Effect of phenylacetamide isolated from lepidium apetalum on myocardial injury in spontaneously hypertensive rats and its possible mechanism

• Published in: Pharmaceutical biology 2020-01, Vol.58 (1), p.597-609
• Main Authors: Zhang, Qi, Yuan, Peipei, Li, Meng, Fu, Yang, Hou, Ying, Sun, Yaping, Gao, Liyuan, Wei, Yaxin, Feng, Weisheng, Zheng, Xiaoke
• Format: Article
• Language: English
• Subjects: Acetamides - isolation & purification; Acetamides - therapeutic use; Acetanilide; Animals; anti-myocardial injury; antihypertensive; Antihypertensive Agents - isolation & purification; Antihypertensive Agents - therapeutic use; Antihypertensives; Biochemical markers; Cardiovascular diseases; Cell viability; Drug development; H9c2; Heart; Hydrogen peroxide; Hypertension; Hypertension - drug therapy; Hypertension - metabolism; Hypertension - pathology; IL-1β; Inflammation; Lepidium; Male; MAP kinase; Molecular modelling; Oxidative stress; Plant Extracts - isolation & purification; Plant Extracts - therapeutic use; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Smad3 protein; Structure-function relationships; Treatment Outcome
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2020.1778043

In the antihypertensive study of phenylacetamide (PA) on spontaneously hypertensive rats (SHR), it was occasionally found that PA prevents myocardial injury. Clarify the protective mechanism of PA on myocardial injury in SHR rats. In vivo, SHR rats were treated with or without PA (15, 30, 45 mg/kg) for 3 weeks (12 per group). In vitro, H9c2 cells were treated with PA (1, 5, 10 μM) for 24 h, and then stimulated with H 2 O 2 (300 μM) for 4 h. Molecular mechanisms were explored through cardiac pathology, cardiac function and biochemical markers. In vivo, PA (15, 30, 45 mg/kg) reduced CVF from 14.8 ± 1.62 to 9.94 ± 1.56, 8.6 ± 1.33, 8.14 ± 1.45%; increased the LVEF relative level from 0.8 ± 0.06 to 0.83 ± 0.04, 0.86 ± 0.05, 0.9 ± 0.04. All three doses can improve the cardiac pathological structure and function (LVEDD, LVESD, LVFS, heart index, NT-proBNP, CKMB, SBP); however, 45 mg/kg works best. But different doses show different molecular mechanisms. PA (15 mg/kg) improves RAAS system (REN, ACE), inflammation (ET-1, IL-1β) and MAPK pathway (p-ERK/ERK, p-JNK/JNK) better. PA (45 mg/kg) improves oxidative stress (SOD, NOX1) and TGF-β pathway (Smad3) better. In vitro, PA improved cell viability, oxidative stress (SOD, NOX1) and Smad3 protein expression. Discussion and conclusions: PA regulates different mechanisms at different concentrations to improve myocardial injury, and high dose is the best. This experiment provides a theoretical basis for the development of new clinical drugs for cardiovascular disease.