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. 2023 Sep 27;14(2):157–176. doi: 10.1016/j.jpha.2023.09.001

Table 3.

Protective effects of constituents from herbal medicine on cardiomyocytes.

Classification/Constituents Chemical structure Animal/Cells Models Dose/Concentration Effects Related molecular targets
 Refs.
Up-regulation Down-regulation
Tanshinone IIA Image 3 SD rats; H9c2 cells LAD-induced HF 1.5 mg/kg; 5 μM Reversing pathological changes; Reducing the ratio of apoptosis; Upregulating autophagy AMPK, Bcl-2, Beclin1 Bax [161]
Tanshinone IIA C57BL/6 mice LAD-induced HF 5, 25 mg/kg Reducing microvascular damage, apoptosis and mitochondrial damage of cardiomyocytes Sirt1, PGC-1α – [162]
Acacetin Image 4 SD rats; H9c2 cells Ang II-induced HF 10 mg/kg; 0.3, 1, 3 μM Protecting cardiomyocyte hypertrophy; Reducing ROS production and apoptosis; Increasing anti-oxidation PGC-1α, PPARα, AMPK, Sirt1 BNP [163]
Acacetin C57BL/6 mice; H9c2 cells Dox-induced cardiomyopathy rats 15 mg/kg; 0.3, 1, 3 μM Improving cardiac function and cell viability; Reducing ROS levels Sirt1, AMPK, Nrf2, HO-1, Bax, cleaved caspase-3 [165]
Acacetin C57BL/6 mice; H9c2 cells D-galactose induced aging mouse 10, 20, 50 mg/kg; 0.3, 1, 3 μM Improving heart function; Decreasing myocardial senescence markers PINK1, Parkin, Sirt6, Sirt1, AMPK – [166]
Mangiferin Image 5 C57BL/6 mice; H9c2 cells LAD-induced HF 40 mg/kg/day; 20 μM Alleviating cardiomyocyte apoptosis; Improving cell viability Sirt1, FOXO3α – [167]
Tilianin Image 6 SD rats LAD-induced MI/RI 5 mg/kg Reducing cardiac infarct size; Improving swollen and ruptured of cells AMPK, Sirt1, PGC-1α, FOXO1 – [169]
Luteolin Image 7 SD rats LAD-induced MI/RI 20, 40 mg/kg Reducing myocardial infarction area; Improving myocardial pathological Sirt1 TNF-α, IL-6, NLRP3 [170]
Quercetin Image 8 SD rats LAD-induced I/R 25, 50, 100 mL/L Reducing the pathological changes and apoptosis Sirt1, PGC-1α, Bcl-2 Bax [171]
Quercetin Human cardiomyocytes Vitro H/R model 50, 100, 150, 200, 250 mg/L Improving the vulnerability of cardiomyocytes; Ameliorating mitochondrial oxidative stress Sirt1, PINK1, Atg5, TMBIM6, Bcl-2 – [172]
Icariin Image 9 C57BL/6 mice Vitro H/R model 2, 4, 8 μM Reducing cell death and apoptosis; Inhibiting oxidative stress; Restoring mitochondrial dysfunction Sirt1, FOXO1, Bcl-2, Sirt6 Bax, caspase-3 [173]
Naringenin Image 10 H9c2 cells H2O2 induced cardiomyocyte injury 10, 30, 100, 300 μM Reducing ROS levels and inflammatory; Alleviating cardiac fibrotic remodeling Sirt1 TNF-α, IL-6 [174]
Rutin Image 11 H9c2 cells Vitro H/R model 50 μM Protecting cell viability; Attenuating myocardial injury and apoptosis Sirt1 caspase-3 [175]
Puerarin Image 12 C57BL/6 mice LAD-induced MI 100 mg/kg Reducing myocardial infarct size; Improving cardiac structural damage Sirt1 NLRP3, NF-κB, IL-18, IL-1β [176]
Dihydromyricetin Image 13 SD rats; H9c2 cells Dox-induced cardiotoxicity rats 100, 200 mg/kg/day; 0.5, 1, 2, 5, 10 μM Preventing cardiac damage; Attenuating the left ventricle dysfunction; Inhibiting apoptosis Bcl-2, Sirt1 Bax, NLRP3, IL-1β [177]
