Apoptosis-inducing anti-proliferative and quantitative phytochemical profiling with in silico study of antioxidant-rich Leea aequata L. leaves

Natural products have been important parts of traditional medicine since ancient times, with various promising health effects. Leea aequata (L. aequata), a natural product, has been widely used for treating several diseases due to its promising pharmacological activities. Therefore, the present study aimed to explore the phytochemical profiling and molecular docking of the antioxidant-rich part of L. aequata leaves and its antiproliferative activity. L. aequata leaves were extracted with methanol, followed by fractionation with the respective solvents to obtain the petroleum ether, chloroform, ethyl acetate, and aqueous fractions. The antioxidant activity was evaluated by spectrophotometric methods. The cytotoxic and antiproliferative activities were detected using MTT colorimetric and confocal microscopy methods, respectively. Phytochemical compositions were analyzed using gas chromatography‒mass spectrometry analysis. Computer aided (molecular docking SwissADME, AdmetSAR and pass prediction) analyses were undertaken to sort out the best-fit phytochemicals present in the plant responsible for antioxidant and anticancer effects. Among the fractions, the ethyl acetate fraction was the most abundant polyphenol-rich fraction and showed the highest antioxidant, reducing power, and free radical scavenging activities. Compared to untreated MCF-7 cells, ethyl acetate fraction-treated MCF-7 cells showed an increase in apoptotic characteristics, such as membrane blebbing, chromatin condensation, and nuclear fragmentation, causing apoptosis and decreased proliferation of HeLa and MCF-7 cells. Furthermore, gas chromatography mass spectrometry data revealed that the ethyl acetate fraction contained 16 compounds, including methyl esters of long-chain fatty acids, which are the major chemical constituents. Moreover, hexadecanoic acid, methyl ester; 9-octadecenoic acid (Z)-, methyl ester; 9,12-octadecadienoic acid, methyl ester (Z, Z) and phenol, 2,4-bis(1,1-dimethylethyl) are known to have antioxidant and cytotoxic activity, as confirmed by computer-aided models. A strong correlation was observed between the antioxidant and polyphenolic contents and the anticancer activity. In conclusion, we explored the possibility that L. aequata could be a promising source of antioxidants and anticancer agents with a high phytochemical profile.