Recently, the team of Tan Renxiang of Nanjing University published a research paper in the National Science Review (NSR). They proposed, designed and verified the concept of "reaction rheology" in vivo, and established a method based on this to interpret gastric acid. The specific steps and determinants of the conversion of I3C into two antitumor molecules (DIM and LTr1) by intestinal bacteria and the mechanisms by which mammals synthesize endogenous I3C and DIM.
Among these two anti-cancer molecules, DIM is the main component of a series of marketed health products, and is also a new anti-cancer drug candidate entering clinical trials. Unexpectedly, LTr1 showed more anticancer effects than DIM in multiple tumor cell lines and mouse models.
The team proposed that some molecules (especially active intermediates) in the metabolic flow of substances in organisms should have the possibility of "slides". Based on this concept, the method of "reaction flux derailing" (RFD) was established, that is, using artificially added and labeled substrate analogs to "reverse" the original reaction pathway and capture intermediates , thereby interpreting the pathways and driving mechanisms of multi-step transformation.
Using this method, the researchers revealed that I3C is first converted to 3,3'-diindolylmethane (DIM) and then to 2-(indol-3-ylmethyl) in the digestive tract using labeled I3C analogs. )-3,3'-diindolylmethane (LTr1) pathway: In the acidic upper gastrointestinal tract, I3C can generate DIM through deformaldehyde (major) and carbon dioxide release (minor) pathways, which are then combined with 3- Methylene indole (3MI) undergoes Michael addition reaction to form LTr1.
In the gastrointestinal tract, I3C released from cruciferous vegetables can be converted into DIM and LTr1. In the large intestine, formaldehyde can couple with indole to generate endogenous I3C and DIM.
The team also found that in the large intestine, endogenous indole (a breakdown product of tryptophan) can couple with formaldehyde (a common metabolite of methanol, creatine, and folic acid) to produce endogenous I3C and DIM, and intestinal bacteria Groups played an important role in this process.
In summary, this work found that LTr1 may have medicinal value; proposed and verified the concept of reactive rheological tract in vivo; established relevant experimental methods, thereby revealing the endogenous synthetic pathway of I3C family molecules and the gastrointestinal The transformation process has led to a new understanding of the importance of cruciferous vegetables (rich in I3C).
