Neohesperidin, as the main flavonoid compound in citrus plants (such as grapefruit and lime), has a multi-target, multi-pathway pharmacological mechanism, and its core mechanisms are introduced from molecular to cellular level:
1. Antioxidant mechanism
Free radical scavenging
Phenolic hydroxyl effect: the A ring and B ring of new hesperidin are rich in phenolic hydroxyl, which can directly neutralize DPPH, ABTS+ and other free radicals and terminate the chain reaction.
Enzyme system regulation: activate superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), enhance the cell’s own antioxidant capacity.
Metal chelation: inhibit Fe²⁺/Cu²⁺-induced Fenton reaction, reduce hydroxyl radical (-OH) generation.
Oxidative stress modulation
Inhibits the generation of lipid peroxidation products (e.g. MDA) and protects cell membrane integrity.
Up-regulates nuclear factor E2-related factor 2 (Nrf2) expression and promotes the synthesis of antioxidant proteins (e.g. heme oxygenase-1).
2. Anti-inflammatory mechanism
Inflammatory signaling blockade
NF-κB pathway: inhibit IκB kinase (IKK) phosphorylation, reduce p65 nuclear translocation, and down-regulate transcription of pro-inflammatory factors such as TNF-α and IL-6.
MAPK pathway: block ERK1/2. p38 phosphorylation, inhibit inflammatory cascade response.
Inflammatory mediator regulation
Inhibit the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), and reduce the production of prostaglandin E2 (PGE2), NO and other inflammatory substances.
Promote the release of anti-inflammatory factor IL-10 to restore the pro-inflammatory/anti-inflammatory balance.
Regulation of lipid metabolism
Lowering cholesterol
Inhibit HMG-CoA reductase activity, reduce cholesterol synthesis.
Promote cholesterol transportation to liver for metabolism, increase HDL-C ratio.
3. Anti-Atherosclerosis
Inhibits oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation.
Reduces vascular endothelial damage and lowers the risk of atherosclerosis.
4. Neuroprotection and Improvement of Cognitive Mechanisms
Antioxidant defense
Reduce β-amyloid (Aβ)-induced oxidative damage to neurons.
Protect mitochondrial function, maintain ATP synthesis and support cellular metabolism.
Synaptic plasticity
Enhances the expression of synapse-associated proteins (e.g. Synapsin I) in the hippocampus to improve learning and memory.
Inhibit the degeneration of dopaminergic neurons, delaying the progression of Parkinson’s disease.
5. Other Mechanisms of Action
Regulate blood pressure: Promote nitric oxide (NO) production, dilate blood vessels, reduce peripheral resistance.
Protecting the liver: reducing hepatocellular damage and promoting hepatocellular regeneration.
Antibacterial and antiviral: inhibit bacterial and viral replication, protect animals from pathogens.