Metabolite Profiling and Distribution of Militarine in Rats Using UPLC-Q-TOF-MS/MS

Abstract

Militarine, a natural glucosyloxybenzyl 2-isobutylmalate, isolated from Bletilla striata, was reported with a prominent neuroprotective effect recently. The limited information on the metabolism of militarine impedes comprehension of its biological actions and pharmacology. This study aimed to investigate the metabolite profile and the distribution of militarine in vivo, which help to clarify the action mechanism further. A total of 71 metabolites (57 new metabolites) in rats were identified with a systematic method by ultra-high-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). The proposed metabolic pathways of militarine include hydrolyzation, oxidation, glycosylation, esterification, sulfation, glucuronidation and glycine conjugation. Militarine and its metabolites were distributed extensively in the treated rats. Notably, six metabolites of militarine were identified in cerebrospinal fluid (CSF), which were highly consistent with the metabolites after oral administration of gastrodin in rats. Among the metabolites in CSF, five of them were not reported before. It is the first systematic metabolic study of militarine in vivo, which is very helpful for better comprehension of the functions and the central nervous system (CNS) bioactivities of militarine. The findings will also provide an essential reference for the metabolism of other glucosylated benzyl esters of succinic, malic, tartaric and citric acids.

Discovery and identification of potential anti-melanogenic active constituents of Bletilla striata by zebrafish model and molecular docking

“…The peak areas of all the identified compounds in EFB were approximately two-fold of that in ETB. Militarine was the most abundant compounds in both EFB and ETB, which possessed significant antioxidant, anti-inflammatory and neuroprotection activities, and was chosen as the chemical markers for the quality control of B. striata in Chinese Pharmacopoeia 2020 edition [ 46 ]. The relative peak area of militarine in EFB (38.39 × 10 6 ) was slightly higher than that in ETB (30.48 × 10 6 ).…”

Chemical Constituents of Species in the Genus Pleione (Orchidaceae) and the Implications from Molecular Phylogeny

“…Various chemical compounds, such as phenanthrenes, bibenzyls, glucosyloxybenzyl succinate derivatives and flavonoids, have been found in pseudobulbs of previous studied Pleione species [9] . Dactylorhin A and militarine characterized in our study were demonstrated to have the effects of neuroprotection and cognitive impairment [21–23] . The determination of these two compounds therefore can be used for the quality control of P. bulbocodioides and P. yunnanensis [24] .…”

Discovery and identification of potential anti-melanogenic active constituents of Bletilla striata by zebrafish model and molecular docking

“…The peak areas of all the identi ed compounds in EFB were approximately two-fold of that in ETB. Militarine was the most abundant compounds in both EFB and ETB, which possessed signi cant antioxidant, anti-in ammatory and neuroprotection activities, and was chosen as the chemical markers for the quality control of B. striata in Chinese Pharmacopoeia 2020 edition [40]. The relative peak area of militarine in EFB (38.39×10 6 ) was slightly higher than that in ETB (30.48×10 6 ).…”