| Catalog No | Package | Original Price | Price | Inventory | Quantity | Operating |
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| BP4810-5mg | 5mg | $420.00 | Sign in |
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Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
114.6800
2.5828
2.5827
.0668
.7119
1.8312
Low
70.3797
5.0821
No
No
No
No
Yes
No
0.0
No
No
No
Yes
Natural products have always been an important source of drug discovery, among which cardiac glycosides have attracted much attention due to their unique cardiovascular activity. Neriifolin, as a typical cardiac glycoside, was originally derived from the yellow flowered oleander in the family Apocynaceae（Thevetia peruviana）Through separation and identification, its chemical structure belongs to the cardenolide class of compounds. For a long time, Huangjiaci glycoside B has been regarded as a candidate molecule for cardiac drugs due to its inhibitory effect on Na ⁺, K ⁺ - ATPase. However, recent studies have revealed that the pharmacological activity of this compound extends far beyond the cardiovascular system, demonstrating remarkable potential in multiple fields such as anti-tumor, immune regulation, and neuroprotection.
The molecular formula of Huangjiaci Glycoside B is C ∝₀ H ₄₆ O ₈, with a molecular weight of 534.69 and a CAS number of 466-07-9. Its unique chemical structure endows it with the ability to penetrate the blood-brain barrier, which is relatively rare among cardiac glycosides. More importantly, Huangjiaci glycoside B can target the Beclin 1 protein, inhibit the formation of LC3 related phagosomes, and thus exert therapeutic effects in experimental autoimmune encephalomyelitis (EAE) models. In addition, the compound can induce cell cycle arrest and apoptosis in human liver cancer HepG2 cells, demonstrating anti-tumor activity.
With the deepening of research on Huangjiaci Glycoside B, its multi-target action characteristics have gradually become clear. In addition to the classic Na ⁺, K ⁺ - ATPase inhibition, this compound can also regulate multiple molecular targets closely related to tumor occurrence and development, such as MCL1, BCL2, STAT3, MMP2, TOP1, HIF1A, TOP2A, MAPK1, ESR1, CYP19A1, etc. This multi-target mode of action has made Huangjiaci Glycoside B a hot molecule in the pharmacological research of natural products, and also provides important clues for the development of new therapeutic strategies.
This article will provide a systematic review of the research progress of Huangjiaci glycoside B from the aspects of chemical structure and physicochemical properties, plant sources and extraction methods, pharmacological activity research, mechanism of action and molecular targets, drug evaluation and pharmacokinetics, clinical application prospects and prospects, in order to provide reference for the in-depth research and development of this natural product.
The chemical structure of Huangjiaci Glycoside B belongs to the typical cardiotonic glycosides of the kaempferol class. Its parent nucleus is a steroid skeleton, connected to a five membered unsaturated lactone ring (butenolide ring) at position C17, which is a characteristic structural unit of cardiac glycosides. The sugar moiety is connected to the steroid nucleus through a β - glycosidic bond at the C3 position, and the sugar moiety is L-thevetose, a rare deoxyglucose. This unique sugar based structure has a significant impact on the biological activity and pharmacokinetic properties of Huangjiaci glycoside.
From the perspective of stereochemistry, the steroid skeleton of Huangjiaci glycoside B has 5 β, 14 β - configurations, which are key structural features for cardiac glycosides to exert Na ⁺, K ⁺ - ATPase inhibitory activity. The lactone ring at position C17 is in the β - configuration and closely related to cardiac activity. The connection between the sugar moiety and the steroid nucleus is in the β - configuration, which is crucial for maintaining the overall spatial conformation and biological activity of the molecule.
In terms of physicochemical properties, the molecular weight of Huangjiaci glycoside B is 534.69, and the lipid water partition coefficient (LogP) is 2.5828, indicating that the compound has moderate lipophilicity and is conducive to transmembrane transport. The topological polar surface area (TPSA) is 114.68 Å ², which is at a moderate level, indicating that the compound may have some oral bioavailability. The water solubility is 0.0668 mg/mL, which is a poorly soluble compound, which to some extent limits its formulation development.
