Metabolites Profiling, In Vitro, In Vivo, Computational Pharmacokinetics and Biological Predictions of Aloe perryi Resins Methanolic Extract

Abstract

Aloe perryi is a traditional herb that has various biological and pharmacological properties such as anti-inflammatory, laxative, antiviral, antidiabetic, and antitumor effects, which have not been deliberated before. The current investigation aims to evaluate in vitro cytotoxicity against several cancer cell lines in addition to in vivo anti-inflammatory activities of Aloe perryi extract using a rat animal model. Moreover, the pharmacokinetic properties of bioactive constituents and possible biological targets were assessed and evaluated. The methanolic extract of Aloe perryi was prepared by maceration, to tentatively identify the biomolecules of the Aloe perryi extract, analytical LC-QTOF-MS method was employed for Aloe perryi methanolic extract. The cytotoxic activity was examined in six cancer cell lines using Titer-Glo assay and the IC_50s were calculated in addition to in silico target predictions and in vivo anti-inflammatory activity assessment. Subsequently, the pharmacokinetics of the identified active components of Aloe perryi were predicted using SwissADME, and target prediction using the Molinspiration webserver. The cytotoxic activity on HL60 and MDA-MB-231 was moderately affected by the Aloe perryi extract with IC₅₀ of 63.81, and 89.85 μg/ml, respectively, with no activity on other cells lines. Moreover, the Aloe perryi extract exhibited a significant increase in wound contraction, hair growth, and complete re-epithelization when compared with the negative control. The pharmacokinetic properties of the bioactive constituents suggested a good pharmaceutical profile for the active compounds and nuclear receptors and enzymes were the two main possible targets for these active compounds. Our results demonstrated the promising activity of Aloe perryi extract with cytotoxic and anti-inflammatory properties, indicating a potential therapeutic utility of this plant in various disease conditions.

Keywords: ADME; Aloe perryi resins methanolic extract; breast cancer; in vivo anti-inflammatory; leukemia cancer; target prediction.

Figure 1

Base peak chromatogram of Aloe perryi crude extract and tentatively identified secondary metabolites, which are Isoaloesin (A), Nataloe emodin-8-methyl ester (B), 7−O−Methylaloeresin A (C), Isorabaichromone (D), 7−hydroxyaloin−4′,6′−O−diacetate and cholesterol (E), Aloe coumarin (F), Aloe emodin and glycosylated dimer derivative elgonicardine (G), Aloe coumarin and cholesterol (H) indicates that m/z implies measured m/z.

Figure 2

HPLC Chromatograms of the Aloe perryi Resins Methanolic Extract at Different Wavelengths (A–C). It is demonstrated from the first chart at wave length 250 nm (A), that there is a single peak eluted at 2.7 min retention time, followed by a bundle of around nine (9) peaks eluted in the area of 5.5 to 7.8 min retention time. The second wave length at 300 nm (B) showed almost the similar elution, with one peak that not eluted at 7.8 min in the area of non-polar compounds. Lastly, there is only a group of a non-polar compounds appears within the retention time of 5.5–6.4 min retention time at wave length 350 (C). It could be concluded that 250 nm represent the best elution and separations for the peaks. nm: nanometers; mAU: milli Absorbance Unit; Em: emission; Ex: excitation.

Figure 3

Graphical Representation of dose–response curve of Aloe perryi extract.

Figure 4

Representation of in vivo testing of the anti-inflammatory activity of negative control, Bepanthine, and Aloe perryi treatment. Aloe perryi and Bepanthine improved wound contraction, hair growth, and the proliferative stage maturation of the blood vessels.

Figure 5

The histological changes in rat skin wounds treated with negative control, Bepanthine, and Aloe perryi extract. Bepanthine, and Aloe perryi treatment demonstrated a complete re-epithelialization, thickening of collagen fibers, and reducing the number of inflammation cells comparable to the negative control group.