TY - JOUR
T1 - A phase I trial of berberine in Chinese with ulcerative colitis
AU - Xu, Li
AU - Zhang, Yujie
AU - Xue, Xianmin
AU - Liu, Jie
AU - Li, Zeng Shan
AU - Yang, Guang Yu
AU - Song, Ying
AU - Pan, Yan
AU - Ma, Yueyun
AU - Hu, Sijun
AU - Wen, Aidong
AU - Jia, Yanyan
AU - Rodriguez, Luz Maria
AU - Tull, Mary Beth
AU - Benante, Kelly
AU - Khan, Seema A.
AU - Cao, Ying
AU - Jovanovic, Borko
AU - Richmond, Ellen
AU - Umar, Asad
AU - Bergan, Raymond
AU - Wu, Kaichun
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2020
Y1 - 2020
N2 - The Chinese natural product, berberine, has biological properties that support its potential efficacy as a colon cancer prevention agent. Its longstanding use in China to treat gastrointestinal tract and rheumatologic disorders is generally regarded as safe, supporting initial investigations in an at-risk population, such as individuals with ulcerative colitis. However, the safety of berberine in this population is not established. Individuals living in China with biopsy-proven ulcerative colitis, ≼grade 2 dysplasia, and with a ulcerative colitis disease activity index (UCDAI) score ≼1 on mesalamine, were randomized 3:1 in a double-blind phase I trial to berberine 900 mg/day or placebo for 3 months, with the primary objective of assessing safety. Blood samples and biopsies of the colorectum, from prespecified locations, were collected prior to and following therapy. Secondary endpoints included changes in UCDAI score, and in tissue and plasma markers of inflammation. Of toxicities at least possibly related, one episode of grade 3 elevation in transaminases and one episode of grade 1 nausea were observed among 12 individuals on berberine, and none were observed among 4 on placebo. The mean plasma berberine concentration was 3.5 nmol/L after berberine treatment, significantly higher than 0.5 nmol/L with placebo. Berberine significantly decreased the Geboes grade in colonic tissue, but had a nonsignificant effect on other tissue or blood biomarkers related to cell growth and inflammation. The combination of berberine and mesalamine is well tolerated in Chinese with ulcerative colitis and may enhance mesalamine's anti-inflammatory effects in colonic tissue.
AB - The Chinese natural product, berberine, has biological properties that support its potential efficacy as a colon cancer prevention agent. Its longstanding use in China to treat gastrointestinal tract and rheumatologic disorders is generally regarded as safe, supporting initial investigations in an at-risk population, such as individuals with ulcerative colitis. However, the safety of berberine in this population is not established. Individuals living in China with biopsy-proven ulcerative colitis, ≼grade 2 dysplasia, and with a ulcerative colitis disease activity index (UCDAI) score ≼1 on mesalamine, were randomized 3:1 in a double-blind phase I trial to berberine 900 mg/day or placebo for 3 months, with the primary objective of assessing safety. Blood samples and biopsies of the colorectum, from prespecified locations, were collected prior to and following therapy. Secondary endpoints included changes in UCDAI score, and in tissue and plasma markers of inflammation. Of toxicities at least possibly related, one episode of grade 3 elevation in transaminases and one episode of grade 1 nausea were observed among 12 individuals on berberine, and none were observed among 4 on placebo. The mean plasma berberine concentration was 3.5 nmol/L after berberine treatment, significantly higher than 0.5 nmol/L with placebo. Berberine significantly decreased the Geboes grade in colonic tissue, but had a nonsignificant effect on other tissue or blood biomarkers related to cell growth and inflammation. The combination of berberine and mesalamine is well tolerated in Chinese with ulcerative colitis and may enhance mesalamine's anti-inflammatory effects in colonic tissue.
UR - http://www.scopus.com/inward/record.url?scp=85077761837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077761837&partnerID=8YFLogxK
U2 - 10.1158/1940-6207.CAPR-19-0258
DO - 10.1158/1940-6207.CAPR-19-0258
M3 - Article
C2 - 31619442
AN - SCOPUS:85077761837
SN - 1940-6207
VL - 13
SP - 117
EP - 126
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 1
ER -