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Product name: Hesperetin
Synonym name: Eriodictyol 4'-monomethyl ether; Hesperitin
Catalogue No.: BP0724
Cas No.: 520-33-2
Formula: C16H14O6
Mol Weight: 302.282
Botanical Source: Brickellia vernicosa, Persica vulgaris (preferred genus name Prunus), Citrus and Mentha spp.
Physical Description: Powder
Type of Compound: Flavonoids
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.
The product could be supplied from milligrams to grams, up to kilograms
Inquire for bulk scale.
Descriptions:
Hesperetin exerts dose dependent chemopreventive effect against 1,2-dimethyl hydrazine induced rat colon carcinogenesis.[1]
Hesperetin has antioxidant activity, plays a protective role against 7,12-dimethylbenz(a)anthracene (DMBA)-induced oxidative stress; suppresses COX-2 gene expression may be a consequence of their antioxidant activity;is a powerful peroxynitrite (ONOO-)- scavenger and promotes cellular defense activity in the protection against ONOO- involved diseases.[2-4]
Hesperetin has inhibitory effects on Kv1.5 potassium channels stably expressed in HEK 293 cells and ultra-rapid delayed rectifier K + current in human atrial myocytes.[5]
Hesperetin,has antiplatelet activity, is mainly mediated by inhibition of PLC-gamma2 phosphorylation and cyclooxygenase-1 activity.[6]
Hesperetin mediates protection against doxorubicin-induced cardiotoxicity through nuclear factor-kappa B, p38, and caspase-3, indicates the protective effect of hesperetin against doxorubicin-induced cardiotoxicity.[7]
References:
[1] Aranganathan S, Selvam J P, Nalini N. Invest New Drugs, 2009, 27(3):203-13.
[2] Choi E J. Life Sci, 2008, 82(21–22):1059-64.
[3] Kim J Y, Jung K J, Choi J S, et al. Free Radical Res, 2004, 38(7):761-9.
[4] Hirata A, Murakami Y, Shoji M, et al. Anticancer Res, 2005, 25(5):3367-74.
[5] Wang H, Wang H F, Chen W, et al. Eur J Pharmacol, 2016 ,789 :98-108.
[6] Jin Y R, Han X H, Zhang Y H, et al. Atherosclerosis, 2007, 194(1):144-52.
[7] Trivedi P P, Kushwaha S, Tripathi D N, et al. Cardiovasc Toxicol, 2011, 11(3):215-25.
[8] Wan L, Sun X, Xu Z, et al. China Pharmacist, 2010, 13(08):1082-4.
HPLC of Hesperetin
HNMR of Hesperetin
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
96.2200
2.1968
1.9110
.3009
4.0135
3.2207
Low
88.3454
2.9119
No
No
Yes
No
Yes
No
0.6
Yes
No
No
No
Hesperetin (CAS No.: 520-33-2) is a natural flavanone compound mainly found in the peel and pulp of citrus fruits. As one of the main active ingredients in citrus flavonoids, hesperitin has attracted widespread attention due to its diverse biological activities. In recent years, with the deepening development of natural product pharmacology, hesperidin has demonstrated significant pharmacological potential in antioxidant, anti-inflammatory, and anticancer fields, making it an important candidate for natural drug development.
Hesperidin not only exhibits good oral bioactivity, but has also been confirmed as a broad-spectrum human uridine diphosphate glucuronyltransferase (UGT) activity inhibitor, capable of regulating the function of drug-metabolizing enzymes in the body and affecting drug metabolism kinetics. Additionally, hesperitin induces apoptosis by activating the p38 MAPK signaling pathway, regulates cell cycle stagnation during the G2/M phase, modulates Bcl-2 family protein expression, inhibits the NF-κB signaling pathway, and exerts its antitumor effects. This paper will systematically review the chemical structure and physicochemical properties of hesperidin, plant origin and extraction methods, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects, providing a theoretical basis for further research in natural product drug development.
