Gastric cancer (GC) is the fifth most malignant disease with more than 1 million new cases every year in the world. Since most GC patients are diagnosed in the middle and late stages with high mortality rate, GC gradually become the third most common cause of death. The death toll is estimated to be 769,000 based on 2020 global statistics (Sung et al., 2021). In China, the overall incidence and mortality of GC is second only to lung cancer (Chen et al., 2016). The natural course of advanced GC is generally less than 1 year (Ajani et al., 2022; Japanese Gastric Cancer, 2021). GC originates from the superficial epithelial cells of the gastric mucosa in most cases. Adenocarcinoma is the most common type of GC which is divided into diffuse type and intestinal type (Bodoor et al., 2016; Mellouki et al., 2014). The specific metastatic sites of GC occur in liver, peritoneal surface, and distant lymph nodes (Oh et al., 2014). GC seriously threatens human life and health for high incidence rate, low early diagnosis rate, and 5-year survival rate of less than 40% (Sun et al., 2019). Palliative chemotherapy is the most vital way to treat recurrent, locally advanced, unresectable or metastatic GC (Smyth et al., 2020). Although the chemotherapy drugs including paclitaxel, oxaliplatin, and capecitabine has prolonged the progression-free survival and overall survival of GC patients (Lordick et al., 2022), while the therapeutic effects are insufficient to completely control GC. Furthermore, various adverse reactions during chemotherapy reduce the patient's tolerance, interrupt the entire treatment process, causing patients to lose the best treatment opportunity, and seriously affecting the patient's life quality and survival time.

Traditional Chinese medicine TCM has been widely accepted in China as a complementary and alternative therapy for GC with unique advantages in preventing and treating GC metastasis (Wang et al., 2021). TCM prescriptions combined with chemotherapy can reverse the chemotherapy resistance, improve clinical efficacy, enhance patients' immunity and quality of life, and reduce the toxic and side effects of chemotherapy (Ye et al., 2023; Li et al., 2021). Banxiaxiexin Decoction (BXXXD) first appeared in Treatise on Febrile Diseases and Miscellaneous Diseases. BXXXD has been used to treat gastrointestinal diseases for more than 1800 years in China. BXXXD is composed of Panax ginseng (Panax ginseng C. A. Mey.), Rhizoma coptidis (Coptis chinensis Franch.), Rhizoma pinelliae praeparatum (Pinellia ternata (Thunb.) Breit.), Scutellariae radix (Scutellaria baicalensis Georgi), Rhizoma Zingiberis (Zingiber officinale Roscoe) and Glycyrrhizae radix praeparatae (Glycyrrhiza uralensis Fisch.) (All herbs have been checked with http://www.theplantlist.org.) (Table 1). BXXXD is clinically used to treat GC and other digestive diseases including gastritis, gastric ulcer, precancerous lesions et al. BXXXD treat GC probably by inhibiting the metabolic activity and colony formation, promoting oxidative stress, and inducing cell apoptosis through Wnt/β-catenin signaling pathway in cancer cells (Cesana et al., 2007). Modified Banxia Xiexin Decoction (MBXXXD) is composed of BXXXD and three other traditional Chinese herbs: Rhizoma atractylodes macrocephalae (Atractylodes macrocephala Koidz.), Rhizoma pleionis (Iphigenia indica Kunth et Benth.) and Yangtao actinidia root (Radix actinidiae Chinensis) (All herbs have been checked with http://www.theplantlist.org.).

Overall survival and progression-free survival are of great significance for evaluating the development and treatment of gastric cancer. Overall survival is the time from the start of the randomisation group until death due to any cause. Overall survival is considered to be the best efficacy endpoint in oncology clinical trials and provides a more intuitive way of knowing whether the treatment used in the trial is benefiting the patient (Rha et al., 2023). Progression-free survival is the period of time between when a patient receives treatment and when disease progression is detected, or death from any cause occurs. Progression-free survival requires a short trial time, low operational difficulty, small sample size, and can indirectly or directly reflect the efficacy and risk of the new treatment regimen versus the prior treatment regimen, and can be used as an indicator for assessing survival with tumor (Janjigian et al., 2021). Therefore, overall survival and progression-free survival were used to evaluate the efficacy of BXXXD in treating GC firstly. Besides, clinical symptoms were also observed to evaluate the efficacy of BXXXD in improving quality of life. Furthermore, in this study, we also aimed to explore the potential anti-cancer mechanism of MBXXXD by Clinical trials, network pharmacology and basic experiment analysis. MBXXXD not only improved overall survival, progression-free survival and clinical symptoms as well as chemotherapy side effects, but also regulated multiple cellular processes in GC including P53 pathway, protein kinase B (AKT) pathway, nuclear factor kappa B (NF-κB) pathway, mitogen-activated protein kinase (MAPK) pathway. MDXXXD benefitted chemotherapy for GC by regulating multiple targets and pathways.