Synonym name: Naringin DC
Catalogue No.: BP0984
Cas No.: 18916-17-1
Formula: C₂₇H₃₄O₁₄
Mol Weight: 582.555
Botanical Source: Synth. from HBH63 by base-induced cleavage, followed by catalytic hydrogenation

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.

For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.

Description:

Naringin Dihydrochalcone is an artificial sweetener derived from naringin. Naringin is a major flavanone glycoside obtained from tomatoes, grapefruits, and many other citrus fruits. Naringin exhibits biological properties such as antioxidant, anti-inflammatory, and antiapoptotic activities. Naringin suppresses NF-κB signaling pathway.

References:

《Fine Chemical Intermediates》 2011-04    

Study on Preparation of Naringin Dihydrochalcone   

The process for preparation of Naringin dihydrochalcone from naringin was investigated.The product was obtained in 90% yield under optimum conditions of pH 13,temperature 45℃,H2 pressure 0.5 MPa,raney nickel loading 5%,and reaction time 4 h.    

Food Research International Volume 54, Issue 1, November 2013, Pages 691–696    

Preparation and physicochemical characterization of the supramolecular inclusion complex of naringin dihydrochalcone and hydroxypropyl-β-cyclodextrin    

Naringin dihydrochalcone (naringin DC) is an intense sweetener and a strong antioxidant with potential applications in many food and pharmaceutical products. However, its low water solubility impedes the realization of these applications. 

METHODS AND RESULTS:

This study investigated the feasibility of using hydroxypropyl-β-cyclodextrin (HP-β-CD) to form a supramolecular inclusion complex with Naringin dihydrochalcone to improve its solubility. The inclusion complex was prepared by stirring an equal molar solution of Naringin dihydrochalcone and HP-β-CD at 30°C for 24 h, followed by freeze-drying.Results showed clearly the formation of a supramolecular complex in which the guest molecule, Naringin dihydrochalcone, was entrapped inside the cavity of the host, HP-β-CD. The close association between naringin DC and HP-β-CD resulted in changes in some of the characteristic spectral, phase transitional and morphological properties of Naringin dihydrochalcone. Furthermore, 1H-NMR analyses demonstrated that it was the B ring of Naringin dihydrochalcone that was inserted into the HP-β-CD cavity to form the supramolecular complex.    

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Naringin dihydrochalcone (NDC) is an artificial sweetener derived from naringin, widely recognized for its unique sweetness and potential biological activity. As a flavonoid glycoside mainly found in grapefruit (Citrus paradisi), tomato (Solanum lycopersicum), and various citrus fruits, naringin has been proven to possess significant antioxidant, anti-inflammatory, and anti-apoptotic pharmacological activities. As a derivative of naringin, NDC not only inherits some biological functions from its parent molecule but also exhibits superior stability and sweetness characteristics due to structural modification, making it a research hotspot in the food industry and drug development.

In recent years, with the prevalence of metabolic syndrome and obesity-related diseases, the potential of natural products and their derivatives in anti-obesity treatment has gradually been explored. NDCs demonstrate good anti-obesity potential due to their regulatory effects on various targets related to lipid metabolism and energy balance. This paper will systematically review the chemical structure and physicochemical properties of NDCs, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetics, as well as their clinical application prospects, aiming to provide comprehensive reference and guidance for research in related fields.

Chemical structure and physicochemical properties

The chemical structure of naringin dihydrochalcone is based on the flavanotone framework of naringin, introducing dihydrogen groups into the chalcone structure through a reduction reaction, forming dihydrochalcone derivatives with chalcone characteristics. Its molecular formula is C_27H_32O_14, molecular weight is 582.5550, and CAS number is 18916-17-1. The structural features of NDC include two aromatic rings connected by a saturated acetone bridge, with the glycoside portion imparting good water solubility and biocompatibility.

In terms of physicochemical properties, the LogP value of NDC is -0.0147, indicating strong hydrophilicity, and a water solubility index of 4.8917, suitable for applications in aqueous environments. Its topological polar surface area (TPSA) is 236.0600, suggesting that the molecule contains a large number of polar groups, which may affect membrane permeability and bioavailability. The blood-brain barrier has low permeability, suggesting its limited distribution in the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames mutagenicity test was 0.0, indicating a low genotoxicity risk and a solid safety foundation.

Plant Origins and Extraction Methods

As the parent molecule of NDCs, naringin is mainly found in the peel and flesh of grapefruit, pomelo, and other citrus fruits. Its content is greatly influenced by variety, maturity, and harvest season. Traditional extraction methods include hot water extraction extraction, ethanol extraction, and ultrasonic-assisted extraction. In recent years, the application of supercritical CO_2 extraction and microwave-assisted extraction technology has improved extraction efficiency and purity.

NDC, as an artificially synthesized derivative, is usually prepared through the chemical reduction reaction of naringin. Common synthetic routes include hydrogenation using palladium-catalyzed reactions, partially reducing the chalcone structure of naringin to dihydrochalcone. This method operates under mild conditions, yields are relatively high, and is easy to scale up. Additionally, enzyme catalysis is being explored to improve selectivity and environmental friendliness.

