What Is Naringenin Used For？

 Naringenin: A New Generation Of Immunomodulators

What is naringenin?

Naringenin Powder, extracted from pomelo peel, is a sweetener that is ring-opened and hydrogenated under alkaline conditions to form dihydrochalcones, which are 2000 times sweeter than sucrose. Naringenin is the aglycone of naringin, a naturally occurring flavonoid compound, which has a strong ability to regulate immunity, and is known as "a new generation of immune regulators". In addition to regulating immunity, naringenin also has antibacterial, anti-inflammatory, scavenging free radicals, anti-oxidation, cough and expectorant, lowering blood lipids, anti-tumor, treating liver diseases, inhibiting platelet aggregation and anti-arteriosclerosis. It is widely used in medicine, food and other fields.

What are the benefits of naringenin?

1. Inhibit bacteria
Naringenin Extract has inhibitory effects on Candida aureus, Escherichia coli, dysentery and typhoid bacillus, and also has inhibitory effects on fungi;
2. Anti-inflammatory
The inhibitory rate of naringenin on inflammatory factors reaches 30.67%. It can also inhibit the cyclooxygenase COX to reduce the synthesis of prostaglandin PGE2, inhibit the expression of COX-2, and reduce the inflammation of immune cells such as macrophages after activation. Cytokines TNF-α, IL-6 and IL-1β, etc.;
3. Antioxidant
Naringenin and naringin has anti-oxidation effect, inhibits LDL oxidation ability, scavenge free radicals through self-supply hydrogen oxidation, also has obvious scavenging ability for active oxygen O2-, and significantly enhances superoxide dismutase (SOD) activity;
4. Lower blood fat
Naringenin powder can reduce the content of serum TC, TG, LDL-C, increase serum HDL-C, balance the content of cholesterol in the body, and effectively reduce blood lipids;
5. Anti-tumor
Grapefruit extract can regulate the level of T lymphocytes in the body, enhance the effect of killing tumor cells, regulate the body's own anti-tumor ability, and also have an inhibitory effect on S180 sarcoma;
6. Antispasmodic and choleretic
Naringenin is a flavonoid compound that can promote the secretion of bile and help promote the health of the liver and gallbladder;
7. Regulate estrogen-like
Grapefruit extract powder can regulate cell proliferation, differentiation and metabolism, gene transcription in response to estrogen signaling, inhibit estrogen-sensitive tumor cells, reduce palmitic acidification of estrogen receptor α, and inhibit the activation of ERK/MAPK and PI3K/AKT pathways , reduced production of skeletal muscle differentiation markers.

Why is naringenin an immunomodulator?

1. Regulation of naringenin on TGF-β signaling pathway
The TGF-β signaling pathway is involved in the growth, differentiation, apoptosis and embryonic development of various cells, and plays an important role in the occurrence and development of tumors. The most common expression in tumor cells is TGF-β1, which acts as a ligand to bind to type I and type II receptors on the cell membrane surface. After binding to the type II receptor, the type I receptor is phosphorylated by the type II receptor, thereby phosphorylating the downstream effector proteins SMAD2 and SMAD3 in the cytoplasm. The phosphorylated SMAD2 and SMAD3 bind to SMAD4 and transfer to the nucleus Regulate the transcription of downstream genes[2]. SMAD7 is a negative regulator in the TGF-β/SMAD signaling pathway, and competes with SMAD3 for SMAD4, thus inhibiting the activation of SMAD3 on downstream gene transcription. In addition to relying on SMAD protein signal transduction In addition, TGF-β can also activate many other enzymes such as PI3K, 38 and small GTPases to transduce signals [1]. TGF-β can inhibit tumor growth and can also promote tumor progression. In the tumor immune response, TGF-β exerts a systemic immunosuppressive effect, suppresses the host immune ability, and can further aggravate the microenvironment of tumor immunosuppression.
2. Naringenin selectively down-regulates SMAD3 expression and inhibits TGF-β signaling pathway
Under the stimulation of TGF-β, naringenin increased the sensitivity of pancreatic cancer cells to the first-line chemotherapy drug gemcitabine, decreased the mesenchymal transition and migration ability of pancreatic cancer cells, and decreased the content of TGF-β in serum [3]. In addition, naringenin can also increase the content of anti-fibrotic cytokines IFN-γ and IL-2.
3. Naringenin reduces the binding of TGF-β to its membrane receptor
In the case of TGF-β treatment, naringenin significantly reduced the formation of TGF-β receptor dimers on the cell membrane surface, suggesting that naringenin exerted an inhibitory effect on the binding of TGF-β to its receptor. Using unimolecular force When further analyzing the binding force and binding probability of naringenin to TGF-β and type II TGF-β receptors, it was found that naringenin did not affect the binding force of TGF-β and type II receptors, but it could significantly reduce the Their binding probabilities (concentration-dependent)[4]. This may be due to the fact that naringenin can bind to the extracellular region of type II TGF-β receptors and increase the rate of conformational changes. If we assume that type II TGF-β The receptor is always in the process of conformational change, and only a part of the receptor molecules that happen to be in the "correct" conformation can bind TGF-β, then the increase in the rate of conformational change will undoubtedly reduce the correct binding between the receptor and TGF-β per unit time. Probability of Pairwise Binding. SB-431542 was not found to alter the binding of TGF-β to its receptor under the same assay conditions regardless of the presence or absence of TGF-β stimulation.
4. Naringenin inhibits the secretion of TGF-β
Under the premise of not affecting the transcription level of TGF-β, naringenin can limit the intracellular transport of TGF-β to reduce the secretion of TGF-β by tumor cells, reduce the secretion of TGF-β, and affect the TGF-β precursor protein. intracellular transport process.

Is naringenin the same as naringin?

​​​​​​​Citrus aurantium extract mainly contains naringenin and naringin, both of which have antioxidant effects, naringenin can reduce the damage caused by oxidation reactions, and naringin has a good scavenging effect on free radicals, which can effectively Inhibit peroxidation reaction, enhance the activity of superoxide dismutase (SOD) and catalase.
1. Anti-tumor aspects: Naringenin flavonoid can avoid tumor lesions caused by gene mutations caused by chemical, physical and biological aspects; naringin can increase the activity of antioxidant enzymes, inhibit tumor cells, and protect normal cells. Protect radioactive DNA from damage;
2. Prevention of cardiovascular and cerebrovascular diseases: Naringenin can reduce blood lipids and vascular permeability, inhibit the formation of thrombus, and has estrogen-like activity, which can relax and expand blood vessels, thereby effectively preventing cardiovascular and cerebrovascular diseases; pomelo peel Glycosides can promote the transport of cholesterol from the blood to the liver, accelerate bile secretion, inhibit the conversion of HDL to VLDL or LDL, and reduce the incidence of coronary heart disease;
3. Anti-inflammation: Naringenin can interfere with the release of arachidonic acid metabolites and histamine inflammatory mediators, and indirectly inhibit inflammatory diseases; naringin can be anti-allergic, anti-inflammatory, antibacterial, antiviral, analgesic, etc. effect.