Phenylindane, a Bioactive Compound Found in Coffee, Exhibits Neuroprotective Properties Against Age-Related Cognitive Decline Disorders

by | Mar 7, 2022 | 2018, Brain Health, Caffeine, Cognitive Health

Written by Taylor Woosley, Staff Writer. Results of the study suggest high levels of phenylindane, a bioactive compound found in coffee, may offer neuroprotective properties against age-related cognitive disorders through the dual inhibition of Aβ and tau aggregation.

caffeine - coffeeCoffee is the second most consumed beverage worldwide and this complex beverage contains more than 1,000 phytochemicals with health-promoting properties 1. Besides caffeine, bioactive compounds such as polyphenols, most notably chlorogenic acids, caffeic acid and phenylindane, alkaloids, especially trigonelline, and the diterpenes, cafestol and kahweol, can all be found in a cup of coffee 2. In particular, the high content of polyphenols, such as chlorogenic acids and phenylindane, share antioxidant and anti-inflammatory properties by inhibiting the expression of cytokine genes and are associated with regeneration of neurons which may contribute to neuroplasticity 3. Furthermore, the diterpenes and alkaloids found in coffee exhibit potent antioxidant effects, leading to the elimination of free radicals, which is directly associated with oxidative stress causing DNA damage in the body 4. The specific presence of these elements depends on a variety of factors: the species of coffee, speed of roasting, coffee brewing conditions, and type of roast all factor into the development of the phytochemicals 5.

The chemical compounds found in coffee may provide neuroprotective properties that lower the risk of age-related cognitive diseases. The main components contributing to neurodegenerative disorders are the extracellular aggregation of β-amyloid peptides (Aβ) and hyperphosphorylated tau protein (neurofibrillary tangles) 6. Past epidemiological studies have shown that moderate coffee intake (two to four cups a day) is associated with the highest neuroprotective benefits. Much of its protective properties are attributed to the effects caffeine and chlorogenic acids have on the adenosine receptors that play a role in preventing β-amyloid peptide deposits in the brain 7.

Mancini et al conducted a study to further explore the potential neuroprotective effects of coffee on age-related cognitive disorders. Researchers compared three different coffee extracts (light roast, dark roast, decaffeinated dark roast) and six bioactive coffee compounds: caffeine, chlorogenic acid, quinic acid, caffeic acid, quercetin, phenylindane). The various coffee extracts and chemical compounds chosen were investigated for their potential ability to inhibit the fibrillization of Aβ and tau proteins and were assessed using thioflavin T (ThT) and thioflavin S (ThS) fluorescence assays, respectively. Furthermore, the three coffee extracts were examined to compare the difference roasting can have on inhibiting oligomerization of Aβ and α-synucelin: IC50 values.

After all the coffee extracts and bioactive compounds were observed, the results are as follows:

  • No significant interaction between caffeine and the aggregation inhibitor of oligomerization of Aβ/tau/α-synuclein was observed.
  • Study data show that quercetin may be an effective inhibitor of Aβ oligomerization (IC50 = 10.3 µM), in addition to its antioxidant and anti-inflammatory properties.
  • Phenylindane is the only coffee component that acts as a potent inhibitor to both Aβ and tau fibrillization, along with inhibiting Aβ oligomerization (IC50 = 42.1 µM).
  • Aβ oligomer assays show more potent levels of aggregation inhibition in both caffeinated and decaffeinated dark roasts (IC50 10 µg/mL) compared to the light roast (IC50 = 40.3 µg/mL), which may be due to the increased roast time providing increased levels of quercetin and phenylindane.
  • All three coffee extracts promote α-synuclein oligomerization and inhibit fibrillization of Aβ and tau at concentrations above 100 µg/mL.
  • Chlorogenic acid, caffeic acid, and quercetin inhibit the fibrillization of Aβ at 100 µM concentration.
  • Caffeic acid and quercetin, at concentrations above 100µM, are the only coffee components that promote the aggregation of α-synuclein oligomerization.

In conclusion, study findings suggest that it is not the caffeine found in coffee that provides potential neuroprotective properties, instead the various bioactive compounds are responsible, most notably phenylindanes. The combination of bioactive components and their interactions aid in inhibiting Aβ oligomerization, but phenylindane alone inhibited Aβ and tau aggregation. Mancini et al are currently conducting further research on phenylindanes’ ability to reduce Aβ, tau and α-synuclein loads in cell and animal models to better understand its effects on neurodegenerative disorders.

Source: Mancini, Ross S., Yanfei Wang, and Donald F. Weaver. “Phenylindanes in brewed coffee inhibit amyloid-beta and tau aggregation.” Frontiers in neuroscience (2018): 735.

© 2018 Mancini, Wang and Weaver. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Posted March 7, 2022.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

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