Antidiabetic Potential and Phytochemical Profiling of Leea indica Leaves: In Vitro and In Silico Analysis

Abstract

Leea indica is a medicinal plant native to tropical Asia, which has been traditionally used to treat various diseases, including diabetes. Therefore, this study aims to investigate the antioxidant, alpha-glucosidase, and alpha-amylase inhibitory activities of L. indica leaf ethanol extract and identify the bioactive compounds using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The extract prepared through maceration with 96% ethanol produced an extraction efficiency of 3.52%. Phytochemical screening showed the presence of alkaloids, flavonoids, saponins, tannins, quinones, and steroids/triterpenoids. The extract had strong antioxidant activity (IC50 = 18.691 ± 0.05 µg/mL) as well as high total phenolic (6.957 ± 0.09 g GAE/100 g) and flavonoid (32.917 ± 0.07 g QE/100 g) contents. Additionally, the extract had potent alpha-glucosidase (IC50 = 7.90 µg/mL) and alpha-amylase (IC50 = 30,663.89 µg/mL) inhibitory activities. LC-MS/MS analysis identified 11 bioactive compounds, including phenylacetic acid (60.89%), shikimate (10.89%), kaempferol (3.67%), and quercetin (2.27%). In silico molecular docking studies showed that 4-[(2s,3s)-4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl]-2-methoxyphenol had a strong binding affinity with key residues in alpha-glucosidase, and 5-(acetyloxy)-2,4-dihydroxy-6-methyloxan-3-yl 3-(4-hydroxyphenyl)prop-2-enoate reacted significantly with crucial residues in alpha-amylase. These results support the traditional use of L. indica in diabetes management and show the potential as a source of natural antidiabetic agents. Further in vivo studies and toxicity tests are necessary to confirm the efficacy and safety for human use.