Research progress on the clinical application and therapeutic mechanism of Chansu in anti-tumor treatment
Malignant tumors pose a serious threat to human health and life, and in clinical practice, comprehensive treatment methods such as surgery, targeted therapy, medication, and radiotherapy and chemotherapy are mainly used. Traditional Chinese medicine has certain advantages and characteristics in the treatment of malignant tumors. Traditional Chinese medicine believes that the pathogenesis of tumors is mainly due to the weakness of positive qi and the invasion of external pathogens. Based on the etiology and pathogenesis of malignant tumors, traditional Chinese medicine treatment is based on syndrome differentiation and treatment, and includes measures such as strengthening the body and consolidating the foundation, softening hardness and dispersing nodules, promoting blood circulation and removing stasis, regulating qi and promoting stagnation, clearing heat and detoxifying. Bufonis Venenum is the dried secretion of Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, both belonging to the family Bufonidae. It has a pungent and warm nature, is toxic, and belongs to the heart meridian. It has the effects of detoxification, pain relief, and awakening the mind. It is used to treat carbuncles, sore throat, heat stroke, dizziness, and bloating, abdominal pain, and vomiting. It is an excellent anti-tumor traditional Chinese medicine. Modern pharmaceutical research has shown that toad venom mainly contains compounds such as bufolactone, bufotaxime, and sterols. It has been proven that bufolactone is the main pharmacological substance basis for the anti-tumor effect of toad venom. Currently, 142 components of this class have been isolated and identified from toad venom. The main components of bufalin, bufalin, and bufalin are used as indicator components for content determination in the 2020 edition of the Chinese Pharmacopoeia’s bufalin medicinal material quality standard, which stipulates that the total content of these three compounds should not be less than 7%. The three formulations of Huachansu (injection, capsule, and tablet) and Chansu injection developed from Chansu single herb have good clinical efficacy in the treatment of advanced tumors, especially in primary liver cancer, lung cancer, esophageal cancer, and gastric cancer. They can enhance the immune system of the body, reduce the toxic side effects of radiotherapy and chemotherapy, and improve the quality of life and prolong the lifespan of patients. Given the excellent anti-tumor effect of Bufonisu, this article reviews the mechanism of action and clinical application of Bufonisu and its preparations in the past five years, providing guidance for the in-depth research and development of Bufonisu.

In clinical applications, in addition to anti-tumor effects, toad venom preparations also have significant immunomodulatory effects on the body. However, no reports directly related to immunity have been found in comparative mechanism studies, which may be due to the fact that research mainly focuses on toad lactone monomers, which have no immunomodulatory effects. The immunomodulatory effect of Chansu preparations may be related to the retention of a large amount of water-soluble substances such as active peptides in the preparation process of Huachansu and Chansu injection, but there are very few related research reports. There are many research reports on the anti-tumor mechanism of Chansu, which involves various processes of tumor occurrence and development. However, most of the research focuses on in vitro cell experiments, and the mechanism research lacks a complete and unified internal environment and neurohumoral regulation of the body. At the same time, multiple literature reports have shown that toad lactones have cytotoxic effects on normal cells within a certain concentration range. For example, the IC50 value of Huachansu toxin base on brain neuron HCN-2 is 42.5 μ mol/L, and its inhibitory effect is mainly related to the imbalance of ROS and Ca2+in cells. The IC50 value on human lung epithelial cell BEAS-2B is 22.3 μ mol/L; The IC50 values of Chandu Ling and Sha Chandu Jing on human esophageal epithelial cell Het-1A were 10.1 and 11.8 μ mol/L, respectively; Lipobufogenin inhibits the activity of HPDE in pancreatic ductal epithelial cells, with an IC50 value of 58.12 μ mol/L. From this analysis, it can be concluded that toad lactones are both anti-tumor active substances and toxic components, but their toxicity is relative. By controlling the safe dosage of medication, the toxic effects on normal cells can be reduced. Therefore, based on cellular level research, it is extremely necessary to conduct in vivo mechanism studies in animals, clarify the therapeutic and toxic doses of toad lactones, and guide clinical safety and effective drug use. In addition, based on the research on the lactone components of toads, studies have been conducted on the pharmacological substances and mechanisms such as toad venom peptides and toad venom serotonin. Further research has been conducted on the dose-response toxic effects and mechanisms of toad venom in anti-tumor treatment, in order to fully utilize its therapeutic advantages of strengthening the body and clearing heat and detoxifying, and provide important scientific basis for the safe and rational use of toad venom in anti-tumor treatment and expanding clinical indications.