Identification of Proapoptopic, Anti-Inflammatory, Anti- Proliferative, Anti-Invasive and Anti-Angiogenic Targets of Essential Oils in Cardamom by Dual Reverse Virtual Screeningand Binding Pose Analysis

Background: Cardamom (Elettaria cardamom), also known as “Queen of Spices”, has been traditionally usedas a culinary ingredient due to its pleasant aroma and taste. In addition to this role, studies on cardamom havedemonstrated cancer chemopreventive potential in in vitro and in vivo systems. Nevertheless, the precise polypharmacologicalnature of naturally occurring chemo-preventive compounds in cardamom has still not beenfully demystified.
Methods:In this study, an effort has been made to identify the proapoptopic, anti-inflammatory,anti-proliferative, anti-invasive and anti-angiogenic targets of Cardamom’s bioactive principles (eucalyptol,alpha-pinene, beta-pinene, d-limonene and geraniol) by employing a dual reverse virtual screening protocol.Experimentally proven target information of the bioactive principles was annotated from bioassay databases andcompared with the virtually screened set of targets to evaluate the reliability of the computational identification.To study the molecular interaction pattern of the anti-tumor action, molecular docking simulation was performedwith Auto Dock Pyrx. Interaction studies of binding pose of eucalyptol with Caspase 3 were conducted to obtainan insight into the interacting amino acids and their inter-molecular bondings.
Results:A prioritized list of targetproteins associated with multiple forms of cancer and ranked by their Fit Score (Pharm Mapper) and descending3D score (Reverse Screen 3D) were obtained from the two independent inverse screening platforms. Moleculardocking studies exploring the bioactive principle targeted action revealed that H- bonds and electrostaticinteractions forms the chief contributing factor in inter-molecular interactions associated with anti-tumoractivity. Eucalyptol binds to the Caspase 3 with a specific framework that is well-suited for nucleophilic attacksby polar residues inside the Caspase 3 catalytic site.
Conclusion:This study revealed vital information aboutthe poly-pharmacological anti-tumor mode-of-action of essential oils in cardamom. In addition, a probabilisticset of anti-tumor targets for cardamom was generated, which can be further confirmed by in vivo and in vitroexperiments.