In-silico prediction and in vitro validation of antioxidant, antibacterial and antifungal potential of Black Turmeric (Curcuma caesia Roxb.) essential oils and its constituents

Abstract

The growing interest in the health and pharmaceutical industries has led to a significant increase in demand for essential oils. Curcuma caesia, as a member of the Zingiberaceae family, has been used for its high-quality essential oils (EOs) with remarkable therapeutic properties. The current study aimed at predicting the in-silico interactions of C. caesia volatile constituents against the protein responsible for oxidative and microbial stress in order to investigate their potential for industrial and pharmaceutical applications. The accuracy of the in-silico predictions was confirmed by carrying out the in vitro validation of the antioxidant, antibacterial, and antifungal activity of the EOs derived from the rhizome and leaves, as well as its volatile constituents. EOs from the rhizome and leaf samples of C. caesia were extracted through the hydro distillation method and yielded a percentage (%) of 1.80 ± 0.02 and 0.95 ± 0.02 (fresh weight basis, v/w), respectively. A total of 38 and 29 volatile constituents were identified in the rhizome and leaf EOs by gas-chromatography mass spectrometry analysis, representing 92.55% and 90.75% of the total peak area, respectively. The rhizome and leaf EOs showed oxygenated sesquiterpene (39.91% and 27.69%) as the predominate fractions followed by sesquiterpene hydrocarbons (13.36% and 18.44%). Curzerenone (18.09%), epicurzerenone (12.47%), eucalyptol (11.57%), camphor (5.94%), and germacrone (4.47%) were the major constituents in the rhizome EO, whereas, the leaf EO was dominated by eucalyptol (12.53%), camphor (7.23%), curzerenone (5.24%), germacrone (4.81%) and curzerene (4.9%). The in vitro biological activities such as antioxidant, antibacterial, and antifungal potential of C. caesia EOs were evaluated. The antioxidant evaluation using enzymatic and non-enzymatic assays, showed excellent potential of C. caesia EOs as compared to standard drugs. Specifically, in the enzymatic assay, leaf EO of C. caesia was resulted into the reduction of ROS and an increase in the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) in OZ-stimulated PMNs. The EOs also displayed a remarkable antibacterial activity against Staphylococcus aureus, elucidating it as the most susceptible strain. Further, the in-silico prediction of the constituents was conducted using Swiss-ADME, and molecular docking analysis. Swiss-ADME revealed the drug-likeness and safety properties of constituents present in C. caesia EOs. The molecular docking study was carried out to interpret the possible interactions of phytoconstituents qualified in the Swiss-ADME study with two bacterial proteins (Tyrosyl-tRNA synthetase from Staphylococcus aureus (PDB ID: 1JIJ) and Glucosamine 6-phosphate synthase from Escherichia coli (PDB ID: 1XFF)), one fungal protein (N-myristoyl transferase from Candida albicans (PDB ID: 1IYL)) and one oxidative protein (Human peroxiredoxin 5 (PDB ID: 1HD2)). Furthermore, to validate the result of molecular docking, the biological activity of higher affinity constituents was also evaluated. As a result, the in vitro findings supported the in-silico prediction. Therefore, C. caesia or its constituents like curzerenone, camphor, eucalyptol, epicurzerenone, germacrone, viridifloral, muurola-4,10(14)-dien-1-ol, and globulol might be a valuable source for developing antioxidant and antimicrobial drugs. To the best of present author’s knowledge, this is the first scientific report on the in-silico prediction of C. caesia constituents against bacterial, fungal and oxidative proteins through molecular docking, which may contribute to the development of various alternatives against multi-drug resistance.