Cryptotanshinone and dihydrotanshinone I exhibit strong inhibition towards human liver microsome (HLM)-catalyzed propofol glucuronidation

Cong, Ming; Hu, Cui-Min; Cao, Yun‐Feng; Fang, Zhong‐Ze; Tang, Shu-Hong; Wang, J.; Luo, Jun

doi:10.1016/j.fitote.2013.01.002

Cited by 8 publications

(5 citation statements)

References 26 publications

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“…For most flavonoids methoxylated compounds, metabolizing enzymes in phases I and II can take part in their metabolism in vivo. 27,28) In this study, the species-specific differences in the NADPH-and UDPGA-dependent metabolism of mulberrin were determined. Four major mulberrin metabolites (M 1 -M 4 ) in phase I, and two (M 5 , M 6 ) in phase II were observed.…”

Section: Discussionmentioning

confidence: 99%

Species Difference in the Metabolism of Mulberrin <i>in Vitro</i> and Its Inhibitory Effect on Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes

Guo

et al. 2022

CHEMICAL & PHARMACEUTICAL BULLETIN

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This study aimed to evaluate the interspecies difference in metabolism of mulberrin and examine the interaction between mulberrin and CYP enzymes or recombinant human uridine 5′-diphosphate (UDP)glucuronosyltransferase (UGT) enzymes. Liver microsomes from human (HLMs), Beagle dog (DLMs), minipig (PLMs), monkey (MLMs), rabbit (RLMs), rat (RAMs), and mouse (MIMs) were used to investigate metabolic diversity among different species. Additionally, recombinant human supersomes were used to confirm that metabolic enzymes are involved in the biotransformation of mulberrin. We also evaluated the influence of mulberrin on protein expression by Western blot analysis. Mulberrin metabolism showed significant interspecies differences. We found four and two metabolites in phase I and II reaction systems, respectively. In phase I metabolism profiles of mulberrin for HLMs, PLMs and MLMs conformed to the classic Michaelis-Menten kinetics, RAMs and MIMs followed biphasic kinetics; phase II reaction of mulberrin in HLMs, DLMs, PLMs, MLMs, RLMs, RAMs and MIMs followed biphasic kinetics. UGT1A1 were the major CYP isoforms responsible for the metabolism of mulberrin. Mulberrin showed potent inhibitory effects against CYP3A4, CYP2C9, CYP2E1, UGT1A1, UGT1A3 and UGT2B7 with IC 50 values of 54.21, 9.93, 39.12, 3.84, 2.01, 16.36 µM, respectively. According to Western blot analysis, mulberrin can upregulate the protein expression of CYP2C19, and downregulate the expression levels of CYP3A5 and CYP2C9 in HepG2 cells as concentration increased. The interspecies comparisons can help find other species with metabolic pathways similar to those in humans for future in vivo studies.

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Section: Discussionmentioning

confidence: 99%

Species Difference in the Metabolism of Mulberrin <i>in Vitro</i> and Its Inhibitory Effect on Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes

Guo

et al. 2022

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Incubation and analytical conditions have been described previously [24]. The mixture (200 μ L total volume) contained recombinant UGTs (final concentrations: 0.125, 0.05, 0.05, 0.025, 0.05, and 0.25 mg/mL for UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A10, and UGT2B4, resp.…”

Section: Methodsmentioning

confidence: 99%

“…If UGTs were strongly inhibited, half inhibition concentration (IC50) values were determined using various concentrations of bavachalcone (100, 80, 60, 40, 20, 10, 5, 1, and 0 μ M for UGT1A1 and 50, 20, 10, 6, 5, 3, 1, 0.5, and 0 μ M for UGT1A7) with previously described methods [24]. Dixon and Lineweaver-Burk plots were adapted to determine the inhibition type, and the second plot with the slopes from the Lineweaver-Burk plot versus the concentrations of components was utilized to calculate the Ki value.…”

Section: Methodsmentioning

confidence: 99%

Comparison of the Inhibitory Potential of Bavachalcone and Corylin against UDP‐Glucuronosyltransferases

