The antioxidant mechanism of phosphatidylserine

Phosphatidylserine (PS), an important phospholipid present in cell membranes, derives its antioxidant mechanisms from stabilizing membrane structures, regulating oxidative stress signals, and synergizing with antioxidant systems, providing multi-layered protection for cells. The following analysis explores its antioxidant mechanisms from a scientific perspective:

I. Maintaining Membrane Integrity: Blocking the "First Line of Defense" Against Oxidative Damage

The cell membrane is the first barrier against external oxidative attacks, and the distribution and structural properties of phosphatidylserine directly influence its antioxidant capacity:

Stabilizing the lipid bilayer structure: The negatively charged head group of phosphatidylserine forms electrostatic or hydrophobic interactions with other membrane lipids (e.g., phosphatidylcholine, cholesterol) and membrane proteins, enhancing the compactness and stability of the lipid bilayer. This structural reinforcement reduces the attack of reactive oxygen species (ROS, such as superoxide anions and hydrogen peroxide) on membrane lipids—ROS readily trigger lipid peroxidation (e.g., disrupting double bonds in unsaturated fatty acids). By maintaining the order of the membrane structure, phosphatidylserine lowers the probability of lipid molecules interacting with ROS, delaying the initiation of membrane lipid peroxidation.

Reducing oxidative damage to membrane proteins: Membrane proteins (e.g., receptors, transporters) are key targets of oxidative stress. Phosphatidylserine binds to specific domains of membrane proteins, stabilizing their spatial conformation and reducing ROS-induced protein denaturation (e.g., thiol oxidation, carbonylation). This ensures that membrane functions such as signal transduction and material transport remain unaffected by oxidation.

II. Regulating Intracellular Antioxidant Systems: Enhancing "Active Defense" Capabilities

Phosphatidylserine not only passively resists oxidation but also actively regulates intracellular antioxidant mechanisms, activating endogenous protective systems:

Activating the expression and activity of antioxidant enzymes: Intracellular antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) are core forces for ROS clearance. Studies have shown that PS can promote the gene expression of these antioxidant enzymes by regulating nuclear factor E2-related factor 2 (Nrf2) signaling pathways. It also enhances their catalytic activity (e.g., by maintaining the structure of the enzyme’s active center), improving the cell’s efficiency in scavenging ROS.

Modulating glutathione (GSH) metabolism: GSH, the most important non-enzymatic antioxidant in cells, directly neutralizes ROS and repairs oxidative damage. Phosphatidylserine promotes GSH synthesis (e.g., by increasing the activity of glutamate-cysteine ligase) while reducing GSH consumption, maintaining intracellular levels of reduced GSH, thereby enhancing the cell’s buffering capacity against oxidative stress.

III. Inhibiting Oxidative Stress-Related Signaling Pathways: Blocking Damage Cascades

When cells encounter oxidative stress, overactivated oxidative signals trigger a series of damage cascades (e.g., inflammation, apoptosis). Phosphatidylserine inhibits this process by interfering with key signaling molecules:

Downregulating pro-oxidant signaling pathways: Oxidative stress activates the mitogen-activated protein kinase (MAPK) family (e.g., JNK, p38), leading to the release of inflammatory factors (e.g., TNF-α, IL-6) and exacerbating oxidative damage. Phosphatidylserine inhibits the phosphorylation of the MAPK pathway, reducing the expression of inflammatory factors and breaking the vicious cycle of "oxidative stress → inflammation → more severe oxidation."

Inhibiting oxidation-triggered cell apoptosis: Sustained oxidative stress disrupts mitochondrial function (e.g., decreased mitochondrial membrane potential, release of cytochrome c), initiating apoptotic programs. Phosphatidylserine stabilizes mitochondrial membrane structures (e.g., reducing the opening of mitochondrial permeability transition pores), inhibits the release of pro-apoptotic factors from mitochondria, and decreases the activation of caspases (apoptosis-related proteases), thereby reducing oxidative stress-induced cell apoptosis.

IV. Synergistic Effects with Other Antioxidants

The antioxidant effect of phosphatidylserine is not isolated; it synergizes with fat-soluble antioxidants such as vitamin E and coenzyme Q10:

Enhancing targeted delivery of fat-soluble antioxidants: As a membrane component, phosphatidylserine binds to vitamin E and similar molecules via hydrophobic interactions, facilitating their efficient integration into cell membranes and enhancing direct inhibition of membrane lipid peroxidation.

Regenerating antioxidant molecules: After scavenging ROS, antioxidants like vitamin E are converted to oxidized forms. Phosphatidylserine assists in their reduction to active forms through electron transfer processes, extending the duration of antioxidant activity.

The antioxidant mechanisms of phosphatidylserine represent a comprehensive integration of "structural protection, system activation, signal regulation, and synergistic enhancement." By stabilizing cell membranes, activating endogenous antioxidant systems, and blocking oxidative stress signaling, it provides comprehensive oxidative defense for cells. This mechanism also offers a scientific basis for its applications in neuroprotection, anti-aging, and other fields.