Synonym name: Piceid
Catalogue No.: BP1118
Cas No.: 27208-80-6
Formula: C₂₀H₂₂O₈
Mol Weight: 390.388
Botanical Source: Picea spp., Pinus sibirica, Polygonum cuspidatum (Japanese knotweed) and Eucalyptus spp.

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.

HPLC of Polydatin

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

Introduction/Overview

Natural products, as an important source of drug discovery, play an irreplaceable role in the history of human disease prevention and treatment. Polydatin, also known as Piceid, chemical name 3,4 ', 5-trihydroxystilbene-3- β - D-glucoside, is a traditional Chinese medicine derived from Polygonum cuspidatum（Polygonum cuspidatum Active stilbene compounds extracted from the roots and stems of Sieb. et Zucc. Its CAS number is 27208-80-6, and it is a glucoside derivative of the star molecule resveratrol. In recent years, with the deepening of modern pharmacological research, Polygonatum sibiricum glycoside has shown extensive and unique biological activities beyond its aglycone, especially in the fields of cardiovascular protection, anti-inflammatory, antioxidant, and organ protection, showing great potential. Its mechanism of action involves multi-target and multi pathway regulation, including but not limited to inhibiting glucose-6-phosphate dehydrogenase (G6PD), regulating oxidative stress and endoplasmic reticulum stress, and intervening in key signaling pathways. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, molecular mechanisms, medicinal properties, and clinical application prospects of Polygonatum sibiricum glycoside, in order to provide comprehensive scientific references for the deep development and transformation research of this natural product.

Chemical structure and physicochemical properties

The molecular formula of Polygonatum sibiricum glycoside is C20H22O8, with a molecular weight of 390.3880. Its core structure is a trans stilbene skeleton. Compared with resveratrol (3,4 ', 5-trihydroxystilbene), its C-3 hydroxyl group is replaced by a β - D-glucosyl group through a glycosidic bond, forming β - D-glucosides. This glycosylation modification significantly altered its physicochemical properties and biological activity.

In terms of physicochemical properties, the introduction of glycosidic bonds greatly enhances the water solubility of Polygonatum sibiricum glycoside. Both computational and experimental data indicate that its water solubility (approximately 2.12 mg/mL) is much higher than that of fat soluble resveratrol. Its topological polar surface area (TPSA) is 139.84 Å ², indicating strong molecular polarity. The calculated LogP value is about 0.60, indicating that it has moderate lipophilicity, between hydrophilic and lipophilic, which is beneficial for its distribution and absorption in organisms. These properties collectively determine the pharmacokinetic behavior of puerarin in vivo, for example, its oral bioavailability is generally considered superior to resveratrol, as the glycosylation structure may facilitate its absorption through glucose transporters (such as SGLT1) on small intestinal epithelial cells.

Plant sources and extraction methods

The main source of Polygonatum sibiricum glycoside is the dried rhizome of the Polygonaceae plant Polygonatum sibiricum. As a traditional Chinese medicine, Polygonum cuspidatum is widely used in Asia, especially in China, Japan, and South Korea, to treat inflammation, infections, hyperlipidemia, and cardiovascular diseases. Polygonatum sibiricum glycoside is also present in plants such as grapes, peanuts, and mulberries, but its content is much lower than that of Polygonatum sibiricum.

The extraction of puerarin from Polygonum cuspidatum is usually carried out using solvent extraction method. The common process includes heating and refluxing the dried and crushed roots and stems of Polygonum cuspidatum with ethanol (such as 60% -80% ethanol) or methanol, or using ultrasound assisted extraction. After filtration and concentration, the crude extract was enriched and purified using macroporous adsorption resins (such as AB-8, D101). Different concentrations of ethanol aqueous solutions were used for gradient elution to effectively separate puerarin. Further refinement can be achieved through methods such as silica gel column chromatography, preparative high-performance liquid chromatography (HPLC), or recrystallization. Modern extraction techniques such as supercritical CO2 extraction and microwave-assisted extraction have also been explored to improve extraction efficiency and purity. During the extraction process, attention should be paid to controlling temperature and avoiding light to prevent the transformation of puerarin from its trans configuration to a less active or different cis configuration.

Pharmacological activity research

Numerous preclinical studies have confirmed that puerarin has broad and significant pharmacological activities, and its spectrum of action is even superior to its glycoside resveratrol in some aspects.

