Isomers of the tomato glycoalkaloids a-Tomatine and dehydrotomatine: Relationship to health benefits

Authors: KOZUKUE, NOBUYUKI - Seowon University, Korea; KIM, DONG-SEOK - Yeungnam University; CHOI, SUK-HYUN - Seowon University, Korea; MIZUNO, MASASHI - Kobe University; Friedman, Mendel

Submitted to: Molecules
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/1/2023
Publication Date: 4/21/2023
Citation: Kozukue, N., Kim, D., Choi, S., Mizuno, M., Friedman, M. 2023. Isomers of the tomato glycoalkaloids a-Tomatine and dehydrotomatine: Relationship to health benefits. Molecules. 28(8). Article 3621. https://doi.org/10.3390/molecules28083621.
DOI: https://doi.org/10.3390/molecules28083621

Interpretive Summary: Interest in tomato compounds called glycoalkaloids arises from the fact that they seem to have important functions in host-plant interactions and have been reported to exhibit several beneficial health-promoting properties. These include activities against pathogenic viruses and disease-causing protozoa that cause sexually transmitted diseases called trichomoniasis in humans and farm animals, induction of decreased plasma low-density (bad) lipoprotein (LDL) cholesterol and triglyceride levels in hamsters fed a high fat diet, inhibition of cancer cells in vitro, as well as the growth of cancer tumors in rainbow trout and in mice. We previously reported on a new glycoalkaloid in tomatoes, which we named dehydrotomatine and that dehydrotomatine, along with a-tomatine is present in all parts of the tomato plant, including fruit, leaves, calyxes, flowers, roots, and stems, as well as in somatic potato hybrids. Dehydrotomatine is found in tomatoes at about 9-10% of the mixture of the two glycoalkaloids. Both glycoalkaloids have the same four sugar (tetra-saccharide) side chain. Dehydrotomatine differs from a-tomatine by only the presence of a double bond. Additional analytical data described in the present study show that commercial tomatine and tomatine extracted from green tomatoes actually consists of mixture of four compounds, a-tomatine, dehydrotomatine, an a-tomatine isomer, and a dehydrotomatine isomer in an approximate ratio of 90:9:1:1, respectively. Our biological studies suggest that the mixture known as tomatine has the potential to serve as a health-promoting functional food against several diseases, including cancer, cardiovascular disease, and trichomoniasis.

Technical Abstract: High-performance liquid chromatography (HPLC) analysis of three commercial tomatine samples and another one isolated from green tomatoes revealed the presence of two small peaks in addition to those associated with the glycoalkaloids dehydrotomatine and a-tomatine. The present study investigated the possible structures of the compounds associated with the two small peaks using high-performance liquid chromatography (HPLC), gas-chromatography and mass spectrometry. Although the two small peaks elute much earlier on chromatographic columns than the elution times of the known tomato glycoalkaloids dehydrotomatine and a-tomatine, isolation of the two compounds by preparative chromatography and subsequent analysis by shows that the two compounds have identical molecular weights, tetra-saccharide side chains, and mass spectral (MS and MS/MS) fragmentation patterns to dehydrotomatine and a-tomatine. On the basis of the cited observations, we suggest that two isolated compounds seem to be isomeric forms of dehydrotomatine and a-tomatine. The analytical data, therefore, indicate that widely used commercial tomatine preparations and those extracted from green tomatoes and tomato leaves consist of a mixture of the following four compounds: a-tomatine, dehydrotomatine, an a-tomatine isomer, and a dehydrotomatine isomer in an approximate ratio of 90:9:1:1, respectively. We do not know if the isomers are biosynthesized in the plant or formed post-translationally during isolation and storage, an aspect that merits further study.