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Synonym name: 4',5,6,7,8-Pentamethoxyflavone; Tangeritin; Ponkanetin
Catalogue No.: BP1360
Cas No.: 481-53-8
Formula: C20H20O7
Mol Weight: 372.373
Botanical Source: the peel of tangerines and of Deuterophoma traceiphila and Fortunella japonica (round kumquat)
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams, up to kgs.
For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.
NMR of Tangeretin
HPLC of Tangeretin
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
76.3600
2.7226
2.7226
.0040
2.7114
32.2590
High
85.4997
2.3742
Yes
No
Yes
No
Yes
No
0.6
No
No
No
Yes
Tangeretin, CAS number 481-53-8, is a polymethoxyflavonoid natural compound widely found in the peel of citrus fruits. As a typical representative of flavonoid compounds, hesperitin has attracted widespread attention in the field of natural product pharmacology in recent years due to its unique chemical structure and diverse biological activities. Research shows that hesperitin not only has significant anti-inflammatory, antioxidant, and neuroprotective effects, but also demonstrates strong anti-tumor potential due to its regulatory ability to regulate various cancer-related signaling pathways. Especially as an effective inhibitor of the Notch-1 signaling pathway, it plays a key role in tumor cell proliferation, apoptosis, and metastasis, making it one of the key targets for current anticancer drug development.
This paper aims to systematically review the chemical structure and physicochemical properties of hesperidin, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics. Combined with research progress on its molecular targets and related diseases, it explores its clinical application prospects and challenges, providing theoretical basis and research directions for natural product pharmacology and new drug development.
Hesperitin belongs to the polymethoxyflavonoid class of compounds, with the chemical formula C20H20O7 and a molecular weight of 372.3730. Its structural feature is that the flavonoid backbone contains five methoxy substituents, giving it strong hydrophobicity and a stable molecular conformation. In the molecular structure, the presence of multiple methoxy groups not only enhances its lipid solubility (LogP is about 2.72), but also affects its ability to bind to biological macromolecules and its cell membrane permeability.
In terms of physicochemical properties, the topological polar surface area (TPSA) of hesperidetin is 76.36 Ų, indicating moderate polarity that facilitates transmembrane absorption. Low water solubility (about 0.0040 mg/mL) suggests that its bioavailability in vivo may be limited, and it often requires formulation improvements or carrier systems to enhance solubility and stability. The high permeability of the blood-brain barrier indicates its potential to enter the central nervous system, supporting research on its neuroprotective effects. The hERG channel inhibition test results were negative, indicating a low risk of hesperidein cardiotoxicity. The Ames-induced mutagenic test score was 0.6, indicating a low genotoxicity risk and a solid safety foundation.
Hesperitin is mainly found in the peel of citrus plants, especially the outer peel of fruits such as oranges (Citrus reticulata), pomelos (Citrus paradisi), and lemons (Citrus limon). Its content varies greatly with variety, maturity, and harvest season. In traditional Chinese medicine, citrus peel (dried tangerine peel) has a long history as a medicinal ingredient, and modern research has confirmed its abundance of hesperidin and other flavonoid active ingredients.
The main extraction methods include solvent extraction, ultrasound-assisted extraction, microwave-assisted extraction, and supercritical fluid extraction. The commonly used solvent is a mixture of ethanol or methanol and water, and combining it with ultrasonic or microwave technology can significantly improve extraction efficiency and purity. After extraction, it is usually separated and purified by methods such as silica gel column chromatography and high-performance liquid chromatography (HPLC). In recent years, the application of nanotechnology and molecular imprinting has provided new ideas for efficient separation and targeted delivery of hesperiretin.
Hesperitin has diverse pharmacological activities, covering anti-inflammatory, antioxidant, anti-tumor, neuroprotection, and metabolic regulation.
Hesperitin effectively reduces inflammatory responses by inhibiting the expression of various inflammatory mediators, such as nitric oxide synthase (NOS2), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines (TNF-α, IL-6, etc.). Its inhibitory effect on the nuclear factor κB (NF-κB) signaling pathway is the core of its anti-inflammatory mechanism, showing potential for application in chronic inflammatory diseases.
