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Published on: January 10, 2025
Lupeol Alleviates Myocardial Ischemia-Reperfusion Injury in Rats by Regulating NF-[Formula: see text]B and Nrf2
Jing Li1, Xuming Ma1, Jun Yang1
1Department of Cardiology, Gansu Provincial Hospital, Gansu, Lanzhou 730000, P. R. China.
Insights
Lupeol, a compound from Chinese herbs, significantly reduces heart damage from ischemia-reperfusion injury (MIRI) in rats. It works by decreasing inflammation, apoptosis, and oxidative stress via NF-κB and Nrf2 pathways.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Cardiovascular diseases, including myocardial infarction and ischemia-reperfusion (I/R) injury, pose a significant global health challenge.
- Understanding the complex mechanisms of myocardial I/R injury (MIRI) is crucial for clinical advancements.
- Lupeol, a bioactive compound found in medicinal herbs, has demonstrated various bioactivities, but its role in MIRI remains largely unexplored.
Purpose of the Study:
- To investigate the cardioprotective effects of lupeol against myocardial ischemia-reperfusion injury (MIRI) in a rat model.
- To elucidate the underlying mechanisms, including anti-inflammatory, anti-apoptotic, and anti-oxidative properties of lupeol in MIRI.
- To explore the potential involvement of NF-κB and Nrf2 signaling pathways in lupeol's protective effects.
Main Methods:
- Establishment of a rat myocardial I/R model.
- Assessment of myocardial infarction size using 2,3,5-triphenyltetrazolium chloride (TTC) staining.
- Quantification of inflammatory cytokines (IL-10, IL-1β, TNF-α, IL-6), CK-MB, and LDH levels via qRT-PCR and ELISA.
- Evaluation of cellular apoptosis using TUNEL staining.
- Analysis of NF-κB and Nrf2 signaling pathway modulation.
Main Results:
- Lupeol administration significantly reduced myocardial infarct size following I/R.
- Lupeol treatment ameliorated I/R-induced myocardial inflammation, apoptosis, and oxidative stress.
- The cardioprotective effects of lupeol were associated with the modulation of NF-κB and Nrf2 signaling pathways.
Conclusions:
- Lupeol exhibits significant cardioprotective effects against myocardial ischemia-reperfusion injury in a rat model.
- These protective effects are attributed to lupeol's anti-oxidant, anti-inflammatory, and anti-apoptotic activities.
- Lupeol's therapeutic potential in mitigating MIRI is linked to its modulation of NF-κB and Nrf2 signaling pathways, suggesting it as a promising therapeutic agent.
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.
