Product name: Sanguinarine
Synonym name: Pseudochelerythrine; ψ-Chelerythrine
Catalogue No.: BP1253
Cas No.: 2447-54-3
Formula: C₂₀H₁₄NO₄+
Mol Weight: 332.334
Botanical Source:
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.

Description:

Sanguinarine possesses anticancer, antimicrobial, anti-inflammatory, and antioxidant properties, it has therapeutic potential in preventing the neurodegenerative diseases, it may be used to develop a potential therapeutic drug for treating cardiac remodeling and heart failure and shows protective effects on teeth and alveolar bone health. Sanguinarine can inhibit osteoclast formation and bone resorption via suppressing RANKL-induced activation of NF-κB and ERK signaling pathways, and can protect against cardiac hypertrophy and fibrosis via inhibiting NF-κB activation.

References:

Clin Cancer Res. 2000 Apr;6(4):1524-8.    

Differential antiproliferative and apoptotic response of sanguinarine for cancer cells versus normal cells.    

Sanguinarine, derived from the root of Sanguinaria canadendid, has been shown to possess antimicrobial, anti-inflammatory, and antioxidant properties. Here we compared the antiproliferative and apoptotic potential of Sanguinarine against human epidermoid carcinoma (A431) cells and normal human epidermal keratinocytes (NHEKs). 

METHODS AND RESULTS:

Sanguinarine treatment was found to result in a dose-dependent decrease in the viability of A431 cells as well as NHEKs albeit at different levels because Sanguinarine-mediated loss of viability occurred at lower doses and was much more pronounced in the A431 carcinoma cells than in the normal keratinocytes. DNA ladder assay demonstrated that compared to vehicle-treated control, Sanguinarine treatment of A431 cells resulted in an induction of apoptosis at 1-, 2-, and 5-microM doses. Sanguinarine treatment did not result in the formation of a DNA ladder in NHEKs, even at the very high dose of 10 microM. The induction of apoptosis by Sanguinarine was also evident by confocal microscopy after labeling the cells with annexin V. This method also identified necrotic cells, and Sanguinarine treatment also resulted in the necrosis of A431 cells. The NHEKs showed exclusively necrotic staining at high doses (2 and 5 microM). We also explored the possibility of cell cycle perturbation by Sanguinarine in A431 cells. The DNA cell cycle analysis revealed that Sanguinarine treatment did not significantly affect the distribution of cells among the different phases of the cell cycle in A431 cells. 

CONCLUSIONS:

We suggest that Sanguinarine could be developed as an anticancer drug.    

Oncotarget. 2015 Apr 30;6(12):10335-49.    

Molecular signatures of sanguinarine in human pancreatic cancer cells: A large scale label-free comparative proteomics approach.   

Pancreatic cancer remains one of the most lethal of all human malignancies with its incidence nearly equaling its mortality rate. Therefore, it's crucial to identify newer mechanism-based agents and targets to effectively manage pancreatic cancer. Plant-derived agents/drugs have historically been useful in cancer therapeutics. Sanguinarine is a plant alkaloid with anti-proliferative effects against cancers, including pancreatic cancer. This study was designed to determine the mechanism of Sanguinarine's effects in pancreatic cancer with a hope to obtain useful information to improve the therapeutic options for the management of this neoplasm. 

METHODS AND RESULTS:

We employed a quantitative proteomics approach to define the mechanism of Sanguinarine's effects in human pancreatic cancer cells. Proteins from control and Sanguinarine-treated pancreatic cancer cells were digested with trypsin, run by nano-LC/MS/MS, and identified with the help of Swiss-Prot database. Results from replicate injections were processed with the SIEVE software to identify proteins with differential expression. We identified 37 differentially expressed proteins (from a total of 3107), which are known to be involved in variety of cellular processes. Four of these proteins (IL33, CUL5, GPS1 and DUSP4) appear to occupy regulatory nodes in key pathways. Further validation by qRT-PCR and immunoblot analyses demonstrated that the dual specificity phosphatase-4 (DUSP4) was significantly upregulated by Sanguinarine in BxPC-3 and MIA PaCa-2 cells. Sanguinarine treatment also caused down-regulation of HIF1α and PCNA, and increased cleavage of PARP and Caspase-7. 

CONCLUSIONS:

Taken together, Sanguinarine appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of Sanguinarine against pancreatic cancer.    

Environ Toxicol Pharmacol. 2014 Nov;38(3):701-10.    

Involvement of heme oxygenase-1 in neuroprotection by sanguinarine against glutamate-triggered apoptosis in HT22 neuronal cells.   

Sanguinarine is a natural compound isolated from the roots of Macleaya cordata and M. microcarpa, has been reported to possess several biological activities such as anti-inflammatory and anti-oxidant effects. 

