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During the last 40 years medicinal effects of the related Basidiomycetes mushrooms, Agaricus blazei Murill (AbM) and Grifola frondosa (GF) from Brazilian and Eastern traditional medicine, respectively, have been documented scientifically. Extracts of the mushrooms also appear to be safe in preclinical and clinical studies. Whereas special focus has been on their antitumor effects, the mushrooms' anti-allergic properties have also been investigated. The anti-allergic mechanism was amelioration of a skewed Th1/Th2 balance. Here, a brief review is given of the preclinical and clinical findings with AbM and GF.
- Antiallergic
- Agaricus blazei
- Grifola frondosa
- mushrooms
- clinical studies
1.Introduction
During the last 40 years medicinal effects of the related Basidiomycetes mushrooms, Agaricus blazei Murill (AbM) and Grifola frondosa (GF) from Brazilian and Eastern traditional medicine, respectively, have been documented scientifically.
2. Antiallergic Effects
An Agaricus blazei (AbM) extract has been shown[1] [1] to inhibit induced anaphylactic reaction, including passive immunization, i.e., ear-swelling, in a mouse model by a treatment effect on the mast cell reaction (Table 1). In another mouse allergic asthma model with orally administered AbM extract, reduced levels were observed of specific immunoglobulin (Ig)E, IgG1 and bronchial eosinophils owing to amelioration of skewed T helper cell (Th)1/Th2 balance[2] [2]. This was confirmed by us with the AbM-based and GF-containing extract, AndosanTM, in the similar ovalbumin (OVA)-induced allergic sensitization mouse model, in which specific IgE and IgG1 were also reduced and Th1 response increased relative to Th2[3] [3]. By use of this OVA sensitization mouse model for allergy, the mechanism behind the reduced specific IgE and improved Th1/Th2 balance was found to be AbM promotion of epithelial cell-induced macrophage (MΦ) activation and naïve T cells differentiation to Th1 cells[4] [4]. Recently, we undertook a placebo-controlled randomized clinical study where blood donors with self-reported and specific IgE-confirmed birch allergy and asthma, were given AndosanTM orally for 2 months prior to the pollen season. They had less general allergy and asthma ailments and used less medication for the diseases[5] [5]. This was caused by reduced specific IgE levels and reduced mast cell sensitization, as shown indirectly by the basophil activation test, a surrogate for mast cell activation (Table 2)[5].
Table 1.
Anti-allergic Effects of
Agaricus blazei
Murill and
Grifola frondosa
(*Human study).
|
Product, Admin. |
Study In, Of |
Effects |
Mechanism |
Author, Year |
|
AbM mycelia water extract incl. HE, GF, p.o. (Andosan) |
Placebo-ctr RCT in blood donors, Pollen allergy & asthma (n = 60) |
↓ General symptoms, and medication |
↓ Spec. IgE, reduced basophil sensitivity |
*Mahmood et al., 2019 (5) |
|
Water AbM extract, p.o. |
Mice, Allergy |
↓ OVA sensitization |
↓ Spec. IgE, improv. Th1/Th2 balance via MF activ. by epithelial cc, diff. promotion of naïve T cc to Th1 cc |
Bouike et al., 2011 (4) |
|
AbM mycelia water extract incl. HE, GF, p.o. (Andosan) |
Mice, Allergy |
↓ OVA sensitization |
↓ Spec. IgE, IgG1 and improved Th1/Th2 balance |
Ellertsen & Hetland 2009 (3) |
|
AbM water extract, p.o. |
Mice, Asthma |
