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Synonym name:
Catalogue No.: BP0475
Cas No.: 25459-91-0
Formula: C19H18NO4+
Mol Weight: 324.355
Botanical Source: Quaternary alkaloid from the stem, roots and tubers of Stephania miyiensis and Thalictrum javanicum (Ranunculaceae)
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.
HPLC of Demethyleneberberine
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
62.8000
.2412
.0608
.5223
.7628
12.1215
Low
37.9622
2.8163
No
No
No
No
Yes
Yes
0.9
No
No
No
No
Demethyleneberberine (CAS No.: 25459-91-0), an important metabolic derivative of berberine, has attracted widespread attention in recent years due to its unique pharmacological activity and good safety profile. As a natural product, demethyleneberine not only possesses significant antioxidant and anti-inflammatory effects, but can also effectively cross the blood-brain barrier, target mitochondria to regulate cellular metabolism, and demonstrate potential therapeutic value in neurodegenerative diseases, metabolic syndromes, and inflammatory diseases. In addition, demethyleneberine also showed certain activity in studies inhibiting resistant strains, suggesting its promising application in the anti-infective field. This article will systematically review the chemical structure, origin, pharmacological activity, mechanism of action, druggability, and clinical application potential of desmethyleneberberine, aiming to provide comprehensive reference materials for researchers in related fields.
Demethylene berberine has a molecular formula of C20H18NO4 and a molecular weight of 324.3560, belonging to the flavonoid alkaloid structure. Its structural feature is the removal of methylene bridge rings from berberine molecules, resulting in a more flexible molecular conformation compared to berberine. The compound has a LogP value of 0.2412, indicating low lipid solubility, and a water solubility of 0.5223, indicating good hydrophilicity, which is beneficial for distribution and absorption in the body. The topological pole surface area (TPSA) is 62.8 Ų, indicating that it has certain membrane permeability, especially its ability to penetrate the blood-brain barrier. Although the permeability of the blood-brain barrier is rated as "low," the moderate polarity and size of its molecular structure allow it to enter the central nervous system to some extent. Notably, demethyleneberine does not inhibit hERG channels, reducing the risk of cardiotoxicity. The Ames test result was 0.9, indicating a low genotoxicity risk and a solid safety foundation.
Demethylene berberine mainly originates from the metabolic transformation product of berberine alkaloids in the traditional Chinese medicinal plant Berberis spp. Berberine is widely found in Chinese medicinal herbs such as Coptis chinensis and Phellodendron amurense. Demethylene berberine is mostly a derivative formed during metabolism in the body or during secondary plant metabolism. Directly extracting demethylene berberine from plants has a relatively low content, usually using berberine as a precursor, and demethylinating is achieved through chemical or biological catalysis methods.
Common extraction methods include:
Solvent extraction: Using methanol, ethanol, or aqueous solutions to extract herbal materials by reflux, preliminarily obtaining crude extracts containing berberine.
Chromatographic separation: Using high-performance liquid chromatography (HPLC), column chromatography, and other techniques, the crude extract is separated and purified to obtain demethylene berberine.
Chemical conversion: Converting berberine into demethylene berberine through alkaline conditions or specific enzyme catalysis, improving yield and purity.
In recent years, advances in biosynthetic engineering and enzyme catalysis have provided new ideas for large-scale preparation of demethylene berberine, especially through microbial fermentation or enzymatic reactions for efficient and green synthesis.
The pharmacological activity of desmethyleneberine mainly focuses on antioxidant, anti-inflammatory, lipid metabolism regulation, and antibacterial effects, covering research on various disease models.
Demethyleneberine can effectively scavenge reactive oxygen species (ROS), reducing oxidative stress damage. Its antioxidant effect mainly targets mitochondria, protecting mitochondrial membrane potentials and reducing the production of ROS within mitochondria, thereby preventing cell apoptosis and tissue damage. Both in vitro and in vivo experiments showed that demethyleneberine significantly increased the activity of intracellular antioxidant enzymes (such as superoxide dismutase SOD and glutathione peroxidase GPx) and reduced levels of lipid peroxidation products (MDA).
Demethyleneberine regulates the expression of inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and nitric oxide synthase (iNOS) by inhibiting nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. In multiple inflammation models (such as the lipopolysaccharide-induced macrophage inflammation model), desmethyleneberine demonstrated significant anti-inflammatory effects.
Demethyleneberine can activate the 5' AMP-activated protein kinase (AMPK) signaling pathway, promote fatty acid oxidation, inhibit lipid synthesis, and thus improve lipid metabolism disorders. Animal experiments have shown that desmethyleneberine can lower serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), providing protective effects against metabolic diseases such as obesity and non-alcoholic fatty liver disease.
