Product name: Berbamine
Synonym name: Berbenine
Catalogue No.: BP0249
Cas No.: 478-61-5
Formula: C₃₇H₄₀N₂O₆
Mol Weight: 608.735
Botanical Source: Phellodendri chinensis cortex
Physical Description:
Type of Compound: Alkaloids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.




Chengdu Biopurify Phytochemicals Ltd. is a leading company in the research, development, manufacture and marketing of High Quality Phytochemicals and Extracts(especially Active Ingredients from Traditional Chinese Medicine，TCM), Natural Active Pharmaceutical Ingredients worldwide.
The main services:
A. Supply active ingredients and reference standards of TCM, from mgs to kgs scale
B. Custom extraction and purification, target Herb Active Ingredients
C. Custom synthesis and semi-synthesis for Natural Active Ingredients
D. CR(contract research), CM(contract manufacture) and PD(process development) services from lab scale, pilot scale to commercial scale(GMP is also available)
E. TCM compounds library for drug screen,more than 3000 compounds available, many of them are rare and unique.

HPLC of Berbamine

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

Introduction/Overview

Natural products, as an important treasure trove for drug discovery and development, play an irreplaceable role in the history of human disease treatment. Among them, isoquinoline alkaloids have always been a hot topic in medicinal chemistry and pharmacology research due to their structural diversity and wide range of biological activities. Berbamine, as a typical bisbenzylisoquinoline alkaloid, has expanded its pharmacological activity research from traditional anti-inflammatory and antibacterial fields to multiple modern medical frontiers such as anti-tumor, immune regulation, cardiovascular protection, and analgesia since its identification. Especially in terms of its potential role in pain management, it involves the regulation of multiple key targets such as transient receptor potential vanillic acid subtype 1 (TRPV1), cannabinoid receptor 1 (CNR1), tumor necrosis factor (TNF), etc., demonstrating a multi pathway and multi-target characteristic of action, providing valuable lead compounds for the development of new analgesics. This article aims to systematically review the chemical properties, plant sources, and pharmacological activities of beriberamine, with a focus on its mechanism of action and molecular target network in pain related diseases. It also evaluates and prospects its pharmacological properties and clinical application prospects.

Chemical structure and physicochemical properties

Berberine (CAS number: 478-61-5) is a bisbenzylisoquinoline alkaloid with a molecular formula of C37H40N2O6 and a molecular weight of 608.7350. Its core structure is composed of two isoquinoline units connected by a double benzyl bond, forming a unique rigid skeleton and multiple chiral centers, which provides a structural basis for its specific interactions with various biological targets.

From the analysis of physical and chemical properties, the lipid water partition coefficient (LogP) of berberine is 5.7795, indicating its strong lipophilicity. Its topological polar surface area (TPSA) is 72.8600 Å ², which is relatively small. These two parameters together determine the poor water solubility of berberiberamine, with a calculated value of approximately 0.0059 mg/mL, which to some extent limits the improvement of its bioavailability. In pharmacokinetic predictions, the ability of berberiberamine to penetrate the blood-brain barrier was evaluated as "low", suggesting that it may not easily enter the central nervous system to exert direct effects. However, its regulation of the peripheral nervous system and immune system may still be the basis for its important activities such as analgesia. In terms of safety warning, in vitro experiments suggest that there may be a risk of hERG potassium channel inhibition (positive), which is associated with potential arrhythmogenic side effects and is a key focus in subsequent structural optimization. It is gratifying that the Ames test result is 0.0, which preliminarily indicates that there is no mutagenicity in this testing system and the risk of genetic toxicity is low.

Plant sources and extraction methods

Berberidaceae and Menispermaceae are mainly derived from various plants in the Berberidaceae and Menispermaceae families. The most famous source among them is the three needles of traditional Chinese medicine (such as Berberis macrophylla) Berberis soulieana Fine leaved Berberis B. poiretii Etc.) and self-defense（Aristolochia fangchi）Wait. In these plants, berberine often coexists with other alkaloids such as berberine and palmatine.

The traditional extraction method mainly relies on solvent extraction. Usually, dried plant roots or stem bark are crushed and soaked or percolated in acidic aqueous solutions (such as dilute sulfuric acid or hydrochloric acid) to dissolve alkaloids into salts. Subsequently, the filtrate is alkalized (such as ammonia water, lime water) to free the alkaloids, and then extracted with organic solvents (such as chloroform, dichloromethane, or ethanol). After concentration, the total alkaloids are obtained. The further purification of berberine requires the use of column chromatography technology, often using silica gel, alumina or macroporous resin as the stationary phase, gradient elution with chloroform methanol mixed solvents in different ratios, combined with thin-layer chromatography (TLC) or high-performance liquid chromatography (HPLC) monitoring, to ultimately obtain high-purity berberine monomers. Modern extraction techniques such as ultrasound assisted extraction, microwave-assisted extraction, and supercritical fluid extraction have also been applied to improve extraction efficiency and reduce solvent consumption.

