Physicochemical properties of dietary phytochemicals can predict their passive absorption in the human small intestine

Abstract

A diet high in phytochemical-rich plant foods is associated with reducing the risk of chronic diseases such as cardiovascular and neurodegenerative diseases, obesity, diabetes and cancer. Oxidative stress and inflammation (OSI) is the common component underlying these chronic diseases. Whilst the positive health effects of phytochemicals and their metabolites have been demonstrated to regulate OSI, the timing and absorption for best effect is not well understood. We developed a model to predict the time to achieve maximal plasma concentration (Tmax) of phytochemicals in fruits and vegetables. We used a training dataset containing 67 dietary phytochemicals from 31 clinical studies to develop the model and validated the model using three independent datasets comprising a total of 108 dietary phytochemicals and 98 pharmaceutical compounds. The developed model based on dietary intake forms and the physicochemical properties lipophilicity and molecular mass accurately predicts Tmax of dietary phytochemicals and pharmaceutical compounds over a broad range of chemical classes. This is the first direct model to predict Tmax of dietary phytochemicals in the human body. The model informs the clinical dosing frequency for optimising uptake and sustained presence of dietary phytochemicals in circulation, to maximise their bio-efficacy for positively affect human health and managing OSI in chronic diseases.

Inhalation Absorption Prediction (IAP) Model for Predicting Medicinal Cannabis Phytochemical Pharmacokinetics

“…By contrast, T ½ showed a negligible correlation with TPSA (r = 0.010), low correlation with nrot (r = 0.329) and log P (r = 0.349) and a moderate correlation with Vol (r = 0.506) and MW (r = 0.528). These results were dissimilar to Selby-Pham et al 12 which observed moderate correlation for molecular weight and high correlation for log P and TPSA to T max following ingestion. Accordingly, physicochemical properties impacting inhalation pharmacokinetics were deemed to be different from those impacting ingestion pharmacokinetics.…”

“…Table S3), with visualisation of either T max or T ½ with singular physicochemical measures (Figure 1) suggesting the possibility for non-linear relationships or the necessity for multiple measures to achieve predictive power. This is consistent with previous pharmacokinetic studies, such as the PCAP model, 12 which have shown that following consumption, individual measures had poor predictive power while a combination of measures could be used to achieve a model with greater predictive power. Pearson's correlation coefficients (Supplement Table S2) were used to assess the power of physicochemical properties to predict pharmacokinetic properties based on the categorisation of strength of correlation as; r < 0.3 negligible, 0.3 < r < 0.5 low, 0.5 < r < 0.7 moderate, 0.7 < r < 0.9 high and r > 0.9 very high.…”

“…While in-vivo approaches may be preferred, in-silico predictive models have proven to be powerful, cost-effective tools, for fast and efficient pharmacokinetic approximations to guide usage and designing future clinical studies. 11 The in-silico phytochemical absorption prediction (PCAP) model presented in Selby-Pham et al 12 has been applied to predict phytochemical pharmacokinetics of plant extracts to guide recommended intake times for maximal health benefits. 13 This optimisation utilises the concept of 'biomatching' , wherein maximal medicinal efficacy is achieved by aligning plasma concentrations of stress-mediating compounds with periods of associated stressors.…”

“…13 This optimisation utilises the concept of 'biomatching' , wherein maximal medicinal efficacy is achieved by aligning plasma concentrations of stress-mediating compounds with periods of associated stressors. 12,14 For example, extracts from Hyptis sp. and Hypericum perforatum were recommended to be ingested two hours prior to meals to achieve maximal stress mediation from absorbed antioxidant phytochemicals by biomatching the time of maximal plasma concentration (T max ) with the period of postprandial oxidative stress.…”

Dietary Phytochemicals Promote Health by Enhancing Antioxidant Defence in a Pig Model

“…As phytochemicals are recognised by the human body as xenobiotics, their presence in the human body is transient [ 40 ] and influenced by their physicochemical properties. Recently, we have developed the phytochemical absorption prediction (PCAP) model, allowing direct calculation of the time required for phytochemicals to reach their maximal plasma concentrations (T max ) after oral consumption, based on their molecular mass and lipophilicity descriptor log P [ 41 ]. Further, a liquid chromatography mass spectrometry (LC-MS) method has been developed to characterise T max ranges of phytochemical mixtures based on molecular mass and log P [ 42 ].…”