Andrographolide protects against endothelial dysfunction and inflammatory response in rats with coronary heart disease by regulating PPAR and NF-κB signaling pathways

Abstract

Background: Andrographolide (Andro) is an active compound extracted from Andrographis, which has protective anti-inflammatory effects. But, its pathological role in coronary heart disease (CHD) is unclear, the aim of this study is to investigate the therapeutic effect of Andro in CHD and explore its potential mechanism.Methods: Here, we established a mouse model of CHD, and rats were randomly divided into 5 groups (n=10): sham, Andro (50 mg/kg), CHD, CHD + Andro (10 mg/kg), and CHD + Andro (50 mg/kg). HE staining was employed to evaluate the pathological changes of myocardial injury cardiac injury. The serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), highdensity lipoprotein cholesterol (HDL-C), nitric oxide (NO), TXA2, ET-1, and prostaglandin I2 (PGI2) were detected by ELISA assay. Myocardial inflammation and the interaction between Andro and PPAR-α/NF-κB axis was measured using western blot.Results: Compared with CHD groups, Andro preserved cardiac injury and decreased the levels of TC, TG, and LDL-C while increasing the level of HDL-C. In addition, Andro also reduced the levels of TNF-α, MCP-1, hs-CRP and IL-1β by shifting the macrophage phenotype and attenuated the endothelial dysfunction by increasing the serum levels of ET-1 and TAX2 and decreasing the levels of NO and PGI2 in mice. Furthermore, Andro impeded cardiac apoptosis and inhibited the activation of PPARα and NF-κB proteins.Conclusions: Andro may represent a medicinal approach for assessing and treating CHD.

A review on the molecular basis underlying the protective effects of Andrographis paniculata and andrographolide against myocardial injury

“…Besides, andrographolide elevated t-PA and reduced PAI-1 content, indicating the improvement of fibrinolytic function and reduction of blood coagulation in mice with chronic heart disease. 46 Microarray analysis also showed a reduction in CAV1 by andrographolide, which might help in maintaining NO• level and improved endothelial function in LPS-stimulated primary rat myocardial microvascular endothelial cells. 59 The postulated mechanisms of A. paniculata (Burm.f.)…”

“…Nees or andrographolide (as seen by reduced interstitial spaces, fibrosis, myocardial degeneration, distortion in the cardiomyocyte arrangement, cell oedema, degree of necrosis, and neutrophil infiltration). 17,[39][40][41]45,46 Administration of A. paniculata (Burm.f.) Nees or andrographolide also reversed cardiac fibrosis [indicated by lowered fibrosis marker such as alpha-smooth muscle actin (α-SMA)] and cardiac hypertrophy [cross-sectional area of cardiomyocytes, heart weight normalised with tibia length or body weight, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and beta-myosin heavy chain were reduced].…”

“…The suppression of inflammatory response was mediated through the inhibition of NF-κB. 46 In diabetic cardiomyopathy, andrographolide blocked NF-κB-mediated inflammatory response. As a result, the protein expression of cyclooxygenase-2 (COX-2), TNF-α, IL-1β, interleukin-6 (IL-6), intercellular cell adhesion molecules-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) were hindered.…”

“…Concomitantly, the protein level of phosphorylated IGF-1R was increased, while the expression of PPAR-α was downregulated after being treated with andrographolide. 45,46 A comprehensive study consisting of in vivo and in vitro experiments found reductions of Bax/Bcl-2 ratio and caspase-3 activity in the andrographolide-treated diabetic mice with myocardial dysfunction and in H9C2 cardiomyocytes stimulated by high concentration of glucose. The authors suggested that the anti-apoptotic activity of andrographolide was mediated through activation of Akt activity.…”

Pharmacological Potential of Andrographis paniculata (Burm. f.) Nees in Preventing Atherosclerosis: A Review

“…TNFα, IFN-γ and Cyt MAP kinase P32 proteins responsible for the anti-atherosclerotic effect. In addition, Andro inhibited the ox-LDL formation and interacted well with the atherosclerosis-protein receptor targets35 Andro analog could lower hepatic lipid peroxides Andro analog may ameliorate steatohepatitis and liver injury in atherosclerosis rats by increasing antioxidant and antiinflammatory activities36 It was stated that Anro able to lowering the TC, TG, and LDL-The study proven that Andro was able to decreasing cardiac ©…”