Pharmacological activity research

The pharmacological activity research of berberine shows extensive and in-depth characteristics, and its effects go far beyond the early recognition of antibacterial and anti-inflammatory properties.

1. Anti inflammatory and immune regulatory effects Berberine is one of the most extensively studied activities. It can significantly inhibit the production of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines such as TNF - α and interleukin-6 (IL-6) in macrophages induced by lipopolysaccharides (LPS). Its immune regulatory effect is reflected in its bidirectional regulation of T lymphocyte and B lymphocyte proliferation, as well as its good therapeutic effect on autoimmune disease models such as rheumatoid arthritis and experimental autoimmune encephalomyelitis.
2. Antitumor activity Recent research hotspots. Berbamine can inhibit the proliferation and induce apoptosis of a variety of leukemia cells (such as K562, HL-60) and solid tumor cells (such as breast cancer, liver cancer, lung cancer). Its mechanism involves regulating the cell cycle (blocking in G0/G1 phase), inhibiting the nuclear factor kappa B (NF - κ B) signaling pathway, regulating the balance of Bcl-2 family proteins, and inhibiting tumor cell migration and invasion.
3. Cardiovascular protective effect Research shows that berbamine has the effects of anti arrhythmia, protection of myocardial ischemia-reperfusion injury, inhibition of myocardial fibrosis and anti atherosclerosis. Its mechanism is related to calcium channel blockade, antioxidant stress, and inhibition of inflammatory response.
4. Analgesic effect This is the core focus of this article. Numerous in vivo experiments have confirmed that berberiberamine exhibits significant analgesic effects in various pain models, such as the acetic acid writhing test, formalin test, and chronic sciatic nerve ligation induced neuropathic pain model. Its analgesic effect is not dependent on opioid receptors and is closely related to anti-inflammatory activity, indicating its potential as a non steroidal or novel multi-target analgesic drug.

Mechanism of action and molecular targets

The analgesic mechanism of berberine is complex, involving the regulation of multiple key targets in the pain pathway, forming a multi-target action network:

1. Inhibit inflammatory mediators and related enzymes：

   • PTGS1 (COX-1) and PTGES (mPGES-1)Berberine can inhibit the activity of cyclooxygenase-1 (COX-1) and prostaglandin E synthase (mPGES-1), reduce the production of pain mediator prostaglandin E2 (PGE2), and alleviate inflammatory pain.
   • NOS2（iNOS）By inhibiting the expression of inducible nitric oxide synthase (iNOS), excessive NO production is reduced, and NO mediated pain sensitization is alleviated.
   • TNF Berberine can effectively inhibit the generation and release of TNF - α. TNF - α is a core pro-inflammatory cytokine in pain and neuropathic pain, which can directly activate nociceptive neurons and promote the release of other inflammatory mediators.

2. Regulating ion channels and receptors：

   • TRPV1 Transient receptor potential vanillic acid subtype 1 channel is a key molecule mediating thermal pain and inflammatory pain. Research has shown that berberine may act as a regulator of TRPV1, inhibiting its excessive activation and thereby blocking the transmission of nociceptive signals to the central nervous system.
   • CHRNA7（α7 nAChR）The α 7-nicotinic acetylcholine receptor is the core of the cholinergic anti-inflammatory pathway. Berberine may activate downstream signaling pathways such as JAK2/STAT3 by stimulating or regulating this receptor, inhibit the activation of immune cells such as macrophages, and exert central and peripheral analgesic effects.
   • CNR1 (CB1 receptor)The cannabinoid CB1 receptor plays an important role in both central and peripheral analgesia. Berberine may directly or indirectly affect the endogenous cannabinoid system, regulate CB1 receptor function, and participate in analgesia.
   • SIGMAR1 (σ -1 receptor)The σ -1 receptor is involved in regulating neurotransmitter release, calcium signaling, and neuroplasticity, and is closely related to neuropathic pain. Berberine may act as a ligand for the σ -1 receptor, intervening in its role in pain.

3. Affects the neurotransmitter system：

   • ACHE and BCHE Berberine exhibits inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Inhibition of AChE can increase the concentration of acetylcholine in synaptic cleft, enhance cholinergic anti-inflammatory and analgesic pathways. This effect may also be related to its improvement of cognitive function.

