Tanshinone IIA Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice Infected with Porphyromonas gingivalis

Jun 25, 2017Inflammation

Tanshinone IIA reduces artery plaque buildup in mice lacking ApoE infected with gum disease bacteria

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Abstract

Tanshinone IIA (TSA) at 60 mg/kg/day may reduce atherosclerotic risk factors in mice infected with Porphyromonas gingivalis.

TSA treatment led to a significant reduction in C-reactive protein (CRP), oxidized low-density lipoprotein (ox-LDL), and various pro-inflammatory cytokines.
Decreased expression of inflammatory markers such as IL-1β, IL-6, and TNF-α was observed in heart and aorta tissues following TSA administration.
Increases in microRNA levels associated with inflammation were downregulated by TSA in the context of P. gingivalis infection.
TSA may exert its effects through anti-inflammatory and anti-oxidative mechanisms, potentially preventing atherosclerosis progression.

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Tanshinone IIA (TSA), a pharmacologically active component isolated from Danshen, may prevent cardiovascular diseases due to its anti-inflammatory, anti-oxidative, and anti-adipogenic effects. Porphyromonas gingivalis, a major periodontal pathogen, may contribute to the progression of atherosclerosis. Here, we studied the effects of TSA on atherosclerosis in ApoEmice with P. gingivalis infection. Eight-week-old ApoEmice were randomized to (a) phosphate-buffered saline (PBS), (b) P. gingivalis, and (c) P. gingivalis + TSA (60 mg kg day). The mice were injected with (a) PBS, or (b) and (c) P. gingivalis 3 times per week for a total of 10 times. After 8 weeks, atherosclerotic risk factors in serum and in heart, aorta, and liver tissues were analyzed in all mice using Oil Red O, atherosclerosis cytokine antibody arrays, enzyme-linked immunosorbent assay (ELISA), real-time PCR, and microRNA array. CD40, G-CSF, IFN-γ, interleukin (IL)-1β, IL-6, MCP-1, MIP-3α, tumor necrosis factor-α (TNF-α), and VEGF were attenuated by TSA in atherosclerosis cytokine antibody arrays. TSA-treated mice showed a significant reduction of C-reactive protein (CRP), ox-LDL, IL-1β, IL-6, IL-12, and TNF-α in ELISA data. Real-time PCR analyses showed that TSA decreased the expression of CCL-2, CD40, IL-1β, IL-6, TNF-α, and MMP-2 in heart and aorta tissues. Moreover, hepatic CRP was downregulated by TSA, although FASN and HMG-CoA were not. The relative expressions of miR-146b and miR-155 were elevated by P. gingivalis infection and were downregulated by TSA treatment. These results suggest that TSA was a potential therapeutic agent that may have the ability to prevent P. gingivalis-induced atherosclerosis associated with anti-inflammatory and anti-oxidative effects. -/--/--1 -1

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Tanshinone IIA Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice Infected with Porphyromonas gingivalis

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