Nimbolide protects against diabetic cardiomyopathy by regulating endoplasmic reticulum stress and mitochondrial

Haitao Zhang1, Xiaolong Zhao1, Wei Wei2

  • 1Dalian Medical University, Dalian 116044, China.

Tissue & Cell
|July 25, 2024
PubMed

Insights

Nimbolide effectively treats diabetic cardiomyopathy (DCM) by improving cardiac function and reducing myocardial damage. This study reveals its mechanism involves activating the Akt/mTOR pathway, suggesting potential as a novel therapeutic agent for DCM.

Area of Science:

  • Pharmacology
  • Cardiology
  • Endocrinology

Background:

  • Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus.
  • Nimbolide has shown protective effects in other diabetes-related conditions, but its role in DCM is unexplored.
  • Understanding nimbolide's mechanism in DCM is crucial for developing new treatments.

Purpose of the Study:

  • To investigate the protective effects of nimbolide against DCM in vivo and in vitro.
  • To elucidate the molecular mechanisms underlying nimbolide's action in DCM.
  • To evaluate nimbolide as a potential therapeutic agent for DCM.

Main Methods:

  • Diabetes was induced in rats using streptozotocin (STZ); diabetic rats were treated with nimbolide.
  • H9c2 cardiomyocytes were exposed to high glucose to model DCM in vitro.
  • Cardiac function, myocardial injury, endoplasmic reticulum (ER) stress, apoptosis, mitochondrial function, and Akt/mTOR signaling were assessed.

Main Results:

  • Nimbolide dose-dependently reduced blood glucose and improved body weight in diabetic rats.
  • Nimbolide treatment improved cardiac function, reduced myocardial fibrosis, ER stress, and apoptosis.
  • Nimbolide activated the Akt/mTOR pathway and improved mitochondrial function, with effects partially blocked by an Akt inhibitor.

Conclusions:

  • Nimbolide exhibits significant cardioprotective effects in DCM by improving cardiac function and alleviating myocardial damage.
  • The protective mechanism involves the activation of the Akt/mTOR signaling pathway and modulation of ER stress and mitochondrial function.
  • Nimbolide represents a promising novel therapeutic candidate for the treatment of diabetic cardiomyopathy.

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