Medicinal Mushrooms & Inflammation

Last Updated on August 25, 2022

Introduction

Inflammation constitutes the cell’s response to pathogens, infection and tissue damage. Involving a drastically ordered and coordinated communication of different immune cells and blood vessels through an intricate cascade of molecular signals, inflammation causes symptoms such as fever, allergy anaphylaxis, etc.
Inflammation has four phases: inflammatory inducers (infection or tissue damage), inflammatory sensors (mast cells and macrophages), inflammatory mediators (cytokines, chemokines, etc.) and the tissues that are affected [3]. Each phase has many options that are triggered based on the type pathogen introduced [1]. For example bacterial pathogens trigger toll- like receptors (TLRs) and viral infections trigger type I interferons (IFN) [3]. Key modulators of inflammatory response pathway are – Nuclear factor kappa-light-chain- enhancer of activated B cells (NF-κB), and signal transducer and activator of transcription (STAT)[5]. NF-κB functions as the regulator of the acute phase of inflammation. 

The acute phase is where homeostasis is re-established after inflammatory induction. NF-κB acts by regulating the expression of the cytokines that are inflammatory mediators. These cytokines include IL-1, IL-6, TNF- α, lymphotoxin and IFN-γ. In addition, IL-1 and TNF-α work to activate NF-κB, therefore creating a feedback loop [2]. The STAT family of proteins serves multiple functions during inflammation depending on the type of inflammatory inducer. The type of inducer determines which cytokines are triggered. Those cytokines activate a STAT protein, which either increases or decreases inflammation. For instance, when the body comes into contact with a viral infection various IFNs are triggered and activate STAT1 and STAT2 that act in an antiviral capacity to decrease inflammation. In contrast, STAT6 helps with differentiation of T helper cells. Subject to the type of differentiation, the T helper cells can positively influence allergic inflammation and negatively affect autoimmunity [6].

Inflammation and Chaga

A plethora of studies have highlighted the potential molecular mechanisms of actions of Chaga mushroom such as its ability to scavenge reactive oxygen species, decrease inflammation and insulin resistance in type 2 diabetes, and stimulate the immune system [7]

The mycelial endopolysaccharide of Chaga was reported to be as an immune response modifier candidate : Enhanced proliferation and polyclonal immunoglobulin M antibody production were observed in B cells when purified with water-soluble Chaga endo-polysaccharide. Nitrite production and expression of IL-1h, IL-6, TNF-a, and iNOS in macrophages were also enhanced. The endo- polysaccharide showed activities similar to lipopolysaccharide (LPS) for B cells and macrophages [8].

In animal model experiments, Chaga was observed to attenuate histamine-induced inflammation conducted vasodilation in second-order arterioles in the gluteus maximus muscle of mice and reduced the disturption of junctionnal integrity [9]

Also, it was reported that Chaga triterpenoids (TAIO) exerced an anti-inflammatory effect when administrated during hyperuricemia, a disease usually accompanied by inflammation, which increases the levels of inflammatory factors such as IL-6 and TNF-α, leading to the serious inflammatory reaction in vivo. TAIO injection to hyperuricemic mice, lowered Interleukin-6 level and it is suggested that TAIO would have effect on controlling hyperuricemia as an active supplement [10].

Inflammation and Cordyceps

There are a number of compounds present in the Cordyceps extracts possessing an immunomodulatory activity. Active constituents of Cordyceps are spotted by TLRs) and C-type lectin receptors during initiation of immunomodulation and hyporesponsiveness in antigen-presenting cells (APCs). These active constituents not only alter the TLRs and CLRs expression in APCs but also masterfully manipulate their intracellular signaling. Active bio-constituents of Cordyceps spp. transmit TLR4 signaling to MAPK pathway and extracellular signal-related kinase 1 and 2 (ERK1/2) activation backing Treg/Th2 induction. Furthermore, active constituents of Cordyceps inactivates the pro-inflammatory molecules MyD88 and NF-κB [11]

