151. Chung Hun Wha Dam Tang attenuates atherosclerosis in apolipoprotein E-deficient mice via the NF-κB pathway
- Author
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Jamal Uddin, Stefan W. Ryter, Gyeong Jae Cho, Min Ho Cha, Hye-Seon Choi, Yeonsoo Joe, Hun Taeg Chung, Jeongmin Park, Jeong Woo Park, and Jinhyun Ryu
- Subjects
0301 basic medicine ,Mitochondrial ROS ,Apolipoprotein E ,Male ,medicine.medical_specialty ,Mice, Knockout, ApoE ,SOD2 ,Inflammation ,RM1-950 ,medicine.disease_cause ,NF-κB ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Western blot ,Enos ,Internal medicine ,Chung Hun Wha Dam Tang ,Human umbilical vein endothelial cells ,medicine ,Animals ,Humans ,Pharmacology ,biology ,U937 cell ,medicine.diagnostic_test ,Dose-Response Relationship, Drug ,Chemistry ,Body Weight ,NF-kappa B ,General Medicine ,U937 Cells ,biology.organism_classification ,Atherosclerosis ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,RAW 264.7 Cells ,Adipose Tissue ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Cytokines ,Therapeutics. Pharmacology ,medicine.symptom ,Reactive oxygen species ,Oxidative stress ,Drugs, Chinese Herbal - Abstract
Chung Hun Wha Dam Tang (CHWDT), a traditional Korean herbal formula, has been used for hundreds of years for alleviating dizziness, phlegm, and inflammation. The inhibitory effects of CHWDT on obesity have been reported. However, the effects of CHWDT in atherosclerosis have not yet been explored. Therefore, the aim of the study was to investigate whether CHWDT could confer protection from oxidative stress and inflammation in a high fat diet (HFD)-induced atherosclerosis model. Atherosclerosis was induced by feeding ApoeE−/− mice with HFD for 6 weeks. To examine the in vivo effects of CHWDT on HFD-induced atherosclerosis, mice on HFD for 6 weeks were orally administrated with CHWDT (400 or 800 mg/kg) every other day for an additional 6 weeks and histological features of aorta were determined by Sudan IV and H&E staining. The mRNA levels of TNF-α, SOD1, SOD2, iNOS or eNOS were determined with RT-PCR analysis or western blot analysis for protein levels. ROS generation was measured by CM-2DCFDA or MitoSox staining using FACS analysis or confocal microscopy. CHWDT decreased the mRNA levels of TNF-α and increased the mRNA levels of SOD1, SOD2 and catalase in both aorta and liver tissues of atherosclerotic mice. CHWDT attenuated TNF-α and iNOS expression in RAW 264.7 cells, U937 cells and HUVECs, and restored eNOS expression in HUVECs. CHWDT decreased H2O2-induced cellular ROS generation in RAW 264.7 cells and U937 cells, and also decreased H2O2-induced mitochondrial ROS generation in RAW 264.7 cells. Furthermore, SOD1, SOD2 and catalase mRNA levels were increased by pre-treatment with CHWDT in H2O2 and LPS-stimulated RAW 264.7 cells, as well as in LPS-treated U937 and HUVECs. CHWDT not only decreased LPS-induced NF-κB p65 phosphorylation but also inhibited the translocation of p65 from the cytosol to the nucleus in RAW 264.7 macrophages. These results suggest that CHWDT exerts inhibitory effects on atherosclerosis-induced oxidative stress and inflammation via the NF-κB pathway.
- Published
- 2019