CORDYCEPS

BACKGROUND

Ingredient Type: Fungi

Also Known As: Cordyceps sinensis, Caterpillar fungus, Catepillar mushroom, Summer grass-winter worm

Cordyceps is a form of the ascomycete fungi that acts parasitically on insects and other arthropods, and some other fungi. This particular fungus has been found in various, high-altitude environments in cold, grassy areas such as the Himalayan mountains’ alpine meadows (2). Cordyceps, for centuries, has a vast history rooted in Traditional Chinese Medicine. Isolation and analysis of the fungus has allowed scientists to identify key bioactive components, shown to be useful in the medical and clinical settings, such as cordycepin, cordycepic acid, ergosterol, polysaccharides, nucleosides, and peptides (1).

The first written documentation of the use of cordyceps was found in China in the late 1600s in Ben-Cao-Bei-Yao, by Wang Ang (1). In Chinese, the name of the fungus, Dong Chong Xia Cao, means “Worm in Winter and Grass in Summer.” In Latin, the name Cordyceps means club and head. The fungus is found parasitizing on the head of the larva of one particular moth species, Hepilaus amoricanus Oberthur, although it is occasionally found also growing on other moth species. Although commonly used in various Asian countries, Cordyceps was brought to the West during the 17th century by an Italian scholar named Cordyceps as Cordyceps sinensis (Berk.) Sacc., which has retained its nomenclature since (1).

TRADITIONAL USES

According to folk and Traditional Chinese and Tibetan Medicine, there are 21 ailments that cordyceps has been and continues to be used for, such as cancer, bronchial asthma, bronchitis, tuberculosis, diabetes, cough/cold, erectile dysfunction, benign prostatic hyperplasia, jaundice, alcoholic hepatitis, hepatic and renal diseases, coronary heart disease, chronic pain, sciatica/backache, low blood pressure and dizziness (2). In Nepal, reports also confirm the use of C. Sinensis mixed with other herbs has been used for cancer (4,5). According to somewhat recent research, in traditional Chinese medicine, C. Sinensis exhibits very broad biological and pharmacological actions in hepatic, renal, cardiovascular, and immunological systems as well as anti-cancer activity (6).

WHAT DOES SCIENCE TELL US?

Cordyceps Possibly Supports Eye Health:

A study analyzed the effects of Cordyceps sinensis and Cordyceps militaris on human glomerular mesangial cell proliferation, induced by native LDL. It was noted from the results that LDL plays a potential role in mediating mesangial cell hypertrophy or proliferation involved in the development of glomerulosclerosis. The cells that received Cordyceps sinensis and Cordyceps militaris inhibited proliferation of the cultured human glomerular mesangial cells, induced by LDL concentrations. It was concluded that Cordyceps sinensis and Cordyceps militaris have the potential to slow the proliferation of human glomerular mesangial cells induced by LDL (14).

In this clinical study, researchers sought to explore Cordyceps sinensis (CS) effects in patients obtaining clinical renal transplantation. Patients (n = 202) were divided in to two groups by lottery, a treatment group (n = 93) and a control group (n = 109). Those in the treatment group received 1.0g of CS TID in addition to an immunosuppressive regimen given to the control group. The following markers were measured to assess the effectiveness of the CS treatment: survival graft, incidence/time/severity of acute rejection episodes, chronic allograft nephropathy, hepatotoxicity and nephrotoxicity, biochemical parameter indicators for the liver/kidney function, fats, proteinuria, dosages as well as whole blood concentrations of cyclosporine. The results revealed that serum uric acid was significantly decreased and the levels of hepatotoxicity and nephrotoxicity in the treatment group compared to the control group. Additionally, the differences in total bilirubin, SCr, serum, UA, and total cholesterol levels were significantly lower in the treatment group vs. the control group. It was concluded from this data that CS might have potential in allowing a decrease in the cyclosporine, causing fewer side effects without an increased risk of acute renal rejection. Reduced cyclosporine dosages may also decrease proteinuria while slowing the progression of chronic allograft nephropathy (8).

Another study investigated the kidney protective ability of N6 –(2-hydroxyethyl)-adenosine (HEA) from cordyceps in alloxan-induced diabetic rats. In this experiment, the diabetes was induced through alloxan monohydrate administration and treated with HEA for 6-weeks. The results showed that the treatment group experienced significantly increased renal antioxidant levels, reduced levels of blood glucose, Scr, BUN, urinary protein, albumin, and pro-inflammatory mediators in a dose-dependent fashion when compared to the control group. It was also indicated that the HEA also ameliorated glomerular and tubular changes. The HEA was seen to simulate the antioxidant enzyme activity in the kidney tissues and reduce pro-inflammatory mediators, indicating its antidiabetic and reno-protective effects (18).

