Antioxidation and Liver Health

By Cocer Peptides         26 days ago.

The liver, as a central organ for metabolism and detoxification in the human body, undertakes critical functions such as biosynthesis, energy storage, and elimination of harmful substances. Oxidative stress, toxin accumulation, and metabolic disorders are primary triggers of liver injury, fatty liver, and hepatic fibrosis. The core of liver protection, detoxification, and antioxidative stress lies in maintaining hepatocyte functional integrity, enhancing detoxifying enzyme activity, and scavenging excessive free radicals. Peptide substances, with their high biological activity and target specificity, can specifically regulate hepatic metabolic pathways, protect hepatocytes from oxidative damage, and promote biotransformation and excretion of toxins, emerging as innovative tools for preventing and intervening in liver diseases—demonstrating significant potential in alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), and drug-induced liver injury.

Figure 1 Risk factors of non-alcoholic fatty liver disease (NAFLD). Source: A Review on the Protecting Effects and Molecular Mechanisms of Berries Against a Silent Public Health Concern: Non-Alcoholic Fatty Liver Disease (2024).

Core Application Areas

1. Hepatic Protection: Maintaining Hepatocyte Structural and Functional Integrity

Peptide substances construct a protective barrier for the liver through anti-apoptosis, pro-repair, and regulation of hepatocyte metabolism.

Inhibition of hepatocyte apoptosis

Mitochondria-targeted peptides (e.g., SS-31) embed in hepatic and mitochondrial membranes, stabilizing mitochondrial membrane potential and inhibiting the release of cytochrome C and activation of caspase-3. This reduces oxidative stress- or drug-induced hepatocyte apoptosis. Their protective effect on mitochondrial complexes maintains hepatocyte energy metabolism, particularly mitigating hepatic lobular necrosis in ischemia-reperfusion injury.

Copper peptides (e.g., GHK-Cu) promote phosphorylation of hepatocyte growth factor receptors, activating downstream pathways to accelerate DNA repair and organelle regeneration in damaged hepatocytes. They also inhibit transforming growth factor-β (TGF-β)-mediated fibrogenic signaling, delaying the progression of hepatic fibrosis.

Hepatic membrane protection

Liver-protective peptides reduce trans-membrane penetration of endotoxins and toxic metabolites by enhancing the expression of tight junction proteins in hepatic membranes, decreasing direct damage to hepatocytes by inflammatory factors. This makes them suitable for early intervention in alcoholic liver disease.

Figure 2 Nuclear factor erythroid 2-related factor 2 (NRF2) regulation and NRF2-mitochondrial interplay in chronic liver disease. Source: The Roles of NFR2-Regulated Oxidative Stress and Mitochondrial Quality Control in Chronic Liver Diseases (2023).

2. Detoxification: Enhancing Hepatic Biotransformation and Excretion Functions

The liver serves as the body’s detoxification organ, responsible for metabolizing and eliminating exogenous substances such as toxins and drugs. Liver-protective peptides participate in hepatic detoxification processes, promoting the metabolism and excretion of toxic substances to reduce their hepatotoxic effects.

Activation of Phase I/II metabolic pathways

Glutathione (GSH, such as GSH precursor peptides), as a vital antioxidant and conjugation substrate in hepatocytes, directly participates in Phase II detoxification reactions by binding to electrophilic toxins to form water-soluble complexes excreted via bile. Certain peptides increase intracellular GSH reserves and enhance the activity of glutathione S-transferase (GST), accelerating detoxification of acetaminophen and alcohol metabolites (e.g., acetaldehyde).

Nicotinamide adenine dinucleotide (NAD, such as NAD-related peptides), as a coenzyme for redox reactions, participates in catalytic reactions of Phase I enzymes such as alcohol dehydrogenase and cytochrome P450, promoting the conversion of lipophilic toxins into polar metabolites. Increased NAD levels enhance the liver’s metabolic efficiency for drugs and toxins.

Regulation of bile acid metabolism

Liver-protective peptides (e.g., Pnc 27) are hypothesized to activate farnesoid X receptor (FXR) or pregnane X receptor (PXR), regulating the expression of key enzymes and transporters involved in bile acid synthesis. This promotes bile acid excretion, reduces intrahepatic accumulation of toxic bile acids, and improves the pathological state of cholestatic liver disease.

3. Antioxidative Stress: Scavenging Free Radicals and Repairing Oxidative Damage

Hepatocyte injury caused by oxidative stress is a critical step in liver disease progression. Peptide substances exert protective effects through multi-target antioxidation.

Free radical scavenging and enzyme activity regulation

Glutathione directly neutralizes free radicals such as superoxide anions and hydrogen peroxide. As a substrate for glutathione peroxidase, it catalyzes the reduction of lipid peroxides, reducing membrane lipid peroxidation damage.

Antimicrobial peptides (e.g., LL37), beyond their antimicrobial functions, inhibit NADPH oxidase to reduce intracellular reactive oxygen species (ROS) production in hepatocytes, blocking oxidative stress-induced pathway activation and thus inhibiting hepatocyte apoptosis and inflammatory factor secretion.

Mitochondrial function protection

Mitochondria-targeted peptides (e.g., SS-31) maintain mitochondrial dynamic balance, reducing mitochondrial fragmentation and dysfunction. This ensures stable energy supply in hepatocytes and indirectly lowers the risk of oxidative damage to DNA and proteins.

Conclusion

The application of peptide substances in antioxidation and liver health focuses on core mechanisms of hepatocyte protection, detoxification pathway enhancement, and oxidative stress regulation, providing multidimensional solutions for the prevention and treatment of liver diseases. By targeting mitochondrial function, detoxifying enzyme systems, and redox balance, these substances not only directly scavenge free radicals and inhibit hepatocyte apoptosis but also reshape hepatic metabolic phenotypes through nuclear receptor regulation—demonstrating mechanistic advantages in the comprehensive management of fatty liver, liver injury, and hepatic fibrosis.

ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE SOLELY FOR INFORMATION DISSEMINATION AND EDUCATIONAL PURPOSES.

The products provided on this website are intended exclusively for in vitro research. In vitro research (Latin: *in glass*, meaning in glassware) is conducted outside the human body. These products are not pharmaceuticals, have not been approved by the U.S. Food and Drug Administration (FDA), and must not be used to prevent, treat, or cure any medical condition, disease, or ailment. It is strictly prohibited by law to introduce these products into the human or animal body in any form.