Undulacin C, Ophiobolin-type sesterterpenoid with anti-autoimmune hepatitis activity from Aspergillus undulatus

Eleven ophiobolin-type sesterterpenoids, including ten novel compounds (1-8, 10, and 11) and one known analogue (9), were isolated from the EtOAc extract of Aspergillus undulatus. Their structures and absolute configurations were elucidated through extensive NMR and HRESIMS analyses, supported both experimental and calculated ECD data. All isolates were evaluated for immunosuppressive activity against Con A-induced T-lymphocyte proliferation. Among them, compound 3 exhibited moderate inhibitory activity with an IC₅₀ value of 9.74 ± 0.62 μM. In a murine model of autoimmune hepatitis, compound 3 could alleviate liver injury and reduce level of multiple inflammatory cytokines. Network pharmacology was used to predict the potential pathways and targets of compound 3, and molecular docking was conducted to predict the binding affinity (-8.0 kcal/mol) between 3 and the top target (SRC). These findings not only enrich the structural diversity of the ophiobolin family but also provide a promising molecular scaffold for the development of therapeutics targeting autoimmune hepatitis.