Leonurine protects cardiac function following acute myocardial infarction through anti‑apoptosis by the PI3K/AKT/GSK3β signaling pathway Corrigendum in /10.3892/mmr.2023.12952

Xu,Lin; Jiang,Xuejun; Wei,Fang; Zhu,Hongling

doi:10.3892/mmr.2018.9084

Leonurine protects cardiac function following acute myocardial infarction through anti‑apoptosis by the PI3K/AKT/GSK3β signaling pathway

Corrigendum in: /10.3892/mmr.2023.12952

Authors:
- Lin Xu
- Xuejun Jiang
- Fang Wei
- Hongling Zhu
View Affiliations

Affiliations: Department of Cardiology, Renmin Hospital of Wuhan University. Wuhan, Hebei 430060, P.R. China
Published online on: May 29, 2018 https://doi.org/10.3892/mmr.2018.9084
Pages: 1582-1590
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Leonurine is a compound derived from Herba leonuri, which has been reported to protect cardiac tissue against ischemic injury via antioxidant and anti‑apoptosis effects. The present study investigated whether these effects may be applied to acute myocardial infarction (MI) and examined the underlying mechanisms of leonurine treatment. A rat model of MI was induced by coronary artery ligation. Leonurine was administered at 15 mg/kg/day by oral gavage following the onset of MI. Rats in the sham group and the saline group were administered with an equal volume of saline. Echocardiography, Masson's trichrome staining, and terminal‑deoxynucleotidyl transferase‑mediated dUTP nick end labeling assays were performed 28 days post MI. The expression of B‑cell lymphoma‑2 and Bax were assessed by western blot analysis and reverse transcription‑quantitative polymerase chain reaction. Phosphoinositide 3‑kinase (PI3K), protein kinase B and glycogen synthase kinase‑3β (GSK3β) protein expression were investigated by western blot analysis. Leonurine significantly alleviated collagen deposition and MI size, inhibited cell apoptosis and improved myocardial function. This was accompanied by significantly increased levels of phosphorylated (p)‑PI3K, p‑AKT, p‑GSK3β and Bcl‑2, as well as significantly decreased levels of caspase3, cleaved‑caspase3 and Bax following MI. The results demonstrated that leonurine exerts potent cardio‑protective effects in a rat model of MI by inducing anti‑apoptotic effects by activating the PI3K/AKT/GSK3β signaling pathway.

