Molecular and cellular functions of natural products

The natural substances are ingredients from medicinal plants such as triterpene acids (boswellic acids, tirucallic acids, lupanic acids, etc.) from frankincense resin (Boswellia species), acylphloroglucinols (e.g. hyperforin, myrtucommulone, garcinol, arzanol, etc.), curcuminoids, cannabinoids, and indirubins, as well as natural products from bacteria and fungi (e.g. α-hemolysin, gliotoxin, and melleolides). The aim is to identify molecular target structures and the underlying molecular/biochemical mechanisms as well as to clarify the pharmacological relevance of the drug-target interactions. Together with collaboration partners, total syntheses of selected natural products are being undertaken in order to create substance libraries for lead optimization. The molecular pharmacological evaluation takes into account important in vivo-relevant regulatory mechanisms and is intended to provide new options/targets for molecular interference with the target structures. This knowledge helps on the one hand, to develop therapeutics and, on the other hand, to reveal new protein functionalities in pathobiochemical processes (active agents as tools).

Key publications:

Peltner L., Gluthmann L., Börner F., Pace S., Hoffstetter R.K., Kretzer C., Bilancia R., Pollastro F., Koeberle A., Appendino G., Rossi A., Newcomer M.E., Gilbert N.C., Werz O.*, Jordan P.M.* (2023) Cannabidiol acts as molecular switch in innate immune cells to promote the biosynthesis of inflammation-resolving lipid mediators. Cell Chem. Biol., 30(12):1508-1524.

Börner F., Pace S., Jordan P.M., Gerstmeier J., Gomez M., Rossi A., Gilbert N.C., Newcomer M.E., Werz O. (2023) Allosteric activation of 15-lipoxygenase-1 by boswellic acid induces the lipid mediator class switch to promote resolution of inflammation. Adv Sci, 10(6):e2205604

Pace S., Zhang K., Jordan P.M., Bilancia R., Wang W., Börner F., Hofstetter K., Potenza M., Kretzer C., Gerstmeier G., Fischer D., Lorkowski S., Gilbert N.C., Newcomer M.E., Rossi A., Chen X., Werz O. (2021) Anti-inflammatory celastrol promotes a switch from leukotriene biosynthesis to formation of specialized pro-resolving lipid mediators. Pharmacol Res, 167:105556

Collaborative Research Centers/Research groups: 

DFG SFB1127 „ChemBioSys“

DFG SFB1278 „Polytarget“

TAB-Forschergruppe “Nature4HEALTH“