induced renal injury. Methods A C57BL/6 mouse model of kidney injury was established by continuous infusion of Ang II for 4 weeks using an osmotic minipump. Treatment with PPT was initiated two weeks after Ang II infusion and administered daily for 14 days. Molecular docking, drug affinity response target stability (DARTS), and cellular thermal shift assay (CETSA) were employed to identify and validate potential targets of PPT in alleviating Ang II-induced renal injury. Additionally, biochemical assays, histopathological analysis, and Western blotting were performed to assess renal function, tissue damage, and signaling pathway modulation. Results Our findings demonstrated that PPT exerted protective effects against Ang II-induced renal dysfunction in mice by significantly attenuating renal fibrosis and inflammation. Mechanistically, PPT targeted PTPN1 and inhibited the AMPK/mTOR signaling pathway, thereby effectively alleviating autophagy dysregulation in both renal tissues of mice and Ang II-stimulated NRK-52E cells in vitro. Molecular docking, DARTS, and CETSA experiments confirmed PTPN1 as a direct target of PPT, providing a molecular basis for its renoprotective effects. Conclusion These findings validate ginseng's traditional use in kidney disorders and demonstrate PPT's potential as a therapeutic agent for hypertensive nephropathy by targeting PTPN1/AMPK/mTOR signaling. Further clinical exploration is needed to translate these results into practice.
研究领域:
药理学
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肾脏病学
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中医中药
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分子生物学
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信号转导
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PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2023
·
IF 5.6
Peng Cao,Yi Wang,Cong Zhang,Mitchell A. Sullivan,Wen Chen,Xiang Jing,Huifan Yu,Fei Li,Qu Wang,Zhongshi Zhou,Qi Wang,Wen Tian,Zhenpeng Qiu,Lianxiang Luo
The global incidence of nonalcoholic fatty liver disease (NAFLD) has been surging in recent years, however, no drug is currently approved to treat this disease. Quercetin, a natural flavonoid abundant in plants and fruits, has been reported to alleviate NAFLD, however, the exact molecular mechanism remains unclear. This study aims to further elucidate its potential mechanism of action. The beneficial effects and the underlying mechanism of quercetin in alleviating NAFLD were explored both in vitro and in vivo, by employing chemical inhibitors of autophagosomes (3-methyladenine, 3-MA), autolysosomes (chloroquine, CQ), AMPK (Compound C, CC) and SIRT1 (selisistat, EX-527). The levels of intracellular lipids, reactive oxygen species, mitochondria function, autophagy, and mitophagy were assessed by fluorescent labeling and examined using flow cytometry or confocal microscopy. Key protein expressions of autophagy, mitophagy, and inflammation were also determined. In vivo, quercetin was shown to dose-dependently effectively alleviate NAFLD, but intraperitoneal injection of 3-MA could block the beneficial effects of quercetin on body weight, liver weight, serum ALT/AST, hepatic ROS and inflammation. In vitro, quercetin could reduce intracellular lipids (Nile Red staining) and ROS/DHE accumulation, which could be also blocked by 3-MA or CQ. Furthermore, we found that CC could abrogate the protective effects of quercetin on lipid and ROS accumulation in vitro. Also, CC abolished the proautophagic and anti-inflammatory effects of quercetin, as shown by western blot determination and Lyso-Tracker labeling. Importantly, mitophagy, a specific form of mitochondria-targeted autophagy, was enhanced by quercetin, as demonstrated by PINK1/Parkin protein variation and immunofluorescence colocalization of autophagosomes and mitochondria, which could also be blocked by the intervention of CC. This study demonstrates that quercetin prevents NAFLD through AMPK-mediated mitophagy and suggests that promoting mitophagy via an upregulation of AMPK may be a promising therapeutic strategy against NAFLD.
