Maitake (Grifola Frondosa)

STUDY 1

Grifola frondosa polysaccharides induce breast cancer cell apoptosis via the mitochondrial-dependent apoptotic pathway

Abstract

Grifola frondosa, a type of food and medical fungus, has been shown to exhibit various pharmacological activities, including anticancer effects. As the most typical cancer diagnosed among female patients, breast cancer remains a huge concern threatening human health globally. In the present study, the anti-breast cancer effects of Grifola frondosa polysaccharides (GFPs) and the underlying mechanisms were investigated in MCF-7 and MDA-MB-231 cells, as well as in nude mice bearing MCF-7 tumor xenografts. GFPs exerted cytotoxic effects on the cells, as indicated by a decrease in cell viability, and an increase in the apoptototic rate, lactate dehydrogenase release and reactive oxygen species accumulation, inducing mitochondrial dysfunction. The increased expression of Bax, cleaved caspase-3 and caspase-8, and the reduced levels of B-cell lymphoma 2 (Bcl-2) and Bcl-extra large (Bcl-xL) were observed in the cells incubated with GFPs and in the tumor tissues of the mice treated with GFPs. Moreover, the GFPs significantly suppressed the phosphorylation of AKT/glycogen synthase kinase-3β and extracellular signal-regulated kinases in a time-dependent manner. Finally, the inhibition of MCF-7 tumor xenograft growth further confirmed the anti-breast cancer effects of GFPs. All these findings revealed that GFPs induced human breast cancer cell apoptosis via the mitochondrial-dependent apoptotic pathway, and provide experimental evidence to support the use of Grifola frondosa as a potential treatment for breast cancer.

Conclusion

The anti-breast cancer effects of GFPs were successfully confirmed in in vitro and in vivo experiments. GFPs reduced cell viability, enhanced the apoptotic rate, increased the ROS and caspase-3 intracellular levels, and caused LDH over-release, as well as MMP dissipation and the abnormal expression of pro-apoptotic proteins. The suppressed activation of ERK and AKT/GSK-3β in the GFP-incubated cells was responsible for mitochondrial dysfunction. All these findings reveal that the mitochondrial-dependent apoptotic pathway contributes to GFP-induced cytotoxicity in the MCF-7 and MDA-MB-231 cells, which provides pharmacological evidence to support the use of GFPs as a potential chemotherapeutic agent.

STUDY 2

Grifola frondosa water extract alleviates intestinal inflammation by suppressing TNF-α production and its signaling

Abstract

TNF-α is a major cytokine involved in inflammatory bowel disease (IBD). In this study, water extract of Grifola frondosa (GFW) was evaluated for its protective effects against colon inflammation through the modulation of TNF-α action. In coculture of HT-29 human colon cancer cells with U937 human monocytic cells, TNF-α-induced monocyte adhesion to HT-29 cells was significantly suppressed by GFW (10, 50, 100 µg/ml). The reduced adhesion by GFW correlated with the suppressed expression of MCP-1 and IL-8, the major IBD-associated chemokines. In addition, treatment with GFW significantly suppressed TNF-α-induced reactive oxygen species production and NF-κB transcriptional activity in HT-29 cells. In differentiated U937 monocytic cells, LPS-induced TNF-α production, which is known to be mediated through NF-κB activation, was significantly suppressed by GFW. In an in vivo rat model of IBD, oral administration of GFW for 5 days (1 g/kg per day) significantly inhibited the trinitrobenzene sulfonic acid (TNBS)-induced weight loss, colon ulceration, myeloperoxidase activity, and TNF-α expression in the colon tissue. Moreover, the effect of GFW was similar to that of intra-peritoneal injection of 5-aminosalicylic acid (5-ASA), an active metabolite of sulfasalazine, commonly used drug for the treatment of IBD. The results suggest that GFW ameliorates colon inflammation by suppressing production of TNF-α as well as its signaling through NF-κB leading to the expression of inflammatory chemokines, MCP-1 and IL-8. Taken together, the results strongly suggest GFW is a valuable medicinal food for IBD treatment, and thus may be used as an alternative medicine for IBD.

Conclusion

In in vitro studies, our present study showed that the inhibitory effects of GFW were even better than the case of 5-ASA, a well known anti-inflammatory drug for IBD. Furthermore, in the TNBS-induced rat colitis, the inhibitory effects of orally administered GFW were similar to those of 5-ASA (i.p.). Taken together, the results strongly suggest that GFW is a valuable medicinal food for IBD treatment, and thus may be used as an alternative medicine for IBD.

STUDY 3

The Mechanisms Underlying the Hypolipidaemic Effects of Grifola frondosa in the Liver of Rats

Abstract

The present study investigated the hypolipidaemic effects of Grifola frondosa and its regulation mechanism involved in lipid metabolism in liver of rats fed a high-cholesterol diet. The body weights and serum lipid levels of control rats, of hyperlipidaemic rats, and of hyperlipidaemic rats treated with oral G. frondosa were determined. mRNA expression and concentration of key lipid metabolism enzymes were investigated. Serum cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels were markedly decreased in hyperlipidaemic rats treated with G. frondosa compared with untreated hyperlipidaemic rats. mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), acyl-coenzyme A: cholesterol acyltransferase (ACAT2), apolipoprotein B (ApoB), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC1) were significantly down-regulated, while expression of cholesterol 7-alpha-hydroxylase (CYP7A1) was significantly up-regulated in the livers of treated rats compared with untreated hyperlipidaemic rats. The concentrations of these enzymes also paralleled the observed changes in mRNA expression. Two-dimensional polyacrylamide gel electrophoresis (2-DE) and Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) were used to identify 20 proteins differentially expressed in livers of rats treated with G. frondosa compared with untreated hyperlipidemic rats. Of these 20 proteins, seven proteins were down-regulated, and 13 proteins were up-regulated. These findings indicate that the hypolipidaemic effects of G. frondosa reflected its modulation of key enzymes involved in cholesterol and triacylglycerol biosynthesis, absorption, and catabolic pathways. G. frondosa may exert anti-atherosclerotic effects by inhibiting LDL oxidation through down-regulation and up-regulating proteins expression in the liver of rats. Therefore, G. frondosa may produce both hypolipidaemic and anti-atherosclerotic effects, and potentially be of use as a functional food for the treatment or prevention of hyperlipidaemia and atherosclerosis.

Conclusion

In in vitro studies, our present study showed that the inhibitory effects of GFW were even better than the case of 5-ASA, a well known anti-inflammatory drug for IBD. Furthermore, in the TNBS-induced rat colitis, the inhibitory effects of orally administered GFW were similar to those of 5-ASA (i.p.). Taken together, the results strongly suggest that GFW is a valuable medicinal food for IBD treatment, and thus may be used as an alternative medicine for IBD.

Empyrean Products That Contain Cordyceps Maitake (Grifola Frondosa)

Maitake Tincture

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Supports lower cholesterol levels, heart health, weight control, healthy digestion, balances blood sugar levels, provides immune benefits, protects against diabetes. Known in Japan for its unique name, “Maitake” which translates to dancing mushroom.

Aegis Tincture

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A proprietary organic adaptogenic blend of mushrooms extracts from Cordyceps, Lion’s Mane, Maitake, Reishi Gold, and Turkey Tail, that promotes respiratory, circulatory, cellular, lymphatic and systemic functions for foundational immunity.

Maitake Capsules

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Maitake assists the body in fighting against any type of mental or physical difficulty. It also regulates a body that has become unbalanced. This product will help support weight control, balance blood sugar levels, and healthy digestion.