College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
College of Animal Sciences, Wenzhou Vocational College of Science and Technology, Wenzhou, Zhejiang, China.
Front Immunol. 2023 Feb 10;14:1108244. doi: 10.3389/fimmu.2023.1108244. eCollection 2023.
Rhizoma Bolbostemmatis, the dry tuber of , has being used for the treatment of acute mastitis and tumors in traditional Chinese medicine. In this study, tubeimoside (TBM) I, II, and III from this drug were investigated for the adjuvant activities, structure-activity relationships (SAR), and mechanisms of action. Three TBMs significantly boosted the antigen-specific humoral and cellular immune responses and elicited both Th1/Th2 and Tc1/Tc2 responses towards ovalbumin (OVA) in mice. TBM I also remarkably facilitated mRNA and protein expression of various chemokines and cytokines in the local muscle tissues. Flow cytometry revealed that TBM I promoted the recruitment and antigen uptake of immune cells in the injected muscles, and augmented the migration and antigen transport of immune cells to the draining lymph nodes. Gene expression microarray analysis manifested that TBM I modulated immune, chemotaxis, and inflammation-related genes. The integrated analysis of network pharmacology, transcriptomics, and molecular docking predicted that TBM I exerted adjuvant activity by interaction with SYK and LYN. Further investigation verified that SYK-STAT3 signaling axis was involved in the TBM I-induced inflammatory response in the C2C12 cells. Our results for the first time demonstrated that TBMs might be promising vaccine adjuvant candidates and exert the adjuvant activity through mediating the local immune microenvironment. SAR information contributes to developing the semisynthetic saponin derivatives with adjuvant activities.
天麻的干燥根茎，在传统中药中用于治疗急性乳腺炎和肿瘤。在这项研究中，研究了来源于该药的三种竹节参皂苷（TBM）I、II 和 III 的佐剂活性、构效关系（SAR）和作用机制。这三种 TBM 显著增强了卵清蛋白（OVA）在小鼠中的抗原特异性体液和细胞免疫应答，并诱导了 Th1/Th2 和 Tc1/Tc2 应答。TBM I 还显著促进了局部肌肉组织中各种趋化因子和细胞因子的 mRNA 和蛋白表达。流式细胞术显示，TBM I 促进了注射肌肉中免疫细胞的募集和抗原摄取，并增强了免疫细胞向引流淋巴结的迁移和抗原转运。基因表达微阵列分析表明，TBM I 调节免疫、趋化和炎症相关基因。网络药理学、转录组学和分子对接的综合分析预测，TBM I 通过与 SYK 和 LYN 相互作用发挥佐剂活性。进一步的研究证实，SYK-STAT3 信号通路参与了 TBM I 诱导的 C2C12 细胞炎症反应。我们的研究结果首次表明，TBM 可能是有前途的疫苗佐剂候选物，通过调节局部免疫微环境发挥佐剂活性。SAR 信息有助于开发具有佐剂活性的半合成皂苷衍生物。
