| Catalog No | Package | Original Price | Price | Inventory | Quantity | Operating |
|---|---|---|---|---|---|---|
| BP0905-100mg | 100mg | $30.00 | Sign in |
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Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
62.1600
.2294
-.0451
2.9941
2.3696
9.1808
High
38.7087
4.2500
No
No
No
No
Yes
No
0.9
Yes
Yes
Yes
Yes
Natural products, as an important source of drug discovery, play an irreplaceable role in the long history of human fight against diseases. The active ingredients isolated and identified from traditional herbs not only provide a unique chemical framework for modern drug development, but also reveal numerous novel pharmacological mechanisms of action. Amaryllidaceae plants, such as Amaryllidaceae（Lycoris radiata）Narcissus（Narcissus Spp.) has attracted much attention due to its unique structure of alkaloid compounds. Among them, Lycorine, as one of the most abundant and extensively studied isoquinoline alkaloids in this family of plants, has been a research hotspot in the fields of natural product chemistry and pharmacology since its discovery in the 19th century.
Lycorine hydrochloride (CAS number: 2188-68-3) is the hydrochloride form of lycorine, which has significantly improved water solubility compared to free bases, making it easier for in vivo and in vitro pharmacological experiments and formulation development. Early research mainly focused on the antiviral and anti-inflammatory effects of lycorine, while in the past two decades, its anti-tumor activity, especially its inhibitory effect on various malignant tumors such as leukemia and melanoma, has attracted high attention from the international academic community. Research has confirmed that allicin hydrochloride can intervene in key biological processes such as tumor cell proliferation, apoptosis, angiogenesis, and drug resistance through multi-target and multi pathway approaches. For example, it has been identified as an effective inhibitor of melanoma angiogenesis and can inhibit the mitotic proliferation of Hey1B cells at low micromolar concentrations (IC50 of 1.2 μ M).
This article aims to provide a systematic review of the research progress of allicin hydrochloride, covering its chemical structure and physicochemical properties, plant sources and extraction processes, extensive pharmacological activities, in-depth molecular mechanisms of action, drug evaluation and pharmacokinetic characteristics. It also looks forward to its future clinical application prospects and challenges, in order to provide comprehensive references for the in-depth development and transformation research of this natural product.
The chemical essence of lycorine hydrochloride comes from lycorine, which is a pyrrolophenanthridine alkaloid with a unique four ring skeleton. Its core structure consists of a partially saturated pyridine ring system fused with a five membered nitrogen-containing heterocyclic ring, specifically including a tetrahydropyrrole ring, a benzene ring, and a trans fused decahydroquinoline ring. There are multiple chiral centers in the molecule of lycorine, and its absolute configuration has been determined. This rigid, highly oxidized polycyclic structure is the structural basis for its interaction with various biological targets.
The molecular weight of lycorine hydrochloride (molecular formula: C16H17NO4 · HCl) is 287.3150 (free base is 287.31). The physicochemical properties parameters are crucial for understanding its biological activity and potential as a drug. The calculated oil-water partition coefficient (LogP) is 0.2294, indicating that the compound has moderate lipophilicity, neither completely hydrophobic nor completely hydrophilic, which is beneficial for its transmembrane transport and distribution in organisms. Its polar surface area (TPSA) is 62.1600 Å ², which is lower than the commonly believed passive diffusion upper limit (about 140 Å ²), indicating its good oral absorption potential. The water solubility parameter is 2.9941, indicating that it has a certain solubility in water, and the hydrochloride form further enhances its solubility in aqueous environments, which is particularly advantageous for in vitro cell experiments and in vivo injection administration.
It is worth noting that the blood-brain barrier (BBB) permeability prediction shows "high". This characteristic has a double-edged sword effect: on the one hand, for the treatment of central nervous system diseases such as brain tumors or neurodegenerative diseases, high BBB permeability is its advantage; On the other hand, it may also increase the risk of central nervous system toxicity, which requires attention in drug development. In addition, hERG inhibition is predicted to be 'no', indicating a low risk of causing cardiac QT interval prolongation and fatal arrhythmias, which is a positive pharmacological signal. The Ames test result is 0.9, indicating a low potential risk of genetic toxicity. These physicochemical properties together outline the profile of allicin hydrochloride as a natural product molecule with good drug like characteristics.
