4. Discussion
COLD
The main objective of the present study was to gain more physiological and mechanistic insights into the underlying processes of localized cold-stimulate stress upon varied doses of highly bioavailable HEPT7G/βCD inclusion complex consumption. The major metabolites of hesperetin in human plasma are conjugated hesperetin-glucuronides that can be hydrolyzed at the vascular level by β-glucuronidase (i.e., deconjugated) in several tissues, releasing the parent hesperetin aglycone, which accumulates intracellularly and enters blood circulation [The HEPT7G/βCD inclusion complex administration may inhibit the non-adrenergic vasoconstrictor response to cold-stimulate stress in the human skin because non-adrenergic involvement is predominant in sudden quenching [Moreover, hesperetin monoglucosides and aglycone hesperetin have also been shown to have antioxidant and anti-inflammatory properties [Furthermore, transient receptor potential (TRP) channels are known as highly sensitive molecular thermometers and have been identified to have a role in regulating skin blood flow. They are expressed in vascular smooth muscle cells and endothelial cells, which are important in controlling blood vessel diameter [Upon immersion of the hand into a cold water tank maintained at 15 ± 2 °C, the TRP channels could sense changes in temperature (see 