Supplementary MaterialsDataSheet_1. to treat many types of gastrointestinal diseases, including gastrointestinal reactions induced by radiotherapy and chemotherapy. However, the exact effect of G-SJZ on intestinal mucositis is usually unclear, and moreover, whether l-glutamine combined with Si-Jun-Zi-Tang is more effective than l-glutamine alone have not been studied. In the current study, we explored the effects of G-SJZ and l-glutamine Nylidrin Hydrochloride in a mouse model of intestinal mucositis induced by 5-fluorouracil (5-Fu). The results revealed that pretreatment with G-SJZ ameliorated the physical manifestations of excess weight loss and the severity of diarrhea following continuous 5-Fu injections in mice. Similarly, the histopathological damage and the destruction of villus and crypt structures in the intestinal mucosa as well as the increase in circulating intestinal injury markers caused by 5-Fu were reversed with G-SJZ pretreatment. Furthermore, the protective effect of G-SJZ was accompanied by modulations in the immunohistochemical expression of tight junction proteins. Interestingly, although treatment with a dose of l-glutamine alone that was equivalent to the dose in G-SJZ also showed a protective effect, it did not appear to be as strong as treatment with G-SJZ. Si-Jun-Zi-Tang in G-SJZ may compensate for the deficiencies of l-glutamine in this model which seems not to be related to the regulation of tight junction proteins. Our study is the first to suggest that the combined use of l-glutamine and Si-Jun-Zi-Tang might be more effective than l-glutamine alone despite exact mechanism still needs further study. Because of the limited quantity of therapeutic agents, G-SJZ is likely to be a preferable choice for intestinal mucositis. their potential to inhibit the division of rapidly dividing malignancy cells. Because epithelial cells from the gastrointestinal system are quickly dividing also, many anticancer medications have a higher tendency to harm these cells while concentrating on cancer cells. As a result, intestinal mucositis, which is generally connected with diarrhea and it is seen as a the ulceration and irritation of intestinal mucosa, becomes one of the most common undesireable effects following anti-neoplastic treatments (Gibson and Stringer, 2009; Bowen et al., 2019). As an unwanted toxicity, intestinal mucositis not only occurs in treatment with traditional chemotherapies, e.g., 5-fluorouracil (5-FU) and irinotecan, but also occurs with targeted therapies, PROK1 such as tyrosine-kinase inhibitors and epidermal-growth-factor inhibitors, which has also posed difficulties in clinical practice, given the increasing exposure of malignancy patients to these brokers (Pusztaszeri et al., 2007; Takeda et al., 2015; Van Sebille et al., 2015). Even though absolute occurrence is usually uncertain, several randomized clinical studies reported grade 3-4 severe diarrhea associated with intestinal mucositis in 5% to 47% of patients who received diverse anticancer regimens, including FOLFOXIRI, irinotecan, FOLFIRI with cetuximab, FLOX with cetuximab, etc. (Andreyev et al., 2014). Erlotinib was reported to induce all grades of diarrhea in 67.9% of patients with advanced nonCsmall-cell lung cancer in a phase III trial, with 12.4% of patients suffering from grade 3 diarrhea (Herbst et al., 2005). Immune checkpoint inhibitors, a novel category of malignancy treatment, may also impact the gastrointestinal tract, leading to severe diarrhea (Kuo et al., 2018). The effective prevention and treatment of intestinal mucositis have become important issues in the clinical practice of oncologic treatment. As an important nonessential amino acid in the gastrointestinal tract, l-glutamine acts not only as the major energy source but also as a necessary substrate for nucleotide synthesis in epithelial cells and other rapidly proliferating cells without Nylidrin Hydrochloride stimulating tumor growth (Klimberg et al., 1990; Klimberg and McClellan, 1996). Hence, in addition to the functions in diseases with significant metabolic stress, e.g., sepsis and multiple trauma, l-glutamine treatment has been suggested and extended to mucositis induced by chemotherapy and radiotherapy due to its supportive role in the trophism of the intestinal epithelium (Skubitz and Anderson, 1996; Garca-de-Lorenzo et al., 2003; Savarese et al., 2003; Beutheu et al., 2014). However, l-glutamine failed to be outlined in the guidelines for the management of malignancy treatment-related gastrointestinal mucositis released by the Multinational Association of Supportive Care in Malignancy/International Society for Oral Oncology (MASCC/ISOO) because there is limited high-level evidence or because inconsistent results Nylidrin Hydrochloride have been shown in clinical research (Gibson et al., 2013; Lalla et al., 2014; Bowen et al., 2019). Early research also indicated that l-glutamine didn’t decrease the occurrence of chemotherapy-induced diarrhea or enhance the dietary status and diet in cancers sufferers, though it relieved mucositis and mucosal atrophy (Bozzetti et al., 1997; Decker-Baumann et al., 1999). Oddly enough, in China, there’s a substance product whose substances include l-glutamine.