Product name: Alpha-Hederin
Synonym name:
Catalogue No.: BP0154
Cas No.: 27013-91-8
Formula: C₄₁H₆₆O₁₂
Mol Weight: 750.967
Botanical Source: Hedera helix; Chinese ivy; Hedera nepalensis K,Koch var.sinensis (Tobl.) Rehd
Physical Description: Powder
Type of Compound: Triterpenoids

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, up to kilograms
Inquire for bulk scale.

Descriptions:
Alpha-hederin as a pro-drug, has cytotoxic and apoptotic/necrotic effects in a dose- and time-dependent manner on on four human cancer cell lines [A549 (lung carcinoma), HEp-2 (larynx epidermoid carcinoma), HT-29 (colon adenocarcinoma) and MIA PaCa-2 (pancreas carcinoma)] .[1]
Alpha-hederin is a saponin isolated from ivy, has anti-oxidant activity and acute anti-inflammatory activity in carrageenan-induced rat paw edema.[2]
Alpha-hederin, chlorophyllin and ascorbic acid have protective effects towards the induction of micronuclei by doxorubicin in cultured human lymphocytes.[3]
Alpha-hederin has antileishmanial activity ,exhibits a strong antiproliferative activity on all stages of development of the parasite by altering membrane integrity and potential in Leishmania .[4]
Alpha-hederin affects the binding behavior, dynamics, and regulation of beta 2-adrenergic receptors.[5]
Alpha-Hederin can increase isoprenaline-induced relaxation indirectly, probably by inhibiting heterologous desensitization induced by high concentrations of muscarinic ligands like .[6]
Alpha-hederin at sub-IC(50) cytotoxic concentrations enhances 5-fluorouracil (5-FU) cytotoxicity about 3.3-fold, suggests that it is possible to optimize colorectal cancer cell sensitivity to 5-FU with alpha-hederin.[7]
Alpha-hederin has anticancer effect on breast cancer cells.[8]

References:
[1] Rooney S, Ryan M F. Anticancer Res, 2005, 25(3B):2199-204.
[2] Gepdiremen A, Mshvildadze V, S?leyman H, et al. Phytomedicine, 2005, 12(6-7):440-4.
[3] Gül?in I, Mshvildadze V, Gepdiremen A,et al. Planta Med, 2004, 70(6):561-3.
[4] Amara-Mokrane Y A, Lehucher-Michel M P, Balansard G, et al. Mutagenesis, 1996, 11(2):161-7.
[5] Delmas F, Di G C R, Gasquet M, et al. Planta Med, 2000, 66(4):343-7.
[6] Sieben A, Prenner L, Sorkalla T, et al. Biochemistry, 2009, 48(15):3477-82.
[7] Anne Wolf, Reinoud Gosens, Herman Meurs, et al. Phytother Res Ptr, 2008, 22(10):1299-302.
[8] Cheng L, Xia T S, Wang Y F, et al. Int J Oncol, 2014, 45(2):757-63.
[9] Li Y, Li J, Huang J, et al. Chinese Agr Sci Bull, 2014, 30(13):190-3.

HPLC of Alpha-Hederin

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

Introduction/Overview

Alpha-Hederin is a typical triterpene saponin natural product, first isolated from the stem bark of Kalopanax pictus. As a derivative formed by hederagenin bonding specific disaccharide residues via glycosidic bonds, alpha-edy saponins play an important role among plant metabolites. In recent years, with the rapid development of natural product pharmacology, Alpha-Ivy saponins have attracted widespread attention due to their diverse bioactivities, especially demonstrating unique pharmacological potential in anti-inflammatory, anti-tumor, antiparasitic, and metabolic disease fields. This paper aims to systematically review the chemical structure, origins, pharmacological activity, and mechanism of action of alpha-ivy saponins, evaluate their druggability and clinical application prospects, and provide theoretical basis and reference for related research and new drug development.

Chemical structure and physicochemical properties

The chemical structure of alpha-ivy saponins belongs to the pentacyclic triterpene saponins, with a molecular formula of C42H66O12 and a molecular weight of about 734.96. Its core structure is hederagenin, which is linked to the third hydroxyl group via glycosidic bonds, forming a 2-O-(6-deoxy-α-L-pyranmanan sugar group)-α-L-arabinopyran sugar residue, forming a mono-bridge sugar triterpene saponin structure. This structure imparts higher polarity, expanding its potential for interaction with biological macromolecules.