↓ Spec. IgE, IgG1 and bronchial eosinophils |
Amelioration of skewed Th1/Th2 balance |
Takimoto et al., 2008 (2) |
|
AbM water extract, p.o. |
Mice, Anaphylaxis |
Inhib. of induced anaphylactic reaction and ear swelling |
Treatment of mast cell mediated anaphylactic reaction |
Choi et al., 2006 (1) |
|
GF alcohol extract and ergosterol, p.o. |
Mice, Allergic inflammation |
Inhib. mast cc degranulation, alleviated anaphylactic cutaneous response |
↓ Type 1 allergic reaction by suppression of mast cc degranulation |
Kawai et al., 2019 (6) |
|
GF polysacch, p.o. |
Mice, AD |
Inhib. AD-like skin lesion |
↓ IgE, mast cc infiltr., cytokine express. controlling Th1/Th2 |
Park et al., 2015 (7) |
|
Product, Admin. |
Study In, Of |
Effects |
Mechanism |
Author, Year |
|
AbM mycelia water extract incl. HE, GF, p.o. (Andosan) |
Placebo-ctr RCT in blood donors, Pollen allergy & asthma (n = 60) |
↓ General symptoms, and medication |
↓ Spec. IgE, reduced basophil sensitivity |
*Mahmood et al., 2019[5] |
|
Water AbM extract, p.o. |
Mice, Allergy |
↓ OVA sensitization |
↓ Spec. IgE, improv. Th1/Th2 balance via MF activ. by epithelial cc, diff. promotion of naïve T cc to Th1 cc |
Bouike et al., 2011[4] |
|
AbM mycelia water extract incl. HE, GF, p.o. (Andosan) |
Mice, Allergy |
↓ OVA sensitization |
↓ Spec. IgE, IgG1 and improved Th1/Th2 balance |
Ellertsen & Hetland 2009[3] |
|
AbM water extract, p.o. |
Mice, Asthma |
↓ Spec. IgE, IgG1 and bronchial eosinophils |
Amelioration of skewed Th1/Th2 balance |
Takimoto et al., 2008[2] |
|
AbM water extract, p.o. |
Mice, Anaphylaxis |
Inhib. of induced anaphylactic reaction and ear swelling |
Treatment of mast cell mediated anaphylactic reaction |
Choi et al., 2006[1] |
|
GF alcohol extract and ergosterol, p.o. |
Mice, Allergic inflammation |
Inhib. mast cc degranulation, alleviated anaphylactic cutaneous response |
↓ Type 1 allergic reaction by suppression of mast cc degranulation |
Kawai et al., 2019[6] |
|
GF polysacch, p.o. |
Mice, AD |
Inhib. AD-like skin lesion |
↓ IgE, mast cc infiltr., cytokine express. controlling Th1/Th2 |
Park et al., 2015[7] |
Abbreviations: immunoglobulin (Ig), ovalbumin (OVA), atopic dermatitis (AD)，Grifola frondosa （GF）.
Form Hetland et al., 2020[8] [8].
Table 2. Basophil maximal (peak) reactivity during intervention in birch pollen allergic blood donors before and after the pollen season
|
Table 2 |
Basophil maximal (peak) reactivity during intervention in birch pollen allergic blood donors before and after the pollen season |
|||
|
Bet v 1 conc. (ng/ml) |
Placebo |
Andosan |
||
|
Peak before |
Peak after |
Peak before |
Peak after |
|
|
|
|
|
|
|
|
100 |
1 (5.2 %) |
|
|
1 (4.1) |
|
10 |
7 (36.8) |
|
4 (16.6) |
1 (4.1) |
|
1 |
11 (57.8) |
17 (89.4) |
20 (83.3) |
19 (79.1) |
|
0.1 |
|
2 (10.5) |
|
3 (12.5) |
|
Mean |
9.52 ±5.12 |
0.90* ±0.06 |
2.50 ±0.69 |
5.38^ ±4.12
|
|
Total |
19 (100%) |
19 (100) |
24 (100) |
24 (100) |
|
Bet v 1 conc. (ng/ml) |
Placebo |
Andosan |
||
|
Peak before |
Peak after |
Peak before |
Peak after |
|
|
|
|
|
|
|
|
100 |
1 (5.2 %) |
|
|
1 (4.1) |
|
10 |
7 (36.8) |
|
4 (16.6) |
1 (4.1) |
|
1 |
11 (57.8) |
17 (89.4) |
20 (83.3) |
19 (79.1) |
|
0.1 |
|
2 (10.5) |
|
3 (12.5) |
|
Mean |
9.52 ±5.12 |
0.90* ±0.06 |
2.50 ±0.69 |
5.38^ ±4.12
|
|
Total |
19 (100%) |
19 (100) |
24 (100) |
24 (100) |
*p=0.004 vs. before pollen season, ^p=0.062 vs. before pollen season.