The chemical name of hesperitin is 3',5,7-trihydroxyflavanone, with the molecular formula C16H14O6 and a molecular weight of 302.2820. Its chemical structure belongs to the flavanone class, featuring a typical tricyclic structure, containing two benzene rings (A and B rings) and one oxygen heterocycle (C ring). The molecule contains three hydroxyl functional groups (located at positions 5, 7, and 3′), which impart excellent antioxidant activity.
In terms of physicochemical properties, the LogP value of hesperitin is 2.1968, indicating moderate lipid solubility that facilitates cell membrane penetration. The polar surface area (TPSA) is 96.22 Ų, indicating a certain polarity that affects its water solubility and bioavailability. Its low water solubility (0.3009 mg/mL) limits its solubility in the aqueous phase, but moderate lipophilic solubility aids oral absorption. The blood-brain barrier has low permeability, suggesting its limited distribution in the central nervous system. The hERG channel inhibition test was negative, indicating that hesperidin has good cardiac safety. The Ames-induced mutagenic test result was 0.6, indicating a low genotoxicity risk.
In summary, the chemical structure of hesperidin endows it with multiple biological activities, moderate physicochemical properties, and good potential for drug development.
Hesperitin is mainly found in citrus plants, especially in the peels and flesh of oranges (Citrus sinensis), pomelos (Citrus paradisi), lemons (Citrus limon), and their related varieties. Its content varies by variety, ripeness, and cultivation conditions, with hesperidin in the peel usually higher than in the flesh.
Traditional hesperitin extraction methods include solvent extraction, ultrasound-assisted extraction, microwave-assisted extraction, and supercritical fluid extraction. Common solvents include ethanol, methanol, ethyl acetate, and their aqueous solutions, known for their excellent solubility and safety. In recent years, green extraction technologies such as ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) have been widely applied, significantly improving extraction efficiency and purity while reducing solvent usage and environmental pollution.
The extraction process generally includes: raw material pretreatment (cleaning, drying, pulverization), solvent extraction (temperature, time, solvent concentration optimization), extraction filtration and concentration, purification (column chromatography, recrystallization), and drying. Higher-purity hesperidin products are commonly used in pharmacological research and formulation development.
Hesperitin exhibits a variety of significant pharmacological activities, covering antioxidant, anti-inflammatory, anticancer, cardiovascular protection, neuroprotection, and more.
As a natural flavonoid antioxidant, hesperidin can effectively eliminate free radicals and reduce oxidative stress damage. By activating the NFE2L2 (NRF2) signaling pathway, it induces the expression of downstream antioxidant enzymes such as superoxide dismutase (SOD1, SOD2), catalase peroxide (CAT), glutathione peroxidase (GPX1), and heme oxygenase-1 (HMOX1), enhancing cellular antioxidant defense capacity and reducing pathological progression of oxidative damage-related diseases.
Hesperitin can inhibit the expression of pro-inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2), thereby reducing inflammatory responses. Its mechanism mainly involves inhibiting activation of the NF-κB signaling pathway, blocking the transcription and release of inflammatory mediators, demonstrating potential anti-inflammatory therapeutic value.
Hesperitin exhibits the ability to inhibit cell proliferation and induce apoptosis across various tumor cell lines. By activating the p38 MAPK signaling pathway, it induces cell cycle stagnation at the G2/M phase, regulates the expression of apoptosis-related proteins (reducing anti-apoptotic protein Bcl-2, enhancing pro-apbototic protein Bax), and promotes mitochondrial pathway cell apoptosis. Additionally, heshein inhibits the NF-κB signaling pathway, blocking survival signals in tumor cells and enhancing its anti-cancer effect. Multiple in vivo and in vitro studies have confirmed its significant inhibitory effects on breast, colorectal, and lung cancers.
Hesperitin also demonstrates cardiovascular protective effects, improving vascular endothelial function, lowering blood lipids, and inhibiting the progression of atherosclerosis. Its neuroprotective effects mainly rely on antioxidant and anti-inflammatory mechanisms to reduce nerve cell damage, giving it potential therapeutic value for neurodegenerative diseases.
