Bioactive Compounds and Pharmacological Activities of the Genus Cordyceps: A Review

Varsha Meshram*; Nagendra Kumar Chandrawanshi

doi:10.52228/NBW-JAAB.2022-4-1-4

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Bioactive Compounds and Pharmacological Activities of the Genus Cordyceps: A Review

Author(s): Varsha Meshram*¹, Nagendra Kumar Chandrawanshi²

Email(s): ¹varshameshram2801@gmail.com, ²chandrawanshi11@gmail.com

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Published In: Volume - 4, Issue - 1, Year - 2022

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Varsha Meshram and Nagendra Kumar Chandrawanshi (2022) Bioactive Compounds and Pharmacological Activities of the Genus Cordyceps: A Review. NewBioWorld A Journal of Alumni Association of Biotechnology,4(1):13-19.

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NewBioWorld A Journal of Alumni Association of Biotechnology (2022) 4(1):13-19

REVIEW ARTICLE

Bioactive Compounds and Pharmacological Activities of the Genus Cordyceps: A Review

Varsha Meshram* and Nagendra Kumar Chandrawanshi

School of Studies in Biotechnology, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India.

varshameshram2801@gmail.com; chandrawanshi11@gmail.com

*Corresponding author Email: varshameshram2801@gmail.com

ARTICLE INFORMATION

ABSTRACT

Article history:

Received

28 March 2022

Received in revised form

17 June 2022

Accepted

21 June 2022

Keywords:

Cordyceps species; Bioactive compounds; Extraction process; Pharmacological activities

For many years, traditional Chinese medicine has relied on medicinal fungi to boost the immune system and revitalize the body due to their diverse biological functions. Among the medicinal fungi, Cordyceps species have been particularly valuable because of their bioactive components that are beneficial for modern medicine and pharmacology. However, most reviews on Cordyceps have only focused on a few species and their specific pharmacological effects, leaving many other species unexplored. This review aims to fill this gap by gathering data on the pharmacological value of various Cordyceps species and their best extraction process for bioactive compounds. By doing so, we can uncover potential therapeutic applications of Cordyceps that have not been explored yet, and contribute to the development of new drugs and treatments.

Graphical Abstract:

1. Introduction

DOI: 10.52228/NBW-JAAB.2022-4-1-4

Cordyceps is a highly regarded traditional Chinese medicine that has been used for centuries. It is made up of dried fungus that grows on the bodies of caterpillars. The fungus belongs to the Cordyceps genus and is considered to have many health benefits (Ng and Wang, 2005). The term "Cordyceps" originates from the fusion of two words: "kordyle," which is a Greek word that refers to "club," and "ceps," a Latin word that means "head." Although various species of Cordyceps differ in terms of their growth location and the type of insects they infect, they share a comparable life cycle and utilize host organisms for their growth. Cordyceps typically exist in a dormant state in the soil and become active when they encounter a suitable host. They are different from other fungi because they produce a unique fruiting body and are a pathogen of insects and the fungal genus Elaphomyces. Some Cordyceps species are easier to grow than others (Kobayasi. Y, 1941). There are around 20 species of Cordyceps that attack the Elaphomyces fungi, while the rest of the species invade insects and other arthropods like spiders, beetles, bugs, wasps, termites, and butterflies (Mains, 1958). Cordyceps are a type of fungus found in many different parts of the world, particularly in humid, tropical forests and high altitude on the Himalayan plateau (Borde and Singh, 2022). They are most commonly found in North America, Europe, and Asian countries like China, Japan, and Korea. However, other species of Cordyceps have also been discovered in different environments across the globe, showing that they can grow in many different places (Winkler, 2010; Panda and Swain, 2011; Holliday and Cleaver, 2008; Li et al., 2022). The two most well-known and researched species of Cordyceps are C. sinensis and C. militaris. These fungi have been found to have positive effects on various health conditions such as respiratory, liver, and kidney problems, heart and lung diseases, high blood sugar, high cholesterol, and even as potential treatments for cancer (Xiao and Zhong, 2007; Qu et al., 2022). Fermentation technology has become a popular method for mass-producing certain species of Cordyceps due to the scarcity and high cost of natural Cordyceps (Zhang et al., 2019; Sun et al., 2019). This article provides a comprehensive overview of the pharmacological acitvites of extracted bioactive compounds of known Cordyceps species.

2. Bioactive compounds

The different species of Cordyceps produce a wide variety of chemicals, both in their natural state and when grown in a lab. Some of the important groups of chemicals found in Cordyceps include nucleosides, sterols, flavonoids, cyclic peptides, phenolics, bioxanthracenes, polyketides, and alkaloids. Cyclic peptides are particularly common in Cordyceps.

