Integrative Phytochemical and Bioinformatics-Based Study of Lemongrass (Cymbopogon citratus) for Potential Anti-Inflammatory Therapy

Abstract

Prolonged inflammatory responses can progress into chronic conditions, representing a leading cause of mortality globally by triggering neurodegenerative diseases, cardiovascular diseases, and cancer. Herbal-based therapeutics have garnered substantial attention due to their minimal adverse effects. Lemongrass (Cymbopogon citratus) is widely recognized for its anti-inflammatory pharmacological properties. However, its efficacy at the molecular level remains poorly understood. This study aimed to characterize the bioactive profile of C. citratus through LC-HRMS coupled with quantitative phytochemical assays, and to evaluate the capacity of these compounds to inhibit pro-inflammatory proteins via molecular docking. The investigation proceeded across three phases: LC-HRMS profiling, quantification of major phytochemical classes (phenols, flavonoids, terpenoids, alkaloids), and computational screening against inflammatory target proteins. LC-HRMS identified 26 compounds spanning phenolic, flavonoid, and terpenoid classes. Quantitative assays showed that terpenoids dominated the phytochemical profile (569.333 ± 9.43 mgEE/g). Conversely, in-silico studies indicated that flavonoid compounds had the greatest inhibitory potential against pro-inflammatory regulators. Specifically, luteolin was predicted to inhibit PTGS2 (-8.8 kcal/mol), JAK2 (-9.3 kcal/mol), TYK2 (-9.5 kcal/mol), and IKBKB (-10 kcal/mol), while pinocembrin inhibited JAK1 (-9 kcal/mol). The acyclic structure of citral resulted in weaker docking scores than flavonoids, which possess aromatic rings and can form more hydrogen bonds. In conclusion, C. citratus has potential as an immunomodulatory agent through targeted inhibition of pro-inflammatory signaling pathways.