Natural compounds regulate the PI3K/Akt/GSK3β pathway in myocardial ischemia-reperfusion injury

References

• Frank A, Bonney M, Bonney S, et al. Myocardial ischemia reperfusion injury: from basic science to clinical bedside. In: Eckle T, editor. Seminars in cardiothoracic and vascular anesthesia. Vol.16. No. 3. Los Angeles, CA: SAGE Publications Sage CA; 2012. p. 123–132.
   Google Scholar
• Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest. 2013;123(1):92–100.
   PubMed Web of Science ®Google Scholar
• Mahdiani S, Omidkhoda N, Rezaee R, et al. Induction of JAK2/STAT3 pathway contributes to protective effects of different therapeutics against myocardial ischemia/reperfusion. Biomed Pharmacother. 2022;155:113751.
   PubMed Web of Science ®Google Scholar
• Rasola A, Bernardi P. The mitochondrial permeability transition pore and its involvement in cell death and in disease pathogenesis. Apoptosis. 2007;12(5):815–833.
   PubMed Web of Science ®Google Scholar
• Wu M-Y, Yiang G-T, Liao W-T, et al. Current mechanistic concepts in ischemia and reperfusion injury. Cell Physiol Biochem. 2018;46(4):1650–1667.
   PubMedGoogle Scholar
• Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007;357(11):1121–1135.
   PubMed Web of Science ®Google Scholar
• Verma S, Fedak PW, Weisel RD, et al. Fundamentals of reperfusion injury for the clinical cardiologist. Circulation. 2002;105(20):2332–2336.
   PubMed Web of Science ®Google Scholar
• Granger DN, Kvietys PR. Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol. 2015;6:524–551.
   PubMed Web of Science ®Google Scholar
• Fitridge R, Thompson M. Mechanisms of vascular disease: a reference book for vascular specialists. Adelaide (AU): University of Adelaide Press; 2011.
   Google Scholar
• Yeh C-C, Hou M-F, Tsai S-M, et al. Superoxide anion radical, lipid peroxides and antioxidant status in the blood of patients with breast cancer. Clinica Chimica Acta. 2005;361(1–2):104–111.
   PubMed Web of Science ®Google Scholar
• Baxter GF. The neutrophil as a mediator of myocardial ischemia-reperfusion injury: time to move on. Basic Res Cardiol. 2002;97(4):268–275.
   PubMed Web of Science ®Google Scholar
• Carden DL, Granger DN. Pathophysiology of ischaemia–reperfusion injury. J Pathol. 2000;190(3):255–266.
   PubMed Web of Science ®Google Scholar
• Granger DN. Ischemia‐reperfusion: mechanisms of microvascular dysfunction and the influence of risk factors for cardiovascular disease. Microcirculation. 1999;6(3):167–178.
   PubMed Web of Science ®Google Scholar
• Marqués M, Kumar A, Cortés I, et al. Phosphoinositide 3-kinases p110α and p110β regulate cell cycle entry, exhibiting distinct activation kinetics in G1 phase. Mol Cell Biol. 2008;28(8):2803–2814.
   PubMed Web of Science ®Google Scholar
• Zeng B, Liu L, Liao X, et al. Thyroid hormone protects cardiomyocytes from H2O2-induced oxidative stress via the PI3K-AKT signaling pathway. Exp Cell Res. 2019;380(2):205–215.
   PubMed Web of Science ®Google Scholar
• Walkowski B, Kleibert M, Majka M, et al. Insight into the role of the PI3K/Akt pathway in ischemic injury and post-infarct left ventricular remodeling in normal and diabetic heart. Cells. 2022;11(9):1553.
   PubMed Web of Science ®Google Scholar
• Fyffe C, Falasca M. 3-Phosphoinositide-dependent protein kinase-1 as an emerging target in the management of breast cancer. Cancer Manage Res. 2013;5:271.
   PubMedGoogle Scholar
• Watcharasit P, Bijur GN, Zmijewski JW, et al. Direct, activating interaction between glycogen synthase kinase-3β and p53 after DNA damage. Proc Nat Acad Sci. 2002;99(12):7951–7955.
   PubMed Web of Science ®Google Scholar
• Zhai P, Sciarretta S, Galeotti J, et al. Differential roles of GSK-3β during myocardial ischemia and ischemia/reperfusion. Circ Res. 2011;109(5):502–511.
   PubMed Web of Science ®Google Scholar
• Nidai Ozes O, Mayo LD, Gustin JA, et al. NF-κB activation by tumour necrosis factor requires the Akt serine–threonine kinase. Nature. 1999;401(6748):82–85.
   PubMed Web of Science ®Google Scholar
• Huang XF, Chen JZ. Obesity, the PI3K/Akt signal pathway and colon cancer. Obesity Rev. 2009;10(6):610–616.
   PubMed Web of Science ®Google Scholar
• Whiteside TL. The role of death receptor ligands in shaping tumor microenvironment. Immunol Invest. 2007;36(1):25–46.
   PubMed Web of Science ®Google Scholar
• Zhu Q, Liu J-Y, H-W X, et al. Mechanism of counterattack of colorectal cancer cell by Fas/Fas ligand system. World J Gastroenterol. 2005;11(39):6125.
   PubMed Web of Science ®Google Scholar
• Zhang C, Li C, Chen S, et al. Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways. Redox Biol. 2017;11:1–11.
   PubMed Web of Science ®Google Scholar
• Bonneau B, Prudent J, Popgeorgiev N, et al. Non-apoptotic roles of Bcl-2 family: the calcium connection. Biochim Biophys Acta -Mol Cell Res. 2013;1833(7):1755–1765.
   Web of Science ®Google Scholar
• Namkoong S, Kim C-K, Cho Y-L, et al. Forskolin increases angiogenesis through the coordinated crosstalk of PKA-dependent VEGF expression and Epac-mediated PI3K/Akt/eNOS signaling. Cell Signal. 2009;21(6):906–915.
