Table 1.
Summary of TCM treatment of MIRI by effects on apoptosis in the past five years
| Type | TCM name | Active constituent | Experimental model | Related pathways | Efficacies and mechanisms | References |
|---|---|---|---|---|---|---|
| Apoptosis | Luteolin (Lu) | Flavonoid compound | Ischemia/reperfusion (I/R) | p38 MAPK pathway | Promoted p-PLB, enhanced the activity and stability of SERCA2a via lysine 585 and Sp1, and relieved calcium overload to promote the recovery of the Δψm. | [11-13] |
| S. miltiorrhiza Bunge, Danshen | Salvianolic acid B (Sal B) | Myocardial ischaemic-reperfusion (I/R) | PI3K/Akt/HMGB1 signaling pathway | Reduced TNF-α, IL-18, IL-1β, HMGB1, and TLR4, and increased Bcl-2 while decreasing Bax. | [14] | |
| Salvia miltiorrhiza Bunge | Tanshinone IIA (TSA) | I/R model | AK003290 and miR-124-5p signaling | Decreased the amount of LDH, MDA, ROS, elevated MMP, and miR-124-5p directly targeted AK003290, and up-regulated the expression of AK00329. | [15] | |
| Danshen | Tanshinone IIA (Tan IIA) | Cardiac microvascular endothelial cells isolation and hypoxia/reoxygenation (HR) model in vitro | SIRT1/PGC1α pathway | Activated SIRT1 to sustain the mitochondrial potential, reduced the mPTP opening, benefited the CMEC survival, and preserved microvascular structure and function. | [16] | |
| Astragalus membranaceus | astragaloside IV (As-IV) | MIRI model of SD rats | PI3K/AKT/GSK-3β signaling pathways | Increased the left ventricular systolic pressure, fractional shortening, and ejection fraction, decreased the left ventricular end-diastolic pressure, decreased the serum LDH, CK levels, the HW/BW ratio, and myocardial infarct size, increased the p-Akt/Akt ratio and pGSK-3β/GSK-3β ratio. | [17] | |
| A hypoxia/reoxygenation (H/R) model in vitro; an SD rat MI/R model in vivo | CaSR/ERK1/2 signaling pathways | Decreased LDH, Ca2+ and CaSR expression, and increased the ERK1/2 phosphorylation levels in vitro. Decreased the myocardium infarct size, CK-MB, and cTnI levels in vivo. | [18] | |||
| H9c2 cardiomyocytes hypoxia/reoxygenation (H/R) cell model | miR-101a/TGFBR1/TLR2/MAPK signaling pathway axis | Promoted SOD activity and the expression level of miR-101a, decreased MDA, LDH, TGFBR1, and TLR2, suppressed p-ERK and p-p38, decreased Bax/Bcl-2 ratio, and cleaved caspase-3/caspase-3 ratio. | [19] | |||
| Scutellaria baicalensis Georgi (Lamiaceae) | Baicalin, a flavonoid active substance | an ischemia/reperfusion (I/R) model | JAK/STAT pathway | Decreased iNOS, IL-1β, and IL-6, up-regulated Arg-1, IL-10, and TGF-β, and inhibited the phosphorylation levels of JAK2 and STAT3. | [20] | |
| SD rats’ heart and myocardial cells I/R model | CaSR/ERK1/2 signaling pathway | Improved LV hemodynamic parameters, down-regulated the protein expression of CaSR, and up-regulated the protein expression of ERK1/2. | [21] | |||
| Ginsenosides | Ginsenoside Rb1 (Rb1) | I/R model | RhoA/ROCK1 signaling pathway | Reduced damaged myocardial structure, increased myocardial blood flow, improved heart function, and microcirculation, reduced cTnI, inhibited the activation of RhoA, and restored the production of ATP. | [22] | |
| Ginsenosides | Rb2 | Myocardial ischemia/reperfusion (MI/R) model | SIRT1 signaling pathway | Reduced myocardial superoxide generation, downregulated gp91phox expression, decreased the mRNA of IL-1β, IL-6, and TNF-α, upregulated SIRT1 expression and downregulated Ac-p53 expression. | [23] | |
| Ginkgo biloba leaves | Ginkgolide B, a flavonoid monomer | Myocardial I/R model | PI3K/AKT/mTOR signaling pathway | Suppressed TNI, TNT, LDH, and Mb and ameliorated the damaged and irregularly arranged myocardial cells, suppressed the expression levels of p-PERK, p-IRE1α, and ATF6, and upregulated p-AKT and p-mTOR expressions. | [24] | |
| Dihydroquercetin (DHQ) | A dihydroxyflavone | Isolated rat hearts and H9c2 cardiomyocytes model | PI3K/Akt pathway | Alleviated cardiac dysfunction, scavenged free radicals, reduced lipid peroxidation, increased the activity of antioxidant enzymes, inhibited the expression of CHOP, Caspase-12, and p-JNK, reduced GRP78, p-PERK, and p-eif2α expression levels, and increased HO-1 expression and Nrf2 binding to antioxidant response elements. | [25] | |
