The antioxidant mechanism of hydroxytyrosol

Hydroxytyrosol, a natural polyphenolic antioxidant widely present in plant-based foods such as olive oil, exhibits potent antioxidant activity. Its antioxidant mechanisms primarily involve the scavenging of reactive oxygen species (ROS) and the protection of mitochondria, which are detailed as follows:

I. Scavenging of Reactive Oxygen Species (ROS)

1. Hydrogen Atom Donation

Hydroxytyrosol contains phenolic hydroxyl groups in its molecular structure, with hydrogen atoms on these groups being highly reactive. When ROS such as superoxide anion radicals (O₂⁻·), hydrogen peroxide (H₂O₂), and hydroxyl radicals (·OH) are generated in the body, hydroxytyrosol rapidly donates hydrogen atoms to these radicals, reducing them to relatively stable molecules while transforming itself into stable phenoxyl radicals.

For example, hydroxytyrosol reacts with hydroxyl radicals to convert them into water, as shown in the reaction:

HO-Tyr + ·OH → HO-Tyr· + H₂O

(where HO-Tyr represents hydroxytyrosol and HO-Tyr· represents the phenoxyl radical). This hydrogen donation effectively interrupts free radical chain reactions, reducing ROS production and accumulation.

2. Electron Transfer

In addition to hydrogen atom donation, hydroxytyrosol scavenges ROS through electron transfer. The conjugated system in its molecule allows electron delocalization, enabling electron transfer to radicals upon encounter. This alters the electron cloud density of radicals, reducing their reactivity.

Taking the superoxide anion radical as an example, hydroxytyrosol can accept an electron from O₂⁻·, reducing it to oxygen while forming corresponding oxidation products, thus scavenging the superoxide anion.

3. Metal Ion Chelation

Many ROS are generated through metal ion catalysis—for instance, iron (Fe²⁺) and copper (Cu²⁺) ions can catalyze the Fenton reaction of H₂O₂ to produce highly oxidative hydroxyl radicals. Hydroxytyrosol contains multiple ortho-phenolic hydroxyl groups that form stable chelates with metal ions.

By chelating metal ions, hydroxytyrosol inhibits their catalytic activity and reduces ROS production. For example, binding to Fe²⁺ lowers its concentration, suppressing the Fenton reaction and indirectly scavenging ROS.

II. Protective Effects on Mitochondria

1. Maintenance of Mitochondrial Membrane Potential Stability

Mitochondrial membrane potential is a critical indicator of normal mitochondrial function. Excessive ROS production causes a decline in mitochondrial membrane potential, damaging mitochondrial structure and function. Hydroxytyrosol maintains membrane potential stability by scavenging ROS and reducing oxidative damage to lipids and proteins on the mitochondrial membrane.

Stable mitochondrial membrane potential ensures normal energy metabolism and substance transport in mitochondria, providing sufficient energy support for cells.

2. Inhibition of Mitochondrial Permeability Transition Pore (mPTP) Opening

The mitochondrial permeability transition pore (mPTP) is a nonspecific channel on the inner mitochondrial membrane. Under stressors like ROS, excessive mPTP opening leads to mitochondrial swelling, membrane rupture, and release of apoptosis-related factors (e.g., cytochrome c), triggering cell apoptosis.

Hydroxytyrosol reduces the risk of excessive mPTP opening by scavenging ROS. Additionally, it may directly act on mPTP-associated proteins to regulate their activity, further inhibiting mPTP opening and protecting mitochondrial integrity.

3. Promotion of Mitochondrial Biogenesis

Hydroxytyrosol activates signaling pathways related to mitochondrial biogenesis, such as the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) pathway. PGC-1α is a key transcriptional coactivator that regulates the expression of multiple genes involved in mitochondrial biogenesis.

By activating the PGC-1α pathway, hydroxytyrosol promotes mitochondrial biogenesis, increasing mitochondrial quantity and function. This enhances cellular energy metabolism and antioxidant capacity, enabling better resistance to ROS-induced damage.