Elm tree (Ulmus parvifolia) bark bioprocessed with Mycelia of Shiitake (Lentinus edodes) mushrooms in liquid culture: Composition and mechanism of protection against allergic asthma in mice

Authors: KIM, S.P. - Ajou University Of Korea; LEE, S.J. - Str Biotech Co Ltd; NAM, S.H. - Ajou University Of Korea; Friedman, Mendel

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/14/2016
Publication Date: 1/25/2016
Citation: Kim, S., Lee, S., Nam, S., Friedman, M. 2016. Elm tree (Ulmus parvifolia) bark bioprocessed with Mycelia of Shiitake (Lentinus edodes) mushrooms in liquid culture: Composition and mechanism of protection against allergic asthma in mice. Journal of Agricultural and Food Chemistry. 64(4):773-784. https://doi.org/10.1021/acs.jafc.5b04972.
DOI: https://doi.org/10.1021/acs.jafc.5b04972

Interpretive Summary: Asthma is a multifaceted chronic inflammatory disease of the lung airways, resulting in bronchial hyper-responsiveness following exposure to an allergen. There is no cure. Protein biomarkers can serve as a powerful detection tool in both clinical and basic research applications. The results of the present study with asthma-associated biomarkers (cytokines in serum and bronchoalveolar fluid, serum IgG and other biomarker levels, and inflammatory cell infiltration in the trachea and lungs) as well as RT-PCR and Western blot analysis of associated genes all show that the bioprocessed bark of the elm tree in a liquid mushroom mycelia culture normalized antigen-triggerred immune imbalance of the of the two T-helper proteins (Th1/Th2) in an mouse asthma model, suggesting that the treatment overcame the manifestations of the numerous biomarkers associated with the asthmatic syndrome. We do not know which of the 116 individual compounds or combination of compounds, characterized by gas chromatography and mass spectrometry, in the bioprocessed product might be responsible for the exceptional anti-allergic properties. The bioprocessed product was not toxic to leukemia cells, suggesting that it might be a safe product. The mouse assays demonstrate the potential value of the bioactive formulation as an anti-inflammatory and anti-allergic formulation that has the potential to prevent and/or treat allergic human diseases such as hay fever and asthma.

Technical Abstract: The present study investigated the antiasthma effect of a bioprocessed Ulmus parvifolia bark extract (BPUBE) from Lentinus edodes liquid mycelia culture against allergic asthma biomarkers in U266B1 leukemia cells and OVA-sensitized/challenged mice. BPUBE suppressed total IgE release from U266B1 cells in a dose dependent manner (6, 7, and 22% suppressions at 1, 10, and 100 µg/mL, respectively) without cytotoxicity. Inhibitory activity of BPUBE against OVA-specific IgE secretion to bronchoalveolar lavage fluid (BALF) was confirmed in OVA-sensitized/challenged asthmatic mice (83% inhibition at 10 mg/kg of oral administration). BPUBE also inhibited OVA-specific IgG and IgG1 secretion into serum from the allergic mice (75 and 83% inhibitions, respectively), suggesting restoration of Th2-biased immune reaction to a Th1/Th2-balanced-status. This was confirmed by the Th2 cytokine profile changes caused by BPUBE in serum or BALF. The release of IL-4, IL-5, and IL-13 was markedly suppressed (74, 72 and 73% inhibition, respectively),, while low inhibitions (~15%) were observed for IL-2, IL-10 and IL-12 release levels. Inflammatory cell counts in BALF and lung histology showed that leukocytosis and eosinophilia induced by OVA-sensitization/challenge were inhibited by oral administration of BPUBE based (62% reduction of leukocytes, 55% of eosinophils). Amelioration of eosinophil infiltration near the trachea was associated with reduced eotaxin and VCAM-1 levels. Changes in pro-inflammatory mediator levels in BALF suggest that BPUBE decreased OVA-sensitization/challenge-induced elevation of LTC4 and PGD2. Suppression by NPUBE of OVA-sensitization/challenge-induced asthma was much lower than by BPUBE, suggesting the usefulness of bioprocessing of bark in a fungal mycelia culture to elevate anti-asthmatic properties. These mechanistic biomarkers of the bioprocessed formulation are similar to those reported by other investigators for anti-asthmatic drugs. The novel formulation has the potential to serve as a new functional food.