St. Johns wort attenuates irinotecan-induced diarhea 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, Rachel Ee, Pui Lai, Koh, Hwee Ling, Huang, Min and Zhou, Shu-Feng 2006, St. Johns wort attenuates irinotecan-induced diarhea 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.

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Title St. Johns wort attenuates irinotecan-induced diarhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis
Author(s) 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
Rachel Ee, Pui Lai
Koh, Hwee Ling
Huang, Min
Zhou, Shu-Feng
Journal name Toxicology and applied pharmacology
Volume number 216
Issue number 2
Start page 225
End page 237
Publisher Academic Press
Place of publication San Diego Calif.
Publication date 2006-10-15
ISSN 0041-008x
Keyword(s) St. John's wort
irinotecan
chemotherapy
diarrhea
TNF-α
apoptosis
Summary 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.
Language eng
Field of Research 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2006, Elsevier Inc.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30009146

Document type: Journal Article
Collection: School of Medicine
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