Protective Effects of Fucoxanthin on Hydrogen Peroxide-Induced Calcification of Heart Valve Interstitial Cells

Abstract

Cardiovascular diseases such as atherosclerosis and aortic valve sclerosis involve inflammatory reactions triggered by various stimuli, causing increased oxidative stress. This increased oxidative stress causes damage to the heart cells, with subsequent cell apoptosis or calcification. Currently, heart valve damage or heart valve diseases are treated by drugs or surgery. Natural antioxidant products are being investigated in related research, such as fucoxanthin (Fx), which is a marine carotenoid extracted from seaweed, with strong antioxidant, anti-inflammatory, and anti-tumor properties. This study aimed to explore the protective effect of Fx on heart valves under high oxidative stress, as well as the underlying mechanism of action. Rat heart valve interstitial cells under H2O2-induced oxidative stress were treated with Fx. Fx improved cell survival and reduced oxidative stress-induced DNA damage, which was assessed by cell viability analysis and staining with propidium iodide. Alizarin Red-S analysis indicated that Fx has a protective effect against calcification. Furthermore, Western blotting revealed that Fx abrogates oxidative stress-induced apoptosis via reducing the expression of apoptosis-related proteins as well as modulate Akt/ERK-related protein expression. Notably, in vivo experiments using 26 dogs treated with 60 mg/kg of Fx in combination with medical treatment for 0.5 to 2 years showed significant recovery in their echocardiographic parameters. Collectively, these in vitro and in vivo results highlight the potential of Fx to protect heart valve cells from high oxidative stress-induced damage.

A Systematic Review on Marine Algae-Derived Fucoxanthin: An Update of Pharmacological Insights

“…Cardiovascular diseases (CVDs) are the most common cause of death worldwide, killing around 17.9 million people each year [ 69 ]. Some CVDs involve inflammatory reactions leading to oxidative damage and apoptosis [ 70 ]. The acute myocardial infarction is also associated with elevated levels of ROS and oxidative stress [ 71 ].…”

“…Fucoxanthin prevented oxidative stress-induced apoptosis by enhancing antioxidant activity and downregulating apoptotic markers caspase-3, caspase-8, and caspase-9, etc. Furthermore, it aided cell survival and protected from calcification [ 70 ].…”

The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products

“…Troxerutin also inactivates acetylcholinesterase and activates PI3K/AKT in Alzheimer’s disease models ( Table 6 ) [ 393 ]. Moreover, fucoxanthin, a marine seaweed-derived carotenoid, suppresses H 2 O 2 -triggered ROS generation and apoptosis by down-regulating H 2 O 2 -activated AKT and ERK expression [ 376 ].…”

Oxidative Stress in Calcific Aortic Valve Stenosis: Protective Role of Natural Antioxidants

“…In addition, fucoxanthin is known to reduce the risk factor of cardiovascular diseases, such as hyperlipidemia, inflammatory markers, hypertension, insulin resistance, and obesity [ 102 ]. Furthermore, fucoxanthin inhibited apoptosis by a decreased ROS formation and reduced calcification and extracellular matrix accumulation through phosphorylation regulation of AKT and ERK in H 2 O 2 -induced calcification [ 67 ]. Moreover, in an in vivo dog model, fucoxanthin improved compensatory cardiac hypertrophy and valve function [ 67 ].…”

“…Furthermore, fucoxanthin inhibited apoptosis by a decreased ROS formation and reduced calcification and extracellular matrix accumulation through phosphorylation regulation of AKT and ERK in H 2 O 2 -induced calcification [ 67 ]. Moreover, in an in vivo dog model, fucoxanthin improved compensatory cardiac hypertrophy and valve function [ 67 ]. Thus, fucoxanthin can protect human valvular interstitial cells from damage from H 2 O 2 -induced oxidative stress via various mechanisms, including cytoprotective efficacy against H 2 O 2 and inhibition of Akt/ERK-related signaling pathways.…”