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 22, 2022.
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.
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
Nobiletin 32 mcM was shown to decrease the production of proinflammatory cytokines in mouse J774A macrophages.Lin 2003
Nobiletin 50 mg/kg intravenously for 1 week prior to liver transplantation suppressed inflammatory response in rats, with less hepatocyte swelling and inflammatory cell infiltration and decreased ALT, AST, and lactate dehydrogenase compared with a group receiving saline only.Wu 2017
Antiobesity activity
Animal data
Nobiletin 17 mg/kg/day for 16 weeks improved glucose tolerance, insulin resistance, and total cholesterol levels in mice fed a high-fat diet, but did not affect food intake, body weight, or adiposity.Kim 2017 In a 5-week study of mice administered nobiletin 100 mg/kg/day, there was a decrease in body weight and fat mass without a reduction in food intake.Lee 2010
Bone loss
Animal data
In a study evaluating the effects of nobiletin on bone loss and arthritis in DBA/1J mice, suppression of reductions of whole bone mineral density comparable to that with 17beta-estradiol was observed, suggesting a role in prevention or treatment of osteoclastogenesis-related disorders, including osteoporosis.Murakami 2007
Cardiovascular activity
Animal data
In rats with streptozotocin-induced diabetes, 4 weeks of nobiletin 10 or 25 mg/kg orally daily resulted in improved mean arterial pressure, heart rate, and left ventricular end diastolic pressure. The 25 mg/kg dose also improved maximal left ventricular systolic pressure.Parkar 2016
CNS effects
Animal data
Nobiletin has been shown to have antioxidant and antidegenerative effects. The effects of nobiletin on cholinergic neurodegeneration in mice have been studied. In one study, intraperitoneal administration of 50 mg/kg/day for 11 days resulted in improvement in impaired memory.Nakajima 2007
When nobiletin was administered to rats for 9 days prior to the induction of brain ischemia, an increase in the neuroprotective effects of propofol was observed, with a decrease in the infarct area, apoptotic cell counts, and brain edema.Zheng 2017 In a study of rats with 1-methyl-4-phenylpyridinium (MPP)–induced Parkinson disease, intraperitoneal injections of nobiletin at doses of 1, 10, and 20 mg/kg for 7 days resulted in variable effects. A dose of 10 mg/kg prevented MPP-induced neuronal death compared with controls (P<0.01); however, the 1 and 20 mg/kg dosages did not result in significant differences.Jeong 2015
Nobiletin may have antidepressant activity, as it has a similar mechanism as the antidepressant minaprine, which has demonstrated effects in the hippocampus of mice.Nakajima 2007
Dosing
There are no specific dosing recommendations for nobiletin.
Interactions
Based on in vitro and in vivo data, nobiletin suppresses platelet activity, (Vaiyapuri 2015) and therefore may increase the bleeding risk of known antiplatelet or antithrombotic agents. Nobiletin is metabolized via cytochrome P450.
Adverse Reactions
There are no known adverse reactions associated with nobiletin.
Toxicology
Safety data sheets state that the lowest dose of nobiletin that caused a toxic effect in a mouse model was 25 mg/kg of body weight if administered intraperitoneally and 70 mg/kg of body weight if administered orally.Cayman 2017
References
Disclaimer
This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.
This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.
Further information
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