肝细胞癌（HCC）是全球最常见的恶性肿瘤之一，是全球重大的公共卫生问题。免疫细胞功能障碍是肝癌免疫抑制微环境形成的关键因素。北沙参 (A.Gray) F.Schmidt ex Miq. (Shashen) 和麦冬 (Ophiopogon japonicus) (Thunb.) Ker Gawl。麦冬是中医滋阴经典药对，广泛应用于治疗肝癌，具有多种免疫调节功能。然而，沙参-麦冬药对 (SS-MD) 在治疗 HCC 方面的作用及其潜在机制尚未阐明。本研究的目的是探讨 SS-MD 药对治疗 HCC 的潜在机制。使用 UPLC-Q-Orbitrap-MS/MS 初步鉴定了 SS-MD 草药对的已知成分。通过构建草药-成分-靶点网络筛选SS-MD药对治疗肝癌的活性成分，并通过构建蛋白质-蛋白质相互作用（PPI）网络探索关键治疗靶点。通过分子对接和分子动力学模拟验证了关键靶点和成分的结合亲和力。通过 GO 生物学功能和 KEGG 通路分析来阐明 SS-MD 草药对治疗 HCC 的潜在机制。并在荷瘤小鼠模型和细胞共培养实验中验证了该机制。网络药理学预测揭示了SS-MD草药对治疗HCC的39个活性成分和138个靶点。 KEGG分析主要关注Notch信号通路和Apopsis信号通路。靶点丰富于淋巴细胞效应功能和淋巴细胞凋亡的生物学功能。体内外实验证明SS-MD药对可以提高HCC免疫微环境中CD8 T细胞的比例，调节其亚群分布。 SS-MD药对促进CD8 T细胞分泌IL-2、TNF-α、IFN-γ、颗粒酶B和穿孔素，并通过调节Notch信号通路抑制细胞凋亡。本研究确定了SS-MD中药的关键成分、靶点和信号通路。 SS-MD药对的研究，证实SS-MD药对在治疗HCC中发挥免疫调节作用，为中医药协同治疗HCC提供理论支持。版权所有©2024。Elsevier B.V.出版。

Hepatocellular carcinoma (HCC) is among the most prevalent malignant tumors globally and represents a significant public health issue worldwide. Immune cell dysfunction is the crucial factor for the formation of immunosuppression microenvironment of HCC. Glehnia littoralis (A.Gray) F.Schmidt ex Miq. (Shashen) and Ophiopogon japonicus (Thunb.) Ker Gawl. (Maidong) are classic herb pair in traditional Chinese medicine (TCM) of nourishing Yin, and is widely applied in the treatment of HCC and possesses multiple immunomodulatory functions. However, the role of the the Shashen-Maidong herb pair (SS-MD) for the management of HCC and the potential mechanisms has not been explicated.The purpose of the research is to investigate the potential mechanism of the SS-MD herb pair for the management of HCC.The known components of the SS-MD herb pair were preliminarily identified using UPLC-Q-Orbitrap-MS/MS. The active ingredients of SS-MD herb pair in treating HCC were screened by constructing herb-component-target network, and the key therapeutic targets were explored by constructing a protein-protein interaction (PPI) network. The binding affinity of the key targets and components were validated through molecular docking and molecular dynamics simulations. GO biological function and KEGG pathway analyses were operated to elucidate the potential mechanisms of the SS-MD herb pair for the management of HCC. And the mechanism was verified in the tumor bearing mice model and cell co-culture experiments.Network pharmacology prediction revealed 39 active components and 138 targets of the SS-MD herb pair for the treatment of HCC. KEGG analysis mainly focused on Notch signaling pathway and Apoptosis signaling pathway. The targets were enriched in biological functions of lymphocyte effector function and lymphocyte apoptosis. In vivo and in vitro experiments proved that the SS-MD herb pair can improve the proportion of CD8+T cells in the HCC immune microenvironment, regulate its subgroup distribution. SS-MD herb pair promoted CD8+T cells to secrete IL-2, TNF-α, IFN-γ, Granzyme B and Perforin, and inhibited apoptosis by regulating Notch signaling pathway.This study identified the key components, targets, and signaling pathways of the SS-MD herb pair, confirm that SS-MD herb pair play an immunomodulatory role in treating HCC, provides theoretical support for the collaborative treatment of HCC with TCM.Copyright © 2024. Published by Elsevier B.V.