Berberine Attenuates Cardiac Hypertrophy Through Inhibition of mTOR Signaling Pathway

Xing Chen1,2, Xingzuan Jiang1, Chuanfang Cheng2

  • 1Department of Geriatrics, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.

Insights

Berberine treatment ameliorates cardiac hypertrophy in rats and H9c2 cells by inhibiting the mammalian target of rapamycin (mTOR) signaling pathway, suggesting its potential as a therapeutic agent for cardiac conditions.

Area of Science:

  • Cardiovascular Biology
  • Pharmacology
  • Molecular Medicine

Background:

  • Cardiac hypertrophy is a significant risk factor for heart failure.
  • Berberine has shown potential benefits for cardiac hypertrophy, but its mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the cellular and molecular mechanisms underlying berberine's effects on cardiac hypertrophy.
  • To evaluate berberine's efficacy in both in vivo and in vitro models of cardiac hypertrophy.

Main Methods:

  • Cardiac hypertrophy was induced in rats via transverse aorta constriction (TAC) and in H9c2 cells using norepinephrine (NE).
  • Berberine treatment was administered to assess its impact on cardiac function, histology, and protein/mRNA expression.
  • Key signaling pathways, including mammalian target of rapamycin (mTOR), were analyzed using Western blot and qRT-PCR.

Main Results:

  • Berberine treatment significantly ameliorated TAC-induced cardiac hypertrophy and fibrosis in rats.
  • Berberine inhibited the activation of the mTOR signaling pathway (phospho-mTOR, phospho-4EBP1, phospho-p70 S6K) in both rat models and NE-treated H9c2 cells.
  • A concentration of 10 μM berberine, but not 1 μM, effectively reduced NE-induced hypertrophy in H9c2 cells.

Conclusions:

  • Berberine demonstrates cardioprotective effects against pressure-overloaded and norepinephrine-induced cardiac hypertrophy.
  • The mechanism involves the inhibition of the mTOR signaling pathway.
  • Berberine represents a potential therapeutic candidate for treating cardiac hypertrophy and failure.
Abstract

Related Concept Videos

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
807
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.5K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.1K
Heart Failure Drugs: β-Blockers01:22

Heart Failure Drugs: β-Blockers

β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation,...
673
Antihypertensive Drugs: Action of β1 Blockers01:17

Antihypertensive Drugs: Action of β1 Blockers

β1-receptors are primarily located in the heart and kidneys. In cardiac myocytes, these receptors interact with neurotransmitters released by the sympathetic nervous system during heightened activity or danger. As a result, β1-receptors get activated, initiating a series of biochemical processes. Excessive activation of beta receptors due to chronic stress can abnormally increase heart rate and contractility, resulting in high blood pressure or hypertension. To counteract this,...
1.8K
Cardiomyopathy V: Interprofessional Care01:29

Cardiomyopathy V: Interprofessional Care

Managing cardiomyopathy involves addressing underlying or precipitating causes, treating heart failure with medications, and implementing dietary changes and a balanced exercise and rest regimen.Lifestyle ModificationsCardiomyopathy patients should adopt a low-sodium diet to reduce fluid retention and manage heart failure. A personalized exercise and rest plan helps maintain physical fitness without overstraining the heart. Avoiding alcohol and tobacco is essential to prevent further damage to...
219