JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2018
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IF 3.412
Fuqiang Liang,Yajing Fang,Weiwei Cao,Zhuo Zhang,Siyi Pan,Xiaoyun Xu
The current study evaluates the protective effects of tangeretin, a representative polymethoxyflavone (PMF) mainly isolated from the peels of citrus fruits, against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells and the potential mechanisms of this protection. Tangeretin suppressed t-BHP-induced oxidative damage, as evaluated by cell viability, reactive-oxygen-species (ROS) levels, lactate dehydrogenase (LDH) leakage and glutathione (GSH) levels. Further mechanistic studies showed that tangeretin up-regulated the expression of heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Moreover, tangeretin induced antioxidant-responsive-element (ARE)-dependent luciferase activation, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation, and mitogen-activated-protein-kinase (MAPK) phosphorylation. Results in the study indicate that the protective effects of tangeretin may be at least partly due to its capacity to up-regulate the antioxidant enzymes NQO1 and HO-1 via the MAPK–Nrf2–ARE signaling pathway. Tangeretin may play an effective protective role in liver injury.
研究领域:
药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Minghao Sun,Weiwei Liu,Yuanyuan Ma,Pengfei Ni,Wenjing Yao,Yingjie Xu,Rui Bao,Jue Wang,Fei Xiong,Xihe Kuang,Teng Zhang,Xiaochen Zhang,Xikuang Yao,Shenghong Ju,Wenpei Fan
Chemodynamic therapy (CDT) efficacy in the tumor microenvironment (TME) remains compromised. Inspired by the potential of fever-like heat to activate a redox-favorable microenvironment, mild photothermal therapy (mPTT) is expected to sensitize tumors to CDT, turning “redox-cold” tumors into “redox-hot” ones. Herein, an injectable gel engine (LMFT@SG-R) is meticulously constructed based on the co-encapsulation of R848 and β-lapachone (LAP)-loaded metal–organic framework-199 (MOF-199) within a lipidic gel reservoir with the unique ability of thermally reversible sol–gel phase transformation. With mPTT reprogramming TME, the custom-designed LMFT@SG-R can realize systemic redox homeostasis remodeling through mPTT-activated chemodynamic immunotherapy (MPCIT). Once reaching the TME, LMFT@SG-R quickly hydrates into solid gel and subsequently undergoes gel-to-sol transformation under mild NIR laser irradiation, resulting in on-demand release of LMFT and R848 for controllable CDT and immunostimulation. LMFT undergoes stepwise degradation for sequential release of Fe 3+ , Cu 2+ and LAP, which can promote ROS cascade amplification owing to the upregulation of HSP70/NQO1 axis upon mild hyperthermia, resulting in robust ICD effects and T lymphocytes infiltrations together with R848. Notably, the controllable immunostimulation can facilitate robust abscopal effects and prominent suppression of distal tumors. The well-designed LMFT@SG-R may represent an updated CDT catalyst with the highly-integrated gel engine for chained-cooperative MPCIT.
研究领域:
癌症治疗
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生物医学工程
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免疫疗法
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化学生物学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOMEDICINE
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2024
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IF 6.7
Maoxing Pan,Yuanjun Deng,Yebei Qiu,Dajin Pi,Chuiyang Zheng,Zheng Liang,Jianwei Zhen,Wen Fan,Qingliang Song,Jinyue Pan,Yuanyou Li,Haizhen Yan,Qinhe Yang,Yupei Zhang
Background Non-alcoholic fatty liver disease (NAFLD) has emerged as a burgeoning health problem worldwide, but no specific drug has been approved for its treatment. Shenling Baizhu powder (SL) is extensively used to treat NAFLD in Chinese clinical practice. However, the therapeutic components and pharmacological mechanisms of SL against NAFLD have not been thoroughly investigated. Purpose This study aimed to investigate the pharmacological impact and molecular mechanism of SL on NAFLD. Methods First, we established an animal model of NAFLD by high-fat diet (HFD) feeding, and evaluated the therapeutic efficacy of SL on NAFLD by physiological, biochemical, pathological, and body composition analysis. Next, the effect of SL on autophagic flow in NAFLD rats was evaluated by ultrastructure, immunofluorescence staining, and western blotting. Moreover, an integrated strategy of targeted energy metabolomics and network pharmacology was performed to characterize autophagy-related genes and explore the synergistic effects of SL active compounds. UPLC-MS/MS, molecular docking combined with in vivo and in vitro experiments were conducted to verify the key compounds and genes. Finally, a network was established among SL-herb-compound-genes-energy metabolites-NAFLD, which explains the complicated regulating mechanism of SL on NAFLD. Results We discovered that SL decreased hepatic lipid accumulation, hepatic steatosis, and insulin resistance, and improved systemic metabolic disorders and pathological abnormalities. Subsequently, an integrated strategy of targeted energy metabolomics and network pharmacology identified quercetin, ellagic acid, kaempferol, formononetin, stigmasterol, isorhamnetin and luteolin as key compounds; catalase (CAT), AKT serine/threonine kinase 1 (AKT), nitric oxide synthase 3 (eNOS), NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1) and hypoxia-inducible factor 1 subunit alpha (HIF-1α) were identified as key genes; while nicotinamide adenine dinucleotide phosphate (NADP) and succinate emerged as key energy metabolites. Mechanistically, we revealed that SL may exert its anti-NAFLD effect by inducing autophagy activation and forming a comprehensive regulatory network involving key compounds, key genes, and key energy metabolites, ultimately alleviating oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction. Conclusion Our study demonstrated the therapeutic effect of SL in NAFLD models, and establishes a basis for the development of potential products from SL plant materials for the treatment of NAFLD.
