Ginseng protects rodent hearts from acute myocardial ischemia–reperfusion injury through GR/ER-activated RISK pathway in an endothelial NOS-dependent mechanism

Zhou, Hua; Hou, Shao Zhen; Luo, Pei; Zeng, Bao; Wang, Jing Rong; Wong, Yuen Fan; Jiang, Zhi‐Hong; Liu, Liang

doi:10.1016/j.jep.2011.03.015

Cited by 63 publications

(52 citation statements)

References 49 publications

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“…A change in heart rate is the most serious side effect of cardiac agents [41, 42]. In the present study, we showed that ginseng generated cardiac tonic action in animals without impacting the heart rate.…”

Section: Discussionsupporting

confidence: 62%

“…In vivo and in vitro investigations have revealed a number of significant actions of ginsenosides and ginseng extracts in cardioprotection, such as reducing myocardial ischemia-reperfusion induced damage via NO pathway in rats and mice [41], slowing down deterioration of cardiac contractions, preventing the development of arrhythmias [42], and relaxing the muscles of the aorta [43]. Also, it has been documented that ginseng increases cardiac lipid metabolism by enhancement of PPAR δ expression and this action of ginseng can be blocked by the specific antagonist GSK0660 [44].…”

Section: Discussionmentioning

confidence: 99%

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Merit of Ginseng in the Treatment of Heart Failure in Type 1-Like Diabetic Rats

Tsai

Chan

Chen

et al. 2014

BioMed Research International

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The present study investigated the merit of ginseng in the improvement of heart failure in diabetic rats and the role of peroxisome proliferator-activated receptors δ (PPARδ). We used streptozotocin-induced diabetic rat (STZ-rat) to screen the effects of ginseng on cardiac performance and PPARδ expression. Changes of body weight, water intake, and food intake were compared in three groups of age-matched rats; the normal control (Wistar rats) received vehicle, STZ-rats received vehicle and ginseng-treated STZ-rats. We also determined cardiac performances in addition to blood glucose level in these animals. The protein levels of PPARδ in hearts were identified using Western blotting analysis. In STZ-rats, cardiac performances were decreased but the food intake, water intake, and blood glucose were higher than the vehicle-treated control. After a 7-day treatment of ginseng in STZ-rats, cardiac output was markedly enhanced without changes in diabetic parameters. This treatment with ginseng also increased the PPARδ expression in hearts of STZ-rats. The related signal of cardiac contractility, troponin I phosphorylation, was also raised. Ginseng-induced increasing of cardiac output was reversed by the cotreatment with PPARδ antagonist GSK0660. Thus, we suggest that ginseng could improve heart failure through the increased PPARδ expression in STZ-rats.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Merit of Ginseng in the Treatment of Heart Failure in Type 1-Like Diabetic Rats

Tsai

Chan

Chen

et al. 2014

BioMed Research International

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“…In agreement with this, our results revealed a marked increase of the phosphorylated form of Akt after IPC in comparison to I/R group. Strong evidences showed that eNOS is an important target of p-Akt [36,37]. Taken together, our results showed that IPC increased Akt phosphorylation, which in turn activated eNOS and NO generation to alleviate the I/R injury of ischemic kidneys.…”

