Jiawei Xianglian Decoction (JWXLD), a Traditional Chinese Medicine (TCM), Alleviates CPT-11-Induced Diarrhea in Mice

Jinhua Lu,Shengyou Lin,Zechen Lin,Jing Jiang,Siyu Huang,Yiwei Shen

doi:10.1155/2020/7901231

Abstract

Irinotecan (CPT-11) is used for therapy of various cancers. However, it has several serious adverse reactions such as diarrhea which is caused by SN-38, the active form of CPT-11. This study aimed to evaluate the effectiveness of Jiawei xianglian decoction (JWXLD), which has been widely used for the treatment of diarrhea in China. In this study, a mouse model with delayed diarrhea was generated by CPT-11. Real-time PCR and enzyme-linked immunosorbent assay (ELISA) were performed to explore intestinal microflora and inflammatory cytokine. Hematoxylin and eosin (H&E) staining was used to analyze tissue morphology. We found that 0.12, 0.23, and 0.46 g JWXLD significantly reduced the severity of CPT-11-induced diarrhea. The levels of Lactobacillus (Lacto) and Bifidobacterium (Bifid) were significantly downregulated by CPT-11, and these effects can be reversed by JWXLD treatment. Furthermore, JWXLD was observed to decrease the activity of β-glucuronidase (β-GD). Histopathological data showed that CPT-11 induced severe intestinal mucosal injury, which was characterized as grade 6, and JWXLD significantly alleviated the injury. In addition, CPT-11 increased the productions of tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-beta (TNF-β), interleukin-6 (IL-6), and interleukin-1 (IL-1), but decreased interleukin-15 (IL-15), interleukin-7 (IL-7), and uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1). In conclusion, JWXLD can counteract these effects caused by CPT-11 treatment. JWXLD could alleviate CPT-11-induced diarrhea.

Highlights

Irinotecan (CPT-11), an agent of camptothecin, was firstly isolated from Camptotheca acuminata in the early 1960s [1]
SN-38 is subsequently metabolized into SN-38 glucuronide (SN-38G) by uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) [7]. e SN-38G can be excreted into the bile and deconjugated to SN38 by β-glucuronidase (β-GD) in the intestine, leading to the accumulation of SN-38 [8, 9]. is SN-38 is considered to induce severe diarrhea [10]
On the third day following the final administration of CPT-11, mice feces were collected to analyze the degree of diarrhea. e severity of diarrhea was scored as follows [20]: 0, normal feces; 1, soft feces or small black feces; 2, wet and unformed feces; and 3, watery feces with severe perianal staining of the coat

Summary

Introduction

Irinotecan (CPT-11), an agent of camptothecin, was firstly isolated from Camptotheca acuminata (family: Nyssaceae) in the early 1960s [1]. CPT-11 exerts a broad spectrum of antitumor activity and has been used for the treatment of many kinds of cancer, including colon cancer [2,3,4]. It can cause serious adverse reactions, such as transient neutropenia and delayed diarrhea. E metabolic pathway of CPT-11 is complex. Is SN-38 is considered to induce severe diarrhea [10]. Delayed diarrhea is considered to be one of the dose-limiting factors of CPT-11, so it is urgent to find therapies to control delayed diarrhea induced by CPT-11

Methods

Results

Conclusion