1. Cardiovascular protective effect This is one of the most highly regarded activities of Polygonatum sibiricum glycoside. Research has shown that puerarin can alleviate myocardial ischemia/reperfusion injury and improve heart function; Inhibit myocardial fibrosis and ventricular remodeling; Anti atherosclerosis, stable plaque; And it has anti arrhythmic effects. Its mechanism is closely related to antioxidant stress, anti-inflammatory, regulation of ion channels, improvement of energy metabolism, and protection of endothelial function.
2. Anti inflammatory and immune regulatory effects Tiger cane glycoside exhibits potent inhibitory effects on both acute and chronic inflammation models. It can significantly reduce the expression of pro-inflammatory factors such as tumor necrosis factor - α (TNF - α), interleukin-1 β (IL-1 β), and interleukin-6 (IL-6) in macrophages stimulated by lipopolysaccharides (LPS), and its anti-inflammatory strength is stronger than resveratrol in some models.
3. Antioxidant and anti stress effects Tiger cane glycoside is an effective free radical scavenger that can enhance the activity of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH Px), and reduce the level of malondialdehyde (MDA). More importantly, it can moderately regulate the levels of reduced coenzyme II (NADPH) and glutathione (GSH) in cells by inhibiting G6PD (a key enzyme in the pentose phosphate pathway), thereby inducing a "beneficial" oxidative stress that selectively acts on abnormally proliferating cells (such as certain tumor cells) while protecting normal cells. It can also alleviate endoplasmic reticulum stress and maintain cellular homeostasis.
4. Organ protection function：
   • Liver protection It has a protective effect on alcoholic liver injury, drug-induced liver injury, non-alcoholic fatty liver disease, and liver fibrosis, with mechanisms involving inhibition of inflammation, reduction of lipid deposition, and anti hepatic stellate cell activation.
   • Kidney protection: It can reduce glomerulosclerosis, tubulointerstitial fibrosis and proteinuria, and protect renal function in the models of diabetes nephropathy and drug-induced renal injury.
   • neuroprotection Despite its low blood-brain barrier permeability, studies have shown that it has protective potential against neurodegenerative disease models such as cerebral ischemia and Alzheimer's disease, possibly through indirect anti-inflammatory or regulation of peripheral central communication.
5. Other activities It also has anti-tumor (inducing apoptosis and inhibiting proliferation), anti diabetes (improving insulin resistance), anti-virus and anti-aging effects.

Mechanism of action and molecular targets

The multiple pharmacological activities of Polygonatum sibiricum stem from its extensive regulation of cellular signaling networks. Its mechanism of action is complex, involving multiple direct or indirect molecular targets and pathways, especially in cardiovascular protection where multiple key targets have been identified:

1. Core enzyme target - G6PD inhibition Tiger cane glycoside has been identified as an effective inhibitor of G6PD. Inhibition of G6PD reduces the production of NADPH, which in turn affects the ability of glutathione reductase to maintain the reduced state of GSH, leading to a shift in intracellular redox balance towards an oxidative state. This moderate oxidative stress can activate adaptive antioxidant pathways such as nuclear factor E2 related factor 2 (Nrf2), but may trigger apoptosis in proliferating cells. This is a unique and important mechanism that distinguishes it from resveratrol.
2. Signal pathway regulation：
   • PI3K/Akt signaling pathway Tiger cane glycoside can activate Akt (protein kinase B, encoded by the AKT1 gene), phosphorylate and inhibit downstream pro apoptotic proteins such as glycogen synthase kinase-3 β (GSK-3 β) and Bad, and activate endothelial nitric oxide synthase (eNOS, encoded by the NOS3 gene) to promote nitrogen monoxide (NO) production, exerting anti apoptotic, pro survival, and vasodilatory effects.
   • NF - κ B signaling pathway By inhibiting the activation of I κ B kinase (IKK) and preventing nuclear factor kappa B (NF - κ B) nuclear translocation, the expression of inflammatory factors such as TNF - α, IL-6, intercellular adhesion molecule-1 (ICAM1), and vascular cell adhesion molecule-1 (VCAM1) is downregulated, which is the core of its anti-inflammatory effect.
   • Nrf2/ARE pathway By inducing oxidative stress or direct action, promoting Nrf2 nuclear translocation, activating antioxidant response elements (ARE), upregulating the expression of phase II detoxifying enzymes and antioxidant proteins such as heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1).
3. Key functional proteins and receptor regulation：
   • Endothelial function related Upregulation of NOS3 (eNOS) promotes NO production; Downregulation of ICAM1 and VCAM1 reduces leukocyte adhesion and endothelial inflammation; Inhibit the expression of P-selectin (SELP) and reduce platelet and leukocyte aggregation.
   • Ion channels and transporters Regulating potassium ion channels (such as hERG, encoded by KCNH2) and participating in antiarrhythmic effects; Affects the sodium calcium exchanger (SLC8A1) and regulates intracellular calcium homeostasis in cardiomyocytes.
   • Nuclear receptors and enzymes As a partial agonist of peroxisome proliferator activated receptor gamma (PPARG), it participates in regulating glucose and lipid metabolism and inflammation; It may indirectly regulate the renin-angiotensin system (RAS) by affecting the activity of angiotensin-converting enzyme (ACE).
   • Adrenergic receptors May affect cardiovascular tension and metabolism by regulating β 2-adrenergic receptors (ADRB2).