   PubMed Web of Science ®Google Scholar
• Liu J, Li Y, Tang Y, et al. Rhein protects the myocardiac cells against hypoxia/reoxygenation-induced injury by suppressing GSK3β activity. Phytomedicine. 2018;51:1–6.
   PubMed Web of Science ®Google Scholar
• Zhao H-F, Wang J, Tony to S-S. The phosphatidylinositol 3-kinase/akt and c-Jun N-terminal kinase signaling in cancer: alliance or contradiction? Int J Oncol. 2015;47(2):429–436.
   PubMed Web of Science ®Google Scholar
• Yang S, Li H, Tang L, et al. Apelin-13 protects the heart against ischemia-reperfusion injury through the RISK-GSK-3β-mPTP pathway. Arch Med Sci. 2015;11(5):1065.
   PubMed Web of Science ®Google Scholar
• Ong SB, Dongworth R, Cabrera‐fuentes H, et al. Role of the MPTP in conditioning the heart–translatability and mechanism. Br J Pharmacol. 2015;172(8):2074–2084.
   PubMed Web of Science ®Google Scholar
• Souder DC, Anderson RM. An expanding GSK3 network: implications for aging research. Geroscience. 2019;41(4):369–382.
   PubMed Web of Science ®Google Scholar
• Lv H, Liu Q, Wen Z, et al. Xanthohumol ameliorates lipopolysaccharide (LPS)-induced acute lung injury via induction of AMPK/GSK3β-Nrf2 signal axis. Redox Biol. 2017;12:311–324.
   PubMed Web of Science ®Google Scholar
• Srinivasulu C, Ramgopal M, Ramanjaneyulu G, et al. Syringic acid (Sa)‒a review of its occurrence, biosynthesis, pharmacological and industrial importance. Biomed Pharmacother. 2018;108:547–557.
   PubMed Web of Science ®Google Scholar
• Cao Y, Zhang L, Sun S, et al. Neuroprotective effects of syringic acid against OGD/R-induced injury in cultured hippocampal neuronal cells. Int J Mol Med. 2016;38(2):567–573.
   PubMed Web of Science ®Google Scholar
• Ding SK, Wang LX, Guo LS, et al. Syringic acid inhibits apoptosis pathways via downregulation of p38 MAPK and JNK signaling pathways in H9c2 cardiomyocytes following hypoxia/reoxygenation injury. Mol Med Rep. 2017;16(2):2290–2294.
   PubMed Web of Science ®Google Scholar
• Tokmak M, Yuksel Y, Sehitoglu MH, et al. The neuroprotective effect of syringic acid on spinal cord ischemia/reperfusion injury in rats. Inflammation. 2015;38(5):1969–1978.
   PubMed Web of Science ®Google Scholar
• Sancak EB, Akbas A, Silan C, et al. Protective effect of syringic acid on kidney ischemia-reperfusion injury. Ren Fail. 2016;38(4):629–635.
   PubMed Web of Science ®Google Scholar
• Liu G, Zhang B-F, Hu Q, et al. Syringic acid mitigates myocardial ischemia reperfusion injury by activating the PI3K/Akt/GSK-3β signaling pathway. Biochem Biophys Res Commun. 2020;531(2):242–249.
   PubMed Web of Science ®Google Scholar
• Mahmoudi M, Zamani Taghizadeh Rabe S, Balali-Mood M, et al. Immunotoxicity induced in mice by subacute exposure to berberine. J Immunotoxicol. 2016;13(2):255–262.
   PubMed Web of Science ®Google Scholar
• Hashemzaei M, Rezaee R. A review on pain‐relieving activity of berberine. Phytother Res. 2021;35(6):2846–2853.
   PubMed Web of Science ®Google Scholar
• Rezaee R, Monemi A, SadeghiBonjar MA, et al. Berberine alleviates paclitaxel-induced neuropathy. J Pharmacopuncture. 2019;22(2):90.
   PubMed Web of Science ®Google Scholar
• Chen K, Li G, Geng F, et al. Berberine reduces ischemia/reperfusion-induced myocardial apoptosis via activating AMPK and PI3K–Akt signaling in diabetic rats. Apoptosis. 2014;19(6):946–957.
   PubMed Web of Science ®Google Scholar
• Wang C, Li J, Lv X, et al. Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin. Eur J Pharmacol. 2009;620(1–3):131–137.
   PubMed Web of Science ®Google Scholar
• Li M-H, Zhang Y-J, Yu Y-H, et al. Berberine improves pressure overload-induced cardiac hypertrophy and dysfunction through enhanced autophagy. Eur J Pharmacol. 2014;728:67–76.
   PubMed Web of Science ®Google Scholar
• Hong Y, Hui S-C, Chan T-Y, et al. Effect of berberine on regression of pressure-overload induced cardiac hypertrophy in rats. Am J Chin Med. 2002;30(04):589–599.
   PubMedGoogle Scholar
• Sambandam N, Lopaschuk GD. AMP-activated protein kinase (AMPK) control of fatty acid and glucose metabolism in the ischemic heart. Progress Lipid Res. 2003;42(3):238–256.
   PubMed Web of Science ®Google Scholar
• Levine YC, Li GK, Michel T. Agonist-modulated regulation of AMP-activated protein kinase (AMPK) in endothelial cells: evidence for an AMPK→ Rac1→ Akt→ endothelial nitric-oxide synthase pathway. J Biol Chem. 2007;282(28):20351–20364.
   PubMed Web of Science ®Google Scholar
• Chang W, Li K, Guan F, et al. Berberine pretreatment confers cardioprotection against ischemia–reperfusion injury in a rat model of type 2 diabetes. J Cardiovasc Pharmacol Ther. 2016;21(5):486–494.
