Cordyceps spp.: A Review on Its Immune-Stimulatory and Other Biological Potentials

doi:10.3389/fphar.2020.602364

Review

. 2021 Feb 8:11:602364.

doi: 10.3389/fphar.2020.602364. eCollection 2020.

Cordyceps spp.: A Review on Its Immune-Stimulatory and Other Biological Potentials

Gitishree Das¹, Han-Seung Shin², Gerardo Leyva-Gómez³, María L Del Prado-Audelo³, Hernán Cortes⁴, Yengkhom Disco Singh⁵, Manasa Kumar Panda⁶, Abhay Prakash Mishra⁷, Manisha Nigam⁸, Sarla Saklani⁹, Praveen Kumar Chaturi⁸, Miquel Martorell¹⁰, Natália Cruz-Martins^{11

12

13}, Vineet Sharma¹⁴, Neha Garg¹⁵, Rohit Sharma¹⁴, Jayanta Kumar Patra¹

Affiliations

¹ Research Institute of Biotechnology and Medical Converged Science, Dongguk University-Seoul, Goyangsi, South Korea.
² Department of Food Science and Biotechnology, Dongguk University-Seoul, Goyangsi, South Korea.
³ Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
⁴ Laboratorio de Medicina Genómica, Departamento de Genética, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México, Mexico.
⁵ Department of Post-Harvest Technology, College of Horticulture and Forestry, Central Agricultural University, Pasighat, India.
⁶ Environment and Sustainability Department, CSIR-Institute of Minerals and Materials Technology, Bhubaneswar, India.
⁷ Adarsh Vijendra Institute of Pharmaceutical Sciences, Shobhit University, Saharanpur, India.
⁸ Department of Biochemistry, H. N. B. Garhwal University, Srinagar Garhwal, India.
⁹ Department of Pharmaceutical Chemistry, H. N. B. Garhwal University, Srinagar Garhwal, India.
¹⁰ Department of Nutrition and Dietetics, Faculty of Pharmacy, and Centre for Healthy Living, University of Concepción, Concepción, Chile.
¹¹ Faculty of Medicine, Alameda Prof. Hernani Monteiro, University of Porto, Porto, Portugal.
¹² Institute for Research and Innovation in Health, University of Porto, Porto, Portugal.
¹³ Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal.
¹⁴ Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
¹⁵ Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

PMID: 33628175
PMCID: PMC7898063
DOI: 10.3389/fphar.2020.602364

Review

Cordyceps spp.: A Review on Its Immune-Stimulatory and Other Biological Potentials

Gitishree Das et al. Front Pharmacol. 2021.

. 2021 Feb 8:11:602364.

doi: 10.3389/fphar.2020.602364. eCollection 2020.

Authors

Affiliations

¹ Research Institute of Biotechnology and Medical Converged Science, Dongguk University-Seoul, Goyangsi, South Korea.
² Department of Food Science and Biotechnology, Dongguk University-Seoul, Goyangsi, South Korea.
³ Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
⁴ Laboratorio de Medicina Genómica, Departamento de Genética, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México, Mexico.
⁵ Department of Post-Harvest Technology, College of Horticulture and Forestry, Central Agricultural University, Pasighat, India.
⁶ Environment and Sustainability Department, CSIR-Institute of Minerals and Materials Technology, Bhubaneswar, India.
⁷ Adarsh Vijendra Institute of Pharmaceutical Sciences, Shobhit University, Saharanpur, India.
⁸ Department of Biochemistry, H. N. B. Garhwal University, Srinagar Garhwal, India.
⁹ Department of Pharmaceutical Chemistry, H. N. B. Garhwal University, Srinagar Garhwal, India.
¹⁰ Department of Nutrition and Dietetics, Faculty of Pharmacy, and Centre for Healthy Living, University of Concepción, Concepción, Chile.
¹¹ Faculty of Medicine, Alameda Prof. Hernani Monteiro, University of Porto, Porto, Portugal.
¹² Institute for Research and Innovation in Health, University of Porto, Porto, Portugal.
¹³ Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal.
¹⁴ Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
¹⁵ Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

PMID: 33628175
PMCID: PMC7898063
DOI: 10.3389/fphar.2020.602364

Abstract

In recent decades, interest in the Cordyceps genus has amplified due to its immunostimulatory potential. Cordyceps species, its extracts, and bioactive constituents have been related with cytokine production such as interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor (TNF)-α, phagocytosis stimulation of immune cells, nitric oxide production by increasing inducible nitric oxide synthase activity, and stimulation of inflammatory response via mitogen-activated protein kinase pathway. Other pharmacological activities like antioxidant, anti-cancer, antihyperlipidemic, anti-diabetic, anti-fatigue, anti-aging, hypocholesterolemic, hypotensive, vasorelaxation, anti-depressant, aphrodisiac, and kidney protection, has been reported in pre-clinical studies. These biological activities are correlated with the bioactive compounds present in Cordyceps including nucleosides, sterols, flavonoids, cyclic peptides, phenolic, bioxanthracenes, polyketides, and alkaloids, being the cyclic peptides compounds the most studied. An organized review of the existing literature was executed by surveying several databanks like PubMed, Scopus, etc. using keywords like Cordyceps, cordycepin, immune system, immunostimulation, immunomodulatory, pharmacology, anti-cancer, anti-viral, clinical trials, ethnomedicine, pharmacology, phytochemical analysis, and different species names. This review collects and analyzes state-of-the-art about the properties of Cordyceps species along with ethnopharmacological properties, application in food, chemical compounds, extraction of bioactive compounds, and various pharmacological properties with a special focus on the stimulatory properties of immunity.

