CORDYCEPS MILITARIS & CORDYCEPS SINENSIS
'The Mushrooms of Vigor, Vitality, & Power '
*People always ask me why Cordyceps are so expensive. After you finish reading this page, you will have the answer!
Cordyceps are Ascomycete fungi, like Truffles, Lobster mushrooms, Morels, Bread & Fermenting Yeasts, Cheese and medicine making Penicillium species etc. They have been a tremendous part of human culture and development, especially in the culinary world. Ascomycetes are different from Basidiomycetes primarily because they generate their spores internally in sac called an "ascus", where Basidiomycetes generate their spores externally. All Cordyceps species are considered Endoparasitoids, as in they parasitize a host, much to the detriment of the hosts health, inevitably killing the host in order to reproduce. There are literally hundreds of species of Cordyceps found globally. Almost all of them are insect parasitizing fungi(with the exception of the truffle parasitizing, Cordyceps capitata), with some unique features and behavioral effects on the host. There is a lot of promising research being done, to see if there is any other significant medicinal Cordyceps species. This page will focus on the 2 main varieties of Cordyceps(Militaris-Sinensis), their effects, and the distinction between the two. I will also cover how to cultivate both of these Cordyceps right at home. It should be noted that like most medicinal mushrooms, the potency of the actual mushroom is much much higher, than the ground up mycelium(Approx 20x). Cordyceps mycelium is not even close to as potent as the actual mushroom. Although companies boast that they are using Cordyceps sinensis in their products, it is almost 100% certain that they are only using the mycelium. Be careful of this, because the potency of the product will disappoint you. A good Cordyceps product will make you feel amazing within an hour of consuming it, if not, you've purchased a weak product. I recommend consuming these powerful mushrooms though either a Potent Dual Extract or in Powdered Capsule form. Traditionally these mushrooms are brewed into a tea, but I find the tea lacks potency, because it only extracts the hot-water soluble compounds. There is a lot of medicine wasted when you consume the tea, I often consume the remaining pieces of Cordyceps by chewing and holding in the side of my cheek, eventually swallowing.
* This page will also help you become an informed customer of Cordyceps products. You will be able to determine the potency of a company's products based on what information they provide and their own understanding of this Genus. You will be able to 'cut through the marketing crap' and get to the truth without being scammed or misinformed. If you find a cheap Cordycep product, ask yourself why the price is so low.
Below: Here's an example of someone trying to promote C.sinensis over C.militaris. They are right, Cordyceps militaris is not Cordyceps sinensis, but it its almost as potent and its 1/20th the cost.
Right: I sell my own cultivated C. militaris for $100/oz and I feel that's expensive enough. With that being said, it takes months to complete a cycle and I can barely keep up with the demand. Each jar only yields about 5 grams, but these mushrooms are potent. They've changed my life and i'm a very healthy person already. Imagine what they could do for you!? You wont know unless you try for yourself!
Cordyceps militaris - NA, Caterpillar Mushroom
-Able to produce fruiting bodies in a lab setting, with the proper ingredients and correct technique. I find it more beautiful than Cordyceps sinensis and nearly as powerful.
-Able to produce fruiting bodies in a lab setting, with the proper ingredients and correct technique. I find it more beautiful than Cordyceps sinensis and nearly as powerful.
Above: Wild Cordyceps militaris on parasitized moth pupa. This species of Cordyceps can be found right here in North America in the late summer and early fall. Cordyceps militaris is unique because it can be cultivated and you can produce your own fruiting bodies. Its an incredibly powerful medicinal ally and the first time you try it, you will feel its powerful effects. Cordyceps militaris is much more common than the sinensis variety and is utilized by a growing number of people who recognize its prominent effects. Its also much cheaper than sinensis, and although many companies will promote the sinensis variety because of its extremely high price(up to $20,000 per kilo of wild harvested specimens), Cordyceps militaris is relatively potent and about 1/20 the cost. Of course, if you can successfully grow it, its even cheaper!
Cordyceps sinensis - Himalayan, Caterpillar Mushroom
-Can grow the mycelium(most typically found in Cordyceps products), but not the actual fruiting body. With the exception of some specialists like my friend in the Philippines(Spring.T), who is changing the whole Cordyceps cultivation game.
-Can grow the mycelium(most typically found in Cordyceps products), but not the actual fruiting body. With the exception of some specialists like my friend in the Philippines(Spring.T), who is changing the whole Cordyceps cultivation game.
Above: Wild Cordyceps sinensis growing on the adult larvae of the Hepialid moth. Cordyceps sinensis is found exclusively in the high altitude of the Himalayan mountains, elevation(3500'-5000'). It was first recognized by Tibetan Sherpa, who noticed that their cattle were consuming these mushrooms(unintentionally) while they ingested grass. They noticed that the cattle were extremely energetic and lively, which lead to human curiosity and the eventual consumption of this mushroom. Ever since, humans have enjoyed Cordyceps sinensis as a powerful medicinal mushroom with immediate effects. It is referred to as the most potent herb in Chinese medicine and is the world's most expensive mushroom.
Above: Fungicopia's Cordyceps militaris - Fruiting in jars on supplemented, organic rice. The variety of supplements necessary for Cordyceps militaris cultivation is complex and expensive, but they will produce very low yields, on just rice. Most growers will not share their micro-nutrient recipe with anyone. Including myself! I do however, sell the exact nutrient mix needed to produce your own C.militaris kits, right at home. We also sell pre-made kits, which are guaranteed to produce. I have 2 different fruiting isolates of C.militaris currently, but im looking for more wild isolates.
