Analysis of the metabolic profile of parishin by ultra‐performance liquid chromatography/quadrupole‐time of flight mass spectrometry

Abstract

Parishin is a dominant active ingredient originating from Gastrodia elata Blume, and has good neuroprotective effects against brain disorders. In the present study, the metabolic profile of parishin by in vitro and in vivo experiments was investigated using ultra-high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UHPLC/Q-TOF MS) combined with an automated MS(E) technique. By comparison with reference compounds, accurate mass measurement, the characteristic fragmentation patterns of the parent drug parishin and gastrodin and relevant bio-transformation knowledge, 14 metabolites (seven hydrolyzates and seven derivatives of gastrodin) were detected and identified in rat plasma and urine after intragastric administration of parishin, including processes of hydrolyzation, oxidation, sulfation and glucuronidation. According to the proposed metabolic pathways of parishin, in vitro hydrolytic experiments and metabolic study of gastrodin in rat plasma, it can be inferred that parishin mainly functions as a prodrug and undergoes hydrolysis before being absorbed into the blood. The hydrolyzate, mainly gastrodin, was involved in further metabolism, which was responsible for pharmacological activities of parishin. In conclusion, this work provides valuable information on parishin metabolism using a rapid and reliable UHPLC/Q-TOF MS method, which could be widely used for the metabolic investigation of natural product.

Pharmacokinetic study of Gastrodia elata in rats

“…In recent years, parishins, a kind of components identified and isolated from G. elata, were formed by the substitution of a citric acid with one to three moieties of gastrodin. Our previous studies have determined that PA acted as prodrug metabolizing to GAS in vivo [19]. Furthermore, it exerted efficient anti-dementia effect by itself.…”

“…In addition, the characteristic fragment ions at m/z 169,143,111 of parishin G/E were also observed in MS 2 spectra of D1 and D2. Therefore, D1 and D2 were tentatively identified as The molecular weight and molecular formula were 742.2320 and C 33 H 42 O 19 , respectively, which was 14.0137 Da (-CH 2 ) higher than that of parishin B/C. Similarly, D3 was tentatively identified as methyl parishin B/C.…”

“…Parishin, a kind of conjugate compounds of citric acid and GAS, has been reported to exert pharmacological effects [15][16][17]. Moreover, they can transform to various active compounds in vivo, such as GAS, HBA and parishin C [18,19]. Therefore, the pharmacological effects of G. elata explained by GAS alone were not abundant.…”

“…Then, GAS underwent abundant phase II reactions by conjugation with endogenous molecule (glucuronic acid, sulfuric acid, etc.) to form conjugated metabolites and excreted via urine [19]. It is worth mentioning that the elimination of GAS was quite rapid and the elimination half-life (t 1/2 ) was almost within 1 h [11,22].…”

Identification of the absorbed components and their metabolites of Tianma‐Gouteng granule in rat plasma and bile using ultra‐high‐performance liquid chromatography combined with quadrupole time‐of‐flight mass spectrometry

“…It is necessary to provide an integrated absorbed and metabolic profile for a scientific understanding of the therapeutic effects as well as theories about TCM formulations. At present, researchers are still focusing on the individual chemical composition and herbs of TGG in vivo (Du et al, ; Huang et al, ; Tang et al, ; Zhao, Qi, Chen, Sun, & Yuan, ). However, to the best of our knowledge, based on overall and systematic experiments, there have been few reports on the absorbed prototype components and the metabolites of TGG.…”