Preventative Effects of Cordyceps cicadae Mycelial Extracts on the Early-Stage Development of Cataracts in UVB-Induced Mice Cataract Model.

Cataracts, a prevalent age-related eye condition, pose a significant global health concern, with rising rates due to an aging population and increased digital device usage. In Taiwan, cataract prevalence is particularly high, reaching up to 90% among individuals aged 70 and above. The lens of the eye absorbs short-wave light, which can lead to oxidative stress in lens epithelial cells and contribute to cataract formation. Exposure to ultraviolet (UV) light further exacerbates the risk of cataracts by generating reactive oxygen species. Heat-shock proteins (HSPs), involved in protein maintenance and repair, have been linked to cataract development. Cordyceps cicadae (C. cicadae), a traditional Chinese medicine, has a long history of use and is known for its pharmacological effects. N6-(2-hydroxyethyl) adenosine (HEA), a bioactive compound found in C. cicadae, exhibits anti-inflammatory, immunomodulatory, and neuroprotective properties. Previous studies have shown that C. cicadae mycelial extracts improve dry eye disease and reduce intraocular pressure in animal models. Additionally, C. cicadae possesses antioxidant properties, which are beneficial for combating cataract formation. In this study, we aim to evaluate the preventive efficacy of C. cicadae mycelial extracts in UV-induced cataract development. By investigating the ameliorative effects of C. cicadae on eye diseases and its potential role in ocular health improvement, we hope to uncover new options for cataract prevention and provide insights into the mechanisms of action. The findings of this research could provide a novel approach for nutritional supplements targeting cataract prevention, offering potential benefits in the field of ocular health.

Efficacy of Cordyceps cicadae (Ascomycota) Mycelium Supplementation for Amelioration of Dry Eye Symptoms: A Randomized, Double-Blind Clinical Pilot Study.

Dry eye disease (DED), a multifactorial inflammatory ocular surface disorder, affects up to 50% of individuals over 50 years old worldwide and is one of the most common reasons for seeking ophthalmologic care. Generally, topical eye drops or oral drugs are administered to treat DED; however, the use of preservatives in eye drops or the adverse effects of oral drugs are disadvantageous for long-term therapy. Cordyceps cicadae, a traditional Chinese medicinal fungus, possesses anti-inflammatory effects without evident toxicity and is obtainable at low price. Our previous study demonstrated that C. cicadae mycelium effectively ameliorates dry eye symptoms in the benzalkonium chloride (BAC)-induced mouse dry eye model by increasing tear volume and tear film breakup time (TBUT). However, the effects of C. cicadae mycelium for human dry eye amelioration remains unknown. Thus, the present study investigated the mitigation of dry eye conditions and related discomforts through oral supplementation of fermented C. cicadae mycelium. A total of 70 healthy individuals were recruited and randomly allocated to receive a daily oral dose of 1,050 mg preparation in sachet containing either freeze-dried C. cicadae mycelium powder with 0.3 mg of adenosine and 1.5 mg of HEA per gram or placebo for 90 days. The participants were subjected to anthropometric measurements, dry eye questionnaires (DEQ), Schirmer's tests, intraocular pressure (IOP) measurements, tear film breakup time (TBUT) tests, tear osmolality measurements, and tear electrolyte analysis prior to and right after completion of the study. The results showed a significantly increased TBUT as well as a significant decrease in tear osmolarity, in parallel with the decrease of tear electrolytes, especially Na+ and Cl ions. Although significant increase of tear volume was not observed, the increased TBUT suggests mitigation of dry eye through improvement of tear quality. Therefore, C. cicadae mycelium supplementation may be used for dry eye alleviation as a novel therapeutic intervention.

Neuroprotective Effects of Cordyceps cicadae (Ascomycetes) Mycelium Extract in the Rat Model of Optic Nerve Crush.

Cordyceps cicadae mycelium is an herbal medicine used to provide anti-inflammatory and antiapoptotic actions. However, little is known about the role of C. cicadae mycelium in neuroprotection. This study aimed to investigate the neuroprotective effects of C. cicadae mycelium extract (CCME) in the optic nerve crush (ONC) model. The optic nerves of adult male Wistar rats (aged 7-8 weeks) were crushed by a standardized method. Rats were divided equally into three groups: 1) a sham-operated group (sham), 2) a phosphate buffered saline-treated control group (crush), and 3) a CCME-treated group (CCME) that received CCME once daily for 7 consecutive days at doses of 100 mg/kg before ONC. Two weeks after ONC in rats, retinal ganglion cell (RGC) density and visual function were determined by using retrograde labeling with FluoroGold and flash visual evoked potentials. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemistry of ED1 (a marker of macrophage/microglia) were used to evaluate the antiapoptotic and anti-inflammatory effects of CCME in the optic nerve section. The P1-N2 amplitude and RGC density in the CCME-treated group were higher than those in the ONC control (crush) group by 5.15- and 3.13-fold, respectively. The numbers of TUNEL-positive cells and ED1-positive cells in the CCME-treated group were reduced by 4.38- and 6.63-fold, respectively, compared to those in the crush group. Oral administration of CCME provided neuroprotective effects in the ONC model via antiapoptotic and anti-inflammatory actions, which provides a potential treatment for patient with traumatic optic neuropathy.