Abbreviation: Bet v 1 is the major birch pollen allergen. Modified from Mahmood et al, 2019[5] [5].
Moreover, in mice with orally administered GF polysaccharide or extract (Table 1), antiallergic effects have also been observed: Atopic dermatitis-like skin lesions and mast cell degranulation were inhibited due to alleviated anaphylactic cutaneous response[6][7] [6,7]. This was found to be caused by reduced IgE and mast cell infiltration, a cytokine expression that ameliorated the Th1/Th2 imbalance[7] [7], and a reduced type I allergic response by suppression of mast cell degranulation[6] [6]. Hence, GF polysaccharides could be used as a novel therapeutic drug instead of corticosteroids or as supplementary treatment[7] [7].
References:
- Choi, Y.H.; Yan, G.H.; Chai, O.H.; Choi, Y.H.; Zhang, X.; Lim, J.M.; Kim, J.H.; Lee, M.S.; Han, E.H.; Kim, H.T.; et al. Inhibitory effects of Agaricus blazei on mast cell-mediated anaphylaxis-like reactions. Biol. Pharm. Bull. 2006, 29, 1366–1371. doi:10.1248/bpb.29.1366.
- Takimoto, H.; Kato, H.; Kaneko, M.; Kumazawa, Y. Amelioration of skewed Th1/Th2 balance in tumor-bearing and asthma-induced mice by oral administration of Agaricus blazei extracts. Immunopharmacol. Immunotoxicol. 2008, 30, 747–760. doi:10.1080/08923970802279092.
- Ellertsen, L.K.; Hetland, G. An extract of the medicinal mushroom Agaricus blazei Murill can protect against allergy. Clin. Mol. Allergy 2009, 7, 6. doi:10.1186/1476-7961-7-6.
- Bouike, G.; Nishitani, Y.; Shiomi, H.; Yoshida, M.; Azuma, T.; Hashimoto, T.; Kanazawa, K.; Mizuno, M. Oral Treatment with Extract of Agaricus blazei Murill Enhanced Th1 Response through Intestinal Epithelial Cells and Suppressed OVA-Sensitized Allergy in Mice. Evid. Based Complement Altern. Med. 2011, 2011, 1–11. doi:10.1155/2011/532180.
- Mahmood, F.; Hetland, G.; Nentwich, I.; Mirlashari, M.R.; Ghiasvand, R.; Nissen-Meyer, L.S.H. Agaricus blazei-Based Mushroom Extract Supplementation to Birch Allergic Blood Donors: A Randomized Clinical Trial. Nutrients 2019, 11, 2339. doi:10.3390/nu11102339.
- Kawai, J.; Mori, K.; Hirasawa, N. Grifola frondosa extract and ergosterol reduce allergic reactions in an allergy mouse model by suppressing the degranulation of mast cells. Biosci. Biotechnol. Biochem. 2019, 83, 2280–2287. doi:10.1080/09168451.2019.1654360.
- Park, H.S.; Hwang, Y.H.; Kim, M.K.; Hong, G.E.; Lee, H.J.; Nagappan, A.; Yumnam, S.; Kim, E.H.; Heo, J.D.; Lee, S.J.; et al. Functional Polysaccharides from Grifola Frondosa Aqueous Extract Inhibit Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice. Biosci. Biotechnol. Biochem. 2015, 79, 147–154. doi:10.1080/09168451.2014.963500.
- Hetland G, Tangen JM, Mahmood F, et al. Antitumor, Anti-Inflammatory and Antiallergic Effects of Agaricus blazei Mushroom Extract and the Related Medicinal Basidiomycetes Mushrooms, Hericium erinaceus and Grifolafrondosa: A Review of Preclinical and Clinical Studies. Nutrients. 2020;12(5):E1339. Published 2020 May 8. doi:10.3390/nu12051339