2.1 Nucleosides

Most of the nucleosides discovered in Cordyceps were found in C. sinensis, C. militaris, and C. cicadae. Cordycepin is the most significant nucleoside found in Cordyceps due to its broad range of pharmacological benefits (Cunningham et al., 1950). Other nucleosides discovered in Cordyceps include adenine, adenosine, uracil, uridine, guanidine, guanosine, hypoxanthine, inosine, thymine, thymidine, and deoxyuridine (Li et al., 2006). These compounds have been shown to have strong abilities to fight cancer, viruses, inflammation, and tumors, as well as to protect the brain and act as antioxidants (Liu et al., 2015)

2.2 Polysaccharides

In recent years, scientists have become increasingly interested in the polysaccharides found in Cordyceps due to their potential medical benefits. These benefits include anti-tumor, immune-boosting, anti-oxidant, anti-inflammatory, anti-aging, and anti-fatigue properties (Shin et al., 2018). Researchers have also found that certain strains of Cordyceps, such as C. militaris, C. taii and C. guangdongensis (Yan et al., 2013), have specific effects, such as anti-cancer and anti-oxidant properties.

2.3 Sterols

Cordyceps species contain sterol-type compounds that have shown potent anti-tumor activity. The main sterols found in Cordyceps are ergosterol and ergosterol peroxide, but other sterols such as 3-sitosterol, campeasterol, daucosterol, and 5α,8α-epidioxy-24(R)-methyl-cholesta-6,22-dien-3β-D-glucopyranoside have also been discovered (Olatunji et al., 2018). These sterols have various pharmacological properties, such as cytotoxic, antiviral, antiarrhythmic, and the ability to alleviate immunoglobulin A nephropathy and suppress activated human mesangial cells (Li et al., 2006). Some other bioactive compounds are shown in Table 1.

3. Extraction of Major Compounds from Cordyceps spp.

Chen et al. (2013) utilized different extraction techniques to isolate specific bioactive compounds from Cordyceps spp. Aqueous extraction using water as the extraction medium was standardized by Sun et al. (2003), yielding between 25-30% and displaying antioxidant activity. Alcoholic extraction with methanol, ethanol, aqueous methanol, and aqueous ethanol was found to be effective in extracting nucleosides, polysaccharides, and proteins, resulting in strong antioxidant activity and cytotoxic effects on cancer cells (Yamaguchi et al., 2000; Jia et al., 2009). Ethyl acetate extraction, despite its low yield, was able to isolate important bioactive components such as ergosterol, cordycepin, and adenosine, and exhibited anticancer and antioxidant activities (Zhang et al., 2004; Wu et al., 2007; Wu et al., 2006). Supercritical CO₂ extraction, a highly efficient and pure method, was able to extract non-polar bioactive compounds from Cordyceps and showed potent scavenging abilities and the ability to inhibit cancer cell proliferation (Wang et al., 2005).

4. Pharmacological activities

Cordyceps has been shown to have various pharmacological activities, including anti-inflammatory, antioxidant, immunomodulatory, anti-tumor, anti-viral, anti-microbial, anti-diabetic, anti-fatigue, and anti-aging effects. Table 2 represents the pharmacological activities of Cordyceps species.

Table 1: Bioactive compounds of Cordyceps species.

S.No.	Bioactive compounds	Species	References
1.	Cordycepin	C.sinesis	Cunningham, 1950
2.	Cordymin	C.sinesis	Qian et al., 2015; Wang et al., 2012
3.	Ergosterol	C.militaris,	Sun et al., 2019
4.	Cordysinin A	C.sinesis	Yang et al., 2011
5.	Cordysinin B	C.sinesis	Yang et al., 2011
6.	5α,8α-epidioxy-22E-ergosta-6,22-dien-3β-ol	C.sinesis	Matsuda et al., 2009
7.	5α,8α-epidioxy-22E-ergosta-6,9(11),22-trien-3β-ol	C.sinesis	Matsuda et al., 2009
8.	Cordycepic acid	C.sinesis	Liu et al., 2015
9.	Fumosoroseain A	C. fumosorosea	Buchter et al., 2020
10.	Fumosoroseanoside A	C. fumosorosea	Buchter et al., 2020
11.	Trichocaranes	C. fumosorosea	Chen et al., 2018
12.	Terreusinone A	C. gracilioides	Wei et al., 2015
13.	Pinophilin C	C. gracilioides	Wei et al., 2015
14.	Beauvericin J	C. cicadae	Wang et al., 2014
15.	3,4-dihydroxy-8-hydroxy-3-(2-hydroxypentyl)-6-methoxyisocoumarin	C.militaris	Haritakun et al., 2010
16.	Luteoride D	C. gunnii	Qu et al., 2022
17.	Pseurotin G	C. gunnii	Qu et al., 2022
18.	Bianthraquinone	C. morakotii	Wang et al., 2019
19.	Cordycicadins A-D	C. cicadae	Li et al., 2022
20.	Cytochalasin	C. taii	Li et al., 2015