Keywords: clinical studies; cordycepin; cordyceps; ethnopharmacology; immune system; immunomodulatory; immunostimulation; natural medicine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

**FIGURE 1**
Chemical structure of the bioactive compounds isolated from *Cordyceps* spp.

**FIGURE 2**
Signal pathway activation by TLRs and CLRs and its interaction with the *Cordyceps* spp. derived constitutes.

See this image and copyright information in PMC

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References

1. Asai T., Luo D., Obara Y., Taniguchi T., Monde K., Yamashita K., et al. (2012). Dihydrobenzofurans as cannabinoid receptor ligands from Cordyceps annullata, an entomopathogenic fungus cultivated in the presence of an HDAC inhibitor. Tetrahedron Lett. 53, 2239–2243. 10.1016/j.tetlet.2012.02.088 - DOI
1. Balon T. W., Jasman A. P., Zhu J.-S. (2002). A fermentation product of Cordyceps sinensis increases whole-body insulin sensitivity in rats. J. Alternative Compl. Med. 8, 315–323. 10.1089/107628002761574581 - DOI - PubMed
1. Bao Z. D., Wu Z. G., Zheng F. (1994). [Amelioration of aminoglycoside nephrotoxicity by Cordyceps sinensis in old patients]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 14, 271–273. - PubMed
1. Baral B., Shrestha B., Teixeira De Silva J. A. (2015). A review of Chinese Cordyceps with special reference to Nepal, focusing on conservation. Environ. Exp. Biol. 13, 61–73.
1. Berdy J. (1989). The discovery of new bioactive microbial metabolites: screening and identification. Prog. Ind. Microbiol. 27, 3–27.

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[1] Asai T., Luo D., Obara Y., Taniguchi T., Monde K., Yamashita K., et al. (2012). Dihydrobenzofurans as cannabinoid receptor ligands from Cordyceps annullata, an entomopathogenic fungus cultivated in the presence of an HDAC inhibitor. Tetrahedron Lett. 53, 2239–2243. 10.1016/j.tetlet.2012.02.088 - DOI

[2] Asai T., Luo D., Obara Y., Taniguchi T., Monde K., Yamashita K., et al. (2012). Dihydrobenzofurans as cannabinoid receptor ligands from Cordyceps annullata, an entomopathogenic fungus cultivated in the presence of an HDAC inhibitor. Tetrahedron Lett. 53, 2239–2243. 10.1016/j.tetlet.2012.02.088 - DOI

[3] Balon T. W., Jasman A. P., Zhu J.-S. (2002). A fermentation product of Cordyceps sinensis increases whole-body insulin sensitivity in rats. J. Alternative Compl. Med. 8, 315–323. 10.1089/107628002761574581 - DOI - PubMed

[4] Balon T. W., Jasman A. P., Zhu J.-S. (2002). A fermentation product of Cordyceps sinensis increases whole-body insulin sensitivity in rats. J. Alternative Compl. Med. 8, 315–323. 10.1089/107628002761574581 - DOI - PubMed

[5] Bao Z. D., Wu Z. G., Zheng F. (1994). [Amelioration of aminoglycoside nephrotoxicity by Cordyceps sinensis in old patients]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 14, 271–273. - PubMed

[6] Bao Z. D., Wu Z. G., Zheng F. (1994). [Amelioration of aminoglycoside nephrotoxicity by Cordyceps sinensis in old patients]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 14, 271–273. - PubMed

[7] Baral B., Shrestha B., Teixeira De Silva J. A. (2015). A review of Chinese Cordyceps with special reference to Nepal, focusing on conservation. Environ. Exp. Biol. 13, 61–73.

[8] Baral B., Shrestha B., Teixeira De Silva J. A. (2015). A review of Chinese Cordyceps with special reference to Nepal, focusing on conservation. Environ. Exp. Biol. 13, 61–73.

[9] Berdy J. (1989). The discovery of new bioactive microbial metabolites: screening and identification. Prog. Ind. Microbiol. 27, 3–27.

[10] Berdy J. (1989). The discovery of new bioactive microbial metabolites: screening and identification. Prog. Ind. Microbiol. 27, 3–27.

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Cordyceps spp.: A Review on Its Immune-Stimulatory and Other Biological Potentials

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Cordyceps spp.: A Review on Its Immune-Stimulatory and Other Biological Potentials

Authors

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Abstract

Conflict of interest statement

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