Serum metabolomics analysis reveals that obvious cardioprotective effects of low dose Sini decoction against isoproterenol-induced myocardial injury in rats

Zhou, Jun; Ma, Xin; Shi, Min; Chen, Cuiwei; Sun, Yue; Li, Jingjing; Xiong, Youxiang; Chen, Junjie; Li, Fanzhu

doi:10.1016/j.phymed.2017.01.009

Cited by 31 publications

(20 citation statements)

References 31 publications

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“…Moreover, diverse structurally phospholipids in plasma have been recognized to be biomarkers for different types of CVDs ( Meikle et al, 2011 ; Stegemann et al, 2014 ; Takeda et al, 2015 ; Fan et al, 2016 ; Sutter et al, 2016 ). Previous metabolomics researches on the animals of ISO-induced MI also demonstrated a significant permutation in plasma and serum phospholipids ( Wang Z. et al, 2016 ; Zhou et al, 2017 ). Our results indicated that the plasma LysoPC (16:0), LysoPC (18:2), LysoPC (18:1), LysoPC (22:6), and LysoPC (20:3) levels exhibited a strong positive association with ISO induced MI for most species with the exception of LysoPC (20:4).…”

Section: Discussionmentioning

confidence: 86%

Integration of Metabolomics With Pharmacodynamics to Elucidate the Anti-myocardial Ischemia Effects of Combination of Notoginseng Total Saponins and Safflower Total Flavonoids

Yuan

et al. 2018

Front. Pharmacol.

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Notoginseng (Sanqi), the roots and rhizomes of Panax notoginseng and safflower, the flowers of Carthamus tinctorius, are widely used traditional Chinese medicines (TCMs) for the treatment of cardiovascular diseases. Positive evidences have fueled growing acceptance for cardioprotective effects of the combination of the notoginseng total saponins and safflower total flavonoids (CNS) against myocardial ischemia (MI). However, the underlying cardioprotective mechanisms of CNS are still obscured. Metabolomics is a comprehensive tool for investigating biological mechanisms of disease, monitoring therapeutic outcomes, and advancing drug discovery and development. Herein, we investigated the cardioprotective effects of CNS on the isoproterenol (ISO)-induced MI rats by using plasma and urine metabolomics based on ultra-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) and multiple pharmacodynamics approaches. The results showed that pretreatment with CNS could attenuate the cardiac injury resulting from ISO, as evidenced by decreasing the myocardial infarct size, converting the echocardiographic, histopathological, and plasma biochemical abnormalities, and reversing the perturbations of plasma and urine metabolic profiles, particularly for the 55.0 mg/kg dosage group. In addition, 44 metabolites were identified as the potential MI biomarkers, mainly including a range of free fatty acids (FFAs), sphingolipids, and glycerophospholipids. CNS pretreatment group may robustly ameliorate these potential MI-related biomarkers. The accumulation of LysoPCs and FFAs, caused by PLA2, may activate NF-κB pathway and increase proinflammatory cytokines. However, our results showed that CNS at 55.0 mg/kg dosage could maximally attenuate the NF-κB signaling pathway, depress the expressions of TNF-α, IL-6, IL-1β, and PLA2. The results suggested that the anti-inflammatory property of CNS may contribute to its cardioprotection against MI. Our results demonstrate that the integrating of metabolomics with pharmacodynamics provides a reasonable approach for understanding the therapeutic effects of TCMs and CNS provide a potential candidate for prevention and treatment of MI.

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Section: Discussionmentioning

confidence: 86%

Integration of Metabolomics With Pharmacodynamics to Elucidate the Anti-myocardial Ischemia Effects of Combination of Notoginseng Total Saponins and Safflower Total Flavonoids

Yuan

et al. 2018

Front. Pharmacol.

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“…Previous studies revealed that SNT has the potential to improve early ventricular remodeling after myocardial infarction [ 15 ] and a benefit of anti-inflammatory effects in MI rats [ 16 ]. The study by Zhou et al [ 17 ] revealed that SNT could protect myocardium in isoproterenol- (ISO-) induced myocardial injury. Liao et al [ 18 ] found that SNT could effectively inhibit ISO-induced myocardial fibrosis.…”

Section: Discussionmentioning

confidence: 99%

The Effect and Mechanism of Chinese Herbal Formula Sini Tang in Heart Failure after Myocardial Infarction in Rats

Zhu

Zhao

Han

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Objective To investigate the effectiveness and mechanism of the Chinese herbal formula Sini Tang (SNT) which consists of Aconitum carmichaelii (Fuzi), Zingiber officinale (Gan Jiang), and Glycyrrhiza uralensis (Gancao) in heart failure after myocardial infarction in rats. Methods We established the heart failure after myocardial infarction in model of SD rats by ligating the anterior descending branch of left coronary artery. Rats were randomly divided into six experimental groups: Sham operation group, HF group, Benazepril group, high dose of SNT group, medium dose of SNT group, and low dose of SNT group. Drugs were administered by oral gavage for eight weeks. The detection indexes include left ventricular function by echocardiogram, Collagen Volume Fraction by Masson staining, level of Plasma Renin, Angiotensin II and Aldosterone by radioimmunoassay, protein and gene level of ACE and AT1R by western-blot, and real-time PCR. Results The outcomes of this study indicated that SNT significantly improved the LVEF and LVFS, thickened both LVAWd and LVAWs, and reduced LVIDs in heart failure after myocardial infarction in rats when compared with control group (P < 0.05). Besides, SNT significantly reduced the Collagen Volume Fraction (P < 0.05). The results of radioimmunoassay showed that SNT decreased the level of Plasma Renin, Angiotensin II, and Aldosterone (P < 0.05). The outcomes of western-blot and real-time PCR analysis showed that SNT significantly downregulated the protein and gene level of ACE and AT1R (P < 0.05). Conclusions The Chinese herbal formula SNT could improve left ventricular systolic function in heart failure after myocardial infarction in rats and decreased the level of Plasma Renin, Angiotensin II, and Aldosterone, as well as downregulating the protein and gene level of ACE and AT1R. Therefore, SNT has potential benefits of improving cardiac function by inhibiting the excessive activation of Renin-Angiotensin-Aldosterone system in heart failure after myocardial infarction in rats.