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
Frontiers in Oncology
·
2021
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IF 6.244
Heng Yongqing,Liang Yupei,Zhang Junqian,Li Lihui,Zhang Wenjuan,Jiang Yanyu,Wang Shiwen,Jia Lijun
The neddylation pathway is overactivated in esophageal cancer. Our previous studies indicated that inactivation of neddylation by the NAE inhibitor induced apoptosis and autophagy in cancer cells. Camptothecin (CPT), a well-known anticancer agent, could induce apoptosis and autophagy in cancer cells. However, whether CPT could affect the neddylation pathway and the molecular mechanisms of CPT-induced autophagy in esophageal cancer remains elusive. We found that CPT induced apoptosis and autophagy in esophageal cancer. Mechanistically, CPT inhibited the activity of neddylation and induced the accumulation of p-IkBa to block NF-κB pathway. Furthermore, CPT induced the generation of ROS to modulate the AMPK/mTOR/ULK1 axis to finally promote protective autophagy. In our study, we elucidate a novel mechanism of the NF-κB/AMPK/mTOR/ULK1 pathway in CPT-induced protective autophagy in esophageal cancer cells, which provides a sound rationale for combinational anti-ESCC therapy with CPT and inhibition AMPK/ULK1 pathway.
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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DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2023
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IF 7.4
Huadong Zhao,Ying Chen,Lu Qian,Luyang Du,Xue Wu,Ye Tian,Chao Deng,Shuai Liu,Wenwen Yang,Chenxi Lu,Yan Zhang,Jun Ren,Yang Yang
Cardiac dysfunction is a common complication in patients with sepsis triggering high morbidity and mortality. Lycorine (LYC), the main effective monomer component extracted from Lycoris bulbs, possesses antiviral, anti-inflammatory, analgesic , liver protection properties. In this study, the effect of LYC pre- and post-treatment as well as the underlying mechanism were evaluated in the cecal ligation and puncture (CLP) model of Balb/c mice. The survival rate, anal temperature, sepsis score, blood biochemical/routine indicators, cardiac function, sepsis-related pathophysiological processes, and AMPK signaling in septic mice were observed by echocardiography , histological staining, western blot , qPCR, and etc. LYC pretreatment attenuated myocardial injury in septic mice by improving survival rate, sepsis score, blood biochemical/routine indicators, cardiac function and structure, inhibiting inflammation and oxidative stress , improving mitochondrial function, modulating endoplasmic reticulum stress , and activating AMPK pathway. In particular, AMPK deficiency and AMPK inhibitor (Compound C) partially reversed the protective effects of LYC in septic mice. In addition, LYC posttreatment also has slight protective phenotypes on septic myocardial injury, but the effect is not as ideal as pretreatment. Taken together, these findings suggest that LYC may be a potential drug for the treatment of sepsis.
研究领域:
药理学
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免疫学
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心脏病学
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分子生物学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2024
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IF 3.9
Chengping Kang,Qianqian Xiao,Xiaoxia Wang,Wanqian Guo,Haoran Zhang,Lilan Yuan,Zhe Zhao,Weidong Hao
Chlormequat chloride (CCC), a widely used plant growth regulator, is a choline analogue that has been shown to have endocrine-disrupting effects. Previous studies have shown that maternal exposure to CCC could induce hyperlipidemia and growth disruption in rat offspring. This study aims to further investigate the effects of peripubertal exposure to CCC on pubertal development and lipid homeostasis, as well as the underlying mechanisms. In vivo , male weanling rats were exposed to CCC (0, 20, 75 and 200 mg/kg bw/day) from post-natal day 21 to 60 via daily oral gavage. The results in rats showed that 75 mg/kg CCC treatment induced hepatic steatosis, predominantly microvesicular steatosis with a small amount of macrovesicular steatosis, in rat livers and 200 mg/kg CCC treatment induced liver damage including inflammatory infiltration, hepatic sinusoidal dilation and necrosis. In vitro , HepG2 cells were treated with CCC (0, 30, 60, 120, 240 and 480 μg/mL) for 24 h. And the results showed that CCC above 120 μg/mL induced an increase in triglyceride and neutral lipid levels of HepG2 cells. Mechanism exploration revealed that CCC treatment promoted the activation of mTOR/SREBP1 signalling pathway and inhibited activation of AMPK in both in vivo rat livers and in vitro HepG2 cells. Treatment with AMPK activator Acadesine (AICAR) could alleviate the lipid accumulation in HepG2 cells induced by CCC. Collectively, the present results indicate that CCC might induce hepatic steatosis by promoting mTOR/SREBP1 mediated lipogenesis via AMPK inhibition.
