Abstract
IntroductionIn patients with obstructive jaundice, biliary drainage sometimes fails to result in improvement. A pharmaceutical-grade choleretic herbal medicine, Inchinkoto (ICKT), has been proposed to exert auxiliary effects on biliary drainage; however, its effects are variable among patients.ObjectivesThe aim of this study is to explore serum biomarkers that are associated with pharmaceutical efficacy of ICKT.MethodsObstructive jaundice patients who underwent external biliary decompression were enrolled (n = 37). ICKT was given orally 3 times a day at daily dose of 7.5 g. Serum and bile samples were collected before, 3 h after, and 24 h after ICKT administration. The concentrations of total bilirubin, direct bilirubin, and total bile acid in bile specimens were measured. Metabolites in serum samples were comprehensively profiled using LC–MS/MS and GC–MS/MS. Pharmacokinetic analysis of major ICKT components was also performed.ResultsICKT administration significantly decreased serum ALT and increased bile volume after 24 h. The serum concentrations of ICKT components were not well correlated with the efficacy of ICKT. However, the ratio of 2-hydroxyisobutyric acid to arachidonic acid and the ratio of glutaric acid to niacinamide, exhibited good performance as biomarkers for the efficacy of ICKT on bile flow and ALT, respectively. Additionally, comprehensive correlation analysis revealed that serum glucuronic acid was highly correlated with serum total bilirubin, suggesting that this metabolite may be deeply involved in the pathogenesis of jaundice.ConclusionsThe present study indicates that ICKT is efficacious and provides candidates for predicting ICKT efficacy. Further validation studies are warranted.
Highlights
In patients with obstructive jaundice, biliary drainage sometimes fails to result in improvement
Despite improvements in surgical techniques and refinements in pre- and postoperative care, hepatectomy in patients with obstructive jaundice is still associated with high morbidity and mortality rates (Yokoyama et al 2016)
The elucidation of mechanisms and cellular components involved in such impairment, will facilitate the development of a novel efficient therapy for hepatectomy in obstructive jaundice patients
Summary
In patients with obstructive jaundice, biliary drainage sometimes fails to result in improvement. A pharmaceutical-grade choleretic herbal medicine, Inchinkoto (ICKT), has been proposed to exert auxiliary effects on biliary drainage; its effects are variable among patients. Serum and bile samples were collected before, 3 h after, and 24 h after ICKT administration. Despite improvements in surgical techniques and refinements in pre- and postoperative care, hepatectomy in patients with obstructive jaundice is still associated with high morbidity and mortality rates (Yokoyama et al 2016). The elucidation of mechanisms and cellular components involved in such impairment, will facilitate the development of a novel efficient therapy for hepatectomy in obstructive jaundice patients. Inchinkoto (ICKT) is a pharmaceutical-grade Japanese traditional herbal medicine having potent anti-apoptotic (Yamamoto et al 2000) and choleretic (Shoda et al 2004) effects. The drug has been reported to exert prominent beneficial effects in severe hepatitis, biliary atresia, and primary
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