Cicada Flower

Metadata

Regulatory Status

Chinese Pharmacopoeia

• Listed: Yes. Chan Hua (蝉花) has been documented in Chinese materia medica for over 1,500 years, with the earliest records in the Lei Gong Pao Zhi Lun (雷公炮炙论, ~470 CE).
• Adenosine content standard: In accordance with the Chinese Pharmacopoeia (2015 Edition), which sets quality standards for adenosine content.
• Traditional classification: Cold nature, attributed to the liver and lung meridians.
• Traditional indications: Childhood convulsions (jing feng), night terrors, fever, palpitations, dizziness, and chronic kidney disease. Used to disperse wind-heat, calm convulsions, and improve vision.
• TCM differentiation from Cordyceps sinensis: While O. sinensis (Dong Chong Xia Cao) is warm in nature and tonifies kidney yang, C. cicadae is cold in nature and attributed to the kidney meridian differently — it is often used for chronic kidney disease without aggravating kidney yin deficiency.

United States

• Not widely marketed as a dietary supplement in the US. Not listed as a specific dietary ingredient under DSHEA. Some specialty supplement companies offer C. cicadae mycelium products.
• FDA GRAS status: No GRAS determination.

European Union

• No novel food authorization for C. cicadae products.
• No EMA/HMPC assessment report or monograph.

Japan and Korea

• Japan: Not listed in the Japanese Pharmacopoeia. Not commonly used in Japanese traditional medicine.
• Korea: Not a major species in Korean traditional medicine (Hanbang), where C. militaris is preferred.

Taiwan

• Significant research base: Taiwanese research institutions (notably National Chung Hsing University) have conducted extensive pharmacological and safety studies on cultivated C. cicadae mycelium, positioning it as a functional health food ingredient.

Conditions & Indications

Primary: Neuroprotection and Cognitive Support (Preclinical Evidence)

• Neuroprotective activity: HEA and adenosine from C. cicadae demonstrate neuroprotective effects through multiple pathways — antiapoptotic, antioxidant, and anti-inflammatory mechanisms. Oral administration of C. cicadae mycelium extract provided neuroprotective effects in optic nerve crush models via suppression of retinal ganglion cell apoptosis.
• Anticonvulsant activity: Traditional TCM use for childhood convulsions (jing feng) is supported by preclinical evidence. Adenosine and HEA are known adenosine receptor agonists, and adenosine is an established endogenous anticonvulsant neurotransmitter.
• Memory improvement: HEA-enriched C. cicadae mycelium fermented with deep ocean water minerals prevented D-galactose-induced memory deficits in mice by inhibiting oxidative inflammatory factors and aging-related risk factors.
• Neurite outgrowth promotion: Combined extracts of C. cicadae and Hericium erinaceus promoted neurite outgrowth of retinal ganglion cells, suggesting potential synergistic neuroprotective applications.

Secondary: Renal Protection (Preclinical Evidence with Clinical Plausibility)

• Chronic kidney disease (CKD): Multiple animal studies demonstrate that C. cicadae mycelia ameliorate chronic renal failure through anti-inflammatory and antifibrotic mechanisms. Polysaccharides, cordycepin, adenosine, and inosine are identified as active renoprotective compounds.
• Acute kidney injury (AKI): C. cicadae mycelia ameliorated cisplatin-induced AKI in mice by suppressing the TLR4/NF-kB/MAPK inflammatory pathway and activating the protective HO-1/Nrf2 and Sirt-1/AMPK pathways.
• Renal fibrosis: C. cicadae ameliorated renal hypertensive injury and fibrosis through regulation of SIRT1-mediated autophagy in preclinical models.

Emerging/Preclinical

• Immunomodulation: Polysaccharide fractions activate macrophages and modulate cytokine production. The immunomodulatory profile is complex, with both immunostimulatory (polysaccharides) and immunosuppressive (myriocin, cyclosporin-like peptides) components.
• Antitumor activity: Sporoderm-broken spores from wild C. cicadae demonstrated antineoplastic properties in vitro. Myriocin (ISP-1), a sphingolipid synthesis inhibitor, has potent immunosuppressive and potential anticancer activity.
• Blood glucose regulation: A small clinical evaluation suggested that C. cicadae mycelium supplementation may support blood glucose regulation, though this requires larger confirmatory studies.
• Anti-inflammatory: HEA attenuates LPS-induced pro-inflammatory responses through suppression of the TLR-4-mediated NF-kB signaling pathway.

