scholarly journals Novel hyaluronic acid-coated polymeric micelles with ROS scavenging to encapsulate statins for alleviating atherosclerosis

2020 ◽  
Author(s):  
Dan Mu ◽  
Jianhui Li ◽  
Yu Qi ◽  
Xuan Sun ◽  
Yihai Liu ◽  
...  

Abstract Inflammation and oxidative stress are two major factors that are involved in the pathogenesis of atherosclerosis. A smart drug delivery system that responds to the oxidative microenvironment of atherosclerotic plaques was constructed in the present study. Simvastatin (SIM)-loaded biodegradable polymeric micelles were constructed from hyaluronic acid (HA)-coated poly(ethylene glycol)-poly(tyrosine-ethyl oxalyl) (PEG-Ptyr-EO) for the purpose of simultaneously inhibiting macrophages and decreasing the level of reactive oxygen species (ROS) to treat atherosclerosis. HA coating endows the micelle system the ability of targeting CD44-positive inflammatory macrophages. Owing to the ROS-responsive nature of PEG-Ptyr-EO, the micelles can not only be degraded by enzymes, but also consumes ROS by itself at the pathologic sites, upon which the accumulation of pro-inflammatory macrophages is effectively suppressed and oxidative stress is alleviated. Consequently, the SIM-loaded micelles demonstrated remarkable therapeutic effects. In conclusion, the SIM-loaded micelle system can synchronically alleviate the accumulation of macrophages and oxidative stress, providing a promising and innovative option against atherosclerosis.

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Dan Mu ◽  
Jianhui Li ◽  
Yu Qi ◽  
Xuan Sun ◽  
Yihai Liu ◽  
...  

AbstractInflammation and oxidative stress are two major factors that are involved in the pathogenesis of atherosclerosis. A smart drug delivery system that responds to the oxidative microenvironment of atherosclerotic plaques was constructed in the present study. Simvastatin (SIM)-loaded biodegradable polymeric micelles were constructed from hyaluronic acid (HA)-coated poly(ethylene glycol)-poly(tyrosine-ethyl oxalyl) (PEG-Ptyr-EO) for the purpose of simultaneously inhibiting macrophages and decreasing the level of reactive oxygen species (ROS) to treat atherosclerosis. HA coating endows the micelle system the ability of targeting CD44-positive inflammatory macrophages. Owing to the ROS-responsive nature of PEG-Ptyr-EO, the micelles can not only be degraded by enzymes, but also consumes ROS by itself at the pathologic sites, upon which the accumulation of pro-inflammatory macrophages is effectively suppressed and oxidative stress is alleviated. Consequently, the cellular uptake experiment demonstrated that SIM-loaded HA-coated micelles can be effectively internalized by LPS-induced RAW264.7 cells and showed high cytotoxicity against the cells, but low cytotoxicity against LO2 cells. In mouse models of atherosclerosis, intravenously SIM-loaded HA-coated micelles can effectively reduce plaque content of cholesterol, resulting in remarkable therapeutic effects. In conclusion, the SIM-loaded micelle system provides a promising and innovative option against atherosclerosis.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1229
Author(s):  
Taehoon Oh ◽  
Mincheol Kwon ◽  
Jae Sik Yu ◽  
Mina Jang ◽  
Gun-Hee Kim ◽  
...  

Studies on ethanol-induced stress and acetaldehyde toxicity are actively being conducted, owing to an increase in alcohol consumption in modern society. In this study, ent-peniciherqueinone (EPQ) isolated from a Hawaiian volcanic soil-associated fungus Penicillium herquei FT729 was found to reduce the acetaldehyde-induced cytotoxicity and oxidative stress in PC12 cells. EPQ increased cell viability in the presence of acetaldehyde-induced cytotoxicity in PC12 cells. In addition, EPQ reduced cellular reactive oxygen species (ROS) levels and restored acetaldehyde-mediated disruption of mitochondrial membrane potential. Western blot analyses revealed that EPQ treatment increased protein levels of ROS-scavenging heme oxygenase-1 and superoxide dismutase, as well as the levels of aldehyde dehydrogenase (ALDH) 1, ALDH2, and ALDH3, under acetaldehyde-induced cellular stress. Finally, EPQ reduced acetaldehyde-induced phosphorylation of p38 and c-Jun N-terminal kinase, which are associated with ROS-induced oxidative stress. Therefore, our results demonstrated that EPQ prevents cellular oxidative stress caused by acetaldehyde and functions as a potent agent to suppress hangover symptoms and alcohol-related stress.


