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Synonym name:
Catalogue No.: BP0044
Cas No.: 7755-01-3
Formula: C30H52O3
Mol Weight: 460.743
Botanical Source:
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 20(R)-Protopanaxadiol
HNMR of 20(R)-Protopanaxadiol
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
60.6900
6.3337
6.3332
.0004
5.3584
8.2280
Low
89.6649
4.8396
No
No
No
No
No
No
0.0
No
No
No
No
20(R)-protoginsenodiol (20(R)-Protopanaxadiol, abbreviated as 20(R)-PPD), as an important aenantiomer of ginsenoside natural products, has attracted widespread attention in recent years in the field of natural product pharmacology. Its unique molecular configuration and multi-target regulatory properties make it highly valuable for the prevention and treatment of cardiovascular and other chronic diseases. 20(R)-PPD is a 20-position hydroxyl-substituted diastereomer of proto-ginsenodiol (PPD), differing from the spatial configuration of 20(S)-PPD, resulting in certain differences in biological activity and pharmacological effects. This paper systematically reviews the chemical structure and physicochemical properties of 20(R)-PPD, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and future clinical application prospects, aiming to provide a theoretical foundation and reference for related research.
The molecular formula of 20(R)-original ginseng diol is C30H52O3, with a molecular weight of 460.7430. Its structure is based on a tetracyclic triterpene skeleton and belongs to the non-sugar part of the original ginseng glycol-type saponins. The main difference between 20(R)-PPD and 20(S)-PPD lies in the spatial configuration of the hydroxyl group on the 20-position carbon atom; the former is the R configuration, the latter the S configuration. This configuration difference not only affects its binding pattern with biomacromolecules but also influences its pharmacokinetic properties.
In terms of physicochemical properties, the LogP value of 20(R)-PPD is 6.3337, indicating strong lipophilus, which facilitates cell membrane penetration but limits its water solubility (solubility is only 0.0004 mg/mL), posing challenges for its bioavailability. Its polar surface area (TPSA) is 60.69 Ų, indicating that the molecule has moderate polarity, which facilitates interactions with biological targets. The blood-brain barrier has low permeability, suggesting its limited role in the central nervous system. In terms of safety, 20(R)-PPD showed no hERG channel inhibitory activity and was negative in Ames-induced mutagenic tests, indicating good safety.
20(R)-Protoginseng diol is mainly found in the plant Panax ginseng of the Araliaceae family and its related species, and is the primary non-sugar component of ginsenoside compounds. After ginsenosides are metabolized in vivo or in vitro, 20(R)-PPD has attracted widespread attention as an important metabolite.
Traditional extraction methods mostly use organic solvents (such as ethanol and methanol) to extract ginseng rhizomes, followed by liquid-liquid separation and silica gel column chromatography for separation and purification. In recent years, modern technologies such as supercritical CO2 extraction, microwave-assisted extraction, and ultrasound-assisted extraction have been introduced, improving extraction efficiency and purity. During purification, reversed-phase high-performance liquid chromatography (RP-HPLC) is widely used for separation and identification of 20(R)-PPD, ensuring the accuracy and purity of its structure.
20(R)-PPD exhibits significant pharmacological activity across various disease models, with particularly in-depth research in cardiovascular diseases. Its main pharmacological effects include anti-inflammatory, antioxidant, energy metabolism regulation, and cell protection.
Anti-inflammatory effects
20(R)-PPD can inhibit the release of inflammatory mediators and reduce inflammatory responses. In vitro experiments have shown that by inhibiting the TLR4 signaling pathway, it reduces the expression of pro-inflammatory cytokines (such as TNF-α and IL-6), thereby alleviating inflammatory damage in the cardiovascular system.
Antioxidant effects
20(R)-PPD can activate the NFE2L2 (Nrf2) signaling pathway, induce the expression of antioxidant enzymes, and enhance cellular resistance to oxidative stress. In animal experiments, 20(R)-PPD significantly reduced oxidative stress markers in myocardial ischemia-reperfusion injury, protecting myocardial cells.
Regulates energy metabolism
By activating the AMPK (5' AMP-activated protein kinase) pathway, 20(R)-PPD promotes the balance of lipid and glucose metabolism, helping to improve cardiovascular metabolic disorders and reduce the risk of atherosclerosis.
Cell protection and anti-apoptosis
20(R)-PPD promotes cell survival, reduces apoptosis, and protects cardiomyocytes from damage by regulating targets such as PRKKA (protein kinase Cα) and APEX1 (DNA repair enzyme).
