Plant sterols are inherent compounds of many nutritional supplements and food additives. Sterols are chemical compounds based on 1,2-cyclopentaneperhydrophenantrene and are characterized by hydroxyl moiety at the 3C position and the side chain at the 17C position. The latter makes them structurally similar to pregnenolone, which is a fundamental molecule for all 17-ketosteroids generation. The major natural source of dietary plant sterols are vegetables, fruits, berries, and vegetable oil.
Plants sterols are believed to be a necessary compound of the human diet and recommended to add as a food supplement or functional food. In the early 1950s, it was discovered and clinically approved cardioprotective effect of plants sterol β-sitosterol caused by its cholesterol-lowering property mediated by the replacement of cholesterol in HDL/LDL particles [52]. Years later, many studies showed that consuming even 2.5 g of plant sterols in a daily diet is enough to decrease the level of circulating triglycerides by 9.5%-13% [33,34,69,90]. Plants sterols make a significant impact on the central nervous system. Due to the presence of the alkyl moiety at the C24 position, plant sterols cannot be converted into more polar molecules, unlike endogenous cholesterol. Therefore, sterols can be irreversibly accumulated and integrated into the cell membrane after entering into the brain circulation [80,99,75].
The exact role of dietary plant sterols is not yet recognized; thus, it cannot be judged as strictly positive or detrimental. Long-term exposure to plant sterols leads to an increased level of sterols in brain cells and sufficiently reduces the density of amyloid plaques in patients with Alzheimer’s disease, but does not lead to the improvement of cognitive function and memory [81,101]. Since the early stage of Alzheimer’s disease is associated with the impairment of BBB functioning, the reduced concentration of plant sterols in cerebrospinal fluid (CSF) was supposed as a promising predictive biomarker with an 85% sensitivity and 75% specificity [103,104]. Application of plant sterols for the management of neurodegenerative diseases therapy was proposed due to their immune-modulating activity engaged in the augmentation of bone-marrow-derived macrophages polarization to anti-inflammatory phenotype caused by the depletion of IL-10α (p < 0.01) but the sustained elevation of interleukins IL-1β, IL-6, and IL-12 in 16 days after treatment [106,107]. Recent findings demonstrate the ability of plant sterols to restore the impaired uptake of cholesterol also in patients with multiple sclerosis, when plant sterols additives, at least in the animal models, may stimulate the re-myelination process [109]. Sterols extract from Aloe vera stimulates the expression of Fatp1, Acox1, and Cpt1 genes in a dose-dependent manner through the activation of PPAR receptors, which produce a sufficient antioxidant response resulting in the increased level of glutathione and the diminished expression of IL-18 supporting the recovery and amelioration of patients with neurodegenerative diseases [83,84].
Skin regeneration and wound healing are currently the main points, where dietary sterols are widely utilized. The regenerative property of plant sterols is mediated in the same manner as the anti-inflammatory effect briefly described above. Ethanolic extract of traditional Thai medical plant parts (seeds, root, and pericarp) obtained from Garcinia mangostana L., Glycyrrhiza glabra L., Nigella sativa L, exhibited an inhibiting property toward superoxide dismutase (SOD) and nitric oxide (NO), while the extracts from G. mangostana and G. glabra at a concentration of 5 µg/mL can enhance cells proliferative activity supporting the positive effect of plant sterols on wound regeneration and recovery after damage [114]. Animals who were given a dermal wound and further treated on topical application with brassinosteroid for 10 days demonstrated almost completely suppressed expression of tumor necrosis factor-α (TNF-α) transforming growth factor-β (TGF-β) indicating the enhanced proliferative activity and stimulation of cells migration caused by PI3K/Akt (phosphoinositide 3-kinases/protein kinase B) signaling pathway [46].
The potential anabolic properties of plants are very attractive in professional sport. Considering the growing offers of plant-based food supplements and additives intended for the intentional improvement of elite athlete abilities, WADA (World Anti-Doping Agency) included some suspected dietary sterols in the monitoring list. Evidence exists that the anabolic effect of some of the sterols (for example, 20β-OH-ecdysone) is caused by the binding with estrogen receptors, thus, such sterols can be even more effective in comparison to some synthetic steroids [116]. There is an accumulating number of reports about the targeted effect of 20β-OH-ecdysone on muscle cell size and elevation of a myonuclear number of the regenerating myocytes, which are very convincing in anabolic and modulating properties of this sterol, albeit mediated in an unknown way [117,118]. The main metabolic product, poststerone, also fosters the increase of muscle type fiber cross-sectional area but to a relatively lower degree compared to its parental compound [119]. Eventually, based on the body tissue analysis (muscle cells growth, an increase of fibers cross-sectional area) and known aspects of the protein synthesis gain, most authors proposed that benefits of 20β-OH-ecdysone are caused by the activation of the PI3K/Akt pathway. Due to possible androgenic and growth-stimulating effects, 20β-OH-ecdysone has been examined on the subject of acceleration of bone mass augmentation. Although the bone mass augmentation is pre-determined by gender-specific hormonal background and, specifically, by estrogen receptor loading, it has been demonstrated that 20β-OH-ecdysone provides equal impact regardless of the gender feature [120,121,122]. The possible implication of estradiol receptors rather than androgen receptor activation has been previously proposed based on the in silico molecular docking [116]. However, the molecular model contradicts the results of the experiment, displaying that the regulatory activity of plant sterols bypasses this way of interaction, and they do not bind with estradiol receptors [122].
The presence and origination of anabolic steroids (in particular, boldione) have been demonstrated in a tested group of volunteers who were administrated with plant sterols, however, no significant correlation was established between the excretion rate of 17-ketosteroids precursors (for example, androstenediol) and the consumed amount or the frequency of plant sterols intake [68]. Before, it has been reported an in vitro transformation of the selected plant sterols into androgenic products (testosterone and androstenedione), which has been explained by the activity of residential gastrointestinal microflora [124,125,126]. Some plant sterols (sitosterol, campesterol, stigmasterol, episterol) can be utilized as precursors for the endogenous synthesis of human 17-ketosteroids, including DHEA (dehydroepiandrosterone) [140,141,142]. The occurrence of anabolic steroids in plants was rigorously reviewed by [144], who documented that the prevalence of progesterone (up to 80 ng/g) was in more than 80%, and the prevalence of androgens (androsterone up to 11.4 ng/g, testosterone up to 80 ng/g, and epitestosterone up to 110 ng/g) was in more than 70%, and 17β-estradiol (in amounts up to 40 pg/g) was in nearly in 50% cases among 128 tested plant species of 50 families. Most of the detected and reported steroids were reported as not being contaminants of plant subjects, but instead, they were substrate-specific intermediates that naturally occur in plants. Detection of androstadienone and androstenedione at a concentration of 2.20 ng/g has been reported for Nicotiana tabacum [152], pine pollen [153], and even in potato, where marginal concentration did not exceed 50 pg/g [154].
So far, the exact effect of plant sterols is poorly predictable and requires a deep investigation of nutrigenomic, epigenetic, and even ecological factors before plan and develop diet recommendations purposed to improve abilities in sport or avoid cardiovascular complications, or retard skin aging, etc. Consequently, a very careful personalized approach based on the highly-specific bioactive compound, including a specific sterol, should be developed, while considering different nutritional needs and different categories of the population.
This entry is adapted from the peer-reviewed paper 10.3390/nu13051623