Development of intestinal bioavailability prediction (IBP) and phytochemical relative antioxidant potential prediction (PRAPP) models for optimizing functional food value of Cannabis sativa (hemp)

Abstract

Oxidative stress and inflammation (OSI) occurs naturally during many biological processes including digestion, metabolism, and exercise. While small, transient amounts of OSI are considered normal, unregulated, or chronic OSI can damage the vascular-circulatory system, which can result in chronic illnesses such as cardiovascular disease (CVD), atherosclerosis, and cancer. Antioxidant phytochemicals have the capacity to mitigate OSI through radical scavenging activity or the induction of endogenous mechanisms, but to achieve optimal reductions in OSI, the timing of antioxidant effects must occur during the onset of OSI – a concept known as ‘bio-matching.’ Additionally, the bioavailability and antioxidant capacity of active phytochemicals should be accounted for during pharmacokinetic assessments to guide bio-matching. Herein two quantitative structure–activity relationship (QSAR) predictive models are presented: the intestinal absorption prediction (IBP) model for predicting compound bioavailability (r2 = 0.93), and the phytochemical relative antioxidant potential prediction (PRAPP) model for predicting antioxidant capacity (r2 = 0.89). Application of these models to a characterized hemp meal phytochemical profile, along with established models for predicting Tmax and T½, generated a composite antioxidant fingerprint, which predicted a peak in antioxidant activity 36 min after ingestion in liquid form. Accordingly, hemp meal-based protein powders (a common exercise supplement) should be consumed 26 min prior to completion of exercise to achieve bio-matching with the onset of exercise-induced OSI 10 min after exercise. The IBP and PRAPP models presented herein could be useful tools in understanding phytochemical complex antioxidant pharmacodynamics and in optimizing the consumption of hemp meal and other functional foods to achieve bio-matching of composite antioxidant activity with OSI profiles. Abbreviations 4-HPP: 4-hydroxyphenylpyruvic acid; ABTS: 2,2ʹ-azinobis(3-ethyl-benzothiazoline-6-sulfonate); DPPH: 1,1-diphenyl-2-picrylhydrazyl; FRAP: Ferric reducing antioxidant power; HPLC: high-pressure liquid chromatography; IAP: inhalation absorption prediction; IBP: intestinal bioavailability prediction; Log P: lipophilicity descriptor; MW: molecular weight; Nrot: number of rotatable bonds; OSI: oxidative stress and inflammation; PCAP: phytochemical absorption prediction; PDC: plasma drug concentration; PRAPP: phytochemical relative antioxidant potential prediction; QSAR: quantitative structure–activity relationship; ROS: reactive oxygen species; T½: elimination half-life; TEAC: Trolox equivalent antioxidant capacity; Tmax: time of maximal plasma concentration; TPSA: topological polar surface area; V: molecular volume.

Keywords

• pharmacokinetics
• pharmacodynamic
• osi
• teac
• bio-matching