Dataset Information

Dan-Lou Prescription Inhibits Foam Cell Formation Induced by ox-LDL via the TLR4/NF-?B and PPAR? Signaling Pathways.

ABSTRACT: Atherosclerosis is the major worldwide cause of mortality for patients with coronary heart disease. Many traditional Chinese medicine compound prescriptions for atherosclerosis treatment have been tried in patients. Dan-Lou prescription, which is improved from Gualou-Xiebai-Banxia decoction, has been used to treat chest discomfort (coronary atherosclerosis) for approximately 2,000 years in China. Although the anti-inflammatory activities of Dan-Lou prescription have been proposed previously, the mechanism remains to be explored. Based on the interaction between inflammation and atherosclerosis, we further investigated the effect of Dan-Lou prescription on macrophage-derived foam cell formation and disclosed the underlying mechanisms. In the oxidative low-density lipoprotein (ox-LDL) induced foam cells model using murine macrophage RAW 264.7 cells, the ethanol extract from Dan-Lou prescription (EEDL) reduced ox-LDL uptake and lipid deposition by inhibiting the protein and mRNA expression of Toll-like receptor (TLR)4 and scavenger receptor (SR)B1. After stimulation with ox-LDL, the metabolic profile of macrophages was also changed, while the intervention of the EEDL mainly regulated the metabolism of isovalerylcarnitine, arachidonic acid, cholesterol, aspartic acid, arginine, lysine, L-glutamine and phosphatidylethanolamine (36:3), which participated in the regulation of the inflammatory response, lipid accumulation and cell apoptosis. In total, 27 inflammation-related gene targets were screened, and the biological mechanisms, pathways and biological functions of the EEDL on macrophage-derived foam cells were systemically analyzed by Ingenuity Pathway Analysis system (IPA). After verification, we found that EEDL alleviated ox-LDL induced macrophage foam cell formation by antagonizing the mRNA and protein over-expression of PPAR?, blocking the phosphorylation of IKK?/?, I?B? and NF-?B p65 and maintaining the expression balance between Bax and Bcl-2. In conclusion, we provided evidences that Dan-Lou prescription effectively attenuated macrophage foam cell formation via the TLR4/NF-?B and PPAR? signaling pathways.

SUBMITTER: Gao LN

PROVIDER: S-EPMC5987004 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dan-Lou Prescription Inhibits Foam Cell Formation Induced by ox-LDL via the TLR4/NF-κB and PPARγ Signaling Pathways.

Gao Li-Na LN Zhou Xin X Lu Yu-Ren YR Li Kefeng K Gao Shan S Yu Chun-Quan CQ Cui Yuan-Lu YL

Frontiers in physiology 20180529

Atherosclerosis is the major worldwide cause of mortality for patients with coronary heart disease. Many traditional Chinese medicine compound prescriptions for atherosclerosis treatment have been tried in patients. Dan-Lou prescription, which is improved from Gualou-Xiebai-Banxia decoction, has been used to treat chest discomfort (coronary atherosclerosis) for approximately 2,000 years in China. Although the anti-inflammatory activities of Dan-Lou prescription have been proposed previously, the ...[more]

