Protective Effect of Aframomum melegueta phenolics Against CCl4-Induced Rat Hepatocytes Damage; Role of Apoptosis and Pro-inflammatory Cytokines inhibition

Aframomum melegueta is a commonly used African spice. Through a hepatoprotective bioassay-guided isolation, the chloroform fraction of A. melegueta seeds yielded one new diarylheptanoid named 3-(S)-acetyl-1-(4'-hydroxy-3', 5'-di methoxyphenyl)-7-(3 '',4 '', 5 ''-trihydroxyphenyl) heptane (1), and two new hydroxyphenylalkanones, [8]-dehydrogingerdione (2) and [6]-dehydroparadol (3), in addition to six known compounds (4-9). The hepatoprotective effect of A. melegueta methanol extract, sub-fractions and isolated compounds was investigated using carbon tetrachloride (CCl4)-induced liver injury in a rat hepatocytes model. The methanol, chloroform extracts and compounds 1, 5, 8 and 9 of A. melegueta significantly inhibited the elevated serum alanine aminotransferase (ALT), thiobarbituric acid reactive substances (TBARS), tumor necrosis factor (TNF alpha), interleukin-1beta (Il-1 beta), caspase3 and 9 and enhanced the reduced liver glutathione (GSH) level caused by CCl4 intoxication. These results indicate that A. melegueta extracts, and isolated compounds play a protective role in CCl4 induced acute liver injury which might be due to elevated antioxidative defense potentials, suppressed inflammatory responses and apoptosis of liver tissue.