Phenylethanol Glycosides Protect Myocardial Hypertrophy Induced By Abdominal Aortic Constriction Via ECE-1 Demethylation Inhibition And PI3K/PKB/eNOS Pathway Enhancement
Mar 06, 2022
Contact: Audrey Hu Whatsapp/hp: 0086 13880143964 Email: audrey.hu@wecistanche.com
Qiong-Ling Fan,1 Jia-Wei Wang,1 Shi-Lei Zhang,2 Tao Liu, & et al.
Phenylethanoild glycosides (CPhGs) are the core material basis of pharmacological activity in Cistanche tubulosa and have a variety of pharmacological effects. However, it is unclear whether CPhGs have an ameliorative effect on pressure overload-induced myocardial hypertrophy. In this study, male SD rats weighing (200 ± 20) g were established cardiac hypertrophy models by abdominal aortic coarctation (AAC). After the operation, the rats were gavaged with corresponding medicine for 6 weeks (CPhGs 125, 250, and 500 mg/kg/d and valsartan 8.3 mg/kg/d). Echocardiography, heart weight index (HWI), cross-sectional area of cardiomyocytes (CSCA), fibrosis area, plasma endothelin 1(ET-1), and proinflammatory factors levels were detected. Our results showed that different CPhGs dosage decreased left ventricular posterior wall thickness (LVPWT), left ventricular end-diastolic diameter (LVED), HWI, CSCA, fibrosis area, ET-1, proinflammatory factors, arterial natriuretic peptide (ANP), brain natriuretic peptide (BNP), endothelin converting enzyme 1(ECE-1) mRNA levels, cyclooxygenase 2 (COX-2), high mobility group box 1 (HMGB-1) protein levels, and ECE-1 demethylation level while increasing left ventricular ejection fractions (LVEF), left ventricular fractional shortening (LVFS), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-PKB), and phosphorylated endothelial nitric oxide synthetase (p-eNOS). -e indexes of the CPhGs 250 and 500 mg/kg group were significantly different from the AAC group; compared with the valsartan group (AV), the indexes of the CPhGs 500 mg/kg group were not significantly different. In conclusion, CPhGs ameliorated myocardial hypertrophy rats by AAC, which may be related to ECE- 1 demethylation inhibition and PI3K/PKB/eNOS enhancement.
Introduction
Myocardial hypertrophy is a common adaptive response to pressure overload in hypertensive patients [1]. But with the aggravation of myocardial hypertrophy, the demand for myocardial blood supply increases, and the decrease of coronary blood follow reserve leads to myocardial injury. -e development of myocardial hypertrophy is known to increase the morbidity and mortality of cardiovascular diseases [2–4]. Since hypertension is the main cause of myocardial hypertrophy, the current treatment of myocardial hypertrophy is mainly based on antihypertensive drugs, such as thiazide diuretics, calcium channel blockers, and angiotensin-converting enzyme inhibitors [5, 6]. However, the electrolyte disturbance, postural hypotension, dry cough, and other adverse reactions caused by taking these drugs remain potential risks for patients. Hence, there is an urgent need to find safer and more effective drugs.
Cistanche tubulosa extract
Cistanche tubulosa, a precious traditional Chinese herb medicine, is widely grown in Xinjiang, China. It has a variety of benefits to the consumer such as strengthening immunity, tonifying kidney impotence, improving intelligence, anti-oxidation, anti-aging, protecting the liver, and lowering blood pressure [7]. -e plant contains phenylethanoid glycosides (CPhGs), oleoterpenes, and polysaccharides. CPhGs are one of the effective substances contained in Cistanche. -eir main components are echinoids and moleniosides (molecular structure diagrams are shown in Figure 1). In in vivo and in vitro studies, CPhGs have been proven to be effective in preventing and treating ischemic heart disease [9, 10]. Myocardial ischemia is also a critical pathological process of hypertrophy, but it is unclear whether the substance has a protective effect on hypertrophy. Xinjiang Kazakh people suffer from a high incidence of essential hypertension (EH) due to long-term consumption of salty milk tea [11, 12]. In the previous study, we used methylation microarray to screen the abnormal methylation sites in the blood samples of Kazakh EH patients and normal people, showing the demethylation level of endothelin converting enzyme 1 (ECE-1) was positively correlated with EH [13]. In previous pathway analysis, it was found that ECE-1 was involved in the phosphatidylinositol 3-kinase/ protein kinase B/endothelial nitric oxide synthase (PI3K/ PKB/eNOS) pathway [13]. PI3K/PKB/eNOS is an important pathway in the formation of myocardial hypertrophy and the downstream pathway of ET-1 [14–16]. A prior study has shown that CPhGs liposome could inhibit the proliferation of hepatic stellate cells by regulating the PI3K/PKB pathway [17].
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Therefore, we hypothesized that CPhGs may play a protective role in the human body by influencing ECE-1 and the PI3K/PKB/eNOS pathway. Hence, we investigated the possible protective effect of CPhGs on myocardial hypertrophy and its effect on ECE-1 demethylation and PI3K/PKB/eNOS pathway with pressure overload myocardial hypertrophy in rats by abdominal aortic coarctation (AAC).
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