Mechanism of Action

Primary Mechanisms

1. N6-(2-Hydroxyethyl)adenosine (HEA) — adenosine analog pharmacology: HEA is the signature bioactive of C. cicadae, structurally analogous to adenosine with an additional hydroxyethyl group at the N6 position. HEA acts as an adenosine receptor agonist, particularly at A1 and A2A receptors, mediating neuroprotective, anti-inflammatory, and vasodilatory effects. Unlike cordycepin (3’-deoxyadenosine from C. militaris), HEA’s modification is at the adenine base rather than the ribose sugar, giving it a distinct pharmacological profile.

2. Neuroprotective signaling via adenosine receptors: Adenosine A1 receptor activation by HEA and adenosine reduces neuronal excitability and glutamate release, providing anticonvulsant and neuroprotective effects. A2A receptor agonism mediates anti-inflammatory activity in the central nervous system, reducing microglial activation and pro-inflammatory cytokine production. These mechanisms are consistent with the traditional TCM use for convulsions and neurological disturbances.

3. NF-kB pathway suppression: HEA suppresses TLR-4-mediated NF-kB activation, reducing downstream production of TNF-alpha, IL-1beta, IL-6, and nitric oxide. This anti-inflammatory mechanism underlies both the neuroprotective and renoprotective activities observed in preclinical models.

Secondary Mechanisms

• Nrf2/HO-1 antioxidant pathway activation: C. cicadae mycelia activate the Nrf2/HO-1 cytoprotective pathway, upregulating endogenous antioxidant defenses (SOD, CAT, GSH-Px) and protecting against oxidative damage in kidney, brain, and retinal tissues.
• SIRT1/AMPK signaling: Activation of SIRT1-mediated autophagy and AMPK signaling contributes to renoprotective and anti-aging effects, promoting cellular homeostasis and reducing fibrotic remodeling.
• Myriocin (ISP-1) immunomodulation: Myriocin inhibits serine palmitoyltransferase, the rate-limiting enzyme in sphingolipid biosynthesis. This potent immunosuppressive activity (originally discovered in Isaria sinclairii, a related species) represents a pharmacologically distinct mechanism from the adenosine-mediated effects.
• Beta-glucan immune stimulation: Polysaccharide fractions stimulate innate immune function through dectin-1 and TLR-2 signaling, providing a counterbalancing immunostimulatory activity alongside the immunosuppressive myriocin pathway.

Pharmacological Distinction from Other Cordyceps Species

C. cicadae is pharmacologically distinct from C. militaris and O. sinensis in several key respects. Its signature adenosine analog is HEA (not cordycepin), giving it a stronger neuroprotective rather than exercise-performance profile. Its TCM classification as “cold in nature” contrasts with the “warm” classification of O. sinensis, and it is traditionally preferred for kidney-yin conditions rather than kidney-yang deficiency. The presence of myriocin adds a unique immunosuppressive dimension not found in other Cordyceps species.

Clinical Evidence Summary

Clinical evidence for Cordyceps cicadae is extremely limited, consisting primarily of one small safety-focused randomized clinical trial and one pilot study on blood glucose. The vast majority of evidence derives from in vitro and animal model studies.

Human Clinical Studies

Key Preclinical Studies

Evidence Limitations

• Only one published randomized clinical trial, which focused on safety rather than efficacy.
• No large-scale, multi-center, double-blind, placebo-controlled efficacy trials have been conducted.
• Most renoprotective evidence comes from chemically induced kidney injury models (adenine, cisplatin) that may not fully represent human CKD progression.
• Neuroprotective effects demonstrated in animal models may not translate directly to cognitive improvement in humans.
• Variable preparation methods (wild-harvested vs. cultivated mycelium, different fermentation conditions) affect HEA and polysaccharide content.
• Much of the research originates from Taiwanese and Chinese institutions; independent replication in Western research settings is limited.
• Publication bias may favor positive preclinical findings.

