The effects of ginseng total saponin, panaxadiol and panaxatriol on ischemia/reperfusion injury in isolated rat heart

doi:10.1016/j.fct.2010.03.018

Food and Chemical Toxicology

Volume 48, Issue 6, June 2010, Pages 1516-1520

https://doi.org/10.1016/j.fct.2010.03.018 Get rights and content

Abstract

The aim of the present study was to evaluate the protective effect of ginseng total saponin, panaxadiol and panaxatriol, which are the major components of Panax ginseng, against myocardial ischemia/reperfusion (I/R) injury in isolated rat hearts. Rats were orally administered once a day with total saponin (20 mg/kg), panaxadiol (5 mg/kg) and panaxatriol (5 mg/kg) for consecutive 7 days. On day 8, the hearts were isolated and perfused with Krebs-Henseleit bicarbonate buffer solution using Langendorff apparatus. After 30 min of global ischemia, hearts were reperfused for 30 min. Myocardial function, coronary flow and biochemical parameters, such as lactate dehydrogenase (LDH), creatine kinase (CK), adenosine triphosphate (ATP), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Total saponin and panaxatriol significantly improved I/R-induced myocardial dysfunction by increasing left ventricular development pressure, (−dP/dt)/(+dP/dt) and time to contracture. Moreover, the increases in the levels of LDH, CK and MDA and the decrease in the levels of GSH were attenuated by total saponin and panaxatriol. However, the ATP levels did not affected by total saponin, panaxadiol and panaxatriol pretreatment. Our findings suggest that pretreatment with ginseng total saponin, especially panaxatriol, ameliorates I/R-induced myocardial damage and this protection is caused by reducing oxidative stress.

Introduction

Myocardial ischemia and reperfusion (I/R) is clinically relevant in situations such as myocardial infarction, coronary angioplasty, thrombolytic therapy, coronary revascularization and heart transplantation (Rao and Viswanath, 2007). Although the nature of this I/R injury has been extensively studied, the mechanisms by which organ damage occurs are not clear.

The production of reactive oxygen species (ROS) from various cellular metabolic processes caused by the restoration of coronary flow after cardiac ischemia is thought to contribute to the observed myocardial damage (Bolli, 1991, Gross et al., 1986, Zweier et al., 1987). These ROS cause non-specific damage to lipids, proteins and DNA, leading to an alteration or loss of the cellular function. The abrupt rise in ROS as a result of the reoxygenation of ischemic or hypoxic cardiac muscle has been associated with a partial irreversible inhibition of mitochondrial respiration (Xie et al., 1996). Alterations in generation and/or use of energy are thought to be important contributing factors to the observed dysfunction caused by I/R (Taniguchi et al., 2001). Rapid resumption of oxidative phosphorylation is critical for the restoration of adequate energy metabolism (ATP and creatine phosphate production) and cellular survival.

Panax ginseng C.A. Mayer (Araliaceae) is one of the most popular natural tonics and has been shown to possess various biological activities such as a protein anabolic effect, anti-tumor activities and an inhibitory effect of tumor angiogenesis and metastasis (Sato et al., 1994). Also, ginseng has been used for treatment of heart failure and to protect tissues from damage when an organism is in stress (Wagner and Liu, 1987). Moreover, ginseng has the advantage that it is free from harmful side effects. Ginsenosides, which are glycosides containing an aglycone (protopanaxadiol or protopanaxatriol), are the major effective components of ginseng and have been shown to have a wide variety of biological activities including immunomodulatory effects, antioxidant, anti-inflammatory and anti-tumor activity (Attele et al., 1999, Kenarova et al., 1990, Park et al., 2003, Shibata, 2001). However, it is still unknown which ginsenosides have beneficial effects on the cardiac injury caused by I/R.

Accordingly, we designed this study to investigate the effects of ginseng total saponin, panaxadiol and panaxatriol on post-ischemic heart injury, particularly on the oxidative stress and energy metabolism.

Section snippets

Materials

Total saponin, panaxadiol, panaxatriol were isolated from 6 years old red ginseng by thin layer chromatography and high performance liquid chromatography, and supplied by Korea Ginseng and Tobacco Research Institute. Sodium pyruvate, lactate dehydrogenase (LDH), creatine kinase (CK) and ATP kits were purchased from Sigma Chemical Co. (St. Louis, MO, USA), and heparin sodium was supplied from Choongwae Pharmaceutical Co. (Suwon, Korea). All other chemicals were of the reagent grades commercially

Cardiac contractility function

As shown Table 1, cardiac contractile function and heart rate were similar for all experimental groups before ischemia. Total saponin, panaxadiol and panaxatriol alone did not affect pre-ischemic cardiac function and heart rate (data not shown). In the vehicle-treated group, cardiac contractile function and heart rate significantly depressed after 30 min reperfusion, indicating severe I/R damage. Total saponin and panaxatriol significantly improved cardiac function as shown in LVDP, DP and

Discussion

We examined the effects of total saponin, panaxadiol and panaxatriol on myocardial injury resulted from global ischemia and reperfusion in isolated rat hearts assessed by mechanical and biochemical evaluation. The main finding of this study indicates panaxatriol, a major saponin of Panax ginseng, provided marked cardioprotection in a well-characterized experimental model of myocardial I/R injury in the rats.

