Evaluation of Toxicity and Efficacy of Inotodiol as an Anti-Inflammatory Agent Using Animal Model

Abstract

Chaga mushroom (Inonotus obliquus) comprises polyphenolic compounds, triterpenoids, polysaccharides, and sterols. Among the triterpenoid components, inotodiol has been broadly examined because of its various biological activities. The purpose of this study is to examine inotodiol from a safety point of view and to present the potential possibilities of inotodiol for medical usage. From chaga mushroom extract, crude inotodiol (INO20) and pure inotodiol (INO95) were produced. Mice were treated with either INO20 or INO95 once daily using oral administration for repeated dose toxicity evaluation. Serum biochemistry parameters were analyzed, and the level of pro-inflammatory cytokines in the serum was quantified. In parallel, the effect of inotodiol on food allergic symptoms was investigated. Repeated administration of inotodiol did not show any mortality or abnormalities in organs. In food allergy studies, the symptoms of diarrhea were ameliorated by administration with INO95 and INO20. Furthermore, the level of MCPT-1 decreased by treatment with inotodiol. In this study, we demonstrated for the first time that inotodiol does not cause any detrimental effect by showing anti-allergic activities in vivo by inhibiting mast cell function. Our data highlight the potential to use inotodiol as an immune modulator for diseases related to inflammation.

Inotodiol suppresses allergic inflammation in allergic rhinitis mice

“…found that consumption of chaga mushrooms caused oxalate nephropathy, which they determined was due to the high oxalate concentration in the mushrooms. Recently, Nguyen et al 25 . reported that inotodiol does not show any mortality or harm to organs of mice treated with pure inotodiol (95% purity, 20 mg/kg) or crude inotodiol (20% inotodiol, 30 mg/kg).…”

“…23 Kikuchi et al 24 found that consumption of chaga mushrooms caused oxalate nephropathy, which they determined was due to the high oxalate concentration in the mushrooms. Recently, Nguyen et al 25 reported that inotodiol does not show any mortality or harm to organs of mice treated with pure inotodiol (95% purity, 20 mg/kg) or crude inotodiol (20% inotodiol, 30 mg/kg). Thus, to the best of our knowledge, there seems to be no definite adverse effect of inotodiol identified, and additional studies are needed to confirm an ideal dosage.…”

Protective Effects of Lanostane Triterpenoids from Chaga Mushroom in Human Keratinocytes, HaCaT Cells, against Inflammatory and Oxidative Stresses

“…Total RNA was isolated from HaCaT cells using TRIzol (Life Technologies, Carlsbad, CA, USA) according to the manufacturer’s protocol and a previously described method with a slight modification [ 17 ]. cDNA was synthesized from 1 µg RNA by a reverse transcriptional reaction.…”

“…Recently, there has been a movement to identify novel, safe, and effective molecules that can be used for the treatment of various diseases, including inflammatory diseases. So far, it has been reported that inotodiol exerts anti-inflammatory activity without showing detrimental effects in in vivo and in vitro studies [ 17 ]. Also, inotodiol shows an anti-aging effect under oxidative stress by inhibiting MAPK-NOX5 and NF-κB signaling pathways [ 16 ].…”

Plasma proteome responses in zebrafish following λ-carrageenan-Induced inflammation are mediated by PMN leukocytes and correlate highly with their human counterparts

“…The first challenge to overcome is the selection of appropriate animal models to achieve the desired goal. Vertebrate animal models have proven their efficacy in screening inflammatory responses and determining specific molecular therapeutic targets in human medicine ( 23 – 25 ). In this context, zebrafish (ZF) emerged as an outstanding genetically tractable and practical model for screening the biological process of inflammation in vivo ( 26 , 27 ).…”