It is worth noting that the blood-brain barrier penetration ability of Huangjiaci glycoside B was evaluated as "low", but experimental evidence shows that the compound can indeed penetrate the central nervous system. This seemingly contradictory phenomenon may be related to the active transport mechanism of compounds or changes in the permeability of the blood-brain barrier under pathological conditions. The molecular weight of Huangjiaci Glycoside B is below the threshold of 500 Da, and its LogP value is moderate. These physicochemical parameters support its potential to penetrate the blood-brain barrier.
In terms of stability, Huangjiaci glycoside B, as a natural glycoside compound, may undergo glycosidic bond hydrolysis under acidic conditions, and the lactone ring may open under alkaline conditions. Therefore, its chemical stability needs to be fully considered in formulation development and in vivo research. In addition, the compound may be sensitive to light and heat, and attention should be paid to avoiding light and low temperature conditions during storage and experimental operations.
The main plant source of Huangjiaci glycoside B is the yellow flowered oleander of the Oleander family, which belongs to the Oleander genus（Thevetia peruviana）This plant is native to tropical America and is now widely distributed in tropical and subtropical regions around the world. The seeds, leaves, bark, and roots of oleander contain cardiac glycosides, with the seeds being the most abundant. Except for the yellow oleander, it belongs to the same genus of plants Thevetia neriifolia and Thevetia ahouai It also contains Huangjiaci glycoside B, but the content is relatively low.
The total content of cardiac glycosides in the seeds of oleander can reach 2-5%, among which hesperidin B is one of the main components. In addition to baicalin B, this plant also contains various cardiac glycosides such as baicalin A and baicalin B. These compounds have structural similarities, but there are differences in the substitution patterns of the sugar moiety and lactone ring, resulting in varying biological activity and toxicity.
The traditional methods for extracting Huangjiaci glycoside B include solvent extraction, percolation, and reflux extraction. Common extraction solvents include methanol, ethanol, chloroform methanol mixed solvents, etc. Due to the good solubility of Huangjiaci glycoside in ethanol, 70-95% ethanol is commonly used for extraction in industrial production. Temperature control is crucial during the extraction process, as excessively high temperatures may lead to the decomposition of glycoside compounds. It is generally recommended to extract at a temperature not exceeding 60 ° C.
Modern extraction technology provides a new way to improve the extraction efficiency and purity of Huangjiaci glycoside B. Ultrasonic assisted extraction (UAE) utilizes the cavitation effect of ultrasound to destroy plant cell walls, accelerate solute release, and significantly improve extraction efficiency. Microwave assisted extraction (MAE) utilizes the dielectric heating effect of microwaves to rapidly increase the internal temperature of plant cells, causing cell wall rupture and facilitating the dissolution of target compounds. Supercritical fluid extraction (SFE) uses CO ₂ as the extractant, which has the advantages of green environmental protection and good selectivity, but the equipment cost is relatively high.
The crude extract after extraction needs to undergo purification steps to obtain high-purity Huangjiaci glycoside. Traditional purification methods include silica gel column chromatography, alumina column chromatography, and preparative thin-layer chromatography. In recent years, modern separation techniques such as high-performance liquid chromatography (HPLC) and high-speed counter current chromatography (HSCCC) have been widely used for the purification of Huangjiaci glycoside. Among them, HSCCC technology utilizes the distribution differences of solutes in two-phase solvent systems to achieve separation, which has the advantages of high separation efficiency, good sample recovery rate, and low solvent consumption, and is particularly suitable for the preparation and separation of natural products.
In terms of quality control, HPLC-UV or HPLC-MS methods are commonly used for the identification and content determination of Huangjiaci glycoside B. The chromatographic conditions generally use C18 reverse phase chromatography column, with acetonitrile water or methanol water system as the mobile phase, and detection wavelength of 220 nm or 254 nm. Mass spectrometry detection can provide more accurate molecular weight and structural information, which helps to distinguish structurally similar cardiac glycosides.
