Black cumin and clove: Litholytic volatile compounds and inhibitors of inflammation-induced gallstone

Gallstones are a serious and widespread disease of the biliary system, which remain a costly disease and the major cause of hospital admissions for gastrointestinal problems. Natural products are a rich source of different volatile compounds such as terpenes that were found to be good dissolving solvents. Whereas, the potential of essential oils and their aromatic constituents has been rarely reported. Herein, we studied for the first time the litholytic activity of essential oils from Nigella sativa and Syzygium aromaticum, and their main compounds; p-cymene (49.25 %) and eugenol (49.92 %), respectively. The gallstone samples were classified as cholesterol and pigment types, using FTIR spectroscopy and UV-spectrophotometer analyses. All samples caused a deterioration in the morphological appearance of cholesterol gallstones with no effect on pigment gallstones. These volatile compounds, seem promising litholytic solvents as they reproduce better or close dissolving capacity to Methyl tertbutyl ether (MTBE) standard. Black cumin essential oil manifested with remarkable litholytic activity reached to a dissolution capacity of 90.07 ± 5.58 %, higher than that of clove with 59.52 ± 5.86 %, and that of MTBE standard (84.86 ± 2.93 %). Fascinating, p-cymene produced the most remarkable litholytic activity of 97.68 ± 2.11 %, leading to almost a total dissolution of the cholesterol gallstone sample, while that of eugenol was of 75.92 ± 6.02 %. The in-silico study suggested a strong lipoxygenase-inhibitory of eugenol compared with zileuton standard. The molecular docking experiments revealed that the important affinity of eugenol involving both hydrophobic and hydrogen bond interactions with human 5-lipoxygenase (5-LOX). Our study highlights for the first time the importance of aromatic structures from essential oils in gallstone dissolution. Eugenol and p-cymene contributed mainly to the activity of their essential oils, and could be effective litholytic agents able also to prevent gallstone formation through their potential anti-inflammatory intervention in the gallbladder.