The pharmacological mechanism of Citrus Bioflavonoids is characterized by multi-targets and multi-pathways, the following is a systematic combing of its core mechanism from molecular to cellular level:
1. Antioxidant mechanism
Free radical scavenging
Phenolic hydroxyl effect: the A-ring 5.7-dihydroxyl structure of flavonoids (e.g., hesperidin, naringin) endows it with strong reducing properties, which can directly neutralize free radicals such as DPPH and ABTS+.
Enzyme system regulation: activate superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) to enhance the cell’s own antioxidant capacity.
Metal chelation: inhibit Fe²⁺/Cu²⁺-induced Fenton reaction and 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.
4. Regulation of gastrointestinal function
Hormone regulation
Pro-secretin: increase secretion of gastrin (GAS) and gastric motrin (MTL), accelerate gastric emptying.
Inhibitory inhibitory hormone: inhibit the release of vasoactive intestinal peptide (VIP), relieve excessive intestinal spasm.
Smooth muscle regulation
Blocks L-type calcium channels, reduces Ca²⁺ concentration in intestinal smooth muscle cells, relieves acetylcholine-induced spasm.
Activate M3 receptor, enhance the smooth muscle tone of gastric fundus, improve the symptoms of gastroparesis.
5. Antibacterial and antiviral mechanism
Bacterial inhibition
Cell wall disruption: insertion of flavonoids into bacterial cell membrane, leading to increased permeability and leakage of contents.
Metabolic interference: Inhibit bacterial DNA rotary enzyme (Topoisomerase), blocking DNA replication.
Virus inhibition
HA blockade: Binds to influenza virus hemagglutinin (HA) and prevents viral adsorption to host cells.
Protease inhibition: Inhibits HIV protease activity and interferes with maturation of viral particles.
Other mechanisms of action
Hypoglycemia: regulates voltage-gated potassium channels (Kv), affects calcium inward flow in pancreatic β-cells, and promotes insulin secretion.
Immunomodulation: Enhance macrophage phagocytic activity, promote lymphocyte proliferation, enhance NK cell toxicity.