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Forsythin extracted from Forsythiae Fructus is widely used to treat fever caused by the common cold or influenza in China, Japan and Korea. The present study aimed to analyze the pharmacokinetics, metabolism and excretion routes of forsythin in humans and determine the major enzymes and transporters involved in these processes. After a single oral administration, forsythin underwent extensive metabolism via hydrolysis and further sulfation. In total, 3 of the 13 metabolites were confirmed by comparison to reference substances, i.e., aglycone M1, M1 sulfate (M2), and M1 glucuronide (M7). Hydrolysis was the initial and main metabolic pathway of the parent compound, followed by extensive sulfation to form M2 and a reduced level of glucuronidation to form M7. In addition, the plasma exposure of M2 and M7 were 86- and 4.2-fold higher than that of forsythin. Within 48 h, ~75.1% of the administered dose was found in urine, with M2 accounting for 71.6%. Further phenotyping experiments revealed that sulfotransferase 1A1 and UDP-glucuronosyltransferase 1A8 were the most active hepatic enzymes involved in the formation of M2 and M7, respectively. The in vitro kinetic study provided direct evidence that M1 showed a preference for sulfation. Sulfated conjugate M2 was identified as a specific substrate of organic anion transporter 3, which could facilitate the renal excretion of M2. Altogether, our study demonstrated that sulfation dominated the metabolism and pharmacokinetics of forsythin, while the sulfate conjugate was excreted mainly in the urine.

The Cr-/Si-modified NiAlHf coatings were produced on single-crystal (SC) superalloy N5 by electron beam physical vapor deposition (EB-PVD). The cyclic oxidation behavior of the coatings at 1100 °C was investigated. The microstructures of the oxide scales grown on the coatings were characterized by scanning electron microscope (SEM) with energy-dispersive X-ray spectrum (EDX), electron probe micro-analyzer (EPMA) and X-ray diffraction (XRD). The effects of Cr and Si on the cyclic oxidation behavior of the NiAlHf coatings were discussed. The addition of Si to the NiAlHfCr coating not only reduces the oxidation rate but also enhances the oxide scale adherence. Owing to the addition of Si in the coating, the segregation of Cr and Mo beneath the oxide scale is effectively avoided, which contributes to enhancing oxide scale adherence.