Above: Cordyceps sinensis. A single fruiting body is produced on each caterpillar. Unfortunately, there is no efficient way to cultivate these mushrooms and they are primarily foraged in the Himalayan mountain range at high altitudes. The cultivation problem doesn't revolve around the altitude where they are found, but rather the complex interaction between the host Hepialid caterpillar. The caterpillar naturally tries to fight off the parasite, but it will inevitably be consumed by its attacker. It is believed that this complex interaction is what causes the formation of the fruiting body.
The Life Cycle of Cordyceps militaris
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Above: C.militaris can also be cultivated on various caterpillar species, by inoculating a live specimen with mycelium. I will try Silkworms in the upcoming months.
The Life Cycle of Cordyceps sinensis
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Cultivating Cordyceps militaris & Cordyceps sinensis
Visit the Cordyceps Cultivation Page for in depth cultivation techniques for both species.
Note** You will only be able to produce the fruiting body of Cordyceps militaris, as well as the mycelium from Cordyceps sinensis(it will not fruit in an artificial lab setting).
My Opinion Concerning Cordyceps miltaris VS. Cordyceps sinensis Potency
"Right off the hop, Ill say that the mushrooms of both species are substantially more potent than their myceliated forms"
So, obviously Cordyceps sinensis gets more attention than Cordyceps militaris, as the prominent medicinal Cordyceps species. This is mostly due to its rarity and very selective region from which it is commercially harvested in the wild, and NOT explicitly due to its medicinal significance. It demands a high price and people make a lot of money off selling it, so often the same people who import sinensis and market it, will promote it as the ONLY significant medicinal Cordycep species. It should be noted that many companies only grow out the mycelium(which will not produce mushrooms), typically the commercial CS-4 strain, and utilize the name Cordyceps sinensis to market an inferior product. Companies that denigrate Cordyceps militaris, are either ill informed or are simply promoting their own product, while attempting to eliminate a cheaper medicine with almost indistinguishable effects. Allow me to explain the differences below and inform you on how to select Cordyceps products that will benefit your life in a significant and profound manner.
-Cordyceps sinensis is most commonly sold in its mycelium form(which is the weakest form), or as an actual fruiting body(most potent & expensive form).
-Cordyceps militaris can be purchased in products, as either mycelium(which is the weakest form), or as an actual fruiting body(most potent form).
Mycelium - The mycelium from both these species have significantly weaker effects than the actual mushrooms. For someone like me, the effects are not even noticeable, unless I ingest large portions(12-15g, per day).
Actual Fruiting Body - The actual fruiting bodies of both on the other hand, are VERY potent. I find both very effective at low doses(1-3g, per day), which means you don't need to consume very much at all. The effects are prominent and incredible for both species. The difference in potency between Cordyceps militaris vs Cordyceps sinensis, is very minimal. I will admit that Cordyceps sinensis is the more powerful mushroom, but the price vs difference in effects, is simply not worth the investment, unless you're more interested in the novelty of its rarity.
I sell a pound of Cordyceps militaris mushrooms for around $900.00 vs. $13,000.00 for a pound of Cordyceps sinensis mushrooms.
I'll try and quantify the qualitative differences to add to your understanding. This is based on my own vast experience with both Cordyceps sinensis & Cordyceps militaris, the below numbers are not from a peer reviewed study, but rather my own dissertations.
Considering that we know Cordyceps sinensis is the more potent species, lets say it has 100% potency of the desired effects. Comparatively, I would place Cordyceps militaris mushrooms at 70-90% the potency of C.sinensis mushrooms, depending on how they are grown. The small difference in effect would hardly be noticed by most consumers, if at all. As you can see, the price does not reflect the difference in its medicinal effects, but rather, its reputation & rarity.
Comparatively, the mycelium of Cordyceps sinensis would sit anywhere from 5-15% of the potency of Cordyceps Sinensis fruiting bodies. Cordyceps militaris mycelium is the weakest of the 4 forms, with a comparative potency of less than 5% of Cordyceps sinensis mushrooms.
In terms of potency, here is the hierarchy:
Fruiting Bodies of Cordyceps
Price per lb/ $13,000.00 #1: Cordyceps sinensis fruiting body(Most potent,100%)
Price per lb/ $900.00 #2: Cordyceps militaris fruiting body(70-85% as potent)
____Mycelium of Cordyceps
#3: Cordyceps sinensis mycelium(10-15% as potent)
#4: Cordyceps militaris mycelium(weakest <5% as potent)
Now that you can visualize the difference between the two species(in terms of effects vs cost) you can clearly see that consuming Cordyceps militaris mushrooms is the most cost effective way to feel the benefits of Cordyceps mushrooms. If you're incredibly wealthy, by all means, purchase the C.sinensis mushrooms and you wont be unsatisfied. In fact, both species are available by the lb on the products page. You can now comprehend how weak Cordyceps mycelium is when compared to the actual mushroom. Keep a close eye on how people market their Cordyceps products and ensure that you are getting the actual mushroom and not the significantly less potent, mycelium. The mycelium is beneficial too, but you have to ingest large amounts to feel the effects. Be careful out there guys and read the labels closely, if a product does not explicitly say that it 'contains Cordyceps Fruiting body or whole mushroom', then you know it was made with the mycelium. Anyone who pays top dollar to make exquisite Cordyceps products will proudly advertise that they use the actual mushrooms and the effects will be prominent and resounding.
