Cheminformatics Application in the Phytochemical and Biological Study of Eucalyptus globulus L. Bark as a Potential Hepatoprotective Drug

Abstract

Natural products are considered as a good source of antifibrotic agents, but identifying and isolating bioactive molecule(s) is still challenging. Fortunately, numerous computational techniques have evolved to save time and efforts in this field. The aim of the current study was to utilize several cheminformatics software to study the chemical and biological features of the bark of Eucalyptus globulus cultivated in Egypt. Sirius software, with the aid of online databases, was used to process liquid chromatography−mass spectrometry (LC−MS) chemical profiling and predict precise molecular formulae, chemical classes, and structures. Accordingly, 37 compounds were tentatively identified, including 15 reported here for the first time from this species. Also, the BioTransformer tool was successfully applied for in silico virtual study of the human metabolism of these compounds, and 1960 different products were obtained through various metabolic pathways. Finally, an electronic library of the identified compounds and their metabolites were developed and docked in silico against eight different protein targets that are involved in the liver fibrosis process. The results revealed that the extract may have a potential hepatoprotective effect through several mechanisms and that the metabolites have the highest binding affinities to the relevant enzymes than their parent compounds. The extract was found to show potent cytotoxic activity against the liver cancer cell lines HEPG2 and HUH-7, and its absorption was enhanced through nanoformulation, as proved using the ex vivo everted gut sac method.

Antiproliferative Activities of the Lipophilic Fraction of Eucalyptus camaldulensis against MCF-7 Breast Cancer Cells, UPLC-ESI-QTOF-MS Metabolite Profile, and Antioxidative Functions

“…A growing number of studies have indicated the antiproliferative properties of Eucalyptus spp extracts, fractions, essential oils, and bioactives against various cancer cell lines including colorectal (HCT-15), pancreatic (PANC-1), non-small cell lung cancer (NCI-H460), hepatocellular carcinoma (HEPG2 and HU-7), human clear renal cell carcinoma (Caki), kidney carcinoma (A495), prostate cancer (PC3), epithelial carcinoma (HeLa) Burkitt’s lymphoma Raji, as well as breast adenocarcinoma (MCF-7 and MDA-MB-231). ,, According to Hrubik et al, the antiproliferative activity of E. camaldulensis methanol, ethyl acetate, n -butanol, and aqueous leaf extracts on MCF-7 and MDA-MB-231 breast cancer cells examined by the MTT assay after 72 h revealed that the extracts were cytotoxic to the cancer cell lines (IC 50 26.7–250.7 μg/mL) .…”

“…8 They observed that the ethyl acetate extract was the most active, while water extract was the least. Similarly, Singab et al, observed that phenolic-rich aqueous acetone extract of E. camaldulensis leaves demonstrated growth inhibitory effects against MCF-7 (IC 50 36.5 μg/mL), Hep-2 (IC 50 57.7 μg/mL), HepG-2 (IC 50 38.7 μg/mL), HeLa (IC 50 49.0 μg/mL), HCT-116 (IC 50 33.3 μg/mL), and Caco-2 (IC 50 38.3 μg/mL). 7 Meanwhile, studies by Mubarak et al found that essential oils of E. camaldulensis leaves exerted cytotoxic action against cancer cell lines, WEHI-3 (IC 50 16.1 μg/mL), HT-29 (IC 50 50.5 μg/mL), and HL-60 (IC 50 42.1), but were less cytotoxic against normal cells, RAW 264.7 macrophage (IC 50 > 100 μg/mL).…”

Chemoinformatics Advances from Egypt: A Review Article

“…The good news is that various computational approaches have emerged in this subject to save time and effort. [29] Eucalyptus globulus Labill. is an evergreen tree of the Myrtaceae family that is grown all over the world.…”

“…In addition, the Bio-Transformer tool was successfully used for an in silico virtual analysis of these chemicals' human metabolism, and 1960 distinct products were created via various metabolic pathways. [29] Moreover, an electronic library of the discovered chemicals and metabolites was created and docked in silico against eight distinct protein targets implicated in the fibrosis process of the liver. The findings suggest that the extract may have a hepatoprotective impact via many pathways and that the metabolites have higher binding affinities to the relevant enzymes than their parent chemicals.…”

“…The extract had high cytotoxic activity against the liver cancer cell lines HEPG2 and HUH-7, and its absorption was improved by nano-formulation, as demonstrated by the ex vivo everted gut sac technique. [29]…”