Medicinal Mushrooms

Recently, more studies have been performed on F. Chlorophorm extracts of the mushroom have demonstrated cytotoxicity, which was almost twice more specific to colorectal cancer cells SW than to control HEK cells. The cytotoxic effect took place through the ROS-mediated apoptotic mechanism. Moreover, the extracts were able to inhibit migration of the SW cells in scratch wound and transwell assays by means of downregulation of matrix metalloproteinases [ 20 ].

The authors claim that one but not the only of the acting compounds of the mushroom is ergosterol, for it was one of the major components of the extracts and could produce similar, although slighter effects on SW cells [ 20 ]. Another study has revealed the potential of F. Interestingly, combined treatment of mice with the extract and a common chemotherapeutic agent cisplatin gave a synergistic effect on slowing down the tumor growth. Taken together, these findings provide a stronger evidence that apart from the unspecific cytotoxic compounds, F.

Regarding the fact that F. Although ergosterol has been pinpointed as one of the candidates, the exact chemical nature of the acting compounds is still elusive. Biomolecular profiling of inedible mushrooms has revealed an unusually high phenolic content in F. Thus, detailed studies on polyphenoles of F. Effects of different mushroom derivatives and their mechanisms of actions in various models are depicted. Arrows up and down reflect up- or down-regulation of respective proteins or pathways.

The mushroom is considered a saprotroph or a weak parasite. It yielded a number of compounds belonging to different classes with potential biological activity, which were tested against multiple targets [ 25 - 27 ]. Among the isolated compounds, certain were characterized, such as erinacines derived from the mycelium or hericenones derived from the fruiting bodies [ 27 ].

A significant part of research has been focused on neuroprotective properties of the mushroom, which are now extensively described in many works [ 28 ]. Another large area of possible therapeutic and anti-carcinogenic application of H. Water and ethanol extracts of the mushroom have demonstrated growth inhibitory effects on gastric NCI , liver HepG2 and Huh-7 , and colon HT cancer cell lines in the MTT proliferation assay, with the highest efficacy against Huh-7 cells IC50 of 0.

Although not comparing these results with non-cancer cell lines of the respective tissues, the same study describes efficient application of the extracts against xenograft tumors formed by aforementioned cancer cell lines in SCID mice. The extracts, given orally, have demonstrated a tumor suppressing activity similar to that of 5-fluoruracil, a most widely used drug clinically applied for the treatment of gastrointestinal cancers, but demonstrated a much lower general toxicity than 5-fluoruracil [ 29 ]. Another study shows that water extracts of H.

6 Mushrooms That Act as Turbo-Shots for Your Immune System

The mechanism of action involves suppression of matrix melalloproteinases 2 and 9, as well as suppression of ERK and JNK kinase activation, also decreasing the general tumor cell viability [ 30 ]. Further research on tumor suppressing activity of the H. Studies on CT derived human colon cancer xenograft tumors in mice have shown a significant reduction in tumor growth after treatment by H. It has been demonstrated that the extracts stimulated the activities of natural killer cells and macrophages on one hand and blocked angiogenesis on the other [ 30 ].

All these activities could contribute to reduction of the tumor growth, although the anticancer properties of the complex extract may not be limited by them. Another study by the same group has demonstrated a pro-apoptotic effect of same water extracts on U human monocytic leukemia cells in comparison to normal human and murine fibroblasts, as measured by flow cytometry. Further concerning the exploration of the immunomodulatory potential of H. Stimulatory effects on intestinal immune system, manifested mainly through increase of surface IgA expression and natural killer cell activation, have also been reported in mouse in vivo experiments, when the polysaccharide fraction of H.

Although these investigations give no clue upon the exact structural and chemical properties of the active polysaccharides, the idea of their immunomodulatory input into the anti-carcinogenic potential of H. Efforts to study anticancer effects of individual compounds isolated from H. Cyanthine diterpenoid Erinacine A, a mycelial derivative of H.

Everything You Need To Know About Medicinal Mushrooms | FOOD MATTERS®

It also showed significant proliferation decrease of the DLD-1 and other colorectal cancer cell line HCT in comparison to the normal human colonic epithelial cells when analyzed by the MTT assay. Finally, Erinacine A has demonstrated an in vivo inhibition of DLD-1 xenograft tumor growth in nude mice [ 35 ].

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Further studies have also shed light on anti-invasive properties of Erinacin A, which it demonstrated on DLD-1 and HCT colorectal cancer cells in the Boyden chamber and scratch wound healing assays. Proteomic studies have revealed the actin-binding proteins cofilin-1 and profilin-1 as downstream actors activated by the Erinacine A-induced ROS response and mediating the anti-invasive effect [ 37 ]. Another class of compounds common for fungi are cerebrosides, and here cerebroside E isolated from H.

