Lupeol Alleviates Myocardial Ischemia-Reperfusion Injury in Rats by Regulating NF-[Formula: see text]B and Nrf2 Pathways

Am J Chin Med. 2022;50(5):1269-1280. doi: 10.1142/S0192415X22500525. Epub 2022 Jun 4.

Abstract

Cardiovascular disease is a global health problem. Previous studies revealed that it involves acute myocardial infarction and ischemia-reperfusion (I/R) injury. The mechanism of myocardial I/R injury is complex. But recognizing its mechanisms will bring important clinical significance. Lupeol is widely found in Chinese medicinal herbs and has been shown to have a variety of bio-activities. However, the pharmacological action of lupeol in the progress of myocardial ischemia-reperfusion injury (MIRI) is unclear. This study used a rat myocardial I/R model and the morphological changes in myocardium were determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The expression levels of IL-10, IL-1[Formula: see text], TNF-[Formula: see text], and IL-6 were assessed by quantitative real-time PCR (qRT-PCR) and ELISA. The expression levels of MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) level and inflammatory cytokines were quantified using ELISA. The cellular apoptotic rate was determined by TUNEL staining. The findings showed that lupeol significantly decreased myocardial infarction after I/R and ameliorated I/R-induced myocardial inflammation, apoptosis, and oxidative stress. Furthermore, our results suggested that lupeol protected against MIRI-induced myocardial infarction through modulation of NF-[Formula: see text]B and Nrf2 signaling pathways. In summary, this study first clarified the cardioprotective effects of lupeol against I/R-induced myocardial infarction in rats, which could be due to its anti-oxidant, anti-inflammatory, and anti-apoptotic activities. Our study also highlighted a mechanism of NF-[Formula: see text]B and Nrf2 signaling, through which lupeol could be a promising agent in protecting against I/R-induced myocardial infarction.

Keywords: Lupeol; Myocardial Infarction; Myocardial Ischemia-Reperfusion Injury; NF-[Formula: see text]B; Nrf2.

MeSH terms

  • Animals
  • Apoptosis
  • Myocardial Infarction* / drug therapy
  • Myocardial Infarction* / genetics
  • Myocardial Reperfusion Injury* / drug therapy
  • Myocardial Reperfusion Injury* / genetics
  • Myocardial Reperfusion Injury* / metabolism
  • NF-E2-Related Factor 2 / genetics
  • Pentacyclic Triterpenes
  • Rats
  • Rats, Sprague-Dawley

Substances

  • NF-E2-Related Factor 2
  • Pentacyclic Triterpenes
  • lupeol