Validating the potential of Plectranthus amboinicus against lung cancer In silico in vitro and in vivo approaches

Abstract

The present investigation was conducted to assess the anticancer potential of Plectranthus amboinicus using in silico, in vitro and in vivo models. In phase I, the methanol, petroleum ether and aqueous extracts of P. amboinicus were subjected to phytochemical screening and the presence of carbohydrates, proteins and amino acids, phenols, saponins, flavonoids, alkaloids, sterols were predominant in methanol extract and maximum yield was also high in methanol extract. In phase II there was a dose dependent free radical scavenging activity exhibited by the methanolic extract of P. amboinicus against DPPH, ABTS, nitric oxide, hydrogen peroxide, and superoxide radical scavengers. In phase III, the phytocompounds present in the methanolic leaf extract of P.amboinicus was screened through GC-MS analysis and validated for its anticancer potential against apoptotic regulator target proteins through in silico approach. The phytocompounds are in good agreement with drug likeness and ADMET properties as it revealed good physico-chemical, pharmacological and pharmacognostic profile. DFT analysis revealed that the phytocompounds possess high softness, low hardness and less energy gap thereby establishing its stability and biological activity. In phase IV, the identification and characterisation of the bioactive principles in the P. amboinicus extract was carried using UV Vis spectral, HPLC and HPTLC analyses to identify the phytocompound of interest, syringic acid. In phase 5, the cytotoxicity of syringic acid fraction was investigated against the human lung cancer cell line (A549) under in vitro conditions. The antiproliferative indices of A549 lung cancer cells showed a dose dependent decrease in cell viability with IC50 values of syringic acid fraction. The syringic acid fraction upregulated the apoptotic and downregulated the antiapoptotic proteins/ genes. In the final phase of the study, in vivo investigations on the impact of syringic acid fraction on benzo(a)pyrene induced lung tumour bearing Swiss albino mice