Erxian Decoction Ameliorates Myocardial Tissue Damage Through Activating PI3K/AKT Signaling Pathway in Ovariectomized Rats

Overview

Journal Ann Med

Publisher Informa Healthcare

Specialty General Medicine

Date 2024 Oct 9

PMID 39382555

Authors

Ying Yang

Haixia Liu

Jing Hu

Yujie Ma

Pei Li

Zhiguo Zhang

Yanjing Chen

Affiliations

Soon will be listed here.

Abstract

Background: Erxian decoction (EXD) is an empirical formula for treating cardiovascular disease, our previous work has shown that EXD could improve the cardiovascular structure and function in ovariectomized (OVX) rats, but its pharmacological mechanism is still unclear.

Materials And Methods: Network pharmacology was utilized to assess the key active components and central targets of EXD in treating postmenopausal cardiovascular disease. Then, an OVX rat model was established, HE staining and transmission electron microscope were utilized to observe myocardial tissue morphology, TUNEL staining was utilized to detect cardiomyocyte apoptosis, western blot, and ELISA were used to confirm efficacy and pathway of EXD.

Results: The network pharmacology prediction results showed that 129 common targets were identified by intersecting EXD targets and postmenopausal cardiovascular disease targets, including AKT1, TNF, IL-6, IL-1β, PTGS2 and other core targets, apoptosis, PI3K/AKT, and other signaling pathways may be closely related to postmenopausal cardiovascular disease. After ovariectomy, the myocardial tissue of rats was damaged, the expression level of PI3K/AKT pathway-related molecules in the myocardial tissue were decreased, the apoptosis index of cardiomyocytes was increased, and the levels of inflammatory factors (TNF-α, IL-6, and IL-1β) were enhanced. EXD intervention could improve myocardial tissue injury, EXD could up-regulate the protein expression of PI3K and p-AKT in myocardial tissue, and thereby prevent myocardial cell apoptosis. At the same time, EXD downregulated the levels of inflammatory factors in serum of ovariectomized rats.

Conclusion: EXD may prevent myocardial tissue damage through induction of the PI3K/AKT signaling pathway, thereby reducing cardiomyocyte apoptosis and inflammation. EXD may be a potential drug for the treatment of postmenopausal cardiovascular disease.

References

Wang S, Tsai K, Chou W, Cheng H, Huang Y, Ou H . Quercetin Mitigates Cisplatin-Induced Oxidative Damage and Apoptosis in Cardiomyocytes through Nrf2/HO-1 Signaling Pathway. Am J Chin Med. 2022; 50(5):1281-1298. DOI: 10.1142/S0192415X22500537. View

Van Weelden W, Massuger L, Pijnenborg J, Romano A . Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review. Front Oncol. 2019; 9:359. PMC: 6513972. DOI: 10.3389/fonc.2019.00359. View

Hung C, Chan S, Chu P, Tsai K . Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation. Mol Nutr Food Res. 2015; 59(10):1905-17. DOI: 10.1002/mnfr.201500144. View

Roque M, Heras M, Roig E, Masotti M, Rigol M, Betriu A . Short-term effects of transdermal estrogen replacement therapy on coronary vascular reactivity in postmenopausal women with angina pectoris and normal results on coronary angiograms. J Am Coll Cardiol. 1998; 31(1):139-43. DOI: 10.1016/s0735-1097(97)00436-1. View

Moreira A, Silva A, Santos M, Sardao V . Phytoestrogens as alternative hormone replacement therapy in menopause: What is real, what is unknown. J Steroid Biochem Mol Biol. 2014; 143:61-71. DOI: 10.1016/j.jsbmb.2014.01.016. View

Rong R, Xijun X . Erythropoietin pretreatment suppresses inflammation by activating the PI3K/Akt signaling pathway in myocardial ischemia-reperfusion injury. Exp Ther Med. 2015; 10(2):413-418. PMC: 4509423. DOI: 10.3892/etm.2015.2534. View

