Molecular Docking and Dynamics Simulation Analysis of Thymoquinone and Thymol Compounds from Nigella sativa L. that Inhibits P38 Protein: Probable Remedies for Hepatocellular Carcinoma.

BACKGROUND: Currently, a novel antagonist against p38 is being designed and applied to inhibit hepatocellular carcinoma. Protein-ligand interaction plays a major role in the identification of the possible mechanism for the pharmacological action. The involvement of p38 remains an important target for anticancer drug development as its activation induces apoptosis in hepatoma cells. OBJECTIVE: The aim is to identify the best candidate from the plants of N. sativa which binds with the hepatocellular carcinoma (HCC) targets by computational approach. MATERIALS AND METHODS: The reported phytoconstituents such as thymoquinone and thymol present in the plant, N. sativa were docked with the HCC target such as p38. Structures of phytoconstituents were prepared using ChemDraw Ultra 10 software and converted into its 3D PDB structure and minimized using Discovery Studio client 2.5. The target protein, p38 was retrieved from RCSB PDB. Lipinski's rule and ADMET toxicity profiling were carried out on the phytoconstituents of the N. sativa, and the compounds were further promoted for molecular docking and MD simulation analysis. RESULTS: The docking results revealed promising inhibitory potential of thymoquinone against p38 with binding energy of -7.67 kcal/mole as compared to its known standard doxorubicin having binding energy of -6.68 kcal/mol respectively. Further, molecular dynamic (MD) simulations for 5ns were conducted for optimization, flexibility prediction, and determination of folded p38 stability. The p38-thymoquinone complex was found to be quite stable with RMSD value of 0.2 nm. CONCLUSION: Obtained results propose thymoquinone binding energy on the selected targets. Hence, this compound bears outstanding potential against hepatocellular carcinoma and has to be taken up for experimental work against hepatocellular carcinoma.

Nigella sativa L. and Its Bioactive Constituents as Hepatoprotectant: A Review.

BACKGROUND: The pharmacological properties of Nigella sativa L. are well attributed to the presence of bioactive compounds, mainly, thymoquinone (TQ), thymol (THY) and α hederin and their antioxidant effects. TQ, THY and alpha-hederin (α-hederin) provide protection to liver from injury via different mechanisms including inhibition of iron-dependent lipid peroxidation, elevation in total thiol content and (GSH) level, radical scavenging, increasing the activity of quinone reductase, catalase, superoxide dismutase (SOD) and glutathione transferase (GST), inhibition of NF-κB activity and inhibition of both (COX) and (LOX) protects liver from injuries. Review and Conclusion: The main aim of this literature review is to reflect the relevant role of ROS in inducing hepatic diseases and also the preventive role of N. sativa L. in hepatic diseases. The present article is directed towards highlighting the beneficial contribution of researchers to explore the pharmacological actions with therapeutic potential of this precious natural herb and its bioactive compounds pertaining to the hepatoprotective effects. We systematically searched for research literature through well-framed review question and presented the data in the tabular forms for the convenience of the readers. Two hundred and forty-one papers were embodied in this review, oxidative effect and the reactive oxygen species (ROS) are known to be the major causes of many diseases such as hepatic cancer. Many drugs and chemicals have shown to incite oxidative damage by generation of ROS in the body. Therefore, this review intends to focus the role of ROS in liver diseases and the mechanisms through which N. sativa prevents hepatic diseases. The mechanisms by which N. sativa impede progression in chronic liver diseases should be used as a preventive medicine in patients with hepatic disorders.