Predicting Inchinkoto efficacy, in patients with obstructive jaundice associated with malignant tumors, through pharmacomicrobiomics.

Abstract

Inchinkoto (ICKT) is a popular choleretic and hepatoprotective herbal medicine that is widely used in Japan. Geniposide, a major ingredient of ICKT, is metabolized to genipin by gut microbiota, which exerts a choleretic effect. This study investigates the relationship between stool genipin-producing activity and diversity of the clinical effect of ICKT in patients with malignant obstructive jaundice. Fifty-two patients with malignant obstructive jaundice who underwent external biliary drainage were included. ICKT was administered as three packets per day (7.5 g/day) for three days and 2.5 g on the morning of the fourth day. Stool samples were collected before ICKT administration and bile flow was monitored on a daily basis. The microbiome, genipin-producing activity, and organic acids in stools were analyzed. The Shannon-Wiener (SW) index was calculated to evaluate gut microbiome diversity. The stool genipin-producing activity showed a significant positive correlation with the SW index. Stool genipin-producing activity positively correlated with the order Clostridia (obligate anaerobes), but negatively correlated with the order Lactobacillales (facultative anaerobes). Moreover, stool genipin-producing activity was positively correlated to the concentration valeric acid, but negatively correlated to the concentration of lactic acid and succinic acid. The change of bile flow at 2 and 3 days after ICKT administration showed significant positive correlation with genipin-producing activity (correlation coefficient, 0.40 and 0.29, respectively, P < 0.05). An analysis of stool profile, including stool genipin-producing activity, may predict the efficacy of ICKT. Modification of the microbiome may be a target to enhance the therapeutic effect of ICKT.

• Authors: Hiromasa Yamashita, Mitsue Nishiyama, Katsuya Ohbuchi, Hitomi Kanno, Kazuaki Tsuchiya, Junpei Yamaguchi, Takashi Mizuno, Tomoki Ebata, Masato Nagino, Yukihiro Yokoyama
• Journal: Pharmacological research (Pharmacol Res) Vol. 175 Pg. 105981 (01 2022) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 34798264 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Carboxylic Acids
• Cholagogues and Choleretics
• Drugs, Chinese Herbal
• Iridoids
• inchinko-to
• genipin

Topics

• Adult
• Aged
• Aged, 80 and over
• Bile (chemistry)
• Carboxylic Acids (metabolism)
• Cholagogues and Choleretics (therapeutic use)
• Clostridium (genetics, metabolism)
• Drugs, Chinese Herbal (therapeutic use)
• Feces (chemistry)
• Female
• Gastrointestinal Microbiome (drug effects, genetics)
• Humans
• Iridoids (metabolism)
• Jaundice, Obstructive (drug therapy, microbiology)
• Lactobacillales (genetics, metabolism)
• Male
• Middle Aged
• Neoplasms (drug therapy, microbiology)
• Treatment Outcome