Cordyceps Possibly Supports Liver Health:

This study was conducted to seek an effective compound to treat patients with hepatitis B. 25 patients with clinically diagnosed hepatitis B were treated with Cordyceps sinensis. The following markers were measured at the beginning and the end of the study: T-lymphocyte subsets (CD4/8), hyaluronic acid, and pro-collagen type III. Following the 3-month study treatment, it was noted that the CD4 and CD4/8 ratios increased significantly while hyaluronic acid and pro-collagen III significantly decreased when compared to the control group. The results suggest that Cordyceps sinensis may be a potential alternative treatment in modulating the T-lymphocyte subset levels in treating hepatic fibrosis in patients with hepatitis B (13).

This study aimed to investigate the inhibitive effect and other Cordyceps sinensis (CS) mechanisms on CCI (4)-plus ethanol-induced hepatic fibrogenesis in experimental rats. The rats were assigned to one of three groups: standard control group, model control group, and the CS group. The model control and the CS group were also administered CCI (4) and an ethanol solution at the beginning of the experiment to induce hepatic fibrosis. The CS group was additionally treated with CS 10-days after administering the CCI (4) & ethanol solutions. Compared to the model control group, serum ALT, AST, HA, and LN content levels were noted to have markedly dropped in the CS group. It was gathered from the results that Cordyceps sinensis indeed could inhibit hepatic fibrogenesis derived from chronic liver injury and retard the development of cirrhosis ameliorate liver function (15).

Cordyceps Possibly Reduces Inflammation:

Much of oxidative stress is reportedly induced by excessive amounts of reactive oxygen species (ROS), which has the potential to induce neurological as well nervous system damage. This study analyzed the effectiveness and mechanisms behind the activity of Cordyceps militaris (CM) as a free radical scavenger of the nervous system in H2O2-induced C6 glial cells. H2O2-induced C6 glial cells were treated with CM at 0.5-2.5ug/mL to measure viability, ROS production, as well as protein expression resulting from the resultant oxidative stress. The treatment of CM on the H2O2-induced C6 glial cells noted a significant increase in cell viability along with a decrease in ROS production. Additionally, many of the protein levels associated with tissue damage were down-regulated upon CM administration. It was concluded from the results that CM exhibits free radical scavenging activity in its ability to increase cell viability, decrease ROS production while down-regulating inflammatory-related protein production, suggesting CM’s potential as an alternative for treatment in glial cell-related oxidative damage and stress (16).

A similar study was conducted to investigate whether the Cordyceps militaris extract (CME) has in vitro protective effects on H2O2-induced oxidative stress in human dermal fibroblasts (HDFs). The study results indicate that the free radical scavenging activity of CME was increased in a dose-dependent manner. It was found that post- H2O2 treatment, there was an increase in ROS generation and cellular death in the control group. In the CME group, however, inhibition of H2O2-induced cell death and apoptotic nuclear condensation was present, suggesting CME was able to inhibit oxidative stress-induced premature senescence. It was concluded from these results that CME may have protective effects against oxidative stress-induced premature senescence through its ROS scavenging qualities (17).

Cordyceps Possibly Supports a Healthy Balance of Hormones:

This study was conducted to demonstrate the mechanism by which Cordyceps sinensis (CS) mycelium is able to regulate Leydig cell steroidogenesis. Leydig cells were treated with forskolin, H89, phorbol 12-myristate 13-acetate, staurosporine, or steroid enzymatic precursors with or without 3mg/ml of CS. The study’s results found that CS inhibited Leydig cell steroidogenesis by suppressing the P450scc enzyme. CS was also able to inhibit Forskolin-induced steroidogenesis. It was concluded from this study that CS can reduce hCG and cAMP-stimulated steroidogenesis (via cAMP-PK-A signal pathway and potentially attenuated P45scc enzyme activity; that which is responsible for converting cholesterol to pregnenolone) (9).

Another study assessed the effects of Cordyceps sinensis (CS) and its extracted fractions on testosterone’s secretion in Leydig cells. The results noted that CS, F2 (water-soluble protein), and F3 (poorly water-soluble polysaccharide) significantly stimulated in vitro testosterone production in the purified Leydig cells. F2 & F3, however, did stimulate in vitro testosterone production in a dose-dependent, time-dependent manner. The in vivo study illustrated that CS, F2, and F3 significantly increased testosterone levels in plasma. From the results, it was concluded that CS might potentially contribute as an alternative medicine to treat certain forms of testosterone insufficiency in males (10,11).