The pharmacological effects of hesperitin involve multiple signaling pathways and molecular targets, mainly including:
NFE2L2/NRF2 signaling pathway
Hesperitin activates the NRF2 transcription factor, promoting its transfer from the cytoplasm to the nucleus, enhancing the expression of antioxidant enzyme genes, improving cellular antioxidant capacity, and reducing oxidative stress-related damage.
p38 MAPK signaling pathway
Hesperitin induces cell cycle arrest and apoptosis by activating p38 MAPK. p38 MAPK is a key regulator of stress responses, controlling cell proliferation, differentiation, and apoptosis. Hesperitin mediates anti-tumor effects through this pathway.
Bcl-2 family proteins are regulated
Hesperitin downregulates the expression of the anti-apoptotic protein Bcl-2 while upregulating the pro-apoptosis protein Bax, disrupting mitochondrial membrane potentials, releasing cytochrome C, activating caspase, and initiating mitochondria-mediated apoptosis.
NF-κB signaling pathway inhibition
NF-κB is an important regulatory factor for inflammation and tumor cell survival. Hesperitin inhibits IκBα phosphorylation and degradation, blocks NF-κB nuclear translocation, reduces the expression of pro-inflammatory factors and anti-apoptotic genes, and exerts anti-inflammatory and anti-cancer effects.
UGT enzyme activity is inhibited
Hesperitin, as a broad-spectrum UGT inhibitor, affects the activity of drug-metabolizing enzymes, may regulate drug metabolism rates in vivo, influence drug interactions, and has important pharmacokinetic significance.
The druggability parameters of hesperitin indicate that it has good potential for drug development. The molecular weight of 302.2820 meets the Lipinski rule, and the LogP is 2.1968, indicating moderate lipid solubility is beneficial for oral absorption. TPSA was 96.22 Ų, indicating moderate polarity, which is favorable for cell membrane penetration. Low water solubility suggests the need to improve bioavailability through formulation technology.
The low permeability of the blood-brain barrier limits its application in the central nervous system, but it helps reduce CNS side effects. hERG channel inhibition was negative, indicating a low risk of cardiotoxicity. Ames test results showed that it carries low genotoxicity risk and is relatively safe.
Pharmacokinetic studies show that hesperidin is well absorbed orally but has significant first-pass metabolism, mainly through glucuronic acid binding metabolism via hepatic UGT enzymes, producing water-soluble metabolites excreted by the kidneys. It has a moderate half-life and is widely distributed in the body, but its concentration in brain tissue is relatively low. Hesperitin's inhibitory effect on UGT enzyme may lead to metabolic interactions with other drugs, which requires attention in clinical application.
Due to its multi-target and multi-mechanism pharmacological activity, hesperitin shows broad application prospects in the prevention and treatment of various diseases. Its antioxidant and anti-inflammatory properties give it potential value in chronic inflammatory diseases, cardiovascular diseases, and neurodegenerative diseases. Its anticancer activity offers new ideas for adjuvant therapy in tumors, especially in combination chemotherapy and targeted therapy, where synergistic effects may be achieved.
However, the clinical application of hesperitin still faces some challenges. Its low water solubility and first-pass effect limit bioavailability, requiring improvements through nanoformulations, liposomes, or other drug delivery systems. Pharmacokinetic and safety data still need further improvement, especially for toxicological evaluation under long-term use and high-dose conditions.
Future research should focus on structural modification of hesperitin to enhance drug properties, deeply analyze its molecular mechanisms, conduct systematic preclinical and clinical studies, and explore its potential for combined application with existing drugs. In addition, the design and development of hesperidin-based drugs will promote the translation and application of natural products in modern medicine.
As a widely sourced and biologically active natural flavanoid, hesperitin has become a hot topic in natural product pharmacology research due to its antioxidant, anti-inflammatory, and anticancer effects. Its unique mechanism of action and good safety provide a solid foundation for the development of novel natural drugs. Despite challenges in bioavailability and metabolic stability, advances in formulation technology and drug design suggest hesperidin is expected to play an important role in future clinical treatments. Systematic and in-depth pharmacological mechanism research and clinical validation will be key to promoting the translational application of hesperitin, and we look forward to its greater potential in the field of natural medicines.
Shenshuai
Wenjing
Hedandan
