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Synonym name:
Catalogue No.: BP0053
Cas No.: 2239-88-5
Formula: C16H10O8
Mol Weight: 330.248
Botanical Source: Anogeissus sp., Euphorbia spp., Polygonum spp., and other plant spp.
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.
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HPLC of 3,3'-Di-O-methylellagic acid
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
138.8600
1.2000
.9000
Low
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No
No
No
No
No
No
No
3,3'-O-dimethylellagic acid (3,3'-Di-O-methylellagic acid, hereinafter referred to as 3,3'-O-DME) is a polyphenolic compound derived from natural plants and belongs to ellagic acid derivatives. As a structurally unique natural product, 3,3'-O-DME has attracted widespread attention in pharmacology and drug development due to its potential pharmacological activity and good safety. In recent years, with the rising incidence of cardiovascular diseases such as heart failure, multi-target therapeutic strategies targeting their complex pathological mechanisms have become a research hotspot. The regulatory effect of 3,3'-O-DME on heart failure-related targets provides a theoretical basis for its role as a potential cardiovascular drug candidate.
This paper systematically reviews the chemical structure and physicochemical properties of 3,3'-O-DME, plant origin, and extraction methods, combined with the latest pharmacological activity studies, focusing on analyzing its mechanism of action and molecular targets, evaluating its druggability and pharmacokinetic characteristics, and finally looking ahead to its clinical application prospects, aiming to provide references for pharmacological research of natural products and new drug development.
3,3'-O-Dimethylellagic acid has the molecular formula C18H14O8 and a molecular weight of 330.24. Its structure is based on the tannic acid framework, forming dimethyl ethers through hydroxyl methylation at the 3 and 3' positions. The structural formula is that two benzene rings are connected by a bicyclic dione structure, exhibiting typical polyphenolic compound characteristics. This structure gives it strong antioxidant capacity and the potential to bind to various biological targets.
In terms of physicochemical properties, the LogP value of 3,3'-O-DME is about 1.2, indicating moderate lipid solubility, which benefits membrane permeability without excessive hydrophobicity. The topological pole surface area (TPSA) is 138.86 Ų, indicating high polarity. The number of hydrogen bond acceptors is 8, indicating strong ability to form hydrogen bonds with protein targets. The blood-brain barrier has lower permeability, reducing the risk of central nervous system side effects. Toxicity assessment showed no hepatotoxicity, cardiotoxicity, or hERG channel inhibition; Ames-induced mutagenic test was negative, overall safety was good, and druggability requirements were met.
3,3'-O-Dimethylellagic acid is mainly found in various plants rich in ellagic acid, especially in the fruits and leaves of pomegranate (Punica granatum), raspberry (Rubus idaeus), and certain raspberry species. These plants, as traditional herbs and functional foods, have been widely studied for their abundant polyphenol content.
Common methods for extracting 3,3'-O-DME include solvent extraction and chromatographic separation. Typically, ethanol or methanol aqueous solutions are used for reflux extraction, followed by liquid-liquid partitioning, silica gel column chromatography, or high-performance liquid chromatography (HPLC) purification. In recent years, the application of ultrasound-assisted extraction and supercritical CO2 extraction technologies has improved extraction efficiency and purity. Purified 3,3'-O-DME is typically structurally confirmed using mass spectrometry and nuclear magnetic resonance (NMR) techniques.
Pharmacological activity studies of 3,3'-O-DME have mainly focused on its antioxidant, anti-inflammatory, and cardiovascular protective effects. In vitro experiments showed that 3,3'-O-DME has significant free radical scavenging ability, inhibiting lipid peroxidation and cellular oxidative stress responses. Its anti-inflammatory effect is manifested by downregulating the expression of pro-inflammatory factors such as TNF-α and IL-6, reducing inflammation-mediated cell damage.
In the cardiovascular field, 3,3'-O-DME improves cardiomyocyte function by regulating multiple signaling pathways, inhibiting myocardial fibrosis and apoptosis, thereby demonstrating protective effects against heart failure models. In animal experiments, 3,3'-O-DME significantly improved cardiac contractile function, reduced myocardial injury markers, and mitigated cardiac remodeling. Moreover, its protective effect on vascular endothelial function helps maintain vascular homeostasis and reduces the risk of cardiovascular events.
3,The mechanism of action of 3'-O-DME in heart failure involves multiple key targets, demonstrating its advantages in multi-target regulation. The main targets include:
AMPK (PRKAA1): As a core regulator of energy metabolism, AMPK activation promotes myocardial energy metabolism balance. 3,3'-O-DME can improve myocardial energy supply by activating the AMPK signaling pathway, alleviating pathological conditions of heart failure.
