Product name:Berbamine Hydrochloride
Synonym name: Berbamine Dihydrochloride
Catalogue No.: BP0250
Cas No.: 6078-17-7
Formula: C₃₇H₄₂Cl₂N₂O₆
Mol Weight: 681.651
Botanical Source:

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 Berbamine Hydrochloride

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

Introduction/Overview

Berberine Hydrochloride (CAS: 6078-17-7) is a bisbenzylisoquinoline alkaloid derived from traditional medicinal plants. Its parent compound, Berberine, has been found in various Berberis and Mahonia plants. This compound has long been used in traditional medicine to treat inflammation, infections, and cardiovascular diseases. In recent years, with the deepening of modern pharmacological research, berberine hydrochloride has demonstrated a wide range of biological activities beyond traditional understanding, especially in the fields of neurodegenerative diseases, tumors, immune regulation, and cardiovascular protection, showing great potential. Among them, the potential therapeutic effect on central nervous system diseases such as dementia has attracted much attention due to its ability to regulate multiple neurotransmitter receptors in the dopaminergic and serotonergic systems. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, mechanisms of action, pharmacological evaluation, and clinical application prospects of berberine hydrochloride, in order to provide comprehensive scientific references for the deep development and transformation research of this natural product.

Chemical structure and physicochemical properties

The molecular formula of berberine hydrochloride is C37H40N2O6 · 2HCl, with a molecular weight of 608.7350. The parent nucleus structure is a bisbenzylisoquinoline skeleton formed by connecting two isoquinoline units through a double benzyl group. The hydrochloride form enhances its water solubility and stability. This compound has multiple chiral centers and exists in stereoisomers, and its biological activity is closely related to specific configurations.

In terms of physical and chemical properties, the calculated lipid water partition coefficient (LogP) is 5.7795, indicating that the compound has high lipophilicity. The topological polar surface area (TPSA) is 72.8600 Å ². Its water solubility is low, about 0.0059 mg/mL, which to some extent limits its bioavailability. These physicochemical parameters suggest that attention should be paid to the solubility and permeability of berberine hydrochloride during the development process. Its crystal morphology, melting point, and spectral characteristics (such as UV, IR, NMR, MS) have been fully characterized, laying the foundation for quality control and structural modification.

Plant sources and extraction methods

Berberidaceae plants, such as Berberis spp., B. poiretii, and Mahonia belei, are the main sources of berberine hydrochloride. These plants have a long history of application in traditional medicine in Asia, especially in China.

The extraction process usually uses dried plant roots and stem bark as raw materials. Classic methods include acid water extraction or acid precipitation after alcohol extraction. The optimization process is as follows: after crushing plant materials, soak or percolate them in low concentration hydrochloric acid or sulfuric acid solution to dissolve alkaloids into salts; The extract is alkalized (such as ammonia water) to precipitate free alkaloids, and then purified by extraction with organic solvents (such as chloroform, ethanol); Finally, the obtained berberine free base is salted with hydrochloric acid and crystallized to obtain pure berberine hydrochloride. The application of modern separation technologies such as macroporous adsorption resin method, high-speed countercurrent chromatography (HSCCC), and preparative high-performance liquid chromatography (HPLC) has significantly improved extraction efficiency and product purity. Sustainable plant cultivation and green extraction technology are important directions for future large-scale production.

Pharmacological activity research

Berberine hydrochloride has diverse and significant pharmacological activities, and its research has expanded from traditional applications to multiple modern disease fields.

1. Neuroprotection and anti dementia activity This is a current research hotspot. Berberine hydrochloride has been shown to improve learning and memory abilities, alleviate neuronal damage, and synaptic dysfunction in various animal models of Alzheimer's disease (AD) and vascular dementia. Its activity is closely related to regulating neurotransmitters, inhibiting oxidative stress, resisting neuroinflammation, and reducing the toxicity of β - amyloid protein (A β).
2. Antitumor activity: It has been widely studied that berbamine hydrochloride can inhibit proliferation, induce apoptosis, block cell cycle, inhibit invasion and metastasis and reverse multidrug resistance of leukemia, lung cancer, liver cancer, breast cancer and other tumor cells. Its function involves multiple signaling pathways and has relatively low toxicity to normal cells.
3. Immune regulatory effect Manifested as bidirectional regulation, it can suppress excessive immune responses in autoimmune disease models and enhance immune function in immunocompromised states. It can regulate the functions of various immune cells such as T lymphocytes, B lymphocytes, and macrophages.
4. Cardiovascular protective effect It has the effects of anti arrhythmias, protection of myocardial ischemia-reperfusion injury, anti atherosclerosis and lowering blood pressure. Its mechanism is related to calcium channel blockade, antioxidant and anti-inflammatory effects.
5. Other activities It also includes antibacterial, anti-inflammatory, and anti osteoporosis effects, reflecting its multi-target properties.

Mechanism of action and molecular targets

The pharmacological effects of berberine hydrochloride stem from its interactions with multiple molecular targets, exhibiting characteristics of multi-target and network regulation.

In terms of anti dementia, its effect is highly correlated with regulating the central monoamine neurotransmitter system. Research has shown that berberine hydrochloride is a regulator of multiple G protein coupled receptors (GPCRs):
* 5-hydroxytryptamine receptor 2B (HTR2B)Regulating this receptor may affect neuroinflammation, synaptic plasticity, and emotional cognitive processes.
* Dopamine D1 like receptors (DRD1, DRD5) and D2 like receptors (DRD2)The dopamine system is crucial for learning, memory, reward, and motor control. Regulating the balance between DRD1/DRD5 (primarily excitatory) and DRD2 (primarily inhibitory) may improve cognitive impairment and neuropsychiatric symptoms associated with dementia.
* Adrenergic alpha 2A receptor (ADRA2A)As a presynaptic negative feedback receptor, it regulates the release of norepinephrine. Regulating ADRA2A may affect attention, wakefulness, and cognitive function.

