Diversity of Plant Sterols Metabolism: The Impact on Human Health, Sport, and Accumulation of Contaminating Sterols

Abstract

The way of plant sterols transformation and their benefits for humans is still a question under the massive continuing revision. In fact, there are no receptors for binding with sterols in mammalians. However, possible biotransformation to steroids that can be catalyzed by gastro-intestinal microflora, microbial cells in prebiotics or cytochromes system were repeatedly reported. Some products of sterols metabolization are capable to imitate resident human steroids and compete with them for the binding with corresponding receptors, thus affecting endocrine balance and entire physiology condition. There are also tremendous reports about the natural origination of mammalian steroid hormones in plants and corresponding receptors for their binding. Some investigations and reports warn about anabolic effect of sterols, however, there are many researchers who are reluctant to believe in and have strong opposing arguments. We encounter plant sterols everywhere: in food, in pharmacy, in cosmetics, but still know little about their diverse properties and, hence, their exact impact on our life. Most of our knowledge is limited to their cholesterol-lowering influence and protective effect against cardiovascular disease. However, the world of plant sterols is significantly wider if we consider the thousands of publications released over the past 10 years.

Keywords: anabolic effect; biotransformation; cholesterol; diet; food matrix; sterols.

Figure 1

General scheme of the major routes of plant sterols in human. Plant sterols and dietary cholesterol are mainly absorbed in intestine, and Niemann-Pick C1-like 1 (NPC1L1) transporter plays a vital role in the regulation of initial absorption. After absorption, sterols are esterified in support with ACAT and transported to the liver following the incorporation into chylomicrons. In contrast, unesterified sterols are pumped out by ABCG5/ABCG8 transporters, which are the major cholesterol and plant sterols transporters. The plasma efflux of both plant sterols and cholesterol is regulated by ABCA1, which is involved in the assembling of HDL-like particles with the assimilated sterols. This transporter is also critically important in plant sterols and cholesterol efflux after delivering chylomicrons from enterocytes to liver cells. Plant sterols are capable of stimulating LXR receptors regulating APOE expression, which is essential for HDL and LDL assembly and uptake; and can be partially catalyzed by microsomal cytochromes. Binding with LXR receptors upregulates ABCG5/G8 transporters, and thus enhances cholesterol and plants sterols absorption. The exported HDL-like particles with the incorporated plant sterols are trapped by SR-IB receptors expressed on the liver and adrenal glands cell surface. This receptor plays a pivotal role in the uptake of cholesterol through HDL and, most importantly, for brain lipids metabolism, where HDL is the primary source of lipids and cholesterol uptake.

Figure 2

The proposed scheme of plant sterols entering the brain system. The mechanism involves HDL-like particles carrying plant sterols and apolipoprotein E (APOE). The HDL-like particles are translocated through SR-B1 HDL receptors on the apical side of the blood-brain barrier (BBB) and released into the brain via ABCA/ABCG1 transporters, which are expressed on the basolateral side of BBB and on the surface of astrocytes. LDL/VLDL receptors trap the released HDL-like particles enriched with plant sterols on the surface of microglia and oligodendrocytes since HDLs associated with APOE are the primary source of lipids transport in the central nervous system. Upon delivery, plant sterols activate mechanisms that decrease inflammation, increase amyloid-β clearance, and reduce the activity of β-secretase. The regulatory mechanism is largely unknown but is supposed to be realized through the activation of LXR/RXR receptors and regulation of APOE expression mediated by PPAR-signaling.

Figure 3

The proposed scheme of biosynthesis of progesterone and pregnenolone in plants. It is assumed that the synthesis starts from the cleavage of 24-alkyl sterols (I) side-chain resulting in the production of pregnenolone (II) following dehydrogenation in the presence of Δ5-3β-hydroxysteroid dehydrogenase (EC 1.1.1.145) activity. The resulting isoprogesterone (III) is further isomerized by Δ5-Δ4-ketosteroid isomerase (EC 5.3.3.1) to progesterone (IV). Further transformation to products (V)-(IX) is accomplished in the presence of Δ5-3β-hydroxysteroid dehydrogenase (EC 1.1.1.145) activity that, eventually, catalyzes the production of glycosides. It is assumed that progesterone and pregnenolone are essential intermediated in plant biosynthesis of glycosides. Both enzymes are ubiquitously distributed among plants and microorganisms, whereas in animals, these two enzymes reside in one-single protein. The Δ5-3β-hydroxysteroid dehydrogenase has a higher preference for NAD instead of NADPH, which is also accepted by lower activity.

Figure 4

It is hypothesized that mammalian-like steroids found in plants are contaminants that enter the plant through the soil and reclaimed water. Up to 1.3 tons of the excrete mammalian steroids (endogenous and synthetic) are wasted in the ocean from China rivers. In the USA, glucocorticoids (hydrocortisone and prednisone) and androgen steroids were found in 27 to 35% of stream water samples taken from 14 states. These polluting steroids enter plants, fungi, and soil microbial cells and can be highly toxic for plants due to low solubility. The absorbed steroids can be accumulated in plant organs (roots, leaves) and consumed by humans. According to the WHO recommendations, the risk associated with steroid-enriched food consumption is considered only if their intake exceeds 3 µg per day. However, it is believed that the specific content of contaminating steroids in plants is 100 to 400 ng/g of plant weight.

Figure 5

The overall effect of plant sterols and, in particularly, functional food is rather positive. Up to nowadays, sterols are widely used in different ways, but their natural effect (such as implication in lipids metabolism and neuro- and immunomodulation) does merit attention and seems to be vital for reason of their steroid-like properties. Therefore, it is not surprising that sterols are used in cosmetics, pharma and sometimes are considered in professional sport as suspicious substances that may improve human abilities.