METHODS AND RESULTS:

In the present study, we demonstrated that Sanguinarine markedly induces the expression of HO-1 which leads to a neuroprotective response in mouse hippocampus-derived neuronal HT22 cells from apoptotic cell death induced by glutamate. Sanguinarine significantly attenuated the loss of mitochondrial function and membrane integrity associated with glutamate-induced neurotoxicity. Sanguinarine protected against glutamate-induced neurotoxicity through inhibition of HT22 cell apoptosis. JC-1 staining, which is a well-established measure of mitochondrial damage, was decreased after treatment with Sanguinarine in glutamate-challenged HT22cells. In addition, Sanguinarine diminished the intracellular accumulation of ROS and Ca(2+). Sanguinarine also induced HO-1, NQO-1 expression via activation of Nrf2. Additionally, we found that si RNA mediated knock-down of Nrf2 or HO-1 significantly inhibited Sanguinarine-induced neuroprotective response. 

CONCLUSIONS:

These findings revealed the therapeutic potential of Sanguinarine in preventing the neurodegenerative diseases.    

Mol Med Rep. 2014 Jul;10(1):211-6.    

Sanguinarine protects against pressure overload‑induced cardiac remodeling via inhibition of nuclear factor-κB activation.    

Cardiac remodeling is a major determinant of heart failure characterized by cardiac hypertrophy and fibrosis. Sanguinarine exerts widespread pharmacological effects, including antitumor and anti‑inflammatory responses. In the present study, the effect of Sanguinarine on cardiac hypertrophy, fibrosis and heart function was determined using the model induced by aortic banding (AB) in mice. 

METHODS AND RESULTS:

AB surgery and sham surgery were performed on male wild‑type C57 mice, aged 8‑10 weeks, with or without administration of Sanguinarine from one week after surgery for an additional seven weeks. Sanguinarine protected against the cardiac hypertrophy, fibrosis and dysfunction induced by AB, as assessed by the heart weight/body weight, lung weight/body weight and heart weight/tibia length ratios, echocardiographic and hemodynamic parameters, histological analysis, and the gene expression levels of hypertrophic and fibrotic markers. The inhibitory effect of Sanguinarine on cardiac remodeling was mediated by inhibiting nuclear factor (NF)‑κB signaling pathway activation. 

CONCLUSIONS:

The findings indicated that Sanguinarine protected against cardiac hypertrophy and fibrosis via inhibiting NF‑κB activation. These findings may be used to develop a potential therapeutic drug for treating cardiac remodeling and heart failure.    

Biochem Biophys Res Commun. 2013 Jan 18;430(3):951-6.    

Sanguinarine inhibits osteoclast formation and bone resorption via suppressing RANKL-induced activation of NF-κB and ERK signaling pathways.   

Sanguinarine is a natural plant extract that has been supplemented in a number of gingival health products to suppress the growth of dental plaque. However, whether Sanguinarine has any effect on teeth and alveolar bone health is still unclear. 

METHODS AND RESULTS:

In this study, we demonstrated for the first time that Sanguinarine could suppress osteoclastic bone resorption and osteoclast formation in a dose-dependent manner. Sanguinarine diminished the expression of osteoclast marker genes, including TRAP, cathepsin K, calcitonin receptor, DC-STAMP, V-ATPase d2, NFATc1 and c-fos. Further investigation revealed that Sanguinarine attenuated RANKL-mediated IκBα phosphorylation and degradation, leading to the impairment of NF-κB signaling pathway during osteoclast differentiation. In addition, Sanguinarine also affected the ERK signaling pathway by inhibiting RANKL-induced ERK phosphorylation. 

CONCLUSIONS:

Collectively, this study suggested that Sanguinarine has protective effects on teeth and alveolar bone health.    

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

Introduction/Overview

Sanguinarine is a natural alkaloid with significant biological activity, mainly derived from the poppy family plant Sanguinarine（Sanguinaria canadensis）. As a multifunctional natural product, sanguinarine is widely used in traditional medicine for anti-inflammatory, antibacterial, and hemostatic purposes. In recent years, with the deepening development of tumor biology and molecular pharmacology, sanguinarine has gradually become a hot topic in natural product pharmacology research due to its unique advantages in inducing cell apoptosis, regulating signaling pathways, and anti-tumor activity. Especially in the treatment research of malignant tumors such as cervical cancer, sanguinarine has shown good anti-cancer potential, involving the regulation of multiple key molecular targets and signaling pathways.

This article will systematically review the chemical structure and physicochemical properties, plant sources and extraction methods, pharmacological activity and mechanism of action of sanguinarine, with a focus on analyzing its molecular targets and signaling pathway regulation in the treatment of cervical cancer, evaluating its pharmacological and pharmacokinetic characteristics, and looking forward to its clinical application prospects, providing theoretical basis and research direction for the subsequent development and clinical translation of related drugs.