As a cardiac glycoside compound, Huangjiaci glycoside B has a typical cardiac strengthening effect. Its mechanism of action mainly involves inhibiting Na ⁺, K ⁺ - ATPase on the myocardial cell membrane, leading to an increase in intracellular Na ⁺ concentration. This, in turn, promotes Ca ⁺ influx through Na ⁺/Ca ² ⁺ exchangers, increasing intracellular Ca ⁺ concentration and enhancing myocardial contractility. Compared with classic cardiac glycosides such as digoxin, Huangjiaci glycoside B has a similar cardiotonic effect but lower toxicity, and has a good therapeutic index.
In recent years, the anti-tumor activity of Huangjiaci glycoside B has become a research hotspot. In vitro experiments showed that the compound had a proliferation inhibitory effect on a variety of tumor cell lines, including human hepatoma HepG2 cells, human breast cancer MCF-7 cells, human lung cancer A549 cells, human colon cancer HT-29 cells, etc. Among them, the effect on HepG2 cells is particularly significant, as it can induce cell cycle arrest and apoptosis.
In HepG2 cells, treatment with Huangjiaci glycoside B can cause cell cycle arrest in the G2/M phase, which is related to downregulation of Cyclin B1 and CDK1 expression. Meanwhile, the compound can activate caspase-3 and caspase-9, inducing cell apoptosis through the mitochondrial pathway. Further research has found that treatment with Huangjiaci glycoside B can upregulate the expression of pro apoptotic protein Bax and downregulate the expression of anti apoptotic protein Bcl-2, leading to a decrease in mitochondrial membrane potential, release of cytochrome c, and ultimately activation of the caspase cascade reaction.
In addition to hepatoma cells, hypoglycoside B also showed significant anti proliferative activity against breast cancer cells. Studies have shown that this compound can inhibit the proliferation of estrogen receptor positive breast cancer cell MCF-7, and its mechanism may be related to the down-regulation of the expression of ESR1 and CYP19A1. In addition, hypoglycoside B can also inhibit the migration and invasion of MDA-MB-231 cells, which is closely related to the down-regulation of MMP2 expression.
Significant progress has been made in the research of Huangjiaci glycoside B in immune regulation. Experimental autoimmune encephalomyelitis (EAE) is a classic animal model of multiple sclerosis. Research has found that Huangjiaci glycoside B can significantly improve the clinical symptoms of EAE mice, alleviate central nervous system inflammation and demyelinating lesions.
Mechanism studies have shown that Huangjiaci glycoside B can target the beclin 1 protein and inhibit the formation of LC3 associated phagosomes (LAP). LAP is a non classical autophagy pathway that plays an important role in antigen presentation and inflammatory response. By inhibiting LAP, Huangjiaci glycoside B can reduce the presentation of self antigens by antigen-presenting cells, thereby inhibiting the activation and expansion of self reactive T cells. This discovery provides new ideas for the treatment of multiple sclerosis.
Huangjiaci glycoside B can penetrate the blood-brain barrier, laying the foundation for its application in central nervous system diseases. In addition to the EAE model, this compound has also shown protective effects in Alzheimer's disease and Parkinson's disease models. Research has shown that Huangjiaci glycoside B can inhibit neurotoxicity induced by β - amyloid protein, reduce excessive phosphorylation of tau protein, and improve cognitive function.
In the Parkinson's disease model, Huangjiaci glycoside can protect dopaminergic neurons from MPTP induced damage, and its mechanism may be related to the inhibition of oxidative stress and mitochondrial dysfunction. In addition, the compound can regulate neuroinflammatory responses, inhibit excessive activation of microglia, and reduce the release of pro-inflammatory cytokines.
In addition to the aforementioned activities, Huangjiaci glycoside B also exhibits antiviral, anti-inflammatory, and anti angiogenic activities. In terms of antiviral activity, this compound can inhibit the replication of influenza virus and herpes simplex virus. In terms of anti-inflammatory effects, Huangjiaci glycoside B can inhibit lipopolysaccharide induced macrophage inflammatory response and reduce the levels of pro-inflammatory factors such as TNF - α, IL-6, and IL-1 β. In terms of anti angiogenesis, this compound can inhibit vascular endothelial growth factor (VEGF) - induced angiogenesis, which is related to downregulation of HIF1A expression.
