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Protective effects of triptolide on TLR4 mediated autoimmune and inflammatory response induced myocardial fibrosis in diabetic cardiomyopathy.
- Source :
-
Journal of Ethnopharmacology . Dec2016, Vol. 193, p333-344. 12p. - Publication Year :
- 2016
-
Abstract
- Ethnopharmacological relevance Triptolide is a most important active ingredient extracted from traditional Chinese medicine Tripterygium, which has been widely used to treat glomerulonephritis as well as immune-mediated disorders, likely for its immunosuppressive, anti-proliferative and anti-inflammatory effects. Aim of the study In this study, we have investigated the potential protective effects of triptolide against diabetic cardiomyopathy (DCM) by regulating immune system, attenuating inflammatory response, thus resulting in decreased cardiac fibrosis and improved left ventricle function. Materials and methods Sprague-Dawley rats were randomly divided into 5 groups: normal group, diabetic group and diabetic rats treated with triptolide (50, 100, or 200 μg/kg/day resp) for 8 weeks. Cardiac function was performed by echocardiography and histopathology of the hearts was examined with HE, Masson staining and scanning electron microscopy. Immune regulation mediator, macrophage infiltration, inflammatory response and cardiac fibrosis related cytokines were measured by RT-PCR, Western blot and Immunohistochemistry staining. Results In the diabetic group, the expressions of TLR4 and NF-κB p65 were both up-regulated, which was associated with increased pro-inflammatory cytokines, coupled with cardiac fibrosis and impaired left ventricular function. Interestingly, pathological structure and function of left ventricle were both significantly improved in the triptolide treated groups. Furthermore, the immune mediator TLR4, downstream activator NF-κB p65, macrophage infiltration (CD68+), pro-inflammatory cytokines (TNF-α, IL-1β), cell adhesion molecule (VCAM-1) and chemokine (MCP-1) were significantly suppressed when treated with medium and high dosage triptolide compared with the diabetic group. Moreover, cardiac fibrosis pathway including α-SMA, TGF-β1, vimentin and collagen accumulations were observed significantly decreased in the triptolide treated groups. Conclusions Our data demonstrated that the protective effects of triptolide against DCM might attribute to inhibition of TLR4-induced NF-κB/IL-1β immune pathway, suppression of NF-κB/TNF-α/VCAM-1 inflammatory pathway and down-regulation of TGF-β1/α-SMA/Vimentin fibrosis pathway. [ABSTRACT FROM AUTHOR]
- Subjects :
- *FIBROSIS
*HEART analysis
*DIABETIC cardiomyopathy
*ALTERNATIVE medicine
*ANIMAL experimentation
*ANTI-inflammatory agents
*CELL adhesion molecules
*CELL migration
*CHEMOKINES
*COLLAGEN
*CYTOKINES
*ECHOCARDIOGRAPHY
*LEFT heart ventricle
*HISTOLOGICAL techniques
*IMMUNE system
*IMMUNOHISTOCHEMISTRY
*INTERLEUKINS
*MEDICINAL plants
*MICROBIOLOGICAL assay
*MICROSCOPY
*POLYMERASE chain reaction
*RATS
*STAINS & staining (Microscopy)
*TUMOR necrosis factors
*WESTERN immunoblotting
*DNA-binding proteins
*PLANT extracts
*STATISTICAL significance
*REVERSE transcriptase polymerase chain reaction
*DESCRIPTIVE statistics
*IN vivo studies
*PHARMACODYNAMICS
*METABOLISM
*PREVENTION
Subjects
Details
- Language :
- English
- ISSN :
- 03788741
- Volume :
- 193
- Database :
- Academic Search Index
- Journal :
- Journal of Ethnopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 119417582
- Full Text :
- https://doi.org/10.1016/j.jep.2016.08.029