What is Nobiletin?
Nobiletin is a herb flavonoid found in orange, lemon, and other citrus fruits. It is a naturally occurring phenolic compound (polymethoxylated flavone) that can support your bone health, fight cancer, lower cholesterol and even provide an anti-aging property.
Pure Nobiletin has a white to off-white powder appearance; its taste is bitter, it is usually soluble in methanol, and can only be sparingly soluble in water and ether.
Nobiletin Sources
Nobiletin naturally occurs in many plant sources. However, citrus fruits are one of the best food sources of Nobiletin, especially those that are darker and more vibrant.
Citrus Aurantium, aka bitter orange, is the most popular resource of Nobiletin in the market.
Nobiletin’s other food sources include blood orange, lemon, tangerine, and grapefruit.
There is a great variety of citrus containing many types of flavonoids. However, of these citrus fruits, the highest natural source of Nobiletin is Tachibana, which is a type of mandarin orange. It contains about 54.3 mg per 100 grams if both the pulp and peel are included.
Citrus peel is the part with the highest content of Nobiletin.
Dansey tangerine peel is the most abundant source, containing 507 mg per 100 grams.
Regular orange juice contains 0.07 to 0.20 mg of Nobiletin per 100 mL.
Lemons and grapefruit have a minuscule amount of Nobiletin.
Constituents of Citrus Aurantium Extract
Citrus Aurantium (bitter orange) is a plant belonging to the family Rutaceae; it has extensive use in Traditional Chinese practices for everything from supporting metabolic function to promoting feelings of well-being and even promoting cognitive function!
Citrus Aurantium is rich in flavonoids, vitamin C, and volatile oil. In addition, it contains flavonoids such as apigenin powder, diosmetin 98%, and Luteolin. However, its nobiletin content is considered the most important biologically active constituent of primary health benefits.
Nobiletin VS luteolin
Nobiletin is a polymethoxyflavonoid mainly found in oranges, lemons, and other citrus fruits.
Luteolin powder (CAS#491-70-3) is a naturally occurring glycosylated form of flavonoids found in different fruits and vegetables. Such as celery, apple peel, onion leaves, and chrysanthemum.
Both Nobiletin and Luteolin have antioxidant, anti-inflammatory, neuroprotection, and memory-enhancing effects. What makes it different is that Nobiletin can also be used in weight loss and adjusting the sleep-wake cycle, which is very popular.
The metabolic properties of Nobiletin are distinct from Luteolin because of their wide distribution and accumulation in tissue. Nobiletin stays in the body longer and works better.
Nobiletin VS tangeretin
Both Nobiletin and tangeretin belong to a class of polymethoxy flavonoids mainly found in citrus fruits.
Nobiletin is a nonpolar polymethoxylated flavone. Its chemical formula is similar to tangeretin and has a typical flavonoid structure and six methoxyl groups, one more than tangeretin. This high level of methoxylation increases the hydrophobicity of tangeretin.
Nobiletin and tangeretin have various similar pharmacological actions. The ordinary benefits include heart health, neuroprotective effects, antioxidant and anti-inflammatory effects. However, Nobiletin tends to be more biologically active than tangerine in anti-inflammatory potential.
Nobiletin and melatonin
Both melatonin and Nobiletin can help with the circadian rhythms and with sleep.
Melatonin is a sleep-inducing hormone made by the brain in response to periods of darkness. As a hormone, the primary benefit of melatonin is to help a person’s body transition to sleep.
Melatonin should work on the central circadian clock. It is a form that provides support for falling asleep and staying asleep. However, Nobiletin is a natural compound that directly activates circadian cell oscillators and may act on the peripheral clock. In a way that is more natural and gentle on your body system, which helps you fall asleep naturally and sleep better.
How does Nobiletin work?
Chemical compounds are biologically active based on their structures and metabolism.
Without a glycoside moiety, Nobiletin is quickly absorbed due to its high lipophilic nature and high permeability.
Nobiletin in the Neural Systems
Accumulated amyloid β contributes to the pathogenesis of Alzheimer’s disease,
Studies have shown that Nobiletin can improve such impairments in amyloid precursor protein transgenic mice. In addition, Nobiletin can also alleviate the aging cognitive impairment and reduce tau phosphorylation and oxidative stress in mice with accelerated aging.
The NMDA receptor plays a vital role in memory & learning. Some reports in PC12 cells show that Nobiletin can upregulate mRNA expression of NMDA receptor subunits NR1, NR2A, NR2B, and c-FOS. Nobiletin can also improve learning disability stimulated by NMDA receptor antagonists by activating extracellular signaling mediated kinases.
Nobiletin in the Digestive System
Nobiletin is involved in the control of ammonia in varying diets and regulates urea circulatory activity through C/ebp-dependent regulatory mechanisms. Nobiletin regulates lipid and glucose metabolism to improve dyslipidemia, obesity, hyperglycemia, and insulin resistance. In addition, Nobiletin reduces plasma triglycerides, weight gain, and white adipose tissue body weight.
Nobiletin has been shown to improve hemodynamic parameters, oxidative stress, and vascular reactivity in rats and down-regulate the expression of MMP-2, MMP-9, and collagen.
The study data showed that Nobiletin reduced the secretion of apoB100 by activating MAPKerk, enhancing LDLR expression, weakening MTP activity and DGAT1/2 expression
Nobiletin in the Skeleton System
The hormone estrogen is vital to bone homeostasis. Studies have shown that Nobiletin may block mass bone decline caused by estrogen deficiency and inhibit bone resorption throughout the body. Nobiletin may inhibit il-1-induced bone resorption and osteoclast formation. Furthermore, Nobiletin down-regulates the expression of the NF-κB signal path, COX-2, and PGE2.
