Can Cordyceps cicadae be used as an alternative to Cordyceps militaris and Cordyceps sinensis? – A review

https://doi.org/10.1016/j.jep.2020.112879Get rights and content

Abstract

Ethnopharmacological relevance

Cordyceps cicadae (Mig.) Massee is one of the oldest and well-known traditional Chinese medicine (TCM), with its uses recorded as far back as the 5th century A.D. For centuries, C. cicadae has been used as food, tonic and folk medicine to treat malaria, palpitations, cancer, fever, diabetes, eye diseases, dizziness, and chronic kidney diseases. Although C. cicadae has been used as TCM for over 1600 years, it is not the most popular amongst the Cordyceps family. Cordyceps Sinensis (C. sinensis) and Cordyceps militaris (C. militaris) are the most studied and widely used, with a number of commercially available products derived from these two Cordyceps species.

Aim of the review

This review seeks to look at the research that has been conducted on C. cicadae over the past 30 years, reporting on the biological activities, development and utilization. This information was compared to that focused on C. sinensis and C. militaris.

Materials and methods

A literature search was conducted on different scientific search engines including, but not limited to “Web of Science”, “ScienceDirect” and “Google Scholar” to identify published data on C. cicadae, I. cicadae, P. cicadae, C. sinensis and C. militaris.

Results

Research conducted on C. cicadae over the past two decades have shown that it poses similar biological properties and chemical composition as C. sinensis and C. militaris. C. cicadae has been reported to grow in many geographic locations, as compared to C. sinensis, and can be artificially cultivated via different methods.

Conclusion

There exists sufficient evidence that C. cicadae has medicinal benefits and contain bioactive compounds similar to those found on C. sinensis and C. militaris. However, more research and standardization methods are still needed to directly compare C. cicadae with C. sinensis and C. militaris, in order to ascertain the suitability of C. cicadae as an alternative source of Cordyceps products.

Introduction

Cordyceps cicadae (Mig.) Massee is one of the oldest and well-known traditional Chinese medicine (TCM), with its uses recorded as far back as the 5th century AD (Li et al., 2019). C. cicadae is an entomogenous fungi that belongs to the Claviciptaceae family and the genus Codyceps, which grows inside the nymph of hosts e.g. Cicada flammata Distant, Platypleura kaempferi Fabricius, Crytotympana pustulata Fabricious, Platylomiapieli Kato, and Oncotympana maculatieollis Motsch, and forms fruiting bodies on the surfaces of these insects (Li et al., 2019; Li et al., 2019b; Fen et al., 2019). It is mainly distributed in Asia, especially in China and has also been reported in Europe and North America (Olatunji et al., 2016a, Olatunji et al., 2016b). In China, the traditional name for C. cicadae is “Da Chan Hua” or simply “Chan Hua”, while scientifically it is also known as Cordyceps cicadae Shing, Isaria cicadae (I. cicadae), Paecilomyces cicadae (P. cicadae) and Cordyceps zhejiangensis (C. zhejiangensis) (Ke and Lee, 2018; Sun et al., 2017) (Fig. 1).

For centuries, C. cicadae has been used as food, tonic and folk medicine to treat malaria, palpitations, cancer, fever, diabetes, eye diseases, dizziness, and chronic kidney diseases (Hsu et al., 2015; Li et al., 2019b; Ke and Lee, 2018; Sun et al., 2017; Liu et al., 2018; Liu et al., 2018; Zha et al., 2019). During the Ming Dynasty, Shi-Zhen Li clarified in Compendium of Materia Medica that C. cicadae exhibits activities of improving eyesight, removing cloudiness of eyes, promoting eruption, dispelling wind and heat, and relieving convulsion (Hsu et al., 2015). Cheng Chen stated, during the Song Dynasty, in the Prescription of the Bureau of Taiping People’s Welfare Pharmacy (Taiping Huimin Heji Ju Fang), that C. cicadae powder is specifically for treatment of acute conjunctivitis, chronic blepharitis, chronic dacryocystitis and pterygium (Hsu et al., 2015).