研究领域:
药理学
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分子生物学
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代谢组学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Xu-guang Zhang,Ai-xia Liu,Yu-xin Zhang,Ming-yan Zhou,Xiang-yi Li,Ming-hai Fu,Yi-peng Pan,Jian Xu,Jun-qing Zhang
Ethnopharmacological relevance Alpinia officinarum Hance, a perennial natural medicine-food herb, has been traditionally used to treat colds, stomachache, and diabetes for thousands of years. 1,7-Diphenyl-4E-en-3-heptanone (DPH5), a diarylheptanoid isolated from the rhizome of A. officinarum has been reported to be safe and to have antioxidant and hypoglycemic effects, suggesting its potential in the treatment of insulin resistance (IR). Aim of the study : Aim of to investigate the protective effect of DPH5 on IR and elucidate its underlying mechanism of action. Materials and methods HepG2 cells were used as the research objects. Glucose uptake and reactive oxygen species (ROS) levels in high glucose–induced insulin-resistant HepG2 cells were assessed using flow cytometry. Glucose consumption and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed using the corresponding assay kits. The expression of mRNA and proteins related to insulin signaling, glucose metabolism, and antioxidant factor, including insulin receptor substrate-1 (IRS1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), translocation of glucose transporter-4, glycogen synthase kinase-3β (GSK3β), glucokinase (GCK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinoneoxidoreductase (NQO1), and glutathione peroxidase (GSH-Px) was determined using real-time quantitative polymerase chain reaction and western blotting . Furthermore, molecular docking was performed to determine the spatial mechanism of DPH5 on the key targets PI3K, AKT, Nrf2 , and GSK3β. Results DPH5 could improve IR that manifested as increased glucose uptake and glucose consumption in insulin-resistant HepG2 cells. Moreover, DPH5 could enhance antioxidant capacity by activating Nrf2/HO-1 elements, including increasing Nrf2, HO-1, SOD, NQO1, and GSH-Px expression and reducing MDA, ROS, and JNK levels, thereby improving oxidative stress and ultimately alleviating IR. Additionally, DPH5 could promote the expression of IRS1, PI3K, AKT, GSK3β, GCK, and PK, and downregulate the expression of PEPCK and G6pase, thereby accelerating glucose utilization and enhancing insulin sensitivity. The mechanism underlying the effect of DPH5 in alleviating IR was related to the PI3K/AKT- and Nrf2/HO-1-mediated regulation of the GSK3β signaling pathway, and the results were further confirmed using the specific inhibitors LY294002 and ML385. Results from molecular docking indicated that there were different regulatory sites and interacting forces between DPH5 and PI3K, AKT, Nrf2, and GSK3β; however, the binding force was relatively strong. Conclusions DPH5 improved oxidative stress and glucose metabolism via modulating the PI3K/AKT-Nrf2-GSK3β pathway, thereby ameliorating IR. Overall, our findings suggest the potential of DPH5 as a natural medicine to treat type-2 diabetes mellitus.
研究领域:
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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内分泌学
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糖尿病
✓ 已验证
DOI
PubMed
高影响因子
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