School of Life Science and Technology, Harbin Normal University (Songbei Campus), No. 1, Shida Road, Hulan District, Harbin, 150025, Heilongjiang Province, China.
College of Life Science, Northeast Forestry University, Harbin, 150040, China.
Sci Rep. 2023 Oct 18;13(1):17745. doi: 10.1038/s41598-023-44394-y.
Triterpenoids, as the main active ingredient of Ganoderma lucidum fermented extract, exert multiple pharmacological activities, including immunomodulatory properties. Our study aimed to reveal the pharmacological effects and potential mechanisms of Ganoderic acid C2 (GAC) against cyclophosphamide (CY)-associated immunosuppression. Target genes were collected from several public databases, including the DisGeNET, Comparative Toxicogenomics Database, GeneCards, and PharmMapper. STRING database was used to construct the protein-protein interaction of network. Subsequently, molecular docking was carried out to visualize the protein-GAC interactions. Experimental validations, including ELISA and qRT-PCR were performed to confirm the pharmacological activities of GAC on CY-induced immunosuppression model. A total of 56 GAC-related targets were identified to be closely associated with CY-induced immunosuppression. Enrichment analyses results revealed that these targets were mainly involved in immune and inflammatory response-related pathways. STAT3 and TNF were identified as the core targets of GAC. Molecular docking indicated that GAC combined well with STAT3 and TNF protein. In addition, animal experiments indicated that GAC improved immunity as well as STAT3 and TNF genes expression in CY-induced immunosuppression, which further verified the prediction through bioinformatics analysis and molecular docking. We successfully revealed the potential therapeutics mechanisms underlying the effect of GAC against CY-induced immunosuppression based on the combination of bioinformatics analysis, molecular docking, and animal experiments. Our findings lay a theoretical foundation for the in-depth development and utilization of Ganoderma lucidum fermentation product in the future, and also provide theoretical guidance for the development of innovative drugs that assist in improving immunity.
三萜类化合物作为灵芝发酵提取物的主要活性成分，具有多种药理活性，包括免疫调节特性。我们的研究旨在揭示灵芝酸 C2（GAC）对环磷酰胺（CY）相关免疫抑制的药理作用和潜在机制。目标基因从 DisGeNET、Comparative Toxicogenomics Database、GeneCards 和 PharmMapper 等多个公共数据库中收集。STRING 数据库用于构建网络的蛋白质-蛋白质相互作用。随后，进行分子对接以可视化蛋白质-GAC 相互作用。进行实验验证，包括 ELISA 和 qRT-PCR，以确认 GAC 对 CY 诱导的免疫抑制模型的药理活性。确定了 56 个与 GAC 相关的靶标与 CY 诱导的免疫抑制密切相关。富集分析结果表明，这些靶标主要涉及免疫和炎症反应相关途径。STAT3 和 TNF 被确定为 GAC 的核心靶标。分子对接表明 GAC 与 STAT3 和 TNF 蛋白结合良好。此外，动物实验表明 GAC 改善了 CY 诱导的免疫抑制中的免疫功能以及 STAT3 和 TNF 基因的表达，这进一步通过生物信息学分析和分子对接验证了预测。我们成功地揭示了 GAC 对抗 CY 诱导的免疫抑制作用的潜在治疗机制，该机制基于生物信息学分析、分子对接和动物实验的结合。我们的研究结果为未来深入开发和利用灵芝发酵产物奠定了理论基础，也为开发有助于提高免疫力的创新药物提供了理论指导。