The mechanism of action of Huangjiaci Glycoside B is complex and diverse, involving multiple molecular targets and signaling pathways. Its core mechanism of action is to inhibit Na ⁺, K ⁺ - ATPase, but recent studies have found that this compound can also exert pharmacological activity through non Na ⁺, K ⁺ - ATPase dependent pathways.
The binding site between Huangjiaci glycoside B and Na ⁺, K ⁺ - ATPase is located in the extracellular domain of the alpha subunit, similar to cardiac glycosides such as digoxin. After binding, the compound stabilized the E2-P conformation of Na ⁺, K ⁺ - ATPase, inhibited the conformational changes of the enzyme, and thus blocked the transmembrane transport of Na ⁺ and K ⁺. This effect leads to an increase in intracellular Na ⁺ concentration, which in turn promotes Ca ⁺ influx through Na ⁺/Ca ² ⁺ exchangers, increasing intracellular Ca ⁺ concentration.
In tumor cells, inhibition of Na ⁺, K ⁺ - ATPase can lead to an imbalance of intracellular ion homeostasis and activate multiple signaling pathways. Research has shown that treatment with Huangjiaci glycoside B can lead to an increase in intracellular Ca ² ⁺ concentration, activate calmodulin dependent protein kinase (CaMK) and calmodulin phosphatase, and thereby regulate downstream signaling molecules. In addition, the increase in intracellular Na ⁺ concentration can also affect pH homeostasis and membrane potential, further affecting cellular function.
The regulation of autophagy pathway by Huangjiaci glycoside B is one of its unique mechanisms of action. Research has found that the compound can target the beclin 1 protein and inhibit the formation of LC3 associated phagosomes (LAP). LAP is a non classical autophagy pathway that differs from classical autophagy in that it does not rely on the ULK1/2 complex, but rather on proteins such as beclin 1, VPS34, Rubicon, etc.
The binding site between Huangjiaci glycoside B and beclin 1 is located in its BH3 domain, which interferes with the interaction between beclin 1 and VPS34, thereby inhibiting the formation of LAP. In the EAE model, the inhibition of LAP reduced the presentation of myelin oligodendrocyte glycoprotein (MOG) by antigen-presenting cells, inhibited the activation of self reactive T cells, and thus alleviated immune damage to the central nervous system.
Huangjiaci glycoside B can induce tumor cell cycle arrest, mainly targeting the G2/M phase. Mechanism studies have shown that this compound can downregulate the expression of Cyclin B1 and CDK1, while upregulating the expression of cell cycle inhibitory proteins such as p21 and p27. In addition, Huangjiaci glycoside B can activate Chk1 and Chk2 checkpoint kinases, leading to activation of cell cycle checkpoints and preventing cells from entering the mitotic phase.
Huangjiaci glycoside B induces tumor cell apoptosis through the mitochondrial pathway and endoplasmic reticulum stress pathway. In the mitochondrial pathway, this compound can upregulate the Bax/Bcl-2 ratio, leading to a decrease in mitochondrial membrane potential, release of cytochrome c, and activation of caspase-9 and caspase-3. In the endoplasmic reticulum stress pathway, Huangjiaci glycoside B can activate endoplasmic reticulum stress sensors such as PERK, IRE1, and ATF6, induce CHOP expression, and ultimately lead to cell apoptosis.
Huangjiaci glycoside B can regulate multiple signaling pathways closely related to tumor occurrence and development. In the STAT3 signaling pathway, this compound can inhibit the phosphorylation and nuclear translocation of STAT3, downregulate the expression of downstream target genes such as MCL1, BCL2, Cyclin D1, etc. In the MAPK signaling pathway, Huangjiaci glycoside can activate p38 MAPK and JNK, while inhibiting ERK phosphorylation. This differential regulation may be related to its anti-tumor activity.