| Curculigo orchioides Gaertn | Curculigoside, a phenolic glycoside antioxidant | H9c2 cells hypoxia/reoxygenation (H/R) model | MPTP opening | Improved cell viability, reduced the infarct size, inhibited MPTP opening and preserved ΔΨm, decreased LDH activity, the expression of cytochrome c, apoptotic protease activating factor-1, and cleaved caspase-9 and cleaved caspase-3. | [26] | |
| Ganoderma lucidum | Ganoderic acid A (GA) | MIR rat model | JAK2/STAT3/NF-κB pathway | Reduced the myocardial infarction extension, decreased LDH, CK, the phosphorylation of JAK2, STAT3, and NF-κB. | [27] | |
| Epimedium brevicornum | Icariin (ICA), a flavonoid | Isolated rat hearts and neonatal rat cardiomyocytes and H9c2 cells model | SIRT1/FoxO1 signaling | Improved heart contraction and limited the infarct size and CK-MB and LDH leakage, decreased MDA, increased SOD activity, MnSOD expression, mitochondrial membrane potential and cytochrome C stabilization, up-regulated SIRT1 and down-regulated Ac-FoxO1. | [28] | |
| The roots of Sophora flavescens (Kushen), Sophora tonkinensis, and Sophora alopecuroides (Kudouzi) | Matrine, a quinolizidine alkaloid | Hypoxia/reoxygenation (H/R) of CMECs in rats’ model | JAK2/STAT3 signaling pathway | Increased cell viability, cell ratio at the S phase, expression levels of p-JAK2 and p-STAT3, increased tube formation ability and decreased the ratio of cells at the G1 phase and Bax/Bcl-2 ratio. | [29] | |
| Platycodon grandiflorum | Platycodin D (PD) | Cardiomyocyte H9c2 cells hypoxia/reoxygenation (H/R) model | Akt/Nrf2/HO-1 pathway | Decreased ROS and MDA, increased SOD and CAT, reduced Bax cleaved caspase-3, and induced Bcl-2. | [30] | |
| Quercetin (QU) | Flavonoids | Ischemia/reperfusion (I/R) model | SIRT1/PGC-1α signaling | Improved myocardial pathological morphology, upregulated SIRT1, PGC-1α, and Bcl-2 proteins expression, and downregulated Bax protein expression. | [31] | |
| Schisandra chinensis | Schisandrin B, Sch B | Ischemia/reperfusion (I/R) injury model | ATF6 and PERK pathway | Decreased CK, LDH, MDA, and the mRNA levels of ATF6, PERK, and CHOP; Downregulated the levels of caspase-9, caspase-3, and Bax, and upregulated the expression of Bcl-2. | [32] | |
| Radix Paeoniae Rubra | Total paeony glycoside (TPG), a monoterpene compound | Ischemia/reperfusion (I/R) injury model | PI3K/Akt signaling pathway | TPG decreased ROS, MDA, and LDH, increased SOD, and GPX activities upregulated the expression levels of pro-caspase-3 and Bcl-2, downregulated cleaved-caspase-3, poly (ADP-ribose) polymerase 1, Bcl-2-associated X protein, and phosphorylated PI3K and Akt expression. | [33] | |
| Apoptosis and Autophagy | Hongjingtian injection (HJT) | Extracts of Rhodiola wallichiana var. cholaensis | Cardiac ischemia-reperfusion (I/R) model | AMPK/mTOR pathway | Decreased the infarct area, the levels of cleaved caspase 3, LC3-II, and p-AMPK expression, increased the Bcl-2/Bax ratio and p-mTOR, increased the mitochondrial membrane potential, intracellular ATP contents, and oxygen consumption. | [64] |
MAPK: mitogen-activated protein kinase, p-PLB: phosphoprotein phosphorylation, SERCA2a: sarco/endoplasmic reticulum Ca2+-ATPase-a, ΔΨm: mitochondrial membrane potential, PI3K: phosphoinositide-3-kinase, HMGB1: high mobility group box 1, TNF-α: tumour necrosis factor-α, IL-18: interleukin-18, IL-1β: interleukin-1β, TLR4: toll-like receptor 4, Bax: bcl-2 associated x, Bcl-2: beclin-2, LDH: lactate dehydrogenase, MDA: malonaldehyde, ROS: reactive-oxygen species, MMP: mitochondrial membrane potential, SIRT1: silent information regulator 1, CMEC: cardiac microvascular endothelial cell, GSK-3β: glycogen synthase kinase 3 beta, CK: creatine kinase, HW/BW: heart weight/body weight, CaSR: calcium-sensing receptor, ERK1/2: extracellular signal-regulated kinase 1/2, TGFBR1: TGFβ type 1 receptor, TLR2: toll-like receptor 2, JAK: janus kinases, STAT: signal transducer and activator of transcription proteins, ROCK-1: RhoA/Rho-associated coiled-coil containing protein kinase-1, mTOR: mammalian target of rapamycin, TnI: troponin I, TnT: troponin T, Mb: myoglobin, PERK: type I transmembrane ER-resident protein kinase, ATF6: activating transcription factor 6, JNK: Jun N-terminal kinase, Nrf2: nuclear factor erythroid 2 related factors 2, MPTP: mitochondrial permeability transition pore, NF-κB: nuclear factor kappa B, FoxO1: forkhead box O 1, SOD: superoxide dismutase, CAT: catalase, GPX: glutathione peroxidase, ATP: adenosine triphosphate.