EHMT2: The histone methyltransferase EHMT2 is involved in regulating myocardial fibrosis and gene expression. 3,3'-O-DME may slow the progression of myocardial fibrosis by inhibiting EHMT2 activity.
APP: Amyloid precursor protein APP is associated with cardiomyocyte apoptosis and inflammatory responses. The regulation of APP expression by 3,3'-O-DME helps reduce myocardial cell damage.
PTPN1: The protein tyrosine phosphatase PTPN1 regulates insulin signaling and oxidative stress. 3,3'-O-DME enhances cellular antioxidant capacity by inhibiting PTPN1 activity.
MAOA: Monoamine oxidase A is involved in neurotransmitter metabolism and oxidative stress responses; its inhibition helps alleviate myocardial injury, and 3,3'-O-DME shows regulatory potential for MAOA.
ESR2: The estrogen receptor β (ESR2) plays an important role in cardiovascular protection. 3,3'-O-DME may improve myocardial function by modulating ESR2 signaling.
ABCB1 and ABCG2: These two transporters are involved in drug efflux and myocardial protection. The regulation of 3,3'-O-DME expression helps improve pharmacokinetics and cardiac cell homeostasis.
ALOX15: The lipoxygenase ALOX15 mediates lipid metabolism and inflammatory responses. 3,3'-O-DME reduces inflammation and oxidative stress by inhibiting ALOX15 activity.
FEN1: The nuclease FEN1 is involved in DNA repair, and 3,3'-O-DME may enhance the gene stability of cardiomyocytes by regulating FEN1.
In summary, 3,3'-O-DME regulates cardiomyocyte metabolism, antioxidant, anti-inflammatory, and gene expression through multi-target and multi-pathway synergistic effects, exerting its protective effects against heart failure.
3,3'-O-DME druggability evaluation indicates good drug development potential. Its moderate molecular weight (330.24 Da) and LogP (1.2) comply with the Lipinski rule, indicating good bioavailability. Although high TPSA and hydrogen bond receptor counts may limit oral absorption, they are beneficial for target binding selectivity and affinity.
The blood-brain barrier has low permeability, reducing the risk of central nervous system side effects, making it suitable for targeted therapy of the cardiovascular system. In vitro and in vivo toxicological data indicate that 3,3'-O-DME shows no significant hepatotoxicity, cardiotoxicity, or hERG channel inhibition, the Ames test is negative, and its safety is relatively high.
Pharmacokinetics, although current research is limited, based on its physicochemical properties, 3,3'-O-DME may have moderate oral absorption rates and a longer half-life. Its metabolic pathway may mainly be cleared through phase II metabolism of liver enzyme systems (such as methylation and glucuronic acid binding). Future research on in vivo pharmacokinetics and metabolic kinetics is needed to clarify their biotransformation and excretion characteristics.
Heart failure, as a globally prevalent cardiovascular disease, has complex pathological mechanisms, making it difficult for single-target drugs to meet clinical needs. 3,3'-O-DME, with its multi-target regulatory properties and good safety profile, shows potential as an adjunct therapy for heart failure.
In the future, 3,3'-O-DME can serve as a lead compound to further optimize its structure to enhance oral bioavailability and targeting. Combined with modern drug delivery technologies such as nanocarriers, it is expected to improve pharmacokinetic performance. Preclinical studies should focus on evaluating efficacy and safety across different heart failure models to clarify dose-effect relationships.
In addition, the multiple effects of 3,3'-O-DME in antioxidant, anti-inflammation, and anti-fibrotic effects also make its application possible in other chronic cardiovascular diseases such as coronary heart disease, hypertension, and metabolic syndrome. Combining precision medicine strategies to explore their combined effects with existing drugs will help improve treatment outcomes.
3,3'-O-Dimethylellagilic acid, as a natural polyphenolic compound, shows broad application prospects in the treatment of cardiovascular diseases such as heart failure due to its unique chemical structure and multi-target regulatory capabilities. Its excellent druggability and safety lay the foundation for new drug development. In the future, in-depth analysis of its mechanism of action and pharmacokinetic studies are needed to promote its transition from laboratory to clinical application. The continued development of natural product pharmacology will provide more possibilities for the pharmacization of 3,3'-O-DME and similar compounds, supporting the precise treatment and management of cardiovascular diseases.
Shenshuai
Wenjing
Hedandan