   PubMed Web of Science ®Google Scholar
• Cabrera C, Artacho R, Giménez R. Beneficial effects of green tea–a review. Am Coll Nutr. 2006;25(2):79–99.
   PubMed Web of Science ®Google Scholar
• Jeong W-S, Kim I-W, Hu R, et al. Modulatory properties of various natural chemopreventive agents on the activation of NF-κB signaling pathway. Pharm Res. 2004;21(4):661–670.
   PubMed Web of Science ®Google Scholar
• Song D-K, Jang Y, Kim JH, et al. Polyphenol (-)-epigallocatechin gallate during ischemia limits infarct size via mitochondrial KATP channel activation in isolated rat hearts. J Korean Med Sci. 2010;25(3):380–386.
   PubMed Web of Science ®Google Scholar
• Aneja R, Hake PW, Burroughs TJ, et al. Epigallocatechin, a green tea polyphenol, attenuates myocardial ischemia reperfusion injury in rats. Mol Med. 2004;10(1):55–62.
   PubMed Web of Science ®Google Scholar
• Rossello X, Yellon DM. The RISK pathway and beyond. Basic Res Cardiol. 2018;113(1):1–5.
   PubMed Web of Science ®Google Scholar
• Kim SJ, Li M, Jeong CW, et al. Epigallocatechin-3-gallate, a green tea catechin, protects the heart against regional ischemia-reperfusion injuries through activation of RISK survival pathways in rats. Arch Pharm Res. 2014;37(8):1079–1085.
   PubMed Web of Science ®Google Scholar
• Kim SJ, Jeong CW, Bae HB, et al. Protective effect of sauchinone against regional myocardial ischemia/reperfusion injury: inhibition of p38 MAPK and JNK death signaling pathways. J Korean Med Sci. 2012;27(5):572–575.
   PubMed Web of Science ®Google Scholar
• Liu S-X, Zhang Y, Wang Y-F, et al. Upregulation of heme oxygenase-1 expression by hydroxysafflor yellow a conferring protection from anoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes. Int J Cardiol. 2012;160(2):95–101.
   PubMed Web of Science ®Google Scholar
• Wang J, Zhang Q, Mei X, et al. Hydroxysafflor yellow a attenuates left ventricular remodeling after pressure overload-induced cardiac hypertrophy in rats. Pharm Biol. 2014;52(1):31–35.
   PubMed Web of Science ®Google Scholar
• Chen M, Wang M, Yang Q, et al. Antioxidant effects of hydroxysafflor yellow a and acetyl-11-keto-β-boswellic acid in combination on isoproterenol-induced myocardial injury in rats. Int J Mol Med. 2016;37(6):1501–1510.
   PubMed Web of Science ®Google Scholar
• Li F, Fan X, Zhang Y, et al. Cardioprotection by combination of three compounds from ShengMai preparations in mice with myocardial ischemia/reperfusion injury through AMPK activation-mediated mitochondrial fission. Sci Rep. 2016;6(1):1–14.
   PubMed Web of Science ®Google Scholar
• Schubert C, Raparelli V, Westphal C, et al. Reduction of apoptosis and preservation of mitochondrial integrity under ischemia/reperfusion injury is mediated by estrogen receptor β. Biol Sex Differ. 2016;7(1):1–9.
   PubMedGoogle Scholar
• Hausenloy DJ, Yellon DM. Reperfusion injury salvage kinase signalling: taking a RISK for cardioprotection. Heart Fail Rev. 2007;12(3):217–234.
   PubMed Web of Science ®Google Scholar
• Davidson SM, Hausenloy D, Duchen MR, et al. Signalling via the reperfusion injury signalling kinase (RISK) pathway links closure of the mitochondrial permeability transition pore to cardioprotection. Int J Biochem Cell Biol. 2006;38(3):414–419.
   PubMed Web of Science ®Google Scholar
• Min J, Wei C. Hydroxysafflor yellow a cardioprotection in ischemia–reperfusion (I/R) injury mainly via Akt/hexokinase II independent of ERK/GSK-3β pathway. Biomed Pharmacother. 2017;87:419–426.
   PubMed Web of Science ®Google Scholar
• Alamolhodaei NS, Tsatsakis AM, Ramezani M, et al. Resveratrol as MDR reversion molecule in breast cancer: an overview. Food Chem Toxicol. 2017;103:223–232.
   PubMed Web of Science ®Google Scholar
• Hashemzaei M, Tabrizian K, Alizadeh Z, et al. Resveratrol, curcumin and gallic acid attenuate glyoxal-induced damage to rat renal cells. Toxicol Rep. 2020;7:1571–1577.
   PubMed Web of Science ®Google Scholar
• Tabrizian K, Musavi S, Rigi M, et al. Behavioral and molecular effects of intrahippocampal infusion of auraptene, resveratrol, and curcumin on H-89-induced deficits on spatial memory acquisition and retention in Morris water maze. Human Exp Toxicol. 2019;38(7):775–784.
   PubMed Web of Science ®Google Scholar
• Tabrizian K, Shahraki J, Bazzi M, et al. Neuro‐protective effects of resveratrol on carbon monoxide‐induced toxicity in male rats. Phytother Res. 2017;31(9):1310–1315.
   PubMed Web of Science ®Google Scholar
• Hashemzaei M, Barani AK, Iranshahi M, et al. Effects of resveratrol on carbon monoxide-induced cardiotoxicity in rats. Environ Toxicol Pharmacol. 2016;46:110–115.
   PubMed Web of Science ®Google Scholar
• Valenzano DR, Terzibasi E, Genade T, et al. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol. 2006;16(3):296–300.
   PubMed Web of Science ®Google Scholar
• Do GM, Jung UJ, Park HJ, et al. Resveratrol ameliorates diabetes‐related metabolic changes via activation of AMP‐activated protein kinase and its downstream targets in db/db mice. Mol Nutr Food Res. 2012;56(8):1282–1291.
