UHPLC-MS metabolomic profile and in silico pharmacokinetic approach of Kalanchoe daigremontiana Raym.-Hamet & H. Perrier aqueous extracts

Throughout humanity's development, the medicinal use of plants has evolved as an observational and empirical matter; Yorubá culture uses Kalanchoe sp. as universal antidotes. They are believed to be "ewé òdúndún" or plants of goodness and are traditionally and religiously used in preparations to treat diseases and physiological disorders. Our main goals were to determine the comparative phytochemical composition panel of two Kalanchoe daigremontiana Raym.-Hamet & H. Perrier aqueous extracts through UHPLC-MS metabolomic approaches and highlight the drug-likeness properties of the most abundant compounds in the complex mixture prepared according to its traditional uses. K. daigremontiana leaf aqueous extracts were prepared by cold water maceration (Kd1) or decoction (Kd2). The metabolomics analysis of the extracts was performed through UHPLC-ESI-MS/MS acquisition in positive and negative modes. An in-house database was built with molecules found in plants from the Crassulaceae family and was applied to the annotation step. Our analysis identified 132 compounds, showcasing variations between negative (ESI(-)) and positive (ESI(+)) ionization modes. Notably, flavonoids such as quercetin and kaempferol glycosides, known for their potent antioxidant properties, were abundant in both extracts. Additionally, bufadienolides, associated with diverse biological activities, were present. Both extracts presented similar phytochemical compositions in terms of the number of compounds. Differential analysis revealed significantly higher intensities for specific molecules in both Kd1 and Kd2 extracts. Considering the relative abundance, Kd1 showed a significant amount of Fatty Acids and Steroids concerning Kd2. Additionally, the 15 most abundant compounds were analyzed using in silico pharmacokinetic and toxicity algorithms (SwissADME, pkCSM, and LAZAR) to predict their drug-likeness profile. The fifteen most abundant molecules (Corchorifatty acid F; 9,12,13-TriHOME; Acetylsagittatin A; Apiin; Kaempferol; L-Malic acid; 19-Oxodesacetylcinobufagin; Lucyoside Q; (12 S,13 S)-Epoxylinolenic acid; Isocitric acid; 4''-O-Acetylafzelin; Hellebrigenin; Senedigitalene; Blumenol C and Sativoside R2) had their ADMET in silico profiles predicted using computational tools. Importantly, our in silico assessments pinpointed six promising compounds with favorable absorption, pharmacokinetics, and drug-likeness properties, suggesting their potential as bioactive agents. This finding underscores the significance of these traditional aqueous extracts in folk medicine. In conclusion, our study not only supports the traditional use of Kalanchoe spp. but also sheds light on the safety and pharmacological potential of these extracts. By exploring different extraction methods and employing metabolomics, we have gained valuable insights into the bioactivity and safety of plant extracts, which can guide future research in this field.