The effect of tanshinone IIA on renal and liver functions in ovine fetuses<i>in utero</i>

Zhang, Yifan; Rui, Can; Mao, Caiping; Zhang, Yuying; Zhu, Liyan; Shao, Hu; Wang, Liping; Wang, Aiqing; Xu, Zhice

doi:10.1080/01480540903176594

Cited by 8 publications

(3 citation statements)

References 16 publications

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“…Responses to MCh were investigated following a 30-min incubation with a combination of CV-6209 (Santa Cruz sc-207461) and WEB 2086 (Tocris 2339). All vascular data were presented as means Ϯ SE of the negative log of the effective concentration that will produce 50% of the maximum response (pEC 50) or the maximum response (Emax).…”

Section: Methodsmentioning

confidence: 99%

Effect of sodium tanshinone IIA sulfonate treatment in a rat model of preeclampsia

Morton

Quon

Cheung

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Morton JS, Quon A, Cheung PY, Sawamura T, Davidge ST. Effect of sodium tanshinone IIA sulfonate treatment in a rat model of preeclampsia. Am J Physiol Regul Integr Comp Physiol 308: R163-R172, 2015. First published December 4, 2014 doi:10.1152/ajpregu.00222.2014.-Preeclampsia is a disorder of pregnancy with a significant impact on maternal and fetal health. The complexity of this multifactorial condition has precluded development of effective therapies and, although many potential pathways have been investigated, the etiology still requires clarification. Our group has investigated the scavenger lectin-like oxidized LDL (LOX-1) receptor, which may respond to factors released from the distressed placenta that contribute to the vascular pathologies observed in preeclampsia. Given the known beneficial effects of sodium tanshinone IIA sulfonate (STS; a component of Salvia miltiorrhiza) on vasodilation, reduction of oxidative stress, and lipid profiles, we have investigated its role as a potential treatment strategy. We hypothesized that STS would improve vascular endothelial function and, combined with a reduction in oxidative stress, would improve pregnancy outcomes in a rat model of preeclampsia (reduced uteroplacental perfusion pressure, RUPP). We further hypothesized this may occur via the action of STS on the LOX-1 and/or platelet-activating factor (PAF) receptor axes. The RUPP model increased maternal blood pressure, vascular oxidative stress, and involvement of the vascular PAF receptor. Treatment with STS during pregnancy decreased both oxidative stress and involvement of the PAF receptor; however, it also increased involvement of the LOX-1 receptor, which is in line with the concept that scavenger receptors, such as LOX-1 and PAF, are upregulated in response to ligand binding and/or under pathological conditions. In this model of preeclampsia, however, the vascular actions of STS did not lead to improvements in pregnancy outcome such as fetal biometrics or maternal blood pressure. preeclampsia; pregnancy; vascular function; tanshinone; LOX-1; PAF receptor PREECLAMPSIA is a major cause of maternal and fetal morbidity and mortality affecting from 2% to 8% of pregnancies worldwide each year with developing countries impacted to a greater extent than industrialized countries (44). It is a highly complex disorder for which many pathological pathways and potential key components have been proposed. In general, poor development of placental spiral arteries is thought to cause the release of circulating factors from a poorly perfused placenta, which impair maternal vascular function, manifested as endothelial dysfunction (4, 17, 27). Impaired maternal vascular function then leads to an abnormal hemodynamic response to pregnancy and reduced perfusion of maternal organs, including the placenta, resulting in a positive feedback loop. Currently, the only known "cure" for preeclampsia is removal of the placenta, and by default the fetus, reinforcing this organ's central role in the disorder. Our own group has demonstr...

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Section: Methodsmentioning

confidence: 99%

Effect of sodium tanshinone IIA sulfonate treatment in a rat model of preeclampsia

Morton

Quon

Cheung

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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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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“…1.1 mg/kg/day) [ 34 , 35 ] and ovine (approx. 1.8 mg/kg/day) [ 36 , 37 ] trials and a median of 20 mg/kg/day in rodent studies [ 5 , 10 , 38 – 41 ]. The timing of treatment was chosen as a clinically relevant time-point during which intervention would be possible in humans.…”

Section: Methodsmentioning

confidence: 99%

The Vascular Effects of Sodium Tanshinone IIA Sulphonate in Rodent and Human Pregnancy

et al. 2015

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Danshen, in particular its derivative tanshinone IIA (TS), is a promising compound in the treatment of cardiovascular diseases and has been used for many years in traditional Chinese medicine. Although many actions of TS have been researched, its vasodilator effects in pregnancy remain unknown. There have been a few studies that have shown the ability of TS to reduce blood pressure in women with hypertensive pregnancies; however, there are no studies which have examined the vascular effects of TS in the pregnant state in either normal or complicated pregnancies. Our aim was to determine the vasoactive role of TS in multiple arteries during pregnancy including: rat resistance (mesenteric and uterine) and conduit (carotid) arteries. Further, we aimed to assess the ability of TS to improve uterine blood flow in a rodent model of intrauterine growth restriction. Wire myography was used to assess vascular responses to the water-soluble derivative, sodium tanshinone IIA sulphonate (STS) or to the endothelium-dependent vasodilator, methylcholine. At mid-pregnancy, STS caused direct vasodilation of rat resistance (pEC50 mesenteric: 4.47±0.05 and uterine: 3.65±0.10) but not conduit (carotid) arteries. In late pregnancy, human myometrial arteries responded with a similar sensitivity to STS (pEC50 myometrial: 3.26±0.13). STS treatment for the last third of pregnancy in eNOS-/- mice increased uterine artery responses to methylcholine (Emax eNOS-/-: 55.2±9.2% vs. eNOS-/- treated: 75.7±8.9%, p<0.0001). The promising vascular effects, however, did not lead to improved uterine or umbilical blood flow in vivo, nor to improved fetal biometrics; body weight and crown-rump length. Further, STS treatment increased the uterine artery resistance index and decreased offspring body weight in control mice. Further research would be required to determine the safety and efficacy of use of STS in pregnancy.

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The effect of tanshinone IIA on renal and liver functions in ovine fetusesin utero

Cited by 8 publications

References 16 publications

Effect of sodium tanshinone IIA sulfonate treatment in a rat model of preeclampsia

Effect of sodium tanshinone IIA sulfonate treatment in a rat model of preeclampsia

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

The Vascular Effects of Sodium Tanshinone IIA Sulphonate in Rodent and Human Pregnancy

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