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

Abstract

Tianma‐Gouteng granule (TGG), a Chinese herbal formula preparation, is clinically used for the treatment of cardio‐cerebrovascular diseases such as hypertension, cerebral ischaemia, acute ischaemic stroke and Parkinson's disease. Although few reports have been published concerning the absorbed prototype components of TGG, the possible metabolic pathways of TGG in vivo remain largely unclear. In this study, a method using UPLC–Q/TOF MS was established for the detection and identification of the absorbed prototype components and related metabolites in rat plasma and bile after oral administration of TGG at high and normal clinical dosages. A total of 68 components were identified or tentatively identified in plasma and bile samples, including absorbed prototypes and their metabolites. The major absorbed components were gastrodin, isorhynchophylline, rhynchophylline, isocorynoxeine, corynoxeine, geissoschizine methyl ether baicalin, baicalein, wogonoside, wogonin, geniposidic acid, leonurine, 2,3,5,4′‐tetrahydroxystilbene‐2‐O‐β‐d‐glucoside and emodin. The main metabolic pathways of these components involved phase I (isomerization, hydrolysis and reduction) and phase II (glucuronidation and sulfation) reaction, and the phase II biotransformation pathway was predominant. The present study provides rich information on the in vivo absorption and metabolism of TGG, and the results will be helpful for further studies on the pharmacokinetics and pharmacodynamics of TGG.

Metabolite profiling and quantification of phytochemicals of Tianma–Gouteng granule in human and rat urine using ultra high performance liquid chromatography coupled with tandem mass spectrometry

“…BCL and WGS demonstrated bimodal phenomenon in drug‐containing rat urine due to enterohepatic circulation . The cumulative excretion rate for GAS during 0–48 h after dosing was 53%, suggesting that urine may be the primary route for GAS elimination in vivo, which is consistent with our previous result that GAS did not detect rat bile after being absorbed into rat blood . The other eight components, GPS, BCL and BCLE, WGS, RIN and IRN, LEO, and ED, showed the cumulative excretion rates <2%, suggesting that they may be absorbed poorly, or not fully excreted, or still distributed in the tissues in 48 h after dosing.…”

“…Concerning the metabolism of TGG, only several metabolic studies on some individual herbs that were composed in the TGG were reported. In our previous studies, 34 absorbed components and 34 related metabolites were characterized in rat plasma and bile after oral administration of TGG . As we know, the identification of plasma metabolites of TCM formulas is limited by the low content of some marker components in their formulations.…”

Targeting the NLRP3 inflammasome for the treatment of hypertensive target organ damage: Role of natural products and formulations

“…Tianma Gouteng Granule (TGG), a well‐known traditional Chinese medicine (TCM) formula, is listed in the Chinese Pharmacopoeia (Y. N. Jiang et al, 2020). As one of the best‐selling herbal products in China, TGG is mainly used to treat cardiovascular and cerebrovascular diseases including hypertension, headache, dementia, and stroke (Zhang, Duan, et al, 2019). A recent study has shown that TGG (3.125 or 6.25 g/kg/day, oral gavage for 6 weeks) significantly reduced the serum levels of NLRP3, caspase‐1, and ASC in rats and protected frontal brain neurons, as well as improved cognitive performance in SHRs (C. Liu et al, 2021).…”

Pharmacokinetics of B-Ring Unsubstituted Flavones

“…Glucuronidation of flavones by UDP-glucuronosyltransferases (UGTs) represents (together with sulfation) the most important metabolic pathway of these natural molecules when ingested by humans [145,146], because phase II metabolism reactions are more important for these natural substances than phase I reactions [147]. In the case of the main Scutellariae radix flavones (baicalein, wogonin, and oroxylin A, and their glycosides baicalin, wogonoside, and oroxylin A 7- O -β- d -glucuronide), following oral administration of an extract to rats, the C max and AUC0-48h of the glucuronides were at least 10 times higher (and up to 130 times higher) than those of the respective aglycones [32].…”