Product name: Polygalic Acid
Synonym name: Senegenic acid
Catalogue No.: BP3322
Cas No.: 1260-04-4
Formula: C₂₉H₄₄O₆
Mol Weight: 488.665
Botanical Source:
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
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.

Description:

Polygalic acid, a triterpenoid saponin, shows expectorant, emetic and stimulant effects.

References:

Biomed Chromatogr. 2012 Feb;26(2):220-4.    

In vivo metabolism study of polygalic acid in rat using HPLC-ESI-MSn.    

A very simple and direct method has been established for the determination of Polygalic acid and its metabolites in rat urine based on HPLC coupled with electrospray ionization multi-stage tandem mass spectrometry (HPLC-ESI-MS(n)). 

METHODS AND RESULTS:

The rats were administered a single dose (100 mg/kg) of Polygalic acid by oral gavage. The urine samples were collected and purified through a C(18) solid-phase extraction cartridge, and then these pretreated samples were injected into a reversed-phase C(18) column with a gradient elution program, whereas acetonitrile-0.5% aqueous formic acid was used as mobile phase and detected by an on-line MS/MS system. As a result, the parent drug and its four metabolites were identified and characterized in rat urine for the first time by comparing their changes in molecular mass (ΔM), retention times and full-scan MS(n) spectra with those of the parent drug. A possible metabolic pathway of Polygalic acid was investigated and proposed. 

CONCLUSIONS:

More importantly, the results demonstrated that the newly developed method (HPLC-ESI-MS(n)) was sensitive, simple and suitable for the determination of Polygalic acid and its metabolites in biological samples. 

HPLC of Polygalic Acid

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

Introduction/Overview

In the vast field where traditional medicine and modern pharmacology intersect, natural products have always been an important source for discovering lead compounds for new drugs. Yuanzhi（Polygala tenuifolia As a traditional Chinese medicine with a long history of calming the nerves and promoting intelligence, the material basis of its pharmacological effects has always been a research hotspot. Among the numerous chemical components of Yuanzhi, Polygalic Acid (CAS number: 1260-04-4) is becoming increasingly important as a key triterpenoid saponin component. In recent years, with the global high incidence of central nervous system diseases such as neurodegenerative diseases and cognitive dysfunction, natural products with neuroprotective activity have attracted much attention. Yuanzhi acid has become a highly promising candidate molecule in this field due to its significant neuroprotective effects demonstrated in various in vitro and in vivo models. This article aims to systematically review the chemical structure, plant origin, pharmacological activity, molecular mechanism of action, pharmacological characteristics, and clinical application prospects of yuanzhi acid, in order to provide comprehensive academic references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

Yuanzhi acid is an Oleanane type pentacyclic triterpenoid saponin. Its molecular formula is C29H44O6 and its molecular weight is 488.6650. Its basic skeleton is oleanolic acid, which is usually connected to one or more sugar groups (such as glucose, xylose, etc.) at the C-3 position to form a saponin structure, which is also an important basis for its biological activity. The specific positions and types of glycosylation connections may vary slightly depending on plant sources and extraction and purification methods, but the core triterpenoid glycoside structure is clear.

From the analysis of parameters related to medicinal properties, Yuanzhi acid exhibits typical physicochemical properties of natural triterpenoid saponins. Its lipophilic water partition coefficient (LogP) is 4.3497, indicating that the compound has moderate to high lipophilicity. The topological polar surface area (TPSA) is 115.0600 Å ², reflecting the presence of multiple polar groups in its molecule, such as hydroxyl, carboxyl, and oxygen atoms on the sugar ring. The low water solubility value (0.0284 mg/mL) suggests poor solubility in water, which may affect its oral bioavailability. It is particularly crucial that its blood-brain barrier (BBB) permeability is predicted to be "low", which is a major challenge for drugs targeting the central nervous system, meaning that its prototype drugs may have difficulty effectively entering brain tissue to exert direct effects. However, its hERG inhibition risk is' no ', and the Ames test result is 0.0 (indicating no mutagenicity), providing favorable information for its preliminary safety assessment.

