CN-122005530-A - New use of lauric acid

Abstract

The invention provides a new application of lauric acid, and by researching the inhibition effect of lauric acid on a cardiac voltage-gated sodium channel Nav1.5 and the action mode of lauric acid in electrophysiological conduction, the invention proves that the natural polyunsaturated fatty acid lauric acid is a potential Nav1.5 sodium channel inhibitor for the first time, and electrophysiological characterization shows that lauric acid is the most effective monomer in natural polyunsaturated fatty acid screened by inhibiting Nav1.5, and the IC50 value is 27.40+/-12.78 mu M.

Inventors

• ZHU YAN
• WANG TAIYI
• WU HONGHUA
• LIANG YINGRAN
• HE SHUANG
• XIE WEIWEI
• GAO JIAMING

Assignees

• 天津中医药大学

Dates

Publication Date

20260512

Application Date

20241112

Claims (4)

1. 1. The use of lauric acid in the preparation of Nav1.5 sodium ion channel inhibitor is characterized in that the lauric acid has the following molecular structural formula:
2. 2. Use of lauric acid in the preparation of antiarrhythmic drugs.
3. 3. A Nav1.5 sodium ion channel inhibitor is characterized in that the main functional component comprises lauric acid.
4. 4. An antiarrhythmic drug is characterized in that the main functional component comprises lauric acid.

Description

New use of lauric acid Technical Field The invention relates to the field of electrophysiology in medical technology, in particular to new application of lauric acid. Background Heart failure and left heart dysfunction are often accompanied by arrhythmia, which can induce reversible dilated cardiomyopathy. Cardiomyopathy caused by arrhythmia is a complex disease, and often leads to a decline in cardiac function. These diseases include tachycardia, atrial fibrillation and ventricular premature beats, suggesting an important link between arrhythmia and heart failure, which highlights the need for timely intervention. Although non-drug therapies have been applied to treat a wide variety of arrhythmias, there is still an urgent need for more effective antiarrhythmic drugs in view of the specific pathological conditions. At present, three main drug strategies for treating atrial fibrillation exist. The first is a sodium channel blocker such as propafenone and flucaine amine, the second is a potassium channel blocker (mainly IKr) such as sotalol and dofetilide, and the third is a mixed ion channel blocker such as androgen and amiodarone. Novel sodium channel inhibitors remain an important target for the discovery of antiarrhythmic drugs. However, the narrow therapeutic window of antiarrhythmic drugs is a significant clinical challenge, limiting clinical application. Heart rhythm is often classified as one of palpitations within the framework of traditional Chinese medicine, and many traditional Chinese medicine formulas have proved to have the efficacy of regulating heart rate. The nav1.5 channel is a voltage-gated sodium channel, and the peak of Na current in the heart and the excitability and conduction of the heart play a critical role. The traditional Chinese medicine is developed, and the exploration of Nav1.5 channel inhibition medicines has important clinical application value for preventing and treating arrhythmia. Disclosure of Invention The technical problem to be solved by the invention is to provide a new application of lauric acid. The technical scheme adopted by the invention is as follows: Use of lauric acid having the molecular formula C 12H24O2 in the preparation of a nav1.5 sodium ion channel inhibitor, the molecular structural formula being as follows: Use of lauric acid in the preparation of antiarrhythmic drugs. Nav1.5 sodium ion channel inhibitor comprises the lauric acid. An antiarrhythmic drug comprises the lauric acid as main effective component. The beneficial effects of the invention are as follows: The application firstly proves that the natural polyunsaturated fatty acid Lauric Acid (LA) is a potential Nav1.5 sodium channel inhibitor by researching the inhibition effect of lauric acid on a cardiac voltage-gated sodium channel Nav1.5 (INa-P) and the action mode of the lauric acid in electrophysiological conduction, and the electrophysiological characterization shows that the lauric acid is the most effective monomer in the natural polyunsaturated fatty acid screened by inhibiting Nav1.5, and the lC50 value is 27.40+/-12.78 mu M. In hiPSC-derived cardiomyocytes, LA shifts the steady state inactivation of INa to more negative potentials and reduces the amplitude of extracellular field potentials. Mechanistically, lauric acid acts on the rapid inactivation of nav1.5, altering the electrophysiological conduction of stem cell-derived cardiomyocytes (hipscs). By analysis of the molecular dynamics simulation optimized receptor-ligand complex, LA was observed to bind to the pore-forming subunit of nav1.5, especially in the cavity below the na+ ion selective filter, LA extended in the intracellular direction along the cavity inner wall with its carboxyl group facing in the extracellular direction, forming two hydrogen bonds with amino acid residues Lys1419 and Asn927 in the ion channel with the carboxyl chain facing the inside of the cell and the terminal methyl group located near the opening at the bottom of the cavity. The binding mode shows that LA can partially block sodium ion inflow, which is consistent with experimental results, and shows that LA has potential of serving as a Nav1.5 channel blocker and has important clinical application value in the aspect of treating arrhythmia. Drawings FIG. 1 is a diagram showing a screening process of natural polyunsaturated fatty acid lauric acid. FIG. 2 shows the inhibition of Nav1.5 ion channels by lauric acid and IC 50. FIG. 3 is a graph showing the effect of lauric acid on the channel kinetics of Nav1.5 ion channels. FIG. 4 is a molecular kinetic interaction plot of lauric acid versus Nav1.5 ion channel. FIG. 5 is a graph showing the effect of lauric acid on the amplitude of myocardial cell field potential (EFP) derived from hiPSC-CMs cells. Detailed Description In order to make the technical scheme of the present invention better understood by those skilled in the art, the technical scheme of the present invention will be further described in d