Quantitative proteomics and bioinformatics analyses reveal the protective effects of cyanidin-3-O-glucoside and its metabolite protocatechuic acid against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced cytotoxicity in HepG2 cells via apoptosis-related pathways

2021 ◽  
pp. 112256
Author(s):  
Lei Zhao ◽  
Fei Pan ◽  
Na Zhou ◽  
Huimin Zhang ◽  
Yong Wang ◽  
...  
PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1628 ◽  
Author(s):  
Kin Weng Kong ◽  
Sarni Mat-Junit ◽  
Norhaniza Aminudin ◽  
Fouad Abdulrahman Hassan ◽  
Amin Ismail ◽  
...  

Barringtonia racemosais a tropical plant with medicinal values. In this study, the ability of the water extracts of the leaf (BLE) and stem (BSE) from the shoots to protect HepG2 cells against oxidative damage was studied. Five major polyphenolic compounds consisting of gallic acid, ellagic acid, protocatechuic acid, quercetin and kaempferol were identified using HPLC-DAD and ESI-MS. Cell viability assay revealed that BLE and BSE were non-cytotoxic (cell viabilities >80%) at concentration less than 250 µg/ml and 500 µg/ml, respectively. BLE and BSE improved cellular antioxidant status measured by FRAP assay and protected HepG2 cells against H2O2-induced cytotoxicity. The extracts also inhibited lipid peroxidation in HepG2 cells as well as the production of reactive oxygen species. BLE and BSE could also suppress the activities of superoxide dismutase and catalase during oxidative stress. The shoots ofB. racemosacan be an alternative bioactive ingredient in the prevention of oxidative damage.


Author(s):  
Li-Yun Lin ◽  
Chi-Yun Huang ◽  
Kuan-Chou Chen ◽  
Robert Y. Peng

AbstractGrapefruit (G) parts contain abundant phenolic acids and flavonoids (PPNs and FLVs). The wastes created from exocarps, mesocarps (G wastes, GW) and waste blanching water (WBW) lead to a considerable loss of PPNs and FLVs. Here, we assessed Buntan (CB), Buntan Hayata (CBH), and Peiyu (CP) cultivars and observed considerable amounts of PPNs and FLVs. The ethanolic extracts of GW (GWE) and WBW contained gallic acid, protocatechuic acid, chlorogenic acid, caffeic acid, ferulic acid, coumaric acid, naringin, hesperidin, diosmin, quercetin, hesperetin, nobiletin, and tangeretin (GWC). GWE has previously been reported to be a relatively active antioxidant, anti-inflammatory (based on the expression of TNF-α in Raw264.7 cells), antihypertensive, and anti-hyperglycemic compound. The IC50 values for antihyperglycemic activity with WBW for α-amylase were as follows: CB (27.96 ± 0.03 mg/mL) < CP (28.13 ± 0.19 mg/mL) < CBH (41.60 ± 0.16 mg/mL), and those for α-glucosidase were CB (1.80 ± 0.03 mg/mL) < CP (2.97 ± 0.29 mg/mL) < CBH (9.10 ± 0.51 mg/mL). GWC upregulated Glut4 in HepG2 cells, as well as the insulin secretion capability, and intracellular levels in RIN-m5F cells, and it downregulated DPP4 in HepG2 cells. The IC50 values for the angiotensin-converting enzyme activity were: CBP (5.10 ± 0.02 mg/mL) < CB (7.24 ± 0.65 mg/mL) < CP (8.60 ± 2.03 mg/mL). Our results indicate that PPNs and FLVs present in GW are worth reclaiming.


2018 ◽  
Vol 19 (8) ◽  
pp. 2180 ◽  
Author(s):  
María Ariza ◽  
Tamara Forbes-Hernández ◽  
Patricia Reboredo-Rodríguez ◽  
Sadia Afrin ◽  
Massimiliano Gasparrini ◽  
...  

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2′-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.


2015 ◽  
Vol 93 (8) ◽  
pp. 625-631 ◽  
Author(s):  
Yan Hu ◽  
Ning Zhang ◽  
Qing Fan ◽  
Musen Lin ◽  
Ce Zhang ◽  
...  

