Isoginkgetin

Isoginkgetin (IGK), a natural biflavonoid extracted from the Ginkgo biloba plant, is a powerful, non-toxic small-molecule activator of the Nrf2/ARE antioxidant pathway for the prevention and treatment of obesity-induced metabolic cardiomyopathy. IGK inserts into the Keap1–Nrf2 pocket, with 6 stable hydrogen bonds between the two proteins, to inhibit the ubiquitin-proteasomal degradation of Nrf2, to extend Nrf2 half-life and to induce its nuclear translocation. This robustly augments transcription of cytoprotective genes (HO-1, NQO1, GSTP1), leading to suppression of oxidative stress and restoration of mitochondrial respiratory chain complexes I–V, enhancement of ATP supply, and reduction of myocardial lipid accumulation and ROS.
IGK reversed high-fat-fed mouse diastolic dysfunction and cardiac hypertrophy and fibrosis without affecting body weight or blood glucose. In vitro, IGK blunted palmitate-induced cardiomyocyte hypertrophy, mitochondrial depolarization and respiratory depression in a Nrf2-dependent manner. These data support the further development of IGK as a safe, natural, first-in-class small-molecule drug candidate for lipotoxic cardiomyopathy and other oxidative-stress related disorders.

Fig. 1 Isoginkgetin preserves mitochondrial function. (Xu M.; et al. 2025)

Yu H et al. designed a ROS-responsive nanodelivery system (IGK@SeNP) for the treatment of intervertebral disc degeneration (IDD), integrating ROS scavenging and autophagy-promoting.
The researchers first synthesized diselenide-incorporated nanoparticles (SeNPs) with micelle-forming ability and encapsulated isoginkgetin (IGK), a natural flavonoid, known to exhibit autophagy-enhancing and ROS-scavenging activities. The resultant IGK@SeNPs remain stable under physiological conditions but release IGK swiftly upon exposure to high ROS levels as seen in degenerated discs. In vitro studies confirmed the biocompatibility of IGK@SeNPs, their effective uptake by NPCs, and significant reductions in ROS. In a rat IDD model, IGK@SeNP treatment effectively preserved disc height, enhanced MRI signals, and maintained tissue structure compared to IGK or SeNP alone. Histological and immunochemical analyses revealed reduced ECM degradation and apoptosis in the IGK@SeNP group.

Fig. 2 Isoginkgetin‑loaded nanoparticles for the treatment of IDD. (Yu H.; et al. 2023)