Product Name: Oxyberberine 
Synonym name:  Berlambine 

Catalogue No.: BP0259
Cas No.: 549-21-3
Formula: C₂₀H₁₇NO₅
Mol Weight: 351.358
Botanical Source: Alkaloid from Arcangelisia gusanlung, Berberis lambertii, other Berberis spp. and Mahonia japonica

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  Oxyberberine 

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

Introduction/Overview

Oxyberberine (CAS No. 549-21-3), also known as Berlambine, is an oxidized derivative of a natural isoquinoline alkaloid. Due to its remarkable biological activity and potential medicinal value, it has attracted widespread attention in the field of natural product pharmacology in recent years. As an orally effective heme oxygenase-1 (HO-1) agonist, oxidized berberine can activate cellular antioxidant defense mechanisms by modulating multiple cellular signaling pathways, especially the PI3K/Akt/AMPK signaling axis, and exhibiting multiple pharmacological effects including anti-inflammatory, antioxidant, neuroprotection, and improvement of metabolic disorders. Its therapeutic potential in various chronic disease models, including type 2 diabetes, traumatic brain injury (TBI), and inflammatory bowel disease, provides a solid theoretical foundation for its clinical translation.

This paper systematically reviews the chemical structure and physicochemical properties of berberine oxide, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics. Combined with its targeting role in related diseases, it explores its clinical application prospects and development directions, aiming to provide references for subsequent research and drug development.

Chemical structure and physicochemical properties

Oxidized berberine is an oxidation product of an isoquinoline alkaloid, with a molecular formula of C20H17NO5 and a molecular weight of 351.36. Its structural features include an oxidized isoquinoline framework with multiple hydroxyl and methoxy substituents, giving it high polarity and bioactivity. Its LogP value is about 1.49, indicating moderate lipid solubility, which facilitates cell membrane penetration but is not prone to excessive lipophilusis that affects bioavailability. The topological pole surface area (TPSA) is 79.47 Ų, and the number of hydrogen bond receptors is 6, indicating that it has excellent intermolecular hydrogen bond formation capability, which is significant for binding to protein targets.

Berberine oxide has a relatively low blood-brain barrier penetration ability, suggesting that its direct role in the central nervous system may be limited, but it is more likely to exert neuroprotective effects indirectly by modulating peripheral signaling pathways. Currently, there is no clear data on its hepatotoxicity, cardiotoxicity, or safety indicators such as hERG channel inhibition, and further systematic evaluation is needed.

Plant Origins and Extraction Methods

Oxidized berberine is mainly found in Berberis spp. and related plants, and is the product of berberine oxidation and transformation within plants or during extraction and processing. Common source plants include Chinese medicinal herbs such as Coptis chinensis and Berberis vulgaris. Traditional extraction methods mostly use alcohol solvents (such as ethanol and methanol) combined with acid-base adjustment, obtaining crude extracts through reflux extraction, ultrasound-assisted extraction, or microwave-assisted extraction.

During purification, liquid-liquid partitioning, column chromatography (silica gel, C18 reversed phase column), and high-performance liquid chromatography (HPLC) techniques are typically used to separate and purify oxidized berberine. In recent years, the application of supercritical fluid extraction and green solvent extraction technologies is expected to improve extraction efficiency and purity, reducing environmental pollution.

Pharmacological activity research

The pharmacological activity of oxidized berberine mainly manifests in its antioxidant, anti-inflammatory, neuroprotection, and metabolic regulation aspects.

1. Antioxidant effects
   Oxidized berberine significantly enhances antioxidant enzyme activity such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) by inducing heme oxygenase-1 (HO-1) expression, reducing reactive oxygen species (ROS) production and protecting cells from oxidative stress damage. It activates the PI3K/Akt/AMPK signaling pathway, promoting an overall enhancement of the intracellular antioxidant defense system.

2. Anti-inflammatory effects
   Oxidized berberine inhibits the nuclear factor κB (NF-κB) signaling pathway, reduces the expression of pro-inflammatory factors such as TNF-α, IL-6, and IL-1β, thereby alleviating inflammatory responses. This effect is particularly pronounced in chronic inflammation models such as inflammatory bowel disease.

3. Neuroprotective effects
   In models of traumatic brain injury (TBI) and neurodegenerative diseases, oxidized berberine demonstrates good neuroprotective potential by reducing oxidative stress and inflammatory responses, protecting nerve cell survival, improving neural function recovery, and improving neural function.

