Cordyceps

Cordyceps is a globally distributed genus of Ascomycetes that includes about 750 species. Most types of this parasitic fungus are native in the moist temperate and tropical forests of Asia. In traditional Chinese medicine, the Chinese caterpillar mushroom (Cordyceps sinensis) is of particular use(1). Cordyceps sinensis comes from the Tibetan highlands and has an extraordinary life cycle. The fungus survives the winter underground as a parasite of larvae, then in spring it grows in a finger-shape up toward the earth's surface. Since this free-growing caterpillar fungus is very rare and a protected species, a cultivated mycelium is used for application in mycotherapy. This undergoes a fermentation and standardization process (CS-4®) and is therefore  suitable for therapeutic use.
 

The medicinal mushroom Cordyceps sinensis is said to have a comprehensive spectrum of action in TCM (2). Above all, it is used to nourish the kidneys and strengthen the lungs (1). A number of studies have focused on the phytochemistry and pharmacological activity of this species. It describes numerous nucleosides, polysaccharides, sterols and cyclopeptides as biologically active ingredients (1)(3). However, the two most important bioactive ingredients are the nucleoside cordycepin (30-deoxyadenosine) and cordycepic acid (1). In pharmacological studies Cordycepin hasshown very good anti-inflammatory and antioxidative effects (4)(5). In addition, in vitro and in vivo studies suggest the following effects: antitumor, neuroprotective, anti-aging, gastroprotective, antidiabetic, aphrodisiac, antiproliferative, anti-fatigue and immunomodulatory activities (1).
 

Medical fungi have a promising therapeutic potential as a complementary immunomodulating measure for the treatment of various diseases. The modulation of the immune system takes place on a local and systemic level. In the animal model, increased lymphocyte proliferation, phagocytosis and interleukin-6 production as well as an increase in the density of Peyer's plaques in the digestive tract were observed after oral supplementation with the medicinal fungus (6). In 2016, Wang et al. published a human study in which the therapeutic effects of supplementation for 3 months with Cordyceps-sinensis  (3 x 1.2 g Cordyceps sinensis/d) were investigated in 120 asthmatics with moderate to severe symptoms (test and control group: n=60 each). If required, both groups could also resort to inhaled corticosteroids and beta-agonists. In the test group disease symptoms, lung function and inflammatory profile (IgE, ICAM-1, IL-4, MMP-9 in serum) improved (7). Organ transplant patients could also benefit from the immunomodulatory effects of the medicinal fungus. In 2017, a systematic review and meta-analysis examined the therapeutic potential of Cordyceps sinensis after kidney transplant. The results showed that the concomitant administration of Cordyceps alonside the usual immunosuppressants led to a significant reduction of proteinuria after 6 to 12 months. In addition, the review showed that the combination of Cordyceps with cyclosporin A was less associated with treatment-related nephrotoxicity than monotherapy alone (8). 
 

The therapeutic use of Cordyceps sinensis has been intensively investigated scientifically, especially in the area of performance enhancement. In studies of trained athletes, Cordyceps sinensis increased maximum oxygen uptake and anaerobic threshold after 6 weeks of supplementation. The positive effects are attributed to the increase in fat mobilization and beta-oxidation, which protects glycogen reserves during periods of stress (9). This effect is particularly interesting for endurance athletes. Promising therapeutic potential of Cordyceps can also be expected in weaker patients. In a pilot study of healthy adults between 50 and 75 years of age, it was shown that taking 333 mg Cordyceps CS-4® 3 times daily over a period of 12 weeks significantly increased the performance. Supplementation led to a significant increase of the lactate threshold by 10.5 % and the ventilatory threshold by 8.5 % (10). In addition, Cordyceps administration in animal models significantly improved stress resistance (11)(12) and animal endurance in exhaustive exercises by increasing corticosteroid production (13). In addition, the medicinal fungus had a beneficial effect on movement-induced oxidative stress by increasing the activity of antioxidative protective enzymes such as SOD and GPx (13). The results support the long traditional use of Cordyceps sinensis to increase performance and reduce fatigue and weakness.
 