As a flavonoid compound, hesperidin has excellent free radical scavenging ability, which can reduce cell damage caused by oxidative stress. By activating the Nrf2/ARE signaling pathway, it enhances the expression of intracellular antioxidant enzymes (such as glutathione peroxidase and superoxide dismutase), protecting cells from oxidative damage, especially in models of neurological diseases.
Hesperidin exhibits significant antiproliferative and pro-apoptotic activities across various tumor cell lines. Its targets include the BCL2 family proteins, STAT3, PI3K/Akt pathway, and MAPK signaling pathway, which can regulate the cell cycle, induce apoptosis, and inhibit tumor cell migration and invasion. In particular, as an inhibitor of the Notch-1 signaling pathway, it blocks the self-renewal of tumor stem cells and supports the tumor microenvironment, enhances the sensitivity of chemotherapy drugs, and demonstrates the potential for synergistic anti-cancer treatment.
Hesperitin can cross the blood-brain barrier and exert neuroprotective effects. Research shows that it alleviates nerve damage in neurodegenerative disease models by inhibiting neuroinflammatory responses, reducing oxidative stress, and regulating neurotransmitter balance. In addition, hesperitin has a regulatory effect on pathological processes related to Alzheimer's and Parkinson's diseases, suggesting its application value in the prevention and treatment of neurological diseases.
The multi-target mechanism of hesperitin forms the basis of its broad pharmacological activity. Its main molecular targets and signaling pathways include:
Through the synergistic regulation of these multiple targets, hesperidin demonstrates a complex and effective pharmacological network, supporting its potential as a multifunctional drug candidate.
The druggability evaluation of hesperitin shows that it has certain advantages and challenges. Moderate molecular weight, LogP value indicates good lipid solubility, facilitating cell membrane penetration. TPSA is moderate, supporting oral absorption and blood-brain barrier crossing ability. Low water solubility is the main limiting factor for bioavailability and requires improvement through pharmacological methods.
In vivo pharmacokinetic studies show that hesperidin is absorbed quickly and widely distributed after oral administration, especially at high concentrations in brain tissue, meeting the requirements for its neuroprotective effects. Hepatic metabolism is the main clearance pathway, primarily through the CYP450 enzyme system; metabolite activity and toxicity require further evaluation. Hesperidin does not significantly inhibit hERG channels, reducing the risk of cardiotoxicity. Low genotoxicity and relatively good safety.
Currently, hesperidin has a medium half-life in the body, making it suitable for multiple doses to maintain effective concentrations. Its interactions with other drugs still require further research, especially pharmacokinetic changes in combination therapy.
Hesperitin, as a versatile natural product, has broad clinical application prospects. Its antitumor activity makes it a potential candidate for adjuvant cancer therapy, especially in tumors targeting Notch-1 and related signaling pathways, potentially enhancing the efficacy and safety of existing treatment regimens. The neuroprotective effects offer new approaches for treating neurodegenerative diseases, especially with potential value in early intervention for diseases such as Alzheimer's and Parkinson's.
However, hesperidin's low water solubility and bioavailability limit its clinical application. Future research should focus on pharmaceutical improvements, such as nanocarriers, liposome encapsulation, and chemical modifications, to enhance in vivo stability and targeting. In addition, systematic toxicological assessment and preclinical studies are key to achieving clinical translation.
The multi-target mechanism of action provides a theoretical basis for the combination therapy of hesperitin. In the future, its synergistic effects with chemotherapy drugs and immunomodulators can be explored, leading to the development of novel combination therapy strategies.
Hesperitin, a uniquely structurally and functionally multifunctional polymethoxyflavonoid natural product, exhibits remarkable anti-inflammatory, antitumor, and neuroprotective multiple pharmacological activities. By regulating Notch-1 and multiple key molecular signaling pathways, it exerts a wide range of biological effects, providing a solid druggability foundation and safety profile. Despite challenges such as water solubility and bioavailability, with continuous advances in extraction and purification technologies and pharmaceutics strategies, hesperidin is expected to become an important direction for natural product drug development.
In the future, by combining modern molecular biology, pharmacology, and clinical research, in-depth analysis of the mechanism of action of hesperidin and optimization of its drug properties will lay a solid foundation for its clinical application and new drug development, promoting the widespread use of natural products in modern medicine.
Shenshuai
Wenjing
Hedandan