In terms of physicochemical properties, the LogP value of alpha-Idy saponins is 3.5, indicating moderate lipid solubility, which facilitates cell membrane penetration. Its topological pole surface area (TPSA) is 213.75 Ų, and the number of hydrogen bond acceptors reaches 12, indicating good solubility and strong hydrogen bond binding ability in aqueous environments. The blood-brain barrier penetration capacity is relatively low, suggesting a lower risk of central nervous system side effects. Currently, there is no clear data on its hepatotoxicity, cardiotoxicity, or safety indicators such as hERG channel inhibition, and further research is needed.

Plant Origins and Extraction Methods

Alpha-ivy saponins are mainly isolated from the stem bark of Kalopanax pictus. Kalopanax pictus is a plant in the Araliaceae family, widely distributed in East Asia, traditionally used to treat rheumatism, arthritis, and various inflammatory diseases. Its stem bark is rich in various triterpene saponin compounds, with alpha-ivy saponins being particularly high.

The extraction method typically uses solvent extraction combined with column chromatography separation technology. The specific steps include:

1. Crude extraction: Ethanol or methanol is used to reflux extract the dried and crushed stem bark, and the extract is concentrated to obtain the crude extract.
2. Separation and purification: The crude extract is separated by silica gel column chromatography or reversed-phase high-performance liquid chromatography (RP-HPLC), using solvent systems of different polarities to enrich the target compound.
3. Identification and confirmation: Techniques such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR) are used to identify the structure of the purified product to ensure the purity and structural accuracy of Alpha-Ivy saponins.

In recent years, new green extraction technologies such as ultrasound-assisted extraction and microwave-assisted extraction have gradually been applied to the extraction of alpha-ivy saponins, improving extraction efficiency and purity while reducing solvent consumption and environmental pollution.

Pharmacological activity research

Alpha-Ivy saponins exhibit a variety of significant biological activities, covering anti-inflammation, anti-tumor, antiparasitic, and metabolic regulation fields.

Anti-inflammatory activity

Multiple in vivo and in vitro experiments have shown that alpha-ivy saponins have significant anti-inflammatory effects. It demonstrated significant anti-inflammatory effects in carrageen-induced rat foot swelling models, inhibiting the release of inflammatory mediators and infiltration of inflammatory cells. In addition, alpha-ivy saponins demonstrate strong antioxidant activity, scavenging free radicals and reducing tissue damage caused by oxidative stress, further enhancing their anti-inflammatory effects.

Antitumor activity

Alpha-ivy saponins exhibit inhibitory effects on various tumor cell lines, especially showing good anti-proliferative and pro-apoptotic activity in gastric cancer cells. Its mechanism mainly involves activating mitochondria-dependent apoptotic pathways, inducing intracellular reactive oxygen species (ROS) production, leading to a decrease in glutathione (GSH) levels, disrupting intracellular redox balance, and ultimately triggering apoptosis. In addition, alpha-ivy saponins can inhibit tumor cell migration and invasion, demonstrating potential anti-metastatic capabilities.

Antiparasitic activity

Alpha-ivy saponins exhibit strong anti-proliferative activity against Leishmania. Its mechanism involves disrupting the membrane integrity and membrane potential of parasites, affecting multiple stages of their growth and development. In addition, alpha-ivy saponins also have insect-repellent and miticidal effects, showing potential in agriculture and veterinary fields.

Other pharmacological effects

Alpha-ivy saponins also exhibit antispasmodic effects, which can relieve smooth muscle spasms, possibly by modulating neurotransmitter receptors and ion channels. Additionally, it can indirectly enhance isoproterenol-induced diastolic response, possibly by inhibiting heterologous desensitization induced by high concentrations of muscarine ligands, suggesting its potential role in cardiovascular regulation.

