Product name: Tenuifolin
Synonym name:
Catalogue No.: BP1374
Cas No.: 20183-47-5
Formula: C₃₆H₅₆O₁₂
Mol Weight: 680.832
Botanical Source: Polygala tenuifolia, Polygala senega, Strophanthus sp. and Pygeum africanum (preferred genus name Prunus)
Physical Description: White 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:
Tenuifolin is an effective compound from tenuigenin, is commonly used in traditional Chinese herbal medicine for memory loss, has no inherent toxicity to either the transfected or wild type cells at the effective concentrations, it inhibits amyloid-β secretion in vitro.[1]
Tenuifolin is one of the active constituents of HPS against the neurotoxicity induced by Aβ25-35 peptides in vitro and in vivo, it possesses neuroprotective effects against Aβ25-35-induced apoptosis in PC12 cells and significantly improves the cognitive deficits induced by the intrahippocampal injection of Aβ25-35 in mice. [2]

References:
[1] Lv J, Jia H, Jiang Y, et al. Acta Physiol, 2009, 196(4):419-25.
[2] Liu Y M, Li Z Y, Hu H, et al. Pharmacol Biochem Be, 2015, 128:14-22.
[3] Dong X B, Jun L I, Jiang Y, et al. China journal of Chinese materia medica, 2007, 32(16):1647-9.

HPLC of Tenuifolin

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

Introduction/Overview

Tenuifolin is a triterpene saponin isolated from the medicinal herb Polygala tenuifolia Willd., and has recently attracted widespread attention for its significant neuroprotective effects and potential therapeutic value for neurodegenerative diseases. As a classic herb in traditional Chinese medicine used to enhance memory, relieve anxiety, and calm, one of its main active ingredients is the polygala saponin in the leaves. Numerous in vivo and in vitro studies have shown that polygala saponins not only have good oral activity but can also regulate nervous system function through multiple targets and pathways, showing unique advantages in the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease (AD).

This paper systematically reviews the chemical structure and physicochemical properties of Polygala saponins from Fine-leaved Leaves, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, pharmacokinetic characteristics, as well as their potential and future development directions for clinical applications, aiming to provide theoretical basis and practical guidance for related research.

Chemical structure and physicochemical properties

Polygala fine-leaved saponins have a molecular formula of C_36H_58O_12 and a molecular weight of 680.8320, belonging to the triterpene saponin class. Its structural core is a typical triterpene backbone, connected to multiple glycosyl residues, giving it high polarity. In terms of physicochemical properties, the LogP value of Polygala saponins in the microleaf is about 2.13, indicating moderate lipid solubility that facilitates cell membrane penetration. Its topological polarity surface area (TPSA) is relatively large, at 214.44 Ų, reflecting its strong polarity and water solubility. Water solubility is 0.15, indicating limited solubility in water but sufficient to support oral administration.

The blood-brain barrier penetration ability is relatively low, suggesting limited efficiency in directly entering the central nervous system, but this does not prevent it from exerting neuroprotective effects through indirect mechanisms. The hERG channel inhibition test was negative, indicating a low risk of cardiac toxicity in polygala saponins. Ames mutagenicity test results were zero, indicating low genotoxicity risk and good safety.

Plant Origins and Extraction Methods

Polygala tenuifolia saponins mainly come from the root of Polygala tenuifolia Willd. Polygala is a plant in the Polygalaceae family, widely distributed in northern China, as well as Korea, Japan, and other regions. In traditional Chinese medicine, Polygala root is used as a calming, intellectual, and expectorant herb.

Common methods for extracting polygala saponins from the fine leaf include:

1. Solvent extraction: Using ethanol or methanol as extraction solvents, with reflux or ultrasonic-assisted extraction, can effectively extract saponin components from Polygala root.
2. Separation and purification: After the initial extract is concentrated, it is separated and purified using liquid-liquid separation, silica gel column chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC) to obtain high-purity polygalgal saponins.
3. Modern technologies: Emerging technologies such as supercritical CO_2 extraction and microwave-assisted extraction have also been attempted to improve extraction efficiency and purity.

The extraction process requires controlling temperature and pH to prevent degradation of saponin structures. Purified polygala saponins are commonly identified by mass spectrometry (MS), nuclear magnetic resonance (NMR), and other methods.

Pharmacological activity research

The pharmacological activity of Polygala saponins is mainly concentrated in neuroprotection and cognitive function improvement, involving various neurodegenerative disease models.

1. Anti-Alzheimer's effects

Polygala saponins in the microphyllar significantly inhibit the activity of β-secretase β(BACE1) through multi-target regulation, reduce the formation and deposition of amyloid β protein (Aβ), especially the Aβ_25-35 fragment, and lessen Aβ-induced neurotoxicity. In vitro experiments showed that polygala saponins inhibited Aβ_25-35-induced apoptosis, reduced activation of caspase-3 and caspase-9, and blocked the apoptosis signaling pathway.

2. Antioxidant and anti-inflammatory effects

Polygala saponins in the fine leaf can activate the NFE2L2 (nuclear factor E2-related factor 2) signaling pathway, enhancing cellular antioxidant capacity and reducing oxidative stress damage. Additionally, it modulates the TLR4 (Toll-like receptor 4) signaling pathway, inhibits neuroinflammatory responses, and reduces inflammatory damage to nerve cells.

