St. John's wort attenuates irinotecan-induced diarrhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis

Ze Ping Hu, Xiao Xia Yang, Sui Yung Chan, An Long Xu, Wei Duan, Yi Zhun Zhu, Fwu Shan Sheu, Urs Alex Boelsterli, Eli Chan, Qiang Zhang, Jian Cheng Wang, Pui Lai Rachel Ee, Hwee Ling Koh, Min Huang, Shu Feng Zhou

Research output: Contribution to journalArticle

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Abstract

Diarrhea is a common dose-limiting toxicity associated with cancer chemotherapy, in particular for drugs such as irinotecan (CPT-11), 5-fluouracil, oxaliplatin, capecitabine and raltitrexed. St. John's wort (Hypericum perforatum, SJW) has anti-inflammatory activity, and our preliminary study in the rat and a pilot study in cancer patients found that treatment of SJW alleviated irinotecan-induced diarrhea. In the present study, we investigated whether SJW modulated various pro-inflammatory cytokines including interleukins (IL-1β, IL-2, IL-6), interferon (IFN-γ) and tumor necrosis factor-α (TNF-α) and intestinal epithelium apoptosis in rats. The rats were treated with irinotecan at 60 mg/kg for 4 days in combination with oral SJW or SJW-free control vehicle at 400 mg/kg for 8 days. Diarrhea, tissue damage, body weight loss, various cytokines including IL-1β, IL-2, IL-6, IFN-γ and TNF-α and intestinal epithelial apoptosis were monitored over 11 days. Our studies demonstrated that combined SJW markedly reduced CPT-11-induced diarrhea and intestinal lesions. The production of pro-inflammatory cytokines such as IL-1β, IFN-γ and TNF-α was significantly up-regulated in intestine. In the mean time, combined SJW significantly suppressed the intestinal epithelial apoptosis induced by CPT-11 over days 5-11. In particular, combination of SJW significantly inhibited the expression of TNF-α mRNA in the intestine over days 5-11. In conclusion, inhibition of pro-inflammatory cytokines and intestinal epithelium apoptosis partly explained the protective effect of SJW against the intestinal toxicities induced by irinotecan. Further studies are warranted to explore the potential for STW as an agent in combination with chemotherapeutic drugs to lower their dose-limiting toxicities.

Original languageEnglish (US)
Pages (from-to)225-237
Number of pages13
JournalToxicology and Applied Pharmacology
Volume216
Issue number2
DOIs
StatePublished - Oct 15 2006

Fingerprint

irinotecan
Hypericum
Diarrhea
Down-Regulation
Apoptosis
Cytokines
Interleukin-1
Tumor Necrosis Factor-alpha
Toxicity
Rats
oxaliplatin
Intestinal Mucosa
Intestines
Interleukin-2
Interleukin-6
Chemotherapy
Interleukins
Pharmaceutical Preparations
Interferons
Weight Loss

Keywords

  • Apoptosis
  • Chemotherapy
  • Diarrhea
  • Irinotecan
  • St. John's wort
  • TNF-α

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

St. John's wort attenuates irinotecan-induced diarrhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis. / Hu, Ze Ping; Yang, Xiao Xia; Chan, Sui Yung; Xu, An Long; Duan, Wei; Zhu, Yi Zhun; Sheu, Fwu Shan; Boelsterli, Urs Alex; Chan, Eli; Zhang, Qiang; Wang, Jian Cheng; Ee, Pui Lai Rachel; Koh, Hwee Ling; Huang, Min; Zhou, Shu Feng.

In: Toxicology and Applied Pharmacology, Vol. 216, No. 2, 15.10.2006, p. 225-237.

Research output: Contribution to journalArticle

Hu, ZP, Yang, XX, Chan, SY, Xu, AL, Duan, W, Zhu, YZ, Sheu, FS, Boelsterli, UA, Chan, E, Zhang, Q, Wang, JC, Ee, PLR, Koh, HL, Huang, M & Zhou, SF 2006, 'St. John's wort attenuates irinotecan-induced diarrhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis', Toxicology and Applied Pharmacology, vol. 216, no. 2, pp. 225-237. https://doi.org/10.1016/j.taap.2006.05.020
Hu, Ze Ping ; Yang, Xiao Xia ; Chan, Sui Yung ; Xu, An Long ; Duan, Wei ; Zhu, Yi Zhun ; Sheu, Fwu Shan ; Boelsterli, Urs Alex ; Chan, Eli ; Zhang, Qiang ; Wang, Jian Cheng ; Ee, Pui Lai Rachel ; Koh, Hwee Ling ; Huang, Min ; Zhou, Shu Feng. / St. John's wort attenuates irinotecan-induced diarrhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis. In: Toxicology and Applied Pharmacology. 2006 ; Vol. 216, No. 2. pp. 225-237.
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AU - Yang, Xiao Xia

AU - Chan, Sui Yung

AU - Xu, An Long

AU - Duan, Wei

AU - Zhu, Yi Zhun

AU - Sheu, Fwu Shan

AU - Boelsterli, Urs Alex

AU - Chan, Eli

AU - Zhang, Qiang

AU - Wang, Jian Cheng

AU - Ee, Pui Lai Rachel

AU - Koh, Hwee Ling

AU - Huang, Min

AU - Zhou, Shu Feng

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