Plant sources and extraction methods

Yuanzhi acid mainly comes from the Polygalaceae family and the Polygalaceae genus（Polygala）Plants, among which are sourced from authentic traditional Chinese medicine Polygala tenuifolia Willd.'s dry roots are the main source. In addition, plants of the same genus Polygala senega(Meiyuanzhi) and others also contain such triterpenoid saponins.

The extraction of jasmonic acid from plant materials usually follows the conventional process of natural product chemistry. Firstly, crush the dried roots of Eucommia ulmoides and extract them using a solvent of suitable polarity. Due to the fact that yuanzhi acid belongs to the saponin class, methanol, ethanol, or ethanol water mixed solutions of different concentrations are commonly used extraction solvents, which can effectively extract highly polar saponin components. Extraction methods include hot reflux extraction, ultrasound assisted extraction, or microwave-assisted extraction to improve extraction efficiency.

After filtration and concentration, the crude extract needs to be further separated and purified to obtain high-purity Yuanzhi acid. The commonly used techniques include:
1. Solvent Extraction Method Preliminary enrichment can be achieved by utilizing the distribution differences of Yuanzhi acid in different polar solvents, such as extracting saponins from aqueous solutions using n-butanol.
2. Macroporous adsorption resin chromatography method It is an effective method for enriching saponin components, often using resins such as D101 and AB-8, which are washed with water to remove impurities, and then gradient eluted with different concentrations of ethanol.
3. Silica gel column chromatography This is a classic method for further separation and purification, which uses a mixed solvent system of chloroform methanol water as the mobile phase for gradient elution.
4. High performance liquid chromatography method Especially for preparative HPLC, it is the final key step to obtain high-purity monomers of jasmonic acid, often using a reverse phase C18 chromatographic column with methanol water or acetonitrile water as the mobile phase.

The optimization of extraction and purification processes aims to improve the yield and purity of Yuanzhi acid, laying the foundation for its subsequent pharmacological activity research and quality standardization.

Pharmacological activity research

Numerous studies have confirmed that the core pharmacological activity of yuanzhi acid is concentrated in neuroprotection The field has demonstrated multiple beneficial effects in related models.

1. Anti neuronal apoptosis In various models of neuronal damage or cell apoptosis induced by β - amyloid (A β), glutamate, hydrogen peroxide, or serum/nutrient deprivation, treatment with oxalic acid can significantly improve cell survival rate, reduce lactate dehydrogenase (LDH) leakage rate, and decrease the expression of apoptosis related markers such as activated caspase-3.
2. Improving synaptic plasticity and cognitive function In Alzheimer's disease (AD) model animals (such as A β injection or transgenic mice), administration of oxalic acid can improve the animals' learning and memory abilities, and perform better in behavioral tests such as water maze and new object recognition. Its mechanism is related to promoting the expression of synaptic related proteins (such as PSD-95, Synapsin I) in the hippocampus and protecting synaptic ultrastructure.
3. anti-oxidative stress Yuanzhi acid can alleviate neuronal damage induced by oxidative stress. It can reduce the level of intracellular reactive oxygen species (ROS), enhance the activity of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH Px), and reduce the production of lipid peroxidation product malondialdehyde (MDA).
4. Anti neuroinflammation In the activation model of microglia, jasmonic acid can inhibit the excessive activation of microglia induced by lipopolysaccharide (LPS), downregulate the production of inflammatory factors such as tumor necrosis factor - α (TNF - α), interleukin-1 β (IL-1 β), and nitric oxide (NO), thereby reducing the damage of neuroinflammation to neurons.
5. Other potential activities Some studies also suggest that resveratrol may have antidepressant and anti anxiety activities, which are related to its regulation of monoamine neurotransmitters and HPA axis function, but further research is needed.