Table 2: The Pharmacological activities of Cordyceps species

Species	Host	Pharmacological activities	References
C. annullata	Plesiophthalmus nigrocyaneus and Coleopterah	Agonistic activity against cannabinoid receptor	Asai et al., 2012
C. pseudomilitaris	Lepidoptera	Antimalarial, cytotoxicity	Jaturapat et al., 2001
C. bassiana	Lepidoptera	Anti-inflammatory, antiproliferative and pro-apoptotic properties	Kim et al. 2015; Kim et al., 2014
C. cardinalis	Lepidopteran	Antitrypanosomal activity	Umeyama et al., 2014
C. cicadae	Icada flammat	Antitumor, antibacterial, immunoregulatory, renoprotective, cytotoxic and sedative effects	Kuo et al., 2003; Zhu et al., 2014
C. communis	Isoptera	Antitubercular	Haritakun et al., 2010
C. kyushuensis	Clanis bilineata	Antioxidant and antitumor activity	Zhang et al., 2015
C. dipterigena	-	Antifungal	Varughese et al., 2012
C. guangdongensis	Elaphomyces	Anti-fatigue, antioxidant, prolonging life, anti-avian influenza, anti-inflammatory and in the treatment of chronic renal failure	Yan et al., 2013; Yan and Zhong, 2014
C. japonica	Silkworm	Antioxidant, immunostimulating, antiaging and antitumor activities	Shin et al., 2001; Shin et al., 2003
C. lanpingensis	Hepialidae	-	Chen et al., 2013
C. militaris	Silkworm	Hypoglycemic, hypolipidemic, anti-inflammatory, antitumor, antibacterial, antifungal, marcrophage activation, antiviral, antimicrobial, antiprotozoal, prosexual, antimalarial, anti-HIV, neuroprotective, antioxidant and immuno-protective activities	Das et al., 2010; Reis et al., 2013
C. ophioglossoides	Carpinus cordata	Antitumor, estrogenic, antioxidant and anti-ageing activities	Kawagishi et al., 2004; Qinqin et al., 2012
C. pruinosa	Lepidoptera	Anti-proliferative properties	Liu et al., 2001
C. sinensis	Lepidoptera	Antitumor, cerebroprotective, antiaging, gastroprotective, immunomodulatory, antioxidant, anti-inflammatory, antidiabetic, aphrodisiac, antiproliferative and anti-fatigue activities	Sun et al., 2014; Jin et al., 2004; Wang et al., 2015; wang et al., 2005; Xiang et al., 2016; Lu et al., 2014
C. sobolifera	Cicada nymphs	Renoprotective, HIV-1 reverse transcriptase- Inhibitory activity	Chyau et al., 2014; Chiu et al., 2014; Wang et al., 2014
C. sphecocephala	Wasps and bees	Anticancer and anti-asthmatic activities	Hywel, 1995; Heo et al., 2010; Oh et al., 2008
C. unilateralis	Ants	Antimalarial and anticancer activities	Kittakoop et al., 1999

5. Future prospect and Conclusion

Although Cordyceps is generally considered safe, most of the research conducted on its pharmacological properties has been in laboratory settings. Further studies are required to confirm the fungus's safety, toxicity, and potential clinical efficacy in vivo. Moreover, more detailed documentation of the traditional uses of various Cordyceps species is necessary to guide future research into their biological activities and the identification of bioactive compounds for the development of new drugs. While earlier reviews have primarily focused on a small number of Cordyceps species, including C. militaris and C. sinensis, this review presents a comprehensive summary of many other species to assist researchers in identifying promising species or compounds for further investigation.

Conflict of interest

Authors had no conflict of interest.

Acknowledgements

The authors are thankful to the Head, School of Studies in Biotechnology, Pt. Ravishankar Shukla University Raipur, for providing necessary facilities. All figures were created with BioRender.com.

Funding supports

The authors wish to acknowledge the Junior Research Fellowship (No. F. 82-44/2020 (SA-III, UGC-Ref. No.: 201610136180), Ministry of Education, Govt. of India, Bahadurshah Zafar Marg, New Delhi-110002, for providing funding support.

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