A phase I trial of berberine in Chinese with ulcerative colitis

Li Xu, Yujie Zhang, Xianmin Xue, Jie Liu, Zeng Shan Li, Guang Yu Yang, Ying Song, Yan Pan, Yueyun Ma, Sijun Hu, Aidong Wen, Yanyan Jia, Luz Maria Rodriguez, Mary Beth Tull, Kelly Benante, Seema A. Khan, Ying Cao, Borko Jovanovic, Ellen Richmond, Asad UmarRaymond Bergan*, Kaichun Wu

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)117-126
Number of pages10
JournalCancer Prevention Research
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2020

Fingerprint

Berberine
Ulcerative Colitis
Mesalamine
Placebos
China
Inflammation
Biopsy
Safety
Transaminases
Biological Products
Colonic Neoplasms
Nausea
Gastrointestinal Tract
Anti-Inflammatory Agents
Biomarkers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Xu, L., Zhang, Y., Xue, X., Liu, J., Li, Z. S., Yang, G. Y., ... Wu, K. (2020). A phase I trial of berberine in Chinese with ulcerative colitis. Cancer Prevention Research, 13(1), 117-126. https://doi.org/10.1158/1940-6207.CAPR-19-0258
Xu, Li ; Zhang, Yujie ; Xue, Xianmin ; Liu, Jie ; Li, Zeng Shan ; Yang, Guang Yu ; Song, Ying ; Pan, Yan ; Ma, Yueyun ; Hu, Sijun ; Wen, Aidong ; Jia, Yanyan ; Rodriguez, Luz Maria ; Tull, Mary Beth ; Benante, Kelly ; Khan, Seema A. ; Cao, Ying ; Jovanovic, Borko ; Richmond, Ellen ; Umar, Asad ; Bergan, Raymond ; Wu, Kaichun. / A phase I trial of berberine in Chinese with ulcerative colitis. In: Cancer Prevention Research. 2020 ; Vol. 13, No. 1. pp. 117-126.
@article{a4af1c38b2ae4a11a6a8c5cadb3d999f,
title = "A phase I trial of berberine in Chinese with ulcerative colitis",
abstract = "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.",
author = "Li Xu and Yujie Zhang and Xianmin Xue and Jie Liu and Li, {Zeng Shan} and Yang, {Guang Yu} and Ying Song and Yan Pan and Yueyun Ma and Sijun Hu and Aidong Wen and Yanyan Jia and Rodriguez, {Luz Maria} and Tull, {Mary Beth} and Kelly Benante and Khan, {Seema A.} and Ying Cao and Borko Jovanovic and Ellen Richmond and Asad Umar and Raymond Bergan and Kaichun Wu",
year = "2020",
month = "1",
day = "1",
doi = "10.1158/1940-6207.CAPR-19-0258",
language = "English (US)",
volume = "13",
pages = "117--126",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
number = "1",

}

Xu, L, Zhang, Y, Xue, X, Liu, J, Li, ZS, Yang, GY, Song, Y, Pan, Y, Ma, Y, Hu, S, Wen, A, Jia, Y, Rodriguez, LM, Tull, MB, Benante, K, Khan, SA, Cao, Y, Jovanovic, B, Richmond, E, Umar, A, Bergan, R & Wu, K 2020, 'A phase I trial of berberine in Chinese with ulcerative colitis', Cancer Prevention Research, vol. 13, no. 1, pp. 117-126. https://doi.org/10.1158/1940-6207.CAPR-19-0258

A phase I trial of berberine in Chinese with ulcerative colitis. / Xu, Li; Zhang, Yujie; Xue, Xianmin; Liu, Jie; Li, Zeng Shan; Yang, Guang Yu; Song, Ying; Pan, Yan; Ma, Yueyun; Hu, Sijun; Wen, Aidong; Jia, Yanyan; Rodriguez, Luz Maria; Tull, Mary Beth; Benante, Kelly; Khan, Seema A.; Cao, Ying; Jovanovic, Borko; Richmond, Ellen; Umar, Asad; Bergan, Raymond; Wu, Kaichun.

In: Cancer Prevention Research, Vol. 13, No. 1, 01.01.2020, p. 117-126.

Research output: Contribution to journalArticle

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

PY - 2020/1/1

Y1 - 2020/1/1

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

VL - 13

SP - 117

EP - 126

JO - Cancer Prevention Research

JF - Cancer Prevention Research

SN - 1940-6207

IS - 1

ER -