Cardiac dysfunction and myocardial enzyme leakage are characteristic of I/R injury in

Conflict of interest

The authors declare that there are no conflicts of interest.

Acknowledgments

We are grateful to Jong-Dae Park (KT&G Central Research Institute) and Dong-Kwon Rhee (Sungkyunkwan University) for the generous gift of total saponin, panaxadiol and panaxatriol and to Jin-Hyuk Park and Kyung-Hwan Yi for their expert technical assistance.

References (33)

M.E. Anderson
Determination of glutathione and glutathione disulfide in biological samples
Methods Enzymol.
(1985)
A.S. Attele et al.
Ginseng pharmacology: multiple constituents and multiple actions
Biochem. Pharmacol.
(1999)
R. Bolli
Superoxide dismutase 10 years later: a drug in search of a use
J. Am. Coll. Cardiol.
(1991)
J.A. Buege et al.
Microsomal lipid peroxidation
Methods Enzymol.
(1978)
J. Duranteau et al.
Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes
J. Biol. Chem.
(1998)
R. Ferrari et al.
Oxygen-mediated myocardial damage during ischaemia and reperfusion: role of the cellular defences against oxygen toxicity
J. Mol. Cell. Cardiol.
(1985)
K. Hensley et al.
Reactive oxygen species, cell signaling, and cell injury
Free Radical Biol. Med.
(2000)
T. Ishikawa et al.
Cardiac transport of glutathione disulfide and S-conjugate. Studies with isolated perfused rat heart during hydroperoxide metabolism
J. Biol. Chem.
(1984)
H. Kaur et al.
Effect of amiloride A Na⁺/H⁺ exchange inhibitor on cardioprotective effect of ischaemic preconditioning: possible involvement of resident cardiac mast cells
Pharmacol. Res.
(1997)
B. Kenarova et al.
Immunomodulating activity of ginsenoside Rg1 from Panax ginseng
Jpn. J. Pharmacol.
(1990)

D.J. Lefer et al.

Oxidative stress and cardiac disease

Am. J. Med.

(2000)

S.C. Lu

Regulation of glutathione synthesis

Mol. Aspects Med.

(2009)

S.R. Maxwell et al.

Reperfusion injury: a review of the pathophysiology, clinical manifestations and therapeutic options

Int. J. Cardiol.

(1997)

N.S. Dhalla et al.

Role of oxidative stress in cardiovascular diseases

J. Hypertens.

(2000)

H. Fliss et al.

Apoptosis in ischemic and reperfused rat myocardium

Circ. Res.

(1996)

G.J. Gross et al.

Beneficial actions of superoxide dismutase and catalase in stunned myocardium of dogs

Am. J. Physiol.

(1986)

Cited by (68)

