In a study published 19 June 2017 in the Journal Frontiers in Pharmacology entitled, “A Systematic Strategy for Discovering a Therapeutic Drug for Alzheimer’s Disease and Its Target Molecule”, researchers from the University of Toyama in Japan identified bioactive compounds from the rhizome of the fern Drynaria which improves memory and reduces Alzheimer’s disease pathologies.
Drynaria is a genus of ferns in the family Polypodiaceae and is commonly known as basket ferns. The family of Polypodiaceae contains around 16 species. They are native to tropical Africa, South Asia, East Asia, Southeast Asia, Australia, and Oceania.
Figure 1. Drynaria fern
Extracts from the rhizomes of some Drynaria species are used extensively in traditional medicine of the Asian countries of China, Taiwan, Vietnam, Thailand, and Laos.
The two species of Drynaria rhizome used for medicinal purposes are:
- Drynaria roosii (also known by its synonym Drynaria fortunei)
- Drynaria quercifolia (used in South Asia)
Figure 2. Drynaria roosii fern
Of the two species, Drynaria roosii is the most often used for medicinal purposes.
Flavan-3-ols and propelargonidins can be isolated from the rhizomes. 1
Bio-Active Components of Drynaria roosii
The Japanese authors from this study conducted a biochemical analysis which led to the identification of the bio-active components of Drynaria roosii that are transferred (crosses the blood brain barrier) to the brain. These bio-active components of Drynaria roosii include:
- glucuronides of naringenin
Naringenin is characterized as a flavanone which is a sub-category of the plant metabolites flavonoids. Flavonoids or bioflavonoids have a yellow color in nature and are bitterless and colorless.
Grapefruit contains naringenin as its predominant flavanone. Naringenin is also found in herbs and fruits, including:
- citrus bergamot
- Greek oregano
- sour orange
- tart cherries
- water mint
Glucuronides of Naringenin
A glucuronide is any substance produced by linking glucuronic acid to another substance via a glycosidic bond.
The glucuronide of naringenin is it glycoside form called naringin which has the addition of the disaccharide neohesperidose attached via a glycosidic linkage at carbon 7.
Naringin is responsible for a fruit’s bitter taste. Naringin (bitter) is metabolized to the aglycone naringenin (not bitter) by the enzyme naringinase present in the gastrointestinal tract.
Figure 3. Naringin and Naringenin molecules (Source)
Drynaria Rhizome may enhance memory function and ameliorate Alzheimer’s disease pathologies
In the study from the University of Toyama in Japan, researchers used mice with a genetic mutation that provided the mice with characteristics of Alzheimer’s disease such as limited memory and an abundance of specific proteins within the brain like tau and amyloid proteins.
The mice were treated with naringenin and after 5 hours following treatment found that naringenin and two of its metabolites crossed the blood brain barrier.
The important findings from the study include: 2
- Drynaria rhizome decreased memory impairments within the brains of mice
- Drynaria rhizome decreased the level of tau and amyloid proteins within the brains of mice
- Naringenin binds to the protein CRMP-2 within neurons which spurs growth of the neurons
CRMP-2 is one of 5 CRMP’s in the CRMP family of proteins. CRMP stands for Collapsin response mediator protein and are predominantly expressed in the nervous system during development and play important roles in axon formation from neurites and in growth cone guidance and collapse through their interactions with microtubules. 3
Phosphorylated CRMP-2 has been connected to the degenerating neuritis in Alzheimer’s disease. The inactivation of CRMP-2 in people with Alzheimer’s disease promotes the expression of neurofibrillary tangles and plaque neurites which are consistent with people suffering from this disease.
Researchers of this study commented that increasing the modulation of CRMP-2 expression might be the mechanism through which naringenin improves the symptoms of Alzheimer’s disease.