Numerous in vitro and in vivo studies attest a broad spectrum of effects to Cordyceps sinensis (1). Recent studies suggest its use in oncological diseases, metabolic disorders and the prevention of liver and kidney diseases (5). The antitumor effect of cordycepin is seen in the activation of adenosine receptors. This leads to the stimulation of protein kinase C, which plays an important role in cellular signal transduction and in the regulation of cellular growth. In a study of human leukemia cells, it was also demonstrated that cordycepin significantly inhibits the cell proliferation of malignant tumor cells. By selectively inhibiting and destabilizing beta-catenin, cordycepin interferes with the WNT signaling pathway that is often involved in tumor development (14). In addition, cordycepin significantly reduced harmful effects of ionizing radiation in animal models. The protective effects are due to the reduction of lipid peroxidation and oxidative damage as well as to the increase in immune activity (15). Furthermore, Cordyceps showed antimetastatic activity in in vitro studies and animal models by downregulating the expression of several metastasizing cytokines (16).

1) Olatunji, O. J. et al. 2018. The genus Cordyceps: An extensive review of its traditonal uses, phytochemistry and pharmacology. Fitoterapia. 129:293-316.
2) Shashidhar, M. P. et al. 2013. Bioactive principles from Cordyceps sinensis: A potent food supplement – A review. Journal of Functional Foods 5, Nr. 3: 1013–1030. doi:10.1016/j.jff.2013.04.018.
3) Yue, K. et al. 2012. The genus Cordyceps : a chemical and pharmacological review. Journal of Pharmacy and Pharmacology 65, no. 4: 474–493.
4) Tuli, H. S. et al. 2013. Pharmacological and therapeutic potential of Cordyceps with special reference to Cordycepin. 3 Biotech 4, no. 1: 1–12.
5) Nie, S. et al. 2013. Bioactive polysaccharides from Cordyceps sinensis: Isolation, structure features and bioactivities. Bioactive Carbohydrates and Dietary Fibre 1, no. 1: 38–52.
6) Koh, J. H. et al. 2002. Activation of Macrophages and the Intestinal Immune System by an Orally Administered Decoction from Cultured Mycelia of Cordyceps sinensis. Bioscience, Biotechnology, and Biochemistry 66, no. 2: 407–411.
7) Wang, N. et al. 2016. Herbal Medicine Cordyceps sinensis improves health-related quality of life in moderate-to-servere asthma. Evid Based Complement Alternat Med. 2016:6134593.
8) Ong, B. Y., Aziz, Z. 2017. Efficacy of Cordyceps sinensis as an adjunctive treatment in kidney transplant patients: A systematic-review and meta-analysis. Complement Ther Med. 30:84–92.
9) Chen, S. et al. 2010. Effect of Cs-4® (Cordyceps sinensis) on Exercise Performance in Healthy Older Subjects: A Double-Blind, Placebo-Controlled Trial. The Journal of Alternative and Complementary Medicine 16, no. 5: 585–590.
10) Nicodemus, K. et al. 2001. Supplementation with Cordyceps Cs-4 Fermentation Product promotes Fat Metabolism during prolonged Exercise. Med Sci Sport Exercise. doi: 10.1097/00005768-200105001-00928.
11) Leu, S. F. et al. 2005. The in Vivo Effect of Cordyceps sinensis Mycelium on Plasma Corticosterone Level in Male Mouse. Biol Pharm Bull. 28(9):1722–5.
12) Koh, J. H. et al. 2003. Antifatigue and Antistress Effect of the Hot-Water Fraction from Mycelia of Cordyceps sinensis. Bio Pharm Bull. 26(5):691–4.
13) Yan, F. et al. 2014. Polysaccharides from Cordyceps sinensis mycelium ameliorate exhaustive swimming exercise-induced oxidative stress. Pharm Biol. 52(2):157–61.
14) Ko, B. S. et al. 2013. Cordycepin Regulates GSK-3β/β-Catenin Signaling in Human Leukemia Cells. PLoS One. 8(9):e76320.
15) Zhang, J. et al. 2011. Effect of polysaccharide from cultured Cordyceps sinensis on immune function and anti-oxidation activity of mice exposed to 60Co. Int Immunopharmacol. 11(12):2251–7.
16) Cai, H. et al. 2018. Extracts of Cordyceps sinensis inhibit breast cancer cell metastasis via down-regulation of metastasis-related cytokines expression. J Ethnopharmacol. 214:106–12.
17) Sellami, M. et al. 2018. Herbal medicine for sports: a review. J Int Soc Sports Nutr. 15:14.

References Interactions
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