New Study! This "acid" can help counteract cognitive decline caused by chronic sleep deprivation

New Study! This "acid" can help counteract cognitive decline caused by chronic sleep deprivation

Among lifestyle-related risk factors, chronic sleep deprivation (CSD) caused by irregular work schedules, prolonged stress, and excessive nighttime screen exposure has been identified as a primary contributor to cognitive decline. It not only disrupts sleep quality but also induces oxidative stress, neuroinflammation, and synaptic dysfunction. 

Recently, an article titled "Research on the Protective Effects and Mechanisms of Gallic Acid Against Cognitive Impairment Induced by Chronic Sleep Deprivation" found that gallic acid helps maintain cognitive health under conditions of chronic sleep deprivation.

Source:MDPI

1. How does gallic acid maintain cognition?

Researchers randomly assigned mice to a control group, a chronic sleep deprivation model group, a Ginkgo biloba extract control group, and low, medium, and high dose groups of gallic acid (administered at 50, 100, and 200 mg/kg/day, respectively), and established a chronic sleep deprivation model (CSD) in mice to simulate the long-term state of human sleep deprivation. Gallic acid (GA) was administered daily throughout the modeling period, synchronized with the deprivation process. After sleep deprivation, researchers conducted multiple behavioral tests on mice and detected biochemical and molecular changes in their serum and hippocampal tissue. 

The behavioral test results showed that compared with the control group, CSD mice had significantly reduced autonomous activity and exploration time, as well as significantly reduced learning and memory abilities. GA intervention showed a dose-dependent effect, with the low to medium dose group showing an increase in autonomous activity compared to the CSD group, while the high dose group showed more significant improvements in both exercise and central exploration.

Movement and exploration of mice in different groups during OFT

In the water maze training, CSD mice maintained a long latency period throughout the entire learning stage, indicating impaired spatial learning ability. The incubation period of the Ginkgo biloba extract control group was effectively shortened, and on the last day it reached a value close to that of the control group. Gallic acid also improved learning ability, with the medium dose group showing the most significant recovery in learning ability, followed by the high-dose group, and the low-dose group having relatively limited effects.

Changes in escape latency duration during water maze training in different groups of mice

Biochemical testing results showed that chronic sleep deprivation can lead to oxidative stress, with elevated levels of malondialdehyde (MDA) in mice, while total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity decrease. Gallic acid can enhance antioxidant defense ability, with the medium dose GA group showing the most stable recovery of T-AOC and SOD activity, while both the medium and high dose groups significantly reduced MDA levels. 

In terms of molecular mechanisms, GA can activate the Nrf2/HO-1/NQO1 antioxidant pathway in the hippocampus, enhance endogenous antioxidant enzyme expression, and inhibit the NF - κ B/p-p65 signaling pathway and the release of downstream inflammatory factors (such as TNF - α, IL-1 β, IL-6), thereby reducing neuroinflammatory responses. The overall results indicate that gallic acid can alleviate peripheral and central inflammatory responses induced by CSD, and improve cognitive dysfunction caused by chronic sleep deprivation by regulating oxidative stress and inflammatory signaling pathways.

2. What is gallic acid?

Gallic acid, also known as 3,4,5-trihydroxybenzoic acid, has a molecular formula of C7H6O5. It appears as white or light yellow needle shaped crystals and turns brown upon absorbing oxygen. It is easily soluble in hot water, ethanol, and acetone. 

Gallic acid is a natural polyphenolic compound that was first extracted from the Chinese medicinal herb gallnut, hence it is also known as "gallic acid". As early as the Ming Dynasty, Li Zhongzi's "Introduction to Medicine" recorded the use of fermentation to extract gallic acid from gallnuts, demonstrating its early application foundation in traditional medicine. In addition to galls, gallic acid is also widely present in plants such as walnuts, tea, and grapes, and is a key component of various plant polyphenols and tannins. 

With its excellent antioxidant properties, it is widely used in various fields such as food preservation and preservation, skincare antioxidant products, drug research and development, and its market attention continues to rise. In modern industry, gallic acid is mainly prepared through various process routes such as acid hydrolysis, alkaline hydrolysis, fermentation, and enzymatic methods to improve extraction efficiency and purity. 

Research Nester data shows that in 2024, the market size of gallic acid will exceed 85.38 million US dollars, and it is expected to reach 165.03 million US dollars by 2037, with a compound annual growth rate of 5.2% during the forecast period.

Source: pixabay

3. Other functions of gallic acid

Modern research has also found that gallic acid has antioxidant, antihypertensive, and gastrointestinal protective effects.

1) Antioxidant

Gallic acid has high anti free radical potential, with each molecule capable of reducing 6 DPPH free radicals. According to the measurement of equivalent antioxidant capacity (TEAC I-III), total free radical capture antioxidant parameter (TRAP), photochemical luminescence (PCL), and plasma iron reduction capacity (FRAP) of Trolox, gallic acid has better antioxidant effect than commonly used antioxidants such as ascorbic acid and Trolox. Multiple studies have confirmed that GA and its derivatives have better antioxidant efficiency compared to caffeine, protocatechuic acid, sesamin, and other substances. In the food industry, GA is widely used as a potent antioxidant to prevent spoilage at various stages of food preparation, storage, and transportation.

2) Antihypertensive treatment

Research has shown that GA can lower blood pressure and promote vasodilation by improving endothelial function and promoting nitric oxide production. In addition, GA can inhibit the activity of angiotensin-converting enzyme, thereby reducing the formation of angiotensin II (a potent vasoconstrictor). In addition, its anti-inflammatory properties help reduce vascular inflammation and further enhance its anti hypertensive efficacy.

3) Gastrointestinal protection

Gallic acid can protect the gastrointestinal mucosa from ulcer damage through various mechanisms, including reducing gastric acid secretion, inducing the release of endogenous antioxidants and defense factors such as SOD, CAT, endothelial nitric oxide synthase (e-NOS), and prostaglandin E2 (PGE2), as well as reducing oxidative stress and lipid peroxidation.