The natural source of allicin hydrochloride is widely present in various plants of the Amaryllidaceae family, including the genus Amaryllidaceae（Lycoris）The plant content is the most abundant. Garlic（Lycoris radiata）Also known as the other shore flower or manjushri, it is the traditional main raw material for extracting lycorine. In addition, the genus Narcissus（Narcissus）Gentiana genus（Clivia）Snow Drop Flower Genus（Galanthus）And the tennis flower genus（Haemanthus）Many plants in the Alliaceae family also contain allicin. The content of lycorine varies significantly among different plant species, production areas, harvest seasons, and tissue parts (such as bulbs, leaves, and scapes), with the highest content usually found in the bulbs.
The traditional extraction method is mainly based on the acid-base properties of alkaloids. The classic process route includes soaking or percolating dried and crushed plant materials (such as garlic bulb powder) in an acidic aqueous solution (such as 0.5% -1% hydrochloric acid or sulfuric acid) to dissolve alkaloids in salt form. After alkalizing the extraction solution (such as adjusting the pH to 9-10 with ammonia or sodium hydroxide), it is extracted with organic solvents (such as chloroform, ethyl acetate, or ether). The crude extract of total alkaloids was obtained by concentrating the organic phase. Subsequently, separation and purification were carried out using the solubility differences of lycorine and its homologues in different solvents or chromatographic techniques such as silica gel column chromatography and alumina column chromatography. Due to the good solubility of lycorine in ethanol, the ethanol reflux extraction method is often used, combined with acid-base treatment and recrystallization techniques, to obtain high-purity lycorine crystals. Finally, the purified lycorine can be reacted with hydrochloric acid to produce lycorine hydrochloride.
With the development of green chemistry and efficient extraction technology, some modern extraction techniques have also been applied to the preparation of lycorine hydrochloride. For example, ultrasound assisted extraction (UAE) and microwave-assisted extraction (MAE) can significantly shorten extraction time and improve extraction efficiency by disrupting cell walls and accelerating solvent permeation. In recent years, supercritical fluid extraction (SFE), especially using carbon dioxide as a solvent, has shown potential applications in extracting alkaloids from the Alliaceae family due to its advantages of no solvent residue, environmental friendliness, and high selectivity. In addition, high-speed countercurrent chromatography (HSCCC), as an efficient liquid-liquid distribution chromatography technique, can achieve efficient separation of lycorine alkaloids from other structurally similar alkaloids in one step without the need for a solid stationary phase, making it an ideal method for preparing high-purity standards. The application of these modern technologies provides reliable material support for the large-scale production and in-depth research of allicin hydrochloride.
Lycorine hydrochloride has demonstrated extensive and significant pharmacological activities, with the most in-depth and systematic research on its anti-tumor effects.
1. Antitumor activity
Hydrochloric acid lycorine exhibits strong inhibitory effects on the proliferation of various types of tumor cell lines. In leukemia research, it can effectively inhibit the vitality of various leukemia cell lines (such as HL-60, K562, U937, etc.) and induce their apoptosis. Its inhibition of mitotic proliferation in Hey1B cells (IC50 of 1.2 μ M) is a typical example of its anti-tumor activity. In addition to leukemia, its anti-tumor spectrum also covers solid tumors, such as liver cancer, lung cancer, breast cancer, stomach cancer, colorectal cancer, melanoma, glioblastoma, etc. Of particular note is that lycorine hydrochloride has been identified as a melanoma angiogenesis inhibitor, which can indirectly inhibit tumor growth and metastasis by suppressing the formation of tumor neovascularization, cutting off the tumor's nutritional supply. In addition, it can reverse the multidrug resistance (MDR) of tumor cells and exhibit synergistic effects when combined with conventional chemotherapy drugs such as doxorubicin and paclitaxel, which is of great significance for overcoming clinical chemotherapy resistance.