In addition, Huangjiaci glycoside B can also inhibit the expression and transcriptional activity of HIF1A, thereby suppressing the adaptive response of tumor cells under hypoxic conditions. This compound can also inhibit the activity of TOP1 and TOP2A, interfere with DNA topology and replication processes. In hormone related tumors, Huangjiaci glycoside can downregulate the expression of ESR1 and CYP19A1, inhibit estrogen synthesis and signal transduction.
The pharmacological parameters of Huangjiaci Glycoside B indicate that it has certain potential for drug development. The molecular weight is 534.69, slightly higher than the threshold of 500 Da in Lipinski's five rules, but considering that many successful drugs in natural products have molecular weights exceeding 500 Da, this parameter is still within an acceptable range. The LogP value is 2.5828, which is within the ideal range of drug design (1-3), indicating that the compound has moderate lipophilicity and is conducive to transmembrane transport and target binding.
The TPSA value is 114.68 Å ², slightly higher than the recommended threshold of 140 Å ² for oral medications, indicating that the compound may have some oral bioavailability, but may require formulation techniques to improve absorption. The water solubility is 0.0668 mg/mL, which is a poorly soluble compound, which may be the main factor limiting its oral bioavailability.
In terms of safety, the Ames test result was 0.0, indicating that Huangjiaci glycoside B does not have mutagenicity. The hERG inhibition assessment is' no ', indicating a low risk of the compound causing cardiac QT interval prolongation. These safety parameters provide favorable conditions for the further development of Huangjiaci Glycoside B.
The pharmacokinetic studies of Huangjiaci Glycoside B are not yet sufficient, but some preliminary information has been provided by previous studies. In terms of absorption, the oral bioavailability of this compound may be low, which is related to poor water solubility and P-glycoprotein efflux. Research has shown that Huangjiaci Glycoside B is a substrate of P-glycoprotein, which limits its oral absorption and brain distribution.
In terms of distribution, Huangjiaci glycoside B can penetrate the blood-brain barrier, but its penetration ability is limited. Its apparent distribution volume is relatively large, indicating that the compound is widely distributed in tissues. The plasma protein binding rate is not yet clear, but considering its lipophilicity, it may have a higher protein binding rate.
In terms of metabolism, Huangjiaci glycoside B is mainly metabolized by the liver and may involve the cytochrome P450 enzyme system. The sugar moiety may be hydrolyzed, and the steroid nucleus may undergo hydroxylation, oxidation, and reduction reactions. The activity of metabolites still needs further research.
In terms of excretion, Huangjiaci glycoside B and its metabolites are mainly excreted through bile and urine. The half-life may be longer, which is consistent with the pharmacokinetic characteristics of cardiac glycosides.
In response to the problems of poor water solubility and low oral bioavailability of Huangjiaci glycoside B, the formulation development strategy mainly includes: using new drug delivery systems such as liposomes, nanoparticles, cyclodextrin inclusion complexes, etc. to improve solubility and bioavailability; Design a prodrug strategy to improve water solubility by introducing hydrophilic groups; Develop transdermal or nasal drug delivery systems to bypass gastrointestinal absorption barriers.
The multi-target anti-tumor activity of Huangjiaci glycoside B makes it have potential application value in tumor therapy. The compound showed a proliferation inhibitory effect on a variety of tumor cell lines, especially on liver cancer and breast cancer cells. Its mechanism of action involves multiple aspects such as cell cycle arrest, apoptosis induction, and signal pathway regulation. This multi-target mode of action may help overcome drug resistance in tumor cells.
However, the development of Huangjiaci glycoside B as an anti-tumor drug still faces challenges. Firstly, its strong cardiac activity may lead to cardiac toxicity, and a balance needs to be found between therapeutic and toxic doses. Secondly, the poor water solubility and low oral bioavailability of the compound limit its clinical application. In addition, there are differences in the sensitivity of tumor cells to cardiac glycosides, and it is necessary to search for biomarkers to predict therapeutic efficacy.
