The Inhibition of the Components from Shengmai Injection towards UDP-Glucuronosyltransferase

Abstract

The mechanism of shengmai injection- (SMI-) related drug-drug interaction remains unclear. Evaluation of the inhibition potential of SMI's ingredients towards UDP-glucuronosyltransferases (UGTs) activity will provide a new insight to understand SMI-related drug-drug interaction. In vitro incubation system to model UGT reaction was used. Recombinant UGT isoforms-catalyzed 4-methylumbelliferone (4-MU) glucuronidation and UGT1A4-catalyzed trifluoperazine (TFP) glucuronidation reactions were employed to phenotype the inhibition profile of maidong's components towards the activity of UGT isoforms. Different inhibition potential of maidong's components towards various UGT isoforms was observed. Based on the inhibition kinetic investigation results, ophiopogonin D (OD) noncompetitively inhibited UGT1A6 and competitively inhibited UGT1A8, ophiopogonin D′ (OD′) noncompetitively inhibited UGT1A6 and UGT1A10, and ruscorectal (RU) exhibited competitive inhibition towards UGT1A4. The inhibition kinetic parameters were calculated to be 20.6, 40.1, 5.3, 9.0, and 0.02 μM, respectively. In combination with our previous results obtained for the inhibition of UGT isoforms by ginsenosides and wuweizi components, the important SMI ingredients exhibiting strong inhibition towards UGT isoforms were highlighted. All the results obtained in the present study provide a new insight to understand SMI-related drug-drug interaction.

Research Progress in Chinese Herbal Medicines for Treatment of Sepsis: Pharmacological Action, Phytochemistry, and Pharmacokinetics

“…Three-week SMS treatment decreased the maximal velocity of intestinal nifedipine oxidation by 50%, while the CYP3A protein level remained unchanged; among the SMS component herbs, the decoction of Ophiopogonis Radix decreased the intestinal nifedipine oxidation activity [195]. Based on an inhibition kinetic investigation of various UGT isoforms, ophiopogonin D was found to noncompetitively inhibit UGT1A6 (K i , 20.6 µmol/L) and competitively inhibit UGT1A8 (40.1 µmol/L); ophiopogonin D' noncompetitively inhibited UGT1A6 (5.3 µmol/L) and UGT1A10 (9.0 µmol/L); and ruscorectal competitively inhibited UGT1A4 (0.02 µmol/L) [106]. The ginsenoside Rg 1 , ophiopogon D', and schisandrin A are potential inhibitors of sodium taurocholate co-transporting polypeptide (NTCP) and probably interact with NTCP-modulating clinical drugs.…”

Herb–herb pharmacokinetic interaction between Glehniae radix and Ophiopogonis radix in rats using superimposed multiple product ion (SMPI) LC-HR-MS/MS

“…27), and ophiopogonin D noncompetitively inhibited UGT1A6 while competitively inhibiting UGT1A8. 28 Thus, furocoumarins, ophiopogonins and ophiopogonones presumably might be responsible for the herb-herb pharmacokinetic interaction between GR and OR in rats.…”

Methylophiopogonanone A is a naturally occurring broad‐spectrum inhibitor against human UDP‐glucuronosyltransferases: Inhibition behaviours and implication in herb‐drug interactions

“…23 Previous studies have found that MOA inhibits propofol-O-glucuronidation, while its structural analogue ophiopogonin D inhibits both UGT1A6 and UGT1A8. 24,25 These findings suggest that MOA may interact with a panel of hUGTs, but the inhibitory effects of MOA against hUGTs and related molecular mechanism have not been well investigated.…”