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''Cordyceps chanhua'' is an
ascomycete Ascomycota is a phylum of the kingdom Fungi that, together with the Basidiomycota, forms the subkingdom Dikarya. Its members are commonly known as the sac fungi or ascomycetes. It is the largest phylum of Fungi, with over 64,000 species. The def ...
fungus that parasitizes
cicada The cicadas () are a superfamily, the Cicadoidea, of insects in the order Hemiptera (true bugs). They are in the suborder Auchenorrhyncha, along with smaller jumping bugs such as leafhoppers and froghoppers. The superfamily is divided into two ...
larvae found in Southern China. It forms white and yellow asexual fruiting structures resembling
synnema A synnema (plural ''synnemata'', also ''coremia''; derivation: "Threads together") is a large, erect reproductive structure borne by some fungi, bearing compact conidiophore A conidium ( ; : conidia), sometimes termed an asexual chlamydospore ...
. It is known in
Traditional Chinese Medicine Traditional Chinese medicine (TCM) is an alternative medicine, alternative medical practice drawn from traditional medicine in China. A large share of its claims are pseudoscientific, with the majority of treatments having no robust evidence ...
as Chan Hua which means "cicada flower". Its medicinal uses date back to the fifth century AD in China. It can also be used in various foods and tonics. Chan-hua is previously misidentified as ''Isaria cicadae'', another pathogen of cicada larvae. However, this name describes a fungus found in Brazil in 1838 with significant morphological and DNA differences. Other misattributed names include ''Cordyceps cicadae'' and ''Cordyceps sobolifera''. Due to widespread misidentification, "Isaria cicadae" has been reported to exist on other continents.


Taxonomy

''Isaria cicadae'' is a severely misused name. It was originally described as ''Isaria cicadae'' by Miquel in 1838 using a Brazilian sample until he synonymized it with ''C. cicadae'' in 1895. ''Paecilomyces cicadae'' was synonymized with ''C. cicadae'' in 1974 by Samson. Soon after, S.Z. Shing described a ''Cordyceps cicadae'' in 1975, but a fairly different sample from China is used. Each of the following is a different species: * ''Isaria cicadae'' , which is the same as ''Cordyceps cicadae'' and ''Paecilomyces cicadae''. The preferred name for this species appears to be ''Cordyceps cicadae'' (Miq.) Massee 1895, especially since ''Isaria'' has proven to be polyphyletic. * ''Cordyceps cicadae'' , which is now properly known as '' Tolypocladium dujiaolongae'' after its local name in TCM ("Du Jiao Long"). Some Chinese sources believe that it is the teleomorph of "Chan Hua", which is now proven false with the discovery of its true teleomorph. * ''Cordyceps sobolifera'' (now ''Ophiocordyceps sobolifera''). Japanese sources incorrectly believe that this is the teleomorph of "Chan Hua", but it is in reality another TCM material known as "Xiao Chan Hua" (small cicada flower). The error has spread to Korean, Taiwanese, and Chinese sources. * '' Cordyceps kobayasii'', another purported teleomorph of "Chan Hua". * ''Cordyceps chanhua'' , which is the correct name of "Chan Hua". In traditional medicine-related papers, each of the names have been used to describe the material known as "Chan Hua". ''C. cicadae'' and ''I. cicadae'' used to be very common in sources written by Chinese researchers, though they have largely adopted the corrected ''C. chanhua'' name. Japanese, Korean, and Taiwanese sources still use ''C. sobolifera''. Other reported synonyms include ''Cordyceps zhejiangensis'' and ''C. sinclairii''.


