Exploring the potential of betalain-derived vegetables to impart anti-inflammatory properties

Metabolic engineering is a field of plant biotechnology that seeks to genetically modify the metabolic pathways of plants to generate plant varieties with improved health benefits. Recently, scientists from Tokyo University of Science and Iwate Biotechnology Research Center engineered potato and tomato plants to express the plant pigment betalain, which is found only in caryophyllales and higher mushrooms. They found that while betalain tomatoes conferred anti-inflammatory effects against macrophages and murine colitis, betalain potatoes did not exhibit such effects.

Betalains are a class of plant pigments responsible for the characteristic red-purple (betacyanin) or yellow (betaxanthin) color of certain fruits and vegetables. These natural, water-soluble, nitrogen-containing pigments are commonly used as food colorings. Recently, research results have highlighted the strong antioxidant potential of betalains, making them potential candidates for producing health foods and fighting against various diseases. Currently, betalains are produced only in plants of the order Caryophyllales and higher mushrooms. Therefore, metabolic engineering has been explored to genetically modify non-Caryophyllales plants, to improve the production and scalability of these pigments.

Although betalain-accumulating transgenic plants have been developed over the years, their applications in the production of health food resources remain to be explored.

To fill this gap, a collaborative research team from Tokyo University of Science (TUS) and Biotechnology Research Center in Iwate, Japan, led by Professor Gen-ichiro Arimura of TUS, attempted to modify genetically engineered potato and tomato plants to produce betacyanin. Their goal was to test the therapy efficiency of betacyanin-producing tomatoes and potatoes against mouse models of colitis and inflammatory macrophages. Their findings were published in Biotechnology & Bioengineering on January 26, 2023. Discussing the results of this study, Professor Arimura says: “We have successfully engineered potato tubers and tomato fruits to co-express betacyanin biosynthetic genes [genes for CYP76AD1 from Beta vulgaris, DOD (DOPA 4,5-dioxygenase) and 5GT (cyclo-DOPA 5-O-glucosyltransferase) from Mirabilis jalapa] under the control of appropriate promoters. This enhanced the endogenous accumulation of betanin and isobetamine; two common types of betacyanin; in these transgenic vegetables. Accumulation of these pigments caused them to appear dark red in color upon maturation, compared to their wild-type counterparts..”

Since macrophages play an important role in several inflammatory diseases, the team then tested the therapeutic efficacy of these transgenic vegetables in macrophage-like cells (RAW264.7), following stimulation of the immune response by lipopolysaccharides (LPS ). They observed that extracts from the transgenic tomato fruit exerted higher anti-inflammatory activity than their wild-type counterparts. This was attributed to a decrease in LPS-stimulated transcription of the pro-inflammatory cytokine gene-;A Tnf-α gene, within transgenic cells.

“These results were consistent with the anti-inflammatory effects of the transgenic tomato we observed in the intestines of mouse models with dextran sulfate sodium (DSS)-induced colitis. Marked improvement in their body weight loss and disease activity index was observed due to suppression of DSS-stimulated transcription of pro-inflammatory genes – genes for Tnf-α, Il6 and Cox-2“, adds Professor Arimura, while discussing the results derived from the other experiment in mice. In addition, the additive and synergistic action of betacyanin with natural fruit components (such as lycopene in tomato) has further stimulated improvement in colitis in mouse models.Interestingly, while significant anti-inflammatory effects were observed with transgenic tomato extracts at 100- to 1000-fold dilutions, this was not the case with transgenic potatoes, despite substantial production of betanin and isobetanin, are antagonists of transgenic potatoes that act against the anti-inflammatory function of betacyanin, but this remains to be confirmed.

Tomatoes genetically modified to produce betacyanins have been shown to have substantial health effects. Although natural plant sources of betalains such as beets exist, these pigments show poor stability at high temperatures and extreme pH. This indicates that betacyanin-producing transgenic tomato lines are more likely to be effective as health foods when ingested in their raw state.”

Professor Gen-ichiro Arimura, Tokyo University of Science

What are the potential applications of these findings? He further adds:Although there is no commercial cultivation of edible genetically modified crops in Japan, we anticipate that their applications as health foods through production in closed plant factories and other facilities will lead to the widespread use of recombinant plants in Japan..”

We are confident that the engineering of betalain will soon become a promising avenue for improving the commercial production of health foods, which boost the food supply while simultaneously imparting health benefits to its consumers.