scholarly journals Oxidized Low-Density Lipoprotein-Deteriorated Psoriasis Is Associated with the Upregulation of Lox-1 Receptor and Il-23 Expression In Vivo and In Vitro

2018 ◽  
Vol 19 (9) ◽  
pp. 2610 ◽  
Author(s):  
Chun-Ming Shih ◽  
Chien-Yu Huang ◽  
Kuo-Hsien Wang ◽  
Chun-Yao Huang ◽  
Po-Li Wei ◽  
...  

Psoriasis is a chronic inflammatory skin disease. Even though scientists predict that abnormalities in lipid metabolism play an important role in the pathogenesis of psoriasis, the actual underlying mechanisms are still unclear. Therefore, understanding the possible relationship between mechanisms of the occurrence of psoriasis and dyslipidemia is an important issue that may lead to the development of effective therapies. Under this principle, we investigated the influences of hyperlipidemia in imiquimod (IMQ)-induced psoriasis-like B6.129S2-Apoetm1Unc/J mice and oxidized low-density lipoprotein (oxLDL) in tumor necrosis factor (TNF)-α-stimulated Hacat cells. In our study, we showed that a high-cholesterol diet aggravated psoriasis-like phenomena in IMQ-treated B6.129S2-Apoetm1Unc/J mice. In vitro analysis showed that oxLDL increased keratinocyte migration and lectin-type oxLDL receptor 1 (LOX-1) expression. Evidence suggested that interleukin (IL)-23 was a main cytokine in the pathogenesis of psoriasis. High-cholesterol diet aggravated IL-23 expression in IMQ-treated B6.129S2-Apoetm1Unc/J mice, and oxLDL induced IL-23 expression mediated by LOX-1 in TNF-α-stimulated Hacat cells. Therefore, it will be interesting to investigate the factors for the oxLDL induction of LOX-1 in psoriasis. LOX-1 receptor expression may be another novel treatment option for psoriasis and might represent the most promising strategy.

2021 ◽  
Author(s):  
Linfeng He ◽  
Cheng Wang ◽  
Yafang Zhang ◽  
Chaocheng Guo ◽  
Yan Wan ◽  
...  

Abstract BackgroundEmodin (EM) is one of bioactive components extracted from Rheum palmatum L. (Dahuang), which possesses numerous pharmacological activities including hypolipidemic effect. However, the potential action of EM on hyperlipidemia (HLP) remains unclear. Here, the theraputic effect of EM against HLP were investigated.MethodsIn this study, the hypolipidemic properties of EM were evaluated using high-cholesterol diet (HCD)-stimulated zebrafish larvae model. The body weight, body length and body mass index (BMI) was measured. The total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) as well as the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by corresponding assay kits. Tg (flil: eGFP) zebrafish were utilized to observe vascular cholesterol accumulation and Tg (mpx: eGFP) zebrafish to visualize and quantify neutrophil inflammation. The hepatic lipid deposition and hepatic histopathology were analyzed by Oil red O staining and H&E staining, respectively. Finally, the underlying mechanism of EM were investigated using real-time quantitative PCR (RT-qPCR) analysis to assess the gene levels of adenosine monophosphate-activated protein kinase alpha (AMPKα), sterol regulatory element binding protein 2 (SREBP-2), proprotein convertase subtilisin kexin 9 (PCSK9), low-density lipoprotein receptor (LDLR), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), adenosine triphosphate binding cassette transporter A1 (ABCA1) and adenosine triphosphate binding cassette transporter G1 (ABCG1).ResultsOur data indicated that EM reduced obesity of zebrafish as evidenced by the decrease in body weight, body length and BMI. EM significantly reduced TC, TG, and LDL-C, and increased HDL-C contents. Moreover, it displayed a prominent inhibitory effect on blood cholesterol accumulation, hepatic lipid accumulation, and neutrophil inflammation in vascular site. Additionally, EM improved the liver function through decreasing ALT and AST levels of zebrafish with HCD-induced hepatosteatosis. Further investigation showed that EM treatment attenuated lipid accumulation via upregulating the expression of AMPKα, LDLR, ABCA1 and ABCG1, and downregulating the expression of SREBP-2, PCSK9 and HMGCR.ConclusionTo conclude, EM alleviated lipid metabolism disorder symptoms caused by HCD via modulating AMPK/SREBP-2/PCSK9/LDLR pathway in larvae, suggesting that EM may be developed into hypolipidmic agent for treating lipid metabolism related diseases.


