Antioxidant, enzyme inhibition, toxicity, and molecular docking analysis of <i>Melaleuca cajuputi</i> leaf extract and fractions

Abstract

<i>Melaleuca cajuputi</i> plant has piqued the interest of researchers due to its pharmacological properties. However, there is scarce information regarding its enzyme inhibitory effects and possible mechanism of action. Thus, this study aimed to investigate the antioxidant, enzyme inhibitory, and potential binding interactions of bioactive components in <i>M. cajuputi</i> extract and fractions with the target enzymes. The 1,1-diphenyl-2-picrylhydrazyl radical scavenging (DPPH) assay was used for the antioxidant activity. The enzyme inhibition potential was assessed using tyrosinase and acetylcholinesterase (AChE) enzymes. <i>M. cajuputi</i> methanolic extract (MCME) demonstrated the most potent scavenging activity in comparison to <i>Melaleuca</i> fraction (MF1) and (MF2), as evidenced by IC<sub>50</sub> values of 28.14 ± 0.96, 35.26 ± 0.64, and 80.90 ± 0.17 μg/mL, respectively. Similarly, the results of the enzyme inhibition assay showed that the MCME (IC<sub>50</sub> 65.81± 0.39 μg/mL) had the highest potency on tyrosinase enzyme compared to MF1 (IC<sub>50</sub> 131.3± 0.43 μg/mL) and MF2 (IC<sub>50</sub> 215.3 ± 0.48 μg/mL). However, MF2 (IC<sub>50</sub> 3.35 ± 0.37 μg/mL) showed a remarkable AChE enzyme inhibition than MCME and MF1. On the other hand, MCME possessed a low toxicity effect with an LC<sub>50</sub> of 781 ± 0.07 μg/mL, whereas MF1 and MF2 were non-toxic. The 10-methylanthracene-9-carboxaldehyde, 2-isopropyl-10-methylphenanthrene, 2-tert butylanthracene, β-eudesmol, and α-eudesmol showed a strong binding propensity ranging from -5.1 to -6.2 and -6.4 to -7.6 kcal/mol towards tyrosinase and AChE respectively. The leaf extract of <i>M. cajuputi</i> could be considered a novel source of naturally occurring antioxidants and promising enzyme inhibitors.