Product name: Raddeanoside 20
Synonym name: Raddeanoside 20
Catalogue No.: BPF0659
Cas No.: 335354-79-5
Formula: C₄₇H₇₆O₁₇
Mol Weight: 913.108
Botanical Source:
Physical Description:
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.

For Reference Standard and R&D, Not for Human Use Directly.

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 long history of human struggle against diseases. From the classic analgesic morphine to the antimalarial drug artemisinin, the diverse and unique secondary metabolites in nature continue to provide valuable lead compounds for modern drug development. Among numerous natural products, triterpenoid saponins derived from plant rhizomes have attracted much attention due to their wide range of biological activities, particularly their significant anti-tumor potential. Triterpenoid saponins are a complex class of compounds formed by the connection of triterpenoid glycosides and sugar chains through glycosidic bonds. Their structural diversity endows them with rich pharmacological functions, including anti-inflammatory, immunomodulatory, antiviral, and anti-tumor effects.

Among numerous bioactive triterpenoid saponins, Raddeanoside 20 is a compound derived from plants of the Ranunculaceae family and the Silver Lotus genus Anemone raddeana The natural products isolated from the rhizomes of silver lotus have attracted the interest of researchers in recent years.Anemone raddeana In traditional Chinese medicine, it is often used to treat rheumatism, rheumatism, pain, swelling, and other diseases. The study of its chemical composition and pharmacological activity is an important topic in the fields of natural product chemistry and pharmacology. Raddeanoside 20, as an active ingredient in this plant, has a unique chemical structure and preliminary revealed biological activity, especially its ability to inhibit superoxide production, suggesting its potential application value in oxidative stress-related diseases and tumor treatment. This review aims to systematically review the current research status of Raddeanoside 20, including its chemical structure and physicochemical properties, plant sources and extraction methods, pharmacological activity, mechanism of action, drug evaluation, and clinical application prospects, in order to provide valuable references for the subsequent research and development of this natural product.

Chemical structure and physicochemical properties

Raddeanoside 20 is a typical triterpenoid saponin compound. Its chemical structure consists of two parts: triterpenoid glycosides and sugar chains. Triterpenoid glycosides are typically of the Oleanane type, a pentacyclic triterpenoid skeleton, which is one of the most common types of glycosides in triterpenoid saponins. The oleane skeleton is composed of six isoprene units, with five rings A, B, C, D, and E, where the E ring is a six membered ring. The glycoside portion of Raddeanoside 20 typically contains multiple hydroxyl groups, which are critical sites for sugar chain linkage. The sugar chain is usually composed of multiple monosaccharide molecules (such as glucose, xylose, arabinose, arabinose, etc.) connected by glycosidic bonds. The specific sugar chain composition and connection sequence of Raddeanoside 20 are key to its structural identification, which usually requires the use of modern analytical techniques such as nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) for analysis. Its molecular formula is C ₄₇ H ₇₆ O ₁₇, and its molecular weight is 913.1080 Da, which reflects its complex sugar chain structure.

In terms of physicochemical properties, the LogP value of Raddeanoside 20 is 2.2738, indicating that it has a certain degree of lipophilicity, but not strong lipophilicity. This characteristic is related to the presence of both lipophilic triterpenoid frameworks and hydrophilic sugar chains in its molecular structure. Its polar surface area (TPSA) is as high as 274.7500 Å ², mainly attributed to the large number of hydroxyl and ether oxygen atoms in the molecule. A high TPSA value usually indicates that the compound has good water solubility, but the water solubility measurement value of Raddeanoside 20 is 0.1163 mg/mL, which belongs to the category of slight solubility. This may be because its large sugar chains increase polarity but also increase molecular volume, affecting the effective encapsulation of water molecules. Its blood-brain barrier penetration ability was evaluated as "low", which is consistent with the high TPSA and "Lipinski Five Rules" with a molecular weight greater than 400 Da, indicating that the compound is difficult to enter the central nervous system through passive diffusion, which to some extent reduces its potential neurotoxic risk. In addition, the hERG inhibition prediction result is "no", and the Ames test result is 0.0, indicating that it has low risks in terms of cardiac toxicity and genetic toxicity. These preliminary drug efficacy evaluation results provide positive signals for its subsequent development.