Additionally, 20(R)-PPD demonstrates potential antithrombotic and anti-diabetic complications in regulating platelet selectin (SELP) and the proteasome-related enzyme AKR1B1, further expanding its application potential in cardiovascular diseases.
The multi-target mechanism of 20(R)-PPD is an important basis for its pharmacological activity. Through molecular docking, gene knockout, and protein expression analysis, researchers have identified its main targets and signaling pathways.
AMPK（PRKAA1）
As a key regulator of cellular energy metabolism, AMPK activation promotes fatty acid oxidation and glucose uptake. 20(R)-PPD improves myocardial energy metabolism by activating AMPK, reducing pathological progression of metabolic heart disease.
TLR4
As a triggerer receptor for inflammatory responses, inhibition of TLR4 helps alleviate cardiovascular inflammation. 20(R)-PPD reduces inflammatory factor release by inhibiting the TLR4-mediated NF-κB signaling pathway.
NFE2L2 (Nrf2)
20(R)-PPD activates the Nrf2 pathway, inducing antioxidant enzyme expression, enhancing cellular antioxidant capacity, and protecting myocardial cells from oxidative damage.
PRKCA
Regulating cell proliferation and apoptosis, 20(R)-PPD promotes cardiomyocyte survival by modulating PRKCA expression.
BACE1、PTPN1、ESR2、APEX1、AKR1B1、SELP
These targets involve multiple pathological processes in cardiovascular diseases, including blood glucose regulation, platelet activation, and DNA repair. Through the synergistic action of multiple targets, 20(R)-PPD achieves a comprehensive effect of cardiovascular protection.
From the perspective of druggability, 20(R)-PPD has certain advantages and disadvantages. Its high lipid solubility (LogP 6.33) facilitates membrane penetration, but its extremely low water solubility limits oral absorption and bioavailability. Additionally, the moderate polar surface area of 20(R)-PPD suggests strong binding ability to target proteins.
Toxicological evaluation showed that 20(R)-PPD did not significantly inhibit the hERG channel, reducing the risk of arrhythmias. A negative Ames test indicates a low genotoxicity risk and good safety.
Pharmacokinetic research is still in its early stages. In vivo studies have shown that 20(R)-PPD has low plasma concentrations after oral administration, indicating limited bioavailability. The metabolic pathway is mainly metabolized via the hepatic CYP450 enzyme system, and the activity of these metabolites requires further research. In the future, formulation improvements (such as nanocarriers and liposomes) will be needed to enhance in vivo stability and absorption efficiency.
As a multi-target small molecule derived from natural products, 20(R)-PPD shows broad application prospects in cardiovascular disease prevention and treatment. Its anti-inflammatory, antioxidant, and metabolic regulatory effects make it a potential candidate for treating diseases such as atherosclerosis, myocardial ischemia, and diabetic heart disease.
Future clinical development should focus on the following directions:
Formulation optimization
To address issues of poor water solubility and low bioavailability, new drug delivery systems (such as nanoparticles, liposomes, solid dispersions) have been developed to improve oral absorption and in vivo stability.
In-depth study of mechanisms
By combining multi-omics techniques, the multi-target synergistic mechanism of 20(R)-PPD in cardiovascular diseases was further revealed, and potential biomarkers and therapeutic targets were uncovered.
Safety and toxicological assessment
Conduct systematic long-term toxicological studies and drug interaction assessments to ensure the safety of clinical applications.
Clinical trial design
Based on existing in vitro and in vitro pharmacological studies, a reasonable clinical trial protocol was designed to verify the efficacy and safety of 20(R)-PPD in patients with cardiovascular disease.
Additionally, 20(R)-PPD also shows potential activity in other disease areas such as oncology and neurodegenerative diseases, warranting further research expansion.
20(R)-original ginseng diol, as a structurally unique natural product, demonstrates promising application potential in cardiovascular disease prevention and treatment due to its multi-target and multi-mechanism pharmacological properties. Although its druggability challenges such as poor water solubility and low bioavailability still need to be overcome, the intervention of modern drug development technologies holds promise for clinical translation. In the future, combining in-depth mechanistic research and innovative formulation technologies, 20(R)-PPD is expected to become an important natural drug resource in the field of cardiovascular disease treatment. Continuing systematic pharmacology, toxicology, and clinical research will provide new ideas and strategies for the development of natural product pharmacology and the treatment of cardiovascular diseases.
Shenshuai
Wenjing
Hedandan