研究领域:
药理学
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毒理学
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内分泌学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Nutrients
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2022
·Vol. 14
·期 12
·2413
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IF 6.706
Jiaqiao Li,Yameng Fan,Yan Zhang,Yamei Liu,Yan Yu,Mao Ma
Resveratrol (RSV) has been reported to induce autophagy and apoptosis in non-small-cell lung cancer A549 cells, and the nerve growth factor receptor (NGFR) regulates autophagy and apoptosis in many other cells. However, the effect of NGFR on autophagy and apoptosis induced by RSV in A549 cells remains unclear. Here, we found that RSV reduced the cell survival rate in time- and concentration-dependent manners, activating autophagy and apoptosis. Lethal autophagy was triggered by RSV higher than 55 μM. The relationship between autophagy and apoptosis depended on the type of autophagy. Specifically, mutual promotion was observed between apoptosis and lethal autophagy. Conversely, cytoprotective autophagy facilitated apoptosis but was unaffected by apoptosis. RSV enhanced NGFR by increasing mRNA expression and prolonging the lifespan of NGFR mRNA and proteins. RSV antagonized the enhanced autophagy and apoptosis caused by NGFR knockdown. As the downstream pathway of NGFR, AMPK-mTOR played a positive role in RSV-induced autophagy and apoptosis. Overall, RSV-induced autophagy and apoptosis in A549 cells are regulated by the NGFR-AMPK-mTOR signaling pathway.Keywords:resveratrol;non-small-cell lung cancer;A549 cell line;autophagy;apoptosis;NGFR-AMPK-mTOR pathway
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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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Huanqi Zhang,Xiaozhe Chen,Fuqing Liu,Yanju Bi,Meichen Gao,Xiaojing Li
Long-term environmental exposure to chlorpyrifos (CPF) can cause intestinal damage. Baicalein (BAI) helps aquatic organisms resist environmental pollution stress. Adenosine 5′-monophosphate activated protein kinase (AMPK) is a key molecule in energy regulation; however, the mechanism by which BAI inhibits CPF-induced autophagy/ferroptosis remains unclear. Based on reported environmental concentrations and IC 50 values of CPF, we established models using the midgut of carp and Epithelioma papulosum cyprini (EPC) cells exposed to CPF with or without BAI treatment. Transcriptomics and network pharmacology were used to analyze the key pathways affected by CPF and BAI. Tissue damage, cell cycle regulation, autophagy, ferroptosis, and mitochondrial function were assessed. The effect of BAI on AMPK–unc-51-like autophagy-activating kinase 1 (ULK1) binding was confirmed by molecular dynamics simulation, co-immunoprecipitation, and laser confocal analysis. In addition, the regulatory impact of an AMPK activator on the autophagy/ferroptosis axis was examined. Results indicated that BAI alleviated CPF-induced pathological changes and mitochondrial damage. CPF exposure caused tight junction disruption, mitochondrial depolarization, and reactive oxygen species and mitochondrial reactive oxygen species production. Transcriptomic analysis revealed that CPF toxicity is related to phagosomes, cell cycle regulation, and ferroptosis. By targeting AMPK, BAI prevents the formation of the AMPK–ULK1 complex and inhibits the CPF-induced cascade involving excessive autophagy, cell cycle arrest, and ferroptosis. In conclusion, BAI targets AMPK to prevent binding with ULK1, thereby suppressing the CPF-activated autophagy/ferroptosis axis, reversing mitochondrial dysfunction, and restoring intestinal homeostasis.
