Grayanane diterpenoids from Rhododendron molle: Structural diversity, mechanisms of antinociceptive action, and structure-activity relationships

Abstract

Rhododendron molle (Blume) G. Don is a plant of great significance in traditional Chinese medicine, particularly valued for its analgesic properties. This review systematically consolidates contemporary research on its phytochemistry, pharmacology, and structure-activity relationships. Over 200 compounds have been identified, with diterpenoids—notably those featuring 12 novel carbon skeletons—recognized as the principal bioactive and toxic constituents. These compounds underpin the plant's broad pharmacological profile, including marked anti-inflammatory, immunomodulatory, and potent antinociceptive activities. A central contribution of this review is a critical structure-activity relationships analysis that systematically identifies key functional groups (e.g., the C-2 and C-3 hydroxyls) as pivotal for the antinociceptive efficacy of grayanane diterpenoids. Promising lead compounds, such as Rhodojaponin III, are highlighted for their potential in developing new therapeutics for rheumatoid arthritis and neuropathic pain, as well as natural insecticides. By integrating traditional knowledge with modern science, this review not only validates the traditional uses of R. molle but also provides a foundational framework for future research, explicitly pointing to the need for in-depth mechanistic studies, comprehensive toxicity profiling, and rational drug development.