Synthesis and antihyperlipidaemic activity of a new piperine derivative

Mungunnaran Damdindorj,Gereltu Borjihan,Bayarmaa Bold,Odontuya Gendaram

doi:10.5564/mjc.v22i48.1782

Abstract

Long pepper (Piper longum Linn.) is widely used as a medicinal substance in traditional Ayurvedic medicine. Its major alkaloid piperine is the main active constituent with various therapeutic activities and has low solubility in water. In this study, a soluble new derivative of a piperine alkaloid, named N-leucinylpiperamide was synthesized. The animal experiment showed that N-leucinylpiperamide has more hypolipidemic effects than commercially available simvastatin and piperine in modulating serum lipids in Wistar male rats. At the amount of 10 mg/kg bw, it significantly reduced TC (-52.4%), TG (-61.7%), and LDL-C (-27.8%), respectively, and increased HDL-C (+147.4%) in the serum of the high-lipid model group. Furthermore, the synthesized N-leucinylpiperamide had no noticeable cytotoxicity against HepG2 cell line in vitro. Thus, our study shows that N-leucinylpiperamide has an ability to improve serum lipid profile in hyperlipidemic model rats and could be a valuable promising agent for the preventing hyperlipidemia.

Highlights

The Piper species have a long history as a condiment in many countries, but they have been more valued for their therapeutic properties and broadly used in Ayurvedic medicine
The N-leucinylpiperamide methyl ester is the critical intermediate product to obtain the final expected product, N-leucinylpiperamide (5) with a yield of 80.1% The purity of synthesized N-leucinylpiperamide was assessed by using Ultra-performance liquid chromatography (UPLC) with a mobile phase of acetonitrile:water, 75:35
The anti-hyperlipidemic activities of samples were expressed as the differences of lipid parameters total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in the rat serum of experimental and control groups

Summary

INTRODUCTION

The Piper species have a long history as a condiment in many countries, but they have been more valued for their therapeutic properties and broadly used in Ayurvedic medicine. Chemistry of N-leucinylpiperamide: Extraction of piperine from Piper longum L. fruits and the following synthesis of piperic acid were carried out according to literature methods described [16, 17]. Experimental design: To test the anti-hyperlipidemic activities, the rats were divided into the following groups: Group I - Normal diet control; Group II - High-fat diet control; Group III - High-fat diet + simvastatin (10 mg/kg bw); Group IV - High-fat diet + piperine (10 mg/kg bw); Group V - High-fat diet + N-leucinylpiperamide (10 mg/kg bw); The normal diet group (I) was fed with a standardized laboratory chow diet, containing the standard composition of necessary macro- and micronutrients (56% carbohydrate, 18.5% protein, 8% fat, 12% fiber, and adequate levels of minerals and vitamins). Significance levels at p < 0.05 and 0.001 were considered to indicate statistical significance

RESULTS AND DISCUSSION

Control II HFD model III Simvastatin IV Piperine V N-leucinylpiperamide

Piperine

CONCLUSIONS