Cornigerin, a new sesqui-lignan from the hepatoprotective fractions of Cynara cornigera L

Abstract

The ethanol extract of Cynara cornigera L. was fractionated and the fractions were subjected to hepatoprotective assays using Wistar albino rats at a dose of 500 and 250 mg/kg. The liver injury was induced in rats using carbon tetrachloride. Biochemical parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin were estimated as reflections of the liver condition, with silymarin as a positive control. Phytochemical investigation and chromatographic separation of the hepatoprotective fractions led to the isolation of a new sesqui-lignan namely cornigerin (1), along with eight known compounds: apigenin (2), luteolin (3), β-sitosterol glycoside (4), apigenin 7-O-β-D-glucopyranoside (5), luteolin-7-O-β-D-glucopyranoside (6), apigenin-7-O-rutinoside (7), cynarin 1,5-di-O-caffeoylquinic acid (8), and apigenin-7-O-β-D-glucuronide (9). This is the first report for the isolation of 8 and 9 from this plant.

Introduction

The liver is one of the largest organs in the human body and the main site for intense metabolism and detoxification [1]. Although liver diseases are worldwide problem, it is much more exaggerated in Egypt [2] and in spite of the great advances in modern medicine, no effective medicines are available that could stimulate liver function after damage or help regeneration [3]. Progressive fibrosis occurs after chronic liver injury of any etiology and removing the causative agent is the only effective therapy to stop or even reverse liver fibrosis [4], [5]. Up till now there are no FDA-approved treatments for alcoholic liver disease [6].

Non-alcoholic fatty liver disease (NAFLD) develops when fat builds up within the liver and the mostly affected people are overweight or obese. If the progression of the condition is severe enough, it can lead to liver failure. It is well established that NAFLD is the most common liver disease worldwide with a prevalence rate of 46% in the general population and even a higher rate of 74% among diabetics [7], [8]. NAFLD is strongly associated with insulin resistance and a large portion of NAFLD patients have postprandial hyperinsulinaemia and abnormal glucose tolerance. Recently several studies had proved that NAFLD is an independent strong risk factor for pre-diabetes [9]. A new US study found that nearly one third of children with NAFLD also have prediabetes or type 2 diabetes [10]. Recent studies have shown that silymarin and silibinin appears to be effective in reducing steatosis and insulin resistance [11], [12], [13].

This fact puts a challenge for scientists to explore the potential of hepatoprotective activity of plants based on traditional use where a large number of medicinal preparations are recommended for the treatment of liver disorders [14]. Members of the family Asteraceae especially the tribe Cynareae are known for their efficacy in relieving some liver disorders. In particular Silybum marianum [15], [16], [17], [18], [19], [20] and Cynara scolymus [21], [22], [23] are well known active hepatoprotective agents. Silymarin, obtained from Silybum marianum is a widely used plant derived hepatoprotective agent. Cynareae tribe is represented in Egypt by many genera such as Silybum, Cynara, Centaurea, Carduus, Onopordon and others [24], [25]. Therefore, in an attempt to confront the growing problem of liver diseases in Egypt and worldwide, some plants belonging to the tribe Cynareae growing in Egypt were evaluated for their hepatoprotective activities [26]. Cynara cornigera was found to be active and was selected to carry out a biologically guided fractionation and phytochemical examination of the active fractions.

In the present study, investigation of the hepatoprotective activity of different fractions prepared from the aerial parts of C. cornigera was carried. This was followed by phytochemical investigation of the active fractions which resulted in the isolation of the new sesqui-lignan, 7,8-trans-7′, 8′ -trans- 7″, 8″-cis- 8, 8′- trans-4, 4″, 9, 9″ - tetrahydroxy-3,3′,3″-trimethoxy-4′,8″-5′,7″-dioxy-7,9′-epoxy-lignan-7′-ol (cornigerin). This is the first report of its isolation from nature.