Glycoalkaloids: Structure, Properties, and Interactions with Model Membrane Systems

Abstract

The glycoalkaloids which are secondary metabolites from plants have proven to be of significant interest for their biological properties both in terms of their roles in plant biology and the effects they exhibit when ingested by humans. The main feature of the action of glycoalkaloids is their strong binding to 3β-hydroxysterols, such as cholesterol, to form complexes with the consequence that membrane structure is significantly perturbed, and leakage or release of contents inside cells or liposomes becomes possible. The glycoalkaloids have been studied for their ability to inhibit the growth of cancer cells and in other roles such as vaccine adjuvants and as synergistic agents when combined with other therapeutics. The glycoalkaloids have rich and complex physical behavior when interacting with model membranes for which many aspects are yet to be understood. This review introduces the general properties of glycoalkaloids and aspects of their behavior, and then summarizes their effects against model membrane systems. While there are many glycoalkaloids that have been identified, most physical or biological studies have focused on the readily available ones from tomatoes (α-tomatine), potatoes (α-chaconine and α-solanine), and eggplant (α-solamargine and α-solasonine).Plants of the Solanaceae family include tomatoes, potatoes, and eggplants, and are well known to produce secondary metabolites known as glycoalkaloids [21]. The glycoalkaloids are produced in the leaves, flowers, and roots of the plant. In the case of potatoes, they are also found in the sprouts [22]. Tomato plants produce the glycoalkaloid α-tomatine, potato plants produce both α-chaconine and α-solanine, and eggplants produce both α-solamargine and α-solasonine (see Figure 1). Green tomatoes can have up to 500 mg kg −1 of tomatine in the fruit, which will decrease to near 5 mg kg −1 upon ripening [5]. The concentration of tomatine in the vines will stay near 500 mg kg −1 . The amount of α-tomatine in red tomatoes consumed by humans is 10-30 mg kg −1 , but if green tomatoes are consumed then the level will be 200-500 mg kg −1 . In eggplants, the average glycoalkaloid concentration for 21 varieties was found to vary from 0.625-20.5 mg kg −1 [23]. The glycoalkaloid content of potatoes varies widely with potato type and conditions of cultivation [24] and will increase in damaged plants [25]. The glycoalkaloid content of normal potato tubers is reported as 12-20 mg kg −1 while green tubers can have 250-280 mg kg −1 and green skin 1500-2200 mg kg −1 [26]. The enzymes involved in the natural synthesis of the oligosaccharides of the glycoalkaloids have been reviewed [27]. Structure of GlycoalkaloidsThe glycoalkaloids consist of a nitrogen-containing steroidal aglycone and an attached oligosaccharide. The prefix αrefers to the compound with fully intact oligosaccharide, whereas removal of one sugar would be denoted by a β-prefix, removal of two sugars by a γ-prefix, and removal of three for a tetrasaccharide by a δ-prefix. The aglycones are referred to as t...

Solanum nigrum Fruit Extract Increases Toxicity of Fenitrothion—A Synthetic Insecticide, in the Mealworm Beetle Tenebrio molitor Larvae

“…The malformation of biological membranes caused by glycoalkaloids (solasonine and solamargine) has been previously described [ 45 ]. They cause easier penetration of toxic substances to the cell [ 46 ], which could be an additive factor to increase FN toxicity. The changes in the chromatin condensation in the fat body after application of FN and with pre-treatment of EXT also suggests a potentiation effect ( Figure A3 ), confirmed by calculated correlation coefficient, which showed strong positive correlation.…”

Solanum nigrum Extract and Solasonine Affected Hemolymph Metabolites and Ultrastructure of the Fat Body and the Midgut in Galleria mellonella

“…Indeed, glycoalkaloids bind to sterols in biological membranes. They may form complexes that affect the permeability of membranes and disturb homeostasis within cells, including osmotic conditions, when cytoplasm content leaks out or the physiological fluids leak into cells [ 35 , 36 ]. The glycoalkaloids may act synergistically, explaining more significant malformations observed within tissues exposed to extracts than to the single alkaloid.…”

Effect of Microwave-Assisted Aqueous Two-Phase Extraction of α-Solanine from S. retroflexum and Analysis on UHPLC-qTOF-MS

“…The surge in concentration levels of steroidal alkaloids (glycoalkaloids) is triggered by the exposure of Solanum plants to the sun's UV light or because of mechanical injury including peeling and slicing (Dao and Friedman 1994;Kasnak and Artik 2018. Some of the toxic effects of glycoalkaloids are due to anticholinesterase effects on the central nervous system (Caprioli et al 2014;Lelario et al 2019) and disruption of cell membranes (Blankemeyer et al 1998;Nepal and Stine 2019. Symptoms of glycoalkaloid poisoning in humans include colic pain in the abdomen and stomach, diarrhoea, vomiting, burning sensation about the lips and mouth, fever, rapid pulse and headache (Uluwaduge et al 2018;Deng et al 2021).…”