Jaceosidin Image 14 C57BL/6 mice; neonatal rat cardiac myocytes Dox-induced cardiotoxicity rats 4 mg/kg; 2.5, 5, 10, 15 μM Suppressing cardiac ROS; Inhibiting inflammation and cell loss; Attenuating cardiac injury and oxidative stress Sirt1, Bax NF-κB, TNF-α, MCP-1, Bcl-2 [178]
Oroxylin A Image 15 C57BL/6 mice; H9c2 cells Dox-induced cardiotoxicity rats 40 mg/kg; 40 μM Suppressing cardiac injury and cardiac dysfunction; Alleviating oxidative damage and apoptosis Sirt1, Nrf2, HO-1, NQO1 TNF-α, IL-6, IL-1β, MMP-2, MMP-9 [180]
Kaempferol Image 16 C57BL/6 mice Ang II-induced mice cardiac injury 2.5, 10 mM Attenuating cardiac disfunction; Reducing inflammation and oxidative stress of cardiac AMPK, Nrf-2 ERK, TNF-α,
IL-6		 [181]
Kaempferol H9c2 cells Vitro A/R model 20 μM Increasing the viability of cardiac; Decreasing ROS level Sirt1, Bcl-2 Caspase-3 [182]
Isorhamnetin Image 17 SD rats;
H9c2 cells		 Vivo A/R model 10, 20, 40 mM Improving cell viability; Reducing oxidative stress and apoptosis Sirt1 caspase-3 [183]
Phloretin Image 18 rats Streptozotocin-induced diabetic mouse model 20 mg/kg Preventing cardiomyocyte injury; Attenuating fibrotic response, apoptotic death Sirt1 IL-6,
TNF-α, ANP,
TGF-β		 [184]
Hesperetin Image 19 Kunming mice ISO-induced MI 25, 50 mg/kg/day Antagonizing the myocardial injury; Improving myocardial injury Bcl-2,
Nrf-2, Sirt1, NQO-1, HO-1		 IL-6,
TNF-α, Bax, caspase-3		 [185]
Silibinin Image 20 H9c2 cells Vitro ISO induced myocardial cells injury 0.3, 0.5 mM Inhibiting cardiac death; Protecting mitochondrial function Bcl2, Sirt1 – [187]
Liquiritin Image 21 H9c2 cells H2O2 induced cardiomyocyte injury 5, 10, 20 μM Promoting cells proliferation; Reducing ROS level and oxidative stress AMPK, Sirt1 NF-κB [188]
Daidzein Image 22 SD rats Streptozotocin-induced diabetes rats 25, 50, 100 mg/kg Improving cardiac function; Reducing oxidative stress AMPK, Sirt1 – [189]
Oxypaeoniflorin Image 23 C57BL/6 mice LAD-induced MI/RI 10, 20, 40 mg/kg Improving cardiac function; Ameliorating cardiac damage; Protecting cardiomyocytes Sirt1,
Bcl-2		 Bax, cleaved caspase-3, FOXO1 [195]
Betulin Image 24 Wistar rats LAD-induced MI/RI 20, 40 mg/kg Alleviating myocardial inflammatory; Relieving myocardial function changes Sirt1, NLRP3 IL-6,
TNF-α,
IL-18		 [196]
Bakuchiol Image 25 C57BL/6 mice LAD-induced MI/RI 0.25, 0.5, 1 μM Reducing myocardial dysfunction and cardiac hypertrophy; Alleviating oxidative stress Sirt1, PGC-1α, Bcl2 Bax, cleaved Caspase3 [197]
Bakuchiol SD rats High-fat diet-induced diabetic rats 60 mg/kg Improving the functional recovery; Reducing apoptosis and oxidative stress Sirt1, Nrf2 TGF-β1 [198]
Geniposide Image 26 Wistar–Kyoto and SHR rats High-fat diet-induced diabetic rats 25, 50 mg/kg/day Reducing myocardial injury; Improving the systolic function of the left ventricle and myocardial hypertrophy AMPK, FOXO1, Sirt1 Bax [199]
Geniposide C57/B6J mice Spontaneously hypertensive rats 50 μM Improving left ventricular function; Inhibiting myocardial inflammation and apoptosis AMPK, Sirt1 cleaved caspase-3, NF-κB, TNF-α,
IL-1		 [200]
