Determination of Bioactive and Anti-Inflammatory Molecules of Thymbra Spicata L. from Mardin by GC-MS and LC-Orbitrap HRMS: A DFT, Molecular Docking, ADMET, Biological Target and Activity Study

Abstract

Objectives In this study, phenolic compounds (PC), volatile compounds (VC), antioxidant, anti-inflammatory, and antimicrobial properties of the Thymbra spicata L. plant grown in the Mardin Yesilli region were investigated. The properties of compounds such as rhoifolin, leucoside, naringenin, rosmarinic acid, gamma-terpinene, and carvacrol, which were found to be higher than other compounds as a result of PC and VC analysis of Thymbra spicata L. plant, and the properties of non-steroidal anti-inflammatory drugs diclofenac and ketoprofen were compared with computer-based calculations. In this context, the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiles of the mentioned molecules were calculated, Density Functional Theory (DFT)-based quantum chemical calculations were performed, and molecular docking analyses were performed. In addition, the pharmacological properties, biological targets, and biological activities of these compounds were comprehensively evaluated. This study provides important data for understanding the therapeutic potential of these plant components. Materials and methods Chromatographic methods (GC-MS and LC-Orbitrap HRMS) were used to look at PC and VC profiles, spectrophotometry (ABTS, DPPH, CUPRAC) to look at antioxidant activities, and the disk diffusion method to look at antimicrobial properties. Results While the most detected volatile compounds were gamma-terpinene (35.34%), carvacrol (17.55%), caryophyllene (10.53%), and p-cymene (9.15%), the most detected phenolic compounds were rosmarinic acid (3334.9 ng/mL), naringenin (2610.00 ng/mL), leucoside (1956.42 ng/mL), and rhoifolin (1288.55 ng/mL). The ethanol extract of Thymbra spicata L. stopped the growth of K. aerogenes in particular. The IC50 value for DPPH was 158.01 mu g/mL, the IC50 value for ABTS was 185.03 mu g/mL, and the C0.5A value was 87.13 for the ethanol extract of Thymbra spicata L. The molecular docking results that the strongest binding energy was between TNF-alpha and naringenin (-6.77 kcal/mol), IL-6 and rosmarinic acid (-5.55 kcal/mol), and NLRP3 and carvacrol (-6.88 kcal/mol). Naringenin, rosmarinic acid, diclofenac, and ketoprofen completely violated the restrictions established by Lipinski, Ghose, Veber, Egan, and Muegge. Rosmarinic acid is the most reactive antioxidant compound with low energy deficit (Eg) and high softness (S). gamma-terpinene and carvacrol, on the other hand, are more stable and durable wit high hardness (eta) and low softness. Conclusion Naringenin, rosmarinic acid, and carvacrol demonstrate significant anti-inflammatory and immunomodulatory properties owing to their high binding affinity for TNF-alpha, IL-6, and NLRP3, positioning them as promising candidates for the treatment of inflammatory disorders. Naringenin and rosmarinic acid effectively target TNF-alpha, whereas carvacrol demonstrates potential in the management of NLRP3 inflammasome-associated diseases. The strong binding of rosmarinic acid to IL-6 shows that it can change the immune system. Thymbra spicata L., abundant in bioactive compounds, may provide benefits compared to conventional NSAIDs and exhibit potential as monotherapy or adjunctive therapies. Their strong anti-inflammatory, antioxidant, antimicrobial, and pharmacological properties, along with their safety, make naringenin, rosmarinic acid, and carvacrol good candidates for more preclinical and clinical research.