Product name: Sibiricose A5
Synonym name: 3′-Feruloylsucrose; Arillanin B
Catalogue No.: BP1558
Cas No.: 107912-97-0
Formula: C₂₂H₃₀O₁₄
Mol Weight: 518.468
Botanical Source: Constit. of Polygala arillata and Polygala sibirica
Physical Description: Powder
Type of Compound: Phenylpropanoids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
The product could be supplied from milligrams to grams. Inquire for bulk scale.
We provide solution to improve the water-solubility of compounds, thereby facilitating the variety of activity tests and clinic uses.

For Reference Standard and R&D, Not for Human Use Directly.

HPLC of Sibiricose A5

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

Introduction/Overview

Sibiricose A5 (CAS No.: 107912-97-0) is a natural oligosaccharide ester product isolated from the medicinal herb Polygalae Radix. As an important calming and intelligence-enhancing herb in traditional Chinese medicine, Polygala has long been used to treat insomnia, forgetfulness, and depression and other neurological disorders. In recent years, with the development of modern pharmacology and natural product chemistry, Siberian Polygala glycoside A5 has attracted widespread attention due to its remarkable antioxidant activity and potential antidepressant effects.

This review aims to systematically summarize the chemical structure and physicochemical properties of Siberian Polygala glycoside A5, plant origin and extraction process, pharmacological activity and mechanism of action, druggability evaluation, and its clinical application prospects in antidepressant and other neuropsychiatric diseases, aiming to provide theoretical basis and directions for subsequent basic research and clinical translation.

Chemical structure and physicochemical properties

Siberian Polygala glycoside A5 belongs to the oligosaccharide ester class of compounds with a molecular weight of 518.4680. Its chemical structure contains multiple hydroxyl and glycosyl units, giving it high polarity and water solubility. Its LogP value is -1.1659, indicating strong hydrophilicity, and its TPSA (topological pole surface area) reaches as high as 225.0600, further indicating its high polarity and possibly affecting membrane permeability and bioavailability.

The water solubility of Siberian Polygala glycoside A5 is 12.7403, making it a well-soluble natural product that facilitates dissolution and absorption after oral administration. The blood-brain barrier (BBB) has low permeability, suggesting its limited ability to enter the central nervous system, but this does not rule out its neuroprotective or antidepressant effects through indirect mechanisms or metabolites. Additionally, this compound does not exhibit hERG channel inhibitory activity, indicating good cardiac safety. The Ames test score was 0.3, indicating a low genotoxicity risk.

Plant Origins and Extraction Methods

Siberian Polygala glycoside A5 mainly originates from the roots of Polygala tenuifolia Willd., a plant of the Polygalaceae family, widely distributed in Northeast, Northwest, and Southwest China. In traditional Chinese medicine, Polygala root is often used as a medicinal herb to calm the mind, expel phlegm, and strengthen the brain.

The process for extracting Siberian Polygala glycoside A5 typically includes the following steps:

1. Raw material pretreatment: Select high-quality, dried Polygala roots and crush them into fine powder.
2. Solvent extraction: Use water or water-alcohol mixed solvents (such as 70% ethanol) for reflux extraction, with extraction time generally lasting 1-3 hours.
3. Concentration and separation: After concentration under reduced pressure, the extract is separated and purified using liquid-liquid partitioning, column chromatography, and other methods.
4. Purification identification: Further purification is performed using silica gel column chromatography, reversed-phase high-performance liquid chromatography (RP-HPLC), and other techniques, combined with mass spectrometry (MS) and nuclear magnetic resonance (NMR) to confirm the structure.

In recent years, green and efficient technologies such as ultrasound-assisted extraction and microwave-assisted extraction have also been applied to extract Siberian Polygala glycoside A5, improving yield and purity.

Pharmacological activity research

Antioxidant activity

Siberian Polygala glycoside A5 exhibits significant antioxidant effects. In vitro studies have shown that this compound can effectively scavenge free radicals, inhibit lipid peroxidation, and protect cells from oxidative stress damage. Its antioxidant activity is mainly attributed to the abundant hydroxyl group structure in the molecule, which can provide hydrogen atoms or electrons to stabilize free radicals.

In vivo models, Siberian Polygala glycoside A5 exerts neuroprotective effects by regulating antioxidant enzyme systems (such as superoxide dismutase SOD, glutathione peroxidase GPx) activity, and lowering levels of oxidative damage markers (such as malondialdehyde MDA).

Antidepressant effects

Research on Siberian Polygala glycoside A5 in the field of antidepressants is gradually increasing. Animal behavioral experiments (such as forced swimming and tail suspension tests) have shown that this compound can significantly shorten the despair duration in depressive model animals and improve depressive-like behaviors.

Mechanistic studies suggest that Siberian Polygala glycoside A5 may exert antidepressant effects by regulating various neurotransmitter systems and signaling pathways, including the regulation of monoamine neurotransmitter metabolism (5-hydroxytryptamine, norepinephrine, dopamine) and the expression of neuroplasticity-related factors.

Additionally, its antioxidant and anti-inflammatory properties help alleviate neuroinflammation and oxidative stress related to depression, promoting neuron survival and functional recovery.