Shan

Yang

Zhang

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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Bavachalcone and corylin are two major bioactive compounds isolated from Psoralea corylifolia L., which has been widely used as traditional Chinese medicine for many years. As two antibiotic or anticancer drugs, bavachalcone and corylin are used in combination with other drugs; thus it is necessary to evaluate potential pharmacokinetic herb-drug interactions (HDI) of the two bioactive compounds. The aim of the present study was to compare the effects of liver UDP-glucuronosyltransferase (UGT) 1A1, UGT1A3, UGT1A7, UGT1A8, UGT 1A10, and UGT2B4 inhibited by bavachalcone and corylin. 4-Methylumbelliferone (4-MU) was used as a nonspecific “probe” substrate. Bavachalcone had stronger inhibition on UGT1A1 and UGT1A7 than corylin which did not inhibit UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A10, and UGT2B4. Data fitting using Dixon and Lineweaver-Burk plots demonstrated the noncompetitive inhibition of bavachalcone against UGT1A1 and UGT1A7-mediated 4-MU glucuronidation reaction. The values of inhibition kinetic parameters (Ki) were 5.41 μM and 4.51 μM for UGT1A1 and UGT1A7, respectively. The results of present study suggested that there was a possibility of UGT1A1 and UGT1A7 inhibition-based herb-drug interaction associated with bavachalcone and provided the basis for further in vivo studies to investigate the HDI potential between bavachalcone and UGT substrates.

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“…For instance, with an in vitro human liver microsome incubation system was demonstrated that cryptotanshinone and dihydrotanshinone I, which are isolated from the roots of Salvia miltiorrhiza Bunge, exhibited UGT1A9 dose‐dependent inhibition (Cong et al, 2013). This same mechanism, mediated by UGTs inhibition, is also proposed for pharmacokinetic interactions of propofol with: isobavalchalcone (Guo et al, 2014); methylophiopogonanone A, isolated from Ophiopogon japonicus (L.f.) Ker Gawl.…”

Section: Herb Interactions With Drugs Acting On the Cns And Pnsmentioning

confidence: 99%

Herb‐drug interactions: A short review on central and peripheral nervous system drugs

Bernardo,

Valentão

2024

Phytotherapy Research

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Herbal medicines are widely perceived as natural and safe remedies. However, their concomitant use with prescribed drugs is a common practice, often undertaken without full awareness of the potential risks and frequently without medical supervision. This practice introduces a tangible risk of herb‐drug interactions, which can manifest as a spectrum of consequences, ranging from acute, self‐limited reactions to unpredictable and potentially lethal scenarios. This review offers a comprehensive overview of herb‐drug interactions, with a specific focus on medications targeting the Central and Peripheral Nervous Systems. Our work draws upon a broad range of evidence, encompassing preclinical data, animal studies, and clinical case reports. We delve into the intricate pharmacodynamics and pharmacokinetics underpinning each interaction, elucidating the mechanisms through which these interactions occur. One pressing issue that emerges from this analysis is the need for updated guidelines and sustained pharmacovigilance efforts. The topic of herb‐drug interactions often escapes the attention of both consumers and healthcare professionals. To ensure patient safety and informed decision‐making, it is imperative that we address this knowledge gap and establish a framework for continued monitoring and education. In conclusion, the use of herbal remedies alongside conventional medications is a practice replete with potential hazards. This review not only underscores the real and significant risks associated with herb‐drug interactions but also underscores the necessity for greater awareness, research, and vigilant oversight in this often‐overlooked domain of healthcare.

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Cryptotanshinone and dihydrotanshinone I exhibit strong inhibition towards human liver microsome (HLM)-catalyzed propofol glucuronidation

Cited by 8 publications

References 26 publications

Species Difference in the Metabolism of Mulberrin <i>in Vitro</i> and Its Inhibitory Effect on Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes

Species Difference in the Metabolism of Mulberrin <i>in Vitro</i> and Its Inhibitory Effect on Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes

Comparison of the Inhibitory Potential of Bavachalcone and Corylin against UDP‐Glucuronosyltransferases

Herb‐drug interactions: A short review on central and peripheral nervous system drugs

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