Shenmai injection (SMI) is a well-defined herbal preparation that is widely and clinically used as an adjuvant therapy for cancer. Previously, we found that SMI synergistically enhanced the activity of chemotherapy on colorectal cancer by promoting the distribution of drugs in xenograft tumors. However, the underlying mechanisms and bioactive constituents remained unknown. In the present work, the regulatory effects of SMI on tumor vasculature were determined, and the potential anti-angiogenic components targeting tumor endothelial cells (TECs) were identified. Multidimensional pharmacokinetic profiles of ginsenosides in plasma, subcutaneous tumors, and TECs were investigated. The results showed that the concentrations of protopanaxadiol-type (PPD) ginsenosides (Rb1, Rb2/Rb3, Rc, and Rd) in both plasma and tumors, were higher than those of protopanaxatriol-type (Rg1 and Re) and oleanane-type (Ro) ginsenosides. Among PPD-type ginsenosides, Rd exhibited the greatest concentrations in tumors and TECs after repeated injection. In vivo bioactivity results showed that Rd suppressed neovascularization in tumors, normalized the structure of tumor vessels, and improved the anti-tumor effect of 5-fluorouracil (5FU) in xenograft mice. Furthermore, Rd inhibited the migration and tube formation capacity of endothelial cells in vitro. In conclusion, Rd may be an important active form to exert the anti-angiogenic effect on tumor after SMI treatment.

参麦注射液（SMI）是一种定义明确的草药制剂，已广泛并在临床上用作癌症的辅助疗法。以前，我们发现SMI通过促进异种移植肿瘤中药物的分布来协同增强化学疗法对大肠癌的活性。但是，其潜在机制和生物活性成分仍然未知。在目前的工作中，确定了SMI对肿瘤血管的调节作用，并确定了靶向肿瘤内皮细胞（TECs）的潜在抗血管生成成分。研究了人参皂苷在血浆，皮下肿瘤和TECs中的多维药代动力学特征。结果显示血浆和肿瘤中原人参二醇型（PPD）人参皂甙（Rb1，Rb2 / Rb3，Rc和Rd）的浓度，高于原托那沙三醇型（Rg1和Re）和齐墩果烷型（Ro）人参皂苷。在PPD型人参皂甙中，Rd在反复注射后在肿瘤和TEC中表现出最高浓度。体内生物活性结果表明，Rd抑制了肿瘤中的新血管形成，使肿瘤血管的结构正常化，并提高了5-氟尿嘧啶（5FU）在异种移植小鼠中的抗肿瘤作用。此外，Rd在体外抑制了内皮细胞的迁移和管形成能力。总之，Rd可能是SMI治疗后对肿瘤发挥抗血管生成作用的重要活性形式。