JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
·
IF 6.1
Mingyuan Cao,Jie Wang,Xueying Jiang,Zhipeng Sun,Liyan Zhao,Guitang Chen
Quinoa is a nutrient-rich pseudocereal with a lower glycemic index and glycemic load. However, its therapeutic potency and underlying mechanism against insulin resistance (IR) have not been fully elucidated. In this work, network pharmacology was applied to screen IR targets and their related pathways. The efficacy and mechanism of black quinoa polyphenols (BQP) on IR improvement were evaluated and uncovered based on the IR model in vitro combined with molecular docking. Ten phenolic constituents of BQP were detected, and the network pharmacology results show that PI3K/Akt pathways are the main pathways in BQP against IR. The in vitro assay proved that BQP increases the glucose consumption and glycogen synthesis via upregulating insulin receptor substrate 1 (IRS1)/PI3K/Akt/glucose transporters (GLUTs) signaling pathways to alleviate IR. Rutin, resveratrol, and catechin show lower binding energy docking with IRS1, PI3K, Akt, and GLUT4 proteins, indicating better interactions. It might be an effective constituent against IR. Hence, BQP could become a potential functional food source for blood glucose management among insulin-resistant people.
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Pharmaceutics
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2023
·Vol. 15
·期 1
·276
·
IF 5.4
Xuanping Zhao,Chuan Liu,Zichao Wang,Yingyuan Zhao,Xuyang Chen,Haizhen Tao,Hong Chen,Xueqin Wang,Shaofeng Duan
Numerous nanocarriers have been developed to deliver drugs for the treatment of hepatocellular carcinoma. However, the lack of specific targeting ability, the low administration efficiency, and insufficient absorption by hepatocellular carcinoma cells, severely limits the therapeutic effect of the current drugs. Therefore, it is still of great clinical significance to develop highly efficient therapies with few side effects for the treatment of hepatocellular carcinoma. Herein, we developed a highly effective nanocarrier, cyclic RGD peptide-conjugated magnetic mesoporous nanoparticles (RGD[email protected]NPs), to deliver the chemotherapeutic drug doxorubicin (DOX) to human hepatocellular carcinoma HepG2 cells, and further explored their synergistic apoptosis-promoting effects. The results showed that the preparedRGD[email protected]NPs had good stability, biosafety and drug-loading capacity, and significantly improved the absorption of DOX by HepG2 cells, and that theRGD[email protected]@DOX NPs could synergistically promote the apoptosis of HepG2 cells. Thus, this cyclic RGD peptide-modified magnetic mesoporous silicon therapeutic nanosystem can be regarded as a potentially effective strategy for the targeted treatment of hepatocellular carcinoma.Keywords:cyclic RGD peptide;anticancer drug delivery;targeted nanoparticles;hepatocellular carcinoma;apoptosis
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ENVIRONMENTAL POLLUTION
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2022
·
IF 9.988
Yuanyuan Zhou,Hanyu Liao,Shanshan Yin,Pengqiao Wang,Xiaoqing Ye,Jianyun Zhang
Organophosphate esters (OPEs) are a group of extensively used man-made chemicals with diverse substituents that are ubiquitously detected in human-related samples including serum, breastmilk, food and house dust. The understanding of their toxicological effects and potential mechanisms on hepatocytes is still limited. In this study, nine most frequently detected OPEs were selected and divided into three subgroups (aryl-, halogenated- and alkyl-OPEs) based on their substituents. The cytotoxicity, apoptosis, oxidative stress, endoplasmic reticulum (ER) stress and NLRP3 inflammasome activation induced by OPEs were evaluated in human hepatocellular carcinomas HepG2 cells. All OPEs induced apoptosis likely through a caspase-dependent apoptotic pathway. The activities of anti-oxidative enzyme SOD and CAT exhibited sensitive responses after OPEs treatment for 6 h. The OPEs induced ROS overproduction, DNA damage, endoplasmic reticulum (ER) stress and NLRP3 inflammasome activation varied among aryl-, halogenated- and alkyl-OPEs. Halogenated- and alkyl- OPEs induced overproduction of ROS and DNA damage, and elevated ER stress and NLRP3 inflammasome activation are observed aryl-OPEs induced cytotoxicity.
