Scientific Evidence

Feruguard: Comprehensive Scientific Explanation

Feruguard is a dietary supplement designed to support cognitive function through the synergistic action of ferulic acid and garden angelica (Angelica archangelica). The formulation is based on research into how these natural compounds can address key pathways involved in cognitive decline.

Ferulic Acid: Detailed Mechanism of Action

Ferulic acid, a phytochemical (naturally occurring plant compound), is extracted from rice bran and provides antioxidant and neuroprotective effects. Its mechanism involves multiple pathways:

• Direct Antioxidant Activity:
  Ferulic acid directly scavenges free radicals, which are unstable molecules that can damage cells and contribute to aging and neurodegenerative diseases. Free radicals can oxidize proteins, DNA, and RNA, leading to cellular dysfunction.
  
  
• Upregulation of the Nrf2/ARE Pathway:
  Ferulic acid indirectly boosts antioxidant defenses by upregulating the Nrf2/ARE (Nuclear factor erythroid 2-related factor 2/Antioxidant Response Element) pathway. This pathway is crucial for maintaining redox balance (oxidative equilibrium) in cells.
  
  
  • Nrf2 Activation:
    Nrf2 is a transcription factor that acts as a signaling switch. When oxidative stress occurs, Nrf2 translocates to the cell nucleus to "tell" the cell to activate its defenses.
    
    
  • Keap1 Interaction:
    The Kelch ECH-associated protein 1 (Keap1) is a protein that binds to Nrf2. When Keap1 is modified (likely by cysteine modifications) due to oxidative stress, Nrf2 is released and can then migrate to the nucleus.
    
    
  • ARE Binding and Gene Expression:
    In the nucleus, Nrf2 binds to the antioxidant response element (ARE). This binding activates the expression of genes that code for antioxidant, anti-inflammatory, and detoxifying proteins.
    
    
  • Heme-Oxygenase 1 (HO-1) Induction:
    Nrf2 activation leads to the upregulation of the HO-1 gene. HO-1 is a stress enzyme that catalyzes the breakdown of heme into biliverdin, which is then converted to bilirubin. Both biliverdin and bilirubin are potent antioxidants that neutralize free radicals. HO-1 also prevents vascular inflammation, which contributes to amyloid-β plaque buildup.

• Inhibition of β-Amyloid Formation:
  Ferulic acid has been shown to inhibit the formation and aggregation of β-amyloid, a protein that accumulates in the brains of individuals with Alzheimer's disease. It can destabilize β-amyloid fibrils and redirect the aggregation process toward the formation of non-toxic, amorphous aggregates.
  
  
• Improved Bioavailability:
  To improve ferulic acid's effectiveness, Feruguard uses a form of ferulic acid that is processed with γ-cyclodextrin (a cyclic oligosaccharide). This increases its bioavailability and extends its metabolism in the body, allowing it to remain active for a longer period (approximately 12 hours).

Garden Angelica: Detailed Mechanism of Action

Garden angelica (Angelica archangelica) is a herb traditionally used in European medicine. It contains various bioactive compounds, including coumarins and furanocoumarins, which contribute to its cognitive benefits:

• Acetylcholinesterase (AChE) Inhibition:
  Key compounds in garden angelica, such as xanthotoxin and decursin, inhibit acetylcholinesterase, the enzyme that breaks down acetylcholine. By inhibiting this enzyme, garden angelica increases acetylcholine levels in the brain. Acetylcholine is a neurotransmitter crucial for memory, learning, and attention.
  
  
• Anti-inflammatory Effects:
  Xanthotoxin has demonstrated anti-inflammatory properties. It inhibits the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), which contribute to tissue damage and various disorders.
  
  
• Antioxidant Properties:
  Garden angelica contains polyphenolic compounds that contribute to its antioxidant activity. These compounds neutralize reactive oxygen species (ROS) and reduce tissue oxidative stress, helping to restore cellular redox balance.
  
  
• Neuroprotective Effects:
  Decursin and decursinol are pyranocoumarins found in garden angelica with neuroprotective effects. Decursinol, in particular, inhibits AChE. Decursin can lower calcium influx in cortical cells and inhibit apoptosis.

Clinical Evidence and Efficacy

• Clinical Trials:
  A multicenter, randomized, double-blind, placebo-controlled trial (Kudoh et al., 2020) found that Feruguard significantly improved Mini-Mental State Examination (MMSE) scores at 24 weeks (p = 0.041) in the intention-to-treat population.
  
  
  • The trial also showed significant improvement in Alzheimer's Disease Assessment Scale-Cognitive Subscale, Japanese version (ADAS-Jcog) scores at 24 (p = 0.035) and 48 weeks (p = 0.015) in the active group, with MMRM analysis indicating a significant between-group difference (p = 0.031).

Synergistic Potential

The combination of ferulic acid and garden angelica in Feruguard offers a synergistic approach to supporting cognitive function:

• Complementary Mechanisms:
  Ferulic acid provides antioxidant and anti-amyloid-β aggregation benefits, while garden angelica inhibits acetylcholinesterase and offers additional neuroprotection.
  
  
• Comprehensive Cognitive Support:
  By addressing multiple pathways involved in cognitive decline, Feruguard aims to provide more comprehensive support for cognitive health.
  
  

References

1. Graf, E. (1992). Antioxidant potential of ferulic acid. Free Radical Biology and Medicine, 13(4), 435–448.
2. Kang, S. Y., Lee, K. Y., Sung, S. H., Park, M. J., & Kim, Y. C. (2001). Coumarins Isolated from Angelica gigas Inhibit Acetylcholinesterase: Structure−Activity Relationships. Journal of Natural Products, 64(5), 683–685.
3. Kudoh, C., Hori, T., Yasaki, S., Ubagai, R., & Tabira, T. (2020). Effects of Ferulic Acid and Angelica archangelica Extract (Feruguard) on Mild Cognitive Impairment: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Prospective Trial. Journal of Alzheimer's Disease Reports, 4(2), 393–398.
4. Kimura, T., Hayashida, H., Murata, M., & Takamatsu, J. (2011). Effect of ferulic acid and Angelica archangelica extract on behavioral and psychological symptoms of dementia in frontotemporal lobar degeneration and dementia with Lewy bodies. Geriatrics Gerontology International, 11, 309-314.