Andrographolide contributes to the attenuation of cardiac hypertrophy by suppressing endoplasmic reticulum stress

• Published in: Pharmaceutical biology Vol. 61; no. 1; pp. 61 - 68
• Main Authors: Tian, Qingxin, Liu, Jianlong, Chen, Qin, Zhang, Mingxiao
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2023; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Angiotensin II; Animals; Aorta; Apoptosis; cardiac fibrosis; Cardiomegaly - drug therapy; Cardiomegaly - pathology; Cardiomyocytes; Diterpenes; Diterpenes - pharmacology; Diterpenes - therapeutic use; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Fibrosis; heart failure; Hypertrophy; Kinases; Male; MAP kinase; Mice; Mice, Inbred C57BL; Myocytes, Cardiac - pathology; pressure overload; Transverse aortic constriction; Tunicamycin; heart failure; Transverse aortic constriction; cardiac fibrosis; pressure overload; angiotensin II
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2022.2157021

Andrographolide (Andr) is a bioactive Andr diterpenoid extracted from herbaceous Andrographis paniculata (Burm. F.) Wall. ex Nees (Acanthaceae). Andr can relieve cardiac dysfunction in mice by inhibiting the mitogen-activated protein kinases (MAPK) pathway. This study investigates the efficacy and underlying mechanism of Andr on cardiac hypertrophy in mice. Male C57 mice (20-25 g, 6-8 weeks) were divided into four groups (n = 10 mice/group) as sham group (sham operation), transverse aortic constriction (TAC) model group, TAC + Andr 100 mg/kg group and TAC + Andr 200 mg/kg group. Andr groups were given intragastric administration of Andr (100 and 200 mg/kg) once a day for 14 consecutive days. An in vitro hypertrophy model was established by adding 1 μM of Ang II to H9c2 cells for 48 h induction. In TAC-mice, Andr improved echocardiographic indices [reduced LVESD (30.4% or 37.1%) and LVEDD (24.8% or 26.4%), increased EF (22.9% or 42.6%) and FS (25.4% or 52.2%)], reduced BNP (11.5% or 23.6%) and Ang II levels (10.3% or 32.8%), attenuates cardiac fibrosis and reduces cardiac cell apoptosis in TAC mice. In vitro, Andr attenuated cardiomyocyte hypertrophy and decreased the protein expression of GRP78 (67.8%), GRP94 (47.6%), p-PERK (44.9%) and CHOP (66.8%) in Ang-II-induced H9c2 cells and reversed after endoplasmic reticulum (ER) stress agonist Tunicamycin (TN) treatment. Andr was found to be an anti-hypertrophic regulator, which could attenuate cardiac hypertrophy by suppressing ER stress. It may be a new therapeutic drug for cardiac hypertrophy.