Isosteviol sodium Image 27 SD rats High fat/high cholesterol-induced rats 1, 10, 20 mg/kg/day Improving cardiac function; Relieving myocardial fibrosis and oxidative stress AMPK, Sirt1 – [201]
Isosteviol sodium H9c2 cells High glucose and ISO induced H9c2 5, 10, 50 μM Reducing ROS accumulation; Protecting cells against cardiomyocyte hypertrophy Sirt1, PGC-1α, AMPK – [202]
Ginkgolide B Image 28 H9c2 cells AngII-induced H9c2 cells hypertrophy 10, 30, 50, 100 μM Preventing cardiomyocyte hypertrophy; Promoting autophagy; Inhibiting oxidative stress Beclin-1, Sirt1, FOXO1 – [203]
Resveratrol Image 29 SD rats; H9c2 cells LAD-induced HF 2.5 mg/kg; 50, 100 μM Improving cardiac function; Reducing mortality of HF AMPK, Sirt1 – [206]
Pterostilbene Image 30 C57BL/6 mice; H9c2 cells Dox-induced cardiotoxicity 10 mg/kg/day; 10 μM Alleviating cell viability inhibition, mitochondrial damage and oxidative stress AMPK, Sirt1, PGC-1α, NRF1, UCP2 – [207]
Punicalagin Image 31 SD rats LAD-induced MI/RI 20, 40, 80 mg/kg/day Reducing apoptosis, inflammation and myocardial infarct size Sirt1,
Nrf2,
HO-1, NQO-1		 caspase-3 [208]
Curcumin Image 32 SD rats; H9c2 cells LAD-induced MI 100 mg/kg/day Reducing apoptosis and oxidative stress; Improving cardiac function Sirt1, PI3K,
Akt, FOXO1, Bcl-2		 Bax [209]
Curcumin C57BL/6J mice Streptozotocin-induced diabetes rats 100 mg/kg/day Alleviating cardiac fibrosis Sirt1 MMP-2, MMP-9 [210]
Ellagic acid Image 33 Wistar rats High-glucose induced diabetic cardiomyopathy mice 20, 50, 100, 200 mg/kg Preserving cardiac systolic and diastolic function; Preventing oxidative stress Sirt1, FOXO1 IL-6,
NF-κB		 [211]
Rosmarinic acid Image 34 C57BL/6 mice High-glucose induced diabetic cardiomyopathy mice 20 mM Ameliorating cardiac function; Preventing mitochondrial injury Sirt1, PGC-1α cleaved caspase-3 [212]
Ginsenoside Rc Image 35 SD rats LAD-induce I/R 10 mg/kg Enhancing mitochondrial biosynthesis and glucose uptake of cardiac; Inhibiting mitochondrial damage Sirt1, GLUT4, HK-Ⅰ/Ⅱ, PFK, PGC-1α Bax [216]
Ginsenoside Rb2 Image 36 Wistar rats LAD-induce I/R 10, 20 mg/kg Reducing oxidative stress and inflammation response; Improving cardiac dysfunction Sirt1,
Bcl-2		 IL-1β,
IL-6,
TNF-α		 [217]
Araloside C Image 37 H9c2 cells H2O2 induced cardiomyocyte injury 6.5, 12.5, 25 μM Inhibiting H9c2 cardiomyocytes mitochomyocytes damage and cytotoxicity of H2O2-induced AMPK, Bcl2 Bax [218]
6-Gingerol Image 38 KunMing mice As2O3-induced MI 10, 20 mg/kg Ameliorating heart injury; Suppressing oxidative stress; Attenuating myocardial mitochondrial damage Bcl-2, AMPK, Sirt1, PGC-1α TNF-α,
IL-6, Bax		 [219]
Salvianolic acid B Image 39 SD rats; H9c2 cells LAD-induced MI 8, 32 mg/kg Ameliorating cardiac function; Reducing infarct size and myocardial apoptosis Sirt1, AMPK, PGC-1α NLRP3, Caspase-1 [220]
Salvianolic acid B C57BL/6 mice LAD-induced MI 40 mg/kg Attenuating cardiac infraction sizes; Improving cardiac function AMPK, eNOS, PI3K, Akt – [221]
Arctigenin Image 40 SD rats; H9c2 cells LAD-induce AMI/R 100 μmol/kg; 0, 25, 50, 100, 200, 400 μM Inhibiting apoptosis of cardiomyocytes, oxidative stress and inflammatory; Improving cardiac functions AMPK, Sirt1,