Mechanism of action and molecular targets

The multi-target mechanism of alpha-ivy saponins forms the basis of their pharmacological activity. For metabolic diseases such as nonalcoholic steatohepatitis (NASH), research reveals that it may act by regulating multiple signaling pathways, with related targets including:

• AMPK (PRKAA1): As a key regulator of cellular energy metabolism, AMPK activation helps promote lipid metabolism and suppress inflammatory responses. Alpha-ivy saponins may improve fatty liver pathology by activating AMPK.
• CES1 (carboxylesterase 1): involved in lipid and drug metabolism, regulating CES1 activity helps maintain lipid homeostasis in the liver.
• PTPN1 (protein tyrosine phosphatase 1B): negatively regulates the insulin signaling pathway; inhibiting PTPN1 helps improve insulin resistance.
• STAT3 (Signal Transduction and Transcription Activator Factor 3): Involved in inflammatory responses and cell proliferation, alpha-ivy saponins may reduce inflammation by inhibiting the STAT3 signaling pathway.
• NFE2L2 (Nuclear Factor 2 Red-Related Factor 2): Regulates antioxidant reactions, activates NFE2L2 to help resist oxidative stress.
• HIF1A (hypoxia-inducing factor 1α): regulates cellular adaptation to hypoxic environments and influences metabolic reprogramming.
• PTGES (Prostaglandin E synthase): Involved in the synthesis of the inflammatory mediator prostaglandin E2, regulating inflammatory responses.
• MAPK1 (Mitogen-activated protein kinase 1): regulates cell proliferation and apoptosis.
• TNF (tumor necrosis factor): a key inflammatory factor that regulates immune responses.
• PPARG (Peroxisome Proliferator-Activated Receptor γ): Regulates lipid metabolism and inflammatory responses.

In the antitumor field, alpha-ivy saponins induce loss of mitochondrial membrane potentials, activate cytochrome C release, initiate the caspase cascade, and promote apoptosis. Additionally, ROS generation and glutathione depletion are important mechanisms by which oxidative stress mediates cell death.

Druggability evaluation and pharmacokinetics

The druggability parameters of alpha-ivy saponins indicate that it has certain potential for drug development. The molecular weight is 734.96, slightly above the 500 recommended by Lipinski's rule, but its LogP value is 3.5, indicating moderate lipid solubility and facilitating cell membrane penetration. High TPSA (213.75) and hydrogen bond receptor count (12) suggest good water solubility, but may affect oral bioavailability and membrane permeability.

The blood-brain barrier penetration ability is relatively low, reducing the risk of central nervous system toxicity, but it also limits its application in central nervous system diseases. There is still a lack of systematic research on safety indicators such as hepatotoxicity, cardiotoxicity, and hERG channel inhibition, which need to be clarified in the future through in vivo and in vitro toxicological assessments and preclinical safety trials.

Pharmacokinetics, there are currently few reports in the literature. It is speculated that its large molecular weight and polar structure may lead to limited oral absorption, and metabolic pathways in the body may involve hepatic enzyme systems, with excretion mainly via bile or urine. To improve bioavailability, drug delivery strategies such as nanocarriers, liposomal encapsulation, and structural modification warrant further research.

Prospects and outlooks for clinical applications

Alpha-ivy saponins, with their multi-target and multi-mechanism pharmacological activity, demonstrate broad clinical application potential. Its anti-inflammatory and antioxidant effects make it a candidate drug for treating chronic inflammatory diseases such as non-alcoholic steatohepatitis (NASH) and rheumatoid arthritis. By regulating key molecules such as AMPK, STAT3, and NFE2L2, alpha-ivy saponins are expected to improve metabolic disorders and the inflammatory microenvironment.

In the field of tumor treatment, the ability of alpha-ivy saponins to induce mitochondria-dependent apoptosis offers new ideas for adjuvant therapy of gastric cancer and other solid tumors. Its antiparasitic activity also provides a natural medicinal resource for the prevention and treatment of parasitic diseases.

However, current clinical research on alpha-ivy saponins is still in its early stages and lacks systematic clinical trial data. In the future, focus should be placed on pharmacokinetics, safety evaluation, and dosage form optimization research, combined with modern drug delivery technologies to enhance bioavailability and targeting. In addition, based on their multi-target characteristics, combination drug strategies and the development of structurally modified derivatives are also important directions.

Conclusion

Alpha-ivy saponins, as a triterpene saponin with rich biological activity, show broad application prospects in anti-inflammation, anti-tumor, antiparasitic, and metabolic disease regulation. Its unique chemical structure and multi-target mechanism of action provide a valuable molecular framework and research foundation for new drug development. Although its druggability and clinical application still face certain challenges, with continuous advances in extraction and purification technology, drug delivery systems, and molecular pharmacology research, alpha-ivy saponins are expected to become an important candidate for future natural product drug development. Future research should focus on systematic pharmacokinetics, safety evaluation, and clinical validation, promoting its transition from laboratory to clinical application for the benefit of human health.