Sesquiterpenoids From Marmoritis complanata (Dunn) A. L. Budantzev With Antioxidant Activity in Zebrafish

Marmoritis complanata (Dunn) A. L. Budantzev, a Tibetan medicinal plant endemic to alpine regions, is traditionally used for its anti-inflammatory properties. A novel sesquiterpenoid, marmoritiolide (1), featuring a novel 14-nor-5, 6-seco-eudesmane-type carbon skeleton with an isopropyl migration from C-7 to C-8, was isolated together with four known sesquiterpenoids (2-5). The structure of 1 was determined by HRESIMS and 1D/2D NMR. A plausible biogenetic pathway is proposed. In an H₂O₂-induced oxidative stress zebrafish model, compound 1 dose-dependently (12.5-50 µM) reduced intracellular ROS levels, achieving 36.9% inhibition at 50 µM (vs. the model group), comparable to the positive control (38.2%). Superoxide dismutase (SOD) activity was restored from 58.0% (model) to 82.8% of control levels at 50 µM. qPCR analysis showed that 1 upregulated the mRNA expression of Nrf2 (1.3-fold), Mn-SOD (1.6-fold), Cu/Zn-SOD (2.6-fold), and NQO1 (2.1-fold) at 50 µM. suggesting modulation of the Nrf2 pathway. Covalent docking further indicated that compound 1 can covalently modify Keap1 at Cys151, providing a mechanistic basis for Nrf2 activation. These findings highlight M. complanata as a source of structurally unique sesquiterpenoids with potent antioxidant activity.