Nobiletin

Scientific Name(s): 2-(3,4)-dimethoxyphenyl)-5,6,7,8-tetramethoxychromen-4-one
Common Name(s): Hexamethoxyflavone

Medically reviewed by Drugs.com. Last updated on Aug 23, 2021.

Clinical Overview

Use

Nobiletin has been shown to exhibit antioxidant, anti-inflammatory, antitumor/cancer, and antiangiogenic activity in vitro and in vivo. Animal and in vitro data also demonstrate nobiletin's potential ability to suppress bone loss, lower cholesterol and atherosclerosis, and improve hyperglycemia and insulin resistance.

Dosing

There are no specific dosing recommendations for nobiletin.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

There are no known adverse reactions associated with nobiletin.

Toxicology

No data.

Scientific Family

• Flavone
• Flavonoid

Botany

Nobiletin is found in the peel of fruits of the Citrus species (eg, king orange [Citrus nobilis], seville orange [Citrus aurantium]), and of the round kumquat (Fortunella japonica).NCBI 2017

History

Nobiletin was discovered by Kwong-Fong Tseng in the 1930s. Nobiletin was isolated from an oily matter from the Chinese drug chen-pi (made from the peel of C. nobilis, Lour [mandarin orange]) using a cold methanol extraction technique.Tseng 1938

Chemistry

Nobiletin is classified as a flavonoid based on its structure of 2-phenylchromen-4-one.NCBI 2017 It contains 6 methoxyl groups responsible for increased lipophilicity.Huang 2016, Li 2014 Nobiletin is a colorless solid with needle-like structures, and has a bitter taste.Kuroda 2016, Sasaki 2002

Uses and Pharmacology

Nobiletin has been shown to exhibit antioxidant, anti-inflammatory, antitumor/anticancer, and antiangiogenic activity in vitro and in vivo.NCBI 2017 Animal and in vitro data also demonstrate nobiletin's potential ability to suppress bone loss, lower cholesterol, reduce atherosclerosis, and improve hyperglycemia and insulin resistance.Lee 2010, Murakami 2007, Sasaki 2002, Whitman 2005

Anticancer activity

Animal and in vitro data

Nobiletin was shown to have a dose-dependent suppressive effect on the proliferation of A549 lung cancer cells.Luo 2008

Administration of a mixture of nobiletin and its major metabolites for 19 weeks to mice with colitis-associated colon carcinogenesis resulted in a decrease in cell cycle progression in the colon tissue, which was at least partially related to down-regulation of inducible nitric oxide synthase (iNOS).Wu 2017

Anti-inflammatory activity

Animal and in vitro data

The anti-inflammatory effects of nobiletin on human synovial fibroblasts and mouse macrophage J774A have been studied.Lin 2003 Nobiletin, at a concentration of 64 mcM, inhibited cyclooxygenase-2 (COX-2) production by 50%. A study of the effect of nobiletin on neuroinflammation found that nobiletin 50 mcM inhibited lipopolysaccharide (LPS)-induced iNOS expression by 71% compared with LPS alone.Cui 2010 Nobiletin was also shown to have a positive inhibitory effect on skin inflammation.Murakami 2000