   PubMed Web of Science ®Google Scholar
• González‐rodríguez Á, Santamaría B, Mas‐gutierrez JA, et al. Resveratrol treatment restores peripheral insulin sensitivity in diabetic mice in a sirt1‐independent manner. Mol Nutr Food Res. 2015;59(8):1431–1442.
   PubMed Web of Science ®Google Scholar
• Aires V, Limagne E, Cotte AK, et al. Resveratrol metabolites inhibit human metastatic colon cancer cells progression and synergize with chemotherapeutic drugs to induce cell death. Mol Nutr Food Res. 2013;57(7):1170–1181.
   PubMed Web of Science ®Google Scholar
• Hashemzaei M, Karami SP, Delaramifar A, et al. Anticancer effects of co-administration of daunorubicin and resveratrol in MOLT-4, U266 B1 and RAJI cell lines. Farmacia. 2016;64(1):36–42.
   Web of Science ®Google Scholar
• Yang L, Yang L, Tian W, et al. Resveratrol plays dual roles in pancreatic cancer cells. J Cancer Res Clin Oncol. 2014;140(5):749–755.
   PubMed Web of Science ®Google Scholar
• Liao Z, Liu D, Tang L, et al. Long‐term oral resveratrol intake provides nutritional preconditioning against myocardial ischemia/reperfusion injury: involvement of VDAC1 downregulation. Mol Nutr Food Res. 2015;59(3):454–464.
   PubMed Web of Science ®Google Scholar
• Li J, Xie C, Zhuang J, et al. Resveratrol attenuates inflammation in the rat heart subjected to ischemia-reperfusion: role of the TLR4/NF-κB signaling pathway. Mol Med Rep. 2015;11(2):1120–1126.
   PubMed Web of Science ®Google Scholar
• Yang L, Zhang Y, Zhu M, et al. Resveratrol attenuates myocardial ischemia/reperfusion injury through up-regulation of vascular endothelial growth factor B. Free Radical Biol Med. 2016;101:1–9.
   PubMed Web of Science ®Google Scholar
• Park MJ, Lee EK, Heo H-S, et al. The anti-inflammatory effect of kaempferol in aged kidney tissues: the involvement of nuclear factor-κ B via nuclear factor-inducing kinase/I κ B kinase and mitogen-activated protein kinase pathways. J Med Food. 2009;12(2):351–358.
   PubMed Web of Science ®Google Scholar
• Verma AR, Vijayakumar M, Mathela CS, et al. In vitro and in vivo antioxidant properties of different fractions of Moringa oleifera leaves. Food Chem Toxicol. 2009;47(9):2196–2201.
   PubMed Web of Science ®Google Scholar
• Gates MA, Tworoger SS, Hecht JL, et al. A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer. Int J Cancer. 2007;121(10):2225–2232.
   PubMed Web of Science ®Google Scholar
• Zhou M, Ren H, Han J, et al. Protective effects of Kaempferol against myocardial ischemia/reperfusion injury in isolated rat heart via antioxidant activity and inhibition of Glycogen Synthase Kinase-3 β. Oxid Med Cell Longevity. 2015;2015:1–8.
   Web of Science ®Google Scholar
• Cain BS, Meldrum DR, Dinarello CA, et al. Tumor necrosis factor-alpha and interleukin-1 beta synergistically depress human myocardial function. Crit Care Med. 1999;27(7):1309–1318.
   PubMed Web of Science ®Google Scholar
• Pan P, Qiao L, Wen X. Safranal prevents rotenone-induced oxidative stress and apoptosis in an in vitro model of Parkinson’s disease through regulating Keap1/Nrf2 signaling pathway. Cell Mol Biol. 2016;62(14):11–17.
   PubMed Web of Science ®Google Scholar
• Kianbakht S, Mozaffari K. Effects of saffron and its active constituents, crocin and safranal, on prevention of indomethacin induced gastric ulcers in diabetic and nondiabetic rats. J Med Plants. 2009;8(29):30–38.
   Google Scholar
• Pathan S, Zaidi S, Jain G, et al. Anticonvulsant evaluation of safranal in pentylenetetrazole-induced status epilepticus in mice. Int J Essent Oil Ther. 2009;3(2/3):106–108.
   Google Scholar
• Rezaee R, Hosseinzadeh H. Safranal: from an aromatic natural product to a rewarding pharmacological agent. Iran J Basic Med Sci. 2013;16(1):12.
   PubMed Web of Science ®Google Scholar
• Sadeghnia H, Boroushaki M, Mofidpour H. Effect of safranal, a constituent of saffron (Crocus sativus l.), on lipid peroxidation level during renal ischemia-reperfusion injury in rats. Iran J Basic Med Sci. 2005;8(3): 179–185.
   Google Scholar
• Catalucci D, Zhang D-H, DeSantiago J, et al. Akt regulates L-type Ca2+ channel activity by modulating Cavα1 protein stability. J cell Biol. 2009;184(6):923–933.
   PubMed Web of Science ®Google Scholar
• Hochhauser E, Kivity S, Offen D, et al. Bax ablation protects against myocardial ischemia-reperfusion injury in transgenic mice. Am J Physiol Heart Circ Physiol. 2003;284(6):H2351–9.
   PubMed Web of Science ®Google Scholar
• Maekawa N, Wada H, Kanda T, et al. Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α. J Am Coll Cardiol. 2002;39(7):1229–1235.
   PubMed Web of Science ®Google Scholar
• Basset O, Boittin F-X, Cognard C, et al. Bcl-2 overexpression prevents calcium overload and subsequent apoptosis in dystrophic myotubes. Biochem J. 2006;395(2):267–276.
   PubMedGoogle Scholar
• Wang H, Zheng B, Che K, et al. Protective effects of safranal on hypoxia/reoxygenation‑induced injury in H9c2 cardiac myoblasts via the PI3K/AKT/GSK3β signaling pathway. Exp Ther Med. 2021;22(6):1–15.
