Oxyepiberberine from the Active Site of Coptidis Rhizoma Inhibits Lung Adenocarcinoma by Regulating SRC-related Pathways in vivo

Abstract

Background: Huanglian (HL), also known as Coptis chinensis Franch., was initially documented in “Sheng Nong’s Herbal Classic” as a high-quality product used to cure ailments such as fever, indigestion, bloating, nausea, dysentery, diarrhea, abdominal pain, and tuberculosis. Nowadays, it is extensively employed in clinical settings to alleviate pulmonary diseases, like tuberculosis, lobular lung disease, and pulmonary abscess, and is worth exploring further. Nevertheless, there is limited research on the precise advancements of anti-lung adenocarcinoma (LUAD). Objectives: Using biological experiments and network pharmacology, the objective of this research was to investigate the most effective parts and chemical constituents of C. chinensis against LUAD and ascertain the probable targets and pathways. Materials and Methods: First, an MTT experiment verified the impact of each part on A549 and BEAS-2B cells. High performance liquid chromatography (HPLC) was then used to identify the chemical components of the effective substance in C. chinensis against LUAD. Then, network pharmacology was used to screen potential pathways and binding target proteins. Finally, a subcutaneous tumor model was established in mice using LLC cells to observe the effects of the effective components of C. chinensis against LUAD in tumor-bearing mice. Results: The MTT assay demonstrated the efficacy of oxyepiberberine (OPB) as an anti-LUAD compound with minimal toxicity and side effects. According to the results of network pharmacology and molecular docking, SRC appears to be the primary target of C. chinensis active substance against LUAD. In vivo experiments revealed that the OPB group exhibited lowered toxicity and side effects. Additionally, the density of tumor cells decreased and the nuclei were destroyed in OPB groups of tumor tissues. Finally, OPB could regulate apoptosis, migration, and protein expression significantly related to the SRC pathway in tumor cells. Conclusion: Our research reveals the anti-LUAD properties of C. chinensis through a combination of experimentation and network analysis. These findings establish a theoretical foundation for C. chinensis as a clinical antitumor agent. Furthermore, our work provided an essential groundwork for further investigations into the medicinal properties of C. chinensis.