Itaru Naitoh and Takahiro Nakazawa. Gut and Liver -0001;0:. https://doi.org/10.5009/gnl210116

Shimotsu-To, which consists of four herbal extracts, has been used clinically for improving abnormal blood coagulation, fibrinolysis, atherosclerosis and chronic inflammation in Japan and China. We have investigated the pharmacological relationship between the effects and chemical components of Shimotsu-To after oral administration to rats. The urinary constituents were separated and identified by three dimensional (3D-) HPLC equipped with a photodiode array detector as a new tool and the chemical structures were determined by spectroscopic methods to be trans-ferulic acid-3-O-sulfate (1), vanillic acid (2), m-hydroxyphenylpropionic acid (3), trans-ferulic acid (4) and cis-ferulic acid (5). Of these compounds, 2–5 strongly inhibited platelet aggregation induced by ADP and arachidonic acid. Compound 1, the sulfate conjugate of 4, did not show any inhibitory effect, which suggested that the inhibitory effect on platelet aggregation was inactivated by sulfate conjugation. These results indicated that compounds 2–5 partly contributed to the anti-Oketsu effect of Shimotsu-To through the inhibition of platelet aggregation.

Background: The diagnostic performance of clinical diagnostic criteria for IgG4‐related sclerosing cholangitis 2020 (IgG4‐SC2020) has not been fully validated since its proposal as a revision of the 2012 criteria (IgG4‐SC2012). Methods: We conducted a multicenter validation study to evaluate the diagnostic performance of IgG4‐SC2020 using clinical data collected from 1034 patients with IgG4‐SC and 447 patients with mimickers, including 143 with pancreatic cancer, 157 with primary sclerosing cholangitis, and 147 with cholangiocarcinoma in Japan. Results: The sensitivity of IgG4‐SC2020 was significantly higher than that of IgG4‐SC2012 (99.0% vs. 89.1%; p < 0.001). The specificities of both IgG4‐SC2020 and IgG4‐SC2012 were 100% for pancreatic cancer and cholangiocarcinoma. For primary sclerosing cholangitis, the specificities of IgG4‐SC2020 and IgG4‐SC2012 were 97.5% and 100%, respectively, with no significant difference ( p = 0.123). A total of 113 patients who could not be diagnosed according to the IgG4‐SC2012 were successfully diagnosed using IgG4‐SC2020. These diagnostic improvements were attributed to the inclusion of MRCP findings ( n = 97), the absence of neoplastic cells on histology ( n = 15), and the presence of IgG4‐related kidney lesions ( n = 1). Conclusions: This Japanese multicenter validation study demonstrated that the diagnostic performance of IgG4‐SC2020 was superior to that of IgG4‐SC2012. Trial Registration: UMIN Clinical Trials Registry (UMIN‐CTR), UMIN000052984.