TABLE 3.
Anti-MIRI effects of other saponins.
| Compound | Major plant source | Geographical distribution of plants | Dose/concentration | Models | Mechanism |
|---|---|---|---|---|---|
| Astragaloside IV | Astragalus membranaceus (Fisch.) Bge. | Northern China | 1, 10 mg/kg, i.g. | Rat MIRI model (in vivo) (Tu et al., 2013) | Regulating energy metabolism |
| 3, 10, 30 μM | Neonatal rat myocardial cells HR model (in vitro) (Xu et al., 2008) | Improving intracellular calcium handling via regulating SERCA | |||
| 5 mg/kg, i.g.; 10, 20, 40, or 80 μM | Rat global MIRI injury model (ex vivo); H9c2 cardiomyocytes HR model (in vitro) (Luo et al., 2019) | Recovering mitochondrial respiration, preventing mPTP opening, decreasing cytochrome C release and preventing apoptosis; regulating KATP channel | |||
| 0.1, 1, 10, 100 μM | H9c2 cardiomyocytes HR model (in vitro) (Yang et al., 2018) | Regulating PI3K/Akt/HO-1 signaling pathway | |||
| 80 mg/kg, i.g.; 60 μM | Rat MIRI model (in vivo); H9c2 cardiomyocytes HR model (in vitro) (Yin et al., 2019) | Inhibiting CaSR/ERK1/2 and the related apoptotic signaling pathways; regulating energy metabolism | |||
| Betulinic acid | Syzygium jambos (L.) Alston; Betula platyphylla Suk. | China, Indochina, Malaysia, Indonesia; China, Russia, Mongolia | 50, 100, 200 mg/kg, i.g. | Rat MIRI model (in vivo) (Xia et al., 2011) | Preventing cardiomyocyte apoptosis by reducing the release of LDH and CK |
| 5, 10, 20 μM | H9c2 cardiomyocytes HR model (in vitro) (Wang D. et al., 2018) | Inhibiting oxidative stress and apoptosis by Nrf2/HO-1, p38 and JNK pathways | |||
| Celastrol | Tripterygium wilfordii Hook.F. | East Asia | 50 nM | H9c2 cardiomyocytes HR model (in vitro) (Li et al., 2017) | Inhibiting the activation of NF-κb |
| 0.01, 0.1, 1 μM | H9c2 cardiomyocytes HR model (in vivo); rat global MIRI injury model (ex vivo) (Aceros et al., 2019) | Modulating HSP90 activity | |||
| 2, 4, 6 mg/kg, i.g. | Rat MIRI model (in vivo) (Tong et al., 2018) | Suppressing apoptosis, inflammatory and oxidative stress via PI3K/Akt pathway activation and HMGB1 inhibition | |||
| Clematichinenoside | Clematis chinensis Osbeck | China, Vietnam | 1, 10, 100 μM | H9c2 cardiomyocytes HR (in vitro) (Ding et al., 2016) | Inhibiting apoptosis through mitochondrial mediated apoptotic signaling pathway |
| 0.001, 0.01, 0.1 mg/ml; 8, 16, 32 mg/kg, i.g.; 1, 10, 100 μM | Rat global rat MIRI injury model (ex vivo); rat MIRI model (in vivo); neonatal rat myocardial cells HR (in vitro) (Zhang et al., 2013) | Restoring an antioxidant effect by restoring the balance between inducible NO synthase and endothelial NO synthase | |||
| Dioscin | Dioscorea oppositifolia L | China, Japan, South Korea | 0.1, 1 nM | Rat global MIRI injury model (ex vivo) (Badalzadeh et al., 2014; Badalzadeh et al., 2015) | Activating mitochondrial KATP channels and NO system, attenuating oxidative stress |
| 50, 100 mg/kg, i.g. | Rat MIRI model (in vivo) (Wang H. W. et al., 2018) | Inhibiting inflammation by regulating p38-MAPK/JNK pathways and NF-κb pathways | |||
| Glycyrrhizin | Glycyrrhiza uralensis Fisch. | China, Russia | 2, 4, 10 mg/kg, i.g. | Rat MIRI model (in vivo) (Han et al, 2011; Zhai et al., 2012) | Inhibiting oxidative stress, iNOS and inflammatory, via HMGB1 and MAPK expression |
| 5, 10, 20 mg/kg, i.g. | Rat MIRI model (in vivo) (Wu et al., 2015) | Prolonging APD, inhibiting Ica-L and Ito; blocking phospho-JNK/Bax pathway | |||
| Ilexsaponin A | Ilex pubescens Hook. et Arn. | China | 10, 40 mg/kg, i.g.; 10, 50, 250 μM | Rat MIRI model (in vivo); neonatal rat myocardial cells HR model (in vitro) (Zhang et al., 2017) | Inhibiting apoptotic pathway |
| Ophiopogonin D | Ophiopogon japonicus (Linn. f.) Ker-Gawl. | China, Japan, Vietnam, India | 20 mg/kg, i.p. | Rat MIRI model (in vivo) (Huang et al., 2018) | Antioxidant and anti-apoptotic effects |
| Sasanquasaponin | Camellia oleifera Abel | Southern China | 0.1, 1, 10 μM | Neonatal rat myocardial cells HR model (in vitro) (Chen et al., 2007) | Inhibiting oxidative stress via attenuating ROS generation and increasing antioxidant activities |
| 0.1, 0.2, 0.4 mg/kg, i.g.; 0.1 μM | Mouse MIRI model (in vivo); adult mouse myocardial cell HR model (in vitro) (Lai et al., 2004) | Modulating intracellular Cl- homeostasis and anti-arrhythmia effects | |||
| Withaferin A | Withania Somnifera | India | 1, 5 mg/kg, i.g. | Rat MIRI model (in vivo) (R. et al., 2019) | Upregulating AMP-activated protein kinase-dependent B-cell lymphoma2 signaling |
| 0.1, 1 μM | Neonatal rat myocardial cells HR model (in vitro) (Yan et al., 2018) | Inhibiting apoptosis via activated Akt-mediated oxidative stress suppression |