Nobiletin Manufacturing process
The Manufacturing process of Nobiletin involves taking citrus Aurantium fruit as the raw material. The fruit is then put through a spray drying process, dry extract, crushing, and sieving to fine powders. The finished product has a 98% purity. To ensure quality, the finished product goes through a series of tests. Once it passes these tests, it is warehoused until it needs to be shipped.
Potential Benefits of Nobiletin
Nobiletin plays a significant role in many activated patterns in the human body. It has various pharmacological activities, such as antioxidant, anti-diabetes, anti-inflammatory, anti-cancer, nerve-protecting, etc.
Brain health
According to some reports, Nobiletin can reduce learning and memory problems, improve I/R damage, and decrease dopaminergic neuronal production. It also helps protect brain cells against damage and improve overall cognitive function by reducing tau phosphorylation and oxidative stress.
Anti-cancer
Nobiletin has been shown to exert anti-cancer effects on various cancer cells.
Nobiletin may induce apoptosis and cell cycle blocking in cancer cells. In addition, Nobiletin can also inhibit oncogene factors such as STAT3, NF-κB, etc.
In addition, Nobiletin upregulates cancer suppressors such as microRNA-7 and -200b during the treatment.
Improve sleep
Nobiletin is a clock amplitude-enhancing small molecule (CEM) that regulates circadian rhythm systems.
Many studies have shown that the compound effectively improves an individual’s circadian rhythm or sleep-wake cycle, which is the unique feature of Nobiletin.
Weight loss
Nobiletin may salvage insulin resistance and restore lipid metabolism disorders. By lowering cholesterol and triglyceride levels and preventing insulin resistance, it is believed that Nobiletin can promote weight loss in obese and overweight people. It also helps to reduce excessive fat buildup in the subcutaneous layer.
Nobiletin side effects
There is currently no data on the severe side effects of Nobiletin. However, some users may experience mild symptoms such as stomach pain and irritation during the initial dose.
Nobiletin dosage
There are not enough clinical trial data to prove the specific dose of Nobiletin. However, the daily dose of Nobiletin may be at least 10 mg, preferably at least 20 mg.
Life Extension recommends taking a 50-milligram Coquitlam capsule once a day. Take it before bed to restore your circadian rhythm and aid sleep.
For pregnant and lactating women and those who are taking other medications, please consult your physicians before using them.
Nobiletin Prices
Nobiletin is very expensive in the market. The average price range is about USD 6500-7200/kg for different quantities. Therefore, Cima will provide the most competitive price for you.
Where to buy bulk Nobiletin powder
Wuxi Cima Science is a professional nutritional manufacturer with three plants in two provinces.
Our company offers the best quality products at the most reasonable price. We also provide shipping services through air, sea, or express delivery like FedEx for your convenience.
If you have any inquiries about the Nobiletin ingredient, please feel free to contact us.
FAQ
When to take Nobiletin?
It’s better to take it before bedtime with melatonin together to restore your circadian rhythm and help with sleep.
If you’re not taking a supplement with melatonin, it is probably a better time to take it at dinner.
Popular nobiletin supplements in the market
- Life Extension — nobiletin+melatonin formulation, help circadian cycle.
- Nootropic —pure citrus-aurantium extract (nobiletin powder 50mg),supporting the cardiovascular system
References
- Nguyen-Ngo C, Salomon C, Quak S, Lai A, Willcox JC, Lappas M. Nobiletin exerts anti-diabetic and anti-inflammatory effects in an in vitro human model and in vivo murine model of gestational diabetes. Clin Sci (Lond). 2020 03 27;134(6):571-92. https://pubmed.ncbi.nlm.nih.gov/32129440/
- Yang X, Wang H, Li T, Chen L, Zheng B, Liu RH. Nobiletin Delays Aging and Enhances Stress Resistance of Caenorhabditis elegans. Int J Mol Sci. 2020 Jan 4;21(1):E341. https://pubmed.ncbi.nlm.nih.gov/31948007/
- Ren, X., Ma, Y., Wang, X., Xu, X., Wu, P., Liu, W., Zhang, K., Goodin, S., Li, D., & Zheng, X. (2021). Nobiletin Inhibits Cell Growth, Migration and Invasion, and Enhances the Anti-Cancer Effect of Gemcitabine on Pancreatic Cancer Cells. In Natural Product Communications (Vol. 16, Issue 4, p. 1934578X2110040). SAGE Publications. https://doi.org/10.1177/1934578×211004062
- Seoka M, Ma G, Zhang L, Yahata M, Yamawaki K, Kan T, et al. Expression and functional analysis of the nobiletin biosynthesis-related gene CitOMT in citrus fruit. Sci Rep. 2020 09 17;10(1):15288. https://pubmed.ncbi.nlm.nih.gov/32943728/
- Whitman SC, Kurowska EM, Manthey JA, Daugherty A. Nobiletin, a citrus flavonoid isolated from tangerines, selectively inhibits class A scavenger receptor-mediated metabolism of acetylated LDL by mouse macrophages. Atherosclerosis. 2005 Jan;178(1):25-32. https://pubmed.ncbi.nlm.nih.gov/15585197/
- Whitman SC, Kurowska EM, Manthey JA, Daugherty A. Nobiletin, a citrus flavonoid isolated from tangerines, selectively inhibits class A scavenger receptor-mediated metabolism of acetylated LDL by mouse macrophages. Atherosclerosis. 2005 Jan;178(1):25-32. https://pubmed.ncbi.nlm.nih.gov/15585197/
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