ABSTRACT:
Indonesia is one of the leading watermelon-producing countries in Asia, with cultivation spread across various regions. A significant portion of the watermelon, particularly the rind (80%), is not consumed, leading to an increase in organic waste. The rind contains the amino acids citrulline and arginine, which are known to have health benefits. This study aims to determine the levels of citrulline and arginine in watermelon rinds sourced from various regions in Indonesia. Furthermore, the research investigates the potential of citrulline and arginine in silico against inflammatory receptors using the Autodock version 4.0 application. The ADME profile and toxicity potential were also assessed computationally using the preADMET application. The analysis of citrulline and arginine levels in watermelon rind showed that citrulline (average: 63.31 mg/g DW) was predominantly found in both the green and white portions of the rind. The highest concentration of citrulline was observed in the white rind (average: 107.43 mg/g DW). Among the various sources, the white rind from Sragen had the highest citrulline content (154.97 mg/g DW). In silico evaluation of the pharmacological potential against inflammatory receptors demonstrated that citrulline and arginine have binding free energies (?G) of -5.81 kcal/mol and -5.07 kcal/mol, respectively, towards IL-6. IL-6 is known to regulate energy, support anti-inflammatory responses, and play a role in the body’s adaptation to exercise. However, elevated IL-6 levels, especially in chronic inflammatory contexts, can trigger fatigue and reduce athletic performance. Citrulline and arginine were predominantly found to accumulate in the white rind of watermelons, particularly those sourced from Sragen. In silico analysis indicated that both amino acids have the potential to inhibit IL-6 activity.