During extraction and purification, techniques such as column chromatography and countercurrent chromatography are often used to obtain high-purity naringin and its derivatives. Improving purity is crucial for subsequent pharmacological activity research and clinical application.

Pharmacological activity research

Research on the pharmacological activity of NDCs mainly focuses on their anti-obesity and metabolic regulatory effects. Numerous in vitro and in vivo experiments have shown that NDCs can regulate lipid metabolism, energy expenditure, and inflammatory response through multiple targets, thereby exerting anti-obesity effects.

Anti-obesity effects

NDCs inhibit the expression of lipogenesis-related genes by regulating adipocyte differentiation and lipid accumulation, such as PPARG (Peroxisome Proliferator-Activated Receptor γ), SREBF1 (sterol-regulating factor-binding protein 1), and FASN (fatty acid synthase). Additionally, NDCs promote fat breakdown and energy metabolism, activating ADRB3 (β3 adrenergic receptor) and UCP1 (uncoupled protein 1), which enhance calorie expenditure in adipose tissue.

Anti-inflammatory and antioxidant

NDC inherits the antioxidant and anti-inflammatory properties of naringin, can inhibit the NF-κB signaling pathway, reduce the release of pro-inflammatory cytokines, and alleviate chronic low-grade inflammatory states, which is of great significance for the prevention and treatment of obesity and related metabolic diseases.

Metabolic syndrome-related effects

NDC regulates metabolic regulators such as LEPR (leptin receptor), LEP (leptin), and ADIPOQ (adiponectin), improving insulin sensitivity and energy homeostasis, and demonstrating potential value in treating type 2 diabetes and fatty liver.

Mechanism of action and molecular targets

The mechanism of action of NDCs involves multiple signaling pathways and molecular targets, mainly including:

• PPARG: As a key transcription factor for adipocyte differentiation, NDCs reduce adipogenesis and lipid accumulation by inhibiting the expression and activity of PPARG.
• SREBF1 and FASN: NDC downregulates genes related to fatty acid synthesis, inhibits fatty acid synthesis, and reduces fat accumulation.
• ADRB3 and UCP1: Activate these two targets to promote adipolysis and thermogenesis in adipose tissue, increasing energy expenditure.
• NF-κB signaling pathway: NDC inhibits this pathway, reduces inflammatory responses, and improves the chronic inflammatory environment associated with obesity.
• LEPR, LEP, and ADIPOQ: regulate the expression of these hormones and their receptors, improving energy metabolism and insulin sensitivity.
• FABP4 and POMC: Influence lipid metabolism and appetite regulation by regulating fatty acid-binding proteins and melanin-releasing hormone.

In summary, NDC regulates lipid metabolism, energy balance, and inflammatory responses through multi-target and multi-pathway synergistic effects, thereby unlocking its potential in anti-obesity and metabolic disease prevention and treatment.

Druggability evaluation and pharmacokinetics

NDC druggability evaluations demonstrate good safety and drug compatibility. It has good water solubility, which is beneficial for the development of oral formulations. The blood-brain barrier has low permeability, reducing the risk of central nervous system side effects. hERG channels have no inhibitory effects, reducing the risk of cardiotoxicity. A negative Ames test indicates a low risk of genotoxicity.

Pharmacokinetics, the high polarity of NDCs and the large TPSA may limit their oral bioavailability, requiring formulation optimization or improved absorption through drug carrier technologies. Metabolism in the body mainly involves glycoside hydrolysis and corresponding phenolic metabolism, with metabolic products possibly retaining some biological activity. Half-life and distribution characteristics still require further systematic study.

Prospects and outlooks for clinical applications

With the increasing number of patients with obesity and metabolic syndrome, developing safe and effective natural product-based drugs has become an urgent issue to address. As a natural product derivative with a clear source and good safety, NDC shows broad clinical application prospects.

Future research should focus on:

• Dosage form development and drug delivery route optimization: Improving the bioavailability of NDCs and exploring novel formulations such as sustained release and nanocarriers.
• Systematic pharmacokinetics and toxicology studies: clarify in vivo metabolic pathways, duration of efficacy, and long-term safety.
• Preclinical and clinical trials: Verify the effectiveness and safety of its anti-obesity and metabolic regulatory effects, and explore indications.
• Combination therapy strategy: combine with other metabolic modulators or lifestyle interventions to achieve synergistic effects.

In addition, NDCs have potential in anti-inflammatory, antioxidant, and neuroprotective fields that deserve further exploration, potentially expanding their applicability.

Conclusion

As a derivative of naringin, naringin dihydrochalcone combines the biological activity of natural products with the structural advantages of artificial synthesis, demonstrating good anti-obesity and metabolic regulatory potential. Its multi-target and multi-mechanism mode of action provides a theoretical foundation and practical direction for developing novel drugs for metabolic diseases. Although research on their pharmacokinetics and clinical applications is still in its early stages, as research deepens, NDCs are expected to become important candidates in the field of natural product pharmacology, contributing new solutions for the prevention and treatment of obesity and related metabolic diseases. Future systematic research and clinical validation will be key to driving its translational application.