View Figures

View References

1	Zhu YZ, Chong CL, Chuah SC, Huang SH, Nai HS, Tong HT, Whiteman M and Moore PK: Cardioprotective effects of nitroparacetamol and paracetamol in acute phase of myocardial infarction in experimental rats. Am J Physiol Heart Circ Physiol. 290:H517–H524. 2006. View Article : Google Scholar : PubMed/NCBI
2	Liu C, Guo W, Maerz S, Gu X and Zhu Y: 3,5-Dimethoxy-4-(3-(2-carbonyl-ethyldisulfanyl)-propionyl)-benzoic acid 4-guanidino-butyl ester: A novel twin drug that prevents primary cardiac myocytes from hypoxia-induced apoptosis. Eur J Pharmacol. 700:118–126. 2013. View Article : Google Scholar : PubMed/NCBI
3	Gallogly MM, Shelton MD, Qanungo S, Pai HV, Starke DW, Hoppel CL, Lesnefsky EJ and Mieyal JJ: Glutaredoxin regulates apoptosis in cardiomyocytes via NFkappaB targets Bcl-2 and Bcl-xL: Implications for cardiac aging. Antioxid Redox Signal. 12:1339–1353. 2010. View Article : Google Scholar : PubMed/NCBI
4	Lee Y and Gustafsson AB: Role of apoptosis in cardiovascular disease. Apoptosis. 14:536–548. 2009. View Article : Google Scholar : PubMed/NCBI
5	Haunstetter A and Izumo S: Toward antiapoptosis as a new treatment modality. Circ Res. 86:371–376. 2000. View Article : Google Scholar : PubMed/NCBI
6	Liu XH, Xin H and Zhu YZ: More than a ‘mother-benefiting’ herb: Cardioprotective effect of Herba leonuri. Sheng Li Xue Bao. 59:578–584. 2007.PubMed/NCBI
7	Kuang PG, Zhou XF, Zhang FY and Lang SY: Motherwort and cerebral ischemia. J Tradit Chin Med. 8:37–40. 1988.PubMed/NCBI
8	Wang ZS, Li DW, Xia WJ, Qiu HQ and Zhu LY: The therapeutic effect of herba leonuri in the treatment of coronary myocardial ischemia. J Tradit Chin Med. 8:103–106. 1988.PubMed/NCBI
9	Liu XH, Xin H, Hou AJ and Zhu YZ: Protective effects of leonurine in neonatal rat hypoxic cardiomyocytes and rat infarcted heart. Clin Exp Pharmacol Physiol. 36:696–703. 2009. View Article : Google Scholar : PubMed/NCBI
10	Liu XH, Chen PF, Pan LL, Silva RD and Zhu YZ: 4-Guanidino-n-butyl syringate (Leonurine, SCM 198) protects H9c2 rat ventricular cells from hypoxia-induced apoptosis. J Cardiovasc Pharmacol. 54:437–444. 2009. View Article : Google Scholar : PubMed/NCBI
11	Liu X, Pan L, Gong Q and Zhu Y: Leonurine (SCM-198) improves cardiac recovery in rat during chronic infarction. Eur J Pharmacol. 649:236–241. 2010. View Article : Google Scholar : PubMed/NCBI
12	Liu XH, Pan LL, Deng HY, Xiong QH, Wu D, Huang GY, Gong QH and Zhu YZ: Leonurine (SCM-198) attenuates myocardial fibrotic response via inhibition of NADPH oxidase 4. Free Radic Biol Med. 54:93–1042. 2013. View Article : Google Scholar : PubMed/NCBI
13	Liu H, Zhang X, Du Y, Ji H, Li S, Li L, Xing Y, Zhang X, Dong L, Wang C, et al: Leonurine protects brain injury by increased activities of UCP4, SOD, CAT and Bcl-2, decreased levels of MDA and Bax, and ameliorated ultrastructure of mitochondria in experimental stroke. Brain Res. 1474:73–81. 2012. View Article : Google Scholar : PubMed/NCBI
14	Yu-Shengyou and LI Y: Dexamethasone inhibits podocyte apoptosis by stabilizing the PI3K/Akt signal pathway. Biomed Res Int. 2013:3269862013. View Article : Google Scholar : PubMed/NCBI
15	Franke TF, Hornik CP, Segev L, Shostak GA and Sugimoto C: PI3K/Akt and apoptosis: size matters. Oncogene. 22:8983–8998. 2003. View Article : Google Scholar : PubMed/NCBI
16	Vara Fresno JA, Casado E, De Castro J, Cejas P, Belda-Iniesta C and González-Barón M: PI3K/Akt signalling pathway and cancer. Cancer Treat Rev. 30:193–204. 2004. View Article : Google Scholar : PubMed/NCBI
