Tanshinone IIA suppresses cholesterol accumulation in human macrophages: role of heme oxygenase-1

Liu, Zhiping; Wang, Jiaojiao; Huang, Erwen; Gao, Si; Li, Hong; Lu, Jing; Tian, Kunming; Little, Peter J.; Shen, X. Y.; Xu, Suowen

doi:10.1194/jlr.m040394

Cited by 80 publications

(65 citation statements)

References 54 publications

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“…Estrogen reduces the plasma cholesterol in ovariectimized apoE -/- mice, and it is an estrogen receptor dependent process [29]. Tanshinone IIA has been shown to reduce the content of macrophages, cholesterol accumulation, and the development of atherosclerotic plaqued [30]. It also attenuates advanced atherosclerotic lesions in apoE -/- mice [21], but it does not alter serum lipid profile and body weight in apoE -/- mice [21].…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effects of Tanshinone IIA on Atherosclerostic Vessels of Ovariectomized ApoE-/- Mice are Mediated by Estrogen Receptor Activation and Through the ERK Signaling Pathway

Liu¹,

Guo²,

Ma³

et al. 2015

Cell Physiol Biochem

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Aims: Estrogen plays a protective role in atherosclerosis. Our preliminary work demonstrated that the active conformation of Tanshinone IIA(TanIIA) is similar to the 17ß-estradiol and it can bind to the estrogen receptor. Here, we hypothesized that Tanshinone IIA might have anti-inflammatory and anti-oxidative effects in atherosclerosis, mediated through estrogen receptor activation. Methods: Subjects for this study were 120 apoE^-/- female mice and 20 C57/BL female mice. The apoE^-/- mice were ovariectomized (OVX) and the C57/BL mice were sham ovariectomized. The sham OVX mice were maintained on a normal diet (NOR) group. The OVX apoE^-/- mice were fed a high fat diet and randomly divided into 6 groups: Model (MOD) group which was fed a high fat diet only, E₂ group were given estrogen (E₂) 0.13mg/kg/d; E₂+ICI group were given E₂:0.13mg/kg/d and ICI182780:65mg/kg/m; TLD group (TanIIA low dose) were given TanIIA: 30mg/kg/d; THD group (TanIIA high dose) were given TanIIA:60mg/kg/d; and TLD+ICI group were given TanIIA 30mg/kg/d and ICI182780 65mg/kg/m. After three months of treatment, the aorta and the blood of the mice from each group was collected. The aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE) and oil red O staining and for testing the expression of p-ERK1/2 by Western blot. The blood was used for testing the serum cholesterol, superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), nuclear factor kappa (NF-κB), soluble intercellular cell adhesion molecule-1 (sICAM-1), activating protein-1 (AP-1), E-selectin and 17ß-estradiol in serum. Results: Tanshinone IIA significantly reduced the lipid deposition in aorta, decreased the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), MDA, NF-κB, sICAM-1, AP-1, and E-selectin in serum but increased the levels of high density lipoprotein (HDL) and SOD in serum. Tanshinone IIA also suppressed the expression of p-ERK1/2. Tanshinone IIA had no effect of level of serum 17ß-estradiol levels. All of the effects of Tanshinone IIA were similar to estrogen and were inhibited by the estrogen receptor antagonist ICI182780. Conclusion: Tanshinone IIA may play an anti-inflammatory and anti-oxidative stress role in OVX atherosclerotic apoE^-/- mice by activating the estrogen receptor through the ERK signaling pathway. Therefore, Tanshinone IIA, as a phytoestrogen, could be used for estrogen replacement therapy for cardiovascular disease of postmenopausal women.

