Nootkatone Natural Sesquiterpene Ketone: Combines Insect Repellent Efficacy with Pleasant Citrus Scent

1. Description

Nootkatone is a naturally occurring sesquiterpene ketone initially isolated from grapefruit juice and peel oil. It appears as a white to pale yellow crystalline powder or a colorless to pale yellow liquid and has a characteristic citrus and grapefruit aroma. It is soluble in DMSO (20 mg/mL), DMF (33 mg/mL), and ethanol (33 mg/mL), and slightly soluble in water. It should be stored at 2–8°C in a light-protected, sealed, and dry container; the powder form can be stored for up to 3 years at –20°C. The U.S. Food and Drug Administration (FDA) lists it as a food additive generally recognized as safe (GRAS).

2. Application

(1) Food and Beverage Industry: Used as a flavoring agent and flavor enhancer in beverages, frozen dairy products, baked goods, and fruit-flavored products to impart a grapefruit flavor.

(2) Fragrance and Flavor Industry: Widely used in perfumes, cosmetics, and personal care products to provide citrus-like aromatic characteristics.

(3) Pest Control Research: Used in the development of repellents and insecticides targeting pests such as mosquitoes, lice, fleas, ticks, and termites.

(4) Research Applications: Used as an analytical standard for quantitative analysis and pharmacological experiments; serves as a tool compound in metabolic studies, platelet function research, and neuroprotective studies.

3. Main Efficacy

(1) Antiparasitic and insecticidal activity: It exhibits lethal effects on mosquitoes, lice, and fleas, with half-lethal concentrations (LC₅₀) of 0.0046%, 0.0029%, and 0.0061% w/v, respectively. Pretreatment of wood reduces the tunnel length, feeding intake, and survival rate of Formosan termites.

(2) Antiplatelet aggregation activity: Inhibits collagen-, thrombin-, and arachidonic acid-induced platelet aggregation in a dose-dependent manner within the concentration range of 10–100 μM, with nearly complete inhibition at the highest concentration.

(3) Metabolic modulatory effects: It dose-dependently activated AMPKα1 and AMPKα2 in C2C12 mouse myoblasts. In mice fed a high-fat, high-sucrose diet, oral administration of 0.1–0.3% dose-dependently reduced body weight and blood glucose levels.

(4) Anti-inflammatory and neuroprotective effects: In a lipopolysaccharide-induced Alzheimer’s disease mouse model, a 10 mg/kg dose improved cognitive impairment, reversed neuronal degeneration and astrocyte activation, and reduced the expression of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α in the hippocampus.

(5) Antioxidant Effects: It exhibits antioxidant activity, scavenges free radicals, and protects cells from oxidative stress damage.