In summary, berberine exerts a synergistic analgesic effect by simultaneously acting on multiple processes such as the production of inflammatory mediators, nociceptive ion channels, neurotransmitter systems, and neuroimmune regulation. This multi-target characteristic may make it more advantageous than single target drugs in treating complex chronic pain, especially pain accompanied by obvious inflammation or neuropathy.

Evaluation of drug properties and pharmacokinetics

Although berberine has a wide range of pharmacological activities, its medicinal properties face certain challenges, mainly due to its physicochemical properties.

• Absorption and bioavailability High LogP and low water solubility may result in poor oral absorption and limited bioavailability. Research has shown that the absolute oral bioavailability of beriberamine in rats is relatively low. The use of nano formulations (such as liposomes, polymer nanoparticles), solid dispersions, or prodrug strategies to improve their solubility and absorption is an important direction for enhancing their therapeutic efficacy.
• distribution The predicted blood-brain barrier permeability is low, which is consistent with the observation that the central axis has a weaker direct effect. But its distribution in peripheral tissues (such as immune organs and inflammatory sites) may be good, which supports its pharmacological effects by regulating peripheral immunity and inflammation.
• Metabolism and excretion The in vivo metabolism research of berberine is not yet sufficient. As an alkaloid, it may be mainly metabolized by the liver cytochrome P450 enzyme system and excreted through bile and urine. It is crucial to clarify its main metabolites, metabolic enzymes, and potential drug drug interactions.
• safety The hERG inhibition warning prompt requires in-depth cardiac safety assessment, including in vitro myocardial cell experiments and in vivo QT interval prolongation detection. Although the Ames test is negative, more comprehensive preclinical genetic toxicity and long-term toxicity studies still need to be completed.

Overall, berberiberamine is a lead compound with clear activity but requires optimization of pharmacological parameters. Future research requires systematic preclinical pharmacokinetic (ADME) studies and structural modifications using medicinal chemistry methods to improve water solubility and reduce hERG inhibition risk while retaining pharmacophores, thereby enhancing its development potential.

Clinical application prospects and prospects

The clinical application prospects of berberine are broad, but the road still needs to be explored solidly.

1. As a development of new analgesic drugs For chronic inflammatory pain (such as osteoarthritis, rheumatoid arthritis) and neuropathic pain, the multi-target mechanism of action of berberberamine has unique advantages. It may be considered to develop its external preparations (such as gel and patch) to avoid systemic toxicity and directly act on the painful parts; Or develop oral sustained-release formulations for the management of systemic inflammatory pain.
2. As an adjuvant therapy drug for tumors Its multiple effects of anti-tumor, sensitizing chemotherapy, and relieving cancer pain make it highly valuable in the comprehensive treatment of tumors. Study its combination with conventional chemotherapy drugs to inhibit tumor growth and metastasis, alleviate chemotherapy-induced neuropathic or cancer-related pain, and improve patients' quality of life.
3. Application in autoimmune diseases Based on its strong immune regulation and anti-inflammatory properties, berberberamine may be used to treat autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus, and its analgesic effect can also simultaneously address the pain symptoms often associated with these diseases.
4. Structural optimization and derivative development This is the core pathway to promote the clinical application of berberine. By using semi synthetic or fully synthetic methods to modify its molecular structure, such as introducing hydrophilic groups to improve solubility, modifying key functional groups to eliminate hERG inhibitory activity, and preparing targeted delivery prodrugs, it is expected to obtain candidate drugs with higher activity and better safety.
5. In depth study of molecular mechanisms Using chemical biology methods such as photoaffinity labeling and proteomics to further accurately identify the direct target proteins and draw clearer pharmacological action network diagrams, providing theoretical basis for precision and combination therapy.

Conclusion

Berberine, as a bisbenzylisoquinoline alkaloid derived from traditional medicinal plants, has shown new vitality in modern pharmacological research due to its unique chemical structure and multi-target pharmacological properties. Especially in the field of pain treatment, it demonstrates great potential for multi pathway collaborative analgesia by regulating multiple key targets such as TRPV1, CNR1, TNF, PTGS1/PTGES, etc. Although the current pharmaceutical challenges it faces, such as poor water solubility and potential cardiac toxicity, cannot be ignored, these challenges are precisely the issues that modern pharmaceutical chemistry and pharmacy can focus on addressing. Through in-depth analysis of its mechanism of action, systematic pharmacokinetic studies, and rational structural optimization, berberine and its derivatives are expected to be developed into new drugs for the treatment of chronic pain, autoimmune diseases, and adjuvant anti-tumor therapy, thus better transforming the intelligence of natural products into therapeutic methods that benefit humanity. Continuous and in-depth research on it is not only an exploration of an active molecule, but also a vivid practice of the natural product drug development model.