This compound also revealed antitoxic properties, reducing the damage of LLC-PK1 kidney cells after cisplatin treatment in culture — properties that may suggest it for the use in complex cancer chemotherapies [ 38 ]. Indeed, a Hericium -derived protein HEP3, which demonstrated a complex immunomodulatory impact in mice, has also been able to strongly reduce growth of CC cell xenograft tumors after intraperitoneal injection. The immunomodulatory effect was induced through stimulation of the gut microbiota with the protein and involved activation of the proliferation and differentiation of T-cells and stimulation of the intestinal antigen-presenting cells [ 39 ].

Another example of bioactive protein from the same mushroom is a glycoprotein HEG-5 that was able to induce apoptosis in a gastric cancer cell line SGC, stimulating the expression of pro-apoptotic factors such as p53, Bax, Caspase 8 and Caspase 3 [ 40 ]. Another possible, though indirect, activity of H. Ethanol extracts of H. Analyses of petroleum ether extracts of the mushroom have been performed, showing ability of the extracts to suppress the growth of six Helicobacter pylori strains in the microdilution assay and in the disk diffusion assay in vitro.

Separation of the extracts yielded two active compounds, namely the 1- 5-chlorohydroxyphenyl methylbutanone and the 2,5-bis methoxycarbonyl terephthalic acid, which were responsible for the inhibitory activity [ 43 ]. A polysaccharide composed of glucose, mannose, and galactose isolated from the cultured mycelia of H.

Regarding the overall anticancer potential of Hericium erinaceus , it can be stated that this medicinal mushroom possesses a complex of active compounds, which are able to block tumorigenesis at different stages and by different mechanisms; most of them are confirmed by both cell culture and xenograft experiments. It has been demonstrated that H. This spectrum of anticancer properties is provided by different compounds: Thus, two possible strategies of application of H. Up to date, most of the cancer-related research of the mushroom has focused on though not limited by gastrointestinal tumors.

Many preclinical trials on tumor-bearing mice indicate H. Nevertheless, up to date no clinical trials on the mushroom or compounds thereof exist, moreover, many active compounds are still unidentified, and many mechanisms of their action remain elusive. Thus, Hericium erinaceus is a relatively well-studied medicinal mushroom possessing a much larger therapeutic potential for the future compared to its currently exploited applications. Regarding the possibility to culture this mushroom on industrial scale [ 46 ], it has a great chance to become a part of modern natural products-based medicinal biotechnology.

Water extracts of I. Extracts obtained from the mushroom by submerged fermentation induced apoptosis in the human colorectal carcinoma cell lines HCT [ 52 ] and HT [ 53 ]. In vivo experiments with I. Growth of human Sarcoma cells-derived xenografts was as well suppressed by different sub-fractions of the Chaga extract [ 56 ]. Regarding the anticancer potential of individual compounds of I. Unique lanostan-type triterpenoids inonotodiol and inonotsuoxides have revealed anti-carcinogenic effects in vivo using the mouse skin [ 48 , 57 ] and human leukemia-derived mouse xenograft tumors [ 58 ].

Low molecular weight polyphenolic compounds demonstrated a topoisomerase II inhibiting activity leading to growth reduction in cultured human colon HCT carcinoma cells, identifying these polyphenoles as putative anticancer chemotherapeutic agents [ 59 ]. As Hericium erinaceus , the Chaga mushroom is extremely rich in polysachharides, which may perform immunomodulatory functions and inhibit tumorigenesis. In vivo trials of different Chaga-derived polysaccharides with different mouse xenograft tumor models have demonstrated reduction of tumor growth along with immunostimulatory effects [ 61 - 63 ].

This is particularly important, because over-activation of this pathway is a cause of many cancer types, such as colon, liver and breast and, moreover, is highly specific to cancer in adult patients being virtually inactive in healthy tissues [ 67 ]. As ergosterol is also found in other medicinal mushrooms including Fomitopsis pinicola discussed above, it can be one of important components of targeted cancer fungotherapy in general. Recent HPLC-tandem mass-spectrometry study of Chaga mushrooms derived from France, Canada and Ukraine suggests that the Chaga of French origin is the most rich on betulin and betulinic acid, whereas Canadian Chaga is more rich on inotodiol [ 69 ].

Taken together, the Chaga mushroom can be regarded as a very promising but somewhat understudied species, because in spite of its broad use in folk medicine and of promising activities of extracts and certain compounds against cancer in vitro and in vivo , not many exact mechanisms of action are determined and no clinical trials on human patients have been performed.

