Related Experiment Video
Updated: May 26, 2025
08:55
The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia
Published on: November 30, 2016
16.1K
Withaferin A Attenuates Muscle Cachexia Induced by Angiotensin II Through Regulating Pathways Activated by
Sham S Kakar1,2, Vasa Vemuri1, Mariusz Z Ratajczak2,3
1Department of Physiology, University of Louisville, Louisville, KY 40202, USA.
Cells
|February 25, 2025
Summary
Withaferin A (WFA) directly combats muscle wasting in cachexia by targeting inflammatory and atrophic pathways. This study shows WFA
Area of Science:
- Biochemistry
- Molecular Biology
- Physiology
Background:
- Cachexia is a severe muscle-wasting syndrome often linked to cancer.
- Withaferin A (WFA) previously showed potential in mitigating cancer-induced cachexia.
- The direct effects of WFA on muscle atrophy were not fully understood.
Purpose of the Study:
- To investigate the direct anti-cachectic effects of Withaferin A (WFA).
- To determine if WFA's protective effects are independent of its antitumor properties.
- To elucidate the molecular mechanisms underlying WFA's action on skeletal muscle.
Main Methods:
- A mouse model of cachexia was established using continuous angiotensin II (Ang II) infusion.
- Muscle mass, grip strength, and molecular markers of inflammation and atrophy were assessed.
- Key pathways including the ubiquitin-proteasome system (UPS) and autophagy were analyzed.
Main Results:
- Ang II infusion induced significant muscle atrophy, reduced strength, and altered molecular markers.
- WFA treatment reversed these effects, restoring muscle mass and function.
- WFA normalized the expression of inflammatory cytokines, UPS, and autophagy-related genes.
Conclusions:
- Withaferin A (WFA) demonstrates direct anti-cachectic effects on skeletal muscle.
- WFA targets key inflammatory and atrophic pathways, including the NLRP3 inflammasome, UPS, and autophagy.
- WFA shows potential as a therapeutic agent for managing muscle wasting in cachexia.
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
371
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...
371
01:25Antihypertensive Drugs: Direct Renin Inhibitors
469
The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
469
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
455
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
455
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
571
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
571
01:17Pathophysiology of Heart Failure
1.5K
Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
1.5K
01:24Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K