   Web of Science ®Google Scholar
• Sugden PH. Ras, Akt, and mechanotransduction in the cardiac myocyte. Circ Res. 2003;93(12):1179–1192.
   PubMed Web of Science ®Google Scholar
• Roberts CK, Vaziri ND, Wang XQ, et al. Enhanced NO inactivation and hypertension induced by a high-fat, refined-carbohydrate diet. Hypertension. 2000;36(3):423–429.
   PubMed Web of Science ®Google Scholar
• Bharti S, Golechha M, Kumari S, et al. Akt/gsk-3β/eNOS phosphorylation arbitrates safranal-induced myocardial protection against ischemia–reperfusion injury in rats. Eur J Nutr. 2012;51(6):719–727.
   PubMed Web of Science ®Google Scholar
• Zhang A, Zheng Y, Que Z, et al. Astragaloside IV inhibits progression of lung cancer by mediating immune function of Tregs and CTLs by interfering with IDO. J Cancer Res Clin Oncol. 2014;140(11):1883–1890.
   PubMed Web of Science ®Google Scholar
• Wang B, Chen M-Z. Astragaloside IV possesses antiarthritic effect by preventing interleukin 1β-induced joint inflammation and cartilage damage. Arch Pharm Res. 2014;37(6):793–802.
   PubMed Web of Science ®Google Scholar
• Qiu L-H, Xie X-J, Zhang B-Q. Astragaloside IV improves homocysteine-induced acute phase endothelial dysfunction via antioxidation. Biol Pharm Bull. 2010;33(4):641–646.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Zhu H, Huang C, et al. Astragaloside IV exerts antiviral effects against coxsackievirus B3 by upregulating interferon-γ. J Cardiovasc Pharmacol. 2006;47(2):190–195.
   PubMed Web of Science ®Google Scholar
• Gui J, Chen R, Xu W, et al. Remission of CVB 3‐induced myocarditis with astragaloside IV treatment requires A20 (TNFAIP 3) up‐regulation. J Cell Mol Med. 2015;19(4):850–864.
   PubMed Web of Science ®Google Scholar
• Chen P, Xie Y, Shen E, et al. Astragaloside IV attenuates myocardial fibrosis by inhibiting TGF-β1 signaling in coxsackievirus B3-induced cardiomyopathy. Eur J Pharmacol. 2011;658(2–3):168–174.
   PubMed Web of Science ®Google Scholar
• Dong Z, Zhao P, Xu M, et al. Astragaloside IV alleviates heart failure via activating PPARα to switch glycolysis to fatty acid β-oxidation. Sci Rep. 2017;7(1):1–15.
   PubMed Web of Science ®Google Scholar
• Zhang W-D, Chen H, Zhang C, et al. Astragaloside IV from Astragalus membranaceus shows cardioprotection during myocardial ischemia in vivo and in vitro. Planta Med. 2006;72(01):4–8.
   PubMedGoogle Scholar
• Tu L, Pan CS, Wei XH, et al. Astragaloside IV protects heart from ischemia and reperfusion injury via energy regulation mechanisms. Microcirculation. 2013;20(8):736–747.
   PubMed Web of Science ®Google Scholar
• Si J, Wang N, Wang H, et al. HIF-1α signaling activation by post-ischemia treatment with astragaloside IV attenuates myocardial ischemia-reperfusion injury. PLoS ONE. 2014;9(9):e107832.
   PubMed Web of Science ®Google Scholar
• Zheng Q, Zhu J-Z, Bao X-Y, et al. A preclinical systematic review and meta-analysis of astragaloside IV for myocardial ischemia/reperfusion injury. Front Physiol. 2018;9:795.
   PubMed Web of Science ®Google Scholar
• Wei D, Xu H, Gai X, et al. Astragaloside IV alleviates myocardial ischemia-reperfusion injury in rats through regulating PI3K/AKT/GSK-3β signaling pathways. Acta Cir Bras. 2019;34(7): e201900708.
   PubMed Web of Science ®Google Scholar
• Bian Q-Y, Wang S-Y, L-J X, et al. Two new antioxidant diarylheptanoids from the fruits of Alpinia oxyphylla. J Asian Nat Prod Res. 2013;15(10):1094–1099.
   PubMed Web of Science ®Google Scholar
• Martineti V, Tognarini I, Azzari C, et al. Inhibition of in vitro growth and arrest in the G0/G1 phase of HCT8 line human colon cancer cells by kaempferide triglycoside from Dianthus caryophyllus. Phytother Res. 2010;24(9):1302–1308.
   PubMed Web of Science ®Google Scholar
• Maruyama H, Sumitou Y, Sakamoto T, et al. Antihypertensive effects of flavonoids isolated from Brazilian green propolis in spontaneously hypertensive rats. Biol Pharm Bull. 2009;32(7):1244–1250.
   PubMed Web of Science ®Google Scholar
• Pei Y-H, Chen J, Xie L, et al. Hydroxytyrosol protects against myocardial ischemia/reperfusion injury through a PI3K/Akt-dependent mechanism. Mediators Inflamm. 2016;2016:1232103.
   PubMed Web of Science ®Google Scholar
• Wang D, Zhang X, Li D, et al. Kaempferide protects against myocardial ischemia/reperfusion injury through activation of the PI3K/Akt/GSK-3β pathway. Mediators Inflamm. 2017;2017:5278218.
   PubMed Web of Science ®Google Scholar
• Ye R, Han J, Kong X, et al. Protective effects of ginsenoside Rd on PC12 cells against hydrogen peroxide. Biol Pharm Bull. 2008;31(10):1923–1927.
   PubMed Web of Science ®Google Scholar
• Guan Y-Y, Zhou J-G, Zhang Z, et al. Ginsenoside-Rd from panax notoginseng blocks Ca2+ influx through receptor-and store-operated Ca2+ channels in vascular smooth muscle cells. Eur J Pharmacol. 2006;548(1–3):129–136.