Hyperspectral discrimination of ginseng variety and age from Changbai Mountain area
2024, Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy
The efficacy and market value of Panax ginseng Meyer are significantly influenced by its diversity and age. Traditional identification methods are prone to subjective biases and necessitate the use of destructive sample processing, leading to the loss and wastage of ginseng. Consequently, non-destructive in-situ identification has emerged as a crucial subject of interest for both researchers and the ginseng industry. The advancement of technology and the expansion of research have introduced spectral technology and image processing technology as novel approaches and concepts for non-destructive in-situ identification.
Hyperspectral imaging (HSI) is a methodology that combines conventional spectroscopy and imaging to acquire comprehensive spectral and spatial data from various samples. In this study, we investigated the use of Support Vector Machine (SVM) and Spectral Angle Mapper (SAM) classifier algorithms, in conjunction with HSI classification technology, for quasi-Artificial Intelligence (quasi-AI) ginseng identification. To enhance the hyperspectral images prior to SVM classification, we compared the efficacy of Principal Component Analysis (PCA), Minimum Noise Fraction (MNF), and Independent Component Analysis (ICA).
The classification of ginseng based on age was accomplished through the utilization of Radial Basis Function (RBF) kernel SVM and SAM algorithm, which was trained on feature enhanced images. The classification of WMG, MCG, and GG is primarily based on age, with the endmember spectrum serving as the foundation for SAM and SVM.
The “endmember spectrum set” derived from the classification outcomes can serve as the “mutation point” for identifying ginseng of different ages.
Exploring the quality markers and mechanism of Bushen Huoxue Prescription in prevention and treatment of diabetic retinopathy based on Chinmedomics strategy
2023, Journal of Ethnopharmacology
Chinese herbal medicines have complex chemical composition; therefore, revealing the effective substances of Chinese herbal medicine becomes a prerequisite for scientific elucidation of the mechanism of action of Bushen Huoxue Prescription (BHP) against diabetic retinopathy (DR) and the development of new drugs.
The Chinmedomics technique was used to evaluate the pharmacodynamic ingredients and mechanism of action of BHP against DR rats.
The overall physiological condition of the rats, including body weight, blood glucose, inflammatory factor levels, histological staining, and urine metabolic profile were examined to evaluate the model and its effects. The chemical composition of BHP in vivo and ex vivo was fully analyzed utilizing UPLC-Q-Exactive Orbitrap MS in conjunction with TCM serum pharmacochemistry. Finally, correlation analysis between biomarkers, and serum migration components was used to identify Quality markers (Q-markers) that were significantly associated with effectiveness.
The UPLC-Q-Exactive Orbitrap MS platform was used to identify a total of 29 chemicals in serum, 17 of which were highly linked with effectiveness and can be potentially employed as pharmacodynamic substances for BHP against DR. In addition, 14 biomarkers related to galactose metabolism, starch and sucrose metabolism, pantothenate and CoA biosynthesis, glycine, serine, and threonine metabolism were identified. These pathways reveal that DR may be inextricably linked to levels of oxidative stress and inflammation in the organism. Finally, five active ingredients were identified as potential Q-markers of BHP against DR, namely ajugol, protocatechuic acid, tanshinone IIA, panaxatriol and puerarin.
This study successfully clarified the efficacy and Q-markers of BHP through the Chinmedomics strategy, which is of great significance in determining the quality standards of BHP.
Panax ginseng against myocardial ischemia/reperfusion injury: A review of preclinical evidence and potential mechanisms
2023, Journal of Ethnopharmacology
Citation Excerpt :
These studies have revealed the role of Rg1 in the energy metabolism disorder caused by myocardial I/R. It has been shown that Rg1 inhibits caspase-3 activation, improves intracellular SOD and glutathione peroxidase (GSH-Px), and reduces the antioxidant capacity of glutathione (GSH), thereby reducing ROS production and MMP depolarization (Kim and Lee, 2010). In addition, ginsenoside Rg1 stimulation seems to lead to the nuclear translocation of Nrf2 (Li et al., 2017).
Panax ginseng C. A. Meyer (P. ginseng) is effective in the prevention and treatment of myocardial ischemia-reperfusion (I/R) injury. The mechanism by which P. ginseng exerts cardioprotective effects is complex. P. ginseng contains many pharmacologically active ingredients, such as molecular glycosides, polyphenols, and polysaccharides. P. ginseng and each of its active components can potentially act against myocardial I/R injury. Myocardial I/R was originally a treatment for myocardial ischemia, but it also induced irreversible damage, including oxygen-containing free radicals, calcium overload, energy metabolism disorder, mitochondrial dysfunction, inflammation, microvascular injury, autophagy, and apoptosis.
This study aimed to clarify the protective effects of P. ginseng and its active ingredients against myocardial I/R injury, so as to provide experimental evidence and new insights for the research and application of P. ginseng in the field of myocardial I/R injury.
This review was based on a search of PubMed, NCBI, Embase, and Web of Science databases from their inception to February 21, 2022, using terms such as “ginseng,” “ginsenosides,” and “myocardial reperfusion injury.” In this review, we first summarized the active ingredients of P. ginseng, including ginsenosides, ginseng polysaccharides, and phytosterols, as well as the pathophysiological mechanisms of myocardial I/R injury. Importantly, preclinical models with myocardial I/R injury and potential mechanisms of these active ingredients of P. ginseng for the prevention and treatment of myocardial disorders were generally summarized.