研究领域:
环境毒理学
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分子生物学
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药理学
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细胞生物学
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生态毒理学
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DOI
PubMed
高影响因子
Journal of Inflammation Research
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2025
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IF 4.1
Han-Xu Zhu,Jin-Ling Ren,Wen-Juan Cao,Rui Wang,Lei-Lei Chen,Qing Gao,Ye-Bo Zhou
Background Atherosclerotic cardiovascular diseases (CVD) are commonly found in obesity. Endothelial inflammation accompanied by oxidative stress is a crucial risk factor and a key initiating step for the pathogenesis of atherosclerosis (AS). In the present study, the role and mechanism of intermedin (IMD), a potent active peptide, in endothelial damage in AS in obese apolipoprotein E-deficient (apoE−/−) mice were investigated.Methods and Results In vivo, IMD1-53 was infused via Alzet mini-osmotic pump in apoE−/− mice with high-fat diet (HFD) for 4 weeks. In vitro, palmitic acid (PA) and oxidized low density lipoprotein (Ox-LDL) were used to stimulate human umbilical vein endothelial cells (HUVECs) for exploring the potential mechanism of IMD1-53 action on endothelial damage. We found that IMD1-53 application remarkably improved plasma lipid profiles, hepatic lipid accumulation and its cholesterol levels, and vascular lipid accumulation and lesion sizes. Moreover, IMD1-53 markedly increased eNOS expression and decreased the levels of vascular inflammatory factors and ROS. In vitro, the combination of PA and Ox-LDL caused more severe inflammatory and oxidative damages and lower expression of eNOS, which were significantly inhibited by IMD1-53. IMD1-53 notably induced AMPK phosphorylation, and the inhibition of AMPK activation markedly reversed the anti-inflammatory and antioxidant effects of IMD1-53 on PA and Ox-LDL-treated HUVECs.Conclusion IMD1-53 improves AS partially by reducing endothelial inflammatory and oxidative damage via AMPK signaling pathway and decreasing vascular lipid accumulation involving the improvement of lipid profiles in blood and in liver in a state of obesity.
研究领域:
心血管疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Probiotics and Antimicrobial Proteins
·
2025
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IF 4.4
Zhao Yuting,Xie Weiqi,Duan Jingyi,Li Fei
Limosilactobacillus reuteri DSM 17938 ( L. reuteri DSM 17938) was one of the most widely used probiotics in humans for gastrointestinal disorders, but few studies have investigated its role in drug-induced liver injury (DILI). Here, we evaluated the efficacy of L. reuteri DSM 17938 using a mouse model of DILI induced by triptolide. Pregavage of L. reuteri DSM 17938 for 1 week remarkably lowered hepatic inflammatory cytokines level and oxidative stress, with diminished serum alanine transaminase and aspartate aminotransferase levels. Metabolomics and RT-qPCR analysis confirmed its ability in ameliorating TP-disrupted hepatic fatty acid β oxidation. Genome annotation of L. reuteri showed its ability to modulate energy metabolism. Targeted metabolomics demonstrated that L. reuteri DSM 17938 modified the short fatty acid profiles in cecum, especially enhancing propionate levels. Further experiments found that L. reuteri DSM 17938 can activate AMPK signaling by upregulating gut microbiota–derived propionate level, thus restoring impaired mitochondrial biogenesis and energy supply processes to recover energy homeostasis, which leads to diminished ROS production and oxidative stress injury in hepatocytes. Besides, AMPK inhibitor dorsomorphin abolished all the effects on propionate protecting mitochondria and energy metabolism. This study established probiotic therapy of L. reuteri DSM 17938 as a preventive intervention for DILI in clinical. We also revealed that L. reuteri DSM 17938 can activate AMPK signaling by propionate, facilitating a deeper understanding of the action mechanism of L. reuteri DSM 17938 against acute liver injury and contributing to the development of its postbiotics and wider applications. Graphical Mechanism illustration of Limosilactobacillus reuteri DSM 17938 alleviating TP-induced liver injury by enhancing AMPK signaling pathway via propionate (Created with Biorender. com).