The emergence of resistant bacteria is a major challenge for global public health. Demethyleneberine exhibits certain inhibitory effects on various drug-resistant strains, with related targets including DNA gyrase, dihydrofolate reductase (DHFR), and penicillin-binding protein (PBP2A). By interfering with key bacterial enzyme activity, demethyleneberine can enhance the efficacy of antibiotics and reduce the occurrence of resistance.
The multi-target mechanism of desmethyleneberine forms the basis of its pharmacological activity, mainly involving the following aspects:
Mitochondria are the main source of intracellular ROS. Demethyleneberine enters mitochondria, stabilizes mitochondrial membrane potentials, reduces ROS release caused by electron transport chain abnormalities, protects mitochondrial function, and prevents cellular oxidative damage and apoptosis.
Methyleneberine activates AMPK, a key regulator of cellular energy metabolism, promotes fatty acid β-oxidation, inhibits fat-synthesis-related enzymes (such as fatty acid synthase FAS), regulates energy balance, and improves metabolic abnormalities.
Methyleneberine blocks nuclear translocation of NF-κB by inhibiting the phosphorylation and degradation of IκBα, thereby reducing the expression of pro-inflammatory factors. At the same time, it inhibits activation of MAPK family members (ERK, JNK, p38), reduces inflammatory signaling, and exerts anti-inflammatory effects.
Demethyleneberine blocks bacterial DNA replication and metabolism by binding to and inhibiting key enzymes such as bacterial DNA gyrase (GYRA) and dihydrofolate reductase (DHFR), thereby inhibiting bacterial growth. Additionally, acting on penicillin-binding protein PBP2A enhances the activity of β-lactam antibiotics and has potential inhibitory effects against resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA).
Demethyleneberine shows good potential in terms of druggability. It has a moderate molecular weight (324.3560), low LogP value (0.2412), and good water solubility (0.5223), which is beneficial for oral absorption and internal distribution. The TPSA value was 62.8 Ų, meeting the requirements for penetrating cell membranes and the blood-brain barrier. Although the permeability of the blood-brain barrier was assessed as low, evidence of its role in central nervous system diseases still exists.
In terms of safety, desmethyleneberine does not inhibit hERG channels, reducing the risk of cardiotoxicity. Ames trial results showed a low genotoxicity risk, supporting its safety as a drug candidate.
Pharmacokinetic studies show that desmethyleneberine is rapidly absorbed orally, has a moderate plasma half-life, and can reach effective concentrations. Its metabolic pathway mainly involves hepatic enzyme systems, and the activity and toxicity of these metabolites require further study. In vivo distribution data show that it can enter brain tissue, supporting its application in neurological diseases.
With its multi-target and multi-mechanism pharmacological activity, desmethyleneberberine demonstrates broad clinical application potential. Its antioxidant and anti-inflammatory properties give it potential therapeutic value in neurodegenerative diseases (such as Alzheimer's disease and Parkinson's disease), metabolic diseases (such as non-alcoholic fatty liver disease, diabetes), and chronic inflammatory diseases.
Moreover, demethyleneberine's inhibitory effect on drug-resistant bacteria offers new ideas in the field of anti-infection. Especially in the context of increasingly severe antibiotic resistance, demethyleneberine can serve as an adjunct drug to enhance the efficacy of traditional antibiotics and delay the development of resistance.
Future research should focus on:
In-depth pharmacokinetics and toxicology studies to clarify its metabolic pathways in vivo and long-term safety.
Optimizing formulations and administration methods to improve bioavailability and targeting.
Preclinical and clinical trial designs to verify efficacy and safety across various diseases.
Exploring combination drug strategies to work synergistically with existing drugs to improve treatment outcomes.
Biosynthesis and chemical modification, development of structurally optimized derivatives, and increased activity and selectivity.
As a natural product derivative, demethyleneberine, with its unique chemical structure and diverse pharmacological activities, has shown broad application prospects in antioxidant, anti-inflammatory, lipid metabolism regulation, and antibiotic-resistant bacteria. Its excellent druggability parameters and safety foundation provide solid support for new drug development. With the ongoing elucidation of molecular mechanisms and advances in clinical research, desmethyleneberine is expected to become a novel candidate drug for treating various diseases, driving the development of natural product pharmacology. In the future, interdisciplinary collaboration should be strengthened, integrating modern drug development technologies to promote the clinical translation of methyleneberine and benefit a wide range of patients.
Shenshuai
Wenjing
Hedandan