Bcl-2,
I-κB		 NF-κB, Caspase3 [222]
Berberine Image 41 C57BL/6 mice; H9c2 cells LAD-induced I/R 5, 10 mg/kg; 5, 20 μM Restoring cardiac function; Protecting cell death and inhibiting autophagy – AMPK, mTORC2, Sirt1 [224]
Berberine SD rats; H9c2 cells Dox-induced aging mice 100, 200 mg/kg Reducing ratio of senescent cells; Improving cell viability Bcl-2, Sirt1 Bax [225]
Echinacoside Image 42 SD rats; AC16 cells ISO-induced HF 20 μg/g; 50 μM Reversing myocardial remodeling; Inhibiting mitochondrial oxidative damage and apoptosis Sirt1, FOXO3a – [226]
Rhein Image 43 C57BL/6 J mice Ang II-induced cardiac remodeling mice 50, 100 mg/kg Inhibiting cardiac hypertrophy and cardiac fibroblasts; Improving cardiac function; Suppressing oxidative stress AMPK FGF-23 [227]
Thymoquinone Image 44 SD rats LAD- induce MI/R 2.5, 5, 10 μM Improving cardiac function; Reducing apoptosis oxidative stress damage Sirt1,
Bcl-2		 Bax, cleaved caspase-3 [228]
Honokiol Image 45 SD rats; H9c2 cells LAD-induced MI/RI 5 mg/kg/day; 5 μM Alleviating cardiac damage; Reducing oxidative stress apoptosis Sirt1, Nrf2, Bcl-2 Bax [229]
Capsaicin Image 46 Sprague Dawley rats Vitro H/R model 20 μM Improving viabilities of cardiomyocytes; Reducing oxidative stress Bcl-2, Sirt1 Caspase-3 [230]
Crocin Image 47 newborn C57BL/6 mice LAD-induced I/R 50 mg/kg/day; 10 μM Reducing apoptosis and ER stress Bcl-2, Sirt1, Nrf2, HO-1 Caspase-3, Bax [231]

SD: Sprague Dawley; LAD: ligation of the left anterior descending coronary artery; HF: heart failure; AMPK: adenosine monophosphate activated protein kinase; Bcl-2: B-cell lymphoma-2; Bax: Bcl2-associated x; Sirt1: silent information regulator 1; PGC-1α: peroxisome proliferator-activated receptor γ coactivator 1α; Ang II: angiotensin II; PPARα: peroxisome proliferator-activated receptor α; BNP: brain natriuretic peptide; DOX: doxorubicin; Nrf2: nuclear factor erythroid2-related factor 2; HO-1: heme oxygenase-1; PINK: PTEN-induced kinase 1; Sirt6: silent information regulator 6; FOXO3: forkhead box family and subfamily O of transcription factor 3; MI/RI: myocardial ischemia-reperfusion injury; FOXO1: forkhead box family and subfamily O of transcription factor 1; TNF-α: tumor necrosis factor α; IL-6: interleukin 6; NLRP3: NOD-like receptor protein 3; I/R: ischemia-reperfusion; H/R: hypoxia/reoxygenation; Atg5: autophagy-related gene 5; TMBIM6: transmembrane BAX inhibitor motif containing 6; NF-κB: nuclear factor-kappa-B; IL-1: interleukin 1; IL-18: interleukin 18; MCP-1: monocyte chemotactic protein-1; NQO1: NAD(P)H-quinone oxidoreductase 1; MMP-2: matrix metalloproteinase 2; MMP-9: matrix metalloproteinase 9; ERK: extracellular signal-regulated kinase; ANP: atrial natriuretic peptide; TGF-β: transforming growth factor-β; NRF-1: nuclear respiratory factor-1; UCP2: uncoupling protein 2; PI3K: phosphoinositide 3-kinase; Akt: protein kinase B; GLUT4: glucose transporter type 4; HK-Ⅰ/Ⅱ: hexokinase-Ⅰ/Ⅱ; PFK: phosphofructokinase; eNOS: endothelial nitric oxide synthase; I-κB: inhibitor kappa B; mTORC2: mammalian target of rapamycin compound 2; ISO: isoprenaline; FGF-23: fibroblast growth factor.