Effect and mechanism of asiatic acid on autophagy in myocardial ischemia‑reperfusion injury <em>in&nbsp;vivo</em> and <em>in&nbsp;vitro</em>

Myocardial ischemia‑reperfusion injury (MIRI) is a major cause of heart failure in patients with coronary heart disease. The excessive accumulation of reactive oxygen species (ROS) during MIRI induces the overactivation of an autophagic response, which aggravates myocardial cell damage. Asiatic acid (AA) is a triterpenoid compound, which is extracted from Centella asiatica and exhibits a variety of pharmacological effects such as hepatoprotective, neuropro‑ tective and antioxidant. However, the association of AA with autophagy in MIRI is not fully understood. In the present study, the positive effects of AA in MIRI injury were deter‑ mined via establishing a MIRI mouse model. Pre‑treatment with AA was indicated to improve cardiac function and decrease cardiomyocyte autophagy in mice subjected to MIRI. To examine the protective effects of AA and the underlying mechanisms in MIRI, a cardiomyocyte glucose deprivation/reperfusion (OGD) model was established. The administration of AA decreased the levels of ROS and malo‑ ndialdehyde and increased the levels of superoxide dismutase activity in OGD‑treated cells. Using western blotting, it was demonstrated that treatment with AA decreased the phos‑ phorylation of p38 and increased the expression of Bcl‑2 in Correspondence to: Professor Qiang Wang, Department of Cardiovascular Surgery, Northern Jiangsu People's Hospital, Clinical Medical College, Yangzhou University, 98 West Nantong Road, Yangzhou, Jiangsu 225001, P.R. China E‑mail: wangqiangyz123@163.com Professor Xiaowei Wang, Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, P.R. China E‑mail: wangxiaowein1@163.com *Contributed equally Key words: coronary heart disease, myocardial ischemic‑reperfusion injury, asiatic acid, autophagy, reactive oxygen species, p38‑mitogen‑ activated protein kinase, B‑cell lymphoma‑2, beclin‑1 OGD‑treated cells. Additionally, the expression of autophagy markers, including beclin‑1 and the microtubule‑associated proteins 1A/1B light chain 3B II/I ratio, were also decreased in AA treated cells compared with OGD‑treated cells. These results demonstrated that AA pretreatment protected cardiomyocytes from ROS‑mediated autophagy via a p38 mitogen‑activated protein kinase/Bcl‑2/beclin‑1 signaling pathway in MIRI.