Section: Discussionsupporting

confidence: 58%

Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide

et al. 2012

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BackgroundAlthough recent studies indicate that renal ischemic preconditioning (IPC) protects the kidney from ischemia-reperfusion (I/R) injury, the precise protective mechanism remains unclear. In the current study, we investigated whether early IPC could upregulate hypoxia inducible transcription factor-1α (HIF-1α) expression and could reduce endoplasmic reticulum (ER) stress after renal I/R and whether pharmacological inhibition of nitric oxide (NO) production would abolish these protective effects.MethodsKidneys of Wistar rats were subjected to 60 min of warm ischemia followed by 120 min of reperfusion (I/R group), or to 2 preceding cycles of 5 min ischemia and 5 min reperfusion (IPC group), or to intravenously injection of NG-nitro-L-arginine methylester (L-NAME, 5 mg/kg) 5 min before IPC (L-NAME+IPC group). The results of these experimental groups were compared to those of a sham-operated group. Sodium reabsorption rate, creatinine clearance, plasma lactate dehydrogenase (LDH) activity, tissues concentrations of malonedialdehyde (MDA), HIF-1α and nitrite/nitrate were determined. In addition, Western blot analyses were performed to identify the amounts of Akt, endothelial nitric oxide synthase (eNOS) and ER stress parameters.ResultsIPC decreased cytolysis, lipid peroxidation and improved renal function. Parallely, IPC enhanced Akt phosphorylation, eNOS, nitrite/nitrate and HIF-1α levels as compared to I/R group. Moreover, our results showed that IPC increased the relative amounts of glucose-regulated protein 78 (GRP78) and decreased those of RNA activated protein kinase (PKR)-like ER kinase (PERK), activating transcription factor 4 (ATF4) and TNF-receptor-associated factor 2 (TRAF2) as judged to I/R group. However, pre treatment with L-NAME abolished these beneficial effects of IPC against renal I/R insults.ConclusionThese findings suggest that early IPC protects kidney against renal I/R injury via reducing oxidative and ER stresses. These effects are associated with phosphorylation of Akt, eNOS activation and NO production contributing thus to HIF-1α stabilization. The beneficial impact of IPC was abolished when NO production is inhibited before IPC application.

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“…25,48 Ginsenoside Rg1 is one of components in TXL based on the result of HPLC. The chemical was showed to be protective against reperfusion injury using the model of CMs, 49,50 and it was able to increase endothelial cell viability under oxidative condition. 51 Some other major ingredients of TXL such as peoniflorin and borneol were also demonstrated to have many beneficial effects, for example, attenuating reperfusion injury and protecting endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Induction of Autophagy by Tongxinluo Through the MEK/ERK Pathway Protects Human Cardiac Microvascular Endothelial Cells From Hypoxia/Reoxygenation Injury

Cui

et al. 2014

Journal of Cardiovascular Pharmacology

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: In contrast to cardiomyocytes, autophagy in cardiac microvascular endothelial cells (CMECs) during ischemia/reperfusion (I/R) injury has not been fully investigated. Tongxinluo (TXL), a traditional Chinese medicine, was shown to be vascular protective. We aimed to elucidate the role of autophagy and its regulatory mechanisms by TXL in CMECs subjected to I/R injury. CMECs were exposed to different treatments for 30 minutes and subjected to hypoxia/reoxygenation each for 2 hours. The results indicated that hypoxia/reoxygenation significantly induced autophagy, as identified by an increased number of monodansylcadaverine-positive CMECs, increased autophagosome formation, and a higher type II/type I of light chain 3 ratio, but not Beclin-1 expression. Autophagy inhibition using 3-methyladenine was proapoptotic, but rapamycin-induced autophagy was antiapoptotic. TXL enhanced autophagy and decreased apoptosis in a dose-dependent manner, reaching its largest effect at 800 μg/mL. 3-methyladenine attenuated the TXL-promoted autophagy and antiapoptotic effects, whereas rapamycin had no additional effects compared with TXL alone. TXL upregulated mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) phosphorylation; however, PD98059 abrogated ERK phosphorylation and decreased autophagy and increased apoptosis compared with TXL alone. These results suggest that autophagy is a protective mechanism in CMECs subjected to I/R injury and that TXL can promote autophagy through activation of the mitogen-activated protein kinase/ERK pathway.

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Ginseng protects rodent hearts from acute myocardial ischemia–reperfusion injury through GR/ER-activated RISK pathway in an endothelial NOS-dependent mechanism

Cited by 63 publications

References 49 publications

Merit of Ginseng in the Treatment of Heart Failure in Type 1-Like Diabetic Rats

Merit of Ginseng in the Treatment of Heart Failure in Type 1-Like Diabetic Rats

Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide

Induction of Autophagy by Tongxinluo Through the MEK/ERK Pathway Protects Human Cardiac Microvascular Endothelial Cells From Hypoxia/Reoxygenation Injury

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