研究领域:
医学
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微生物学
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代谢组学
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PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2023
·
IF 2.4
Ce XU,Jiahui HAN,Di JIA,Jimin CAI,Jianming YUAN,Xin GE
Increasing studies have suggested that oxidative stress and inflammation play momentous roles in acute pulmonary embolism (APE). Honokiol, a bioactive biphenolic phytochemical substance, is known for its strong anti-oxidative and anti-inflammatory effects and here serves as an activator of sirtuin3 (SIRT3). The purposes of the study are to explore the effects of Honokiol on APE rats, and investigate whether the function of Honokiol is mediated by SIRT3 activation. In this study, the rats received a right femoral vein injection with dextran gel G-50 particles (12 mg/kg) to establish the APE model, which were administrated with Honokiol and/or selective SIRT3 inhibitor 3- (1H-1, 2, 3-triazol-4-yl) pyridine (3-TYP; 5 mg/kg) intraperitoneally. The data showed that SIRT3 activation by Honokiol attenuated the loss in lung function, ameliorated inflammatory response and oxidative damage as well as inhibited apoptosis in lung tissues of the rats with APE, which was reversed by 3-TYP. In addition, we found AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway might be activated by Honokiol but restrained by 3-TYP. These results indicated that Honokiol was capable of suppressing APE’s adverse effects, which was diminished by SIRT3 suppression, implying that activation of SIRT3 might serve as a therapeutic method for APE.
研究领域:
药理学
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肺科学
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分子生物学
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DOI
PubMed
高影响因子
Metallomics
·
2019
·Vol. 11
·期 7
·1200-1206
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IF 3.571
Huang Hui,Zhou Mengxue,Ruan Lifo,Wang Dongqing,Lu Huiru,Zhang Jiayu,Chen Jun,Hu Yi,Chai Zhifang
Environmental factors may play a critical role in the etiology and pathogenesis of Parkinson's disease (PD). However, the association of PD with specific chemical species remains largely unknown. Here we prepared three kinds of iron oxide nanoparticles and examined their cytotoxicity in a cellular model of PD. We found that lysosome-targeted nanoparticles showed significant cytotoxicity in SH-SY5Y cells. Inhibition of AMPK could aggravate the neurotoxicity of lysosome-targeted nanoparticles as well as mitochondrion-targeted nanoparticles. Alteration of mitochondrial membrane potentials was found to be in agreement with the neurotoxicity of iron nanoparticles. These results suggested an important role of AMPK in regulating iron nanoparticle-associated neurotoxicity.
研究领域:
神经科学
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毒理学
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纳米技术
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Geriatric Cardiology
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2022
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IF 3.189
Peng-Zhou HANG,Pei-Feng LI,Jie LIU,Feng-Feng LI,Ting-Ting CHEN,Yang PAN,Man-Ru ZHANG,Hua-Qing YU,Hong-Yu JI,Zhi-Min DU,Jing ZHAO
BACKGROUND Pathological cardiac hypertrophy is a compensated response to various stimuli and is considered a key risk factor for heart failure. 7,8-Dihydroxyflavone (7,8-DHF) is a flavonoid derivative that acts as a small-molecule brain-derived neurotrophic factor mimetic. The present study aimed to explore the potential role of 7,8-DHF in cardiac hypertrophy. METHODS Kunming mice and H9c2 cells were exposed to transverse aortic constriction or isoproterenol (ISO) with or without 7,8-DHF, respectively. F-actin staining was performed to calculate the cell area. Transcriptional levels of hypertrophic markers, including ANP, BNP, and β-MHC, were detected. Echocardiography, hematoxylin-eosin staining, and transmission electron microscopy were used to examine the cardiac function, histology, and ultrastructure of ventricles. Protein levels of mitochondria-related factors, such as adenosine monophosphate-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), were detected. RESULTS 7,8-DHF inhibited compensated and decompensated cardiac hypertrophy, diminished the cross-sectional area, and alleviated the mitochondrial disorders of cardiomyocytes. Meanwhile, 7,8-DHF reduced the cell size and repressed the mRNA levels of the hypertrophic markers of ISO-treated cardiomyocytes. In addition, 7,8-DHF activated AMPK and PGC-1α signals without affecting the protein levels of mitochondrial dynamics-related molecules. The effects of 7,8-DHF were eliminanted by Compound C, an AMPK inhibitor. CONCLUSIONS These findings suggest that 7,8-DHF inhibited cardiac hypertrophy and mitochondrial dysfunction by activating AMPK signaling, providing a potential agent for the treatment of pathological cardiac hypertrophy.
研究领域:
心脏病学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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