Chemical constitutes from Tuber indicum with immunosuppressive activity uncovered by transcriptome analysis

• Published in: Fitoterapia Vol. 173; p. 105773
• Main Authors: Li, Si-Ning, Li, Xin-Ai, Zhang, Qi, Hu, Yun-Jie, Lei, Hao-Ran, Guo, Da-Le, Jiang, Li-Shi, Deng, Yun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2024
• Subjects: Chemical composition; Immunosuppressive activity; Transcriptome analysis; Tuber indicum; Zebrafish; Zebrafish; Transcriptome analysis; Chemical composition; Immunosuppressive activity; Tuber indicum
• ISSN: 0367-326X; 1873-6971
• DOI: 10.1016/j.fitote.2023.105773

Three previously undescribed compounds including a polyketide (1) and two lactams (2 and 3) were obtained from Tuber indicum. The structures of new findings were elucidated by HRESIMS, NMR as well as NMR and ECD calculations. Transcriptome analysis through RNA-seq revealed that compound 2 exhibits immunosuppressive activity. Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were employed as a model to explore the effect of these compounds in immunosuppressive activity. The results showed that 2 could reduce the generation of inflammatory mediators including nitric oxide (NO), reactive oxygen species (ROS), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Western blotting analysis demonstrated that 2 could suppressed the PI3K pathway by decreasing the levels of p-PI3K and p-Akt, while increasing the levels of p-PTEN. The anti-inflammatory activity of 2 was further confirmed using a zebrafish in vivo model. [Display omitted] •The absolute configurations of three new compounds (1–3) from Tuber indicum were elucidated.•Transcriptome analysis indicated 2 have immunosuppressive activity.•2 could inhibit the PI3K pathway by decreasing p-PI3K and p-Akt and increasing p-PTEN.•The anti-inflammatory activity of 2 was also confirmed in vivo by a zebrafish model.