| 内容提要: |
Magnolol (MG) and honokiol (Hon), the main polyphenol
compounds in Magnolia, have been
reported to treat digestive diseases. But, no studies have investigated their pharmacological
activity on the intestinal toxicity induced by irinotecan hydrochloride
(CPT-11). The purpose of this study is to evaluate the intestinal
protective effect of MG in CPT-11 induced intestinal toxicity group and
investigate its potential mechanisms. MG was found to exert
stronger inhibition effect on E. coli
β-glucuronidase than Hon in vivo fecal to reduce intestinal toxicity. The
intestinal toxicity was induced by CPT-11 and treated by MG. Body weight loss
and diarrhea score was measured. Intestinal damage was characterized by Hematoxylin
and eosin (HE) staining. The mechanism of MG to prevent the toxicity induced by
CPT-11 was involved with immune reaction, inflammatory response, intestinal
barrier and E. coli β-glucuronidase
activity changes. Molecular docking was applied to illustrate the interaction
between MG and enzyme. MG attenuated body weight loss, diarrhea and
intestinal damage characterized by the shortening of villi and destruction of
intestinal crypts. Oxidative stress and inflammation were repressed by MG
through increasing the activities of SOD, decreasing expression levels of TLR-4
and NF-κB, and then downregulating the following pro-inflammatory cytokines.
The expression of tight junction proteins occludin and ZO-1 were significantly
reduced after CPT-11, MG administration promoted these expressions. MG could prevent the
intestinal toxicity induced by CPT-11 through inhibiting inflammatory pathway
and E. coli β-glucuronidase activity. |