Theaflavins may mitigate aging associated cognitive dysfunction via the microbiota−gut−brain axis

© Irina Vodneva / Getty Images
© Irina Vodneva / Getty Images

Related tags Tea Theaflavins Catechin Polyphenols gut brain axis

Emerging reports linking the gut microbiota to cognitive dysfunction have provided researchers a potential avenue to enhance cognition via gut microbiota modulation.

As reduced gut microbial diversity demonstrated increased cognitive deficits in previous animal studies (Fröhlich​, 2016), researchers from China aimed to investigate the link between the gut microbiota and cognitive function, under theaflavins (TFs) treatment in D-galactose-induced aging mice.

Results published in the Journal of Agriculture and Food Chemistry​, demonstrated TFs’ potential beneficial effects on cognitive decline via the bidirectional communication between the gut and the brain.

Theaflavins (TFs)

A significant body of epidemiological and clinical studies support the health promoting effects of black tea, with a focus on bioactives such as catechins and theaflavins (TFs).

Known to comprise the red pigment of black tea leaves, TFs are a group of polyphenolic compounds formed from the oxidation of catechins during the fermentation process of black tea manufacturing.

Theaflavin-3-gallate, theaflavin-3'-gallate, and theaflavin-3-3'-digallate, are derivatives of Theaflavin, that are known for their anti-inflammatory, antibacterial, antioxidant, cardioprotective, nephroprotective, and neuroprotective effects.

Due to their high molecular weight, large polar surface area, and gastrointestinal instability, TFs have low bioavailability so most studies have used whole tea extracts or polyphenolic extracts. 

Material and Methods

The study used 50 lab mice randomly divided into five groups: The control check group (CK), the aging D-galactose treated group (Model), the vitamin C treated group (VC) and the TFs treated group (TF).

The CK treated group received daily intraperitoneal injections of 0.9% saline, the Model treated group received daily injections of 250 mg kg daily of D-galactose to artificially induce senescence​, the VC treated group was injected with 250 mg kg D-galactose with 100 mg kg vitamin C daily, and the TF treated group was injected with 250 mg kg D-galactose and 50 mg kg TFs daily.

Antibiotic-induced gut microbiota depletion was also conducted in the TFs plus antibiotics treated group (TFAT).  Mice in this group were injected with 250 mg kg D-galactose daily, oral gavage with 100 mg kg TFs daily and oral gavage with antibiotics twice a day.

Study results

Results from the Morris Water Maze (MWM) test, which is commonly used to assess spatial learning and memory, revealed that aging mice showed cognitive dysfunction in remembering the platform as well as the target quadrant, and it took a longer time for the mice in the Model group to find the platform than the healthy mice. 

Mice consuming the TFs showed a dramatic increase in distance and time in the target quadrant and a reduction in the escape time compared with the Model group.  The intake of TFs improved the time of aging mice that stayed in the target quadrant.  Antibiotic treatment weakened the TFs-induced protective effect on memory in both the hidden platform test and the probe trial test.

TFs increased the number of neurons in the hippocampus, and dramatically decreased the levels of oxidation products (8-OHdG, AGEs), marker of astrocyte activation (GFAP), and neurotransmitters (GABA, GLU) and increased the level of the brain-derived neurotrophic factor (BDNF).

Intake of TFs significantly decreased the levels of IL-6, IL-1β, and TNF-α compared with D-galactose induced aging mice.  TFs effectively reduced high levels of oxidative stress in D-galactose-induced aging mice by increasing the activity of antioxidant enzymes SOD, CAT, and GSH-PX and decreasing the accumulation of toxic oxidation products MDA, 8-OHdG, and AGEs. 

Gut inflammation was reduced and the expressions of tight junction proteins ZO1, occludin, and claudin were up regulated with TFs.  These beneficial effects of TFs were found to be weakened in antibiotic induced microbiome depleted mice.

The intake of TFs largely restored the gut microbiota diversity, by increasing the relative abundances of Actinobacteria​ and the ratio of Firmicutes​ to Bacteroidetes​, and decreasing the relative abundances of Bacteroidetes​ and Proteobacteria​.  TFs effectively reversed the D-galactose induced decrease in gut microbiota metabolites (SCFAs and AAs).

Li et al. stated: “This research suggests a novel and convincing link between the gut microbiota and cognitive function, microbiota−gut−brain axis, under TFs treatment in D-galactose-induced aging mice.” 

Although, the results of the study demonstrated significant beneficial effects of TFs on the microbiota−gut−brain axis, the authors called for further study.

In the future, TFs could become a novel dietary interventional approach for age related cognitive dysfunction via the microbiota−gut−brain axis.

Source: Journal of Agriculture and Food Chemistry                                                                                          
Published online 31 January 2023 doi: https://doi.10.1021/acs.jafc.2c06679​               
“Theaflavins in Black Tea Mitigate Aging-Associated Cognitive Dysfunction via the Microbiota−Gut−Brain Axis.” 
Authors: Li et al.

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