UGT1A1 and UGT1A9 Are Responsible for Phase II Metabolism of Tectorigenin and Irigenin In Vitro

Abstract

Tectorigenin and irigenin are biologically active isoflavones of Belamcanda chinensis (L.) DC. Previous studies indicated that both compounds could be metabolized in vivo; however, the kinetic parameters of enzymes involved in the metabolization of tectorigenin and irigenin have not been identified. The aim of this study was to investigate UGTs involved in the glucuronidation of tectorigenin and irigenin and determine enzyme kinetic parameters using pooled human liver microsomes (HLMs) and recombinant UGTs. Glucuronides of tectorigenin and irigenin were identified using high-performance liquid chromatography (HPLC) coupled with mass spectrometry and quantified by HPLC using a response factor method. The results showed that tectorigenin and irigenin were modified by glucuronidation in HLMs. One metabolite of tectorigenin (M) and two metabolites of irigenin (M1 and M2) were detected. Chemical inhibition and recombinant enzyme experiments revealed that several enzymes could catalyze tectorigenin and irigenin glucuronidation. Among them, UGT1A1 and UGT1A9 were the primary enzymes for both tectorigenin and irigenin; however, the former mostly produced irigenin glucuronide M1, while the latter mostly produced irigenin glucuronide M2. These findings suggest that UGT1A1 and UGT1A9 were the primary isoforms metabolizing tectorigenin and irigenin in HLMs, which could be involved in drug–drug interactions and, therefore, should be monitored in clinical practice.

Inhibitory effects of Belamcanda extract on inflammatory response and antiviral mechanism in H9N2 Avian influenza virus: insights from in vitro and in vivo studies

“…Moreover, through Western blot analysis, we observed an effective reduction in the expression of immune signaling molecules like TLR3, TRIF, and NF-κB by Belamcanda extract. The modulation of these pathways is crucial for the immune response to viral infections, aligning with findings from other studies that have explored the impact of natural compounds on viral pathogenesis ( Li et al, 2022 ; Patel, 2023 ).…”

“…Belamcanda, a revered herb in traditional Chinese medicine documented in “Shennong's Herbal,” exhibits a rich pharmacological profile. Contemporary studies have elucidated its diverse array of bioactive components, notably tectoridin, tectorigenin, irigenin ( Li et al, 2022 ; Patel, 2023 ), and others, encompassing flavonoids, terpenoids, quinones, phenolic compounds, ketones, and organic acids ( Zhang et al, 2016 ). These constituents have demonstrated potent anti-inflammatory, antiviral, and antioxidant capabilities, modulating the immune system and mitigating inflammation-induced tissue damage ( Woźniak and Matkowski, 2015 ).…”

Potential herb–drug interactions between anti-COVID-19 drugs and traditional Chinese medicine

“…The principal metabolic pathway of iridin was glucuronidation after demethylation and was mediated by UGT1A7, 1A8, 1A9 and 1A10 227 . UGT1A1 and UGT1A9 were the main enzymes for tectorigenin metabolism, which could be involved in DDIs 228 .…”

Tectorigenin: A Review of Its Sources, Pharmacology, Toxicity, and Pharmacokinetics

“…After rat oral administration, tectorigenin can be directly absorbed from the intestinal tract by passive diffusion, and it then undergoes glucuronidation and/or sulfation metabolic pathways by UDP-glucuronosyltransferases (UGT) and sulfotransferases to form corresponding metabolites [171]. UGT1A1 and UGT1A9 were identified as the primary enzymes catalyzing the glucuronidation of tectorigenin in human liver microsomes [172]. Several investigators have conducted HPLC-MS analyses of metabolites in plasma, urine, and bile after oral tectorigenin consumption in rats.…”