Chemical structure and physicochemical properties

Blood root alkaloid (CAS number: 2447-54-3) is a typical isoquinoline alkaloid with a molecular formula of C20H14NO4 and a molecular weight of 332.3350. Its structural features include a polycyclic system containing an oxygen-containing heterocyclic ring, with conjugated benzene rings and methylene bridging structures, endowing it with strong electron delocalization ability and biological activity. The LogP value of sanguinarine is 0.4141, indicating its moderate lipophilicity, which facilitates the penetration of cell membranes; The TPSA is 40.8 Å ², indicating that its polarity is moderate and conducive to binding with biological targets. The low water solubility (0.0426 mg/mL) to some extent limits its oral bioavailability, but also suggests the need for formulation optimization to improve its solubility and absorption.

Blood root alkaloids have a high ability to penetrate the blood-brain barrier, indicating their potential application value in the treatment of central nervous system diseases. The hERG channel inhibition experiment showed a negative result, indicating a low risk of cardiac toxicity. The Ames test value is 2.4, indicating that sanguinarine has a certain genotoxicity risk and needs to be given special attention in preclinical safety evaluation.

Plant sources and extraction methods

Bloodroot alkaloids are mainly found in the poppy family plant Bloodroot Grass（Sanguinaria canadensis）In the roots and rhizomes. This plant is widely distributed in North America and has traditionally been used to treat skin diseases, inflammation, and oral diseases. The extraction of sanguinarine is usually carried out by organic solvent extraction, combined with liquid-liquid separation and column chromatography purification techniques.

Common extraction techniques include:

1. Solvent extraction Using ethanol, methanol, or ethyl acetate as solvents, repeatedly extract dried and crushed roots of blood roots to extract blood root alkaloids and related alkaloids.
2. Acid-base separation By utilizing the alkaline properties of sanguinarine, enrichment and separation of sanguinarine can be achieved by adjusting the pH value.
3. Column chromatography purification Using silica gel column chromatography or reverse phase C18 column chromatography, further purify sanguinarine to obtain high-purity compounds.
4. Crystallization and drying The purified sanguinarine is subjected to solvent crystallization and drying treatment to obtain a stable solid preparation.

In recent years, green extraction techniques such as ultrasound assisted extraction, microwave-assisted extraction, and supercritical fluid extraction have gradually been applied to the extraction of sanguinarine, significantly improving extraction efficiency and purity, reducing solvent consumption and environmental pollution.

Pharmacological activity research

Blood root alkaloids exhibit various pharmacological activities, including anti-tumor, anti-inflammatory, antibacterial, and antioxidant effects. Its anti-tumor activity is particularly prominent and has been confirmed in a variety of tumor cell lines, including cervical cancer, lung cancer, breast cancer, colorectal cancer, etc.

Antitumor activity

Blood root alkaloids exert anticancer effects by inducing tumor cell apoptosis, inhibiting cell proliferation, blocking cell cycle, and inhibiting tumor cell migration and invasion. Multiple in vitro studies have shown that sanguinarine can significantly reduce the survival rate of cervical cancer cells, induce cell apoptosis, and inhibit tumor related signaling pathways.

Anti inflammatory and antibacterial activity

Blood root alkaloids have the ability to inhibit the release of inflammatory mediators and regulate immune responses, which can alleviate inflammatory reactions. In addition, sanguinarine exhibits inhibitory effects on various Gram positive and Gram negative bacteria, and has potential anti infective value.

Antioxidant and neuroprotective effects

Although sanguinarine can induce cell apoptosis by activating reactive oxygen species (ROS), it also exhibits the ability to regulate oxidative stress within a certain concentration range, which may have a protective effect on neurological diseases.

Mechanism of action and molecular targets

The mechanism of cell apoptosis induced by sanguinarine is complex and involves the regulation of multiple signaling pathways. The core mechanism mainly includes ROS mediated oxidative stress, activation of JNK (c-Jun N-terminal kinase) and NF - κ B (nuclear factor kappa B) signaling pathways.

ROS mediated cell apoptosis

Blood root alkaloids can promote the production of intracellular ROS, leading to an increase in oxidative stress levels, disruption of mitochondrial membrane potential, release of cytochrome c, activation of caspase cascade reaction, and ultimately triggering cell apoptosis. The accumulation of ROS can also activate various stress-related signaling pathways and enhance anti-tumor effects.

JNK signaling pathway

JNK, as a stress kinase, plays a crucial role in cell apoptosis induced by sanguinarine. Blood root alkaloids activate JNK signaling, promote the expression of pro apoptotic proteins such as BAX, inhibit anti apoptotic protein BCL2, and regulate cell fate. The activation of JNK can also enhance the production of ROS, form positive feedback, and promote tumor cell death.