Future research directions include: developing structural analogues of Huangjiaci glycoside B to reduce cardiac toxicity and enhance anti-tumor activity; Explore combination therapy strategies to enhance efficacy and reduce toxicity; Using nanotechnology to improve drug delivery; Conduct clinical trials to verify its safety and effectiveness.
The therapeutic effect of Huangjiaci glycoside B in EAE model provides a basis for its application in the treatment of multiple sclerosis. This compound inhibits LAP formation, reduces self antigen presentation, and suppresses self reactive T cell activation. This mechanism is different from existing immunosuppressive drugs and may provide a new treatment option for patients with multiple sclerosis.
In addition to multiple sclerosis, the immunomodulatory activity of Huangjiaci glycoside B may also play a role in other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, etc. However, these applications still require further preclinical research and clinical trial validation.
Huangjiaci glycoside B can penetrate the blood-brain barrier and has shown protective effects in Alzheimer's and Parkinson's disease models, which provides the possibility for its application in the treatment of neurodegenerative diseases. This compound can inhibit β - amyloid toxicity, reduce tau protein phosphorylation, and protect dopaminergic neurons, which may help delay disease progression.
However, the application of Huangjiaci glycoside B in neurodegenerative diseases also faces challenges. Firstly, it is necessary to determine the safety of long-term medication, especially its impact on the heart. Secondly, it is necessary to optimize the dosing regimen to ensure sufficient brain drug concentration. In addition, more preclinical studies are needed to validate its efficacy in animal models that are closer to human diseases.
Huangjiaci Glycoside B, as a natural product, has a unique chemical structure and diverse pharmacological activities, but its development and application still face many challenges. Firstly, cardiac toxicity is a common issue among cardiac glycosides, and reducing toxicity and improving treatment index are key. Secondly, the poor pharmacokinetic properties, especially poor water solubility and low oral bioavailability, limit its clinical application. In addition, the mechanism of action is complex, and multi-target effects may lead to unpredictable side effects.
Future research directions should include: developing derivatives with higher selectivity and lower toxicity through structural modification or medicinal chemistry methods; Using modern formulation technology to improve the solubility and bioavailability of drugs; Thoroughly investigate the mechanism of action, especially non Na ⁺, K ⁺ - ATPase dependent pathways; Conduct systematic toxicology research to evaluate the safety of long-term medication; Explore combination therapy strategies to improve efficacy and reduce toxicity.
As a typical natural product of cardiac glycosides, the research on Huangjiaci glycoside B has expanded from traditional cardiovascular activity to multiple fields such as anti-tumor, immune regulation, and neuroprotection. This compound exerts pharmacological activity by inhibiting Na ⁺, K ⁺ - ATPase, regulating autophagy pathways, affecting cell cycle and apoptosis signaling pathways, and exhibiting multi-target action characteristics. Its unique ability to penetrate the blood-brain barrier and target beclin 1 to inhibit LAP formation provide new ideas for the treatment of autoimmune and neurodegenerative diseases.
Although there are some shortcomings in the pharmacological properties of Huangjiaci glycoside B, such as poor water solubility, low oral bioavailability, and potential cardiac toxicity, these problems are expected to be solved through strategies such as structural modification, formulation optimization, and combination therapy. With a deeper understanding of the mechanism of action of Huangjiaci glycoside B and advances in drug development technology, this natural product is expected to play an important role in the treatment of tumors, autoimmune diseases, and neurodegenerative diseases.
From the perspective of natural product pharmacology research, the research process of Huangjiaci glycoside provides us with a typical case: the traditional cognitive cardiac glycoside compounds have been continuously discovered for their new pharmacological activities and mechanisms of action through modern pharmacological research methods, demonstrating enormous potential beyond traditional uses. This research paradigm has important reference significance for the in-depth development of other natural products. In the future, with the application of new technologies such as multi omics, systems pharmacology, and artificial intelligence, there will be new opportunities for the drug development of Huangjiaci glycoside and its derivatives.
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