Activation of transsulfuration pathway by salvianolic acid a treatment: a homocysteine-lowering approach with beneficial effects on redox homeostasis in high-fat diet-induced hyperlipidemic rats

Zhang, Wenting; He, Hua; Wang, Haidong; Wang, Shijun; Li, Xi; Liu, Yao; Jiang, Huiyong; Jiang, Hao; Yan, Yi–Dan; Wang, Yixuan; Liu, Xiaoquan

doi:10.1186/1743-7075-10-68

Cited by 14 publications

(12 citation statements)

References 42 publications

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“…The oxidative stress module, represented by the ratio between SOD and MDA, is widely regarded as the first and key event in the activation of pathways involved in the pathogenesis of diabetic complications [36] . In the present investigation, combination treatment was observed to possess potent antioxidant capacity, which was consistent with previous studies [15,37] . Simultaneously, hyperglycemia was reported to induce the overproduction of superoxide and inhibit eNOS activity, which accelerated vasculature impairment in diabetes [38,39] .…”

Section: Discussionsupporting

confidence: 93%

“…Polyphenols have been reported to regulate glucose and lipid homeostasis, reducing the risk of metabolic syndromes and T2DM complications [47] . Sal A is a polyphenolic derivative and has recently been validated to exert multifactorial effects and significantly contributes to preventing diabetes and its complications [15,16,37] . In the present study, the radar chart of combination therapy indicated that less homeostatic disruption occurred and that the balances among modules were remarkably restored.…”

Section: Discussionmentioning

confidence: 99%

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A mini-network balance model for evaluating the progression of cardiovascular complications in Goto-Kakizaki rats

et al. 2017

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Cardiovascular complications represent a leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). During such complicated progression, subtle variations in the cardiovascular risk (CVR)-related biomarkers have been used to identify cardiovascular disease at the incipient stage. In this study we attempt to integrally characterize the progression of cardiovascular complications and to assess the beneficial effects of metformin combined with salvianolic acid A (Sal A), in Goto-Kakizaki (GK) rats with spontaneous T2DM. The rats were treated with metformin ( , ip) at ages from 8 to 22 weeks. During the treatment, the levels of asymmetric dimethylarginine, L-arginine, superoxide dismutase, malondialdehyde, glucose, high density lipoprotein and low density lipoprotein were assessed. Based on alterations in these biomarkers, a mini-network balance model was established using matrixes and vectors. Radar charts were created to visually depict the disruption of CVR-related modules (endothelial function, oxidative stress, glycation and lipid profiles). The description for the progression of cardiovascular disorder was quantitatively represented by u, the dynamic parameter of the model. The modeling results suggested that untreated GK rats tended to have more severe cardiovascular complications than the treatment groups. Metformin monotherapy retarded disease deterioration, whereas the combination treatment ameliorated the disease progression via restoring the balance. The current study, which focused on the balance of the mini-network and interactions among CVR-related modules, proposes a novel method for evaluating the progression of cardiovascular complications in T2DM as well as a more beneficial intervention strategy.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

A mini-network balance model for evaluating the progression of cardiovascular complications in Goto-Kakizaki rats

et al. 2017

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“…The elevation of homocysteine level in NAFLD/NASH may result from inhibition of CBS activity [11][12][13] or protein expression [15]. However, the underlying molecular mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…However, some researchers have reported that plasma homocysteine level was elevated in patients with NAFLD [9], NASH [10], and murine models of nutritionally induced obesity [11][12][13][14]. The elevation of homocysteine level in NAFLD/NASH may result from inhibition of CBS activity [11][12][13] or protein expression [15].…”

Section: Introductionmentioning

confidence: 99%

Exendin-4 regulates redox homeostasis in rats fed with high-fat diet

Niu

Wang

et al. 2015

ABBS

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Non-alcoholic fatty liver disease (NAFLD) is associated with increased plasma homocysteine level, which is caused by down-regulation of hepatic cystathionine beta-synthase (CBS) activity. CBS catalyzes the first step in the transsulfuration of homocysteine to cysteine, which contributes ∼50% of the cysteine required for hepatic biosynthesis of glutathione (GSH), the most abundant antioxidant in cells. As the glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. exendin-4) effectively reverse hepatic steatosis, the effect of exendin-4 on both homocysteine and redox status was investigated in the livers of rats fed with high-fat diet (HFD). It was found that HFD down-regulated CBS protein expression, which was probably due to induction of rno-miR-376c expression in the liver. The level of GSH was markedly reduced, whereas the level of malonydialdehyde, an indicator of lipid peroxidation, was significantly increased in the livers of rats fed with HFD. Exendin-4 treatment increased hepatic CBS protein and GSH levels, and reduced malonydialdehyde level in hyperlipidemic rats. Our findings suggest that GLP-1 receptor agonists have beneficial effects on redox homeostasis in NAFLD.

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“…Further investigation of the relationship between methylation of Danshen catechols and hyperhomocysteinemia risk may facilitate hazard identification for this herbal injection. This may also improve understanding of the endothelial protection properties of Danshen catechols (Chan et al, 2004;Cao et al, 2009;Yang et al, 2010;Zhang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Systemic Exposure to and Disposition of Catechols Derived from Salvia miltiorrhiza Roots (Danshen) after Intravenous Dosing DanHong Injection in Human Subjects, Rats, and Dogs

Wang

Huang

et al. 2015

Drug Metab Dispos

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DanHong injection is a Danshen (Salvia miltiorrhiza roots)-based injectable solution for treatment of coronary artery disease and ischemic stroke. Danshen catechols are believed to be responsible for the injection's therapeutic effects. This study aimed to characterize systemic exposure to and elimination of Danshen catechols in human subjects, rats, and dogs receiving intravenous DanHong injection. A total of 28 catechols were detected, with content levels of 0.002-7.066 mM in the injection, and the major compounds included tanshinol, protocatechuic aldehyde, salvianolic acid B, rosmarinic acid, salvianolic acids A and D, and lithospermic acid with their daily doses ‡10 mmol/subject. After dosing, tanshinol, salvianolic acid D, and lithospermic acid exhibited considerable exposure in human subjects and rats. However, only tanshinol had considerable exposure in dogs. The considerable exposure to tanshinol was due to its having the highest dose, whereas that to salvianolic acid D and lithospermic acid was due to their relatively long elimination half-lives in the human subjects and rats. Protocatechuic aldehyde and rosmarinic acid circulated in the bloodstream predominantly as metabolites; salvianolic acids A and B exhibited low plasma levels with their human plasma metabolites little or not detected. Tanshinol and salvianolic acid D were eliminated mainly via renal excretion. Elimination of other catechols involved hepatobiliary and/or renal excretion of their metabolites. Methylation was found to be the primary metabolism for most Danshen catechols and showed intercompound and interspecies differences in rate and degree in vitro. The information gained here is relevant to pharmacological and toxicological research on DanHong injection.

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Activation of transsulfuration pathway by salvianolic acid a treatment: a homocysteine-lowering approach with beneficial effects on redox homeostasis in high-fat diet-induced hyperlipidemic rats

Cited by 14 publications

References 42 publications

A mini-network balance model for evaluating the progression of cardiovascular complications in Goto-Kakizaki rats

A mini-network balance model for evaluating the progression of cardiovascular complications in Goto-Kakizaki rats

Exendin-4 regulates redox homeostasis in rats fed with high-fat diet

Systemic Exposure to and Disposition of Catechols Derived from Salvia miltiorrhiza Roots (Danshen) after Intravenous Dosing DanHong Injection in Human Subjects, Rats, and Dogs

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