The discovery of bioactive compounds for non-invasive therapy has been the goal of research groups focused on pharmacotherapy. Phytonutrients have always been attractive for researchers because they are a significant source of bioactive phytochemicals. Still, it is challenging to determine which components show high biomedical activity and bioavailability after administration. However, based on the chemical structure of these phytochemicals, their physicochemical properties can be calculated to predict the probability of gastrointestinal (GI) absorption after oral administration. Indeed, different researchers have proposed several rules (e.g., Lipinski’s, Veber’s, Ghose’s, and Muegge’s rules) to attain these predictions, but only for synthetic compounds. Most phytochemicals do not fully comply with these rules even though they show high bioactivity and high GI absorption experimentally. Here, we propose a detailed methodology using scientifically validated web-based platforms to determine the physicochemical properties of five phytochemicals found in ginger, echinacea, and tobacco. Furthermore, we analyzed the calculated data and established a protocol based on the integration of these classical rules, plus other extended parameters, that we called the Phytochemical Rule, to obtain a more reliable prediction of the GI absorption of natural compounds. This methodology can help evaluate bioactive phytochemicals as potential drug candidates and predict their oral bioavailability in patients.

The discovery of more bioactive compounds for non-invasive administration has been the goal of research groups focused on pharmacotherapy. Phytonutrients have always been attractive for researchers because they are a significant source of bioactive phytochemicals, but it is challenging to determine which components show high biomedical activity. However, based on the chemical structure of these active compounds, their physicochemical properties can be calculated to predict the probability of gastrointestinal (GI) absorption after oral administration. Indeed, different researchers have proposed several rules (e.g., Lipinski's, Veber's, Ghose's, and Muegge's rules) to attain these predictions for synthetic compounds. Most phytochemicals do not fully comply with these rules even though they show high bioactivity and high GI absorption experimentally. Here, we provide a detailed methodology using web-based platforms to determine the physicochemical properties of five phytochemicals in the phytonutrients ginger, echinacea, and tobacco. Furthermore, we analyzed the calculated data and established a protocol based on the combination and integration of these rules, plus other extended parameter ranges, to reliably predict the GI absorption of natural compounds. The presented data and methodology can be beneficial for evaluating bioactive natural compounds as potential drug candidates and predicting their oral bioavailability in patients.