Gencel V, Benjamin M, Bahou S, Khalil R . Vascular effects of phytoestrogens and alternative menopausal hormone therapy in cardiovascular disease. Mini Rev Med Chem. 2011; 12(2):149-74. PMC: 3288319. DOI: 10.2174/138955712798995020. View

Siasos G, Tousoulis D, Tsigkou V, Kokkou E, Oikonomou E, Vavuranakis M . Flavonoids in atherosclerosis: an overview of their mechanisms of action. Curr Med Chem. 2013; 20(21):2641-60. DOI: 10.2174/0929867311320210003. View

Chen H, Cho W, Sze S, Tong Y . Treatment of menopausal symptoms with Er-xian decoction: a systematic review. Am J Chin Med. 2008; 36(2):233-44. DOI: 10.1142/S0192415X08005746. View

10.

Wang X, Wang Z, Zheng J, Li S . TCM network pharmacology: A new trend towards combining computational, experimental and clinical approaches. Chin J Nat Med. 2021; 19(1):1-11. DOI: 10.1016/S1875-5364(21)60001-8. View

11.

Vinogradova Y, Coupland C, Hippisley-Cox J . Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019; 364:k4810. PMC: 6326068. DOI: 10.1136/bmj.k4810. View

12.

Fang F, Li D, Pan H, Chen D, Qi L, Zhang R . Luteolin inhibits apoptosis and improves cardiomyocyte contractile function through the PI3K/Akt pathway in simulated ischemia/reperfusion. Pharmacology. 2011; 88(3-4):149-58. DOI: 10.1159/000330068. View

13.

Suchal K, Malik S, Gamad N, Malhotra R, Goyal S, Bhatia J . Kampeferol protects against oxidative stress and apoptotic damage in experimental model of isoproterenol-induced cardiac toxicity in rats. Phytomedicine. 2016; 23(12):1401-1408. DOI: 10.1016/j.phymed.2016.07.015. View

14.

Zhang Z, Xiang L, Zhao L, Jiao H, Wang Z, Li Y . The protective effect of Er-Xian decoction against myocardial injury in menopausal rat model. BMC Complement Altern Med. 2018; 18(1):245. PMC: 6122672. DOI: 10.1186/s12906-018-2311-9. View

15.

Wang Y, Jiang Y, Hu J, Yang Y, Liu Y, Liu H . Dynamic Evolution of Cardiac Function and Glucose and Lipid Metabolism in Ovariectomized Rats and the Intervention Effect of Erxian Decoction. Evid Based Complement Alternat Med. 2022; 2022:8090868. PMC: 9789914. DOI: 10.1155/2022/8090868. View

16.

Knowlton A, Lee A . Estrogen and the cardiovascular system. Pharmacol Ther. 2012; 135(1):54-70. PMC: 5688223. DOI: 10.1016/j.pharmthera.2012.03.007. View

17.

Marino M, Galluzzo P, Ascenzi P . Estrogen signaling multiple pathways to impact gene transcription. Curr Genomics. 2008; 7(8):497-508. PMC: 2269003. DOI: 10.2174/138920206779315737. View

18.

Dominguez-Lopez I, Yago-Aragon M, Salas-Huetos A, Tresserra-Rimbau A, Hurtado-Barroso S . Effects of Dietary Phytoestrogens on Hormones throughout a Human Lifespan: A Review. Nutrients. 2020; 12(8). PMC: 7468963. DOI: 10.3390/nu12082456. View

19.

Xiong X, Yang X, Li X, Yue G, Xing Y, Cho W . Efficacy and safety of Chinese herbal medicine for patients with postmenopausal hypertension: A systematic review and meta-analysis. Pharmacol Res. 2019; 141:481-500. DOI: 10.1016/j.phrs.2019.01.018. View

20.

Chen T, Zhang X, Zhu G, Liu H, Chen J, Wang Y . Quercetin inhibits TNF-α induced HUVECs apoptosis and inflammation via downregulating NF-kB and AP-1 signaling pathway in vitro. Medicine (Baltimore). 2020; 99(38):e22241. PMC: 7505396. DOI: 10.1097/MD.0000000000022241. View