Medicinal mushrooms and plants have high nutritional value due to their high contents of proteins, fats, polysaccharides, volatile oils, carotenoids, phenolic compounds, flavonoids, vitamins and steroids (Elkhateeb et al., 2019; Mohammadhosseini et al., 2017, 2019; Wansi et al., 2018, 2019). Globally, medicinal mushrooms and plants are highly recognised as functional foods, and are available as over-the counter health supplements used in complementary and alternative medicines (Elkhateeb et al., 2019; Mohammadhosseini et al., 2017). The diversity of compounds extracted from mushrooms and plants has attracted attention as a source of novel compounds with new mode of actions against a number of diseases, and use as scaffold in designing and synthesis of new active bioactive compounds.

Although C. cicadae has been used as TCM for over 1600 years, it is not the most popular amongst the Cordyceps family. Cordyceps sinensis (C. sinensis) and Cordyceps militaris (C. militaris) are the most studied and widely used, with the former being most explored (Patterson, 2008; Olatunji et al., 2018; Zhao et al., 2014; Zhang et al., 2019a, Zhang et al., 2019b). In fact, of all available literature reporting on Cordyceps, C. sinensis and C. militaris accounted for 60% of the total reports. Cordyceps sinensis, the most popular amongst the Cordyceps family, has been used as TCM for over 300 years to treat diverse chronic diseases (Patterson, 2008; Olatunji et al., 2018; Zhao et al., 2014; Guo et al., 2015; Chen et al., 2018). It is known to have beneficial effects on hepatic and renal functions, and an immunomodulation-related anticancer activities. Commercial products such as “Cobrin”, “Ningxinbao”, “Golden Sun Cordyceps” and “Wanji Cordyceps” have been developed from C. sinensis (Dong et al., 2015). In China, Corbrin capsule is a national class I new drug, one of the state-protected traditional Chinese medicines (Dong et al., 2015). The growth of C. sinensis has a very restricted habited, and its yields are decreasing each year, leading to limited resources and high prices (Zhao et al., 2014). Artificial cultivation of C. sinensis has also proven to be difficult as it also requires strict set of conditions. Cordyceps militaris has been used as tonic in China for hundreds of years, and has been reported to have similar health benefits as C. sinensis and is used as an alternative (Zhang et al., 2019a, Zhang et al., 2019b; Chen et al., 2018; Sun et al., 2018). C. militaris is known to grow at different regions and climates, and its cultivation has been widely explored, leading to its large scale production (Zhang et al., 2019a, Zhang et al., 2019b). “C. militaris mycelia powder and capsule” are commercial products used for nourishing the lung, invigorating the kidney, treating cough, asthma phlegm, amongst other diseases (Dong et al., 2015). “Cikaria” is a commercial product, derived from C. cicadae, sold as health supplement in Sweden (Scanafarma, 2020). However, the market for C. cicadae derived products in China is still very small as compared to C. sinensis and C. militaris derived products (Dong et al., 2015).

The popularity and high demand for C. sinensis and C. militaris has led to the scarcity of these TCMs, leading to their classification as protected endangered species. A number of methods have been developed for artificial cultivation and fermentation of these species in order to meet the demands. Despite the technological advances, Cordyceps are still a rare commodity, with prices for C. sinensis ranging from US$18 726 to $30 250/Kg in Lu et al. (2017) (Cunningham and Long, 2019). Research done on C. cicadae over the past two decades have shown that it poses similar biological properties and bioactive compounds as C. sinensis and C. militaris, and suggested that it can be used as an alternative source of Cordyceps. This review seeks to look at the research that has been done on C. cicadae over the past 30 years, focusing on the biological studies, chemical profile, cultivation and fermentation processes.

