# Extracts from Cordyceps cicadae and Hericium erinaceus promote the neurite outgrowth of retinal ganglion cells

**Authors:** Fang-Yi Chen, Chin-Chu Chen, Chuan-Chin Chiao

PMC · DOI: 10.1371/journal.pone.0342244 · PLOS One · 2026-02-06

## TL;DR

This study shows that extracts from Cordyceps cicadae and Hericium erinaceus can promote the growth of retinal ganglion cell neurites, suggesting potential for neural regeneration therapies.

## Contribution

The novel finding is that moderate concentrations of these fungal extracts enhance neurite outgrowth in mammalian retinal ganglion cells.

## Key findings

- Aqueous Cordyceps cicadae and ethanol Hericium erinaceus extracts promote neurite outgrowth in retinal explants.
- Erinacine S, a compound from Hericium erinaceus, directly enhances neurite growth in isolated retinal ganglion cells.
- These extracts do not significantly increase cell apoptosis at moderate concentrations.

## Abstract

The regenerative capacity of mammalian RGC neurites after damage, such as glaucoma, is limited. Numerous studies have utilized herbal extracts to promote neural regeneration and exert neuroprotective effects in the hope of mitigating glaucoma. In the present study, we investigated the effect of extracts from the cicada fungus (Cordyceps cicadae) and the Lion’s mane mushroom (Hericium erinaceus) on neurite outgrowth of retinal explants and isolated RGCs. We also examined whether these extracts affect the number of apoptotic cells and neurite outgrowth activity of RGCs. The results showed that an aqueous extract of Cordyceps cicadae, an ethanol extract of Hericium erinaceus, and the purified compound Erinacine Sare able to promote neurite outgrowth in retinal explants. Given its role as a key bioactive compound, Erinacine S was further investigated on isolated RGCs, where it also significantly enhanced neurite outgrowth, demonstrating a direct effect on RGC regeneration. In addition, these extracts have no significant drawbacks in terms of cell apoptosis and RGC neurite outgrowth activity at specific concentrations. The present study thus demonstrates that while excessively high concentrations of these extracts may inhibit neurite growth, at moderate concentrations some extracts from Cordyceps cicadae and Hericium erinaceus have the potential of promoting neurite regeneration in the mammalian retina. Further research targeting the molecular mechanisms behind these effects may shed light on their potential application as a medicine or nutraceutical for facilitating neural regeneration.

## Linked entities

- **Chemicals:** Erinacine S (PubChem CID 127047879)
- **Diseases:** glaucoma (MONDO:0005041)
- **Species:** Cordyceps cicadae (taxon 218633), Hericium erinaceus (taxon 91752)

## Full-text entities

- **Genes:** Elk1 (ETS transcription factor ELK1) [NCBI Gene 314436], Pten (phosphatase and tensin homolog) [NCBI Gene 50557] {aka MMAC1, Mmac, TEP1}, NTRK1 (neurotrophic receptor tyrosine kinase 1) [NCBI Gene 4914] {aka MTC, TRK, TRK1, TRKA, Trk-A, p140-TrkA}, Thy1 (thymus cell antigen 1, theta) [NCBI Gene 21838] {aka CD90, T25, Thy-1, Thy-1.2, Thy1.1, Thy1.2}, Ngf (nerve growth factor) [NCBI Gene 310738] {aka Ngfb, beta-NGF}, NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, Ntrk1 (neurotrophic receptor tyrosine kinase 1) [NCBI Gene 59109] {aka Trk}, Rest (RE1-silencing transcription factor) [NCBI Gene 83618] {aka Nrsf}, REST (RE1 silencing transcription factor) [NCBI Gene 5978] {aka DFNA27, GINGF5, HGF5, NRSF, WT6, XBR}, Ngf (nerve growth factor) [NCBI Gene 18049] {aka Ngfb, beta-NGF}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}
- **Diseases:** Parkinson's disease (MESH:D010300), elevated (MESH:D006937), inflammatory (MESH:D007249), pain (MESH:D010146), overdose (MESH:D062787), astrocytoma (MESH:D001254), blind (MESH:D001766), retinal (MESH:D012173), Glaucoma (MESH:D005901), spinal cord injury (MESH:D013119), Alzheimer's disease (MESH:D000544), cytotoxicity (MESH:D064420), eye diseases (MESH:D005128), neurodevelopmental disorders (MESH:D002658), neurological diseases (MESH:D020271), cancer (MESH:D009369), neuroinflammatory (MESH:D000090862), dry eye (MESH:D015352), cataract (MESH:D002386), neurodegenerative disease (MESH:D019636)
- **Chemicals:** Pen (MESH:C058388), isoflurane (MESH:D007530), H2O (MESH:D014867), H2O2 (MESH:D006861), H (MESH:D006859), polysaccharides (MESH:D011134), HEPES (MESH:D006531), Forskolin (MESH:D005576), Xylazine (MESH:D014991), I (MESH:D007455), CO2 (MESH:D002245), HE (MESH:D006371), cAMP (MESH:D000242), ROS (MESH:D017382), Cordycepin (MESH:C058120), DPBS (MESH:C012939), DMSO (MESH:D004121), K (MESH:D011188), NaHCO3 (MESH:D017693), Streptomycin (MESH:D013307), EtOH (MESH:D000431), sodium azide (MESH:D019810), Erinacine A (MESH:C000595639), Penicillin (MESH:D010406), paraformaldehyde (MESH:C003043), Triton X-100 (MESH:D017830), S (MESH:D013455), Triiodo-thyronine (MESH:D014284), acetonitrile (MESH:C032159), L-Glutamine (MESH:D005973), C. cicadae extract (-), Ketamine (MESH:D007649), A- (MESH:D001151), ergothioneine (MESH:D004880), adenosine (MESH:D000241), Glucose (MESH:D005947), HEA (MESH:C528186), DAPI (MESH:C007293), glutaraldehyde (MESH:D005976), NaOH (MESH:D012972), Erinacine S (MESH:C000608927)
- **Species:** Cordyceps militaris (species) [taxon 73501], Homo sapiens (human, species) [taxon 9606], Lignosus rhinocerus (species) [taxon 483020], Hypericum perforatum (species) [taxon 65561], Mus musculus (house mouse, species) [taxon 10090], Ophiocordyceps sinensis (species) [taxon 72228], Cordyceps cicadae (species) [taxon 218633], Paeonia lactiflora (Chinese peony, species) [taxon 35924], Rattus norvegicus (brown rat, species) [taxon 10116], C. sinensis [taxon 128511], Panax quinquefolius (American ginseng, species) [taxon 44588], Hericium erinaceus (bearded tooth mushroom, species) [taxon 91752]
- **Cell lines:** /6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985), P2-4 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_B3T8), 1321N1 — Homo sapiens (Human), Astrocytoma, Cancer cell line (CVCL_0110)

## Full text

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## Figures

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## References

64 references — full list in the complete paper: https://tomesphere.com/paper/PMC12880703/full.md

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Source: https://tomesphere.com/paper/PMC12880703