Diosmetin NOX4 Suppressor: Attenuates Vascular Endothelial Oxidative Stress via NADPH Oxidase 4 Inhibition

1.  Description

Diosmetin is a naturally occurring methoxyflavonoid compound, a 4'-methoxy derivative of luteolin, and the aglycone of the flavonoid glycoside diosmetin. Its molecular formula is C₁₆H₁₂O₆, and its molecular weight is approximately 300.26 Da. It appears as a yellow powder or yellow needle-like crystals, with a melting point of 256–258°C. Regarding solubility, it is soluble in DMSO (≥60 mg/mL), slightly soluble in organic solvents such as dichloromethane and acetone, and poorly soluble in water. It should be stored in a sealed container at 2–8°C away from light; the powder form can be stored for 3 years at -20°C. This compound occurs naturally in various plants, including lemons, citrus fruits, peppermint, and oregano.

2.  Application

(1) Analytical Standards and Research Tools: Used as analytical standards for content determination, identification, pharmacological experiments, and bioactivity screening, as well as in research experiments such as cellular administration, gavage studies, and internal quality control at pharmaceutical companies.

(2) Oncology Research: Used in the B16/F10 mouse melanoma model to study tumor growth inhibition and the blocking of tumor angiogenesis. In HepG2 liver cancer cells, it is used to investigate the mechanisms underlying the induction of apoptosis.

(3) Inflammation and Immunology Research: Used in acute pancreatitis models to evaluate effects on serum amylase and lipase levels and the secretion of pro-inflammatory cytokines. In acute liver injury mouse models, it is used to study its antioxidant, anti-inflammatory, and anti-apoptotic protective effects.

(4) Respiratory Disease Research: Used in an ovalbumin-induced chronic asthma mouse model to investigate its inhibitory effects on airway remodeling, goblet cell hyperplasia, and collagen deposition.

(5) Oxidative Stress Research: Used in an AAPH-induced oxidative stress model to investigate its inhibitory effects on reactive oxygen species (ROS) and malondialdehyde (MDA) levels in red blood cells.

(6) Drug Metabolism Research: As inhibitors of cytochrome P450 enzymes (CYP1A1 and CYP1B1), they are used to study drug interactions and the activation mechanisms of carcinogens.

3. Main Efficacy

(1) Antioxidant effects: Concentration-dependent inhibition of reactive oxygen species (ROS) production, reduction of malondialdehyde levels, scavenging of free radicals, and protection of cells from oxidative stress damage. Its antioxidant activity is associated with its iron-chelating capacity.

(2) Anti-inflammatory effects: Inhibits the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6. Exerts anti-inflammatory effects by inhibiting NF-κB activation and demonstrates protective effects in a model of endotoxin-induced acute liver failure.

(3) Antitumor activity: Concentration-dependently inhibits the proliferation of HepG2 liver cancer cells and induces apoptosis. In skin cancer models, it inhibits tumor development and tumor angiogenesis.

(4) Cytochrome P450 Enzyme Inhibition: Effectively inhibits CYP1A1 and CYP1B1 enzyme activity (Ki values of 89 nM and 16 nM, respectively), suppresses carcinogen activation, and influences the pharmacokinetics of combination drug therapy.

(5) Cardiovascular protection: Exhibits vasodilatory effects and inhibits dopamine uptake in neuroblastoma cells, which may be related to the regulation of vascular tone in vivo.

(6) Bone density protection: Studies indicate it has a protective effect on bone density.

(7) Anti-apoptotic effects: Demonstrates anti-apoptotic activity in a model of endotoxin-induced acute liver failure.

(8) Anti-asthmatic effects: In chronic asthma models, it inhibits airway goblet cell hyperplasia and collagen deposition, and reduces the number of eosinophils and neutrophils in bronchoalveolar lavage fluid.