{"title":"Effect of daikenchuto (TU-100) on carcinogenesis in non-alcoholic steatohepatitis.","authors":"Shinichiro Yamada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saito, Mayuko Shimizu, Koichi Tsuneyama, Mitsue Nishiyama, Shiori Ishizawa, Mitsuo Shimada","doi":"10.2152/jmi.70.66","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Non-alcoholic steatohepatitis (NASH) is associated with a higher risk of hepatocellular carcinoma (HCC), and the importance of the gut?liver axis has been recognized in NASH-associated HCC. We investigated the effect of TU-100 on the intestinal microbiome and hepatocarcinogenesis in a NASH model.</p><p><strong>Methods: </strong>Seven-week-old Tsumura Suzuki obese diabetes mice, a model that shows the spontaneous onset of NASH and HCC, were used. They were divided into a TU-100 treated group and a control group. Mice were sacrificed at 24 and 48 weeks to evaluate hepatic steatosis, fibrosis, carcinogenesis, cytokine expression, and microbiome abundance.</p><p><strong>Results: </strong>At 24 weeks, the TU-100 group showed significantly lower expression of IL6, IL1B, and ACTA2 mRNA in the liver (P?<?0.05). At 48 weeks, the TU-100 group showed significantly lower levels of serum alanine aminotransferase. The TU-100 group also showed a lower rate of NASH than the control group (28% vs 72%?;?P?=?0.1). Tumor diameter was significantly smaller in the TU-100 group compared with that in the control group (P?<?0.05). Regarding the intestinal microbiome, the genera Blautia and Ruminococcus were increased in the TU-100 group (P?<?0.05), whereas Dorea and Erysipelotrichaceae were decreased in the TU-100 group (P?<?0.05).</p><p><strong>Conclusions: </strong>TU-100 regulates the intestinal microbiome and may suppress subsequent hepatocarcinogenesis in the NASH model. J. Med. Invest. 70 : 66-73, February, 2023.</p>","PeriodicalId":46910,"journal":{"name":"JOURNAL OF MEDICAL INVESTIGATION","volume":"70 1.2","pages":"66-73"},"PeriodicalIF":0.7000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JOURNAL OF MEDICAL INVESTIGATION","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2152/jmi.70.66","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Non-alcoholic steatohepatitis (NASH) is associated with a higher risk of hepatocellular carcinoma (HCC), and the importance of the gut?liver axis has been recognized in NASH-associated HCC. We investigated the effect of TU-100 on the intestinal microbiome and hepatocarcinogenesis in a NASH model.
Methods: Seven-week-old Tsumura Suzuki obese diabetes mice, a model that shows the spontaneous onset of NASH and HCC, were used. They were divided into a TU-100 treated group and a control group. Mice were sacrificed at 24 and 48 weeks to evaluate hepatic steatosis, fibrosis, carcinogenesis, cytokine expression, and microbiome abundance.
Results: At 24 weeks, the TU-100 group showed significantly lower expression of IL6, IL1B, and ACTA2 mRNA in the liver (P?0.05). At 48 weeks, the TU-100 group showed significantly lower levels of serum alanine aminotransferase. The TU-100 group also showed a lower rate of NASH than the control group (28% vs 72%?;?P?=?0.1). Tumor diameter was significantly smaller in the TU-100 group compared with that in the control group (P?0.05). Regarding the intestinal microbiome, the genera Blautia and Ruminococcus were increased in the TU-100 group (P?0.05), whereas Dorea and Erysipelotrichaceae were decreased in the TU-100 group (P?0.05).
Conclusions: TU-100 regulates the intestinal microbiome and may suppress subsequent hepatocarcinogenesis in the NASH model. J. Med. Invest. 70 : 66-73, February, 2023.