Unprecedented Neoverrucosane and Cyathane Diterpenoids with Anti-Neuroinflammatory Activity from Cultures of the Culinary-Medicinal Mushroom Hericium erinaceus

Summary

This research examined compounds from Lion’s Mane mushroom (Hericium erinaceus) and discovered new molecules that could help protect brain cells and reduce inflammation in the brain. The findings are particularly relevant for developing treatments for neurodegenerative diseases like Alzheimer’s. Impacts on everyday life: • Provides scientific evidence supporting the traditional use of Lion’s Mane mushroom for brain health • Identifies new compounds that could lead to better treatments for Alzheimer’s and other brain diseases • Demonstrates the potential of natural products from edible mushrooms as safe therapeutic options • Supports the inclusion of Lion’s Mane mushroom in dietary supplements for brain health • Shows promise for developing new drugs from natural sources that could help aging populations

Background

The culinary medicinal mushroom Hericium erinaceus has significant global recognition and increased interest in aging societies due to its neuroprotective and anti-neuroinflammatory properties. It has a long history of use in traditional Chinese medicine and as a delicacy. Most Alzheimer’s disease drugs only alleviate symptoms without halting disease progression, creating an urgent need for safe and effective treatments. Studies show H. erinaceus-derived compounds like erinacines promote nerve growth factor synthesis and have anti-neuroinflammatory activities, providing a basis for its effects against neurodegeneration.

Objective

To isolate and characterize novel bioactive compounds from H. erinaceus and evaluate their neurotrophic and anti-neuroinflammatory activities. The study aimed to discover new diterpenes and assess their potential for treating neurodegenerative diseases.

Results

Two novel diterpenes were isolated: 16-carboxy-13-epi-neoverrucosane (1) and Erinacine L (2), along with three known xylosyl cyathane diterpenoids, four lanostane-type triterpenoids, three cyclic dipeptides, and orcinol. Compound 1 represents the first verrucosane diterpene from basidiomycetes. Compounds 2-5 showed neurotrophic activity and significantly inhibited lipopolysaccharide-induced nitric oxide production in BV2 cells with IC50 values as low as 5.82 μM.

Conclusion

The study discovered novel diterpenes with promising anti-neuroinflammatory and neurotrophic activities from H. erinaceus. Compound 2, containing an unconventional hemiacetal moiety, showed particular promise for preventing neurodegenerative diseases. The findings expand fungal diterpene structural diversity and provide additional evidence supporting cyathane diterpenes’ role in treating neurodegenerative conditions.
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