Synonym name: Raddeanoside R13
Catalogue No.: BP0706
Cas No.: 106577-39-3
Formula: C₄₇H₇₆O₁₆
Mol Weight: 897.109
Botanical Source: Hedera colchica and Thinouia coriacea

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.

NMR of Hederacolchiside A1

HPLC of Hederacolchiside A1

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

Introduction/Overview

Hederacolchiside A1 (CAS No.: 106577-39-3) is a type of herb derived from the traditional Chinese medicine Pulsatilla chinensis (scientific name: Pulsatilla chinensis). ) natural triterpene saponin compounds. In recent years, with the deepening of natural product pharmacology, Black Sea Ivy Saponin A1 has attracted widespread attention due to its remarkable antitumor and antiparasitic activity. It induces tumor cell apoptosis by modulating the PI3K/Akt/mTOR signaling pathway, inhibits tumor cell proliferation, and also shows good inhibitory effects against schistosomes and other parasites. As a malignant tumor with a high incidence and poor prognosis worldwide, liver cancer faces limitations such as drug resistance and toxic side effects from existing treatments. As a natural product is an important source of new anti-tumor drugs, research on Black Sea Idy Saponin A1 offers new ideas for liver cancer treatment.

This paper reviews the chemical structure and physicochemical properties, plant origin, and extraction methods of Black Sea Ivy Saponin A1, systematically summarizes its pharmacological activity and mechanism of action, focuses on its molecular targets and druggability evaluation in liver cancer treatment, and finally looks ahead to its clinical application prospects and future research directions, aiming to provide theoretical basis and reference for drug development and clinical translation of this natural product.

Chemical structure and physicochemical properties

Black Sea Ivy Saponin A1 is a complex triterpene saponin with a molecular formula of C_47H_74O_17 and a molecular weight of 897.1090. Its structure includes a triterpene backbone connecting multiple glycosyl residues, giving it high polarity and bioactivity. Glycosidic bonds and hydroxyl groups in the molecular structure have significant effects on their water solubility and biocompatibility.

In terms of physicochemical properties, the LogP value of Black Sea Ivy saponin A1 is about 2.90, indicating moderate lipid solubility that facilitates cell membrane penetration. Its polar surface area (TPSA) is 254.52 Ų, and a higher TPSA value suggests strong polarity and hydrogen bond formation, which may limit its ability to cross the blood-brain barrier (in reality, the blood-brain barrier permeability is low). Water solubility is 0.0768 mg/mL, indicating limited solubility in water but still some solubility, suitable for distribution in the body. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test result was 0.0, indicating no significant mutagenicity and good safety.

Plant Origins and Extraction Methods

Black Sea Ivy saponin A1 is mainly extracted from the root of the White-headed Bulrush. The White-headed Wengle is a plant of the Ranunculaceae family, widely distributed in northern China and East Asia. In traditional Chinese medicine, its root is often used medicinally, with effects of clearing heat, detoxifying, reducing swelling, and relieving pain.

During extraction, alcohol extraction methods (such as 70% ethanol) are typically used to extract dried Lycodon roots, followed by liquid-liquid partitioning, column chromatography (silica gel, C18 reversed-phase column), and high-performance liquid chromatography (HPLC) for separation and purification. Purified Black Sea Ivy Saponin A1 can be structurally confirmed by mass spectrometry (MS), nuclear magnetic resonance (NMR), and other methods. In recent years, the application of new technologies such as ultrasound-assisted extraction and microwave-assisted extraction has improved extraction efficiency and purity, while reducing production costs.

Pharmacological activity research

Antitumor activity

Black Sea Ivy Saponin A1 exhibits significant antiproliferative effects in various tumor cell lines, especially exhibiting strong cytotoxicity in liver cancer cells (such as HepG2 and Huh7). In vitro experiments have shown that this compound can significantly inhibit the proliferation of liver cancer cells, induce cell cycle arrest, and promote apoptosis. Animal model studies further confirmed its inhibitory effect on liver cancer tumor growth with minimal toxic side effects.

It has anti-schistosomiasis activity

Schistosomiasis is a tropical parasitic disease caused by parasites of the genus Schistosomiasis, posing a serious threat to public health safety. Black Sea Ivy Saponin A1 shows a killing effect on adult schistosomes and their larvae, affecting the parasite's survival and reproductive capacity. Both in vivo and in vitro experiments have shown that it can effectively reduce parasite load and alleviate pathological damage caused by infection, showing potential value in the development of anti-schistosomiasis drugs.

Other pharmacological effects

In addition to its antitumor and antiparasitic activities, Black Sea Ivy Saponin A1 also exhibits certain anti-inflammatory, immunomodulatory, and antioxidant effects, which may synergistically enhance its overall efficacy.