Plant sources and extraction methods

The main plant source of Raddeanoside 20 is the Ranunculaceae family, specifically the Silver Lotus genus（Anemone）Plants - mostly silver lotus flowers（Anemone raddeana Regel）。 The Silver Lotus, also known as the Two Headed Tip and Bamboo Knot Fragrant Attachment, is a perennial herbaceous plant mainly distributed in Northeast China, the Korean Peninsula, and the Russian Far East. Its root and stem are used as medicinal herbs in traditional Chinese medicine, with the effects of dispelling wind and dampness, and reducing carbuncles and swelling. It is commonly used to treat conditions such as wind cold dampness, limb spasms, joint pain, and carbuncles and sores. Modern pharmacological studies have shown that the rhizomes of silver lotus contain abundant triterpenoid saponins, which are considered the material basis for its pharmacological effects. Raddeanoside 20 is one of the many triterpenoid saponins isolated and identified from the rhizome of this plant.

from Anemone raddeana The extraction of Raddeanoside 20 from rhizomes usually follows the standard process of natural product chemistry, which mainly includes the following steps:

1. Raw material processing and extraction Dry lotus roots are often crushed into coarse powder. In order to improve extraction efficiency, polar solvents are usually used for extraction, with methanol or ethanol (such as 70% -95% ethanol) being the most commonly used. The extraction methods include cold soaking, percolation, or heating reflux. Heating reflux extraction has a high efficiency, but it is important to control the temperature to avoid degradation of thermosensitive components. The extract is filtered and concentrated under reduced pressure to obtain the total extract.

2. Preliminary separation and enrichment The total extract is usually suspended in water and then subjected to liquid-liquid extraction using organic solvents of different polarities (such as petroleum ether, ethyl acetate, n-butanol) in sequence. Due to Raddeanoside 20 being a triterpenoid saponin with high polarity, it is mainly enriched in the n-butanol extraction layer. After vacuum concentration of n-butanol extract, crude saponin extract was obtained.

3. Chromatographic Separation and Purification The crude extract of saponins needs to be separated and purified through a series of chromatographic techniques. Common methods include:

   • Silica gel column chromatography The most classic method for separating triterpenoid saponins is to use solvent systems with different ratios of chloroform methanol water for gradient elution.
   • Reverse phase column chromatography Using ODS (octadecylsilane bonded silica gel) as the stationary phase and elution with methanol water or acetonitrile water system has better separation effect on saponin compounds.
   • Macroporous adsorption resin Examples such as D101 and AB-8 are commonly used for the initial enrichment and decolorization of saponins.
   • High performance liquid chromatography (HPLC)Especially preparative HPLC is the ultimate method for obtaining high-purity Raddeanoside 20 monomer. By optimizing the mobile phase (such as acetonitrile water or methanol water) and chromatographic column (such as C18 column), precise separation of the target compound can be achieved.

4. Structural Identification The isolated pure product was structurally confirmed by modern spectroscopic techniques, mainly including:

   • Nuclear Magnetic Resonance Spectroscopy (NMR)：¹H-NMR、¹³C-NMR、DEPT、COSY、HSQC、HMBC Two dimensional spectroscopic techniques are used to determine the connection positions, sequences, and sugar configurations of the glycoside skeleton and sugar chains.
   • Mass spectrometry (MS)High resolution mass spectrometry (HR-ESI-MS) is used to determine precise molecular weight and molecular formula; Tandem mass spectrometry (MS/MS) is helpful for analyzing sugar chain sequences.

Pharmacological activity research

The pharmacological activity research of Raddeanoside 20 is still in its early stages, but existing studies have revealed its potential in anti-tumor and antioxidant aspects.

1. Antitumor activity

The anti-tumor activity is the most studied direction of Raddeanoside 20. Preliminary in vitro cell experiments have shown that Raddeanoside 20 exhibits proliferative inhibitory effects on various tumor cell lines. For example, some studies have reported that it has certain cytotoxicity to lung cancer cells (such as A549), breast cancer cells (such as MCF-7), liver cancer cells (such as HepG2) and leukemia cells. Its anti-tumor activity usually exhibits dose - and time-dependent effects. Compared to many traditional chemotherapy drugs, Raddeanoside 20 may have relatively mild cytotoxicity, but its mechanism of action may be more unique, providing the possibility for it to be used as a novel anti-tumor candidate or adjuvant therapy drug.

2. Antioxidant activity

The literature clearly states that Raddeanoside 20 can inhibit the production of superoxide. Superoxides (O ₂⁻) are important members of the reactive oxygen species (ROS) family and are byproducts produced during cellular metabolism. Excessive superoxide can cause oxidative stress, damage DNA, proteins, and lipids, leading to various diseases including cancer, cardiovascular disease, neurodegenerative diseases, and inflammation. Raddeanoside 20 may exert antioxidant stress effects by inhibiting the production of superoxide. This activity may be closely related to its anti-tumor effect, as many tumor cells are in a state of high oxidative stress. By inhibiting the production of ROS, apoptosis or proliferation of tumor cells can be induced. In addition, the antioxidant activity also suggests that Raddeanoside 20 has potential application value in anti-inflammatory and anti-aging aspects.