2. Anti inflammatory and immune regulatory activity
Lycorine hydrochloride has significant anti-inflammatory activity. Research has shown that it can inhibit the production of nitric oxide (NO), prostaglandin E2 (PGE2), and various pro-inflammatory cytokines (such as TNF - α, IL-6, IL-1 β) in macrophages induced by lipopolysaccharide (LPS). The mechanism is related to the inhibition of the activation of nuclear factor kappa B (NF - κ B) and mitogen activated protein kinase (MAPK) signaling pathways. In animal models, allicin hydrochloride has shown protective effects on acute and chronic inflammation models induced by carrageenan, such as toe swelling and cotton ball granuloma. In addition, it can also regulate immune function, such as affecting the proliferation and differentiation of T lymphocytes.
3. Antiviral activity
Lycorine is one of the earliest natural products reported to have antiviral activity. It exhibits broad-spectrum antiviral effects, including inhibitory effects on SARS coronavirus, influenza virus, herpes virus, poliovirus, yellow fever virus, and human immunodeficiency virus (HIV). Its antiviral mechanism may involve inhibiting viral nucleic acid replication, interfering with viral protein synthesis, or affecting the assembly and release of viral particles. During the fight against COVID-19, lycorine and its derivatives have also been found to have potential inhibitory effects on SARS-CoV-2 virus, sparking a new round of research interest.
4. Other pharmacological activities
In addition to the main activities mentioned above, lycorine hydrochloride has also been reported to have anti parasitic and microbial activities such as anti malaria parasites, anti amoebic parasites, and anti fungi. In terms of the nervous system, due to its high BBB permeability, research has found that it may have potential therapeutic value for neurodegenerative diseases such as Alzheimer's disease by inhibiting acetylcholinesterase (AChE) activity. In addition, its anti fibrotic and anti platelet aggregation activities have occasionally been reported.
The pharmacological activity of allicin hydrochloride is the result of its interaction with multiple molecular targets within cells and regulation of multiple signaling pathways. Its mechanism of action has the characteristics of multiple targets and pathways, which is also a significant feature that distinguishes natural products from single target synthetic drugs.
1. Inducing cell apoptosis and autophagy
One of the core mechanisms of allicin hydrochloride in anti-tumor treatment is the induction of tumor cell apoptosis. It can:
- Activate mitochondrial apoptosis pathway By downregulating the expression of anti apoptotic protein BCL2 (B-cell lymphoma 2) and upregulating the expression of pro apoptotic protein BAX, mitochondrial membrane potential is lost, cytochrome c is released, and Caspase-9 and Caspase-3 are activated, ultimately executing the apoptotic program.
- Regulating STAT3 signaling STAT3 (Signal transducer and activator of transcription 3) is a key oncogenic transcription factor. Lycorine hydrochloride can inhibit the phosphorylation and nuclear translocation of STAT3, thereby downregulating its downstream target genes, including MCL1 (Myeloid cell leukemia 1, an anti apoptotic protein) and cell cycle regulatory proteins, promoting tumor cell apoptosis.
- Inducing endoplasmic reticulum stress By interfering with protein folding, it triggers unfolded protein response (UPR) and activates endoplasmic reticulum specific apoptotic pathways such as Caspase-12.
- Inducing autophagic death In certain cell types, allicin hydrochloride can induce protective or lethal autophagy by inhibiting the mTOR signaling pathway and activating AMPK (AMP activated protein kinase, encoded by the PRKAA1 gene).
2. Inhibit cell proliferation and cycle arrest
Salicylic acid lycorine can arrest the tumor cell cycle in the G2/M phase or G0/G1 phase. The mechanism includes:
- Inhibit mitosis By directly or indirectly interfering with the dynamic balance of microtubule proteins, it affects the formation of the spindle and leads to mitotic arrest. This is consistent with its potent inhibitory effect on the mitotic proliferation of Hey1B cells.
- Regulating cell cycle proteins Downregulate the expression of Cyclin D1, Cyclin B1, and cyclin dependent kinases (CDKs), while upregulating the levels of CDK inhibitors p21 and p27.
- Intervention of NOTCH1 signal The NOTCH1 (Notch receptor 1) signaling pathway plays a crucial role in maintaining self-renewal of leukemia stem cells. Lycorine hydrochloride can inhibit the activation of NOTCH1, thereby suppressing the proliferation of leukemia cells.
3. Inhibit angiogenesis
As an inhibitor of melanoma angiogenesis, allicin hydrochloride can:
- Inhibition of VEGF signaling Downregulate the expression of vascular endothelial growth factor (VEGF) and its receptor (VEGFR), and block the proliferation and migration of endothelial cells.