Mechanism of action and molecular targets

The antitumor mechanism of Black Sea Ivy Saponin A1 mainly regulates the PI3K/Akt/mTOR signaling pathway. This pathway plays a central role in cell proliferation, apoptosis, and metabolic regulation, with abnormal activation commonly seen in various tumors, especially liver cancer.

The specific mechanisms include:

• Induction of apoptosis: Black Sea Ivy saponin A1 regulates the expression of BCL2 family proteins by activating apoptosis-related proteins within cells, thereby promoting mitochondrial apoptosis. Downregulation of the BCL2 protein enhances apoptosis signaling.
• Inhibition of STAT3 signaling: STAT3 plays an important role in tumor cell growth and immune evasion. Black Sea ivy saponin A1 inhibits its phosphorylation activity, blocking the expression of downstream tumor-causing genes.
• Regulation of TOP1 and MAPK1: By affecting DNA topoisomerase 1 (TOP1) and mitogen-activated protein kinase 1 (MAPK1), they interfere with DNA replication and signal transduction in tumor cells.
• Affects TERT and MMP9 expression: inhibits telomerase reverse transcriptase (TERT) activity, limiting unlimited tumor cell proliferation; At the same time, it downregulates matrix metalloproteinase 9 (MMP9) to inhibit tumor invasion and metastasis.
• Regulates EGFR and PTGS2: inhibits epidermal growth factor receptor (EGFR) signaling, reducing tumor growth signaling; Reduces cyclooxygenase 2 (PTGS2) expression and lessens the tumor-promoting effect of the inflammatory microenvironment.
• Activation of the TP53 pathway: promotes the expression and function of tumor suppressor protein p53, enhancing cell cycle arrest and apoptosis.

Additionally, Black Sea Ivy Saponin A1 further inhibits the PI3K/Akt signaling pathway by modulating PIK3CA (the catalytic subunit of PI3K), achieving a comprehensive antitumor effect.

Druggability evaluation and pharmacokinetics

Black Sea Ivy Saponin A1 has a relatively large molecular weight (897.1090) and a high TPSA (254.52 Ų), indicating strong polarity that may affect oral bioavailability and cell membrane permeability. Its LogP value is about 2.9, indicating moderate lipid solubility that favors intracellular distribution, but its water solubility is relatively low (0.0768 mg/mL), with limited in vivo solubility, so bioavailability may be improved through formulation optimization.

The low permeability of the blood-brain barrier suggests its limited distribution in the central nervous system, reducing the potential risk of neurotoxicity. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. Ames test results showed no mutagenicity and good safety.

Pharmacokinetics, there are currently few related studies. Preliminary data indicate that this compound is metabolically stable in the body and is mainly processed by the hepatic metabolic enzyme system. Future studies on in vivo absorption, distribution, metabolism, and excretion (ADME) are needed to clarify its pharmacokinetic characteristics and potential drug interactions.

Prospects and outlooks for clinical applications

Black Sea Ivy Saponin A1, as a natural product with multiple targets and mechanisms, demonstrates excellent antitumor and antiparasitic activity, especially with broad application prospects in liver cancer treatment. By regulating PI3K/Akt/mTOR and related signaling pathways, it induces tumor cell apoptosis, inhibits proliferation and metastasis, and compensates for the shortcomings of traditional chemotherapy drugs.

Future research should focus on the following aspects:

1. In-depth mechanistic research: Using techniques such as genomics and proteomics, the molecular network of Black Sea Ivy saponin A1 and its interaction with the tumor microenvironment were further clarified.
2. Pharmacokinetics and toxicology evaluation: Systematic in vivo ADME studies and long-term toxicology trials are conducted to ensure safety and effective dose range.
3. Formulation development: To address water solubility and bioavailability, new drug delivery systems (such as nanocarriers and liposomes) are developed to improve in vivo stability and targeting.
4. Preclinical and clinical research: Conduct efficacy validation and safety evaluation of animal models, gradually advancing to clinical trial stages to assess their therapeutic potential in liver cancer and schistosomiasis.
5. Combination therapy strategies: Explore synergies with existing antitumor drugs, optimize treatment regimens, and overcome resistance.

Conclusion

Black Sea Ivy Saponin A1, a natural triterpene saponin derived from the white-headed bulb, demonstrates significant pharmacological activity in anti-tumor and antiparasitic fields due to its unique chemical structure and multi-target regulatory capabilities. By modulating the PI3K/Akt/mTOR signaling pathway and related molecular targets, it achieves proliferation inhibition and apoptosis induction of liver cancer cells, demonstrating good safety and drug potential. Although there are still certain challenges in pharmacokinetics and clinical applications, with deeper research and technological advancements, Black Sea Ivy Saponin A1 is expected to become an important candidate for the new generation of natural antitumor drugs, providing new strategies and options for treating liver cancer and schistosomiasis. Future systematic research and clinical translational efforts will be key to advancing drug development.