TABLE 1.

Preclinical phytosterol (PS) bioactive effects and the respective mechanisms of action.

Bioactive effects	Mechanism of action	Reference
Anticancer	Decrease the number of aberrant crypt and crypt multiplicity. Attenuate ß-catenin and PCNA expression. Trigger apoptosis, through increasing Fas protein expression, caspase 8, TRAIL, BAD dephosphorylation, mitochondrial depolarization and caspase 3-dependent PARP cleavage, intracellular Ca2+ influx, rise in ROS levels, cell cycle arrest at phase G0/G1 and S, and cell necrosis Decrease mammary hyperplastic lesions and total tumor burden Cell cycle arrest at G2/M phase Interfere in DNA fragmentation	Daniel et al. (2001); Awad et al. (2007); Baskar et al. (2010); Herbst et al. (2010); Cilla et al. (2015); López-García et al. (2017); Alvarez-Sala et al. (2018a)
Antioxidant	Free radical scavenger Cell membranes stabilizer Antioxidant enzyme booster	Van Rensburg et al. (2000)
Anti-inflammatory	Macrophage- and neutrophil-mediated inflammatory process Evoke Th1 cell response Decrease edema Decrease proinflammatory cytokine levels Interfere in matrix degradation mediators Increase the remission periods in GI tract diseases, improving colon shortening and blocking mucosal colonic damage	Nashed et al. (2005); Brüll and Mensink (2009); López-García et al. (2019); López-García et al. (2020)
Antidiabetic	Glucose metabolism modulation Interfere with AMPK and peroxisome proliferator-activated receptors	Zakłos-Szyda (2015)
Antiatherosclerotic/effects on lipid profile	Cholesterol absorption blockage Decrease LDL-C and VLDL secretion and accumulation Decrease plasma and hepatic TG levels	Moghadasian (2000)
Neuroactive effects	Reduce Aβ plaque formation, counteract memory deficits, increase the acetylcholine levels in brain, and increase Aβ clearance	Schepers et al. (2020)
Antieryptotic and antihemolytic effects	Prevent eryptosis; reduce Ca2+ influx, ROS overproduction, GSH depletion, and hemolysis	Alvarez-Sala et al. (2018d)
Microbiota modulation effects	Promoters of beneficial species abundance, affecting the Erysipelotrichaceae and Eubacterium family proportions	Cuevas-Tena et al. (2018)

AMPK, adenosine monophosphate (AMP)-activated kinase; DNA, deoxyribonucleic acid; GI, gastrointestinal; LDL-c, low-density lipoprotein cholesterol; PCNA, proliferating cell nuclear antigen; PSs, phytosterols; TG, triglycerides; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; VLDL-C, very-low-density lipoprotein cholesterol.