Description

''C. chanhua'' forms its fruiting structures on the surface of its host, a
cicada The cicadas () are a superfamily, the Cicadoidea, of insects in the order Hemiptera (true bugs). They are in the suborder Auchenorrhyncha, along with smaller jumping bugs such as leafhoppers and froghoppers. The superfamily is divided into two ...
nymph A nymph (; ; sometimes spelled nymphe) is a minor female nature deity in ancient Greek folklore. Distinct from other Greek goddesses, nymphs are generally regarded as personifications of nature; they are typically tied to a specific place, land ...
. The fruiting structure can either cover the entire nymph body or only partially cover it. Sexual structures are not produced on these fruiting structures. Much more information is known about the asexual morph of this fungus because the sexual morph has been reportedly observed once in nature and never in the lab. Its asexual fruiting structures are
synnema A synnema (plural ''synnemata'', also ''coremia''; derivation: "Threads together") is a large, erect reproductive structure borne by some fungi, bearing compact conidiophore A conidium ( ; : conidia), sometimes termed an asexual chlamydospore ...
-like and produce
conidiophores A conidium ( ; : conidia), sometimes termed an asexual chlamydospore or chlamydoconidium (: chlamydoconidia), is an asexual, non- motile spore of a fungus. The word ''conidium'' comes from the Ancient Greek word for dust, ('). They are also ...
and conidia. The fruiting bodies have yellow stalk-looking structures with a white-ish, fluffy tip where the conidiophores are located.  


Ecology

''C. chanhua'' is an entomogenous fungi that parasitizes the
nymphs A nymph (; ; sometimes spelled nymphe) is a minor female nature deity in ancient Greek folklore. Distinct from other Greek goddesses, nymphs are generally regarded as personifications of nature; they are typically tied to a specific place, land ...
of its
cicada The cicadas () are a superfamily, the Cicadoidea, of insects in the order Hemiptera (true bugs). They are in the suborder Auchenorrhyncha, along with smaller jumping bugs such as leafhoppers and froghoppers. The superfamily is divided into two ...
hosts and forms fruiting structures on the surface. These fruiting structures are produced from June–August, and they protrude from the nymph, up through the soil after the fungus kills it. Asexual means of reproduction occur once temperatures rise following
sclerotium A sclerotium (; : sclerotia () is a compact mass of hardened fungal mycelium containing food reserves. One role of sclerotia is to survive environmental extremes. In some higher fungi such as ergot, sclerotia become detached and remain dormant u ...
development and is done so through
conidia A conidium ( ; : conidia), sometimes termed an asexual chlamydospore or chlamydoconidium (: chlamydoconidia), is an asexual, non- motile spore of a fungus. The word ''conidium'' comes from the Ancient Greek word for dust, ('). They are also ...
, dispersed by air and water. It is said that this fungal species is rare and scarce because it propagates slowly and lacks resistance. This could also be due to the fact that it is largely asexual and clonal in nature, as sexual structures have yet to be reliably observed in lab or in nature. Despite this, there is evidence supporting that it is
heterothallic Heterothallic species have sexes that reside in different individuals. The term is applied particularly to distinguish heterothallic fungi, which require two compatible partners to produce sexual spores, from homothallic ones, which are capable ...
being that a study found a truncated MAT1-1-1 type found in the MAT1-2 locus that is not due to asexual fruiting. Its
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
has been sequenced and found to be 33.9Mb including
serine protease Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. Serin ...
s and chintinases which target host tissues and are characteristic of other entomopathogenic fungi. The fungus also produces
metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
s such as
beauvericin Beauvericin is a depsipeptide with antibiotic and insecticidal effects belonging to the enniatin family. It was isolated from the fungus ''Beauveria bassiana'', but is also produced by several other fungi, including several ''Fusarium'' species; i ...
s and oosporein which have non-selective insecticidal properties. This would suggest that the fungus could infect more than one host, but this has only been seen in the lab on silkworm pupae and beetle wings.