The Medicinally Significant Compounds Found In Cordyceps sinensis
Fenilalanin: Viagra for women
Arginine: Viagra for men
The Medicinally Significant Compounds Found In Cordyceps militaris
The Super Compounds of Cordyceps
The present investigation reports the synthesis of a phenylalanine-rich N-methylated cyclopeptide, cordyheptapeptide A (8), previously isolated from the insect pathogenic fungus Cordyceps sp. BCC 1788, accomplished through the coupling of N-methylated tetrapeptide and tripeptide fragments followed by cyclization of the linear heptapeptide unit. Structure elucidation of the newly synthesized cyclopolypeptide was performed by means of FT-IR, ¹H-NMR, 13C-NMR, and fast atom bombardment mass spectrometry (FABMS), and screened for its antibacterial, antidermatophytic, and cytotoxic potential. According to the antimicrobial activity results, the newly synthesized N-Methylated cyclopeptide exhibited potent antibacterial activity against Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae and antifungal activity against dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL, in comparison to the reference drugs, gatifloxacin and griseofulvin. In addition, cyclopolypeptide 8 displayed suitable levels of cytotoxicity against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines.
Kumar S. 2017. Total Synthesis and Pharmacological Investigation of Cordyheptapeptide A. Institute of Pharmaceutical Sciences, 27;22(6). pii: E682
One new ribonucleotide, 5'-(3''-deoxy-β-D-ribofuranosyl)-3'-deoxyadenosine (1), and 14 known compounds (2-15) were isolated from an ethanol extract of Cordyceps militaris. The chemical structures of these compounds were determined from 1D and 2D NMR (1H-1H COSY, HMBC, HMQC and NOESY) and HR-ESI-MS spectra, and results were compared with data from the literature. The effects of all isolated compounds were measured on NF-κB activation, with compound 2 exhibiting significant inhibitory activity against TNF-α-induced NF-κB reporter gene expression in HeLa cells from 3 to 100 μM.
Sun J, et al. 2017. A new ribonucleotide from Cordyceps militaris. Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, 31(21):2537-2543.
Effects of Corcyceps On Asthma
Moderate-to-severe asthma has a substantial impact on the health-related quality of life (HR-QOL) of the patients. Cordyceps sinensis is a traditional Chinese medicine that is evaluated clinically for the treatment of many diseases, such as chronic allograft nephropathy, diabetic kidney disease, and lung fibrosis. In order to investigate the effects of Cordyceps sinensis on patients with moderate-to-severe persistent asthma, 120 subjects were randomized to receive Corbin capsule containing Cordyceps sinensis for 3 months (treatment group, n = 60), whereas the control group (n = 60) did not receive treatment with Corbin capsule. Inhaled corticosteroid and as-needed β-agonists were used in the treatment of both groups. HR-QOL was measured with the Juniper's Asthma Quality of Life Questionnaire (AQLQ). The incidence of asthma exacerbation, pulmonary function testing, and serum measurements of inflammatory mediators were also evaluated. The results showed that the treatment group indicated a significant increase in AQLQ scores and lung function compared with the control group. The expression levels of the inflammation markers IgE, ICAM-1, IL-4, and MMP-9 in the serum were decreased and IgG increased in the treatment group compared with the control group. Therefore, the conclusion was reached that a formulation of Cordyceps sinensis improved the HR-QOL, asthma symptoms, lung function, and inflammatory profile of the patients with moderate-to-severe asthma. This trial is registered with ChiCTR-IPC-16008730.
Wang N. 2016. Herbal Medicine Cordyceps sinensis Improves Health-Related Quality of Life in Moderate-to-Severe Asthma. Department of Traditional Chinese Medicine, 2016:6134593.
Anti-Fatigue Properties of Cordyceps
Fatigue is a biological phenomenon that involves a feeling of extreme physical or mental tiredness that could potentially cause some severe chronic diseases. Recently, diet therapy has provided a new alternative to alleviate physical fatigue. In our previous study, addition of Cordyceps militaris (C. militaris) into an extruded product was shown to provide high nutrition and unique flavors; however, little is known whether this product has some scientific evidence regarding anti-fatigue property. The purpose of this study was to evaluate the anti-fatigue effects of extruded products of cereal grains (EC) and EC mixed with C. militaris (ECC).
EC and ECC prolonged the swimming endurance time of mice compared to the control. The content of BLA at high dose of ECC group (20 g/kg) was significantly lower than that in the negative control group. CK, BUN and MDA levels were significantly reduced by treatment with EC and ECC compared to the negative control, while the low and middle dose of EC had no significant effect on MDA levels. Additionally, only the middle and high dose of EC (10, 20 g/kg) could significantly decrease the BUN level. EC and ECC treatments increased glycogen, LDH, SOD, CAT and GSH-Px levels. Low and middle dose of EC had no significant effects on muscle glycogen. Moreover, low dose of EC could increase the level of SOD but it was not statistically significant. Compared to the EC treatment groups, ECC demonstrated the efficacy of anti-fatigue potential, particularly at a high dose of ECC, the best performance in relieving fatigue.CONCLUSIONS:
These results suggest that EC and ECC could prevent exercise-induced fatigue in mice and ECC provided a better effect. In addition, C. militaris in ECC might play a crucial role in the anti-fatigue activity of ECC
Zhong L, et al. 2017. Evaluation of anti-fatigue property of the extruded product of cereal grains mixed with Cordyceps militaris on mice. College of Food Science and Technology, 2;14:15.