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“…Histological assessment of the myocardium by hematoxylin and eosin (HE) staining Myocardial tissues were cut into 5-μm thick sections and stained with HE after para n embedding as described previously [21]. We used paraformaldehyde (4%) to immerse the myocardial tissues for 24 h and then transferred the tissues to ethanol (70%).…”

Section: Cardiac Function Analysismentioning

confidence: 99%

“…The terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was used to detect apoptosis with an In Situ Cell Death Detection Kit, POD (Roche, Mannheim, Germany). We used 5μm thick sections for TUNEL staining [21]. The sections were incubated for 15 min in Protease K (10 μg/mL) after depara nization and rehydration.…”

Section: Apoptosis Assessment Of the Myocardial Tissue Using Tunelmentioning

confidence: 99%

Tanshinone IIA Combined With CsA Inhibit Myocardial Cell Apoptosis Induced by Renal Ischemia-reperfusion Injury by Modulating Mitochondrial Function Through PI3K/Akt/Bad Pathway in Obese Rats 

Tai¹,

Jiang²,

Li³

et al. 2020

Preprint

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Background: Acute myocardial injury (AMI), which is induced by renal ischemia-reperfusion (IR), is a significant cause of acute kidney injury (AKI)-related associated death. Obesity increases the severity and frequency of AMI and AKI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) pretreatment was used to alleviate myocardial cell apoptosis induced by renal IR, and to determine whether TIIA combined with CsA would attenuate myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats. Methods: Male rates were fed a high fat diet for 8 weeks to generate obesity. AKI was induced by 30 min of kidney ischemia followed 24 h of reperfusion. Obese rats were given TIIA (10 mg/kg·d) for 2 weeks and CsA (5 mg/kg) 30 min before renal IR. Related indicators were examined.Results: TIIA combined with CsA alleviated the pathohistological injury and apoptosis induced by renal IR in myocardial cells. In addition, TIIA combined with CsA improved cardiac function and decreased the serum myocardial enzyme spectrum in obese rats after renal IR. At the same time, TIIA combined with CsA improved mitochondrial function. Abnormal function of mitochondria was supported by decreases in the respiration controlling rate (RCR), intracellular adenosine triphosphate (ATP), oxygen consumption rate, and mitochondrial membrane potential (MMP), and increases in mitochondrial reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore (mPTP), mitochondrial DNA damage, and mitochondrial respiratory chain complex enzymes (Ⅰ, Ⅱ, Ⅲ, Ⅳ, and Ⅴ). The injury of mitochondrial dynamic function was assessed by a decrease in Drp1, and increases in Mfn1 and Mfn2, and mitochondrial biogenesis injury was assessed by decreases in PGC-1, NRF1, and TFam. TIIA combined with CsA can attenuate apoptosis through modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.Conclusion: We used isolated mitochondria from rat myocardial tissues to demonstrate that myocardial mitochondrial dysfunction occurred along with renal IR to induce myocardial cell apoptosis; obesity aggravated apoptosis. TIIA combined with CsA attenuated myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.

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Serum metabolomics analysis reveals that obvious cardioprotective effects of low dose Sini decoction against isoproterenol-induced myocardial injury in rats

Cited by 31 publications

References 31 publications

Integration of Metabolomics With Pharmacodynamics to Elucidate the Anti-myocardial Ischemia Effects of Combination of Notoginseng Total Saponins and Safflower Total Flavonoids

Integration of Metabolomics With Pharmacodynamics to Elucidate the Anti-myocardial Ischemia Effects of Combination of Notoginseng Total Saponins and Safflower Total Flavonoids

The Effect and Mechanism of Chinese Herbal Formula Sini Tang in Heart Failure after Myocardial Infarction in Rats

Tanshinone IIA Combined With CsA Inhibit Myocardial Cell Apoptosis Induced by Renal Ischemia-reperfusion Injury by Modulating Mitochondrial Function Through PI3K/Akt/Bad Pathway in Obese Rats

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Serum metabolomics analysis reveals that obvious cardioprotective effects of low dose Sini decoction against isoproterenol-induced myocardial injury in rats

Cited by 31 publications

References 31 publications

Integration of Metabolomics With Pharmacodynamics to Elucidate the Anti-myocardial Ischemia Effects of Combination of Notoginseng Total Saponins and Safflower Total Flavonoids

Integration of Metabolomics With Pharmacodynamics to Elucidate the Anti-myocardial Ischemia Effects of Combination of Notoginseng Total Saponins and Safflower Total Flavonoids

The Effect and Mechanism of Chinese Herbal Formula Sini Tang in Heart Failure after Myocardial Infarction in Rats

Tanshinone IIA&nbsp;Combined With CsA&nbsp;Inhibit Myocardial Cell Apoptosis Induced by Renal Ischemia-reperfusion Injury by Modulating Mitochondrial Function Through PI3K/Akt/Bad Pathway in Obese Rats&nbsp;

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Tanshinone IIA Combined With CsA Inhibit Myocardial Cell Apoptosis Induced by Renal Ischemia-reperfusion Injury by Modulating Mitochondrial Function Through PI3K/Akt/Bad Pathway in Obese Rats