Section snippets

Chemical constituents and their biological activities

Chemicals isolated from C. cicadae include nucleosides, sterols, cyclic dipeptides, sugars, polysaccharides, fatty acids, amino acids, aromatic compounds and other small organic compounds (Sun et al., 2017; Patterson, 2008; Olatunji et al., 2018; Zhao et al., 2014; Zhang et al., 2019b). A number of these chemicals have been linked with the biological activities of C. cicadae (Fig. 2, Fig. 3, Fig. 4, Fig. 5 and Table 1) and most of them have also been isolated from C. sinensis and C. militaris,

Availability and sustainability of C. cicadae

C. cicadae has been reported to grow in many geographic locations, altitudes and different climates, similar to C. miitaris (Olatunji et al., 2016a, Olatunji et al., 2016b; Shrestha et al., 2005; Chiu et al., 2016). Despite the relative abundance of C. cicadae over C. sinensis, it is still a rare and precious commodity, which may limit its applications on a large scale (Sun et al., 2019). A number of research groups have reported on the cultivation of C. cicadae and I. cicadae, although the

Safety of C. cicadae

Chen at al., (2015) investigated the possible toxicity that may arise on rats, from repeated exposure to freeze-dried submerged mycelia culture of C. cicadae for 90 days. The study found no animal deaths and no treatment-related clinical signs, even at dosages of 2 g/kg on both male and female rats. The aqueous extract of wild C. cicadae fruiting bodies was found to be non-toxic to mice at a dosage of 80 g/kg, which is 444 times than the clinical daily dosage (Hsu et al., 2015; Zhang et al.,

Outlook and future perspectives

A patent on “Preparation and application of active ingredients and its drug combinations of C. cicadae” for the treatment of xerophthalmia, induced by physical and chemical injuries, has been filed in Taiwan, China and USA (Hsu et al., 2015). With more information available on the chemical composition, biological activities and artificial culturing technologies, more patents and products may be derived from C. cicadae. However, more research and standardization guidelines are still needed. For

Conclusion

There exists sufficient evidence that C. cicadae has medicinal benefits and contain bioactive compounds similar to those found on C. sinensis and C. militaris. Compounds such as cordycepin, ergosterol peroxide, cordycecin and beauvericins were reported to exhibit anti-cancer properties against a number of cell lines. Ethanol and water extracts from C. cicadae were also reported to exhibit anti-cancer properties. N6-(2-Hydroxyethyl)-adenosine (HEA) was reported to exhibit liver protective,

Declaration of competing interest

The authors declare that there is no conflict of interest.

Acknowledgments

This work was supported by grants as follows: The Public Welfare Technology Research from Science and Technology Project of Zhejiang Province (No. LGN18C030005), the Opening Project of Zhejiang Provincial Preponderant and Characteristic Subject of Key University (Traditional Chinese Pharmacology), Zhejiang Chinese Medical University (No. ZYAOX2018005), Zhejiang Sci-Tech University (2019048) and the Academication Workstation of Zhejiang Province. W. Nxumalo is thankful to Talented Young

References (77)

  • O.J. Olatunji et al.

    Cordycepin protects PC12 cells against 6-hydroxydopamine induced neurotoxicity via its antioxidant properties

    Biomed. Pharmacother.

    (2016)
  • H. Sun et al.

    Preservation affects the vegetative growth and fruiting body production of Cordyceps militaris

    World J. Microbiol. Biotechnol.

    (2018)
  • Y.F. Sun et al.

    Comprehensive evaluation of wild Cordyceps cicadaefrom different geographical origins by TOPSIS method based on the macroscopic infrared spectroscopy (IR) fingerprint

    Spectrochim. Acta, Part A-Mol. Biomolec.Spectrosc.

    (2019)
  • J. Tang et al.

    Enhancing cordycepin production in liquid static cultivation of Cordyceps militaris by adding vegetable oils as the secondary carbon source

    Bioresour. Technol.

    (2018)
  • O. Taofiq et al.

    Anti-inflammatory potential of mushroom extracts and isolated metabolites

    Trends Food Sci. Technol.

    (2016)
  • J.H. Wang et al.

    Chemical constituents from mycelia and spores of fungus cordyceps cicadae

    Chin. Herb. Med.

    (2017)
  • J. Wang et al.

    Cyclodepsipeptides from the ascocarps and insect-body portions of fungus Cordyceps cicadae

    Fitoterapia

    (2014)
  • Y. Wang et al.