Xu YF. 2016. Effect of Polysaccharide from Cordyceps militaris (Ascomycetes) on Physical Fatigue Induced by Forced Swimming. Department of Physical Education, 18(12):1083-1092.
Diabetic Focused Therapeutic Properties of Cordyceps
Recent living condition improvements, changes in dietary habits, and reductions in physical activity are contributing to an increase in metabolic syndrome symptoms including diabetes and obesity. Through such societal developments, humankind is continuously exposed to metabolic diseases such as diabetes, and the number of the victims is increasing. This study investigated Cordyceps militaris water extract (CMW)-induced glucose uptake in HepG2 cells and the effect of CMW treatment on glucose metabolism.
CMW induced glucose uptake in HepG2 cells by increasing GLUT2 through HNF-1α expression stimulation. Glucose in the cells increased the CMW-induced phosphorylation of AMPK. In turn, glycolysis was stimulated, and glyconeogenesis was inhibited. Furthermore, by studying the mechanism of action of PI3k, Akt, and GSK-3β, and measuring glycogen content, the study confirmed that the glucose was stored in the liver as glycogen. Finally, CMW resulted in a higher level of α-glucosidase inhibitory activity than that from acarbose.CONCLUSION:
CMW induced the uptake of glucose into HepG2 cells, as well, it induced metabolism of the absorbed glucose. It is concluded that CMW is a candidate or potential use in diabetes prevention and treatment.
Male Reproductive Dysfunction and Cordyceps
Antioxidant Properties of Cordyceps
Chemical composition analysis of mycelial samples revealed carbohydrates (46.72 ± 0.7% to 63.40 ± 0.3%), protein (14.19 ± 0.2% to 26.16 ± 0.1%), crude fibers (0.93 ± 0.0% to 1.22 ± 0.0%), and ash (0.77 ± 0.0% to 0.98 ± 0.0%). The amounts of calcium and iron in mycelia were significantly higher than amounts of magnesium, copper, and manganese. The amount of β-carotene ranged from 0.67 to 1.17 μg/100 g; lycopene, from 0.30 to 0.57 μg/100 g; phenolic compounds, from 29.16 to 43.12 mg/100 g; polysaccharides, from 104 to 126 mg/g; and flavonoids, from 2.15 to 4.25 mg/g. All tested species showed significant (P ≤ 0.05) antioxidant activities measured based on half-maximal effective concentrations. C. cicadae possessed the lowest half-maximal effective concentration compared with the other species. All 4 species showed a broad spectrum of antibacterial activity against 7 tested pathogenic bacterial strains.
Sharma SK. 2017. Chemical Composition and Antioxidant and Antibacterial Activities of Cultured Mycelia of Four Clavicipitaceous Mushrooms (Ascomycetes) from the Indian Himalayas. Department of Botany, 19(1):45-54.
Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by degeneration and loss of dopaminergic neurons of the substantia nigra. Increasing evidence has indicated that oxidative stress plays a pivotal role in the pathogenesis of Parkinson's disease (PD). Therapeutic options that target the antioxidant machinery may have potential in the treatment of PD. Cordycepin, a nucleoside isolated from Cordyceps species displayed potent antioxidant, anti-inflammatory and anticancer properties. However, its neuroprotective effect against 6-OHDA neurotoxicity as well as underlying mechanisms is still unclear. In this present study, we investigated the protective effect of cordycepin against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity and its underlying mechanism. We observed that cordycepin effectively inhibited 6-OHDA-induced cell death, apoptosis and mitochondrial dysfunction. Cordycepin also inhibited cell apoptosis induced by 6-OHDA as observed in the reduction of cytochrome c release from the mitochondrial as well as the inhibition of caspase-3. In addition cordycepin markedly reduced cellular malondialdehyde (MDA) content and intracellular reactive oxygen species (ROS) level. Cordycepin also significantly increased the antioxidant enzymes; superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in 6-OHDA-treated cells. The results obtained unambiguously demonstrated that cordycepin protects PC12 cells against 6-OHDA-induced neurotoxicity through its potent antioxidant activity.
Olatunji OJ, et al. 2016. Cordycepin protects PC12 cells against 6-hydroxydopamine induced neurotoxicity via its antioxidant properties. School of Pharmacy, 81:7-14.
Multiple Sclerosis & Cordyceps
As a traditional Chinese medicine, Cordyceps sinensis (CS) possesses a variety of immunoregulatory properties. This study aimed to explore the therapeutic potential of CS in a mice model of multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE).
Over the 15 and 30 days of CS treatment, the clinical assessment for EAE demonstrated that both high-CS group (2.51 ± 0.31 and 2.26 ± 0.39 scores, respectively) and low-CS group (2.99 ± 0.40 and 2.69 ± 0.46, respectively) had lower disease severity scores than those of control group (3.57 ± 0.53 and 3.29 ± 0.53, all P < 0.01, respectively). Meanwhile, after 15 and 30 days, the high-CS group (19.18 ± 1.34 g and 20.41 ± 1.56 g, respectively) and low-CS group (18.07 ± 1.18 g and 19.48 ± 1.69 g, respectively) had a lower body weight, as compared with control group (16.85 ± 1.15 g and 18.22 ± 1.63 g, all P < 0.01, respectively). At 30 days post-CS treatment, there was a lower Th1 frequency in the lymph nodes (2.85 ± 1.54% and 2.77 ± 1.07% vs. 5.35 ± 1.34%, respectively; P < 0.05) and spleens (3.96 ± 1.09% and 3.09 ± 0.84% vs. 5.07 ± 1.50%, respectively; P < 0.05) and less inflammatory infiltration and demyelination in the brain of CS-treated mice than that of control group.CONCLUSIONS:
Our preliminary study demonstrated that CS efficiently alleviated EAE severity and EAE-related pathology damage and decreased the number of Th1s in the periphery, indicating its effectiveness in the treatment of murine EAE. Thus, our findings strongly support the therapeutic potential of this agent as a new traditional Chinese medicine approach in MS treatment.
