Toxico-metabolomics study of a deep eutectic solvent comprising choline chloride and urea suggests in vivo toxicity involving oxidative stress and ammonia stress

2021 ◽  
Vol 23 (3) ◽  
pp. 1300-1311 ◽  
Author(s):  
Dasom Jung ◽  
Jae Back Jung ◽  
Seulgi Kang ◽  
Ke Li ◽  
Inseon Hwang ◽  
...  

The in vitro and in vivo studies suggest that choline chloride-based deep eutectic solvents may not be considered as pure, safe mixtures even if they consist of safe compounds.

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0117934 ◽  
Author(s):  
Maan Hayyan ◽  
Chung Yeng Looi ◽  
Adeeb Hayyan ◽  
Won Fen Wong ◽  
Mohd Ali Hashim

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2110 ◽  
Author(s):  
Xianchao Shang ◽  
Jia-Neng Tan ◽  
Yongmei Du ◽  
Xinmin Liu ◽  
Zhongfeng Zhang

Deep eutectic solvents (DESs) are commonly employed as environmentally-friendly solvents in numerous chemical applications owing to their unique physicochemical properties. In this study, a novel and environmentally-friendly extraction method based on ultrasound assisted-deep eutectic solvent extraction (UAE-DES) was investigated for the extraction of flavonoids from Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus) leaves, and the antioxidant activities of these flavonoids were evaluated. Nine different DES systems based on either two or three components were tested, and the choline chloride/1,4–butanediol system (1:5 molar ratio) was selected as the optimal system for maximizing the flavonoid extraction yields. Other extraction conditions required to achieve the maximum flavonoid extraction yields from the leaves of C. paliurus were as follows: DES water content (v/v), 30%; extraction time, 30 min; temperature, 60 °C; and solid-liquid ratio, 20 mg/mL. Liquid chromatography-mass spectrometry allowed the detection of five flavonoids in the extract, namely kaempferol-7-O-α-l-rhamnoside, kaempferol, quercetin, quercetin-3-O-β-d-glucuronide, and kaempferol-3-O-β-d-glucuronide. In vitro antioxidant tests revealed that the flavonoid-containing extract exhibited strong DPPH and ABTS radical-scavenging abilities. Results indicate that UAE-DES is a suitable approach for the selective extraction of flavonoids from C. paliurus leaves, and DESs can be employed as sustainable extraction media for other bioactive compounds.


2015 ◽  
Vol 48 (06) ◽  
Author(s):  
G Antonios ◽  
H Borgers ◽  
T Pilot ◽  
V Pena ◽  
T Bayer

2020 ◽  
Vol 26 (22) ◽  
pp. 2610-2619 ◽  
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Huansheng Yang ◽  
Muhammad S. Kalhoro ◽  
Dildar H. Kalhoro

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.


2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.


2018 ◽  
Vol 15 (4) ◽  
pp. 564-575 ◽  
Author(s):  
Arehalli S. Manjappa ◽  
Popat S. Kumbhar ◽  
Prajakta S. Khopade ◽  
Ajit B. Patil ◽  
John I. Disouza

2018 ◽  
Vol 15 (4) ◽  
pp. 345-354 ◽  
Author(s):  
Barbara D'Orio ◽  
Anna Fracassi ◽  
Maria Paola Cerù ◽  
Sandra Moreno

Background: The molecular mechanisms underlying Alzheimer's disease (AD) are yet to be fully elucidated. The so-called “amyloid cascade hypothesis” has long been the prevailing paradigm for causation of disease, and is today being revisited in relation to other pathogenic pathways, such as oxidative stress, neuroinflammation and energy dysmetabolism. The peroxisome proliferator-activated receptors (PPARs) are expressed in the central nervous system (CNS) and regulate many physiological processes, such as energy metabolism, neurotransmission, redox homeostasis, autophagy and cell cycle. Among the three isotypes (α, β/δ, γ), PPARγ role is the most extensively studied, while information on α and β/δ are still scanty. However, recent in vitro and in vivo evidence point to PPARα as a promising therapeutic target in AD. Conclusion: This review provides an update on this topic, focussing on the effects of natural or synthetic agonists in modulating pathogenetic mechanisms at AD onset and during its progression. Ligandactivated PPARα inihibits amyloidogenic pathway, Tau hyperphosphorylation and neuroinflammation. Concomitantly, the receptor elicits an enzymatic antioxidant response to oxidative stress, ameliorates glucose and lipid dysmetabolism, and stimulates autophagy.


2019 ◽  
Vol 16 (6) ◽  
pp. 696-710
Author(s):  
Mahmoud Balbaa ◽  
Doaa Awad ◽  
Ahmad Abd Elaal ◽  
Shimaa Mahsoub ◽  
Mayssaa Moharram ◽  
...  

Background: ,2,3-Triazoles and imidazoles are important five-membered heterocyclic scaffolds due to their extensive biological activities. These products have been an area of growing interest to many researchers around the world because of their enormous pharmaceutical scope. Methods: The in vivo and in vitro enzyme inhibition of some thioglycosides encompassing 1,2,4- triazole N1, N2, and N3 and/or imidazole moieties N4, N5, and N6. The effect on the antioxidant enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) was investigated as well as their effect on α-glucosidase and β-glucuronidase. Molecular docking studies were carried out to investigate the mode of the binding interaction of the compounds with α- glucosidase and β -glucuronidase. In addition, quantitative structure-activity relationship (QSAR) investigation was applied to find out the correlation between toxicity and physicochemical properties. Results: The decrease of the antioxidant status was revealed by the in vivo effect of the tested compounds. Furthermore, the in vivo and in vitro inhibitory effects of the tested compounds were clearly pronounced on α-glucosidase, but not β-glucuronidase. The IC50 and Ki values revealed that the thioglycoside - based 1,2,4-triazole N3 possesses a high inhibitory action. In addition, the in vitro studies demonstrated that the whole tested 1,2,4-triazole are potent inhibitors with a Ki magnitude of 10-6 and exhibited a competitive type inhibition. On the other hand, the thioglycosides - based imidazole ring showed an antioxidant activity and exerted a slight in vivo stimulation of α-glucosidase and β- glucuronidase. Molecular docking proved that the compounds exhibited binding affinity with the active sites of α -glucosidase and β-glucuronidase (docking score ranged from -2.320 to -4.370 kcal/mol). Furthermore, QSAR study revealed that the HBD and RB were found to have an overall significant correlation with the toxicity. Conclusion: These data suggest that the inhibition of α-glucosidase is accompanied by an oxidative stress action.


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