Shashen-Maidong草药对的机理在使用网络药理学和实验验证治疗肝细胞癌方面

肝细胞癌（HCC）是全球最普遍的恶性肿瘤之一，在全球范围内是一个重大的公共卫生问题。免疫细胞功能障碍是形成HCC免疫抑制微环境的关键因素。 glehnia littoralis（a.gray）f.schmidt ex miq。 （Shashen）和Ophiopogon Japonicus（Thunb。）Ker Gawl。 （纪念）是滋养阴的传统中药（TCM）的经典草药对，并广泛应用于HCC的治疗中，并具有多种免疫调节功能。 However, the role of 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.通过构建草药 - 成分目标网络筛选了治疗HCC中SS-MD草药对的活性成分，并通过构建蛋白质 - 蛋白质相互作用（PPI）网络来探索关键的治疗靶标。通过分子对接和分子动力学模拟验证了关键靶标和组件的结合亲和力。进行GO生物学功能和KEGG途径分析，以阐明SS-MD草药对的潜在机制以进行HCC的管理。并在肿瘤轴承小鼠模型和细胞共培养实验中验证了该机制。网络药理学预测显示，SS-MD草药对的39个活性成分和138个靶标，用于治疗HCC。 KEGG分析主要集中于Notch信号通路和凋亡信号通路。靶标富含淋巴细胞效应子功能和淋巴细胞凋亡的生物学功能。体内和体外实验证明，SS-MD草药对可以改善HCC免疫微环境中CD8+T细胞的比例，从而调节其亚组分布。 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对HCC与TCM的合作处理的理论支持。

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 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.