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JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
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2021
·
IF 1.571
Fang Chen,Shi-Yun Huang,Shu-Qing Xiang,Xiao-Xu Qiao,Guo-Chao Liao,Zhong-Qiu Liu,Hua Zhou,Peng Wu
Two new phenolic glycosides (1-2), along with six existing compounds (3-8), were isolated from the ethanolic extract of Ilex pubescens roots, a traditional folk medicine. These structures were determined using HR-ESI-MS, IR, UV, and NMR (including 1 D, 2 D-NMR). The anti-inflammatory activities of three phenolic glycosides (1-3) were evaluated in the human HepG2 cell lines. The results showed that compound 3 could induce P-gp and BCRP expression through the Nrf2-mediated pathway.
研究领域:
天然产物化学
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药理学
·
分子生物学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2021
·
IF 5.279
Guiling Li,Yuanyuan Li,Baoping Xiao,Dongyue Cui,Yanqi Lin,Jun Zeng,Jian Li,Min-Jie Cao,Jingwen Liu
Reactive oxygen species (ROS) are single-electron-bearing oxidation–reduction products that are mainly produced in mitochondria. Excessive ROS accumulation may lead to oxidative damage. Docosahexaenoic acid (DHA) is an essential component of brain phospholipids and is mainly derived from the diet. Its antioxidant activities have been extensively studied. However, its regulatory roles in mitochondria and the underlying mechanism remain to be elucidated. In this study, the DHA’s effect on cellular antioxidant capacity and mitochondrial functions was examined in HepG2 cells. The results showed that 100 μM DHA decreased cellular and mitochondrial ROS levels to 75.2 ± 9.4% (P < 0.05) and 55.1 ± 1.4% (P < 0.01), respectively. It also increased the total antioxidant capacity by 55.6 ± 0.1 and 49.2 ± 1.1% (P < 0.05), based on ABTS and FRAP assay results, respectively. Consistently, it increased the activities and gene expression of major antioxidant enzymes by at least 35 and 40% (P < 0.05), respectively. Furthermore, DHA promoted mitochondrial functions and biogenesis. These data suggested that DHA’s antioxidant activity can be attributed to its enhancement of mitochondrial functions and biogenesis. This study may shed light on the molecular mechanisms underlying DHA’s function in improving resistance to and relieving the symptoms of chronic disease.
研究领域:
营养学
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分子生物学
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医学
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CHEMICAL RESEARCH IN TOXICOLOGY
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2015
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IF 3.529
Chuanyang Su,Pu Zhang,Xiufang Song,Qiong Shi,Juanli Fu,Xiaomin Xia,Huiyuan Bai,Lihua Hu,Demei Xu,Erqun Song,Yang Song
Tetrachlorobenzoquinone (TCBQ), a metabolite of industrial herbicide pentachlorophenol, showed hepatotoxicity and genotoxicity through reactive oxygen species (ROS) mechanism in vivo and in vitro models. Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a cellular sensor of oxidative or electrophilic stress, which controls the expression of detoxifying enzymes and antioxidant proteins. Using the human hepatoma HepG2 cell line as an in vitro model, we demonstrated a significant induction of Nrf2 but not its negative regulator Kelch-like ECH-associated protein 1 (Keap1), following exposure to TCBQ. Also, our results clearly demonstrated the translocation of cytosolic Nrf2 into the nucleus. After translocation, Nrf2 subsequently binds to the antioxidant response element (ARE), up-regulated heme oxygenase-1 (HO-1), and NADH quinone oxidoreductase subunit 1 (NQO1), which may be considered as an antioxidative response to TCBQ-intoxication. The luciferase reporter assay confirmed the formation of the Nrf2-ARE complex. Furthermore, mechanism studies proposed that TCBQ promoted the formation of the Keap1 cross-linking dimer, a ubiquitination switch from Nrf2 to Keap1 but not the dissociation of the Keap1-Cullin3 (Cul3) complex.