   PubMed Web of Science ®Google Scholar
• Li XY, Liang J, Tang YB, et al. Ginsenoside Rd prevents glutamate‐induced apoptosis in rat cortical neurons. Clin Exp Pharmacol Physiol. 2010;37(2):199–204.
   PubMed Web of Science ®Google Scholar
• Shi Y, Han B, Yu X, et al. Ginsenoside Rb3 ameliorates myocardial ischemia-reperfusion injury in rats. Pharm Biol. 2011;49(9):900–906.
   PubMed Web of Science ®Google Scholar
• Wang Z, Li M, Wu W-K, et al. Ginsenoside Rb1 preconditioning protects against myocardial infarction after regional ischemia and reperfusion by activation of phosphatidylinositol-3-kinase signal transduction. Cardiovasc Drugs Ther. 2008;22(6):443–452.
   PubMed Web of Science ®Google Scholar
• Chen S, Liu J, Liu X, et al. Panax notoginseng saponins inhibit ischemia-induced apoptosis by activating PI3K/Akt pathway in cardiomyocytes. J Ethnopharmacol. 2011;137(1):263–270.
   PubMed Web of Science ®Google Scholar
• Wang Y, Li X, Wang X, et al. Ginsenoside Rd attenuates myocardial ischemia/reperfusion injury via Akt/GSK-3β signaling and inhibition of the mitochondria-dependent apoptotic pathway. PLoS ONE. 2013;8(8):e70956.
   PubMed Web of Science ®Google Scholar
• Panahi Y, Hosseini MS, Khalili N, et al. Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: a randomized controlled trial and an updated meta-analysis. Clin Nutr. 2015;34(6):1101–1108.
   PubMed Web of Science ®Google Scholar
• Panahi Y, Alishiri GH, Parvin S, et al. Mitigation of systemic oxidative stress by curcuminoids in osteoarthritis: results of a randomized controlled trial. J Diet Suppl. 2016;13(2):209–220.
   PubMedGoogle Scholar
• Hassani S, Sepand M, Jafari A, et al. Protective effects of curcumin and vitamin E against chlorpyrifos-induced lung oxidative damage. Human Exp Toxicol. 2015;34(6):668–676.
   PubMed Web of Science ®Google Scholar
• Momtazi-Borojeni AA, Haftcheshmeh SM, Esmaeili S-A, et al. Curcumin: a natural modulator of immune cells in systemic lupus erythematosus. Autoimmun Rev. 2018;17(2):125–135.
   PubMed Web of Science ®Google Scholar
• Mirzaei H, Naseri G, Rezaee R, et al. Curcumin: a new candidate for melanoma therapy? Int J Cancer. 2016;139(8):1683–1695.
   PubMed Web of Science ®Google Scholar
• Mokhtari‐zaer A, Marefati N, Atkin SL, et al. The protective role of curcumin in myocardial ischemia–reperfusion injury. J Cell Physiol. 2019;234(1):214–222.
   Web of Science ®Google Scholar
• Kim SJ, Yoo KY, Jeong CW, et al. Urinary trypsin inhibitors afford cardioprotective effects through activation of PI3K-Akt and ERK signal transduction and inhibition of p38 MAPK and JNK. Cardiol. 2009;114(4):264–270.
   PubMed Web of Science ®Google Scholar
• Naeimi AF, Alizadeh M. Antioxidant properties of the flavonoid fisetin: an updated review of in vivo and in vitro studies. Trends Food Sci Technol. 2017;70:34–44.
   Web of Science ®Google Scholar
• Khan N, Afaq F, Khusro FH, et al. Dual inhibition of phosphatidylinositol 3‐kinase/Akt and mammalian target of rapamycin signaling in human nonsmall cell lung cancer cells by a dietary flavonoid fisetin. Int J Cancer. 2012;130(7):1695–1705.
   PubMed Web of Science ®Google Scholar
• Pal HC, Pearlman RL, Afaq F. Fisetin and its role in chronic diseases. Adv Exp Med Biol. 2016;928:213–244.
   PubMed Web of Science ®Google Scholar
• Shanmugam K, Ravindran S, Kurian GA, et al. Fisetin confers cardioprotection against myocardial ischemia reperfusion injury by suppressing mitochondrial oxidative stress and mitochondrial dysfunction and inhibiting glycogen synthase kinase 3β activity. Oxid Med Cell Longevity. 2018;2018:9173436.
   PubMed Web of Science ®Google Scholar
• Lee SE, Jeong SI, Yang H, et al. Fisetin induces Nrf2‐mediated HO‐1 expression through PKC‐δ and p38 in human umbilical vein endothelial cells. J Cell Biochem. 2011;112(9):2352–2360.
   PubMed Web of Science ®Google Scholar
• Xu R, Hu Q, Ma Q, et al. The protease Omi regulates mitochondrial biogenesis through the GSK3β/PGC-1α pathway. Cell Death Amp Dis. 2014;5(8):e1373.
   PubMedGoogle Scholar
• Shanmugam K, Boovarahan SR, Prem P, et al. Fisetin attenuates myocardial ischemia-reperfusion injury by activating the reperfusion injury salvage kinase (RISK) signaling pathway. Front pharmacol. 2021;12:566470.
   PubMed Web of Science ®Google Scholar
• Song X, Wang T, Zhang Z, et al. Leonurine exerts anti-inflammatory effect by regulating inflammatory signaling pathways and cytokines in LPS-induced mouse mastitis. Inflammation. 2015;38(1):79–88.
   PubMed Web of Science ®Google Scholar
• Sun J, Huang SH, Zhu YC, et al. Anti-oxidative stress effects of Herba leonuri on ischemic rat hearts. Life Sci. 2005;76(26):3043–3056.