Safety Profile

General Assessment

Cordyceps cicadae has a long history of traditional medicinal use in China spanning over 1,500 years. A randomized clinical trial of HEA-enriched mycelium (1,050 mg/day for 3 months) found no significant adverse effects on liver function, kidney function, CNS, cardiovascular system, or respiratory system. Safety assessment studies in mice (including Ames test and chromosomal aberration assays) showed no genotoxicity.

Contraindications

• Pregnancy and lactation: Insufficient human safety data. Avoid medicinal use during pregnancy and breastfeeding.
• Autoimmune disease: The complex immunomodulatory profile (containing both immunostimulatory polysaccharides and immunosuppressive myriocin) warrants caution in autoimmune conditions.
• Pre-surgical: Discontinue at least 2 weeks before surgery due to potential interactions with anesthesia and theoretical anticoagulant activity.

Drug Interactions

• Immunosuppressants (cyclosporine, tacrolimus): Myriocin has potent immunosuppressive activity. Co-administration with pharmaceutical immunosuppressants could theoretically potentiate immunosuppression. Conversely, beta-glucan fractions may counteract immunosuppressive therapy. This unpredictable interaction warrants avoidance of concurrent use.
• Anticonvulsant medications: HEA and adenosine have adenosine receptor agonist activity, which contributes to anticonvulsant effects. Theoretical additive or synergistic effects with pharmaceutical anticonvulsants; caution and physician supervision advised.
• Antidiabetic medications: Preliminary evidence suggests hypoglycemic effects. Monitor blood glucose if co-administered with insulin or oral hypoglycemics.
• Anticoagulants: Theoretical interaction based on adenosine-mediated vasodilation and platelet effects. Clinical significance uncertain.

Side Effects (at Study Doses)

• Common: Generally well-tolerated in the clinical trial at 1,050 mg/day for 3 months. No significant adverse effects reported.
• Uncommon: Mild GI discomfort possible.
• Rare: No serious adverse events reported in published clinical or preclinical studies.

Toxicology

• Ames test: No dose-dependent increase in reversion mutation (negative for mutagenicity).
• Chromosomal aberration test: No dose-dependent increase in chromosomal aberration.
• Organ toxicity assessment: No toxicity observed in kidney or liver function at study doses.
• Quality control: Wild-harvested specimens may contain heavy metals from soil; cultivated mycelium under controlled conditions is preferred for consistent quality and safety.

Clinical Dosage

Cultivated Mycelium (HEA-Enriched)

• Clinical trial dose: 1,050 mg/day of freeze-dried C. cicadae mycelium powder (in capsule form), taken daily for 3 months
• This is the only preparation evaluated in a human clinical trial
• HEA content: Standardization to HEA content varies by manufacturer; research-grade preparations typically specify HEA concentration

Traditional Preparation (Dried Whole Specimen)

• Traditional dose: 3—9 g/day in decoction (dried parasitized cicada nymph with stroma)
• Preparation: Typically decocted in water for 30—60 minutes as part of a multi-herb TCM formula
• Note: Traditional preparations use the wild-harvested cicada-fungus complex; modern cultivated mycelium products have different bioactive profiles

Mycelium Extract

• Typical supplement dose: 500—2,000 mg/day of mycelium powder or extract
• Standardization: Preferably standardized to adenosine and/or HEA content in accordance with Chinese Pharmacopoeia standards (adenosine >0.02%)
• Extraction method: Hot-water extraction captures polysaccharides; ethanol extraction captures HEA and other nucleosides more efficiently

Form Selection Guidance

Cultivated mycelium (liquid fermentation) is the most practical and standardizable form, with the strongest safety data from the Fu et al. (2021) clinical trial. Wild-harvested specimens, while traditional, face supply constraints and quality variability. For neuroprotective applications specifically driven by HEA, ethanol or dual-extraction products that concentrate nucleoside fractions may be preferable to purely water-extracted polysaccharide preparations.

