Discrepant incidence has been reported regarding the incidence of herb-induced liver injury (HILI). To address the growing worldwide concern of HILI, we evaluated the risk of HILI in a nationwide prospective study. Between April 2013 and January 2016, 1001 inpatients (360 males and 641 females) from 10 tertiary hospitals throughout South Korea were treated with herbal drugs and had their liver enzymes periodically measured. A total of six patients met the criteria for HILI with RUCAM scores ranging from 4 to 7. All these participants were women and developed the hepatocellular type of HILI. One HILI participant met the criteria for Hy’s law; however, none of six cases presented clinical symptoms related to liver injury. This is the first nationwide prospective study that estimated the extent of the incidence of HILI [total: 0.60%, 95% confidence interval (CI) 0.12–1.08; women: 0.95%, 95% CI 0.19–1.68] and described its features in hospitalized participants.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-017-2007-9) contains supplementary material, which is available to authorized users.

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Cytokines produced by immune cells infiltrating pancreatic islets are important mediators of ß-cell destruction in insulin-dependent diabetes mellitus. Cytokines stimulate an inducible form of nitric oxide synthase (iNOS) expression and nitric oxide (NO) production, leading to insulin insufficiency. In the present study, the effects of Artemisia capillaris extract (ACE) on cytokine-induced ß-cell damage were examined. Treatment of RINm5F (RIN) rat insulinoma cells with interleukin-1ß (IL-1ß) and interferon-γ (IFN-γ) induced cell damage. ACE completely protected IL-1ß and IFN-γ-mediated cytotoxicity in a concentration-dependent manner. Incubation with ACE resulted in a significant reduction in IL-1ß and IFN-γ-induced NO production, a finding that correlated well with reduced levels of the iNOS mRNA and protein. The molecular mechanism by which ACE inhibited iNOS gene expression appeared to involve the inhibition of NF-κB activation. The IL-1ß and IFN-γstimulated RIN cells showed increases in NF-κB binding activity and p65 subunit levels in the nucleus, and IκB• degradation in cytosol compared to unstimulated cells. Furthermore, ACE restored the cytokine-induced inhibition of insulin release from isolated islets. These results suggest that ACE protects ß-cells by suppressing NF-κB activation.

The inhibition of aflatoxin B1 (AFB1) metabolism by a water extract of the root of Scutellaria baicalensis and its flavonoids was examined in liver microsomes. AFB1 is known to be metabolized to aflatoxin M1 (AFM1), aflatoxin Q1 (AFQ1), and AFB1-8,9-epoxide (AFBO). The water extract potently inhibited the production of AFM1 by cytochrome P450 (CYP)1A1/2 and slightly reduced AFBO formation by CYP1A1/2, CYP2B1, CYP2C11 and CYP3A1/2 in TCDD-treated rat liver microsomes. IC50 values for AFM1 and AFBO formation were 6.8 and 122.4 microg/ml, respectively. Wogonin showed the highest inhibitory activity towards AFM1 formation among the flavonoids isolated from the extract. On the other hand, the extract had no effects on the formation of AFBO and AFQ1 in human liver microsomes, and on the activities of CYP2B1, CYP2C11 and CYP3A1/2 which were detected by hydroxylation patterns of testosterone. These results demonstrated that the extract of the root of Scutellaria baicalensis has a specific inhibitory effect on CYP1A1/2 among CYP enzymes involved in AFB1 metabolism by rat and human microsomes.

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