Tanshinone II A attenuates inflammatory responses of rats with myocardial infarction by reducing MCP-1 expression

Ren, Zhiguang; Tong, Yinghui; Xu, Wei; Ma, Jing; Chen, Y.

doi:10.1016/j.phymed.2009.08.010

Cited by 98 publications

(79 citation statements)

References 28 publications

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“…The cardiovascular and cerebrovascular efficacies of TSA were recognized early in the 1970s, and its sodium sulfonate derivative was marketed in China as a cardiovascular drug in the 1980s. More recently, various other pharmacological activities, including anti-inflammation (Ren et al, 2010), liver-and renal-protective effects (Zhang et al, 2009a), learning and memory improvement (Kim et al, 2009), and particularly its anticancer potential Lu et al, 2009;Shi et al, 2009;Zhang et al, 2009b), have been extensively studied and have attracted much attention from researchers worldwide. Previous reports strongly suggest that TSA is a promising leading compound for novel anticancer and cardiovascular drug development.…”

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confidence: 99%

Regioselective Glucuronidation of Tanshinone IIa after Quinone Reduction: Identification of Human UDP-Glucuronosyltransferases, Species Differences, and Interaction Potential

Wang¹,

Hao²,

Zhu³

et al. 2010

Drug Metab Dispos

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ABSTRACT:We have previously identified that the predominant metabolic pathway for tanshinone IIa (TSA) in rat is the NAD(P)H:quinone oxidoreductase 1 (NQO1)-mediated quinone reduction and subsequent glucuronidation. The present study contributes to further research on its glucuronidation enzyme kinetics, the identification of human UDP-glucuronosyltransferase (UGT) isoforms, and the interaction potential with typical UGT substrates. A pair of regioisomers (M1 and M2) of reduced TSA glucuronides was found from human, rat, and mouse, whereas only M1 was found in dog liver S9 incubations. The overall glucuronidation clearance of TSA in human liver S9 was 11.8 ؎ 0.8 l/min/mg protein, 0.7-, 0.8-, and 3-fold of that in the mouse, rat, and dog, respectively. Using intrinsic clearance M2/M1 as a regioselective index, opposite regioselectivity was found between human (0.7) and mouse (1.3), whereas no significant regioselectivity was found in rat. In a sequential metabolism system, by applying human liver cytosol as an NQO1 donor combined with a screening panel of 12 recombinant human UGTs, multiple UGTs were found involved in the M1 formation, whereas only UGT1A9 and, to a very minor extent, UGT1A1 and UGT1A3 contributed to the M2 formation. Further enzyme kinetics, correlation, and chemical inhibition studies confirmed that UGT1A9 played a major role in both M1 and M2 formation. In addition, TSA presented a potent inhibitory effect on the glucuronidation of typical UGT1A9 substrates propofol and mycophenolic acid, with an IC 50 value of 8.4 ؎ 1.8 and 8.9 ؎ 1.9 M, respectively. This study will help to guide future studies on characterizing the NQO1-mediated reduction and subsequent glucuronidation of other quinones.Quinones are a large group of compounds ubiquitous in nature and characterized with great biological, pharmacological, and/or toxicological significance. Humans are unavoidably exposed to many endogenous quinones such as coenzyme Q, vitamin K, oxidized products of endogenous phenols, and some xenobiotic quinones from foods, environmental pollutants, and drugs. The carbonyl group in the quinone structure is often a determining functional factor for their activities (Oppermann, 2007). For example, the quinone/hydroquinone interconversion of coenzyme Q plays an important role in the electron transport involved in cellular respiration, and the one-electron and/or two-electron reduction of the quinone carbonyl group-triggered redox cycle also largely explains the pharmacological or toxicological activities of many quinones. Note that the quinone carbonyl reduction and subsequent conjugation constitute the major biotransformation and metabolic elimination pathway of most quinones. Therefore, the biotransformation study of quinones is essential for understanding their bioactivation, detoxification, and/or inactivation process.Tanshinones are a class of diterpene phenanthrenequinone compounds isolated from the dried root of Salvia miltiorrhiza (Fam. Labiatae), which is a widely used traditional Chinese medicine with w...

