Metabolic profiling of corylin in vivo and in vitro

Abstract

Corylin, an phenolic compound from Psoralea corylifolia, has been reported with various pharmacological properties but has poor bioavailability due to massive metabolism. In this study, twelve metabolites of corylin mainly involving in oxidation, hydration, glucuronidation and sulfation were detected in mice. Furthermore, the oxidation and hydration of corylin (M4) in human liver microsomes (HLM) and human intestine microsomes (HIM) were both efficient with high CL (intrinsic clearance) values of 24.29 and 42.85 μL/min/mg, respectively. CYP1A1, 1B1 and 2C19 contributed most for M4 with the CL values of 26.63, 33.09 and 132.41 μL/min/mg, respectively. Besides, M4 was strongly correlated with phenacetin-N-deacetylation (r = 0.885, p = 0.0001) and tolbutamide-4-oxidation (r = 0.727, p = 0.001) in twelve individual HLMs, respectively. In addition, corylin was efficiently glucuronidated (M7) in HLM (125.33 μL/min/mg) and in HIM (108.74 μL/min/mg). UGT1A1 contributed the most for M7 with the CL value of 122.32 μL/min/mg. Meanwhile, M7 was significantly correlated with β-estradiol-3-O-glucuronidation (r = 0.742, p = 0.006) in twelve individual HLMs. Moreover, the metabolism of corylin showed marked species differences. Taken together, corylin was subjected to massive first-pass metabolism in liver and intestine, while CYP1A1, 1B1, 2C19 and UGT1A1 were the main contributors. Finally, the proposed metabolic pathway of corylin involed CYP and UGT isoforms were summarized, which could help to understand the metabolic fate of corylin in vivo.

Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3 inflammasome in microglia

“…Flavonoids are abundantly present in plant, fruits and vegetables, and have been indicated to exert several types of anti-inflammatory effects [ 21 , 22 ]. Psoralea corylifolia L. has been widely used as a kidney tonifying herbal medicine for treating many diseases such as osteoporosis [ 23 ], leucoderma and inflammatory diseases of the skin in Asian countries [ 24 ]. Corylin is a main flavonoid that is isolated from Psoralea corylifolia L. Previous studies indicated that corylin has various pharmaceutical effects, including anti-cancer [ 25 , 26 ] and anti-inflammatory properties [ 27 , 28 ].…”

An investigation of the metabolic activity, isozyme contribution, species differences and potential drug–drug interactions of PI-103, and the identification of efflux transporters for PI-103-O-glucuronide in HeLa1A9 cells

“…38 In addition, UGT1A1 polymorphisms (1A1*6, 1A1*28) should be investigated to reduce or avoid the dose-limiting toxicities of chemotherapy drugs. 23 In contrast, two-fold higher glucuronidation toward several carcinogenic environmental contaminants was observed in UGT1A9*22/*22 livers compared with UGT1A9*1/*1 and UGT1A9*1/*22 livers. 39 UGT1A10 codon 139 (Glu > Lys) polymorphism exhibited higher catalytic activities against polycyclic aromatic hydrocarbons, and this genotype is most likely an important determinant in the risk for tobaccorelated cancers.…”

“…Notably, CYP1A1 and UGT1A10 in extrahepatic tissues (mainly the intestine) as well as CYP1A2 and UGT1A1 mainly in the liver all, accounted for the signicant contributions to the metabolism of PI-103. 23 Apart from the metabolism in the liver and the intestine, the lung and kidney may also participate in its metabolic fate because CYP1A1 is also present in these tissues, and UGT1A9 is mainly expressed in the kidney. 24 Therefore, the metabolic roles of the lung and kidney should not be underestimated.…”

Potential metabolism determinants and drug–drug interactions of a natural flavanone bavachinin

“…Phase I metabolism and glucuronidation are essentially incubation assays performed routinely in our laboratory. 11,25,30 The incubation system for phase I metabolism included contained Tris-HCl buffer (50 mM, pH ¼ 7.4), MgCl 2 (5 mM), substrates (bavachinin, or specic substrate for each CYP enzyme), enzyme materials (HLM, HIM, animal liver microsomes, or CYP enzymes). The reaction was initiated by addition of NADPH (1 mM) aer a pre-incubation at 37 C for 5 min.…”

“…Of these, metabolism (phase I and II reactions) participated more in determining drug exposure at target sites (pharmacodynamics) and toxicity proles (detoxication). 10,11 Isomerization, glucuronidation, sulfonation, hydroxylation, and reduction were considered as the main metabolic pathways in rat samples and rat liver microsomes. 12,13 Poor bioavailability (5.27-36.39%) 13,14 and low plasma concentration (2.13-908.8 ng mL À1 ) [13][14][15][16][17][18] were mainly attributed to massive metabolism aer oral administration of bavachinin or bavachinin-containing extracts.…”