4. Antidiabetic effects
   Berberine oxide can improve insulin sensitivity, regulate glucose metabolism, and lower blood sugar levels. Its targets involve key metabolic enzymes such as AMPK (PRKAA1), glucokinase (GCK), and protein tyrosine phosphatase 1B (PTPN1), promoting glucose uptake and utilization, and inhibiting diabetes-related complications.

Mechanism of action and molecular targets

The multi-target mechanism of oxidized berberine mainly revolves around its regulation of oxidative stress and inflammatory pathways:

• Activation of heme oxygenase-1 (HO-1).
  HO-1, as an important intracellular antioxidant enzyme, catalyzes the breakdown of hemoglobin, producing carbon monoxide, iron ions, and biliverd, and has antioxidant and anti-inflammatory effects. Oxidized berberine enhances cellular defense by activating HO-1 expression.

• PI3K/AKT/AMK signal path regulation
  Oxidized berberine activates the PI3K/Akt pathway, promoting cell survival and metabolic regulation, while also activating AMPK, a key regulator of energy metabolism, promoting the balance of glucose and lipid metabolism and improving metabolic syndrome status.

• NF-κB signaling pathway inhibition
  Berberine oxidation inhibits nuclear translocation of NF-κB, reduces the release of inflammatory mediators, and alleviates chronic inflammatory responses.

• Relevant target proteins
  Research shows that oxidized berberine acts on various targets related to type 2 diabetes and related metabolic diseases, including AMPK (PRKAA1), glucokinase (GCK), anti-apoptotic protein MCL1, amyloid precursor protein (APP), protein tyrosine phosphatase 1B (PTPN1), tyrosinase (TYR), DNA repair enzyme APEX1, aldose reductase AKR1B1, and transcription factor NFE2L2, demonstrating its multi-target synergistic regulation.

Druggability evaluation and pharmacokinetics

The druggability parameters of berberine oxide indicate its potential for drug development:

• Molecular weight and physicochemical properties
  The molecular weight was 351.36, which is in the medium molecular weight range; LogP was 1.49, indicating moderate lipid solubility, which is beneficial for oral absorption; The TPSA was 79.47, indicating good polarity balance that facilitates biofilm penetration.

• Blood-brain barrier permeability
  The prediction is low, which may limit its direct application in the central nervous system, but it is more likely to exert neuroprotective effects through peripheral regulatory mechanisms.

• Safety evaluation
  Currently, data on hepatotoxicity, cardiotoxicity, hERG channel inhibition, and genotoxicity (Ames assay) are still unclear, requiring further systematic toxicological research.

• Pharmacokinetic characteristics
  There are few current literature reports, and systematic studies are needed on its absorption, distribution, metabolism, and excretion (ADME) characteristics. Given its oral efficacy, future research should focus on its bioavailability, metabolic pathways, and potential drug interactions.

Prospects and outlooks for clinical applications

With its multi-target and multi-mechanism pharmacological activity, oxidized berberine shows broad clinical application prospects:

• Type 2 diabetes and metabolic syndrome
  By activating the AMPK signaling pathway and improving insulin sensitivity and glucose metabolism, oxidized berberine is expected to become an adjunctive therapy for diabetes and its complications.

• Neuroprotection and brain injury
  In traumatic brain injury and neurodegenerative diseases, berberine oxide alleviates nerve damage and promotes functional recovery through antioxidant and anti-inflammatory effects, showing potential as a neuroprotective agent.

• Inflammatory diseases
  It inhibits NF-κB-mediated inflammatory responses, giving it potential therapeutic value in chronic inflammatory diseases such as inflammatory bowel disease.

Future research should strengthen preclinical pharmacokinetics and toxicology studies of berberine oxide, optimize dosage forms and administration regimens, and conduct systematic clinical trials to verify its safety and efficacy. At the same time, based on its multi-target mechanism of action and combined with modern drug design technologies, structurally modified derivatives are being developed to enhance efficacy and druggability.

Conclusion

As a naturally derived heme oxygenase-1 agonist, oxidized berberine, with its unique chemical structure and diverse pharmacological activity, demonstrates significant potential in the fields of antioxidant, anti-inflammatory, neuroprotection, and metabolic regulation. By regulating key signaling pathways such as PI3K/Akt/AMPK and NF-κB, it exerts multi-target synergistic effects, providing new ideas for the treatment of type 2 diabetes, traumatic brain injury, and inflammatory diseases.

Although current research on its safety and pharmacokinetics remains limited, with further research, berberine oxide is expected to become an important candidate molecule in natural drug development. In the future, by combining modern medicinal chemistry and pharmacological technologies, systematically evaluating its clinical application value will promote its advancement toward clinical translation and benefit more patients.