drimane and Inflammation

A new spiroaxane sesquiterpenoid talaminoid A (1) and two drimane sesquiterpenoid talaminoids B and C (2 and 3), together with four known compounds (4-7), were isolated from the solid culture broth of fungus Talaromyces minioluteum. The structures were determined by extensive 1D and 2D NMR and HRESIMS spectroscopic data analyses, and the absolute configuration of these new compounds were undoubtedly confirmed by X-ray crystal diffrations. Compound 1 is a rare spiroaxane sesquiterpenoid and the absolute configuration of spiroaxane sesquiterpenoid was determined for the first time. Compound 2 is the first drimane-type sesquiterpenoid containing both amino acid residue and butanediol group. Compounds 1, 4, and 5 showed significant suppressive effect on the production of NO on LPS induced BV-2 cells, with IC

Topics: Animals; Anti-Inflammatory Agents; Cells, Cultured; Humans; Inflammation; Inflammation Mediators; Lactones; Lipopolysaccharides; Mice; Molecular Structure; Nitric Oxide; Polycyclic Sesquiterpenes; Sesquiterpenes; Talaromyces

Plants, fungi, and animals generate a diverse array of deterrent natural products that induce avoidance behavior in biological adversaries. The largest known chemical family of deterrents are terpenes characterized by reactive alpha,beta-unsaturated dialdehyde moieties, including the drimane sesquiterpenes and other terpene species. Deterrent sesquiterpenes are potent activators of mammalian peripheral chemosensory neurons, causing pain and neurogenic inflammation. Despite their wide-spread synthesis and medicinal use as desensitizing analgesics, their molecular targets remain unknown. Here we show that isovelleral, a noxious fungal sesquiterpene, excites sensory neurons through activation of TPRA1, an ion channel involved in inflammatory pain signaling. TRPA1 is also activated by polygodial, a drimane sesquiterpene synthesized by plants and animals. TRPA1-deficient mice show greatly reduced nocifensive behavior in response to isovelleral, indicating that TRPA1 is the major receptor for deterrent sesquiterpenes in vivo. Isovelleral and polygodial represent the first fungal and animal small molecule agonists of nociceptive transient receptor potential channels.

Topics: Analgesics; Animals; Chemoreceptor Cells; Inflammation; Mice; Mice, Knockout; Pain; Polycyclic Sesquiterpenes; Sesquiterpenes; Transient Receptor Potential Channels; TRPA1 Cation Channel