Immunomodulatory Properties of Cordyceps
Results showed that PA-824 combined with CS led to the lowest lung colony-forming units (CFU) counts among treated groups. Furthermore, this beneficial outcome might be associated with the decreased CD11a on CD4+ cells in mice lungs and spleens. Moreover, the suppressed secretion of IFN-γ and IL-10, and IL-10 expressions, as well as the decreased IFN-γ and IL-10 double-positive CD4+ cells in blood, could also be associated with the positive effect. However, no significant effect on IL-2 production was found. The combination of PA-824 and CS had more effective bacteriostatic and immunomodulatory effects on M.tb infected mice than PA-824 alone. In conclusion, CS has the potential to be an effective adjuvant in TB treatment.
LI DG, et al. 2017. Cordyceps sinensis promotes immune regulation and enhances bacteriostatic activity of PA-824 via IL-10 in Mycobacterium tuberculosis disease. Department of Respiratory Medicine, 7;50(9):e6188.
Cancer Inhibiting Properties of Cordyceps
Brain cancer, in particular neuroblastoma and glioblastoma, is a global challenge to human health. Cordycepin, extracted from Cordycepsssp., has been revealed as a strong anticancer agent through several ways; however, the mechanism, by which cordycepin counteracts brain cancers, is still poorly understood. In this study, the underlying mechanisms of cordycepin against human brain cancer cells were explored. SH-SY5Y and U251 cells were being a model to represent human nseuroblastoma and glioblastoma, respectively. Here, it was found that cordycepin inhibited cell growth, and induced apoptosis in a dose-dependent manner in both SH-SY5Y and U-251 cell lines. The expression of pro-apoptotic genes, including P53, BAX, Caspase-3, and Caspase-9, were upregulated, whereas the expression of anti-apoptotic gene, BCL-2, was suppressed. Besides, cordycepin induced the generation of reactive oxygen species (ROS) along with the suppression of antioxidant genes, including GPX, SOD, and Catalase. Importantly, cordycepin was shown to involve in the activation of autophagy, which was evidenced by the increment of LC3I/II. The combination of cordycepin with chloroquine, an autophagy inhibitor, further inhibited the growth, and enhanced the death of brain cancer cells. Altogether, this finding suggested that cordycepin induced apoptosis of human brain cancer cells through mitochondrial-mediated intrinsic pathway and the modulation of autophagy. Therefore, cordycepin could be a promising candidate for the development of anticancer drugs targeting human brain cancers.
Chaicharoenaudomrung N. 2018. Cordycepin induces apoptotic cell death of human brain cancer through the modulation of autophagy. Laboratory of Cell-Based Assays and Innovations, 46:113-121.
This prime objective of this study was to explore the anti-cancer activity of fermented Asterina pectinifera with Cordyceps militaris mycelia (FACM) in B16F10 murine melanoma cells. The effect of FACM on cell viability was assessed using MTT assay. Furthermore, the effect of FACM was compared with unfermented A. pectinifera on cell viability. The results demonstrated that the fermented FACM extract has a higher inhibitory activity on the proliferation of B16F10 murine melanoma cells than unfermented A. pectinifera. In addition, FACM also promoted the expression of pro-apoptotic protein Bax leading to stimulate apoptosis in B16F10 cells. Therefore the present study demonstrates that the FACM might be a potential effective anti-cancer agent, as a result of its stronger anti-proliferative effect and apoptosis inducing effect than A. pectinifera or C. militaris on melanoma cells.
Kim YS, et al. 2017. Fermented Asterina pectinifera with Cordyceps militaris Mycelia Induced Apoptosis in B16F10 Melanoma Cells.
Department of Biotechnology, 975:1141-1152.
Levels of the phosphorylated forms of p85 and AKT were clearly decreased in the group administered with Cm-EE. This result indicated that levels of phosphoglycogen synthase kinase 3β (p-GSK3β) and cleaved caspase-3 were increased with orally administered Cm-EE. In addition, Cm-EE directly inhibited the viability of cultured RMA cells and C6 glioma cells. The number of proapoptotic cells was significantly increased in a Cm-EE treated group compared with a control group. Our results suggested that C. militaris might be able to inhibit cancer growth through regulation of p85/AKT-dependent or GSK3β-related caspase-3-dependent apoptosis.
Park JG, et al. 2017. Anticancer Efficacy of Cordyceps militaris Ethanol Extract in a Xenografted Leukemia Model.
Department of Genetic Engineering, 2017:8474703.
Bladder cancer is a neoplasm originated from bladder epithelial cells. The therapy for bladder cancer is so far not satisfactory. In this study, we examined the effects of Cordyceps militaris hot water extracts containing cordycepin on human bladder cells. Cordyceps militaris hot water extracts containing cordycepin was used to treat human T24 bladder carcinoma cells, and we found that Cordyceps militaris hot water extracts containing cordycepin decreased T24 cell survival in a dose-dependent manner, which was seemingly mediated by activation of A3 adenosine receptor and the subsequent inactivation of Akt pathways, resulting in increases in cleaved Caspase-3 and apoptosis. Overexpression of A3 adenosine receptor in T24 cells mimicked the effects of Cordyceps militaris hot water extracts, while A3 adenosine receptor depletion abolished the effects of Cordyceps militaris hot water extracts containing cordycepin. Together, these data suggest that Cordyceps militaris hot water extracts containing cordycepin may be a promising treatment for bladder cancer via A3 adenosine receptor activation.