Mechanism of action and molecular targets

The neuroprotective effect of Yuanzhi acid is not achieved through a single pathway, but involves a complex multi-target regulatory network. Existing research has revealed that it is closely related to multiple key neuroprotective targets and pathways:

• Regulating apoptosis related proteins (BCL2, CASP9)Yuanzhi acid can upregulate the expression of anti apoptotic protein Bcl-2, while downregulating the expression of pro apoptotic protein Bax, and inhibiting the activation of caspase-9 and its downstream caspase-3, thereby blocking the mitochondrial mediated endogenous apoptosis pathway.
• Intervention of AD pathological core targets (APP, BACE1, MAPT, GSK3B)Yuanzhi acid can reduce the production of A β by inhibiting the activity of β - secretase 1 (BACE1). At the same time, it can inhibit the overactivation of glycogen synthase kinase-3 β (GSK3B), thereby reducing abnormal hyperphosphorylation of tau protein (related to tau protein encoded by MAPT gene) and alleviating the formation of neurofibrillary tangles.
• Activate endogenous protective pathways (NFE2L2, SIRT1)Yuanzhi acid is an effective activator of the nuclear factor E2 related factor 2 (Nrf2, encoded by NFE2L2) pathway. It can promote Nrf2 nuclear translocation, enhance the expression of downstream phase II detoxifying enzymes such as heme oxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO1), and antioxidant proteins, which is the core mechanism of its antioxidant stress response. In addition, it can upregulate the expression of the deacetylase SIRT1, which regulates transcription factors such as PGC-1 α and FOXO through deacetylation and plays an important role in energy metabolism, antioxidant and anti apoptotic effects.
• Regulating the signal transduction pathway (MAPK1)The mitogen activated protein kinase (MAPK) pathway, especially the extracellular signal regulated kinase (ERK, encoded by MAPK1) pathway, plays a critical role in cell survival and proliferation. Research has shown that jasmonic acid can activate the ERK signaling pathway, and its neuroprotective effect can be blocked by ERK inhibitors, indicating that the activation of the ERK pathway is an important link in its function.

In summary, Yuanzhi acid synergistically acts on multiple targets and pathways mentioned above, forming a comprehensive neuroprotective network that inhibits pathological damage (A β, p-tau), enhances cellular defense (antioxidant, anti-inflammatory), and promotes cell survival (anti apoptosis).

Evaluation of drug properties and pharmacokinetics

Although Yuanzhi acid exhibits excellent pharmacological activity, there are some challenges in its drug likeness, which directly relates to whether it can be developed into a clinical drug.

1. Absorption, distribution, metabolism, excretion (ADME)：

   • absorb As a saponin compound, its larger molecular weight and more polar groups may limit its passive transmembrane diffusion, resulting in poor and irregular oral absorption. The gut microbiota may hydrolyze its glycosyl portion to generate aglycones, which may undergo changes in absorption and activity.
   • distribution As mentioned earlier, its predicted blood-brain barrier permeability is low, which is the main bottleneck in the development of central nervous system drugs. Prototype drugs may be difficult to achieve effective therapeutic concentrations in the brain.
   • Metabolism and excretion Triterpenoid saponins may undergo extensive phase I (such as oxidation) and phase II (such as glucuronidation and sulfation) metabolism in the body. Its metabolites may be active or inactive. The main excretion pathways may be through bile and feces.

2. Analysis of drug properties parameters Based on its molecular weight (488.7), LogP (4.35), and TPSA (115.1), Yuanzhi acid basically conforms to Lipinski's "five rules" boundary (molecular weight<500, LogP<5, hydrogen bond donor<5, hydrogen bond acceptor<10), but poor water solubility and low BBB permeability are the two core defects.

