Alkaloids from the medicinal plant Incarvillea sinensis: Molecular diversity, synthesis, pharmacological properties and mechanism of action

The plant genus Incarvillea includes several species used in traditional medicine for the treatment of inflammatory diseases and neurodegenerative pathologies in Central Asia. This is the case for the species Incarvillea sinensis Lam. (jiao-hao) used in Chinese medicine for the treatment of rheumatism and various ailments. A variety of alkaloids has been isolated from the plant, including molecules with analgesic properties but also natural products endowed with antitumor activities. The present review provides a survey of the alkaloids isolated from I. sinensis, with a focus on incarvilline-type compounds including incarvillateine, incarvine and incasine derivatives. Bioactive compounds have been identified and used as template for the design of antinociceptive agents or antitumor agents, in the incarvillateine and incarvine series, respectively. The incarvillateine series is difficult to exploit because of the compound has been suspected to trigger neuroinflammation. However, incarvillateine derivatives incorporating a truxillic acid-like moiety are studied as antinociceptive agents. The incarvine series looks more promising with the discovery of antimetastatic products, like incarvine C targeting the GTPase Rac1, frequently overexpressed or mutated in solid tumors. Incarvines C and G represent interesting scaffold to design compounds interfering with the cytoskeleton dynamic via Rac1 inhibition. Altogether, the review shed light on the medicinal interest of Incarvillea sinensis and its bioactive phytoconstituents. The goal is to encourage further studies into the discovery of new Incarvillea natural products and the elucidation of their mechanism of action, while promoting the responsible use of the natural resources.