3. Neurotransmitter regulation

Polygala saponins in the leaves can effectively reduce acetylcholinesterase (AChE) activity, increase acetylcholine levels in the brain, and improve cholinergic nerve conduction. At the same time, it can also increase levels of neurotransmitters such as norepinephrine and dopamine, promote neuronal function recovery, and improve learning and memory abilities.

4. Cognitive function improvement

In an aging mouse model, oral Vestifolia saponins significantly improved spatial learning and memory abilities, with shortened latency and enhanced spatial memory in the water maze experiment, suggesting potential therapeutic value for cognitive impairment.

5. Other neuroprotective effects

Polygala saponins in the leaf are also reported to have antidepressant, anti-anxiety, and neuroregenerative effects, possibly through regulation of PRKCA (protein kinase Cα) and MAPK1 (mitogen-activated protein kinase 1) signaling pathways.

Mechanism of action and molecular targets

The mechanism of action of Polygala saponins is complex, involving multiple molecular targets and signaling pathways, reflecting their multi-target pharmacological characteristics.

1. Inhibits β-secretase (BACE1)

BACE1 is a key enzyme in Aβ production. Polygala saponins in the microleaf directly or indirectly inhibit BACE1 activity, reduce the cleavage of Aβ precursor protein (APP), decrease the production of toxic Aβ, and slow the formation of amyloid plaques.

2. Anti-apoptotic effect

Polygala saponins inhibit the activation of caspase-3 and caspase-9, blocking mitochondrial pathway-mediated apoptosis. Its regulation of BCL2 protein enhances the cell's anti-apoptosis ability and protects neuronal survival.

3. Regulates neurotransmitter metabolism

By inhibiting AChE activity, polygala saponins increase acetylcholine content, improving neurotransmission efficiency. It also increases norepinephrine and dopamine levels, regulating central nervous system function.

4. Antioxidant and anti-inflammatory signaling pathways

Polygala saponins in the fine leaf activate the NFE2L2 pathway, promote antioxidant enzyme expression, and reduce oxidative stress. By suppressing TLR4 signaling, it reduces the release of pro-inflammatory factors and alleviates neuroinflammation.

5. Other signal pathways

Polygala saponins may regulate signaling molecules such as PRKCA and MAPK1, affecting nerve cell proliferation, differentiation, and survival, and promoting nerve repair and functional recovery.

Druggability evaluation and pharmacokinetics

1. Drug-Yielding Parameters

Polygala saponins have a relatively large molecular weight (680.8 Da) and a high TPSA (214.44 Ų), suggesting strong polarity that may limit their ability to cross cell membranes and the blood-brain barrier. A LogP value of 2.13 indicates moderate lipid solubility, which is beneficial for oral absorption.

Water solubility is 0.15, making it a low-solubility drug that may affect its bioavailability. The blood-brain barrier has a relatively low penetration ability, suggesting limited efficiency in direct entry into the central nervous system, but it can still play a role by modulating the peripheral nervous system or by indirect mechanisms.

The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test result was 0, indicating low genotoxicity risk and good safety.

2. Pharmacokinetic characteristics

Currently, there is limited systematic pharmacokinetic research on polygala saponins from the leaf leaves. Existing studies show that polygala saponins are absorbed quickly after oral administration, and the timing of plasma concentration peaks is moderate. Its metabolism in the body mainly passes through the liver enzyme system, and the metabolites still require further identification.

Due to the low permeability of the blood-brain barrier, the distribution of polygala saponins in the central nervous system is limited, and it may be necessary to increase their concentration in the brain through structural modification or formulation optimization.

Prospects and outlooks for clinical applications

Polygala saponins in the microphyllar show promising application potential in the treatment of neurodegenerative diseases, especially Alzheimer's disease. Its multi-target, multi-mechanism pharmacological effects are expected to overcome the limitations of single-target drugs, providing more comprehensive neuroprotection and cognitive improvement.

The key to future clinical applications lies in:

1. Formulation and Administration Route Optimization: Improving oral bioavailability and brain distribution, such as nanocarriers, liposomes, and other novel formulation technologies.
2. Safety and efficacy evaluation: Conduct systematic preclinical toxicology and clinical trials to clarify dosage ranges and long-term drug safety.
3. Structural modification and lead compound development: Chemical modification enhances blood-brain barrier penetration and efficacy, developing derivatives with greater clinical value.
4. Combination therapy strategy: Combined with other anti-AD drugs to achieve synergistic effects and improve treatment outcomes.

In addition, the potential of Polygala saponins in the micro-leaf for antidepressant, anxiety-relieving, and neural repair is also worth further exploration, providing new ideas for comprehensive treatment of neurological diseases.

Conclusion

As an important triterpene saponin in Polygala, the polygala saponin has become a hot natural product in research on neurodegenerative diseases, especially Alzheimer's disease, due to its multi-target neuroprotective effects and good safety. By inhibiting β-secretase activity, anti-apoptotic, antioxidant, and neurotransmitter regulation, it significantly improves cognitive function and shows broad clinical application prospects.

In the future, in-depth research into its pharmacokinetic characteristics and mechanisms of action should be strengthened, formulation technology optimized, and clinical translation promoted. Polygala saponins are expected to become important neuroprotective agents in the field of natural product pharmacology, providing new drug candidates and therapeutic strategies for the treatment of neurodegenerative diseases.