Immunology and Immunopharmacology Laboratory, College of Pharmacy and Pharmaceutical Science, Chungnam National University, 99 Daehak-ro Yuseong-gu, Daejeon 34134, Republic of Korea.
Natural Products Laboratory, College of Pharmacy and Pharmaceutical Science, Chungnam National University, 99 Daehak-ro Yuseong-gu, Daejeon 34134, Republic of Korea.
Int Immunopharmacol. 2020 Apr;81:106244. doi: 10.1016/j.intimp.2020.106244. Epub 2020 Feb 5.
Inotodiol is a lanostane triterpenoid found only in Chaga mushroom. In the previous study investigating anti-allergic effects of fractionated Chaga mushroom extracts, we have found evidence that purified inotodiol holds an activity to suppress the mast cell function in vivo. To address the therapeutic relevance of the finding, in this study, we investigated whether inotodiol could also alleviate allergy symptoms observed in a chicken ovalbumin (cOVA)-induced mouse model of food allergy. Like the crude 70% ethanol extract of Chaga mushroom (320 mg/kg), oral administration of inotodiol (20 mg/kg), regardless of whether that was for preventive or treatment purpose, resulted in a significant improvement in allergic symptoms and inflammatory lesions in the small intestine appearing after repeated oral challenge with cOVA. Despite the results that inotodiol (20 mg/kg) and the Chaga mushroom extract (320 mg/kg) took effect to a similar extent, immunological mechanisms underlying those effects were found to be distinct from each other. That is, the results obtained from several in vivo assays, including mast cell-mediated passive systemic anaphylaxis, activation/proliferation of adoptively transferred antigen-specific T cells and immunoglobulin (IgG1, IgE, IgA) production by antigen-specific B cells, illustrated that inotodiol selectively inhibited the mast cell function without having any noticeable effect on other immune responses while the crude Chaga mushroom extract indiscriminately suppressed diverse immune responses. The strong anti-allergic activity of inotodiol, along with its remarkable selectivity to mast cell, makes it an excellent therapeutic candidate for food allergy with both high efficacy and outstanding safety.
桦褐孔菌醇是一种仅存在于桦褐孔菌中的羊毛甾烷三萜。在之前研究桦褐孔菌提取物的抗过敏作用的研究中，我们发现纯化的桦褐孔菌醇具有抑制体内肥大细胞功能的活性。为了探讨这一发现的治疗相关性，在本研究中，我们研究了桦褐孔菌醇是否也可以减轻鸡卵白蛋白（cOVA）诱导的食物过敏小鼠模型中观察到的过敏症状。与桦褐孔菌的 70%乙醇粗提物（320mg/kg）一样，桦褐孔菌醇（20mg/kg）的口服给药，无论是预防还是治疗，均能显著改善反复口服 cOVA 后出现的过敏症状和小肠炎症病变。尽管桦褐孔菌醇（20mg/kg）和桦褐孔菌提取物（320mg/kg）的效果相当，但它们的免疫机制彼此不同。也就是说，从几项体内试验中获得的结果，包括肥大细胞介导的被动全身性过敏反应、过继转移的抗原特异性 T 细胞的激活/增殖以及抗原特异性 B 细胞产生的免疫球蛋白（IgG1、IgE、IgA），表明桦褐孔菌醇选择性抑制肥大细胞功能，而对其他免疫反应没有明显影响，而粗桦褐孔菌提取物则无差别地抑制多种免疫反应。桦褐孔菌醇具有强大的抗过敏活性，并且对肥大细胞具有显著的选择性，使其成为一种具有高效和出色安全性的食物过敏的理想治疗候选药物。
