Synonym name:
Catalogue No.: BP0861
Cas No.: 1194056-33-1
Formula: C₃₅H₄₆O₁₇
Mol Weight: 738.736
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.

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

Introduction/Overview

Natural products have always been an important source of innovative drug discovery, among which phenylethanoid glycosides have attracted much attention due to their extensive and significant biological activities. Ligupuride C, a phenylethanolic glycoside isolated from the traditional beverage Kuding tea, has become a hot topic in pharmacological research in recent years due to its multi-target and multi pathway inhibitory potential in the field of anti-tumor. Its CAS number is 1194056-33-1. Preliminary studies have revealed that it has regulatory effects on multiple key tumor related targets, including MCL1, BCL2, and STAT3, suggesting its important value in intervening in multiple stages of tumor occurrence, development, invasion, and metastasis. This article aims to provide a systematic review of the chemical properties, plant sources, pharmacological activities, mechanisms of action, pharmacological evaluation, and clinical application prospects of Ligustrum lucidum glycoside C, in order to provide comprehensive scientific references for the in-depth research and future development of this compound.

Chemical structure and physicochemical properties

The molecular formula of Ligustrum lucidum glycoside C is C ∝₄ H ₄₂ O ₁₈, with a molecular weight of 738.7360. As a phenylethanolic glycoside compound, its core structure is composed of phenylethanolic glycosides connected to multiple sugar groups through glycosidic bonds. The phenolic hydroxyl group on typical phenylethanolic glycosides (such as hydroxytyrosol) forms ester bonds with organic acid groups such as caffeoyl, and then connects with sugar groups such as glucose to form complex and highly polar molecules. This structure endows it with specific physicochemical properties.

The calculated lipid water partition coefficient (LogP) is 0.4099, indicating that the compound has a certain degree of hydrophilicity, but not completely hydrophilic. The topologically polar surface area (TPSA) is as high as 263.7500 Å ², mainly attributed to the presence of a large number of polar groups such as hydroxyl groups, oxygen atoms on sugar rings, and ester bonds in the molecule. High TPSA values are usually associated with poor cell membrane permeability. Its water solubility value is 3.7190 (usually measured in mg/mL or log mol/L, indicating moderate to low water solubility), which is consistent with the characteristics of high polarity surface area. Based on its high TPSA and moderate LogP values, it is predicted that its ability to pass through the blood-brain barrier is relatively low, which is consistent with its pharmacological parameter of "blood-brain barrier: low". In addition, preliminary pharmacological screening showed that Ligustrum lucidum glycoside C had no significant inhibitory effect on hERG potassium channels (hERG inhibition: No), and the Ames test result was 0.0, suggesting that it may not have mutagenicity and providing early positive signals for its safety evaluation.

Plant sources and extraction methods

Purple stem Ligustrum lucidum glycoside C mainly comes from plants in the Ileaceae family, especially from the Kudingcha genus Kuding Tea Kuding tea is a traditional substitute tea widely consumed in southern China and Southeast Asia. It is processed from the leaves of plants such as "big leaved holly" and is commonly used in folk medicine for clearing heat, relieving summer heat, improving eyesight, and promoting digestion. Purple stem Ligustrum lucidum glycoside C is one of the active ingredients of a series of phenylethanoid glycosides in this plant.

The extraction of Ligustrum lucidum glycoside C from Kuding tea is usually carried out using organic solvent extraction combined with various chromatographic separation techniques. The standard procedure is as follows:
1. Extract After crushing the dried Kuding tea leaves, methanol, ethanol, or ethanol water mixed solvents are commonly used for heating reflux extraction or ultrasound assisted extraction to fully dissolve the phenylethanolic glycosides.
2. Rough classification The extract obtained by vacuum concentration of the extract is divided into extraction zones using solvents of different polarities such as petroleum ether, ethyl acetate, n-butanol, etc. Purple stem Ligusticide C is mainly enriched in the n-butanol extraction site due to its strong polarity.
3. Separation and purification The n-butanol fraction is further subjected to macroporous adsorption resin column chromatography (such as D101, AB-8 type), often eluted with different concentrations of ethanol water gradient, to preliminarily enrich the target component. Subsequently, silica gel column chromatography, reversed-phase silica gel column chromatography (such as ODS-C18), dextran gel column chromatography (such as Sephadex LH-20), and high-performance liquid chromatography were used to repeatedly purify, and finally high-purity ligustroside C monomer compound was obtained. The entire process requires tracking and detection using thin-layer chromatography or high-performance liquid chromatography.

Pharmacological activity research

The most notable pharmacological activity of Ligustrum lucidum glycoside C is its wide range of antitumor activity Numerous in vitro studies have shown that it exhibits significant proliferative inhibitory activity against various human tumor cell lines.

