Abstract：Objective: To investigate the protective effect of ginsenoside Rg1 (G-Rg1) on adriamycin-induced myocardial injury in rats. Methods: A total of 75 SPF grade SD male rats were randomly divided into control group, model group, low, high dose G-Rg1 group and high-dose G-Rg1+SIRT1 inhibitor EX-527 group, with 15 rats in each group. The rat myocardial injury model was constructed by intraperitoneal injection of adriamycin. The rats in the low and high dose G-Rg1 groups were given 25 and 50mg/kg G-Rg1, respectively; the rats in the high dose G-Rg1+SIRT1 inhibitor EX-527 group were given 50mg/kg G-Rg1 by gavage and injected with 5μg/kg EX-527 in the tail vein; the control group and the model group were given gavage and intraperitoneally injected with the same amount of normal saline. The cardiac function of rats were detected; the levels of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), oxidative stress indicator superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by enzyme-linked immunosorbent assay (ELISA). The pathological changes of myocardial tissue in rats were observed by hematoxylin-eosin (HE) staining. Apoptosis in rat myocardial tissue was detected by terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) staining. The contents of nicotinamide adenine dinucleotide (NAD+), adenosine monophosphate (AMP) and adenosine triphosphate (ATP) in myocardial tissue were determined by high performance liquid chromatography. The expression of silencing information regulator 1 (SIRT1)/adenylate activated protein kinase (AMPK)/peroxisome proliferators-activated receptor γ coactivator α (PGC1α) pathway-related proteins was detected by Western-Blot. Results: High dose G-Rg1 significantly improve the pathological damage, such as myocardial cell hypertrophy, swelling and deformation, inflammatory cell infiltration (P<0.05). Increased left ventricular ejection fraction, left ventricular shortening fraction, serum SOD level, myocardial NAD+ and ATP, SIRT1, PGC1α protein expression and AMPK phosphorylation level, and decreased left ventricular end diastolic diameter, left ventricular end-systolic diameter, serum LDH , CK , CK-MB, MDA levels, AMP, AMP/ATP and myocardial cell apoptosis rate in adriamycin-induced myocardial injury rats (P<0.05). However, all the above improvement effects of G-Rg1 at high dose were mitigated or inhibited by EX-527 (P<0.05). Conclusion: G-Rg1 may play a role in alleviating adriamycin-induced myocardial injury in rats by activating the SIRT1/AMPK/PGC1α signaling pathway.
[1] Sun Z,Zhou D,Yang J,et al.Doxorubicin promotes breast cancer cell migration and invasion via DCAF13[J].FEBS Open Bio,2022,12(1):221-230. [2] Kong CY,Guo Z,Song P,et al.Underlying the mechanisms of doxorubicin-induced acute cardiotoxicity:oxidative stress and cell death[J].Int Biol Sci,2022,18(2):760-770. [3] Yu L,Hao YJ,Ren ZN,et al.Ginsenoside Rg1 relieves rat intervertebral disc degeneration and inhibits IL-1β-induced nucleus pulposus cell apoptosis and inflammation via NF-κB signaling pathway[J].In Vitro Cell Dev Biol Anim,2024,60(3):287-299. [4] Tian G,Li J,Zhou L.Ginsenoside Rg1 regulates autophagy and endoplasmic reticulum stress via the AMPK/mTOR and PERK/ATF4/CHOP pathways to alleviate alcohol induced myocardial injury[J].Int Mol Med,2023,52(1):56-68. [5] Abu-risha SE,Sokar SS,Elzorkany KE,et al.Donepezil and quercetin alleviate valproate-induced testicular oxidative stress,inflammation and apoptosis:Imperative roles of AMPK/SIRT1/ PGC-1α and p38-MAPK/NF-κB/ IL-1β signaling cascades[J].Int Immunopharmacol,2024(134):112240. [6] Wang G.Aerobic exercise ameliorates myocardial ischemia/reperfusion injury and thrombosis of diabetic rats via activation of AMPK/Sirt1/PGC-1α pathway[J].Gen Physiol Biophys,2022,41(4):319-328. [7] Hsieh PL,Chu PM,Cheng HC,et al.Dapagliflozin mitigates doxorubicin-caused myocardium damage by regulating akt-mediated oxidative stress,cardiac remodeling,and inflammation[J].Int Mol Sci,2022,23(17):10146. [8] Sheibani M,Azizi Y,Shayan M,et al.Doxorubicin-induced cardiotoxicity:an overview on pre-clinical therapeutic approaches[J].Cardiovasc Toxicol,2022,22(4):292-310. [9] Songbo M,Lang H,Xinyong C,et al.Oxidative stress injury in doxorubicin-induced cardiotoxicity[J].Toxicol Lett,2019,307(1):41-48. [10] Di Y,Zhao S,Fan H,et al.Mass production of Rg1-loaded small extracellular vesicles using a 3D bioreactor system for enhanced cardioprotective efficacy of doxorubicin-induced cardiotoxicity[J].Pharmaceutics,2024,16(5):593. [11] Liu C,Cao Q,Chen Y,et al.Rhein protects retinal Müller cells from high glucose-induced injury via activating the AMPK/Sirt1/PGC-1α pathway[J].Recept Signal Transduct Res,2023,43(2):62-71. [12] Yu S,Qian H,Tian D,et al.Linggui Zhugan Decoction activates the SIRT1-AMPK-PGC1α signaling pathway to improve mitochondrial and oxidative damage in rats with chronic heart failure caused by myocardial infarction[J].Front Pharmacol,2023,14(1):107-117. [13] Tabrizi FB,Yarmohammadi F,Hayes AW,et al.The modulation of SIRT1 and SIRT3 by natural compounds as a therapeutic target in doxorubicin-induced cardiotoxicity:a review[J].Biochem Mol Toxicol,2022,36(1):229-238.
2025, Vol. 31 
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