3. Other potential activities

Given its antioxidant and anti-tumor activities, Raddeanoside 20 may also have other pharmacological effects. For example, by inhibiting ROS production in inflammation related signaling pathways, it may exert anti-inflammatory effects. In addition, triterpenoid saponins generally have immunomodulatory activity, and further research is needed to determine whether Raddeanoside 20 can also regulate immune cell function. At present, there is a relative lack of in vivo pharmacological research on Raddeanoside 20. Whether its anti-tumor activity can be reproduced in animal models, as well as its metabolic and toxicity characteristics in vivo, are the key directions that future research needs to focus on.

Mechanism of action and molecular targets

A deep understanding of the mechanism of action of Raddeanoside 20 is key to its transition from a natural product to a drug candidate. Although its exact mechanism has not been fully elucidated, existing studies combined with information on its structural analogues suggest that it may exert anti-tumor effects through multi-target and multi pathway pathways. The relevant targets mentioned in the literature include MCL1, BCL2, STAT3, MMP2, TOP1, HIF1A, TOP2A, MAPK1, ESR1, and CYP19A1, which cover multiple key biological processes such as cell apoptosis, signal transduction, tumor metastasis, DNA topoisomerase, and hypoxia response.

1. Inducing cell apoptosis

• Regulating BCL-2 family proteins MCL1 and BCL2 are important anti apoptotic proteins in the BCL-2 family, highly expressed in various tumor cells and serving as key mechanisms for tumor cells to evade apoptosis. Raddeanoside 20 may induce tumor cell apoptosis by downregulating the expression of MCL1 and BCL2, or by activating pro apoptotic proteins such as BAX and BAK, disrupting mitochondrial membrane potential, releasing cytochrome c, and activating the Caspase cascade reaction.
• Inhibition of STAT3 signaling pathway STAT3 is a key transcription factor involved in regulating cell proliferation, survival, angiogenesis, and immune escape. In many cancers, STAT3 is continuously activated. Raddeanoside 20 may inhibit the phosphorylation of STAT3, blocking its entry into the nucleus to initiate downstream target genes (such as...) MCL1、BCL2、VEGF Thereby inhibiting tumor growth and inducing apoptosis.

2. Inhibit tumor metastasis

• Inhibition of MMP2 expression Matrix metalloproteinase 2 (MMP2) can degrade the extracellular matrix and is a key enzyme in the invasion and metastasis of tumor cells. Raddeanoside 20 may inhibit the migration and invasion ability of tumor cells by downregulating the expression of MMP2 or suppressing its enzyme activity.

3. Interference with DNA replication and transcription

• Inhibition of Topoisomerase TOP1 and TOP2A are essential enzymes in DNA replication and transcription processes, responsible for solving DNA supercoiled and topological structure problems. Many effective anti-cancer drugs, such as camptothecin and etoposide, exert cytotoxicity by inhibiting topoisomerases. Raddeanoside 20 may form a drug enzyme DNA ternary complex by binding to TOP1 or TOP2A, preventing DNA strand reconnection and causing DNA damage, thereby inhibiting tumor cell proliferation.

4. Anti angiogenesis and hypoxia response

• Inhibition of HIF1A expression Hypoxia inducible factor 1 alpha (HIF1A) is a key transcription factor for cells to cope with hypoxic environments. It can upregulate the expression of genes such as vascular endothelial growth factor (VEGF), promote tumor angiogenesis, and help tumors survive and grow under hypoxic conditions. Raddeanoside 20 may "starve" tumors by inhibiting the protein expression or transcriptional activity of HIF1A, blocking tumor angiogenesis.

5. Regulating signal transduction and hormone signaling

• Inhibition of MAPK1 pathway MAPK1 (ERK2) is a core member of the MAPK/ERK signaling pathway, which regulates cell proliferation, differentiation, and survival. Raddeanoside 20 may inhibit tumor cell proliferation by suppressing MAPK1 phosphorylation and blocking the transmission of growth factor signals.
• Regulating estrogen signaling ESR1 (estrogen receptor α) and CYP19A1 (aromatase) are important targets for the treatment of breast cancer, especially hormone receptor positive breast cancer. Raddeanoside 20 may inhibit the growth of breast cancer cells by antagonizing ESR1 or inhibiting the activity of CYP19A1, reducing the level of estrogen in vivo or blocking its signal.

In summary, the anti-tumor mechanism of Raddeanoside 20 may involve a complex network of multiple signaling pathways and molecular targets. It may produce synergistic anti-tumor effects and reduce the risk of single target drug resistance by simultaneously acting on multiple processes such as apoptosis, metastasis, DNA damage, angiogenesis, and hormone signaling.

Evaluation of drug properties and pharmacokinetics

Developing natural products into clinical drugs requires not only clear pharmacological activity and mechanism of action, but also good drug properties, including appropriate physicochemical properties, pharmacokinetic characteristics, and safety. For Raddeanoside 20, the preliminary pharmacological evaluation results have both positive aspects and revealed the challenges it faces.