P. ginseng and its active components can regulate oxidative stress related proteins, inflammatory cytokines, and apoptosis factors, while protecting the myocardium and preventing myocardial I/R injury. Therefore, P. ginseng can play a role in the prevention and treatment of myocardial I/R injury.
P. ginseng has a certain curative effect on myocardial I/R injury. It can prevent and treat myocardial I/R injury in several ways. When ginseng exerts its effects, should be based on the theory of traditional Chinese medicine and with the help of modern medicine; the clinical efficacy of P. ginseng in preventing and treating myocardial I/R injury can be improved.
Biodistribution and pharmacokinetic evaluation of Korean Red Ginseng components using radioisotopes in a rat model
2023, Journal of Ginseng Research
Citation Excerpt :
When absorbed into the body, the major ginsenosides, such as Rg1, Rb1, Rg3, are subjected to stepwise deglycosylation in the intestines and converted to the metabolites compound K (CK), 20(S)-protopanaxadiol (PPD), and 20(S)-protopanaxatriol (PPT) [9]. Past studies on the efficacy, content, and structure of ginsenosides in KRG mention that ginsenoside Rg1 and Rb1, the major hydrophilic ginsenosides, have antioxidative, anti-inflammatory, vasorelaxant, and angiogenic properties [10–14]. In addition, ginsenoside Rg3, a minor hydrophobic ginsenoside, has anti-metastatic and anticarcinogenic properties [15,16].
Although many studies have evaluated the efficacy and pharmacokinetics of Korean Red Ginseng (KRG) components (Rg1, Rb1, Rg3, Rd, etc.), few have examined the in vivo pharmacokinetics of the radiolabeled components. This study investigated the pharmacokinetics of ginsenosides and their metabolite compound K (CK), 20(s)-protopanaxadiol (PPD), and 20(s)-protopanaxatriol (PPT) using radioisotopes in rat oral administration.
Sprague-Dawley rats were dosed orally once with 10 mg/kg of the tritium(3H) radiolabeled samples, and then the blood was collected from the tail vein after 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 96, and 168 h. Radioactivity in the organs, feces, urine, and carcass was determined using a liquid scintillation counter (LSC) and a bio-imaging analyzer system (BAS).
After oral administration, as the ³H-labeled ginsenosides were converted to metabolites, C_max and half-life increased, and T_max decreased. Interestingly, Rb1 and CK showed similar values, and after a single oral administration of components, the cumulative excretion ratio of urine and feces was 88.9%–92.4%. Although most KRG components were excreted within 96–168 h of administration, small amounts of components were detected in almost all tissues and mainly distributed to the liver except for the digestive tract when observed through autoradiography. This study demonstrated that KRG components were distributed to various organs in the rats. Further studies could be conducted to prove the bioavailability and transmission of KRG components to confirm the mechanism of KRG efficacy.
Possibility as role of ginseng and ginsenosides on inhibiting the heart disease of COVID-19: A systematic review
2022, Journal of Ginseng Research
Citation Excerpt :
This suggests that 20(S)-ginsenoside Rg3 and 20(R)-ginsenoside Rg3 can effectively protect heart and lung tissue against SARS-CoV-2 infections, which are currently threatening human health worldwide. Inflammation is an immunological response to infection or injury and is associated with numerous human diseases [9]. Normal balance between inflammatory cytokines (TNF-α and IL-1)) and anti-inflammatory cytokines (IL-2, IL-4, IL-10) in vivo is critical for vivo homeostasis, and imbalance between inflammatory cytokines and excessive production of such cytokines causes very serious inflammatory diseases [20,21].
Coronavirus has been spreading rapidly around the world since it broke out in China in 2019. Respiratory diseases caused by coronavirus infection cause various diseases ranging from asymptomatic subclinical infections to severe pneumonia and cardiovascular complications, leading to death. In this regard, natural products are being studied to prevent various diseases caused by COVID-19. In current review, we would like to present mechanisms related to the inhibition of heart disease in ginseng and ginsenoside against SARS-CoV-2. In many previous studies, ginseng and ginsenoside are known to have antioxidant, blood flow improvement, improvement of vascular and heart function, blood pressure control, suppression of myocardial infarction and heart failure, and antiarrhythmia. Therefore, ginseng and ginsenoside have a possibility to suppress cardiovascular complications caused by COVID-19. Many of research provide evidence for ginseng and ginsenoside as treatments for the risk of cardiovascular complications. However, in this review, more specific contents on the proposition of the efficacy of ginseng and ginsenoside for COVID-19 should be presented. Therefore, we hope that researches to reduce cardiovascular complications of ginseng and ginsenoside for COVID-19 should be presented to reduce mortality for COVID-19.
Effects of Panax ginseng and ginsenosides on oxidative stress and cardiovascular diseases: pharmacological and therapeutic roles
2022, Journal of Ginseng Research
Traditionally, Asian ginseng or Korean ginseng, Panax ginseng has long been used in Korea and China to treat various diseases. The main active components of Panax ginseng is ginsenoside, which is known to have various pharmacological treatment effects such as antioxidant, vascular easing, anti-allergic, anti-inflammatory, anti-diabetes, and anticancer. Most reactive oxygen species (ROS) cause chronic diseases such as myocardial symptoms and cause fatal oxidative damage to cell membrane lipids and proteins. Therefore, many studies that inhibit the production of oxidative stress have been conducted in various fields of physiology, pathophysiology, medicine and health, and disease. Recently, ginseng or ginsenosides have been known to act as antioxidants in vitro and in vivo results, which have a beneficial effect on preventing cardiovascular disease. The current review aims to provide mechanisms and inform precious information on the effects of ginseng and ginsenosides on the prevention of oxidative stress and cardiovascular disease in animals and clinical trials.

View all citing articles on Scopus

View full text