Life cycle

The life cycle of ''C. chanhua'' in southern China as observed and described by Zha, Ling-Sheng et al. in 2019 follows. During mid-late summer, conidia of ''C. chanhua'' attach to the surface of a
cicada The cicadas () are a superfamily, the Cicadoidea, of insects in the order Hemiptera (true bugs). They are in the suborder Auchenorrhyncha, along with smaller jumping bugs such as leafhoppers and froghoppers. The superfamily is divided into two ...
nymph A nymph (; ; sometimes spelled nymphe) is a minor female nature deity in ancient Greek folklore. Distinct from other Greek goddesses, nymphs are generally regarded as personifications of nature; they are typically tied to a specific place, land ...
’s body within the soil which germinate and form
germ tube A germ tube is an outgrowth produced by spores of spore-releasing fungi during germination. The germ tube differentiates, grows, and develops by mitosis to create somatic hyphae.C.J. Alexopolous, Charles W. Mims, M. Blackwell, ''Introductory My ...
s that can penetrate below the surface and form
hypha A hypha (; ) is a long, branching, filamentous structure of a fungus, oomycete, or actinobacterium. In most fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium. Structure A hypha consists of one o ...
e. After two to three days of absorbing the cicada’s nutrients and reproducing, they can occupy the entire body. Hyphae turn to
mycelia Mycelium (: mycelia) is a root-like structure of a fungus consisting of a mass of branching, thread-like hyphae. Its normal form is that of branched, slender, entangled, anastomosing, hyaline threads. Fungal colonies composed of mycelium are fo ...
which cause the nymph to die from absorbing water and nutrients and producing
mycotoxin A mycotoxin (from the Greek μύκης , "fungus" and τοξικός , "poisonous") is a toxic secondary metabolite produced by fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' is usually rese ...
s. After the nymph is killed, the fungus forms a
sclerotium A sclerotium (; : sclerotia () is a compact mass of hardened fungal mycelium containing food reserves. One role of sclerotia is to survive environmental extremes. In some higher fungi such as ergot, sclerotia become detached and remain dormant u ...
and produce
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
s to keep the body from rotting. When temperatures rise again, either that year or the following, mycelia are produced once more to form synnemata that eventually break through the soil to grow above ground. The synnema branches to form multiple
conidiophores A conidium ( ; : conidia), sometimes termed an asexual chlamydospore or chlamydoconidium (: chlamydoconidia), is an asexual, non- motile spore of a fungus. The word ''conidium'' comes from the Ancient Greek word for dust, ('). They are also ...
and chained conidia. The conidia are dispersed by air or water, leading them back to the soil, where they use water flow to infiltrate the soil until they make contact with another nymph and infect.


Habitat and distribution

''Cordyceps chanhua'' is found in warm, humid, low-elevational regions (below 2,500m), on cicada nymphs in sunny soils. Habitats that fit these criteria include bamboo, broad-leaved, coniferous, and broad-leaved mixed forests. Fungi reported to be "chan-hua" or ''Cordyceps cicadae'' are most commonly found in China, but they are also found across Asia, Europe, and North America, with some studies showing other continents as well. As newer taxonomic data has shown, this view involves a great deal of conflation.


Medicinal properties

''C. chanhua'' is one of the oldest, most valued and well-known forms of
Traditional Chinese Medicine Traditional Chinese medicine (TCM) is an alternative medicine, alternative medical practice drawn from traditional medicine in China. A large share of its claims are pseudoscientific, with the majority of treatments having no robust evidence ...
, dating back to the fifth century AD. When used as a medicine, it is referred to as Chan Hua. Many of its medicinal properties relate it to the more commonly used ''Cordyceps sinensis'' and ''
Cordyceps militaris ''Cordyceps militaris'', commonly known as the caterpillar fungus, is a species of fungus in the family Cordycipitaceae, and the type species of the genus ''Cordyceps'', which consists of hundreds of species. The species was originally described ...
'', making it a potential substitute for these highly sought after medicinal fungi. Obstacles to using Chan-hua on a larger scale alongside its relatives ''C. sinensis'' and ''C. militaris'' include its scarcity and its cryptic taxonomy which make it difficult to study, cultivate, and harvest. It has been shown to be helpful for a multitude of health issues and concerns and nonsignificant toxicity has been reported meaning it is thought to be safe to use as treatment. On the other hand, oosporein, which is produced by the fungus, has been shown to cause issues in some species including birds and chickens, canines.
Oxalic acid Oxalic acid is an organic acid with the systematic name ethanedioic acid and chemical formula , also written as or or . It is the simplest dicarboxylic acid. It is a white crystalline solid that forms a colorless solution in water. Its name i ...
also produced by the fungus could be cause for kidney stone disease in high levels.