- Interference with HIF-1 α stability Inhibit the accumulation of hypoxia inducible factor-1 alpha (HIF-1 alpha), thereby reducing the transcription of downstream angiogenic factors.
4. Reverse multidrug resistance
Lycorine hydrochloride can effectively reverse multidrug resistance in tumor cells, and its mechanism mainly involves:
- Inhibit drug efflux pump Directly inhibit the function of ABCB1 (ATP binding cassette sub family B member 1, P-glycoprotein, P-gp), reduce the efflux of chemotherapy drugs from cells, and increase intracellular drug concentration.
- Regulating resistance related signals By inhibiting signaling pathways such as NF - κ B and STAT3, downregulating anti apoptotic proteins such as MCL1, and restoring the sensitivity of drug-resistant cells to chemotherapy drugs.
5. Other targets
- IDH1（Isocitrate dehydrogenase 1）In acute myeloid leukemia (AML) carrying IDH1 mutations, allicin hydrochloride may exert anti leukemia effects by affecting the activity of mutant IDH1 and regulating the levels of intracellular metabolites such as 2-hydroxyglutarate.
- NFE2L2 (Nuclear factor erythroid 2-related factor 2, also known as NRF2)NRF2 is a key transcription factor for cellular antioxidant stress. The regulation of NRF2 by allicin hydrochloride has a dual nature, which may activate NRF2 in some cases to protect normal cells, while in other cases it may inhibit NRF2 to increase the sensitivity of tumor cells to oxidative stress.
- MAPT（Microtubule-associated protein tau）By interacting with microtubule associated protein Tau, it may affect microtubule stability and participate in its anti mitotic and neural activity.
- PRKCA（Protein kinase C alpha）PKC α is involved in cell proliferation, differentiation, and apoptosis. Hydrochloric acid lycorine may affect downstream signal transduction by regulating the activity of PKC α.
Based on the aforementioned physicochemical parameters, allicin hydrochloride exhibits good medicinal properties. Its moderate LogP, reasonable TPSA, good water solubility, and low risk of hERG and Ames toxicity lay the foundation for it to become a candidate drug. However, pharmacokinetic (PK) characteristics are the key factors determining whether a compound can ultimately become a drug.
There have been some preliminary but important findings regarding the pharmacokinetic study of allicin hydrochloride. In terms of absorption, due to its moderate LogP and good water solubility, it can theoretically be absorbed by the gastrointestinal tract after oral administration. However, alkaloid compounds are often affected by first pass effects and intestinal P-gp efflux, which may result in low oral bioavailability. Animal experiments have shown that after oral administration of lycorine hydrochloride, the peak time of blood drug concentration is relatively fast, but the absolute bioavailability data is not sufficient and further systematic research is needed. Its high BBB permeability suggests that drugs can quickly enter brain tissue, which is advantageous for treating brain diseases, but potential side effects on the central nervous system also need to be considered.
In terms of distribution, lycorine hydrochloride is widely distributed in the body, with higher concentrations in organs with abundant blood flow such as the liver, kidneys, and lungs, in addition to brain tissue. The binding rate with plasma proteins still needs to be clarified. In terms of metabolism, lycorine is mainly metabolized in the liver. Preliminary research suggests that its metabolic pathway may involve oxidative reactions mediated by the cytochrome P450 (CYP450) enzyme system, such as hydroxylation and demethylation, as well as binding reactions of glucuronic acid or sulfuric acid. The identification of specific metabolic enzyme subtypes (such as CYP3A4, CYP2D6, etc.) and the structure of metabolites is a weak link in current research and a key breakthrough direction in the future. In terms of excretion, allicin hydrochloride and its metabolites are mainly excreted through urine and bile.
Although the preliminary pharmacological evaluation is optimistic, the pharmacokinetics of allicin hydrochloride still face challenges. For example, the optimization of oral bioavailability, improvement of metabolic stability, and potential drug drug interaction (DDI) risks (especially DDI related to CYP450 enzymes) all need to be elucidated through more in-depth preclinical studies. In addition, the central nervous system toxicity caused by its high BBB permeability, such as possible tremors and ataxia, needs to be rigorously evaluated in animal toxicology experiments.