研究领域:
毒理学
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细胞生物学
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分子生物学
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TOXICOLOGY IN VITRO
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2015
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IF 2.903
Lizhen Huang,Shuxiang Zou,Jifeng Deng,Tianming Dai,Jingwei Jiang,Ying Jia,Renke Dai,Shuilin Xie
Drug-induced hepatotoxicity is often caused by cytochrome P450 (CYP)-dependent metabolism of drugs into reactive metabolites. Assessment of hepatotoxicity induced by bioactive compounds is hampered by low CYP expression within in vitro cell lines. To overcome this limitation, piggyBac transposition and monoclonal expansion were used to generate a HepG2 cell line with stable and homogenously high expression of CYP3A4, a prominent CYP isoform. Our studies demonstrate the generated line's constant CYP3A4 expression and activity for over 40 cell passages; to date, it has been in subculture for more than a year without addition of Puromycin. This cell line was utilized to evaluate cytotoxicity of two bioactive (troglitazone and acetaminophen) and two non-bioactive (citrate and galactosamine) compounds by MTT assay. Cell viability significantly decreased upon treatment with bioactive drugs. Moreover, cell lines used in the present study were more sensitive to toxic effects of troglitazone than previously reported. Therefore, this HepG2 cell-based assay system may provide a suitable hepatic model for predicting CYP3A4-mediated hepatotoxicity during preclinical drug development.
研究领域:
药理学
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分子生物学
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毒理学
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BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
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2017
·Vol. 65
·期 2
·263-273
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IF 1.413
Dongsheng Sun,Yang Liu,Hao Wu,Ying Ren,Xiaojun Ma,Huijian Wu,Guangwei Sun
Optimizing alginate gel beads is necessary to support the survival, proliferation, and function of entrapped hepatocytes. In this study, gelling bath was modified by decreasing calcium ion concentration and increasing sodium ion concentration. Alginate gel beads (using 36% G sodium alginate) prepared in the modified gelling bath had more homogeneous structure and better mass transfer properties compared with the traditional gelling bath that contains only calcium ions. Moreover, alginate gel beads generated in the modified gelling bath could significantly promote the HepG2 cell proliferation and the growth of cell spheroids, and maintain the albumin secretion ability similar to alginate gel beads prepared in the traditional gelling bath with only calcium ions. The mass transfer properties and cell proliferation were similar in ALG beads with different M/G ratio (36% G and 55% G) generated in the modified gelling bath, whereas they were significantly increased compared with alginate gel beads (55% G) in traditional gelling bath. These results indicated that adjusting the gelling bath was a simple and convenient method to enhance the mass transfer properties of alginate gel beads for 3D hepatocyte culture, which might provide more hepatocytes for the bioartificial liver support system.
研究领域:
生物技术
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细胞生物学
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组织工程
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2021
·Vol. 413
·期 5
·1353-1361
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IF 4.157
Sun Qi-Xuan,Wei Xing,Zhang Shang-Qing,Chen Ming-Li,Yang Ting,Yu Yong-Liang,Wang Jian-Hua
Copper transporter 1 (CTR1) is a transport protein involved in copper and cisplatin uptake. The visualization of cellular CTR1 migration and its redistribution is highly important in copper/cisplatin exposure/transport. However, to the best of our knowledge, this is a highly challenging task. Herein, a dual-mode imaging strategy for CTR1 is developed by hyphenating confocal laser scanning microscopy (CLSM) and laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) with a fluorescent/elemental bifunctional tag conjugated with anti-CTR1 antibody. The tag consists of rhodamine B and zirconium metal-organic frameworks (Zr-MOF) for CLSM fluorescence imaging and LA-ICPMS element imaging for a same group of HepG2 cells in a designated visual zone. This dual-mode imaging strategy facilitates visualization of CTR1 migration and meanwhile provides information of CTR1 redistribution in HepG2 cells by uptake of divalent copper or cisplatin. The present dual-mode imaging strategy provides in-depth information for the elucidation of CTR1 involved biological processes.
