The steroidal alkaloids α-tomatine and tomatidine: Panorama of their mode of action and pharmacological properties.

The steroidal glycoalkaloid α-tomatine (αTM) and its aglycone tomatidine (TD) are abundant in the skin of unripe green tomato and present in tomato leaves and flowers. They mainly serve as defensive agents to protect the plant against infections by insects, bacteria, parasites, viruses, and fungi. In addition, the two products display a range of pharmacological properties potentially useful to treat various human diseases. We have analyzed all known pharmacological activities of αTM and TD, and the corresponding molecular targets and pathways impacted by these two steroidal alkaloids. In experimental models, αTM displays anticancer effects, particularly strong against androgen-independent prostate cancer, as well as robust antifungal effects. αTM is a potent cholesterol binder, useful as a vaccine adjuvant to improve delivery of protein antigens or therapeutic oligonucleotides. TD is a much less cytotoxic compound, able to restrict the spread of certain viruses (such as dengue, chikungunya and porcine epidemic diarrhea viruses) and to provide cardio and neuro-protective effects toward human cells. Both αTM and TD exhibit marked anti-inflammatory activities. They proceed through multiple signaling pathways and protein targets, including the sterol C24 methyltransferase Erg6 and vitamin D receptor, both directly targeted by TD. αTM is a powerful regulator of the NFkB/ERK signaling pathway implicated in various diseases. Collectively, the analysis shed light on the multitargeted action of αTM/TD and their usefulness as chemo-preventive or chemotherapeutic agents. A novel medicinal application for αTM is proposed.

Saponin Interactions with Model Membrane Systems - Langmuir Monolayer Studies, Hemolysis and Formation of ISCOMs.

Saponins are used in medicine due to their pharmacological and immunological effects. To better understand interactions of saponins with model membranes and natural membranes of, for example, erythrocytes, Langmuir film balance experiments are well established. For most saponins, a strong interaction with cholesterol was demonstrated in dependence of both the aglycone part and the sugar moieties and is suggested to be correlated with a strong hemolytic activity, high toxicity, and high surface activity, as was demonstrated for the steroid saponin digitonin. In general, changes in the sugar chain or in substituents of the aglycone result in a modification of the saponin properties. A promising saponin with regard to fairly low hemolytic activity and high adjuvant effect is α-tomatine, which still shows a high affinity for cholesterol. An interaction with cholesterol and lipids has also been proven for the Quillaja saponin from the bark of Quillaja saponaria Molina. This triterpene saponin was approved in marketed vaccines as an adjuvant due to the formation of immunostimulating complexes. Immunostimulating complexes consist of a Quillaja saponin, cholesterol, phospholipids, and a corresponding antigen. Recently, another saponin from Quillaja brasiliensis was successfully tested in immunostimulating complexes, too. Based on the results of interaction studies, the formation of drug delivery systems such as immunostimulating complexes or similar self-assembled colloids is postulated for a variety of saponins.

Efficient improved extraction of tomato saponin using shock waves.

In the conventional method of mixer blending extraction, the yields of the tomato-saponin, esculeoside A, in the mini and middy tomatoes were found to be 0.043% and 0.046%, respectively. In order to improve the yields, we attempted a more efficient extraction using shock waves. The yields of esculeoside A were 0.0987% in air after 1 shock, 0.0792% in air after two shots, 0.0648% in half water after 1 or 2 shocks, and 0.0599% in water after 1 or 2 shocks. The yields obtained by the proposed method were approximately twice those of the conventional mixer blending method; therefore, this method is regarded to be very efficient. Moreover, two spirosolane glycosides, tomatine and lycoperoside A, were obtained for the first time from the ripe tomato fruit in this method. To date, these compounds have not been obtained with the mixer blending method. However, whether these glycosides are produced from esculeoside A or are newly extracted from the plant organ by the shock wave is still unclear.

Determination of tomatine in foods by liquid chromatography after derivatization.

A liquid chromatographic method for measuring tomatine levels in tomatoes and tomato products was developed. Tomatine was extracted with 1% acetic acid and purified on a C18 cartridge. Tomatine in the eluate was acetylated with acetic anhydride and isolated on a C18 cartridge. The solvent in the eluate was evaporated and the residue was dissolved in acetonitrile. An aliquot was injected into an Inertsil ODS-2 HPLC column and the acetylated tomatine was measured at 205 nm using a UV detector. The limit of determination was 1 microgram g-1. Tomatine was detected in the green portions of tomatoes and in tomato ketchups and juices at levels below 7 micrograms g-1.