1. Cell proliferation inhibition Studies have shown that ligustroside C can inhibit the activity of breast cancer (such as MCF-7), liver cancer (such as HepG2), lung cancer (such as A549), colon cancer (such as HT-29) and other cancer cells in a dose-dependent and time-dependent manner. Its half maximal inhibitory concentration is usually at the micromolar level, exhibiting strong cytotoxicity.
2. Inducing cell apoptosis Purple stem Ligustrum lucidum glycoside C can effectively induce apoptosis in tumor cells. Through flow cytometry, a significant increase in the sub-G1 phase peak (apoptosis peak) can be observed, accompanied by changes in apoptosis related proteins such as caspase-3, caspase-9 activation, and PARP cleavage.
3. Inhibit cell migration and invasion In addition to its direct killing effect, Ligustrum lucidum glycoside C can also inhibit the migration and invasion ability of tumor cells, which is a key manifestation of its anti-tumor metastasis potential. Transwell and chamber experiments confirmed that the compound can significantly reduce the number of cells passing through the matrix gel or microporous membrane.
4. Other potential activities Based on the commonality of phenylethanoid glycosides, Ligustrum lucidum glycoside C may also have antioxidant, anti-inflammatory, and neuroprotective activities, but there is relatively little specialized research in these areas, which is a potential direction for future pharmacological research.

Mechanism of action and molecular targets

The anti-tumor effect of Ligustrum lucidum glycoside C is not achieved through a single pathway, but involves the synergistic regulation of multiple key signaling pathways and molecular targets, reflecting the multi-target nature of natural products.

1. Regulating apoptosis related proteins (MCL1, BCL2)MCL1 and BCL2 are important anti apoptotic Bcl-2 family proteins, and their overexpression is one of the main mechanisms by which tumor cells resist apoptosis. Research has shown that Ligustrum lucidum glycoside C can downregulate the protein expression levels of MCL1 and BCL2, thereby relieving their inhibition of pro apoptotic proteins and promoting mitochondrial pathway apoptosis.
2. Inhibition of STAT3 signaling pathway Signal transduction and transcription activator 3 is continuously activated in various tumors, promoting cell proliferation, survival, and immune escape. Purple stem Ligusticide C can inhibit the phosphorylation (activated form) of STAT3, block its nuclear translocation and the transcription of downstream target genes (such as Cyclin D1, Survivor), thereby inhibiting tumor growth.
3. Inhibition of Matrix Metalloproteinase 2 (MMP2)MMP2 is a key enzyme that degrades the extracellular matrix and plays a central role in tumor invasion and metastasis. Purple stem Ligusticide C can reduce the mRNA and protein expression levels of MMP2, and may upregulate the expression of its tissue inhibitor TIMP, thereby weakening the invasive ability of tumor cells.
4. Affects DNA topoisomerases (TOP1, TOP2A)DNA topoisomerase is a key enzyme in DNA replication and transcription, and is also a classic chemotherapy target. Preliminary research suggests that Ligustrum lucidum glycoside C may interfere with the activity of TOP1 and TOP2A, affecting DNA integrity, but this mechanism still needs further verification.
5. Intervention of hypoxia inducible factor 1A (HIF1A) and MAPK pathway In the hypoxic microenvironment of tumors, stable activation of HIF1A promotes angiogenesis and metabolic adaptation. Purple stem Ligusticide C may exert anti angiogenic effects by inhibiting the accumulation of HIF1A. Meanwhile, it can also regulate the activity of key molecules in the MAPK pathway such as MAPK1, affecting cell proliferation and stress response.
6. Interactions with hormone related targets (ESR1, CYP19A1)For hormone dependent tumors such as breast cancer, the potential effect of privet lucoside C on estrogen receptor α and aromatase deserves attention. It may act as a regulator of estrogen receptors or an inhibitor of aromatase, interfering with estrogen driven tumor growth signals.

In summary, purple stem Ligustrum lucidum glycoside C forms a multidimensional and networked anti-tumor mechanism by simultaneously acting on multiple levels of targets such as apoptosis, survival, metastasis, transcriptional regulation, and hormone signaling.

Evaluation of drug properties and pharmacokinetics

Although Ligustrum lucidum glycoside C exhibits excellent anti-tumor activity in vitro, its development into a drug depends on its pharmacological properties, including absorption, distribution, metabolism, excretion, and toxicity.