   PubMed Web of Science ®Google Scholar
• Mao F, Zhang L, Cai M-H, et al. Leonurine hydrochloride induces apoptosis of H292 lung cancer cell by a mitochondria-dependent pathway. Pharm Biol. 2015;53(11):1684–1690.
   PubMed Web of Science ®Google Scholar
• Zhu YZ, Wu W, Zhu Q, et al. Discovery of Leonuri and therapeutical applications: from bench to bedside. Pharmacol Ther. 2018;188:26–35.
   PubMed Web of Science ®Google Scholar
• Liu X, Pan L, Gong Q, et al. Leonurine (SCM-198) improves cardiac recovery in rat during chronic infarction. Eur J Pharmacol. 2010;649(1–3):236–241.
   PubMed Web of Science ®Google Scholar
• Rao AV, Ray M, Rao L. Lycopene. Adv Food Nutr Res. 2006;51:99–164.
   PubMedGoogle Scholar
• Xu J, Hu H, Chen B, et al. Lycopene protects against hypoxia/reoxygenation injury by alleviating ER stress induced apoptosis in neonatal mouse cardiomyocytes. PLoS ONE. 2015;10(8):e0136443.
   PubMed Web of Science ®Google Scholar
• Yue R, Hu H, Yiu KH, et al. Lycopene protects against hypoxia/reoxygenation-induced apoptosis by preventing mitochondrial dysfunction in primary neonatal mouse cardiomyocytes. PLoS ONE. 2012;7(11):e50778.
   PubMed Web of Science ®Google Scholar
• Miki T, Miura T, Hotta H, et al. Endoplasmic reticulum stress in diabetic hearts abolishes erythropoietin-induced myocardial protection by impairment of phospho–glycogen synthase kinase-3β–mediated suppression of mitochondrial permeability transition. Diabetes. 2009;58(12):2863–2872.
   PubMed Web of Science ®Google Scholar
• Duan L, Liang C, Li X, et al. Lycopene restores the effect of ischemic postconditioning on myocardial ischemia‑reperfusion injury in hypercholesterolemic rats. Int J Mol Med. 2019;43(6):2451–2461.
   PubMed Web of Science ®Google Scholar
• Huang Q, Lu G, Shen HM, et al. Anti‐cancer properties of anthraquinones from rhubarb. Med Res Rev. 2007;27(5):609–630.
   PubMed Web of Science ®Google Scholar
• Liu J, Chen Z, Zhang Y, et al. Rhein protects pancreatic β-cells from dynamin-related protein-1–mediated mitochondrial fission and cell apoptosis under hyperglycemia. Diabetes. 2013;62(11):3927–3935.
   PubMed Web of Science ®Google Scholar
• Xue L, Wu Z, Ji X-P, et al. Effect and mechanism of salvianolic acid B on the myocardial ischemia-reperfusion injury in rats. Asian Pac J Trop Med. 2014;7(4):280–284.
   PubMed Web of Science ®Google Scholar
• Wang B, Sun J, Shi Y, et al. Salvianolic Acid B inhibits high‐fat diet‐induced inflammation by activating the Nrf2 pathway. J Food Sci. 2017;82(8):1953–1960.
   PubMed Web of Science ®Google Scholar
• Fan H, Yang L, Fu F, et al. Cardioprotective effects of salvianolic Acid a on myocardial ischemia-reperfusion injury in vivo and in vitro. Evid Based Complement Alternat Med. 2012;2012:508938.
   PubMed Web of Science ®Google Scholar
• Li X-L, Fan J-P, Liu J-X, et al. Salvianolic acid a protects neonatal cardiomyocytes against hypoxia/reoxygenation-induced injury by preserving mitochondrial function and activating Akt/GSK-3β signals. Chin J Integr Med. 2019;25(1):23–30.
   PubMed Web of Science ®Google Scholar
• Peng L, Junguo R, Changling D, et al. The effects of three components of Salviae miltiorrhizae radix on anoxia and peroxidation injuries in neonatal cardiomyocytes. Pharmacol Clin Chin Mater Med. 2009; 25(5): 29–31.
   Google Scholar
• Chen X, Yang L, Oppenheim JJ, et al. Cellular pharmacology studies of shikonin derivatives. Phytother Res. 2002;16(3):199–209.
   PubMed Web of Science ®Google Scholar
• Wang Z, Liu T, Gan L, et al. Shikonin protects mouse brain against cerebral ischemia/reperfusion injury through its antioxidant activity. Eur J Pharmacol. 2010;643(2–3):211–217.
   PubMed Web of Science ®Google Scholar
• Liu T, Zhang Q, Mo W, et al. The protective effects of shikonin on hepatic ischemia/reperfusion injury are mediated by the activation of the PI3K/Akt pathway. Sci Rep. 2017;7(1):1–13.
   PubMedGoogle Scholar
• Yang J, Wang Z, Chen D-L. Shikonin ameliorates isoproterenol (ISO)-induced myocardial damage through suppressing fibrosis, inflammation, apoptosis and ER stress. Biomed Pharmacother. 2017;93:1343–1357.
   PubMed Web of Science ®Google Scholar
• Wang S, Zhu Y, Qiu R. Shikonin protects H9C2 cardiomyocytes against hypoxia/reoxygenation injury through activation of PI3K/Akt signaling pathway. Biomed Pharmacother. 2018;104:712–717.
   PubMed Web of Science ®Google Scholar
• Liu J, Zhai W-M, Yang Y-X, et al. GABA and 5-HT systems are implicated in the anxiolytic-like effect of spinosin in mice. Pharmacol Biochem Behav. 2015;128:41–49.
   PubMed Web of Science ®Google Scholar
• Lee Y, Jeon SJ, Lee HE, et al. Spinosin, a C-glycoside flavonoid, enhances cognitive performance and adult hippocampal neurogenesis in mice. Pharmacol Biochem Behav. 2016;145:9–16.