Salicylic acid lycorine, with its multi-target pharmacological effects and good drug like properties, has shown promising clinical application prospects in multiple therapeutic fields, especially in the field of anti-tumor.
1. Anti tumor therapy
- leukemia Given its potent inhibitory effect on multiple leukemia cell lines and its ability to target key leukemia targets such as STAT3, NOTCH1, IDH1, ABCB1, etc., lycorine hydrochloride is expected to be developed as a novel drug for the treatment of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), especially for patients who are resistant to conventional chemotherapy or have relapsed.
- solid tumor As an inhibitor of melanoma angiogenesis, it has unique advantages in combating melanoma. At the same time, its activity on liver cancer, lung cancer, breast cancer and other common solid tumors makes it have the potential of broad-spectrum anti-cancer. In the future, it can be explored to combine it with immune checkpoint inhibitors (such as PD-1/PD-L1 antibodies) or targeted drugs in order to achieve better therapeutic effects.
- Overcoming drug resistance Its ability to reverse multidrug resistance (MDR) makes it an ideal chemotherapy sensitizer. The development of a combination therapy of allicin hydrochloride with first-line chemotherapy drugs such as doxorubicin and paclitaxel is a highly translational research direction.
2. Antiviral therapy
Given its potential in combating SARS-CoV-2, influenza virus, and other viruses, hydrochloric acid lycorine or its structurally optimized derivatives may be developed into broad-spectrum antiviral drugs to address potential new outbreaks of infectious diseases in the future.
3. Neurodegenerative diseases
Its high BBB permeability and AChE inhibitory activity make it potentially valuable in the treatment of Alzheimer's disease. More in vivo pharmacological experiments are needed in the future to verify whether it can improve cognitive function and evaluate the safety of long-term medication.
4. Challenges and Future Directions Faced
Despite its broad prospects, the clinical translation of lycorine hydrochloride still faces many challenges:
- Toxicity issue Lycorine has certain cytotoxicity, and its toxicity to normal cells needs to be systematically evaluated. Especially its high BBB permeability may pose a risk of neurotoxicity. It is necessary to conduct structure-activity relationship (SAR) studies to search for derivatives with higher activity and lower toxicity.
- Pharmacokinetic optimization Low oral bioavailability and metabolic instability are common bottlenecks for natural products. Through prodrug design, nano formulations (such as liposomes, polymer micelles), or structural modification, it is expected to improve its PK characteristics.
- Deepening the mechanism of action Although numerous targets have been identified, their exact main functional targets and signaling networks still need further clarification. Using modern omics techniques (such as proteomics and transcriptomics) and chemical biology methods (such as activity-based proteomic analysis, ABPP) for systematic research can help reveal its "multi pharmacological" nature.
- Clinical research advancement At present, research on allicin hydrochloride mainly remains in the preclinical stage. Advancing it into standardized clinical trials to validate its safety, tolerability, and efficacy in the human body is a crucial step towards ultimately realizing its clinical value.
Hydrochloric acid lycorine, an ancient alkaloid derived from plants in the lycorine family, has undergone over a hundred years of research and its rich pharmacological activities and unique molecular mechanisms have been continuously revealed. From initially being used as antiviral and anti-inflammatory drugs, it has now shown great potential in the field of anti-tumor therapy, especially in multi-target regulation of refractory tumors such as leukemia and melanoma, making it a highly valuable natural product lead compound for development. Its good drug like parameters, such as moderate lipophilicity, low hERG risk, and low genetic toxicity, provide strong support for its drug development.
However, from laboratory research to clinical application, allicin hydrochloride still faces key bottlenecks such as toxicity and poor pharmacokinetic properties. Future research should focus on: guiding structural optimization through in-depth structure-activity relationship studies, and developing highly efficient and low toxicity derivatives; Utilizing advanced drug delivery systems to improve their in vivo fate; And use modern molecular biology techniques to thoroughly elucidate its functional network. With the gradual resolution of these issues, we have reason to believe that allicin hydrochloride and its derivatives have the potential to become important members of the drug family for treating major human diseases, especially malignant tumors, in the future, continuing the glorious chapter of natural products in the history of drug discovery.
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