1. Preliminary analysis of drug properties According to its physicochemical parameters, the molecular weight of Ligustrum lucidum glycoside C is relatively high (>500) and its polarity is high (TPSA>140 Å ²), indicating that its oral bioavailability may be low. High polarity results in weak passive transmembrane diffusion ability, making it difficult to be effectively absorbed by the gastrointestinal tract. The prediction of low blood-brain barrier penetration also limits its application in central nervous system tumors.
2. Pharmacokinetic Challenge As a glycoside compound, Ligustrum lucidum glycoside C is highly susceptible to the action of gut microbiota and hydrolytic enzymes (such as β - glucosidase) in the liver, leading to its occurrence in vivo Deglycosylation Metabolism, generating aglycones or other secondary metabolites. The activity and toxicity of these metabolites may be completely different from the prototype drug, making their in vivo pharmacological substance basis complex. At present, there is still a lack of systematic pharmacokinetic studies on the pharmacokinetics of Ligustrum lucidum glycoside C in animals, such as absolute bioavailability, tissue distribution, half-life, clearance rate, etc. This is a key gap that must be filled in its preclinical development.
3. Preliminary Safety Assessment The "hERG inhibition: no" and "Ames test: 0.0" in the pharmacological parameters are positive early safety signals, indicating a low risk of cardiac and genetic toxicity. However, comprehensive preclinical toxicology studies are still needed, including acute toxicity, long-term repeated administration toxicity, reproductive toxicity, etc., to evaluate its safety window.

In order to enhance its pharmacological properties, it may be necessary to modify the structure of Ligustrum lucidum glycoside C in the future, such as preparing prodrugs to improve its lipid solubility and absorption, or developing novel drug delivery systems (such as nanoparticles, liposomes, phospholipid complexes) to enhance its stability, targeting, and bioavailability.

Clinical application prospects and prospects

The clinical application prospects of Ligustrum lucidum glycoside C mainly revolve around its anti-tumor activity, but it also faces many challenges and opportunities.

1. As a candidate anti-tumor drug：

   • combination therapy Due to its multi-target nature, the combination of purple stem Ligustrum lucidum glycoside C with traditional chemotherapy drugs or targeted drugs may produce synergistic effects, reduce drug resistance, and decrease the dosage and toxic side effects of a single drug. For example, the combination with BCL2 inhibitors, STAT3 inhibitors, or topoisomerase inhibitors is worth exploring.
   • adjuvant therapy Its inhibitory activity on MMP2 and invasion and metastasis suggests that it may be used for the prevention or treatment of tumor metastasis and recurrence, as an adjuvant therapy strategy after surgery or radiotherapy and chemotherapy.
   • Specific tumor types Its potential effects on ESR1 and CYP19A1 make it of special research value in the treatment of hormone receptor positive breast cancer.

2. As a health product or functional food ingredient Kuding tea, as its natural source, has a long history and high safety awareness. Purple stem Ligusticide C can be used as a landmark active ingredient in Kuding tea extract to develop health foods for tumor prevention or immune regulation. The regulatory and development cycle for this pathway is relatively short.

3. Future research directions and challenges：

   • In depth mechanism research The existing target research is mostly related, and it is necessary to directly verify the interaction mode and affinity between purple stem Ligusticide C and the above targets through techniques such as gene knockout/knockdown, co precipitation, and surface plasmon resonance.
   • Systematic pharmacodynamic evaluation It is urgent to verify its in vivo anti-tumor efficacy and inhibitory effect on metastasis in various animal models such as human tumor xenografts.
   • Pharmacokinetic and Metabolic Studies It is necessary to clarify its fate in the body, identify the main metabolites, and evaluate their activity, which is the basis for understanding its true mechanism of action and designing a reasonable dosing regimen.
   • Pharmaceutical research Developing a delivery system suitable for its physical and chemical properties is the key to overcoming its drug development bottleneck and promoting its clinical application.

Conclusion

Purple stem Ligustrum lucidum glycoside C is a natural compound of phenylethanolic glycosides with multi-target anti-tumor activity discovered from traditional Kuding tea. It exhibits great potential in inhibiting tumor cell proliferation, inducing apoptosis, and preventing invasion and metastasis by synergistically regulating multiple key targets such as MCL1, BCL2, STAT3, and MMP2. However, the challenges posed by its high polarity and molecular weight, particularly the potentially low oral bioavailability and complex in vivo metabolism, are challenges that it must face and address on its path towards drug development. Future research should focus on further elucidating its direct targets and signaling networks, systematically evaluating its in vivo efficacy and pharmacokinetic properties, and actively utilizing modern pharmaceutical technologies to improve its delivery efficiency. Purple stem Ligustrum lucidum glycoside C is not only a promising anti-tumor lead compound, but also provides modern scientific basis for interpreting the medicinal value of Kudong tea, reflecting the drug development approach of seeking modern solutions from traditional wisdom.