Existing Forms of Notoginsenoside R1 in Rats and Their Potential Bioactivities

Notoginsenoside R₁ (NG-R₁) is a primary active constituent in Panax notoginseng, a medicinal and edible plant. It is a saponin with protopanaxatriol (PPT) as its aglycone. UHPLC–ESI-Q–TOF–MS/MS was used to clarify the existing forms of NG-R₁ and their distributions in rats. The nomenclature of the ESI MS fragmentation pathway and ions of PPT was proposed for the first time. Totally, 105 metabolites with 89 new metabolites were identified. In terms of their LC–MS data, 7 were accurately identified by comparison with reference compounds, and 41 were clearly identified. Polyhydroxylation, pentosylation, acetylation, glucuronidation, and amino acid conjugation are new metabolic reactions of NG-R₁. In total, 69, 48, 47, 43, 24, 15, and 7 metabolites were detected in the large intestine, stomach, small intestine, liver, lungs, kidneys, and heart, respectively. Then, 48 metabolites were predicted to be effective by PharmMapper, and their mechanisms of action on three diseases were predicted by network pharmacology. Finally, the antitumor effects on cell proliferation and the anti-inflammatory effects of the eight compounds were verified by cellular experiments. These results help further elucidate the in vivo existing forms of dammarane-type triterpenoids and form the basis for discovering their effective forms in the future.