Sources

• Fu TY, Wang SH, Lin CH, et al. Safety assessment of HEA-enriched Cordyceps cicadae mycelium: a randomized clinical trial. J Am Nutr Assoc. 2021;40(2):121-132
• Fu TY, Lin CH, Wang SH, et al. Safety assessment of HEA-enriched Cordyceps cicadae mycelia on the central nervous system (CNS), cardiovascular system, and respiratory system in ICR male mice. Food Sci Nutr. 2021;9(9):4942-4951
• Ke BJ, Lee CL. Potential therapeutic effects of Cordyceps cicadae and Paecilomyces cicadae on adenine-induced chronic renal failure in rats and their phytochemical analysis. J Ethnopharmacol. 2018;227:146-153
• Lu MY, Chen CC, Lee LY, Lin TW, Kuo CF. Cordyceps cicadae mycelia ameliorate cisplatin-induced acute kidney injury by suppressing the TLR4/NF-kB/MAPK and activating the HO-1/Nrf2 and Sirt-1/AMPK pathways in mice. Oxid Med Cell Longev. 2020;2020:7912763
• Wu PK, Tao Z, Ouyang Z, et al. Cordyceps cicadae ameliorates renal hypertensive injury and fibrosis through the regulation of SIRT1-mediated autophagy. Front Pharmacol. 2021;12:801094
• Huang YS, Wang LC, Chang YL, Lee EJ. Neuroprotective effects of Cordyceps cicadae (Ascomycetes) mycelium extract in the rat model of optic nerve crush. Int J Med Mushrooms. 2022;24(5):29-40
• Chen CC, Lu MY, Lee LY, et al. Cordyceps cicadae NTTU 868 mycelia fermented with deep ocean water minerals prevents D-galactose-induced memory deficits by inhibiting oxidative inflammatory factors and aging-related risk factors. Nutrients. 2023;15(8):1913
• Wu PY, Lin KH, Chen CC, et al. Extracts from Cordyceps cicadae and Hericium erinaceus promote the neurite outgrowth of retinal ganglion cells. PLoS One. 2024;19(11):e0342244
• Lin CH, Wang SH, Chen CC, et al. Clinical evaluation of blood glucose regulation and safety of Cordyceps cicadae mycelium. J Food Nutr Res. 2017;5(2):137-143
• Weng SC, Chou CJ, Lin LC, et al. Immunomodulatory functions of extracts from the Chinese medicinal fungus Cordyceps cicadae. J Ethnopharmacol. 2002;83(1-2):79-85
• Zhu R, Chen YP, Deng YY, et al. Cordyceps cicadae extracts ameliorate renal malfunction in a remnant kidney model. J Zhejiang Univ Sci B. 2011;12(12):1024-1033
• Olatunji OJ, Feng Y, Olatunji OO, et al. Cordycepin protects PC12 cells against 6-hydroxydopamine induced neurotoxicity via its antioxidant properties. Biomed Pharmacother. 2016;81:7-14
• Li L, Zhang T, Li C, et al. Can Cordyceps cicadae be used as an alternative to Cordyceps militaris and Cordyceps sinensis? — A review. J Ethnopharmacol. 2021;257:112879
• Chinese Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China. 2015 Edition

Connections

• Cordyceps genus comparison: C. cicadae is pharmacologically distinct from Cordyceps (O. sinensis/C. militaris) — its signature adenosine analog is HEA rather than cordycepin, giving it a stronger neuroprotective profile rather than the exercise-performance focus of cordycepin. The TCM classification as “cold” vs. “warm” for O. sinensis reflects genuinely different pharmacological properties and traditional indications. See also Cordyceps militaris.
• Neuroprotective medicinal mushrooms: The neuroprotective effects of C. cicadae HEA complement the nerve growth factor-stimulating properties of Lion’s Mane (Hericium erinaceus). Combined extracts have shown synergistic neurite outgrowth promotion in vitro, suggesting potential for combined neuroprotective protocols.
• Renoprotective fungi: The kidney-protective properties of C. cicadae parallel those reported for Cordyceps and Poria, though through distinct mechanisms (adenosine receptor-mediated anti-inflammation vs. diuretic and immunomodulatory activity).
• Adenosine analog pharmacology: The adenosine analog strategy appears repeatedly across the Cordyceps genus — cordycepin in C. militaris, adenosine in O. sinensis, and HEA in C. cicadae. Each analog has a distinct receptor affinity profile, explaining the differentiated clinical applications across species.
• Immunomodulatory complexity: The presence of both immunostimulatory (polysaccharides) and immunosuppressive (myriocin) components in C. cicadae makes it one of the most pharmacologically complex species in medicinal mycology, analogous to the dual immunomodulatory activity of Reishi triterpenoids and polysaccharides.