Synonym name:
Catalogue No.: BP1011
Cas No.: 80418-25-3
Formula: C₄₁H₇₀O₁₃
Mol Weight: 770.998
Botanical Source: Panax notoginseng (San qi)

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 Notoginsenoside R2

HNMR of Notoginsenoside R2

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

Introduction/Overview

Panax notoginseng, as a traditional Chinese medicinal herb, is widely used in the prevention and treatment of cardiovascular and cerebrovascular diseases due to its remarkable effects of activating blood circulation, removing blood stasis, stopping bleeding, and anti-inflammatory. Sanqi saponins are the main active ingredient in Sanqi, possessing diverse pharmacological activities and good clinical value. Notoginsenoside R2 (CAS No. 80418-25-3), as one of the triterpene saponin compounds, has attracted widespread attention in recent years for its potential in cardiovascular protection. This paper aims to systematically review the chemical structure, origin, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of Sanqi saponin R2, providing a theoretical basis for subsequent basic and clinical research.

Chemical structure and physicochemical properties

Sanqi saponin R2 is a natural product of the triterpene saponin class, with a molecular formula of C42H70O13 and a molecular weight of 770.9980. Its structural core is the pentacyclic triterpene parent nucleus, which connects multiple sugar groups to form a typical saponin structure. In terms of physicochemical properties, the LogP value of Sanqi saponin R2 is 2.7013, indicating moderate lipid solubility that facilitates cell membrane penetration. The polar surface area (TPSA) is 218.99, indicating high molecular polarity and low water solubility (0.0463), which may affect its oral absorption and bioavailability. The blood-brain barrier penetration capacity is relatively low, indicating limited exposure to the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames mutagenic test scored 0.0, indicating low genotoxicity risk and good safety.

Plant Origins and Extraction Methods

Sanqi saponin R2 is mainly found in Sanqi root and its rhizome. Sanqi is a plant of the genus Panax in the Araliaceae family, mainly distributed in Yunnan, Guangxi, and other regions of China. Traditional extraction methods usually use ethanol or methanol as solvents, and crude extracts are obtained through reflux extraction or ultrasound-assisted extraction. Subsequently, techniques such as liquid-liquid separation, silica gel column chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC) were used for separation and purification, ultimately yielding high-purity Sanqi saponin R2. Modern extraction processes are continuously optimized, such as supercritical CO2 extraction and membrane separation technologies, aiming to improve extraction efficiency and purity while reducing production costs.

Pharmacological activity research

Sanqi saponin R2 has demonstrated significant cardiovascular protective effects in multiple in vivo and in vitro experiments. Its main pharmacological effects include:

1. Anti-ischemia-reperfusion injury: Sanqi saponin R2 can reduce myocardial cell apoptosis, alleviate myocardial damage caused by ischemia-reperfusion, and improve cardiac function indicators.
2. Anti-inflammatory effect: By inhibiting the expression of inflammatory factors, it reduces the inflammatory response of vascular endothelial cells and slows the progression of atherosclerosis.
3. Antioxidant effect: Enhances the activity of endogenous antioxidant enzymes, eliminates free radicals, and protects the cardiovascular system from oxidative stress damage.
4. Vasodilation and improved blood flow: Promotes nitric oxide (NO) production, improves endothelial function, and regulates blood pressure.
5. Anti-platelet aggregation and antithrombosis: Inhibits platelet activation factors and reduces the risk of thrombosis.

In addition, Sanqi saponin R2 also shows potential in regulating lipid metabolism and improving myocardial energy metabolism, demonstrating its multi-target, multi-mechanism comprehensive therapeutic advantages.

