Bioactive triterpenoids and water-soluble melanin from Inonotus obliquus (Chaga) with immunomodulatory activity

Abstract

• A water-soluble I. obliquus melanin inhibited the human complement cascade. • The melanin fraction was nontoxic against bacteria commonly found in the human gut. • The triterpenoid 3β-hydroxy-8,24-dien-21-al activated the human complement cascade. • Several triterpenoids were highly active against colon carcinoma cell line HT29-MTX. The fungus Inonotus obliquus has historically been used in traditional medicine in Europe and Asia. A melanin fraction and six triterpenoids were obtained from I. obliquus sclerotia, and evaluated in various bioassays including for immunomodulatory, cytotoxicity and enzyme-interacting properties . The water-soluble, nitrogen-free melanin fraction and the triterpenoids 3β-hydroxy-8,24-dien-21-al ( 1 ) and inotodiol ( 2 ) displayed potent activity in a human complement assay. The melanin fraction inhibited the complement cascade, whereas 1 and 2 activated the same cascade. Compound 2 , as well as betulinic acid ( 3 ) and betulin ( 4 ) had anti-proliferative properties against the colon adenocarcinoma cell line HT29-MTX. Further, the melanin fraction and betulin-3- O- caffeate ( 6 ) reduced nitric oxide production in primary murine macrophages. Furthermore, the metabolites were nontoxic against the common gut bacteria E. coli and B. subtilis . The results demonstrate the anti-inflammatory and immunomodulatory effects of I. obliquus melanin and triterpenoids, which could potentially justify the consumption of this increasingly popular “edible” fungus.