PMID: 29896109

Similar Datasets

Project description:BackgroundAlthough, Dan-Lou prescription (DLP) is used for antagonizing check discomfort and heartache, the pharmacological mechanism has not been clearly illustrated. Our present study aimed to design inflammatory models induced by LPS in vivo and in vitro to investigate the anti-inflammation of DLP ethanol extract (EEDL) and the potential mechanisms.MethodsEEDL was prepared and then analyzed by high performance liquid chromatography (HPLC). Further, the anti-inflammatory effects of EEDL in vivo was evaluated by measuring inflammation-associated factors includingcytokines, chemokines and acute phase proteins in lipopolysaccharide (LPS)-induced mice serum and liver. The anti-inflammatory mechanism exploration of EEDL was performed in LPS-stimulated RAW 264.7 cells. Different effects of EEDL on nitric oxide (NO) and prostaglandin (PG)E2 secretion were investigated by Griess reagent method and enzyme-linked immunosorbent assay (ELISA) respectively. Then the mRNA and protein expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were measured by real-time reverse-transcription polymerase chain reaction (RT-PCR), ELISA and Western blot. Other chemokines and acute phase proteins were determined by proteome profile array. Finally, the ELISA based transcription factor assay was applied to measure the DNA-binding activity of nuclear transcription factor (NF)-κB p65.ResultsEight compounds from EEDL have been identified as gallic acid, salvianic acid, puerarin, daidzin, paeoniflorin, salvianolic acid B, cryptotanshinone, and tanshinone IIA, with amounts of 0.26, 9.84, 10.41, 2.55, 9.44, 3.82, 0.24 and 0.3 mg/kg, respectively. In vivo, EEDL administration antagonized the up-regulation of more than 17 kinds of cytokines, chemokines and acute phase proteins in LPS-treated mice serum, and inhibited LPS-induced IL-6 mRNA and protein expression in mice liver tissue. In vitro, LPS-induced NO and PGE2 over-productions were decreased by EEDL treatment. The mRNA and protein expression of iNOS, COX-2 and IL-6 were similarly inhibited by EEDL treatment, which might be attributed to decrease the DNA-binding activity of NF-κB p65.ConclusionEEDL was valid for anti-inflammation and the potential molecular mechanisms might be due to the inhibition of of LPS-induced iNOS/NO, COX-2/PGE2 and cytokines expression by antagonizing the activation of NF-κB p65.

Project description:Introduction: Atherosclerosis is the main cause of many cardiovascular diseases and contributes to morbidity and mortality worldwide. The formation of macrophage-derived foam cells plays a critical role in the early stage of atherosclerosis pathogenesis. Diterpenoids found in the flowers of Callicarpa rubella Lindl., a traditional Chinese medicine, have been reported to have anti-inflammatory activity. However, little is known about the effects of these diterpenoids on macrophage foam cell formation. Methods: A macrophage-derived foam cell formation model was established by treating RAW264.7 cells with oxidized low-density lipoprotein (ox-LDL) for 24 h. Oil red O staining were used to detect the intracellular lipids. The cholesterol efflux capacity was assayed by labeling cells with 22-NBD-cholesterol. Western blots and real-time PCRs were performed to quantify protein and mRNA expressions. Results: Two diterpenoid molecules, 14α-hydroxyisopimaric acid (C069002) and isopimaric acid (C069004), extracted from the flowers of Callicarpa rubella Lindl., significantly attenuated ox-LDL-induced foam cell formation in RAW264.7 macrophages. Further investigation showed that these two diterpenoids could promote cholesterol efflux from RAW264.7 macrophages to apolipoprotein A-I or high-density lipoproteins, which was associated with upregulated expression of ATP-binding cassette A1/G1 (ABCA1/G1), liver X receptor-α (LXRα), and peroxisome proliferator-activated receptor-γ (PPARγ). Unexpectedly, the diterpenoids C069002 and C069004 failed to enhance the mRNA transcription of the ABCG1 gene in macrophage-derived foam cells induced by ox-LDL. To evaluate the effects of diterpenoids on macrophage foam cell formation and determine the underlying mechanism, two drugs (lovastatin and rosiglitazone) were used as positive controls. Although both drugs could reduce macrophage foam cell formation and promote cholesterol efflux, they each had distinctive abilities to modulate the expression of cholesterol efflux-related genes. In contrast to lovastatin, rosiglitazone showed a similar influence on the expression of cholesterol efflux-related genes (including ABCA1, LXRα, and PPARγ) as the diterpenoids regardless of the presence or absence of ox-LDL, implying a similar mechanism by which they may exert atheroprotective effects. Conclusion: Our research indicates that diterpenoids effectively inhibit ox-LDL-induced macrophage foam cell formation by promoting cholesterol efflux from macrophages via the PPARγ-LXRα-ABCA1 pathway. Further investigation of diterpenoids as potential drugs for the treatment of atherosclerosis is warranted.

Dataset Information

Dan-Lou Prescription Inhibits Foam Cell Formation Induced by ox-LDL via the TLR4/NF-?B and PPAR? Signaling Pathways.

Publications

Dan-Lou Prescription Inhibits Foam Cell Formation Induced by ox-LDL via the TLR4/NF-κB and PPARγ Signaling Pathways.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets