Role of Trans-ferulic Acid in Heart Failure

Abstract

cardiovascular disorder known for reducing the capability of the heart to pump the blood leading to insufficient circulation to fulfill the metabolic demands of organs and tissues. According to the Center of Disease Control and Prevention (CDC)
it as affected more than 6.2 million people in the United States1 and incidence rate is increasing. Various other clinical conditions increases the risk factors for HF, including hypertension, myocardial infarction, arrhythmias, coronary artery disease (CAD), heart attacks, diabetes, obesity, congenital malformations and unhealthy life habits like smoking, cocaine and alcohol abuse2. HF is an escalating disease that damages cardiac structure and its function. Pathophysiological mechanism involved in heart failure are low level of Ca 2+ affecting the excitation-contraction coupling of the cardiomyocytes. Extracellular-signal-regulated kinase (ERK) pathway also causes the progression of cardiac hypertrophy to heart
failure. Oxidative stress seems to have a key role during the transition from compensated hypertrophy to heart failure. Additionally, stimulation of reactive oxygen species, increased activity of NADPH oxidase and cardiomyocyte apoptosis by oxidative stress also contributes in heart failure. Several studies have been evident of limited antioxidant capacity in heart failure3. Common symptoms include dyspnea, fatigue, a n d  Fl u i d  r e t e n t i o n . C u r r e n t  t h e r a p y
recommended for heart failure includes for diuretics for fluid retention, angiotensin converting enzyme inhibitors, β-blockers, a l d o s t e r o n e a n t a g o n i s t s , hydralazine/isosorbide dinitrate, and digoxin4.Other than regular medications, use of nutraceuticals for preventive and treatment for is increasing. These are basically dietary supplements containing bioactive agents andu s e f u l i n m a n y a i l m e n t s . V a r i o u s epidemiological, animal and clinical studies
have been evident that that nutraceuticals reduce the risk of cardiovascular diseases. Main groups including in nutraceutical are dietary fibers, polyunsaturated fatty acids, phytosterols, vitamins and polyphenols5. The popular group
polyphenols is known for its potent and effective role in cardiovascular disease with its vasodilatory, antioxidant and anti-inflammatory effects. They also modulate apoptotic processes6. Trans-ferulic (ferulic acid) is a well know polyphenol, commonly found in rice, wheat, oats, grains, vegetables and flowers, fruits, leaves and seeds of many plants. It can be extracted in the trans-isomeric form from cell wall of many planta and grains. It is also available commercially. Trans-ferulic has many applications including in manufacturing of drugs, functional foods and nutraceuticals7. Transferulic acid has been extensively studied in animal experimental studies to identify its role in cardiovascular disease by different mechanism.
It was found that oxidative damage caused by cigarette smoking due to increase lipid peroxidation can be reversed by use of ferulic acid. It increases the anti-oxidant capacity. Trans-ferulic acid also found to lower the blood pressure while sodium salt of trans-ferulic acid is effective in preventing platelet aggregation, lower lipid profile and prevention of thrombus formation8. The other anti-oxidant mechanism of trans-ferulic acid includes reducing levels of CKMB, LDH, IL-1β, and IL-6, while uplifting GSH and returning membrane enzymes and calcium homeostasis to normal leading to regularization of, heart rate, blood pressure, ECG and cardiac fibrosis9. Trans-ferulic acid is also found to be effective in reducing blood glucose level in streptozotocin induced diabetic animals. This reduction in oxidative stress helps in insulinsecretion by beta cells. This increased insulin secretion enhances glucose utilization by the extra hepatic tissues and reduce the blood glucose level. Amide compounds of trans-ferulic acid has also showed stimulation capability on insulin secretion in rat pancreatic cells10. Trans-ferulic acid has been found to be effective in reducing various risk factors for heart failure with different mechanism. This make it an ideal phenolic compound to be tested for its role in heart failure. It has been thoroughly studied at on animal studies, however clinical trials are needed to conrm and evident its positive role in heart failure.