2017 ◽  
Vol 8 (2) ◽  
pp. 271-280 ◽  
Author(s):  
F. Bendali ◽  
K. Kerdouche ◽  
S. Hamma-Faradji ◽  
D. Drider

Lactobacillus pentosus KF923750 was characterised for probiotic related properties and then characterised for cholesterol uptake in vitro as well as in vivo using rabbits fed a high-cholesterol diet. The survival percentage of L. pentosus KF923750 was 100% at pH 3, 52.18% at pH 2 and 36.21% at pH 2 plus pepsin. Similarly, this strain appeared resistant to bile (0.1% [98.42%], 0.3% [88.52%], 0.5% [75.60%] and 1% [71.15%]), after 4 h exposure. Moreover, L. pentosus KF923750 controlled growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 through the production of a bacteriocin-like inhibitory substance and anti-adhesive capabilities. L. pentosus KF923750 was non-cytotoxic to eukaryotic cells but sensitive to some antibiotics. Compared with rabbits fed a high-cholesterol diet but without L. pentosus KF923750 supplementation, the plasma total cholesterol, low-density lipoprotein cholesterol and triglycerides levels were significantly decreased in L. pentosus KF923750-fed rabbits by 11.54, 16.00 and 18.00%, respectively, with no significant change in high-density lipoprotein cholesterol levels. The histological sections of livers revealed lesions in all the rabbits that were fed a high-cholesterol diet, but these were less pronounced in rabbits ingesting L. pentosus KF923750. This study highlights the potential of lactobacilli, such as L. pentosus KF923750, in the treatment or prevention of hypercholesterolemia.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Abhilasha Singh ◽  
Ashok Kumar Srinivasan ◽  
Lakshmi Narasimhan Chakrapani ◽  
Periandavan Kalaiselvi

Background. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major receptor for oxidized low-density lipoprotein (Ox-LDL) in the aorta of aged rats. Ox-LDL initiates LOX-1 activation in the endothelium of lipid-accumulating sites of both animal and human subjects of hypercholesterolemia. Targeting LOX-1 may provide a novel diagnostic strategy towards hypercholesterolemia and vascular diseases. Hypothesis. This study was planned to address whether aegeline (AG) could bind to LOX-1 with a higher affinity and modulate the uptake of Ox-LDL in hypercholesterolemia. Study Design. Thirty-six Wistar rats were divided into six groups. The pathology group rats were fed with high-cholesterol diet (HCD) for 45 days, and the treatment group rats were fed with HCD and aegeline/atorvastatin (AV) for the last 30 days. In vivo and in vitro experiments were carried out to assay the markers of atherosclerosis like Ox-LDL and LOX-1 levels. Histopathological examination was performed. Oil Red O staining was carried out in the IC-21 cell line. Docking studies were performed. Results. AG administration effectively brought down the lipid levels induced by HCD. The lowered levels of Ox-LDL and LOX-1 in AG-administered rats deem it to be a potent antihypercholesterolemic agent. Compared to AV, AG had a pronounced effect in downregulating the expression of lipids evidenced by Oil Red O staining. AG binds with LOX-1 at a higher affinity validated by docking. Conclusion. This study validates AG to be an effective stratagem in bringing down the lipid stress induced by HCD and can be deemed as an antihypercholesterolemic agent.


2016 ◽  
Vol 21 (4) ◽  
pp. NP62-NP66 ◽  
Author(s):  
Mohammad Reza Saidi ◽  
Mohammad Hosein Farzaei ◽  
Shahram Miraghaee ◽  
Atefeh Babaei ◽  
Bahareh Mohammadi ◽  
...  

Prosopis farcta root has been proposed as an efficacious natural drug for cardiovascular disorders in traditional medicine. The present study evaluates the efficacy of aqueous extract of Prosopis farcta root on experimental atherosclerosis development in rabbits with high cholesterol diet–induced hypercholesterolemia. Serum lipid parameters were significantly increased in the high cholesterol diet groups in comparison with the normal control group ( P < .050). Histopathological findings revealed that atheromatous plaques were formed in both thoracic and abdominal aorta of hypercholestrolemic rabbits. Treatment with Prosopis farcta root significantly reduced total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, and very low density lipoprotein levels compared to high cholesterol diet rabbits ( P < .050). This finding may reflect a reduction of chest pain or the beneficial effects of this plant root extract on cardiovascular health. The present study can serve as a basis for future investigations on the other effects of this plant on cardiovascular health.


2002 ◽  
Vol 8 (6) ◽  
pp. 307-313 ◽  
Author(s):  
Edgars Abele ◽  
Kira Rubina ◽  
Ramona Abele ◽  
Olegs Dzenitis ◽  
Pavel Arsenyan ◽  
...  

Silacyclic derivatives of heteroaromatic sulfides have been prepared by using phase transfer catalytic (PTC) system thiol / silacyclopropyl iodide / solid K2CO3 / 18-crown-6 / toluene. The target sulfides were isolated in yields up to 70 %. The S-derivatives of N-methylimidazolyl, benzoxazolyl and 1,3,4-triazolyl thiols selectively lowered the low density lipoprotein (LDL) level in mice with the high cholesterol diet in nutrition.


Sign in / Sign up

Export Citation Format

Share Document