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Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effects of Tanshinone IIA on Atherosclerostic Vessels of Ovariectomized ApoE-/- Mice are Mediated by Estrogen Receptor Activation and Through the ERK Signaling Pathway

Liu¹,

Guo²,

Ma³

et al. 2015

Cell Physiol Biochem

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“…Cellular uptake DiI-HDL assay was performed as described by Liu et al ( 38 ). HepG2 cells were incubated with RUT (0.035, 0.35, 3.48, and 34.80 M) in MEM medium for 24 h. After incubation, the cells were washed twice with PBS and incubated with DiI-HDL (5 g/ml) at 37°C for additional 4 h. At the end of incubation period, cells were washed and examined by Eclipse TE2000-U Inverted Microscope (Nikon,Tokyo, Japan).…”

Section: Cellular Uptake Of Dii-hdlmentioning

confidence: 99%

Rutaecarpine suppresses atherosclerosis in ApoE−/− mice through upregulating ABCA1 and SR-BI within RCT

Yang

Liu

et al. 2014

Journal of Lipid Research

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Excessive accumulation of cholesterol in macrophages results in a transformation of the macrophage into foam cells and eventually causes atherosclerosis ( 1, 2 ). The pathogenic process represents a chronic and complicated interaction involving multiple factors. Reverse cholesterol transport (RCT) is a process by which extrahepatic (peripheral) cholesterol is returned to the liver for excretion in the bile and ultimately the feces, thus reducing the risk of atherosclerosis ( 3, 4 ). Although there have been great efforts in discovering drugs against atherosclerosis ( 5 ), the output has been unsatisfactory. Removal of excess cholesterol from macrophage foam cells is considered to be one of the therapeutic strategies ( 6 ). The crucial cellular transporters and receptors that relate to cholesterol effl ux include,

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“…After 8 weeks, the mice were continued on Western diet for an additional 4 weeks and orally administered (by oral gavage) once per day during this period with GSK1016790A (10 mg/kg/d) which was dissolved in 2% carboxymethyl cellulose sodium (CMC-Na, Sigma) [50, 51]. Atherosclerotic lesion areas in en face aorta and aortic sinus were analyzed as we previously described [47, 52].…”

Section: Methodsmentioning

confidence: 99%

“…The pictures presented were a composite of 4-6 images captured at different regions of the same aorta. Percentage of Oil Red O-positive stained area in relation to total luminal surface area was quantified using computer-assisted morphometry (NIH ImageJ software version 1.48) [50]. …”

Section: Methodsmentioning

confidence: 99%

A novel TRPV4-specific agonist inhibits monocyte adhesion and atherosclerosis

Liu

Yin

et al. 2016

Oncotarget

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TRPV4 ion channel mediates vascular mechanosensitivity and vasodilation. Here, we sought to explore whether non-mechanical activation of TRPV4 could limit vascular inflammation and atherosclerosis. We found that GSK1016790A, a potent and specific small-molecule agonist of TRPV4, induces the phosphorylation and activation of eNOS partially through the AMPK pathway. Moreover, GSK1016790A inhibited TNF-α-induced monocyte adhesion to human endothelial cells. Mice given GSK1016790A showed increased phosphorylation of eNOS and AMPK in the aorta and decreased leukocyte adhesion to TNF-α-inflamed endothelium. Importantly, oral administration of GSK1016790A reduced atherosclerotic plaque formation in ApoE deficient mice fed a Western-type diet. Together, the present study suggests that pharmacological activation of TRPV4 may serve as a potential therapeutic approach to treat atherosclerosis.

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Tanshinone IIA suppresses cholesterol accumulation in human macrophages: role of heme oxygenase-1

Cited by 80 publications

References 54 publications

Anti-Inflammatory Effects of Tanshinone IIA on Atherosclerostic Vessels of Ovariectomized ApoE-/- Mice are Mediated by Estrogen Receptor Activation and Through the ERK Signaling Pathway

Anti-Inflammatory Effects of Tanshinone IIA on Atherosclerostic Vessels of Ovariectomized ApoE-/- Mice are Mediated by Estrogen Receptor Activation and Through the ERK Signaling Pathway

Rutaecarpine suppresses atherosclerosis in ApoE−/− mice through upregulating ABCA1 and SR-BI within RCT

A novel TRPV4-specific agonist inhibits monocyte adhesion and atherosclerosis

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