This fungus has been used as a therapeutic agent worldwide [ 70 ]. It grows on tree trunks throughout the world in many diverse climates, including North America [ 71 ]. Human, mouse and cell icons indicate results obtained in human patients, animal and cell models, respectively. IL — Interleukin A solid body of data exists on T. Water-ethanol extracts of the mushroom caused the proliferation inhibition on three human breast cancer cell lines TD, ZR and MCF-7 , human cervical cancer cell line Bcap37, human B-cell lymphoma Raji , human promyelocytic leukemia HL, NB-4 , and human liver cancer cell line [ 72 , 73 ].

Such results do not prove anticancer function per se , but provide some clues and fit well within the context of other, more detailed data. Other studies have shown anti-proliferative effects of an aqueous extract of T. The results demonstrated that the T. Studies of the T. The most remarkable among them is the polysaccharide fraction which, along with some isolated carbohydrates and proteoglycans, possessed complex immunomodulatory potential similar to that of Hericium erinaceus and relevant for the anticancer treatment. As a recent example, a new glucan has been isolated from this mushroom by hot water extraction and subsequent chromatographic purification and has demonstrated an ability to significantly inhibit the xenograft sarcoma growth in mice [ 75 ].

Most clinically relevant representatives of T. Both have underwent excessive clinical and preclinical studies as immunotherapeutic anticancer agents [ 77 ]. Immunotherapy employing PSP has already become a routine clinical practice in Japan since and in China since Some studies have been performed to reveal the mechanism of PSP interaction with the immune system. It has also been found out that PSP treatment leads to increased proliferation of the peripheral blood monocytes, but does not directly affect the proliferation of T, B, and NK cells [ 80 ].

Nevertheless, orally given combination of PSP with acaccia resin as an adjuvant has led to a significant increase of a hapten-induced specific T-cell dependent B-cell response in mice, suggesting a complex mechanism of PSP action [ 81 ]. It is able to activate different types of immune cells. In another study, PSK enhanced the effect of trastuzumab-mediated anti-breast cancer therapy when given orally, activating the NK cells both directly and via interleukin [ 84 ]. It as well potentiated docetaxel-induced tumor suppression and antitumor immune response in an immunocompetent murine model of human prostate cancer [ 86 ].

Interestingly, a protein YZP purified from T. It is also worth-mentioning that PSK has been shown to downregulate the over-activated Hedgehog signaling cascade under hypoxic conditions and to suppress the malignant phenotype in pancreatic cancer in vitro and in mouse models [ 88 ]. This may be extremely important, for Hedgehog upregulation is a well-known hallmark of many cancer types and a desired therapeutic target [ 89 ].

Here we, again, observe a complex and synergistic action of several chemically diverse compounds from the same fungal species. Nevertheless, results on clinical trials exist that do not prove high therapeutic efficacy of PSK in human patients. Indeed, in Japan, PSK has been used for adjuvant immunotherapy against gastric cancer. All patients received oral fluorinated pyrimidine anti-metabolites with or without PSK after the operation, and no significant difference between the control and the PSK group in relapse free survival was detected [ 90 ].

Such examples reflect that not all data obtained in model systems are applicable to real clinical practice, and cancer therapies have to be chosen very carefully to yield the desired effects. Successful applications of PSK in human patients have been demonstrated when the polysaccharide was applied to treat lung cancer. Different sets of data on non-randomized and randomized controlled clinical trials exist that show improvement of various survival measures including median survival and 1-, 2-, and 5-year survival, improvement of immune function and reduction of tumor-associated symptoms [ 91 ].

In any case, larger and more rigorous randomized controlled trials for PSK in lung cancer patients have to be performed [ 91 ]. Alongside the lung cancer, T. Many studies and some clinical trials exist that describe the effect of the mushroom in animal models and human patients. Thus, a natural dietary supplement BreastDefend, which contains extracts from medicinal mushrooms including T. There are single-case reports [ 93 ] and Phase I clinical trial results [ 86 ] confirming that T.

The mushroom preparations are widely used in up-to-date integrative oncology and prescribed to patients on a regular basis [ 94 ]. It is mostly used as an adjuvant for cancer immunotherapy, with data on clinical trials available, and has led to development of several commercial medicines, mostly acting as activators of the immune cells by the mushroom polysaccharide fractions through Toll-like receptors.

Nevertheless, data on selective growth inhibition of certain cancer cell lines in culture, without any immune cells involved, suggest that there may be other specific mechanisms of action at play, besides the ones described before. The complex anticancer potential of medicinal mushrooms may be embodied not only through inhibition of certain cancer-specific processes or targeted activation of tumor-specific apoptosis, but also through indirect actions such as immunomodulation [ 95 ].