Putative active functions

* Treatment of childhood
convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is often used as a synony ...
*
Analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...
activity and
sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...
function * Anti-fatigue effects * Antitumor activity * Amelioration of renal function *
Immunomodulatory Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunothera ...
effects * Immunoregulatory


Medicinal uses and treatments

*
Malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
*
Palpitations Palpitations occur when a person becomes aware of their heartbeat. The heartbeat may feel hard, fast, or uneven in their chest. Symptoms include a very fast or irregular heartbeat. Palpitations are a sensory symptom. They are often described as ...
*
Cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
*
Fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
*
Diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
* Eye diseases * Dizziness * Chronic kidney diseases * Acute
conjunctivitis Conjunctivitis, also known as pink eye or Madras eye, is inflammation of the conjunctiva, the thin, clear layer that covers the white surface of the eye and the inner eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness ...
  * Chronic
blepharitis Blepharitis, sometimes known as granulated eyelids, is one of the most common ocular conditions characterized by inflammation, scaling, reddening, and crusting of the eyelid. This condition may also cause swelling, burning, itching, or a grainy ...
,
dacryocystitis Dacryocystitis is an infection of the lacrimal sac, secondary to obstruction of the nasolacrimal duct at the junction of the lacrimal sac. The term derives . It causes pain, redness, and swelling over the inner aspect of the lower eyelid and e ...
, and
pterygium A pterygium (: ''pterygia'' or ''pterygiums'') is any wing-like triangular membrane occurring in the neck, eyes, knees, elbows, ankles or digits. The term comes from the Greek word ''pterygion'' meaning "wing". Types * Popliteal pterygium syn ...


Other uses

* Improving eyesight, removing eye cloudiness * Neuroprotection * Promoting eruption * Liver and kidney protection * Blood fat reduction


Chemical constituents

Chemicals isolated from Chan-hua include
nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
s and
nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotid ...
s,
sterol A sterol is any organic compound with a Skeletal formula, skeleton closely related to Cholestanol, cholestan-3-ol. The simplest sterol is gonan-3-ol, which has a formula of , and is derived from that of gonane by replacement of a hydrogen atom on ...
s (
ergosterol Ergosterol (ergosta-5,7,22-trien-3β-ol) is a mycosterol found in cell membranes of fungi and protozoa, serving many of the same functions that cholesterol serves in animal cells. Because many fungi and protozoa cannot survive without ergostero ...
,
mannitol Mannitol is a type of sugar alcohol used as a sweetener and medication. It is used as a low calorie sweetener as it is poorly absorbed by the intestines. As a medication, it is used to decrease pressure in the eyes, as in glaucoma, and to l ...
), cyclic
dipeptide A dipeptide is an organic compound derived from two amino acids. The constituent amino acids can be the same or different. When different, two isomers of the dipeptide are possible, depending on the sequence. Several dipeptides are physiological ...
s, sugars,
polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long-chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wat ...
s,
fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...
s,
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
s,
aromatic compound Aromatic compounds or arenes are organic compounds "with a chemistry typified by benzene" and "cyclically conjugated." The word "aromatic" originates from the past grouping of molecules based on odor, before their general chemical properties were ...
s,
galactomannan Galactomannans are polysaccharides consisting of a mannose backbone with galactose side groups, more specifically, a (1-4)-linked beta-D-mannopyranose backbone with branchpoints from their 6-positions linked to alpha-D-galactose, (i.e. 1-6-linked ...
,
adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside build ...
,
uridine Uridine (symbol U or Urd) is a glycosylated pyrimidine analog containing uracil attached to a ribose ring (or more specifically, a ribofuranose) via a β-N1- glycosidic bond. The analog is one of the five standard nucleosides which make up nuc ...
,
inosine Inosine is a nucleoside that is formed when hypoxanthine is attached to a ribose ring (also known as a ribofuranose) via a β-N9-glycosidic bond. It was discovered in 1965 in analysis of RNA transferase. Inosine is commonly found in tRNAs and is ...
,
guanosine Guanosine (symbol G or Guo) is a purine nucleoside comprising guanine attached to a ribose ( ribofuranose) ring via a β-N9- glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate (GMP), cyclic guanosine monophosp ...
, cyclopeptides, myriocin, and inorganic elements.


References

{{Taxonbar , from1=Q133848761 , from2=Q10536893 , from3=Q49607961 , from4=Q103817346 , from5=Q11314463 , from6=Q108123598 Cordycipitaceae Fungus species