Erinacine S from Hericium erinaceus mycelium promotes neuronal regeneration by inducing neurosteroids accumulation

Chun-Yu Lin ^a,b,c,d,e,1, Yi-Ju Chen ^f,1, Chih-Hsuan Hsu ^f,1, Yu-Hsuan Lin ^f,1, Peng-Tzu Chen ^f, Ting-Han Kuo ^b, Chris T. Ho ^f, Hsin-Hua Chen ^a, Sih-Jia Huang ^a, Ho-Chieh Chiu ^f, Chin-Chu Chen ^g,h,i, Eric Hwang ^a,b,c,d,f,*

^a Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Taiwan

^b Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Taiwan

^c Institute of Data Science and Engineering, National Yang Ming Chiao Tung University, Taiwan

^d Center for Intelligent Drug Systems and Smart Bio-devices, National Yang Ming Chiao Tung University, Taiwan

^e School of Dentistry, Kaohsiung Medical University, Taiwan

^f Institute of Molecular Medicine and Bioengineering, National Yang Ming Chiao Tung University, Taiwan

^g Biotech Research Institute, Grape King Bio, Taiwan

^h Institute of Food Science and Technology, National Taiwan University, Taiwan

ⁱ Department of Food Science, Nutrition, and Nutraceutical Biotechnology, Shih Chien University, Taiwan

Erinacines derived from Hericium erinaceus have been shown to possess various health benefits including neuroprotective effect against neurodegenerative diseases, yet the underlying mechanism remains unknown. Here we found that erinacine S enhances neurite outgrowth in a cell autonomous fashion. It promotes post-injury axon regeneration of PNS neurons and enhances regeneration on inhibitory substrates of CNS neurons. Using RNA-seq and bioinformatic analyses, erinacine S was found to cause the accumulation of neurosteroids in neurons. ELISA and neurosteroidogenesis inhibitor assays were performed to validate this effect. This research uncovers a previously unknown effect of erinacine S on raising the level of neurosteroids.

Keywords: Axotomy, Bioactive, Erinacines, Neurodegenerative disease, Neurotrophic factor

https://doi.org/10.38212/2224-6614.3446