TABLE 1.
Anti-MIRI effects of saponins from ginseng.
| Compound | Major plant source | Geographical distribution of plants | Dose/concentration | Models | Mechanism |
|---|---|---|---|---|---|
| Ginseng total saponins | Panax ginseng C. A. Mey | Southwest China, East Asia and North America | 100, 200 mg/kg, i.g. | Guinea pig MIRI model (in vivo) (Aravinthan et al., 2015) | Anti-oxidative and anti-inflammatory properties by reducing inflammatory cytokines and NF-kB |
| 50 mg/L for 60 min | Rat global MIRI model (ex vivo) (Wang et al., 2012) | Modulating TCA cycle protein expression to enhance cardiac energy metabolism; reducing oxidative stress | |||
| Panax notoginseng saponins | Panax notoginseng (Burk.) F. H. Chen | Southwest China | 200, 500 μg/ml | Neonatal rat MIRI model (in vitro) (Wang et al., 2019) | Inhibiting oxidative stress via MiR-30c-5p |
| 30, 60 mg/kg, i.p. | Rat MIRI model (in vivo) (Liu X.-W. et al., 2019) | Regulating the HIF-1a/BNIP3 pathway of autophagy | |||
| 30, 60 mg/kg, i.g.; 0.05, 0.25, 2.25 mg/ml | Rat MIRI model (in vivo); H9c2 cardiomyocytes HR model (in vitro) (Chen et al., 2011) | Inhibiting apoptosis by activating PI3K/Akt pathway | |||
| Gypenoside | Panax notoginseng (Burk.) F. H. Chen; Gynostemma pentaphyllum (Thunb.) Mak | Southwest China; East Asia and Southeast Asia | 50, 100, 200 mg/kg, i.g.; 5, 10, 20 μM | Rat MIRI model (in vivo); H9c2 cardiomyocytes HR model (in vitro) (Yu et al., 2016a; Yu et al., 2016b) | Inhibiting ER-stress and apoptosis via CHOP pathway and PI3K/Akt pathway; inhibiting NF-kB p65 activation via MAPK signaling pathway |
| 100 mg/kg, i.g. (in vivo); 10, 20 μM (in vitro) | Rat MIRI model (in vivo); H9c2 cardiomyocytes HR model (in vitro) (Chang et al., 2020) | Suppressing miR-143-3p level via the activation of AMPK/Foxo1 signaling pathway | |||
| Ginsenoside Rb1 | Panax ginseng C. A. Mey.; Panax notoginseng (Burk.) F. H. Chen | Southwest China, East Asia and North America; Southwest China | 40 mg/kg, i.g. | Rat MIRI model (in vivo) (Xia et al., 2011; Li et al., 2016) | Enhancing eNOS expression and NO content and inhibiting p38-MAPK signaling pathway |
| 20, 40, 80 mg/kg, i.g.; 1, 5, 10, 20 μM | Rat global MIRI model (ex vivo); rat MIRI model (in vivo) (Li C. Y. et al., 2020) | Activating mTOR signal pathway | |||
| 2.5, 5, 7.5 mg/kg, i.g. | Rat MIRI model (in vivo) (Cui et al., 2017) | Regulating energy metabolism by RhoA signaling pathway | |||
| Ginsenoside Rb3 | Panax ginseng C. A. Mey.; Panax notoginseng (Burk.) F. H. Chen | Southwest China, East Asia and North America; Southwest China | 2, 5 μM | H9c2 cardiomyocytes HR model (in vitro) (Ma et al., 2014) | Inhibiting JNK-mediated NF-kB activation |
| 5, 10, 20 mg/kg, i.g. | Rat MIRI model (in vivo) (Shi et al., 2011; Liu et al., 2013) | Anti-oxidantive, anti-apoptotic and anti-inflammatory activity; improving microcirculatory | |||
| Ginsenoside Rd | Panax ginseng C. A. Mey.; Panax notoginseng (Burk.) F. H. Chen | Southwest China, East Asia and North America; Southwest China | 50 mg/kg, i.p. | Rat MIRI model (in vivo) (Zeng et al., 2015) | Activating Nrf2/HO-1 signaling pathway |
| 50 mg/kg, i.p.; 10 μM | Rat MIRI model (in vivo); neonatal rat myocardial cells HR model (in vitro) (Wang et al., 2013) | Activating Akt/GSK-3β signaling pathway and inhibiting mitochondria-dependent apoptotic pathway | |||
| Ginsenoside Re | Panax ginseng C. A. Mey.; Panax notoginseng (Burk.) F. H. Chen | Southwest China, East Asia and North America; Southwest China | 0.3, 1, 3, 10, 20 μM | Guinea-pig cardiomyocyte electrophysiology (in vivo) (Bai et al., 2004) | NO-dependent modulation of the delayed rectifier K+ current and the L-type Ca2+ current |
| 30, 100 μM | Rat MIRI model (in vivo) (Lim et al., 2013) | Ameliorating the electrocardiographic abnormality and inhibiting TNF-α level | |||
| Ginsenoside Rg1 | Panax ginseng C. A. Mey.; Panax notoginseng (Burk.) F. H. Chen | Southwest China, East Asia and North America; Southwest China | 5 mg/kg/h, 30 min, i.v | Rat MIRI model (in vivo) (Li et al., 2018, Yuan et al. 2019) | Inhibiting apoptosis and modulating energy metabolism through binding to RhoA; activating HIF-1 α-ERK signaling pathways |
| 100 μM | H9c2 cardiomyocytes HR model (in vitro) (ZL et al., 2012; Qin et al, 2018) | Inhibiting autophagosomal formation and apoptosis; activating the PI3K/AKT/mTOR pathways | |||
| Ginsenoside Rg3 | Panax ginseng C. A. Mey.; Panax notoginseng (Burk.) F. H. Chen | Southwest China, East Asia and North America; Southwest China | 5, 20 mg/kg, i.g. | Rat MIRI model (in vivo) (Zhang et al., 2016) | Anti-apoptosis and anti-inflammation properties |
| 60 mg/kg, i.p.; 10 mM | Rat MIRI model (in vivo); neonatal rat myocardial cells HR model (in vitro) (Wang Y. et al., 2015) | Regulating Akt/eNOS signaling pathway and Bcl-2/Bax signaling pathway | |||
| Notoginsenoside R1 | Panax notoginseng (Burk.) F. H. Chen | Southwest China | 5, 10, 20 μM | Rat global MIRI injury model (ex vivo); H9c2 cardiomyocytes HR model (in vitro) (Yu et al., 2016c) | Inhibiting oxidative stress and ERS |
| 5 mg/kg, i.g.; 10, 100 nM | Rat MIRI model (in vivo); H9c2 cardiomyocytes HR model (in vitro) (He et al., 2014) | Preventing energy metabolism disorder via inhibiting ROCK | |||
| 20, 40, 60 mg/kg, i.g. | Rat MIRI model (in vivo) | Regulating vitamin D3 upregulated protein 1/NF-κB signaling pathway |