2019 ◽  
Vol 133 (13) ◽  
pp. 1523-1536 ◽  
Author(s):  
Xiao Sun ◽  
Xiuli Feng ◽  
Dandan Zheng ◽  
Ang Li ◽  
Chunyan Li ◽  
...  

Abstract Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). CS heightens inflammation, oxidative stress and apoptosis. Ergosterol is the main bioactive ingredient in Cordyceps sinensis (C. sinensis), a traditional medicinal herb for various diseases. The objective of this work was to investigate the effects of ergosterol on anti-inflammatory and antioxidative stress as well as anti-apoptosis in a cigarette smoke extract (CSE)-induced COPD model both in vitro and in vivo. Our results demonstrate that CSE induced inflammatory and oxidative stress and apoptosis with the involvement of the Bcl-2 family proteins via the nuclear factor kappa B (NF-κB)/p65 pathway in both 16HBE cells and Balb/c mice. CSE induced epithelial cell death and increased the expression of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), malondialdehyde (MAD) and the apoptosis-related proteins cleaved caspase 3/7/9 and cleaved-poly-(ADP)-ribose polymerase (PARP) both in vitro and in vivo, whereas decreased the levels of superoxide dismutase (SOD) and catalase (CAT). Treatment of 16HBE cells and Balb/c mice with ergosterol inhibited CSE-induced inflammatory and oxidative stress and apoptosis by inhibiting the activation of NF-κB/p65. Ergosterol suppressed apoptosis by inhibiting the expression of the apoptosis-related proteins both in vitro and in vivo. Moreover, the usage of QNZ (an inhibitor of NF-κB) also partly demonstrated that NF-κB/p65 pathway was involved in the ergosterol protective progress. These results show that ergosterol suppressed COPD inflammatory and oxidative stress and apoptosis through the NF-κB/p65 pathway, suggesting that ergosterol may be partially responsible for the therapeutic effects of cultured C. sinensis on COPD patients.


2015 ◽  
Vol 35 (3) ◽  
pp. 276-281 ◽  
Author(s):  
H Elbe ◽  
Z Dogan ◽  
E Taslidere ◽  
A Cetin ◽  
Y Turkoz

Ciprofloxacin is a broad-spectrum quinolone antibiotic commonly used in clinical practice. Quercetin is an antioxidant belongs to flavonoid group. It inhibits the production of superoxide anion. In this study, we aimed to evaluate the effects of quercetin on renal injury and oxidative stress caused by ciprofloxacin. Twenty-eight female Wistar albino rats were divided into four groups: control, quercetin (20 mg kg−1 day−1 gavage for 21 days), ciprofloxacin (20 mg kg−1 twice a day intraperitoneally for 10 days), and ciprofloxacin + quercetin. Samples were processed for histological and biochemical evaluations. Malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD), and catalase (CAT) activities were measured in kidney tissue. The ciprofloxacin group showed histopathological changes such as infiltration, dilatation in tubules, tubular atrophy, reduction of Bowman’s space, congestion, hemorrhage, and necrosis. In the ciprofloxacin + quercetin group, these histopathological changes markedly reduced. MDA levels increased in the ciprofloxacin group and decreased in the ciptofloxacin + quercetin group. SOD and CAT activities and GSH levels significantly decreased in the ciprofloxacin group. On the other hand, in the ciprofloxacin + quercetin group, SOD and CAT activities and GSH levels significantly increased with regard to the ciprofloxacin group. We concluded that quercetin has antioxidative and therapeutic effects on renal injury and oxidative stress caused by ciprofloxacin in rats.


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