This study investigated the spermatogenic effect of Cordyceps militaris (CM) on Sprague-Dawley rats. A total of 90 subjects were selected and divided into three groups, a group subject to a regular diet, a diet supplemented with CM 1% or 5% for a duration of 6-weeks. Epididymal sperm were collected during each selected interval. The results indicated that CM supplementation significantly increased serum cordycepin concentration and sperm count compared to the control group. As to hormone level changes, it was only noted that serum testosterone and estradiol-17 (E2) concentrations were elevated in response to the CM treatment, while other hormones did not see any fluctuations. Additionally, it was noted that there was a significant increase in the percentage of motile sperm cells in the CM treatment group. The results indicate the supplementation with CM improves sperm quantity and quality in rats while also increasing serum testosterone and E2 levels in rats (12).

Cordyceps Possibly Supports Healthy Cell Growth:

Cordyceps militaris (CM) was examined in this study for its antioxidant and anti-cancer qualities. In this study, analysis of the metabolite profile in 50% ethanol extracts of CM fruit bodies from 3-developmental stages of the plant was conducted to identify the bioactive components and their metabolically useful qualities. The older the stage, the more significant the increase of metabolites containing cordycepin, mannitol, and b-glucan were present amongst the three development periods of the CM fruit. According to current research, these bioactive metabolites are positively correlated with anti-tumor growth. The extract of the furthest aging showed significant inhibition of HepG2 hepatic cancer cell proliferation. It was concluded from the results that the aged components of the CM fruit bodies have bioactive metabolites that are associated with the biological effect of cancer cell growth inhibition (19).

According to studies, hepatocellular carcinoma is the most common liver cancer among different types of cancer. In Traditional Chinese Medicine, Cordyceps militaris (CM) is a commonly used alternative medicine used for various ailments. This study investigated the gold nanoparticles, which play a key role in developing anti-cancer drugs, with CM on hepatocellular carcinoma. The synthesized gold nanoparticles’ stability and integrity were studied at different time intervals. The gold nanoparticles have the potential to halt the growth of HepG2 cells at specific concentrations. It was noted that the gold nanoparticle-CM extract caused damage to the mitochondrial membrane potential in the hepatocellular carcinoma HepG2 cells. From these results, it was concluded that gold nanoparticles and C. militaris have the potential to be an effective chemotherapeutic drug against hepatocellular carcinoma cells (20).

This study was conducted to investigate the anti-tumor effect of Cordyceps militaris extract (CME) on A549 cisplatin-resistant lung cancer cells. It was noted from the results, CME suppressed the proliferation of A549/CR cells via induced apoptosis. Proteomic profile analysis showed that H-Ras was downregulated in the CME-treated cells, further supported through western blot analysis. It was concluded from the data and supporting research that CME is an alternative treatment with anti-cancer qualities (21).

Cordyceps Possibly has Aphrodisiac Properties:

Cordyceps sinensis (Berk) sacc. is a fungus commonly used in traditional Chinese medicine as well as in other Asian cultures as an aphrodisiac and tonic. The people of North Sikkim have relied on C. sinensis for centuries to increase sexual arousal, desire, and drive, especially in their harsh, high altitude environment. It has been claimed by the Sikkim Hima-laya people as well as researchers from a study conducted between 2008-2009 that Cordyceps sinensis can combat sexual dysfunction and will be a potential alternative to challenge impotence-associated medications like Viagra (3).

SAFETY

The majority of cordyceps research has been conducted on animals or in vivo or in vitro, with limited research on human subjects. Cordyceps is considered potentially safe if consumed orally in medicinal quantities for short periods. There is no real conclusive safety and or toxicity information available for cordyceps at this time. It is therefore recommended to consume with caution. If you are with or think you may be with any medical conditions, please consult your healthcare professional before supplementing with cordyceps.

Side-Effects:

Those with auto-immune conditions such as multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, or similar conditions are advised to take precautions as cordyceps may cause the immune system to become more active, which can potentially exacerbate the symptoms of auto-immune such auto-immune diseases (7).

Additionally, those with bleeding disorders, taking blood thinners, or those preparing for surgery should consult their healthcare professional before consumption as cordyceps may have the ability to slow the blood clotting process, thereby potentially increasing the risk of bleeding (7).

Interactions:

Please consult your healthcare provider if you are taking any of the following medications as they may have adverse, exacerbated, or hindered effects on the respective, associated conditions.

Those taking medications that suppress the immune system (cyclophosphamide, azathioprine, basiliximab, cyclosporine, daclizumab, muromonab-CD3, mycophenolate, tacrolimus, sirolimus, prednisone, or other corticosteroids) should take precautions when consuming cordyceps as it may potentially have increased immunomodulatory effects, thereby canceling out the effectivity of the medication (7).

Additionally, precaution should be taken for those taking anticoagulants or blood thinners (aspirin, clopidogrel, dalteparin, enoxaparin, heparin, ticlopidine, warfarin, amongst others) as cordyceps may potentially slow the blood clotting process, thereby exacerbating the effects of the anticoagulant, which could lead to increased risk of bruising or bleeding (7).