The polysaccharide-mediated antitumor immunomodulatory action seems to be rather common for many medicinal mushrooms and gives a major input into the therapeutic potential of at least three out of the four reviewed species, which is probably determined by similar carbohydrate composition and thus similar effects on the immune system of different mushrooms.

Extrapolating these data, we can suppose that other, less studied, polysaccharide-rich mushroom species could possess similar or even superior immuno-stimulatory properties. Moreover, some of additional biological activities can be used for cancer prevention, diminishing the risk of tumorigenic conditions; to such activities we can attribute antioxidant, antibacterial and anti-inflammatory properties.

That is why research on whole fungal extracts sometimes reaching to the clinical trials and even on extracts of complex mixtures of different medicinal mushrooms [ 96 ] are the important part of the given research field. The four mushrooms reviewed in this article illustrate different stages of natural product-derived drug development. Each medicinal plant or fungus undergoes multiple stages of extraction, fractionation and purification of active compounds. At the same time these extracts, fractions and compounds are tested against different cancer models, from tumor-derived cell lines to animal models and clinical trials.

Another dimension is studying the mechanisms-of-action and targets of the natural products and their derivatives. Maximum progress in all these trials brings us closer to a perfect natural drug for targeted cancer therapy. The mushroom discussed first in our review, Fomitopsis pinicola , is closer to the initial stages of involvement into modern cancer treatment: Inonotus obliquus is a better-studied mushroom: Hericium erinaceus and especially Trametes versicolor are much more advanced in terms of medical applications due to their uncovered strong and complex immunomodulatory potential provided by rich polysaccharide and proteoglycan diversity.

There are numerous clinical trials confirming applicability of these mushrooms and their extracts as components of modern anticancer chemotherapy. But the complex modes of action and molecular targets as well as exact structures of the active molecules from these mushrooms still have to be studied in more detail. In general, there has been a strong progress in the field of medicinal mushroom research in terms of anticancer drug development, but this work continues and much more progress still awaits us, especially in the fields of molecular targets of the medicinal mushrooms and the complex synergistic interplay of their different components.

The photographs of the mushrooms were kindly provided by Eugenia M. The authors declare that there are no conflicts of interest between them for this manuscript. National Center for Biotechnology Information , U.

Immune Modulation From Five Major Mushrooms: Application to Integrative Oncology

Journal List Oncotarget v. Published online Jun Author information Article notes Copyright and License information Disclaimer. Received Apr 11; Accepted Jun 4. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3. Abstract Medicinal mushrooms have been used throughout the history of mankind for treatment of various diseases including cancer.

Table 1 The metabolites found in medicinal mushrooms and their therapeutic potential against cancer. Open in a separate window. The anticancer properties of Fomitopsis pinicola Effects of different mushroom derivatives and their mechanisms of actions on various models are depicted. The anticancer properties of Hericium erinaceus Effects of different mushroom derivatives and their mechanisms of actions in various models are depicted. The anticancer properties of Inonotus obliquus Effects of different mushroom derivatives and their mechanisms of actions in various models are depicted.

Add a spoonful of turkey tail for an immune-boosting smoothie. Try your hand at making some turkey tail ale! Feeling low on energy or need a pre-workout boost? Cordyceps is the fungus for you. This mushroom is known for being very stimulating — for both energy and the libido.

Coriolus versicolor (Turkey Tails)

Cordyceps can help the body utilize oxygen more efficiently and enhance blood flow. This can be especially helpful for athletes or those who regularly work out. This mushroom has been shown to not only improve exercise and athletic performance , but also speed up post-workout muscle recovery. Add a spoonful of Cordyceps to your favorite pre- or post-workout meal for a boost in energy or quicker recovery.

Adding a spoonful of mushroom powder to your favorite recipes is a great way to reap their magical health benefits. And do a little research about the fungus that tickles your fancy before committing. Certain mushrooms can cause side effects like an upset stomach or allergies. With all of these amazing medicinal mushrooms to choose from, which one are you most excited to try first?

Healthline and our partners may receive a portion of revenues if you make a purchase using a link above. Tiffany La Forge is a professional chef, recipe developer, and food writer who runs the blog Parsnips and Pastries. Her blog focuses on real food for a balanced life, seasonal recipes, and approachable health advice.

Visit her at her blog or on Instagram. Reishi mushroom has been used to fight symptoms of aging for 2, years. I drank apple cider vinegar every day and found benefits that went far beyond helping my IBS symptoms. A component in mushrooms showed promise in helping ''reset'' people from depression. However, experts say don't start eating them as a treatment.

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Get your antioxidant dose with free radical-fighting chaga. Chaga can help with aging inflammation lowering LDL. Reach for heart-friendly shiitake. Shiitake can help with lowering cholesterol heart health blood pressure and circulation.