In addition to receptor targets, its neuroprotective mechanism also involves: inhibition of A β aggregation and toxicity; Inhibit excessive phosphorylation of Tau protein; Activate the Nrf2/ARE antioxidant pathway; Inhibit NF - κ B-mediated neuroinflammation; And regulate survival and apoptosis signaling pathways such as PI3K/Akt and MAPK.

In the field of anti-tumor, its key targets include inducing DNA damage and activating the ATM/Chk2/p53 pathway; Inhibit the activity of transcription factors such as STAT3 and NF - κ B; Regulating the Bcl-2/Bax ratio to induce apoptosis; Inhibit MMPs and reduce metastasis; And reversing multidrug resistance by inhibiting the function of P-glycoprotein (P-gp).

Evaluation of drug properties and pharmacokinetics

Despite its significant pharmacological activity, the pharmacological properties of berberine hydrochloride face some challenges and require rational evaluation.

• Absorption, distribution, metabolism, excretion (ADME)：

  • absorb Due to its low water solubility and high LogP, oral bioavailability may be limited. Research has shown that it has some absorption in the intestine, but the first pass effect may be significant.
  • distribution High molecular weight and lipophilic, theoretically able to distribute to various tissues. However, the key parameter 'blood-brain barrier (BBB) permeability' was evaluated as' low ', which poses a major obstacle to its treatment of central nervous system diseases such as dementia. How to improve its brain delivery efficiency is the focus of research and development.
  • Metabolism Mainly metabolized by cytochrome P450 enzymes (such as CYP3A4) in the liver, producing hydroxylated or demethylated products. Attention should be paid to the risk of drug drug interactions.
  • excretion The prototype drug and metabolites are mainly excreted through bile and kidneys.

• Preliminary evaluation of safety：

  • HERG inhibition The data shows that it has hERG potassium channel inhibitory activity, which suggests a potential risk of arrhythmia (prolonged QT interval) and is a key toxicity indicator that must be strictly monitored in preclinical and clinical development.
  • Genotoxicity The Ames test result is 0.0 (negative), indicating that there is no mutagenicity in this experimental system, but a more complete genetic toxicity test combination is needed for verification.
  • Acute and subacute toxicity tests have shown that its toxicity is controllable at therapeutic doses, and the main toxic target organs may involve the liver and heart.

• Optimization strategy for drug properties To improve its drug properties, strategies that can be adopted include: preparing prodrugs to increase solubility and BBB penetration; Developing novel drug delivery systems such as nano formulations (such as liposomes, polymer micelles) or microemulsions; Perform structural modifications to reduce hERG inhibitory activity and optimize metabolic stability.

Clinical application prospects and prospects

The clinical application prospects of berberine hydrochloride are broad, but the transformation path needs to overcome existing bottlenecks.

1. Potential indications：

   • Dementia and related cognitive impairments As a multi-target neuroprotective agent, it is particularly suitable for mixed dementia. The combination with existing single target drugs (such as AChE inhibitors) may produce synergistic effects.
   • neoadjuvant therapy Combined with chemotherapy, radiotherapy, or targeted therapy to enhance efficacy and overcome drug resistance, especially in the maintenance treatment phase of hematological and solid tumors.
   • Autoimmune diseases Such as rheumatoid arthritis, systemic lupus erythematosus, etc., utilize their immunosuppressive activity.
   • cardiovascular disease As a candidate for antiarrhythmic or cardioprotective drugs.

2. R&D Challenge：

   • Insufficient brain permeability Low BBB permeability is a core obstacle in the treatment of central nervous system diseases.
   • Potential cardiac toxicity The risk of hERG inhibition needs to be avoided through structural optimization or formulation methods.
   • The complexity of multi-target characteristics Its network of action brings both advantages (comprehensive therapeutic effect) and disadvantages (unclear mechanism of side effects, difficult to accurately control).
   • Poor pharmaceutical properties Water solubility and bioavailability need to be improved.

3. Future Prospects：

   • Rational drug design based on target structure Develop derivatives or analogues with higher selectivity and better drug properties by modifying the structure of identified targets such as DRD2 and STAT3.
   • Advanced delivery system development Focus on building brain targeted nano delivery systems that can penetrate the BBB, or developing long-acting injectable formulations.
   • In depth mechanism research Using omics techniques (proteomics, metabolomics) and systems pharmacology methods, comprehensively elucidate its multi-target action network and "component target pathway disease" association.
   • High quality clinical research On the basis of fully completing preclinical safety evaluations (especially cardiac safety), promote rigorously designed clinical trials for specific indications (such as mild cognitive impairment, specific subtypes of leukemia) to obtain conclusive evidence of human efficacy and safety.

Conclusion

Berberine hydrochloride, as a natural product with a long history of application, is constantly being re recognized and explored for its modern pharmacological value. Its unique bisbenzylisoquinoline structure endows it with multi-target and multi pathway properties, demonstrating remarkable potential in anti dementia, anti-tumor, immune regulation, and other fields. Despite facing challenges such as insufficient brain permeability, potential cardiac toxicity, and poor physicochemical properties in terms of drug properties, these challenges are being actively addressed through modern medicinal chemistry, pharmacy, and pharmacology methods. In the future, through in-depth mechanism analysis, rational structural optimization, and innovative formulation strategies, berberine hydrochloride is expected to successfully transform from a traditional natural compound into a modern drug for treating major diseases such as neurodegenerative diseases and tumors, or provide an important lead compound skeleton for new drug development, demonstrating the sustained vitality of natural products in innovative drug discovery.