Since the synthesis of NO by iNOS is elevated in inflammatory ailments and leads to cellular injury, the activity of Cordyceps militaris on nitric oxide synthase (iNOS) expression confirms its anti- inflammatory action [12]. The extract (ethanolic) of cultured mycelia of Cordyceps .militaris had been shown to have anti-inflammatory activity in the carrageenan-triggered edema and by reducing nitric oxide synthase (iNOS) levels in macrophages. In lipopolysaccharide -induced macrophage, NO production was restrained by butanolic fraction of Cordyceps militaris particularly Cordycepin which inhibited the phosphorylation of protein kinase B (Akt), IκBα, and p38 and also suppressed TNF-α, cyclooxygenase-2 (COX-2), and NF-κB translocation in these macrophages. Thus, hinted at the use of Cordycepin for inflammation-linked disorders [13].Cordyceps sinensis extracts are also used as an alternative cost effective immunosuppressive agent with few adverse effects [14]. Moreover, in vitro experiments had demonstrated Cordycepin and Cordyceps. sinensis are regulating the functions of human immune cells by inducing IL-1β, -6, -8, -10 and TNF-α expression of resting cells, and by inhibiting the phytohemagglutinin-induced expression of IL-2, -4, -5, -12 and IFN-γ and TNF-α [15].
A heteropolysaccharide extracted from Cordyceps. sinensis was reported to be an immune-stimulator during experimentations on mice exposed to ionizing radiation by reducing oxidative injury and modulating the secretion of cytokines (IL-4, -5 and -17) [16].Also, the immunosuppressive effect of methanolic fractions of Cordyceps. sinensis is observed in the inhibition of blastogenesis, NK cells activity, and phytohemagglutinin induced IL-2 and TNF-α production in human mononuclear cells[17]. The treatment of macrophages with diverse concentrations of Cordyceps militaris had suppressed inflammatory mediators production as NO , TNF-α, and IL-6 [18].

Inflammation and Lion’s Mane

It was demonstrated that Lion’s Mane attenuates the excessive generation of NO, ROS and PGE 2 suppresses the expression of pro-inflammatory genes through the inhibition of NF-κB and JNK pathways activity [18].

Inflammation and Reishi

It had been demonstrated that Reishi possesses a strong anti-inflammatory activity through inhibiting the overproduction of NO and pro-inflammatory cytokines, like interleukin-6 (IL-6) and interleukin-1β (IL-1β) induced by LPS, results that implied the potential of GLSP on gut barrier protection [23] as well as to reduce levels of pro-inflammatory cytokines and increase the expression and serum levels of growth factors and anti-inflammatory cytokines in oral ulcer animal models [24].

The Dermatophagoides pteronyssinus induced allergy and subsequent inflammation in male rats used as animal model had been treated with Reishi extracts preparations and had shown signs of an effective immunotherapy [19].

Also, during peanut-induced allergy in a rat model Reishi extract had shown a mitigation effect due to β-glucans available in Reishi which had stimulated the production of T-cells, IFN- γ, CD81 and conferred a long-term protection from anaphylactic shock [21-22]. 

References

1. Medzhitov R. (2008). Origin and physiological roles of inflammation. Nature, 454(7203), 428– 435. https://doi.org/10.1038/nature07201 

2. Ghosh, S., May, M. J., & Kopp, E. B. (1998). NF-kappa B and Rel proteins: evolutionarily  conserved mediators of immune responses. Annual review of immunology, 16, 225–260.  https://doi.org/10.1146/annurev.immunol.16.1.225 

3. Medzhitov R. (2010). Inflammation 2010: new adventures of an old flame. Cell, 140(6), 771– 776. https://doi.org/10.1016/j.cell.2010.03.006 

4. Aggarwal, B. B., Vijayalekshmi, R. V., & Sung, B. (2009). Targeting inflammatory pathways for  prevention and therapy of cancer: short-term friend, long-term foe. Clinical cancer research :  an official journal of the American Association for Cancer Research, 15(2), 425–430.  https://doi.org/10.1158/1078-0432.CCR-08- 