These targets do not exist in isolation, but form an interconnected network. For example, activation of Akt can simultaneously inhibit GSK-3 β and activate eNOS, and cross talk to inhibit NF - κ B, thereby synergistically achieving anti-inflammatory, antioxidant, and cell protection.

Evaluation of drug properties and pharmacokinetics

Based on its physicochemical properties and preliminary research, Polygonatum sibiricum glycoside has shown certain potential as a drug, but there are also challenges.

Analysis of drug properties parameters Its good water solubility is beneficial for the development of formulations; Moderate LogP values indicate balanced membrane permeability; A higher TPSA may affect its passive transmembrane diffusion, but the presence of glucose groups may mediate active transport. The key toxicity warning indicators show that the hERG inhibition risk is "no", and the Ames test result is negative (0.0), indicating a low risk of cardiac and genetic toxicity and a good safety basis. However, its blood-brain barrier permeability is "low", which limits its direct effect on central nervous system diseases.

Pharmacokinetic characteristics After oral administration, the absorption of Polygonatum sibiricum may partially rely on the glucose transporter (SGLT1) in the small intestine, and its bioavailability has been reported differently, but it is generally believed to be higher than resveratrol. In the body, puerarin can be hydrolyzed by β - glucosidase in the gut microbiota or tissues, and converted into resveratrol, which is further metabolized into sulfate or glucuronide conjugates. Therefore, the pharmacological effects of Polygonatum sibiricum may be the result of the joint contribution of its prototype, metabolite resveratrol, and their combination, which increases the complexity of its mechanism of action. It is widely distributed and accumulates to some extent in target organs such as the heart, liver, and kidneys. Mainly excreted through urine and feces.

Challenges and Strategies The main challenges include the need to improve the absolute oral bioavailability, complex metabolic transformation in vivo, and unclear substance basis of action. Future formulation strategies may include the development of nanocarrier systems (such as liposomes, nanoparticles), prodrug modification, or co administration of β - glucosidase inhibitors to regulate their metabolic conversion, with the aim of improving their stability, targeting, and bioavailability.

Clinical application prospects and prospects

The clinical application prospects of Polygonatum sibiricum glycoside are broad, but currently it is mainly in the preclinical research and early clinical trial stage.

1. Potential indications：

   • cardiovascular disease As an auxiliary drug, it is the most promising direction for the prevention and treatment of coronary heart disease, myocardial infarction, heart failure, arrhythmia and atherosclerosis.
   • Metabolic diseases: It is used for the treatment of nonalcoholic fatty liver disease (NAFLD), diabetes and its complications (such as diabetes nephropathy).
   • Inflammatory and immune diseases Such as acute lung injury, arthritis, inflammatory bowel disease, etc.
   • Organ ischemia/reperfusion injury Used as a protective agent in surgeries or transplants of organs such as the heart, liver, and kidneys.

2. Translation Research Challenge：

   • Mechanism depth Further clarification is needed on the respective contributions of its prototype and metabolites, as well as the precise regulatory mechanisms of its unique targets (such as G6PD) under different pathological conditions.
   • Clinical Evidence It is urgent to design rigorous randomized controlled clinical trials to verify their effectiveness and safety in humans, and determine the optimal dosing regimen.
   • Formulation optimization Develop a new drug delivery system to overcome its drug weakness.
   • quality control Establish a comprehensive quality control standard from raw materials to finished products to ensure product consistency and stability.

3. Future direction Combining systems biology, network pharmacology, and artificial intelligence to deeply analyze the action network of "multi-component multi-target multi-path"; Explore its potential for combination therapy with other drugs (such as conventional cardiovascular drugs); Explore its value in age-related diseases.

Conclusion

Tiger cane glycoside, as a natural stilbene glycoside derived from traditional Chinese medicine, has become a hot molecule in natural product pharmacology research due to its wide pharmacological activity, multi-target mechanism of action, and relatively good safety characteristics. Its unique G6PD inhibitory activity and differentiated biological effects associated with resveratrol provide new ideas for the development of novel cardiovascular protectants, anti-inflammatory agents, and metabolic regulators. Despite facing challenges such as pharmacokinetic optimization, elucidation of the substance basis of action, and obtaining high-level clinical evidence on the path towards clinical drug development, with the continuous integration of modern scientific and technological means, Polygonatum sibiricum is expected to successfully move from experimental research to clinical application, providing a unique natural drug choice for the prevention and treatment of various major chronic diseases. Continuous and in-depth research on it will not only help promote the development of innovative drugs, but also make positive contributions to interpreting the scientific connotation of traditional Chinese medicine.