Molecular Simulation-based Combinatorial Modeling and Antioxidant Activities of Zingiberaceae Family Rhizomes

The main aim of this scientific report was to investigate a series of phytochemicals in silico and the pharmacology of four plants found at higher altitude in the ginger family, Zingiberaceae (incl. Costaceae) from North-East India, particularly Sikkim. First, the goal was to determine the biological activities of the four herbs (used under Zingiberaceae family) using antioxidant assays to identify the best species. Second, previously reported compounds in litero were subsequently screened for their anticancerous activities using in silico methods.

Using the methanolic extracts of herbs, quantitative detection of phytochemicals such as total phenols and total flavonoids was detected, and the free radical scavenging activity was also studied using 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. Docking process was studied, using Discovery Studio version 3.5, to identify suitable molecules at the protein-binding sites through annealing and genetic simulation algorithms. Grids centered on active sites were obtained with spacing of 54 × 55 × 56, and 0.503 grid spacing was calculated. The methods adopted and used in this study were comparisons of Global and Local Search Methods to determine the parameters such as maximum number of 250,000 energy evaluations as well as generations of 27,000, followed by mutation and crossover rates of 0.02 and 0.80. The number of docking runs was set to 10. Molecular dynamics study was done to check the stability of the complex.

Among all the genus of Zingiberaceae family investigated in this study, Curcuma angustifolia and Hedychium sp. exhibited the highest 537 ± 12.45; 292 ± 9.16 mg gallic acid equivalent/g total polyphenols and 38 ± 1.54; 75 ± 6.75 mg quercetin equivalent/g flavonoids, respectively. Depending on the concentration, the Hedychium sp. extract exerted the highest scavenging activity on DPPH radical (IC₅₀ 36.4 μg/mL). In silico result demonstrated that the synergetic effects of β-phellandrene with other compounds might be responsible for its anticancerous activity. β-phellandrene and farnesene epoxide showed bonding with Leu²⁹⁸, Ala³⁰², Met³³⁶, Leu³³⁹, Leu³⁴³, Phe³⁵⁶, Ala³⁰², Glu³⁰⁵, Met³⁴⁰, Leu³⁴³, Arg³⁴⁶, Phe³⁵⁶, Ile³⁷³, Ile³⁷⁶, Leu³⁸⁰, His⁴⁷⁵, Leu⁴⁷⁶, and Leu⁴⁹¹.

Based on the current available literature, this is the first study to understand the interaction of compounds found in the rhizomes of Zingiberaceae family.

The aqueous methanolic extract of Zingiberaceae family Curcuma angustifolia and Hedychium sp. has potent antioxidant activity as assessed by 2,2-diphenyl-1-picryl-hydrazyl assaysHedychium sp. is understood to possess more active compounds than other varietiesIn silico studies indicated synergetic effects of β-phellandrene and other compounds for its anticancerous activity. Abbreviations used: CADD: Computer-aided drug designing; ROS: Reactive oxygen species; ADMET: Absorption, distribution, metabolism, and excretion-toxicity; FeCl₃: Ferric chloride; DPPH: 2,2-diphenyl-1-picryl-hydrazyl; NaNO₂: Sodium nitrite; TCA: Trichloroacetic acid; K₂HPO₄: Di-potassium hydrogen phosphate; H₂O₂: Hydrogen peroxide; KH₂PO₄: Potassium di-hydrogen phosphate, K₂Fe (CN)₆: Potassium ferricyanide; KOH: Potassium hydroxide; NaOH: Sodium hydroxide; Na₂CO₃: Sodium carbonate; CH₃COONa: Sodium acetate; AlCl₃: Aluminum chloride.