   PubMed Web of Science ®Google Scholar
• Ko SY, Lee HE, Park SJ, et al. Spinosin, a C-Glucosylflavone, from Zizyphus jujuba var. spinosa Ameliorates Aβ1–42 Oligomer-Induced Memory Impairment in Mice. Biomol Ther. 2015;23(2):156.
   PubMed Web of Science ®Google Scholar
• Xu F, He B, Xiao F, et al. Neuroprotective effects of spinosin on recovery of learning and memory in a mouse model of Alzheimer’s disease. Biomol Ther. 2019;27(1):71.
   PubMed Web of Science ®Google Scholar
• Gu M, He P, Lyu C, et al. Spinosin and 6’’‘‑feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats. J Mol Med Rep. 2019;20(5):4253–4261.
   PubMed Web of Science ®Google Scholar
• Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial ROS-induced ROS release: an update and review. Biochim Biophys Acta –Bioenergetics. 2006;1757(5–6):509–517.
   PubMed Web of Science ®Google Scholar
• Juhaszova M, Zorov DB, Yaniv Y, et al. Role of glycogen synthase kinase-3β in cardioprotection. Circ Res. 2009;104(11):1240–1252.
   PubMed Web of Science ®Google Scholar
• Marchand B, Arsenault D, Raymond-Fleury A, et al. Glycogen synthase kinase-3 (GSK3) inhibition induces prosurvival autophagic signals in human pancreatic cancer cells. J Biol Chem. 2015;290(9):5592–5605.
   PubMed Web of Science ®Google Scholar
• Shintani T, Klionsky DJ. Autophagy in health and disease: a double-edged sword. Science. 2004;306(5698):990–995.
   PubMed Web of Science ®Google Scholar
• Rogov V, Dötsch V, Johansen T, et al. Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Molecular Cell. 2014;53(2):167–178.
   PubMed Web of Science ®Google Scholar
• Gozzelino R, Jeney V, Soares MP. Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol. 2010;50:323–354.
   PubMed Web of Science ®Google Scholar
• Djekic D, Shi L, Brolin H, et al. Effects of a vegetarian diet on cardiometabolic risk factors, gut microbiota, and plasma metabolome in subjects with ischemic heart disease: a randomized, crossover study. J Am Heart Assoc. 2020;9(18):e016518.
   PubMed Web of Science ®Google Scholar
• Gencer B, Li XS, Gurmu Y, et al. Gut microbiota‐dependent trimethylamine N‐oxide and cardiovascular outcomes in patients with prior myocardial infarction: a nested case control study from the PEGASUS‐TIMI 54 trial. J Am Heart Assoc. 2020;9(10):e015331.
   PubMed Web of Science ®Google Scholar
• Nemet I, Saha PP, Gupta N, et al. A cardiovascular disease-linked gut microbial metabolite acts via adrenergic receptors. Cell. 2020;180(5):862–77. e22.
   PubMed Web of Science ®Google Scholar
• Landete J. Ellagitannins, ellagic acid and their derived metabolites: a review about source, metabolism, functions and health. Food Res Int. 2011;44(5):1150–1160.
   Web of Science ®Google Scholar
• Dey P. Gut microbiota in phytopharmacology: a comprehensive overview of concepts, reciprocal interactions, biotransformations and mode of actions. Pharmacol Res. 2019;147:104367.
   PubMed Web of Science ®Google Scholar
• Espín JC, Larrosa M, García-Conesa MT, et al. Biological significance of urolithins, the gut microbial ellagic acid-derived metabolites: the evidence so far. Evid Based Complement Alternat Med. 2013;2013: 270418.
   PubMed Web of Science ®Google Scholar
• González-Sarrías A, Larrosa M, Tomás-Barberán FA, et al. NF-κB-dependent anti-inflammatory activity of urolithins, gut microbiota ellagic acid-derived metabolites, in human colonic fibroblasts. Br j nutr. 2010;104(4):503–512.
   PubMed Web of Science ®Google Scholar
• Piwowarski JP, Kiss AK, Granica S, et al. Urolithins, gut microbiota‐derived metabolites of ellagitannins, inhibit LPS‐induced inflammation in RAW 264.7 murine macrophages. Mol Nutr Food Res. 2015;59(11):2168–2177.
   PubMed Web of Science ®Google Scholar
• Zheng D, Liu Z, Zhou Y, et al. Urolithin B, a gut microbiota metabolite, protects against myocardial ischemia/reperfusion injury via p62/Keap1/Nrf2 signaling pathway. Pharmacol Res. 2020;153:104655.
   PubMed Web of Science ®Google Scholar
• Ryu D, Mouchiroud L, Andreux PA, et al. Urolithin a induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nature Med. 2016;22(8):879–888.
   PubMed Web of Science ®Google Scholar
• Tang L, Mo Y, Li Y, et al. Urolithin a alleviates myocardial ischemia/reperfusion injury via PI3K/Akt pathway. Biochem Biophys Res Commun. 2017;486(3):774–780.
   PubMed Web of Science ®Google Scholar
• Xu L, Jiang X, Wei F, et al. Leonurine protects cardiac function following acute myocardial infarction through anti‑apoptosis by the PI3K/AKT/GSK3β signaling pathway. J Mol Med Rep. 2018;18(2):1582–1590.
   PubMed Web of Science ®Google Scholar
• Ajzashokouhi A, Bostan H, Jomezadeh V, et al. A review on the cardioprotective mechanisms of metformin against doxorubicin. Human Exp Toxicol. 2020;39(3):237–248.
   PubMed Web of Science ®Google Scholar
• Wang J, Liu J, Xie L, et al. Bisoprolol, a β1 antagonist, protects myocardial cells from ischemia–reperfusion injury via PI3K/AKT/GSK3β pathway. Fundam Clin Pharmacol. 2020;34(6):708–720.
   PubMed Web of Science ®Google Scholar