Lowering the Intraocular Pressure in Rats and Rabbits by Cordyceps cicadae Extract and Its Active Compounds.

Cordyceps cicadae (CC), an entomogenous fungus that has been reported to have therapeutic glaucoma, is a major cause of blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) death, mostly due to elevated intraocular pressure (IOP). Here, an ethanolic extract of C. cicadae mycelium (CCME), a traditional medicinal mushroom, was studied for its potential in lowering IOP in rat and rabbit models. Data showed that CCME could significantly (60.5%) reduce the IOP induced by microbead occlusion after 56 days of oral administration. The apoptosis of retinal ganglion cells (RGCs) in rats decreased by 77.2%. CCME was also shown to lower the IOP of normal and dextrose-infusion-induced rabbits within 60 min after oral feeding. There were dose effects, and the effect was repeatable. The active ingredient, N6-(2-hydroxyethyl)-adenosine (HEA), was also shown to alleviate 29.6% IOP at 0.2 mg/kg body weight in this rabbit model. CCME was confirmed with only minor inhibition in the phosphorylated myosin light chain 2 (pMLC2) pathway.

Safety assessment of HEA-enriched Cordyceps cicadae mycelia on the central nervous system (CNS), cardiovascular system, and respiratory system in ICR male mice.

Cordyceps cicadae, an entomopathogenic fungus, is a source of traditional Chinese medicine in China. Due to the low yield of wild C. cicadae, artificial cultivation approaches will be needed to meet the increasing market demand. Using bioreactor culture can increase mass production and the abundance of the active component, N6-(2-hydroxyethyl)-adenosine (HEA). Here, we describe a safety assessment for a novel mycelium preparation method. Many studies have confirmed the safety of C. cicadae mycelia. However, the acute safety pharmacology of the C. cicadae enriched with the high HEA (3.90 mg/g) compound has not been evaluated. This study evaluated the central nervous system (CNS), cardiovascular system, and respiratory system in ICR male mice via oral gavage administration. For each requested item, two batches of eight mice tested on a vehicle (0.5% carboxymethyl cellulose, CMC) and C. cicadae mycelia (1,000 mg/kg) were performed. The heart rate at 60 min for the vehicle and C. cicadae mycelium treatment was 700.3 ± 55.4 and 603.0 ± 42.3 bpm, respectively (p = .4279). For echocardiographic analysis, the LV mass of the vehicle and drug treatment was 86.7 ± 6.4 and 80.2 ± 7.7, respectively (p = .0933). In the respiratory test, the tidal volume of the vehicle and drug treatments was 0.11 ± 0.01 and 0.14 ± 0.01 at 60 min, respectively (p = .4262). These results demonstrate that the oral administration of HEA-enriched C. cicadae mycelia is safe for the CNS, cardiovascular, and respiratory systems.

Safety Assessment of HEA-Enriched Cordyceps cicadae Mycelium: A Randomized Clinical Trial.

Objective:Cordyceps cicadae, a medicinal fungus, is assessed as having many functions: anti-cancer, anti-fatigue, anti-aging, immune-boosting, renal and liver protection. Since the industrial production of C. cicadae mycelium consistently manufactures bioactive compounds superior to wild fruiting bodies, there is a need to confirm the toxicity of liquid fermented C. cicadae mycelium. Studies showed the toxicity evaluation of C. cicadae mycelium in animal models, but safety reports in clinical studies are scarce. As such, a safety assessment of oral N6-(2-hydroxyethyl) adenosine (HEA-enriched) C. cicadae mycelium in humans is provided here.Method: After 49 participants ingested granules of 1.05 g of freeze-dried C. cicadae mycelium once a day for 3 months, their blood samples were collected at the beginning and end of the experiment for analysis.Results: There were no significant differences between the initial and final measurements in renal and liver function. Also, there was no influence on blood electrolytes as well as blood lipid levels. In clinical observation, there were also no side effects or adverse feelings mentioned by participants.Conclusion: These results suggested that HEA-enriched C. cicadae mycelium produced by liquid fermentation is safe and can be developed as a functional health food.

Cordyceps cicadae mycelia and its active compound HEA exert beneficial effects on blood glucose in type 2 diabetic db/db mice.

BACKGROUND: This is the first study to investigate the therapeutic effects of Cordyceps cicadae (C. cicadae) mycelia and its active compound N6 -(2-hydroxyethyl)adenosine (HEA) on blood glucose in genetically diabetic mice. RESULTS: Forty mice, 9 weeks of age, were divided into normal control, diabetic control, and three C. cicadae mycelia treated diabetic groups. After 9 weeks of continuous supplementation, the oral glucose tolerance test (OGTT) and homeostasis model of assessment-insulin resistance index showed significant glucose tolerance with C. cicadae mycelia. Furthermore, the effect of HEA is similar to that of C. cicadae mycelia in an OGTT, suggesting that HEA could be the major factor responsible for the functional properties of C. cicadae mycelia. CONCLUSION: Based on these findings, it is suggested that the therapeutic effect of C. cicadae mycelia may be driven by one of its active components, HEA, which could alleviate many diabetes complications in genetically obese mice and may offer promise as a supplement for diabetes management. © 2018 Society of Chemical Industry.