    Structural elucidation, antioxidant and immunomodulatory activities of a novel heteropolysaccharide from cultured Paecilomyces cicadae (Miquel.) Samson

    Carbohydr. Polym.

    (2019)
  • H.L. Wang et al.

    Cordyceps cicadae induces G2/M cell cycle arrest in MHCC97H human hepatocellular carcinoma cells: a proteomic study

    Chin. Med.

    (2014)
  • C-y. Wei et al.

    Structure and chain conformation of a neutral intracellular heteropolysaccharide from mycelium of Paecilomyces cicadae

    Carbohydr. Polym.

    (2016)
  • H. Xie et al.

    Ethanolic extract of Cordyceps cicadae exerts antitumor effect on human gastric cancer SGC-7901 cells by inducing apoptosis, cell cycle arrest and endoplasmic reticulum stress

    J. Ethnophamarcol.

    (2019)
  • Z.C. Xu et al.

    Two heteropolysaccharides from Isaria cicadae Miguel differ in composition and potentially immunomodulatory activity

    Int. J. Biol. Macromol.

    (2018)
  • X.W. Ye et al.

    Novel propanamide analogue and antiproliferative diketopiperazines from mangrove Streptomyces sp Q24

    Nat. Prod. Res.

    (2017)
  • J. Zhang et al.

    Advance in Cordyceps militaris (Linn) link polysaccharides: isolation, structure, and bioactivities: a review

    Int. J. Biol. Macromol.

    (2019)
  • Y. Zhang et al.

    The antibacterial activity and antibacterial mechanism of a polysaccharide from Cordyceps cicadae

    J. Funct. Foods

    (2017)
  • J. Zhao et al.

    Advanced development in chemical analysis of Cordyceps

    J.Pharm. Biomed. Anal.

    (2014)
  • R. Zhu et al.

    Ergosterol peroxide from Cordyceps cicadae ameliorates TGF-beta 1-induced activation of kidney fibroblasts

    Phytomedicine

    (2014)
  • M. Adnan et al.

    Effect of pH, temperature and incubation time on cordycepin production from Cordyceps militaris using solid-state fermentation on various substrates

    CyTA - J. Food

    (2017)
  • L. Chen et al.

    Metabolomic comparison between wild Ophiocordyceps sinensis and artificial cultured Cordyceps militaris

    Biomed. Chromatogr.

    (2018)
  • J-w. Cheng et al.

    Optimization of fermentation process for the production of intracellular polysaccharide from Paecilomyces cicadae and the immuno-stimulating activity of intracellular Polysaccharide

    World J. Microbiol. Biotechnol.

    (2012)
  • Z.B. Chu et al.

    Chemical constituents of cordyceps cicadae

    Nat. Prod. Commun.

    (2015)
  • C. Dong et al.

    Cordyceps industry in China

    Mycology

    (2015)
  • W.A. Elkhateeb et al.

    Medicinal mushroom as a new source of natural therapeutic bioactive compounds, Egypt Phramarceut

    J

    (2019)
  • W-w. Fen et al.

    The complete mitochondrial genome of the Chan- hua fungus Isaria cicadae: a tale of intron evolution in Cordycipitaceae

    Environ. Microbiol.

    (2019)
  • L-x. Guo et al.

    Morphological observations and fatty acids composition of indoor-cultivated Cordyceps sinensis at a high-altitude laboratory on Sejila Mountain, Tibet

    PloS One

    (2015)
  • L. He et al.

    Anticancer action and mechanism of ergosterol peroxide from Paecilomyces cicadae fermentation broth

    Int. J. Mol. Sci.

    (2018)
  • Y.Q. He et al.

    Metabolomic variation in wild and cultured cordyceps and mycelia of Isaria cicadae

    Biomed. Chromatogr.

    (2019)
  • T. He et al.

    Dual- directional immunomodulatory effects of corbin capsule on autoimmune thyroid diseases

    Evid. Based Complement. Alternat. Med.

    (2016)
  • Cited by (0)

    1

    The authors are co-corresponding authors.

    View full text