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

ABSTRACT

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 H ₂ O ₂ ‐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.