Cao HL, et al. 2017. Cordycepin induces apoptosis in human bladder cancer cells via activation of A3 adenosine receptors. Department of Medical Oncology, 39(7):1010428317706915.
Anti-Tumor Compounds, other than Cordycepcin:
Anti-tumor activity of each fraction was assessed by a Hoechst staining-based apoptosis assay using malignant melanoma MeWo cells. By these repeated approaches through chromatographic segregation and cell biological assay, we finally succeeded in identifying the target substance from a certain fraction that included neutral hydrophilic components using a pre-column and post-column chlorine adduct ionization LC-APCI-MS method. The target substance was a mono-carbohydrate, xylitol, that induced apoptotic cell death in MeWo cells but not in normal human OUMS-24 fibroblasts. This is the first study showing that Cordyceps militarisextract contains a large amount of xylitol. Thus, our results will contribute greatly to uncovering the mysterious multifunctional herbal drug Cordyceps militaris as an anti-tumor agent.
Wada T, et al. 2017. Identification of a novel component leading to anti-tumor activity besides the major ingredient cordycepin in Cordyceps militaris extract. Chemicals Evaluation and Research Institute, 1;1061-1062:209-219.
In the present work, three fractions of selenized Cordyceps militaris polysaccharides (SeCPS) named SeCPS- I, SeCPS- II and SeCPS- III were isolated and purified by ultra-filtration. Their selenium content were measured as 541.3, 863.7 and 623.3μg/g respectively by a graphite furnace atomic absorption spectroscopy. The monosaccharide comformation analysis showed that they were mainly consisted of D-Mannose, D-Glucose, and D-Galactose in mole ratios of 1:7.63:0.83, 1:1.34:0.31 and 1:3.77:0.41 respectively. Their structure characteristics were compared by IFR and NMR spectroscopy. Scanning electron microscopy (SEM) and Congo red (CR) spectrophotometric method were used to investigate their morphological characteristics and conformational transition. SeCPS-II showed the strongest anti-tumor effects judging from the result of in vitro anti-tumor assays against two tumor cell lines (hepatocellular carcinoma HepG-2 cells and lung adenocarcinom A549 cells).
Cordycepin (3'-deoxyadenosine) is a natural compound abundantly found in Cordyceps sinesis in natural and fermented sources. In this study, we examined the effects of cordycepin in a human oral squamous cell carcinoma (OSCC) xenograft model. Cordycepin was administered in a regular, low-dose and prolonged schedule metronomic therapy. Two doses of cordycepin (25 mg/kg, 50 mg/kg) were administrated five days a week for eight consecutive weeks. The tumor volumes were reduced and survival time was significantly prolonged from 30.3 ± 0.9 days (control group) to 56 days (50 mg/kg group, the day of tumor-bearing mice were sacrificed for welfare consideration). The weights of mice did not change and liver, renal, and hematologic functions were not compromised. Cordycepin inhibited the OSCC cell viability in vitro (IC50 122.4-125.2 μM). Furthermore, morphological characteristics of apoptosis, increased caspase-3 activity and G2/M cell cycle arrest were observed. In wound healing assay, cordycepin restrained the OSCC cell migration. Cordycepin upregulated E-cadherin and downregulated N-cadherin protein expression, implying inhibition of epithelial-mesenchymal transition (EMT). The immunohistochemical staining of xenograft tumor with E-cadherin and vimentin validated in vitro results. In conclusion, metronomic cordycepin therapy showed effective tumor control, prolonged survival and low toxicities. Cytotoxicity against cancer cells with apoptotic features and EMT inhibition were observed.
Sun NW, et al. 2017. Metronomic Cordycepin Therapy Prolongs Survival of Oral Cancer-Bearing Mice and Inhibits Epithelial-Mesenchymal Transition. Division of Medical Oncology and Hematology, 13;22(4).
Cordycepin, a main active composition extracted from Cordyceps militaris, has been reported to exert anti-tumor activity in a broad spectrum of cancer types. However, the function of cordycepin on human non-small cell lung cancer cells is still obscure. Our present work showed that cordycepin inhibited cell growth by inducing apoptosis and autophagy in human NSCLC cells. Further study revealed that cordycepin triggered extrinsic apoptosis associated with down-regulation of c-FLIPL which suppresses the activity of caspase-8. And ectopic expression of c-FLIPL dramatically prevented cordycepin-caused apoptosis. Meanwhile, cordycepin stimulated autophagy through suppressing mTOR signaling pathway in lung cancer cells. When autophagy was blocked by Atg5 siRNA or PI3K inhibitor LY294002, the levels of apoptosis caused by cordycepin were obviously attenuated. In addition, suppression of autophagy could also elevate the level of c-FLIPL which indicated cordycepin-triggered autophagy promoted the degradation of c-FLIPL. Therefore, we conclude that cordycepin induces apoptosis through autophagy-mediated downregulation of c-FLIPL in human NSCLC cells. Taken together, our findings provide a novel prospect on the anti-tumor property of cordycepin, which may further prompt cordycepin to serve as a promising therapeutic approach in NSCLC treatment.