Mechanism of action and molecular targets

The cardiovascular protective effects of Sanqi saponin R2 involve multiple molecular targets and signaling pathways, mainly including:

• SELP (Selector P): Sanqi saponin R2 inhibits platelet adhesion to white blood cells by downregulating SELP expression, reducing inflammatory responses and thrombosis.
• PPARG (Peroxisome Proliferator-Activated Receptor γ): Activates the PPARG signaling pathway, regulates lipid metabolism, inhibits inflammation, and promotes vascular repair.
• ACE (angiotensin-converting enzyme): inhibits ACE activity, reduces angiotensin II production, exerts antihypertensive and anti-myocardial remodeling effects.
• AKT1 (protein kinase B): activates the AKT1 pathway, promotes cell survival and proliferation, and inhibits cardiomyocyte apoptosis.
• ADRB2 (β2 adrenergic receptor): regulates myocardial contraction and vasodilation, improving heart function.
• KCNH2 (human cardiac potassium channels): regulates cardiac electrical activity, reducing the risk of arrhythmias.
• NOS3 (endothelial nitric oxide synthase): promotes NO synthesis, improves vascular endothelial function, and dilates blood vessels.
• ICAM1 and VCAM1 (cell adhesion molecules): Reduce their expression to alleviate vascular inflammation and atherosclerosis.
• SLC8A1 (sodium-calcium exchange protein): regulates cardiac cell calcium homeostasis and protects myocardial function.

The synergistic regulation of these targets forms the molecular basis for the multidimensional protection of Sanqi saponin R2 in cardiovascular health.

Druggability evaluation and pharmacokinetics

The druggability evaluation of Sanqi saponin R2 shows good safety and potential medicinal value. It has a large molecular weight, high polarity, and poor water solubility, which may limit oral bioavailability, suggesting the need for formulation optimization or structural modification to improve pharmacokinetic properties. The blood-brain barrier has low permeability, reducing the risk of central nervous system side effects. The hERG channel has no inhibitory effect, reducing the drug safety risks associated with arrhythmias. Ames test was negative, indicating no significant mutagenicity.

Pharmacokinetic studies show that Sanqi saponin R2 is slowly absorbed orally and widely distributed in the body, mainly metabolized through the liver, with excretion primarily via bile and urine. Its half-life is moderate, making it suitable for routine administration. In the future, further research on metabolic pathways, drug interactions, and long-term toxicology is needed to provide a basis for clinical development.

Prospects and outlooks for clinical applications

Based on the multi-target and multi-mechanism effects of Sanqi saponin R2 in cardiovascular protection, it has broad application prospects in adjunctive treatment of coronary heart disease, myocardial ischemia, atherosclerosis, hypertension, and other diseases. Currently, Sanqi saponin R2 is still in the basic and preclinical research stages, and future research should focus on the following areas:

1. Clinical trial validation: Design scientific and reasonable clinical trials to evaluate efficacy, safety, and dosage regimens.
2. Formulation development: Improving bioavailability and targeting through novel formulations such as nanocarriers and liposomes.
3. Structural optimization: Based on the drug-efficacy-toxicity relationship, molecular structure is optimized to enhance pharmacodynamics and pharmacokinetic performance.
4. Combination drug research: Exploring synergistic effects with existing cardiovascular drugs to enhance treatment outcomes.
5. Multi-field expansion: Given its anti-inflammatory and antioxidant effects, further exploration of its potential in metabolic syndrome, neurodegenerative diseases, and other fields.

Overall, Sanqi saponin R2, as a natural triterpene saponin compound, has significant potential as a novel cardiovascular drug due to its unique pharmacological activity and good safety.

Conclusion

Sanqi saponin R2, as an important active ingredient in Sanqi, demonstrates significant application value in cardiovascular protection due to its multi-target regulation and multiple pharmacological effects. Its excellent safety and druggability lay the foundation for clinical translation. In the future, through in-depth mechanistic research, pharmacokinetic optimization, and clinical validation, Sanqi saponin R2 is expected to become a new natural drug for cardiovascular disease prevention and treatment. Ongoing multidisciplinary collaboration and innovative research will accelerate the transition from the laboratory to clinical practice, benefiting a wide range of patients.