REFERENCES

1. Yue K, Ye M, Zhou Z, Sun W, Lin X. The Genus Cordyceps: A Chemical and Pharmacological Review. Wiley Online Library. 2012;54(4): 474-493.
2. Panda AK, Swain KC. Traditional Uses and Medicinal Potential of Cordyceps sinensis of Sikkim. J Ayurveda Integr Med. 2011;2(1): 9-13.
3. Pranda AK. Tracing the Historical Prospective of Cordyceps sinensis – an Aphrodisiac in Sikkim Himalaya. Ind J Hist Sci. 2010;45: 189-198.
4. Adhikari MK, Devkota D, Tiwari RD. Ethnomycological Knowledge on Uses of Wild Mushrooms in Western and Central Nepal. Our Nature. 2005;3(1): 13-19.
5. Devkota, S. Yarsagumba: Traditional Utilization in Dolpa District, Western Nepal. Our Nature. 2006;4(1): 48-52.
6. Wang Sy, Shiao MS. Pharmacological Functions of Chinese Medicinal Fungus C. Sinensis and Related Species. J Food Drug Anal. 2000;8(4): 248-257.
7. Cordyceps. https://www.rxlist.com/codyceps/supplements.htm Accessed 25 August 2019.
8. Li Y, Xue WJ, Tian PX, Ding XM, et al. Clinical Application of Cordyceps sinensis on Immunosuppressive Therapy in Renal Transplantation. Transplant Proc. 2009;41(5): 1565-1569.
9. Hsu CC, Tsai SJ, Huang YL, Huang BM. Regulatory Mechanism of Cordyceps sinensis Mycelium on Mouse Leydig Cell Steroidogenesis. FEBS Lett. 2003;543(1-3): 140-143.
10. Hsua CC, Huanga YL, Tsaib SJ, Sheuc CC, Huang BM. In vivo and in vitro Stimulatory Effects of Cordyceps sinensis on Testosterone Production in Mouse Leydig Cells. Life Sci. 2003;73(16): 2127-2136.
11. Huang BM, Hsu CC, Tsai SJ, Sheu CC, Leu SF. Effects of Cordyceps sinensis on Testosterone Production in Normal Mouse Leydig Cells.  Life Sci. 2001;69(22): 2593-2602.
12. Chang Y, Jeng KC, Huang KF, et al. Effect of Cordyceps militaris Supplementation on Sperm Production, Sperm Motility and Hormones in Sprague-Dawley Rats. Am J Chin Med. 2008;36(5): 849-859.
13. Gong HY, Wang KQ, Tang SG. Effects of Cordyceps sinensis on T-Lymphocyte Subsets and Hepatofibrosis in Patients with Chronic Hepatitis B. Hunan Yi Ke Da Xue Xue Bao. 2000;25(3): 248-250.
14. Zhao-Long W, Xiao-Xia W, Wei-Ying C. Inhibitory Effect of Cordyceps sinensis and Cordyceps militaris on Human Glomerular Mesangial Cell Proliferation Induced by Native LDL. Cell Biochem Funct. 2000;18(2): 93-97.
15. Liu YK, Shen W. Inhibitive Effect of Cordyceps sinensis on Experimental Hepatic Fibrosis and its Possible Mechanism. World of Gastroenterol. 2003;9(3): 529-533.
16. He MT, Lee AY, Park CH, Cho EJ. Protective Effect of Cordyceps militaris Against Hydrogen Peroxide-Induced Oxidative Stress in vitro. Nutr Res Pract. 2019;13(4): 279-285.
17. Park JM, Lee JS, Lee KR, Ha SJ, Hong EK. Cordyceps militaris Extract Protects Human Dermal Fibroblasts Against Oxidative Stress-Induced Apoptosis and Premature Senescence. Nutrients. 2014;6(9): 3711-3726.
18. Wang X, Qin A, Xiao F, et al. N6 –(2-hydroxyethyl)-adenosine from Cordyceps Cicadae Protects Against Diabetic Kidney Disease via Alleviation of Oxidative Stress and Inflammation. J Food Biochem. 2019;43(2): e12727.
19. Oh J, Choi E, Yoon DH, et al. H-NMR Based Metabolic Profiling of Cordyceps militaris to Correlate the Development Process and Anti-Cancer Effect. J Microbiol Biotechnol. 2019; 29(8): 1212-1220.
20. Ji Y, Cao Y, Song Y. Green Synthesis of Gold Nanoparticles using a Cordyceps militaris Extract and their Anti-Proliferative Effect in Liver Cancer Cells. Artif Cells Nanomed Biotechnol. 2019;47(1): 2737-2745.
21. Jeong MK, Yoo HS, Kang IC. The Extract of Cordyceps militaris Inhibited the Proliferation of Cisplatin-Resistant A549 Lung Cancer Cells by Downregulation of H-Ras. J Med Food. 2019;22(8): 823-832.