ALD-Induced Oxidative Damage
Today’s polls estimate that illness associated with oxidative liver damage, and chronic alcohol consumption constitute 5.9% of all deaths in our globe. In addition to this, one in eight American adults have been medically diagnosed with an alcohol consumption disorder. Symptoms of Alcohol liver disease (ALD) include liver inflammation, disturbance of hepatocyte metabolism, and oxidative stress brought upon by free radicals.
Pu-erh Tea. Image Credit: HelloRF Zcool/Shutterstock.com
When alcohol is metabolized within the liver, reactive oxygen species (ROS) are promoted by the physiological pathways that the hydroxyl functional group can undergo, such as the formation of superoxide radicals (O2• -) and hydroxyl radicals (OH• -). This will rouse the activity of cytochrome P450s enzymes, which further increases radical propagation in addition to eliminating antioxidants- antagonists to ROS. These free radicals are highly reactive on the account of their unstable valance shell electrons, leading to abnormal alterations in proteins, lipids, amino acids, and other vital macromolecules.
Recent studies suggest that Pu-erh Tea can induce healthy enzymatic activity, can promote healthier bacteria within our gut biome, and can reduce the overall strain that ethanol has on the liver.
Methodologies Employed of Pu-erh Tea Extract (PTE) Analysis
Pu-erh tea extract (PTE) was used to assess the therapeutic use of the beverage. The effectiveness and veracity of the results were made sound by various methodologies. The first involved the determination of the total antioxidant activity through the use of a Trolox equivalent antioxidant capacity (TEAC) assay. This particular assay relies on the potency of antioxidants in medium to scavenge blue-green 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic) acid (ABTS). This ABTS compound is the standard for observing the enzymatic kinetics of varying metabolic systems and is generally used to detect the binding modes for different molecules.
Assays of the scavenging effects of hydroxyl radicals, and superoxide radicals, were also implemented through the use of an ultraweak luminescence analyzer (BPLC). Finally, 16S rRNA high-throughput sequencing was conducted on the fecal matter of C57BL/6 mice (weighing 20 ± 2g) after one week of PTE accumulation was conducted. This method of analysis is superlative to all others when categorizing the taxonomic levels of a myriad of different macrobacteria.
Positive Correlation Between PTE and Healthy Enzymatic Activity
At the molecular level, ethanol undergoes a reaction where it is converted to acetaldehyde by alcohol dehydrogenase (ADH) and can be processed further into acetate through aldehyde dehydrogenase. It was found that PTE stimulated ethanol metabolism by increasing the levels of ADH and Aldehyde dehydrogenase (ALDH).
In addition to ADH and ALDH, there exists an archetypical antioxidant system within humans, comprised of key enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA). These key facets of our metabolic system help regulate the formation of ROS in an endeavor to maintain homeostasis.
Excess ROS, and endotoxins such as lipopolysaccharides (LPS) are harmful metabolites brought about by the excess consumption of ethanol and can damage the integrity of the hepatic cells in one’s liver. In addition to these metabolic systems, an increase of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) exist to metabolize excess amino acids.
The antioxidative nature of PTE and its metabolites not only antagonize the activity of antioxidant enzymes SOD, GSH-Px, and MDA, they also antagonize the metabolic activity of ALT and AST. Ranking the PTE by its 50% inhibition concentration (IC50) it was found that the ability of PTE to scavenge excess ROS is substantial (*p < 0.05, **p < 0.01).
In addition to reducing the accumulation of LPS, all data collected correlates to the fortification of hepatocytes and a reduction in ALD symptoms in alcohol-exposed C57BL/6 mice. This makes the antioxidant potency of Pu-erh tea substantially higher than that of most other tea, including typical green tea.
The Bacterial effect of our Gut Biome
The gut microbiota of our species has been scrutinized extensively. While good bacteria such as Allobaculum and Bifidobacterium maintain a necessitous low pH by mainlining indole acrylic acid (IAA and indole lactic acid), harmful bacteria such as Helicobacter can proliferate the intestine, produce an excess amount of endotoxin, and result in gut inflammation. This again is a result of excessive ethanol metabolism.
To evaluate these factors 16S rRNA sequencing of the gut microbiota was taken. The sequencing of 16S rRNA sequencing has become a standard in bacterial taxonomic and microbial classification because it is more rapidly sequenced and contains enough philologically relevant information.
In mice that drank 0.4% PTE water, 70% of the PTE polyphenols reached their target microbiota sites. This increased the abundance of firmicutes within the gut while diminishing Bacteroidetes. Fecal matter was later assayed through the use of a liquid chromatography-quadrupole time-of-flight mass spectrometry apparatus (UHPLC-QTOF-MS), determining an increase of the relative abundance of Norank F Muribaculaceae from 36.1% to 48.3% on a genus level.
In addition, bacterial strains Allobaculum and Bifidobacterium were also significantly promoted following PTE intervention, while Helicobacter, Bacteroides, and Prevotellaceae UCG were all diminished.
PTE on the Liver
An indicator of chronic alcohol consumption is steatosis via increased fatty acid synthesis. Hepatic steatosis is characterized by an increase in intrahepatic fat resulting in a 5% increase in liver weight.
Prolonged exposure to these triacylglycerols in the liver could result in inflammation, further metabolic dysfunction, and even nonalcoholic fatty acid liver disease. This accumulation of fatty acids will inhibit fatty acid transport and oxidation, resulting in necrosis and alcoholic steatohepatitis.
Extensive research shows that hepatic fat accumulation was significantly reduced by PTE. This was later confirmed by a sonicated analysis of Lecithin (580 mg), exhibiting a reduction in liver weight, decreased inflammation, and more regulated pH levels.
The results garnered from the following papers highly suggest that PTE, and in turn Pu-erh tea, can regulate ALD caused by excessive ethanol metabolism. This is done by cultivating a healthier array of bacteria, diminishing the concentration of free radicals within the digestive tract, and providing auxiliary support to metabolic antioxidant enzymes.
References:
- Liu, Y. & Luo, Y. et al. Gut Microbiome and Metabolome Response of Pu-erh Tea on Metabolism Disorder Induced by Chronic Alcohol Consumption. https://pubs-acs-org. (2020). Available at: https://pubs-acs-org.providence.idm.oclc.org/doi/10.1021/acs.jafc.0c01947.
- Jie, G. Shibboleth. et al.. https://pubs.acs.org/ (2006). Available at: https://pubs-acs-org.providence.idm.oclc.org/doi/10.1021/jf061663o.
- Duh, P. D., Yen, G. C. & Yen, W. J. et al. Effects of Pu-erh Tea on Oxidative Damage and Nitric Oxide Scavenging. Shibboleth Authentication Request (2004). Available at: https://pubs-acs-org.providence.idm.oclc.org/doi/10.1021/jf0490551.
- Lu, X., Liu, J. & Zhang, N. et al. Ripened Pu-erh Tea Extract Protects Mice from Obesity by Modulating Gut Microbiota Composition. https://pubs-acs-org. (2019). Available at: https://pubs-acs-org.providence.idm.oclc.org/doi/10.1021/acs.jafc.8b04909.
- Ingraham, C. One in eight American adults is an alcoholic, a study says. The Washington Post (2019). Available at: https://www.washingtonpost.com/news/wonk/wp/2017/08/11/study-one-in-eight-american-adults-are-alcoholics/#:~:text=One%20in%20eight%20American%20adults%2C%20or%2012.7%20percent%20of%20the,disorder%2C%20according%20to%20the%20study
Further Reading