17	Ohashi H, Takagi H, Oh H, Suzuma K, Suzuma I, Miyamoto N, Uemura A, Watanabe D, Murakami T, Sugaya T, et al: Phosphatidylinositol 3-kinase/Akt regulates angiotensin II-induced inhibition of apoptosis in microvascular endothelial cells by governing survivin expression and suppression of caspase-3 activity. Circ Res. 94:785–793. 2004. View Article : Google Scholar : PubMed/NCBI
18	Tramontano AF, Muniyappar R, Black AD, Blendea MC, Cohen I, Deng L, Sowers JR, Cutaia MV and El-Sherif N: Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway. Biochem Biophys Res Commun. 308:990–994. 2003. View Article : Google Scholar : PubMed/NCBI
19	Cai Z and Semenza GL: Phosphatidylinositol-3-kinase signaling is required for erythropoietin-mediated acute protection against myocardial ischemia/reperfusion injury. Circulation. 109:2050–2053. 2004. View Article : Google Scholar : PubMed/NCBI
20	Rayasam GV, Tulasi VK, Sodhi R, Davis JA and Ray A: Glycogen synthase kinase 3: More than a namesake. Br J Pharmacol. 156:885–98. 2009. View Article : Google Scholar : PubMed/NCBI
21	Maixner DW and Weng HR: The role of glycogen synthase kinase 3 beta in neuroinflammation and pain. J Pharm Pharmacol (Los Angel). 1:0012013.PubMed/NCBI
22	Cross DA, Alessi DR, Cohen P, Andjelkovich M and Hemmings BA: Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 378:785–789. 1995. View Article : Google Scholar : PubMed/NCBI
23	Descamps S, Pawlowski V, Révillion F, Hornez L, Hebbar M, Boilly B, Hondermarck H and Peyrat JP: Expression of nerve growth factor receptors and their prognostic value in human breast cancer. Cancer Res. 61:4337–4340. 2001.PubMed/NCBI
24	Morisco C, Zebrowski D, Condorelli G, Tsichlis P, Vatner SF and Sadoshima J: The Akt-glycogen synthase kinase 3beta pathway regulates transcription of atrial natriuretic factor induced by beta-adrenergic receptor stimulation in cardiac myocytes. J Biol Chem. 275:14466–14475. 2000. View Article : Google Scholar : PubMed/NCBI
25	Badorff C, Ruetten H, Mueller S, Stahmer M, Gehring D, Jung F, Ihling C, Zeiher AM and Dimmeler S: Fas receptor signaling inhibits glycogen synthase kinase 3 beta and induces cardiac hypertrophy following pressure overload. J Clin Invest. 109:373–381. 2002. View Article : Google Scholar : PubMed/NCBI
26	Gong R, Rifai A and Dworkin LD: Activation of PI3K-Akt-GSK3beta pathway mediates hepatocyte growth factor inhibition of RANTES expression in renal tubular epithelial cells. Biochem Biophys Res Commun. 330:27–33. 2005. View Article : Google Scholar : PubMed/NCBI
27	Wagner C, Tillack D, Simonis G, Strasser RH and Weinbrenner C: Ischemic post-conditioning reduces infarct size of the in vivo rat heart: Role of PI3-K, mTOR, GSK-3beta and apoptosis. Mol Cell Biochem. 339:135–147. 2010. View Article : Google Scholar : PubMed/NCBI
28	Somervaille TC, Linch DC and Khwaja A: Growth factor withdrawal from primary human erythroid progenitors induces apoptosis through a pathway involving glycogen synthase kinase-3 and Bax. Blood. 98:1374–1381. 2001. View Article : Google Scholar : PubMed/NCBI
29	Sun J, Huang SH, Zhu YC, Whiteman M, Wang MJ, Tan BK and Zhu YZ: Anti-oxidative stress effects of Herba leonuri on ischemic rat hearts. Life Sci. 76:3043–3056. 2005. View Article : Google Scholar : PubMed/NCBI
30	Liu X, Pan L, Wang X, Gong Q and Zhu YZ: Leonurine protects against tumor necrosis factor-α-mediated inflammation in human umbilical vein endothelial cells. Atherosclerosis. 222:34–42. 2012. View Article : Google Scholar : PubMed/NCBI
31	Loh KP, Qi J, Tan BK, Liu XH, Wei BG and Zhu YZ: Leonurine protects middle cerebral artery occluded rats through antioxidant effect and regulation of mitochondrial function. Stroke. 41:2661–2668. 2010. View Article : Google Scholar : PubMed/NCBI