Carnosic acid (CA), found in rosemary, has been reported to have antioxidant and antiadipogenic properties. Here, we investigate the molecular mechanism by which CA inhibits hydrogen peroxide (H2O2)-induced injury in HepG2 cells. Cells were pretreated with 2.5–10 μmol/L CA for 2 h and then exposed to 3 mmol/L H2O2 for an additional 4 h. CA dose-dependently increased cell viability and decreased lactate dehydrogenase activities. Pretreatment with CA completely attenuated the inhibited expression of manganese superoxide dismutase (MnSOD) and the B-cell lymphoma-extra large (Bcl-xL), and reduced glutathione activity caused by H2O2, whereas it reversed reactive oxygen species accumulation and the increase in cleaved caspase-3. Importantly, sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, was significantly increased by CA. Considering the above results, we hypothesized that SIRT1 may play important roles in the protective effects of CA in injury induced by H2O2. As expected, SIRT1 suppression by Ex527 (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) and siRNA-mediated SIRT1 silencing (si-SIRT1) significantly aggravated the H2O2-induced increased level of cleaved caspase-3 but greatly reduced the decreased expression of MnSOD and Bcl-xL. Furthermore, the positive regulatory effect of CA was inhibited by si-SIRT1. Collectively, the present study indicated that CA can alleviate H2O2-induced hepatocyte damage through the SIRT1 pathway.


2016 ◽  
Vol 35 (12) ◽  
pp. 1252-1263 ◽  
Author(s):  
SS Palabiyik ◽  
E Karakus ◽  
Z Halici ◽  
E Cadirci ◽  
Y Bayir ◽  
...  

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.


2012 ◽  
Vol 22 (6) ◽  
pp. 432-437 ◽  
Author(s):  
Jianqing Li ◽  
Guang Yang ◽  
Shaopeng Wang ◽  
Liping Jiang ◽  
Xiaofang Liu ◽  
...  

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Zhecheng Wang ◽  
Yan Zhao ◽  
Ruimin Sun ◽  
Yu Sun ◽  
Deshun Liu ◽  
...  

Abstract p66Shc, a master regulator of mitochondrial reactive oxygen species (mtROS), is a crucial mediator of hepatocyte oxidative stress. However, its functional contribution to acetaminophen (APAP)-induced liver injury and the mechanism by which it is modulated remain unknown. Here, we aimed to assess the effect of p66Shc on APAP-induced liver injury and to evaluate if circular RNA (circRNA) functions as a competitive endogenous RNA (ceRNA) to mediate p66Shc in APAP-induced liver injury. p66Shc-, miR-185-5p-, and circ-CBFB-silenced mice were injected with APAP. AML12 cells were transfected with p66Shc, miR-185-5p, and circ-CBFB silencing or overexpression plasmids or siRNAs prior to APAP stimulation. p66Shc was upregulated in liver tissues in response to APAP, and p66Shc silencing in vivo protected mice from APAP-induced mitochondrial dynamics perturbation and liver injury. p66Shc knockdown in vitro attenuated mitochondrial dynamics and APAP-induced hepatocyte injury. Mechanically, p66Shc perturbs mitochondrial dynamics partially by inhibiting OMA1 ubiquitination. miR-185-5p, which directly suppressed p66Shc translation, was identified by microarray and bioinformatics analyses, and its overexpression attenuated mitochondrial dynamics and hepatocyte injury in vitro. Furthermore, luciferase, pull-down and RNA immunoprecipitation assays demonstrated that circ-CBFB acts as a miRNA sponge of miR-185-5p to mediate p66Shc in APAP-induced liver injury. circ-CBFB knockdown also alleviated APAP-induced mitochondrial dynamics perturbation and hepatocyte injury. More importantly, we found that the protective effects of circ-CBFB knockdown on p66Shc, mitochondrial dynamics and liver injury were abolished by miR-185-5p inhibition both in vivo and in vitro. In conclusion, p66Shc is a key regulator of APAP-induced liver injury that acts by triggering mitochondrial dynamics perturbation. circ-CBFB functions as a ceRNA to regulate p66Shc during APAP-induced liver injury, which may provide a potential therapeutic target.


2017 ◽  
Vol 16 (1) ◽  
pp. 597-602 ◽  
Author(s):  
Bing Zhang ◽  
Jing-Lin Dong ◽  
Ying-Li Chen ◽  
Yang Liu ◽  
Shi-Shun Huang ◽  
...  

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