Journal of ethnopharmacology · 2025
Inducible effects of evodiamine on the uptake of glutamine in Caco-2 cells.
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Somehara Sho, Mizuno Fumika, Ishida Tomoaki, Mizukami Hajime, Makino Toshiaki
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM) and traditional Japanese Kampo medicine, the symptoms associated with malabsorption syndrome correspond to "spleen deficiency", which can be treated with the prescriptions containing spleen-tonifying drugs. However, there is a lack of scientific evidence for this effect.
AIM OF THE STUDY: We hypothesized that one potential mechanisms of action of spleen-tonifying drugs is to enhance nutrient transporter function in the gastrointestinal epithelium. Glutamine is an amino acid that aids in intestinal function. In addition, we develop crude drugs with this efficacy and to clarify the active ingredients and their mechanisms of action.
MATERIALS AND METHODS: We screened 99 crude drugs used in Kampo preparations to identify those that promote the uptake of glutamine into human colon-derived Caco-2 cells.
RESULTS: We found 7 active crude drugs on the promotion of glutamine uptake, however, no activity was observed for the representative spleen-tonifying drugs such as Ginseng Radix and Astragali Radix. Instead of spleen-tonifying drugs, we observed that the extract of Euodiae Fructus (dried fruit of Tetradium ruticarpum) had the strongest effect on glutamine uptake. Euodiae Fructus extract induced mRNA expression of the amino acid transporter B0 (ATB0), also known as system alanine-serine-cysteine transporter 2 or solute carrier 1A. The active ingredient in Euodiae Fructus was evodiamine, and when Caco-2 cells were incubated with medium containing evodiamine (3 μM) for 24 h, the glutamine uptake and the mRNA expression of ATB0 were significantly induced by 1.6-times and 4.1-times, respectively. The inducible effects of evodiamine were significantly suppressed by each inhibitor of protein tyrosine kinase, protein kinase C, phosphatidylinositol-3 kinase, or epidermal growth factor receptor (EGFR). Evodiamine induced mRNA expression level of EGFR.
CONCLUSIONS: It is incorrect to interpret the spleen-tonifying effect as an effect of enhanced glutamine uptake. Evodiamine, an ingredient of Euodiae Fructus, promotes glutamine absorption in intestinal cells to improve malabsorption syndrome.
AIM OF THE STUDY: We hypothesized that one potential mechanisms of action of spleen-tonifying drugs is to enhance nutrient transporter function in the gastrointestinal epithelium. Glutamine is an amino acid that aids in intestinal function. In addition, we develop crude drugs with this efficacy and to clarify the active ingredients and their mechanisms of action.
MATERIALS AND METHODS: We screened 99 crude drugs used in Kampo preparations to identify those that promote the uptake of glutamine into human colon-derived Caco-2 cells.
RESULTS: We found 7 active crude drugs on the promotion of glutamine uptake, however, no activity was observed for the representative spleen-tonifying drugs such as Ginseng Radix and Astragali Radix. Instead of spleen-tonifying drugs, we observed that the extract of Euodiae Fructus (dried fruit of Tetradium ruticarpum) had the strongest effect on glutamine uptake. Euodiae Fructus extract induced mRNA expression of the amino acid transporter B0 (ATB0), also known as system alanine-serine-cysteine transporter 2 or solute carrier 1A. The active ingredient in Euodiae Fructus was evodiamine, and when Caco-2 cells were incubated with medium containing evodiamine (3 μM) for 24 h, the glutamine uptake and the mRNA expression of ATB0 were significantly induced by 1.6-times and 4.1-times, respectively. The inducible effects of evodiamine were significantly suppressed by each inhibitor of protein tyrosine kinase, protein kinase C, phosphatidylinositol-3 kinase, or epidermal growth factor receptor (EGFR). Evodiamine induced mRNA expression level of EGFR.
CONCLUSIONS: It is incorrect to interpret the spleen-tonifying effect as an effect of enhanced glutamine uptake. Evodiamine, an ingredient of Euodiae Fructus, promotes glutamine absorption in intestinal cells to improve malabsorption syndrome.