Yu X, et al. 2017. Cordycepin induces autophagy-mediated c-FLIPL degradation and leads to apoptosis in human non-small cell lung cancer cells. Laboratory of Animal Cells and Developmental Biology, 24;8(4):6691-6699.
Cordyceps Repairs Tissue and Facilitates Recovery
This study was designed to investigate the action and mechanism of cordyceps polysaccharide on rat acute liver failure (ALF).METHODS:
Sixty rats were randomly divided into five groups: normal group, model group, and cordyceps polysaccharide groups with high, middle and low doses (20, 10 and 5 mg/ml). Apoptosis was detected through TUNEL method. Protein expressions of caspase 1, IL-18, IL-10, VEGF, and SDF-1α in liver tissue are detected by Western Blot. PCNA and sIRPα1 contents were measured by PCR method. Rat ALF is modeled with a D-galactosamine induced by lipopolysaccharide (LPS).RESULTS:
The results after modelling showed tissue HE staining wiith typical manifestation of acute liver injury. Compared with the medicated group, serum ALT and AST, as well as hepatocyte apoptosis are significantly higher in the liver failure group, in a time-dependent way. This suggests that medication can effectively inhibit the expression of caspase 1, IL-18, and IL-10, while simultaneously increasing the expression of VEGF and SDF-1α, as well as of PCNA and sIRPα1. Cordyceps polysaccharide can alleviate the immune inflammatory response in acute liver failure, and may be specifically homing to the damaged liver, thus promoting the secretion of VEGF, proliferation of hepatocyte, regeneration of liver vessels, and repair of liver tissues.CONCLUSION:
Medication can reduce the IL-10 level, regulate the equilibrium of pro-inflammatory and anti-inflammatory factors, and decrease the level of caspase 1 and IL18
Sun YJ, et al. 2017. Relationship between ncRNAs and gastric cancer: meta-analysis. 118(9):535-538.
Cerebral ischemia is caused by reduced cerebral blood flow due to a transient or permanent cerebral artery occlusion. Ischemic injury in the brain leads to neuronal cell death, and eventually causes neurological impairments. Cordyceps, the name given to the fungi on insects, has abundant useful natural products with various biological activities. Cordyceps is known to have nephroprotective, hepatoprotective, anti-inflammatory, antioxidative, and antiapoptotic effects. We investigated the effects of Cordyceps on short-term memory, neuronal apoptosis, and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils. For this study, a step-down avoidance test, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunohistochemistry for caspase-3 and 5-bromo-2'-de-oxyuridine, and western blot for Bax, Bcl-2, brain-derived neurotrophic factor (BDNF), and tyrosin kinase B were performed. In the present study, Cordyceps alleviated cerebral ischemia-induced short-term memory impairment. Cordyceps showed therapeutic effects through inhibiting cerebral ischemia-induced apoptosis in the hippocampus. Cordyceps suppressed cerebral ischemia-induced cell proliferation in the hippocampal dentate gyrus due to the reduced apoptotic neuronal cell death. Cordyceps treatment also enhanced BDNF and TrkB expressions in the hippocampus of ischemic gerbils. It can be suggested that Cordyceps overcomes cerebral ischemia-induced neuronal apoptosis, thus facilitates recovery following cerebral ischemia injury.
Cordycepin is an active component extracted from Traditional Chinese medical herb Cordyceps militaris. Many reports demonstrated that cordycepin harbors antitumor activity in a broad spectrum of cancer types. In this study the actions and the underneath molecular mechanisms of cordycepin were investigated in renal cell carcinoma Caki-1 cell line. Results showed that cordycepin induced apoptotic cell death and inhibited cell migration in Caki-1 cells. Quantitative real-time PCR results and western blot analyses indicated cordycepin dose-dependently decreased microRNA-21 expression and Akt phosphorylation levels in Caki-1 cells, but increased PTEN phosphatase levels. Block of cordycepin-induced microRNA-21 decrease or PTEN increase in Caki-1 cells by transfection of microRNA-21 mimic or PTEN siRNA significantly attenuated cordycepin-induced cell death and inhibition of cell migration. Taken together, findings in present study suggested that cordycepin induced apoptotic cell death in renal cell carcinoma through regulation of microRNA-21 and PTEN phosphatase. Furthermore, present study also firstly illustrated that cordycepin inhibited cell migration of renal cell carcinoma, which also involved microRNA-21 and PTEN phosphatase.
Yang C, et al. 2017. Cordycepin induces apoptotic cell death and inhibits cell migration in renal cell carcinoma via regulation of microRNA-21 and PTEN phosphatase. Department of Anorectal Surgery, 38(5):313-320.
Inhibiting oxidative stress and Inflammation:
Acute lung injury (ALI) is a common severe clinical syndrome in intensive care unit. Inflammation has been reported to play a critical role in the development of ALI. Cordycepin, an active component isolated from Cordyceps militaris, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effects of cordycepin on LPS-induced ALI remain unclear. Therefore, in the present study, we assessed whether cordycepin could attenuate ALI induced by LPS. The mice were conditioned with cordycepin 1h before intranasal instillation of LPS. Lung wet/dry (W/D) ratio, MPO activity, MDA content, and inflammatory cytokines production were detected. The expression of NF-κB p65, I-κB, Nrf2, and HO-1 were detected by western blot analysis. We found that LPS significantly increased lung wet/dry (W/D) ratio, MPO activity, MDA content, and inflammatory cytokines production. However, the increases were significantly inhibited by treatment of cordycepin. LPS-induced NF-κB activation was also suppressed by cordycepin. In addition, cordycepin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. In conclusion, our results demonstrated that cordycepin could attenuate LPS-induced ALI effectively, probably due to inhibition of inflammation and oxidative stress.
