OEM Custom Package Natural Macrocephalae Rhizoma oil

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As an efficient chemotherapeutic agent, 5-fluorouracil (5-FU) is widely applied for treatment of malignant tumors in the gastrointestinal tract, head, neck, chest, and ovary. And 5-FU is the first-line drug for colorectal cancer in clinic. The action mechanism of 5-FU is to block the transformation of uracil nucleic acid into thymine nucleic acid in the tumor cells, then affect the synthesis and repairing of DNA and RNA to achieve its cytotoxic effect (Afzal et al., 2009; Ducreux et al., 2015; Longley et al., 2003). However, 5-FU also produces chemotherapy-induced diarrhea (CID), one of the most common adverse reactions that plagues many patients (Filho et al., 2016). The incidence of diarrhea in patients treated with 5-FU was up to 50%–80%, which seriously affected the progress and efficacy of chemotherapy (Iacovelli et al., 2014; Rosenoff et al., 2006). Consequently, it is of significant importance to find effective therapy for 5-FU induced CID.

At present, non-drug interventions and drug interventions have been imported into the clinical treatment of CID. Non-drug interventions include reasonable diet, and supplement with salt, sugar and other nutrients. Drugs such as loperamide and octreotide are commonly used in anti-diarrhea therapy of CID (Benson et al., 2004). In addition, ethnomedicines are also adopted to treat CID with their own unique therapy in various countries. Traditional Chinese medicine (TCM) is one typical ethnomedicine that has been practiced for more than 2000 years in East Asian countries including China, Japan and Korea (Qi et al., 2010). TCM holds that chemotherapeutic drugs would trigger Qi consumption, spleen deficiency, stomach disharmony and endophytic dampness, resulting in conductive dysfunction of intestines. In TCM theory, the treatment strategy of CID should be mainly depended on supplementing Qi and strengthening spleen (Wang et al., 1994).

The dried roots of Atractylodes macrocephala Koidz. (AM) and Panax ginseng C. A. Mey. (PG) are the typical herbal medicines in TCM with same effects of supplementing Qi and strengthening spleen (Li et al., 2014). AM and PG are usually used as herb pair (the simplest form of Chinese herbal compatibility) with the effects of supplementing Qi and strengthening spleen to treat diarrhea. For example, AM and PG were documented in classical anti-diarrheal formulae such as Shen Ling Bai Zhu San, Si Jun Zi Tang from Taiping Huimin Heji Ju Fang (Song dynasty, China) and Bu Zhong Yi Qi Tang from Pi Wei Lun (Yuan dynasty, China) (Fig. 1). Several previous studies had reported that all the three formulae possess the ability of alleviating CID (Bai et al., 2017; Chen et al., 2019; Gou et al., 2016). In addition, our previous study showed that Shenzhu Capsule which only contains AM and PG have potential effects on the treatments of diarrhea, colitis (xiexie syndrome), and other gastrointestinal diseases (Feng et al., 2018). However, no study has discussed the effect and mechanism of AM and PG in treating CID, whether in combination or alone.

Now gut microbiota is deemed to be a potential factor in understanding the therapeutic mechanism of TCM (Feng et al., 2019). Modern studies indicate that gut microbiota plays a crucial role in maintaining intestinal homeostasis. Healthy gut microbiota contributes to the intestinal mucosal protection, metabolism, immune homeostasis and response, and pathogen suppression (Thursby and Juge, 2017; Pickard et al., 2017). Disordered gut microbiota impairs the physiological and immune functions of the human body directly or indirectly, inducing side reactions like diarrhea (Patel et al., 2016; Zhao and Shen, 2010). Researches had shown that 5-FU remarkably shifted the structure of gut microbiota in diarrheic mice (Li et al., 2017). Therefore, the effects of AM and PM on 5-FU induced diarrhea may be mediated by gut microbiota. However, whether AM and PG alone and in combination could prevent 5-FU induced diarrhea by modulating gut microbiota is still unknown.

In order to investigate anti-diarrhea effects and underlying mechanism of AM and PG, we used 5-FU to simulate a diarrheal model in mice. Here, we focused on the potential effects of the single and combined administration (AP) of Atractylodes macrocephala essential oil (AMO) and Panax ginseng total saponins (PGS), the active components respectively extracted from AM and PG, on diarrhea, intestinal pathology and microbial structure after 5-FU chemotherapy.