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confidence: 99%

Regioselective Glucuronidation of Tanshinone IIa after Quinone Reduction: Identification of Human UDP-Glucuronosyltransferases, Species Differences, and Interaction Potential

Wang¹,

Hao²,

Zhu³

et al. 2010

Drug Metab Dispos

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“…In the present study, the observed inhibition of PERK (figure 9A), eIF2α (figure 9B), and the activation of ATF-4 ( figure 9C) by Tanshinone II A suggests that the Tanshinone II A relieves adriamycin-induced myocardial injury in rat model by down-regulation ERS related apoptosis. It was evidenced that Tanshinone II A had anti-inflammatory response (Ren et al, 2010). Finally, we tested heart tissue levels of TNF-α and TGF-β, and found tanshinone II A reduce adriamycin-induced inflammatory response.…”

Section: Ultrastrucmentioning

confidence: 99%

Tanshinone II A Relieves Adriamycin-induced Myocardial Injury in Rat Model

Wang¹,

Chai²,

Wang³

et al. 2015

IJC

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As an effective antineoplastic agent, adriamycin (ADR) remains a use for the treatment of cancer. However, it is limited by the serous cardiotoxicity. Tanshinone II A is the main effective component of Salvia miltiorrhiza Bunge which has been used for treatment of cardiovascular diseases. The purpose of this study is to evaluate the protective effect of Tanshinone II A on adriamycin-induced myocardial injury in rat and explore the mechanism of this effect. Male Wistar rats (200 ± 20 g) were divided into three groups, control (CON) group, adriamycin (ADR) group and ADR + Tanshinone II A (TRA) group. At the end of the 4 week treatment period, cardiac function was evaluated by transthoracic echocardiography. Molecular and cellular measurements were performed in atrial muscle to examine histopathological changes, the formation of fibrosis, Inflammation and apoptosis. Cardiac dysfunction was induced by adriamycin, as indicated by significant decreases in ventricular fractional shortening and ejection fraction. This adriamycin-induced cardiac dysfunction was prevented by the treatment of Tanshinone II A. Adriamycin induced pathological changes and fibrosis, activated apoptosis (increased TUNEL index, apoptotic DNA fragmentation,and caspase-3 activity and decreased Bcl-2/Bax ratio), inflammation and suppressed phosphorylation status (eIF2α and PERK) in atrial. All these molecular and cellular alterations induced by ADR were not found in the rats treated with Tanshinone II A. These findings demonstrate clearly that Tanshinone II A protects the cardiomyocytes against the ADR-induced cardiomyopathy by preventing the activation of cardiac fibrosis and apoptosis, and the effects are probably mediated through ERS pathway.

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“…It is also widely used in the treatment of coronary heart disease, angina pectoris, and other cardiovascular diseasesl (Liu et al, 2009;Ren et al, 2010). Recent studies have shown that TanIIA has potential as a cancer treatment (Lu et al, 2009) and can lead to the reversal of the malignant phenotype of cancers and reduce metastasis and invasion.…”

Section: Introductionmentioning

confidence: 99%

In vitro inhibition of invasion and metastasis in colon cancer cells by TanIIA

Zhang¹,

Liu²,

Xie³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The purpose of this study was to investigate the effect of the traditional Chinese medicine TanIIA on the viability, invasion, and metastasis of SW480 cells. SW480 cells were treated with TanIIA for 24 h, and MTT assays were performed to determine the effect of TanIIA on cell viability. Transwell transmembrane experiments were applied to test the effect of 1.0 mg/mL TanIIA on SW480 cell invasion and metastasis abilities. Western blotting was performed to determine the expression of the tumor cell metastasis proteins E-cadherin, vimentin, and MMP-9. The cell growth inhibition rates were 0%, 26 ± 4.3%, 43.47 ± 4.0%, 63.0 ± 5.5%, and 76.8 ± 7.8% for treatment with 0, 0.5, 1.0, 2.0, and 5.0 mg/L TanIIA, respectively. The differences in the cell viability inhibitory rates among all groups were statistically significant (P < 0.05). The Transwell assay results indicated that SW620 cell invasion and metastasis abilities were strongly inhibited by 1.0 mg/mL TanII. The western blotting results showed that the expression of E-cadherin was significantly increased and that the expression levels of vimentin and MMP-9 were significantly decreased after treatment with 1.0 mg/mL TanII for 24 h (P < 0.05). Tan II can effectively inhibit the biological activity of colon cancer in vitro and prevent the invasion of colon cancer cells.

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Tanshinone II A attenuates inflammatory responses of rats with myocardial infarction by reducing MCP-1 expression

Cited by 98 publications

References 28 publications

Regioselective Glucuronidation of Tanshinone IIa after Quinone Reduction: Identification of Human UDP-Glucuronosyltransferases, Species Differences, and Interaction Potential

Regioselective Glucuronidation of Tanshinone IIa after Quinone Reduction: Identification of Human UDP-Glucuronosyltransferases, Species Differences, and Interaction Potential

Tanshinone II A Relieves Adriamycin-induced Myocardial Injury in Rat Model

In vitro inhibition of invasion and metastasis in colon cancer cells by TanIIA

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