3. Formulation and structural modification strategies To overcome these obstacles, future research may focus on:

   • New drug delivery system Develop drug delivery systems such as nanoparticles, liposomes, and microemulsions to improve their solubility, stability, and targeting, particularly enhancing their brain targeted delivery capabilities.
   • Prodrug strategy Preparation of higher lipid soluble prodrugs through chemical modification to improve their BBB permeability, and release of the original drug through hydrolysis after entering the brain.
   • structural optimization On the premise of retaining its pharmacophore, structural modifications are made to its glycosyl portion or aglycone to optimize its physicochemical properties and pharmacokinetic characteristics.

At present, there is still a relative lack of complete preclinical pharmacokinetic research data on the Yuanzhi acid system, which is a key link that must be supplemented for its development.

Clinical application prospects and prospects

Yuanzhi acid, as an active ingredient derived from traditional Chinese medicine, has a clinical application prospect mainly focused on Neurological disorders Prevention and treatment, especially in the fields of neurodegenerative diseases and vascular cognitive impairment.

1. Potential indications：

   • Alzheimer's disease (AD) and mild cognitive impairment (MCI)As a multi-target intervention agent, Yuanzhi acid has the potential to be developed as a disease modifying therapy by targeting multiple aspects of AD, including A β deposition, tau protein pathology, oxidative stress, and neuroinflammation.
   • Vascular dementia (VaD)Its antioxidant, anti apoptotic, and anti-inflammatory effects may have a protective effect against cognitive decline caused by vascular factors such as cerebral ischemia/reperfusion injury and chronic cerebral hypoperfusion.
   • Parkinson's disease (PD)Its antioxidant and Nrf2 pathway activating effects theoretically benefit the protection of dopaminergic neurons and are worth exploring in PD models.
   • Post stroke neural repair During the acute and recovery phases of ischemic stroke, its neuroprotective effects may help reduce infarct size and promote functional recovery.

2. Development Challenges and Prospects：

   • challenge The primary challenge is to address the issue of low brain delivery efficiency. Secondly, it is necessary to complete a systematic preclinical safety evaluation (long-term toxicity, reproductive toxicity, etc.) and conduct human pharmacokinetic studies that meet drug registration requirements. Thirdly, as a natural product, the stability of its raw material sources, standardization of extraction and purification processes, and cost control also need to be considered.
   • prospect Future research should focus on: ① constructing efficient brain targeted delivery systems using modern pharmaceutical technologies; ② Conduct in-depth pharmacokinetic/pharmacodynamic (PK/PD) correlation studies to clarify its in vivo mode of action and concentration; ③ Validate its long-term efficacy in complex animal models that are closer to human diseases, such as 3xTg AD mice; ④ Explore the synergistic effects of its combination with other drugs, such as cholinesterase inhibitors. In addition, using it as a lead compound for structural optimization and creating new chemical entities with independent intellectual property rights and better drug properties is a more attractive path for new drug development.

Conclusion

Yuanzhi acid is one of the key triterpenoid saponins in Yuanzhi medicinal materials that exert neuroprotective effects. Research has shown that it exhibits clear multiple pharmacological activities in cell and animal models, including anti apoptotic, antioxidant, anti-inflammatory, and cognitive improvement, by regulating multiple targets and pathways such as BCL2, CASP9, APP/ACE1, GSK3B, NFE2L2, SIRT1, and MAPK. These findings not only explain the traditional efficacy of Yuanzhi's "intelligence enhancing and calming" approach from a modern scientific perspective, but also provide a solid theoretical basis for its development as a potential drug for treating neurodegenerative diseases such as Alzheimer's disease. However, its inherent pharmaceutical bottlenecks such as poor water solubility and low blood-brain barrier permeability are important obstacles that restrict its clinical translation. Future research should focus on utilizing advanced drug delivery technologies and rational drug chemical modification strategies to overcome these shortcomings, and advance systematic preclinical and clinical studies, with the ultimate goal of transforming this ancient natural wisdom into new treatment options that benefit modern patients.