Antibiotic-associated diarrhea (AAD) is a disease with diarrhea as the main clinical manifestation, which is caused by the imbalance of intestinal microbiota resulting from the improper use of antibiotics (Bartlett, 1992). The occurrence of AAD in adults ranges from 5% to 70% (McFarland, 2008). With the extensive utilization of antibiotics, the incidence of AAD has been steadily increasing over the years, posing a significant threat to people’s overall well-being (Chow et al., 2018; Pozzoni et al., 2012). The pathophysiology of AAD is elusive, and current treatment primarily involves supplementing probiotics to enhance the balance of intestinal flora in patients (Hempel et al., 2012). While there are minimal adverse reactions, the certainty of the evidence in the Cochrane review is considered moderate due to bias related to the specific probiotic strains used (Goldenberg et al., 2019). As a result, the final curative effect remains uncertain and requires further improvement.

AAD is classified as a type of ‘diarrhea’, from the perspective of Traditional Chinese Medicine (TCM) syndrome differentiation, the primary cause of AAD is the dysfunction of the spleen yang and the imbalance of qi in the spleen and stomach. Based on the unique theory of treatment through syndrome differentiation in long-term clinical trials, TCM has been proven to be highly effective in treating diarrhea (Liu et al., 2023; Xue et al., 2022). Shenlingbaizhu (SLBZ) formula, derived from the ancient medical text ‘Taiping Huimin Heji Jufang’, is known for its ability to invigorate the spleen, remove dampness, and alleviate diarrhea. SLBZ comprises 10 medicinal plants, including Panax ginseng C.A.Mey., Atractylodes macrocephala Koidz., Poria cocos (Schw.) Wolf., Platycodon grandiflorum (Jacq.) A.DC., Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle, Amomum villosum Lour., Coix lacryma-jobi L.var.mayuen (Roman.) Stapf, Dolichos lablab L., Dioscorea opposita Thunb., Nelumbo nucifera Gaertn (Committee, 2020). With its notable clinical efficacy, SLBZ shows promise as a potential drug for the treatment of AAD (Shen et al., 2022). However, the mechanism is still unknown.

Therefore, this study adopted a network pharmacology approach as well as in vivo and in vitro experiments to illustrate the potential mechanism of SLBZ in the treatment of AAD.