Graphical abstract
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Journal of Functional Foods
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2020
·
IF 3.701
Vemana Gowd,Lianghua Xie,Chongde Sun,Wei Chen
Bayberry (BB) fruits contain high levels of polyphenols and possess good bioactivities. However, there are no specific studies to illustrate the impact of human gut microbiota fermentation (HGMF) on BB polyphenols subjected to gastrointestinal digestion (GID). Therefore, in this study, BB was subjected to simulated GID and HGMF (0–48 h) in order to study the fate of BB bioactive components. Phenolic gut metabolites were identified and quantified by relevant standards using HPLC. Cyanidin-3- O -glucoside was the only anthocyanin in BB and could be detected in its free form even after gut fermentation for 24 h. Gut metabolites of BB showed better hypoglycemic activity by improving hepatic glucose consumption and glycogen content. Furthermore, gut metabolites significantly ameliorated glucolipotoxicity induced oxidative stress. Since BB gut metabolites showed good hypoglycemic and antioxidant activities, BB can be considered as a functional food and dietary supplementation of BB could help in maintenance of good health.
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JOURNAL OF FOOD BIOCHEMISTRY
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2020
·Vol. 44
·期 9
·e13361
·
IF 1.662
Yongsheng Chen,Sheng Geng,Benguo Liu
The demand for plant-derived antidiabetic nutraceuticals is increasing. In this study, the effects of three common caffeoylquinic acids (CQAs) (chlorogenic acid, isochlorogenic acid A, and cynarin) on α-glucosidase activity and glucose consumption in HepG2 cells were systematically compared. Their α-glucosidase inhibitory activities followed the order of isochlorogenic acid A > chlorogenic acid > cynarin. The fluorescence analysis indicated that they exerted the inhibitory role by forming the complex with α-glucosidase at the molar ratio of 1:1. Isochlorogenic acid A possessed the highest binding capacity, followed by chlorogenic acid and cynarin. The effect of caffeoyl group distribution on the α-glucosidase inhibitory activity was clarified by the molecular docking results. In the HepG2 cells, isochlorogenic acid A also showed the best glucose consumption with negligible cytotoxicity, which might be related to its reactive oxygen species scavenging capacity in cells. Our results confirm its potential application as the antidiabetic nutraceutical. Practical applications The hypoglycemic activities of three common CQAs (chlorogenic acid, isochlorogenic acid A, and cynarin) were systemically evaluated in this study. Isochlorogenic acid A exhibited the strongest α-glucosidase inhibitory activity and highest glucose consumption in HepG2 cells with low cytotoxicity. The results suggest that isochlorogenic acid A can be used as the potential hypoglycemic nutraceutical in functional foods.
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Evidence-based Complementary and Alternative Medicine
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2021
·
IF 2.63
Jian Zhao,Hewei Li,Wanying Li,Zixian Wang,Zhewen Dong,Huan Lan,Chengqiang Wang,Jia-Le Song
Sinapic acid (Sa) is a small-molecule phenolic acid compound predominant in fruits, vegetables, and grains. This study investigated the antitumor effects of cisplatin (DDP) combined with Sa (Sa/DDP) on the hepatic cancer cells (HCC), HepG2 and SMMC-7721. The HepG2 and SMMC-7721 cells were treated with Sa or Sa/DDP, and the cell proliferation and cell cycle were detected using the MTT assay. The cell migration was detected using the transwell and scratch assays, while apoptosis and autophagy were detected using Hoechst, MDC, and Annexin V-FITC/PI staining. The protein expression was quantitated using the western blot. Sa/DDP was found to not only inhibit cancer cell proliferation and migration but also induce cell apoptosis. Simultaneously, the Sa/DDP combination was found to activate autophagy, and the HCQ autophagy inhibitor enhanced the apoptosis in the Sa/DDP-induced liver cancer cells. The combined use of Sa and DDP makes it an attractive adjuvant therapy strategy for tumors, establishing the prospect of phenolic acid compounds for the adjuvant treatment of hepatocellular carcinoma.
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