Synergistic potentiation of the anti-metastatic effect of a Ginseng-Salvia miltiorrhiza herbal pair and its biological ingredients via the suppression of CD62E-dependent neutrophil infiltration and NETformation

作者：Keqin Lu, Yawen Xia, Peng Cheng, Yanan Li, Liang He, Tao Li, Zhonghong Wei, Yin Lu · 发表于：Journal of Advanced Research · 年份：2024 · DOI：10.1016/j.jare.2024.10.036 · 被引用次数：25 · 研究领域：Immune cells in cancer、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Traditional Chinese Medicine Analysis

• The ginseng and Salvia miltiorrhiza herbal pair significantly reduced tumor metastasis compared to individual treatments • Anti-tumor metastatic effects of ginseng and Salvia miltiorrhiza were associated with modulation of neutrophil-associated tumor microenvironment • Cryptotanshinone inhibited neutrophil recruitment to metastatic sites by downregulating CD62E expression • Ginsenoside Rg1 inhibited NET formation and reversed the tumor-promoting effects of NETs • The combination of ginsenoside Rg1 and cryptotanshinone demonstrated synergistic anti-tumor metastatic effects The combination of the roots of ginseng and Salvia miltiorrhiza is an effective approach for treating metastatic cancer in patients with Qi stagnation and blood stasis patterns. However, the molecular mechanism underlying the combined use of ginseng and Salvia miltiorrhiza is unknown. This study unveils the pharmacological foundation of ginseng and Salvia miltiorrhiza by examining the involvement of neutrophils in the critical process of tumor hematogenous metastasis. Additionally, by employing a reverse pharmacology research model (effect–target–constituent), potential potent components were screened, and the dominant component formulations were determined. An experimental lung metastatic model was constructed to compare the antitumor effects of ginseng and Salvia miltiorrhiza . RNA sequencing was employed to identify pivotal biological events and key targets, while the detection of CD62E expression and n...