5. Porta, C., Larghi, P., Rimoldi, M., Totaro, M. G., Allavena, P., Mantovani, A., & Sica, A. (2009).  Cellular and molecular pathways linking inflammation and cancer. Immunobiology, 214(9- 10), 761–777. https://doi.org/10.1016/j.imbio.2009.06.014 

6. Kaplan M. H. (2013). STAT signaling in inflammation. JAK-STAT, 2(1), e24198.  https://doi.org/10.4161/jkst.24198 

7. Duru, K. C., Kovaleva, E. G., Danilova, I. G., & van der Bijl, P. (2019). The pharmacological  potential and possible molecular mechanisms of action of Inonotus obliquus from preclinical  studies. Phytotherapy research : PTR, 33(8), 1966–1980. https://doi.org/10.1002/ptr.6384 

8. Kim, Y. O., Han, S. B., Lee, H. W., Ahn, H. J., Yoon, Y. D., Jung, J. K., Kim, H. M., & Shin, C. S.  (2005). Immuno-stimulating effect of the endo-polysaccharide produced by submerged  culture of Inonotus obliquus. Life sciences, 77(19), 2438–2456.  https://doi.org/10.1016/j.lfs.2005.02.023 

9. Javed, S., Mitchell, K., Sidsworth, D., Sellers, S. L., Reutens-Hernandez, J., Massicotte, H. B.,  Egger, K. N., Lee, C. H., & Payne, G. W. (2019). Inonotus obliquus attenuates histamine induced microvascular inflammation. PloS one, 14(8), e0220776.  https://doi.org/10.1371/journal.pone.0220776 

10. Luo, L. S., Wang, Y., Dai, L. J., He, F. X., Zhang, J. L., & Zhou, Q. (2022). Triterpenoid acids from  medicinal mushroom Inonotus obliquus (Chaga) alleviate hyperuricemia and inflammation in  hyperuricemic mice: Possible inhibitory effects on xanthine oxidase activity. Journal of food  biochemistry, 46(3), e13932. https://doi.org/10.1111/jfbc.13932 

11. Das, G., Shin, H.S., Leyva-Gómez, G., Prado-Audelo, M.L.D., Cortes, H., Singh, Y.D., Panda, M.K., Mishra, A.P., Nigam, M., Saklani, S., Chaturi, P.K., Martorell, M., Cruz-Martins, N.,  Sharma, V., Garg, N., Sharma, R., Patra J.K.( 2021) Cordyceps spp.: A review on its immune stimulatory and other biological potentials. Frontiers of Pharmacology .11:602364.  https://doi.org/10.3389/fphar.2020.602364 

12. Won, S. Y., & Park, E. H. (2005). Anti-inflammatory and related pharmacological activities of  cultured mycelia and fruiting bodies of Cordyceps militaris. Journal of  ethnopharmacology, 96(3), 555–561. https://doi.org/10.1016/j.jep.2004.10.009 

13. Kim, H. G., Shrestha, B., Lim, S. Y., Yoon, D. H., Chang, W. C., Shin, D. J., Han, S. K., Park, S. M.,  Park, J. H., Park, H. I., Sung, J. M., Jang, Y., Chung, N., Hwang, K. C., & Kim, T. W. (2006). 

Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF kappaB through Akt and p38 inhibition in RAW 264.7 macrophage cells. European journal of  pharmacology, 545(2-3), 192–199. https://doi.org/10.1016/j.ejphar.2006.06.047 

14. Li, T., & Li, W. (2008). Impact of Polysaccharides from Cordyceps on Anti-fatigue in mice. Sci  Res Essay. 4. 

15. Zhou, X., Luo, L., Dressel,W., Shadier,G., Krumbiegel,D., Schmidtke,P., Zepp F., and Meyer  C.U.,(2008). Cordycepin is an immunoregulatory active ingredient of Cordyceps sinensis. The  American Journal of Chinese Medicine 36(05) 967-980  https://doi.org/10.1142/S0192415X08006387 