Mechanism of action and molecular targets

The antidepressant effect of Siberian Polygala glycoside A5 involves regulation through multiple targets and pathways, with main targets including:

• Monoamine oxidase A and B (MAOA, MAOB): these two enzymes are involved in the metabolism of monoamine neurotransmitters. Siberian polygala glycoside A5 has a certain inhibitory effect, prolonging the neurotransmitter's duration in the synaptic cleft and improving nerve conduction efficiency.

• Glycogen synthase kinase 3β (GSK3B): GSK3B plays a key role in neuronal signal transduction and neuroplasticity. Siberian Polygala glycoside A5 may promote neuronal survival and functional recovery by regulating GSK3B activity.

• Serotonin transporter (SLC6A4) and 5-hydroxytryptamine receptor 1A (HTR1A): regulate serotonin reuptake and receptor activity, improve serotonin signaling, and alleviate depressive symptoms.

• γ-Aminobutyric acid A receptor subunit 1 (GABRA1): As a major inhibitory neurotransmitter receptor regulating neural excitability, Siberian Polygala glycoside A5 may exert sedative and anxiolytic effects by modulating GABRA1 activity.

• cAMP Responsive Element Binding Protein 1 (CREB1) and Brain-Derived Neurotrophic Factor (BDNF): CREB1 is a key transcription factor regulating neuronal gene expression, while BDNF is an important factor in neuroplasticity and neuroprotection. Siberian Polygala glycoside A5 promotes neuronal growth and repair by activating the CREB1-BDNF signaling pathway, improving depression-related neurological dysfunction.

• Catechol-O-methyltransferase (COMT): involved in the metabolism of neurotransmitters such as dopamine, Siberian Polygala glycoside A5 regulates COMT and helps maintain neurotransmitter balance.

In summary, Siberian Polygala glycoside A5 regulates neurotransmitter metabolism, receptor function, and neuronal signal transduction through multi-target synergistic effects, comprehensively exerting antidepressant and neuroprotective effects.

Druggability evaluation and pharmacokinetics

Physicochemical properties of the drug

The molecular weight of Siberian Polygala glycoside A5 is 518.4680, which is relatively large and highly polar (TPSA 225.0600), with a LogP of -1.1659, indicating strong hydrophilicity but poor lipid solubility. This property limits its ability to be orally absorbed and cross lipid membranes, especially since the blood-brain barrier has low permeability, which may affect direct effects on the central nervous system.

Safety evaluation

The hERG channel inhibition test results were negative, indicating that this compound carries a low risk of prolonged cardiac QT intervals and is relatively safe. The Ames trial scored 0.3, indicating a low genotoxicity risk and meeting the safety requirements of the proprietary drug.

Pharmacokinetic characteristics

Currently, there is limited systematic pharmacokinetic research on Siberian Polygala glycoside A5. Based on its physicochemical properties, it is speculated that its oral bioavailability may be limited and its blood-brain barrier penetration rate is low, suggesting the need to optimize the administration route or structural modification to enhance the efficacy of the central nervous system.

Future research should focus on its in vivo absorption, distribution, metabolism, and excretion (ADME) characteristics, especially metabolic stability and brain tissue distribution, to guide clinical dosage formulation design and dose optimization.

Prospects and outlooks for clinical applications

Siberian Polygala glycoside A5, as a natural compound with multi-target antidepressant potential, possesses excellent antioxidant and neuroprotective effects, demonstrating potential as a novel antidepressant drug. Its multi-target mechanism aligns with the multifactorial pathological characteristics of current neuropsychiatric diseases and is expected to overcome the limitations of traditional single-target drugs.

However, its druggability still faces certain challenges, especially due to low oral bioavailability and blood-brain barrier permeability, which limits its direct application in central nervous system diseases. In the future, modern pharmacokinetic strategies such as nanocarriers, liposomes, and prodrug design can be used to improve their pharmacokinetic profiles.

Moreover, by combining modern molecular pharmacology and systems biology approaches, in-depth analysis of its network of action and signaling pathways will help clarify its therapeutic advantages and potential side effects, advancing its clinical translational process.

Preclinical animal models and early clinical trials are key steps to verify their safety and efficacy. Combined with the overall pharmacodynamics study of Yuanzhi, Siberian Polygala glycoside A5 is expected to become an important active ingredient in the development of Yuanzhi-type drugs, providing new ideas and options for the treatment of depression and related neuropsychiatric disorders.

Conclusion

Siberian Polygala glycoside A5, as an important oligosaccharide ester natural product isolated from Polygala, exhibits significant antioxidant and antidepressant activities, with a mechanism involving coordinated regulation of multiple targets and pathways. Its good safety profile and unique pharmacological effects provide new candidate molecules for the treatment of neuropsychiatric diseases.

Future research should focus on breaking through its druggability bottleneck, optimizing pharmacokinetic characteristics, and integrating modern pharmaceutics and molecular biology techniques to promote its transition from laboratory to clinical application. In-depth research on Siberian Polygala glycoside A5 has not only enriched the theoretical framework in the field of natural product pharmacology, but also laid a solid foundation for developing new safe and effective antidepressant drugs.