Lei J, et al. 2017. Cordycepin inhibits LPS-induced acute lung injury by inhibiting inflammation and oxidative stress. Department of Thoracic Surgery, 18;818:110-114.
Anti-Inflammatory Properties of Cordyceps
Department of Food Science & Technology, 18;54:238-244.
Cordyceps militaris is an ingredient of traditional Chinese medicine and have been widely used for inflammatory diseases and cancer. Cordycepin is one of the major bioactive components of Cordyceps militaris, and has been known to have anti-inflammatory and anti-oxidant effects.RESULTS:
We found that WIB-801C significantly attenuated BSCB disruption by inhibiting MMP-9 expression and activation after injury. The infiltration of neutrophils at 1 d and macrophage at 5 d after SCI was also ameliorated by WIB-801C as compared with vehicle control. In addition, the expression of inflammatory cytokines and mediators such as Tnf-α, IL-1β, IL-6, Cox-2, and inos as well as chemokines such as Gro-α and Mip-2α was significantly inhibited by WIB-801C. Furthermore, WIB-801C inhibits p38MAPK activation and proNGF production in microglia after injury. These events eventually led to the inhibition of apoptotic cell death of neurons and oligodendrocytes, improved functional recovery and attenuated demyelination and axon loss after SCI.CONCLUSION:
Our results suggest that WIB-801C can be used as a therapeutic agent after SCI by attenuating BSCB disruption followed inflammation.
Immunostimulatory Activity of Cordyceps
A new polysaccharide (CMPB90-1) was isolated from cultured Cordyceps militaris by alkaline extraction. The chemical structure of CMPB90-1 was determined by analysis of physicochemical and spectral data. The backbone of CMPB90-1 is composed of (1→6)-linked α-d-glucopyranosyl and (1→3)-linked α-d-glucopyranosyl residues, with branching at O-6, which consists of (1→4)-linked β-d-mannopyranosyl and (1→6)-linked α-d-glucopyranosyl residues, respectively. β-d-Galactopyranosyl residues is the terminal unit. In vitro immunomodulatory assay revealed that CMPB90-1 promoted proliferation of splenic lymphocytes, enhanced cytotoxicity of NK cells and promoted lymphocyte secretion of the cytokine interleukin-2. Besides, CMPB90-1 upregulated T-cell subpopulation, strengthened phagocytosis function of macrophages and induced their M1 polarization. The mechanism of the effects might be due to the activation of TLR2, MAPK and NF-κB pathways. The results proposed that CMPB90-1 can be researched and developed as a new functional food.
BI S, et al. 2017. Structural elucidation and immunostimulatory activity of a new polysaccharide from Cordycepsmilitaris. Department of Pharmacology, doi: 10.1039/c7fo01147d.
The medicinal mushroom Cordyceps militaris has been reported to possess anticancer and immunomodulatory effects. We investigated the immunostimulatory effects of culture supernatant of C. militaris (WIB-801CE) by examining its in vitro enhancing effects on cell proliferation and cytokine releases in splenocytes and its in vivo effects on cyclophosphamide-induced immunosuppressed mice. WIB-801CE enhanced normal and methotrexate-induced cell proliferation. WIB-801CE significantly ameliorated interleukin (IL)-2, interferon-γ, and tumor necrosis factor-α secretion in methotrexate-induced splenocytes. Oral administration of WIB-801CE effectively increased the cyclophosphamide-suppressed splenocyte proliferation and natural killer cytotoxic activity. WIB-801CE effectively recovered cyclophosphamide-induced decreases in IL-2, interferon-γ, tumor necrosis factor-α, and IL-10 level. The collective data implicate WIB-801CE as a therapeutic candidate in ameliorating the immunosuppression through immunostimulatory properties.
Shin JS, et al. 2017. Immunostimulatory effects of cordycepin-enriched WIB-801CE from Cordyceps militaris in splenocytes and cyclophosphamide-induced immunosuppressed mice. Department of Pharmaceutical Biochemistry, doi: 10.1002/ptr.5960.
Immunosuppressive Activity of Cordyceps
Cordyceps sinensis (cordyceps) is a fungus used in traditional Chinese medicine as adjuvant immunosuppressive agent in patients with kidney transplant. This review evaluates current evidence on the efficacy and safety of natural and fermented cordycepspreparations in patients with kidney transplant.
Nine studies were eligible for inclusion. These studies were considered to be at moderate risk of bias due to poor reporting of methods. Four studies that compared cordyceps-based therapy with azathioprine-based therapy gave comparable acute rejection rates, and graft and patient survival. The cordyceps-treated group however showed better kidney function and lower incidences of hyperuricemia, hyperlipidemia, hyperglycemia and liver injury. Cordyceps used with different combinations of immunosuppressant therapy showed significant reduction in proteinuria after 6-12 months. Compared to the group receiving cyclosporine A monotherapy, treatment with a combination of cordyceps and cyclosporine A showed less treatment-induced nephrotoxicity. Adverse events were either not monitored or poorly documented in most trials.CONCLUSIONS:
Current evidence shows that cordyceps as an adjuvant to routine immunosuppressant therapy may benefit kidney transplant patient, however, better quality evidence is still required.
Ong BY, et al. 2017. Efficacy of Cordyceps sinensis as an adjunctive treatment in kidney transplant patients: A systematic-review and meta-analysis. Department of Pharmac, 30:84-92.