16. Zhang, J., Yu, Y., Zhang, Z., Ding, Y., Dai, X., & Li, Y. (2011). Effect of polysaccharide from  cultured Cordyceps sinensis on immune function and anti-oxidation activity of mice exposed  to 60Co. International immunopharmacology, 11(12), 2251–2257.  https://doi.org/10.1016/j.intimp.2011.09.019 

17. Kuo, Y. C., Tsai, W. J., Shiao, M. S., Chen, C. F., & Lin, C. Y. (1996). Cordyceps sinensis as an  immunomodulatory agent. The American journal of Chinese medicine, 24(2), 111–125.  https://doi.org/10.1142/S0192415X96000165 

18. Jo, W. S., Choi, Y. J., Kim, H. J., Lee, J. Y., Nam, B. H., Lee, J. D., Lee, S. W., Seo, S. Y., & Jeong,  M. H. (2010). The Anti-inflammatory Effects of Water Extract from Cordyceps militaris in  Murine Macrophage. Mycobiology, 38(1), 46–51.  https://doi.org/10.4489/MYCO.2010.38.1.046 

19. Kim, Y. O., Lee, S. W., Oh, C. H., & Rhee, Y. H. (2012). Hericium erinaceus suppresses LPS induced pro-inflammation gene activation in RAW264.7  macrophages. Immunopharmacology and immunotoxicology, 34(3), 504–512.  https://doi.org/10.3109/08923973.2011.633527 

20. Liu, Y. H., Tsai, C. F., Kao, M. C., Lai, Y. L., & Tsai, J. J. (2003). Effectiveness of Dp2 nasal  therapy for Dp2- induced airway inflammation in mice: using oral Ganoderma lucidum as an  immunomodulator. Journal of microbiology, immunology, and infection = Wei mian yu gan  ran za zhi, 36(4), 236–242. 

21. Li, X. M., Zhang, T. F., Huang, C. K., Srivastava, K., Teper, A. A., Zhang, L., Schofield, B. H., &  Sampson, H. A. (2001). Food Allergy Herbal Formula-1 (FAHF-1) blocks peanut-induced  anaphylaxis in a murine model. The Journal of allergy and clinical immunology, 108(4), 639– 646. https://doi.org/10.1067/mai.2001.118787 

22. Srivastava, K. D., Kattan, J. D., Zou, Z. M., Li, J. H., Zhang, L., Wallenstein, S., Goldfarb, J.,  Sampson, H. A., & Li, X. M. (2005). The Chinese herbal medicine formula FAHF-2 completely  blocks anaphylactic reactions in a murine model of peanut allergy. The Journal of allergy and  clinical immunology, 115(1), 171–178. https://doi.org/10.1016/j.jaci.2004.10.003 

23. Wen, L., Sheng, Z., Wang, J., Jiang, Y., & Yang, B. (2022). Structure of water-soluble  polysaccharides in spore of Ganoderma lucidum and their anti-inflammatory activity. Food  chemistry, 373(Pt A), 131374. https://doi.org/10.1016/j.foodchem.2021.131374 

24. Wen, S. D., Sans-Serramitjana, E., Santander, J. F., Sánchez, M. R., Salazar-Aguilar, P., Zepeda,  A. B., Alvarado, S. I., & Miranda, I. B. (2021). Effects of natural extracts in the treatment of  oral ulcers: A systematic review of evidence from experimental studies in animals. Journal of  clinical and experimental dentistry, 13(10), e1038–e1048.  https://doi.org/10.4317/jced.58567

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DISCLAIMER
The information on this website is not intended to diagnose, treat, cure or prevent any disease. All information found here is not meant as a substitute for, or alternative to, information from your doctor for ongoing medical treatment you currently receive. If unsure, please consult with your doctor before using medicinal mushrooms. Any content related to cancer should not be considered as prescriptive medical advice and should not be a substitute for any cancer treatment, unless advised by your doctor first. The efficacy of these products has not been confirmed by TGA and FDA-approved research. If you are pregnant or on prescription drugs that thin the blood, consult with your medical professional before using medicinal mushrooms.
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