NF - κ B signaling pathway

NF - κ B is an important transcription factor that regulates cell survival, inflammation, and immune response. Blood root alkaloids can regulate the activity of NF - κ B, inhibit its pro survival signal, and promote cell apoptosis. Research has shown that sanguinarine reduces cell anti apoptotic ability and enhances chemotherapy sensitivity by inhibiting NFKB1 gene expression.

Related molecular targets

In the study of cervical cancer, the action of sanguinarine involves multiple key genes and proteins:

• BCL2/BAX Regulating apoptotic proteins in the mitochondrial pathway, hemoglobin downregulates BCL2, promotes BAX expression, and induces apoptosis.
• TP53 Tumor suppressor genes, such as sanguinarine, can activate the p53 pathway, promote cell cycle arrest and apoptosis.
• EGFR Hemogen alkaloids inhibit EGFR signaling and block tumor cell proliferation signaling.
• TOP1 DNA topoisomerase and sanguinarine may interfere with DNA replication and repair by affecting TOP1 activity.
• CDKN1A (p21)、CDKN2A Cell cycle regulatory factors, induced by sanguinarine, inhibit cell cycle progression.
• RB1 Cell cycle inhibitory protein, sanguinarine promotes cell cycle arrest by regulating RB1 activity.
• HPVE6 Cervical cancer-related viral proteins and sanguinarine may inhibit HPV E6 expression and restore p53 function.

In summary, sanguinarine achieves effective inhibition of cervical cancer cells through multi-target and multi pathway synergistic effects.

Evaluation of drug properties and pharmacokinetics

The pharmacological evaluation of sanguinarine shows that it has certain potential for drug development, but there are still challenges.

Pharmacokinetic characteristics

The molecular weight of sanguinarine is moderate, and the LogP value indicates that it has good membrane permeability, and TPSA is suitable for oral absorption. Its low water solubility limits its oral bioavailability, and pharmaceutical methods such as nanocarriers, liposomes, or solid dispersions are needed to improve solubility and stability.

The high penetration ability of the blood-brain barrier suggests its potential application in central nervous system diseases, but it may also pose a risk of central neurotoxicity.

safety assessment

The hERG channel inhibition experiment was negative, indicating a low risk of cardiac toxicity, which is beneficial for clinical development. The Ames test shows that sanguinarine has certain genotoxicity, and systematic genotoxicity and carcinogenicity assessments need to be conducted before clinical practice.

Pharmacokinetic study

Existing research indicates that the metabolism of sanguinarine in the body is mainly through the liver enzyme system, and the activity and toxicity of metabolites still need to be further explored. The half-life, central distribution, and excretion pathway of sanguinarine are not yet clear, and further pharmacokinetic and toxicological studies are needed in vivo.

Clinical application prospects and prospects

As a natural product with multi-target anti-tumor activity, sanguinarine has shown broad application prospects in the treatment of malignant tumors such as cervical cancer. Its ability to induce tumor cell apoptosis and regulate key tumor related signaling pathways provides an important foundation for the development of new anti-cancer drugs.

Future research directions include:

1. Pharmaceutical optimization Develop efficient and low toxicity drug delivery systems to improve the water solubility and bioavailability of sanguinarine.
2. Combination therapy strategy Combined use with existing chemotherapy drugs or targeted drugs to enhance anti-tumor efficacy and overcome drug resistance.
3. Safety and Toxicological Assessment Systematically evaluate the genetic toxicity, hepatorenal toxicity, and long-term safety of sanguinarine to ensure its safe clinical application.
4. Clinical trial design Conduct preclinical and clinical studies based on molecular targets to validate the efficacy and safety of sanguinarine in cervical cancer and other tumors.
5. In depth analysis of the mechanism of action Using multi omics techniques, comprehensively analyze the molecular network of the action of sanguinarine, and explore potential biomarkers and new targets.

In addition, considering the blood-brain barrier penetration ability of sanguinarine, its potential application in neurological diseases and brain tumors is also worth paying attention to.

Conclusion

As a natural plant derived isoquinoline alkaloid, sanguinarine has shown significant research value and application potential in the field of anti-tumor therapy due to its unique chemical structure and multi-target pharmacological effects. Especially in the treatment of cervical cancer, sanguinarine effectively inhibits tumor cells by activating ROS, regulating JNK and NF - κ B signaling pathways. Although there are certain challenges in terms of its water solubility and genotoxicity, with the assistance of modern pharmaceutical and molecular biology technologies, sanguinarine is expected to become an important candidate for novel anti-cancer drugs.

In the future, combining systematic pharmacokinetic studies and preclinical safety evaluations, the clinical translation prospects of sanguinarine are broad. Continuous in-depth mechanism research and innovative drug development strategies will promote the greater role of sanguinarine in natural product pharmacology and tumor therapy, benefiting patients.