Laricifomes officinalis – a rich source of pharmacologically active triterpenes

Laricifomes officinalis, (Vill.) Kotl. & Pouzar (Polyporaceae) is a wood rotting fungus growing on living or dead conifers, particularly on larches. It is also known as agarikon, quinine conk, or in German speaking regions as “Apothekerschwamm” referring to its relevance in traditional medicine. L. officinalis might be considered as the most common and versatile used medicinal fungus of the past, used to treat tuberculosis, asthma and cough, night sweats, as laxative, or as bitter to aid digestion [1,2]. In the course of an ongoing project aiming at the search for new therapeutic treatment options for metabolic syndrome, extracts of L. officinalis were tested in a protein tyrosine phosphatase 1B (PTB1B) assay. This enzyme is a key regulator of insulin-receptor activity reversing the autophosphorylation of the receptor, and also acting at downstream signalling components. As an elevated PTP1B expression can be associated with obesity and insulin resistance, PTP1B is discussed as possible new target for the treatment of diabetes type 2 and obesity [3]. A methanolic and an ethyl acetate extract showed significant inhibitory activity on PTP1B (> 85% at 30 µg/mL). A first fast fractionation of the ethyl acetate extract revealed that agaricinic acid (82% at 30 µg/mL), as well as a terpenoid containing fraction (84% at 30 µg/mL) distinctively contributed to this activity. Furthermore, known constituents of L. officinalis [2] were screened with two sets of structure-based pharmacophore models (Discovery Studio and Ligandscout) resulting in the identification of several triterpene derivatives as potential PTP1B inhibitors. These findings led to the phytochemical investigation of the terpene-profile of this fungus. In a first step a HPLC-DAD-APCI-MS/MS method was developed for the comprehensive profiling and characterisation of the terpenoids in L. officinalis. The following phytochemical work-up of the extract resulted in the isolation and structural characterisation of the sesquiterpene lacrinolic acid and 24 lanostane triterpenes. Nine compounds were already known as constituents from this fungus, seven triterpenes are described the first time for L. officinalis, and further eight triterpenes were identified as new natural products. Evaluation of the isolated compounds for their inhibitory effects on PTP1B is in progress.

Keywords: Laricifomes officinalis, Polyporaceae, protein tyrosine phosphatase 1B, lanostane-type triterpenes, HPLC-DAD-APCI-MS/MS.

References:

[1] Molitoris HP. Pilze in Medizin, Folklore und Religion. Feddes Repertorium 2002; 113: 165 – 182

[2] Grienke U, Zöll M, Peintner U, Rollinger JM. European medicinal polypores – A modern view on traditional uses. J Ethnopharmacol 2014; 154: 564 – 583

[3] Johnson TO, Ermolieff J, Jirousek MR. Protein Tyrosine Phosphatase 1b Inhibitors for diabetes. Nat Rev Drug Discov 2002; 1: 696 – 709

No conflict of interest has been declared by the author(s).