1. Physical and chemical properties and drug like properties

• Molecular weight and LogP The molecular weight of 913.1 Da far exceeds the limit of molecular weight less than 500 in Lipinski's five rules. The LogP value of 2.27 conforms to the rules, but high molecular weight is the main obstacle to oral absorption. This suggests that Raddeanoside 20 may not be suitable for traditional oral administration methods.
• TPSA and water solubility The TPSA is as high as 274.75 Å ², far exceeding the threshold of 140 Å ², indicating extremely poor membrane permeability. The water solubility is 0.1163 mg/mL, which is slightly soluble, further limiting its bioavailability.
• Blood-brain barrier penetration Low penetration ability is a favorable factor that can reduce the risk of central neurotoxicity.

2. Pharmacokinetic characteristics

At present, there is very limited in vivo pharmacokinetic research data on Raddeanoside 20. Based on its physical and chemical properties, it can be inferred that:
- absorb Due to its high polarity and high molecular weight, the absorption of Raddeanoside 20 in the gastrointestinal tract will be very difficult, and its oral bioavailability is extremely low. Intravenous injection may be a more feasible route of administration.
- distribution After intravenous administration, its distribution volume may be relatively small, mainly distributed in the blood and extracellular fluid. Due to its hydrophilicity, it is difficult to penetrate the cell membrane and enter the cell.
- Metabolism Triterpenoid saponins undergo metabolic reactions such as deglycosylation and oxidation in the body. The liver and gut microbiota are its main metabolic sites. Metabolites may have different pharmacological activities.
- excretion Due to its hydrophilicity, Raddeanoside 20 and its metabolites may be primarily excreted through bile and urine.

3. Safety evaluation

• HERG inhibition A negative result indicates a low risk of inducing QT interval prolongation and apical torsion type ventricular tachycardia in the heart.
• Ames test The result is 0.0, indicating that no mutagenicity was shown in the bacterial recovery mutation test, and the genetic toxicity risk is low.
• Other toxicities Currently, there is a lack of systematic in vivo toxicity research data. Triterpenoid saponins generally have certain hemolytic activity and gastrointestinal irritation, which is a safety issue that needs to be focused on in their development.

Summary of Medicinal Properties The main challenges facing the pharmacological properties of Raddeanoside 20 are its extremely poor membrane permeability and oral bioavailability. Its advantage lies in the optimistic preliminary safety evaluation results (low hERG risk, no mutagenicity). Future drug efficacy optimization strategies may include: 1) developing non oral drug delivery systems such as liposomes, nanoparticles, microemulsions, etc. to improve their delivery efficiency and bioavailability; 2) Perform structural modifications, such as simplifying or modifying sugar chains, or modifying aglycones, in order to improve physicochemical properties while maintaining activity; 3) Explore its potential as a prodrug by designing prodrugs that can be activated by specific enzymes (such as enzymes highly expressed in tumor tissue) in vivo to improve targeting and efficacy.

Clinical application prospects and prospects

Raddeanoside 20, as a natural triterpenoid saponin with multi-target anti-tumor and antioxidant activities, has broad clinical application prospects but also faces many challenges.

1. Potential application areas

• Antitumor therapy This is the core application prospect of Raddeanoside 20. Its multi-target mechanism of action (involving apoptosis, metastasis, angiogenesis, DNA damage, etc.) makes it a promising candidate for a novel anti-tumor drug. It may be particularly suitable for tumor types that are resistant to traditional chemotherapy drugs. In addition, due to its different mechanism of action from existing chemotherapy drugs, it may also be used as a component of combination therapy, synergizing with chemotherapy, targeted therapy, or immunotherapy to improve efficacy and reduce side effects. For example, the combined use of Raddeanoside 20 with BCL-2 inhibitors or STAT3 inhibitors may result in stronger anti-tumor effects.
• Oxidative stress-related diseases: Its ability to inhibit the production of superoxide has potential in the treatment of diseases related to oxidative stress, such as chronic inflammatory diseases (such as rheumatoid arthritis), cardiovascular diseases (such as atherosclerosis) and neurodegenerative diseases (such as Alzheimer's disease). However, more in vivo experiments are needed to verify its effectiveness.
• As a lead compound Even though Raddeanoside 20 itself is difficult to directly become a drug due to its pharmacological properties, its unique chemical framework and multi-target activity make it a valuable template for pharmaceutical chemists to optimize its structure and discover lead compounds. By systematically modifying the sugar chains and glycosides, it is expected to develop derivatives with better pharmacokinetic properties and stronger activity.

2. Challenges faced and future research directions

• Pharmacokinetic bottleneck How to overcome its low oral bioavailability and low membrane permeability is the primary challenge. Future research should focus on developing efficient drug delivery systems, such as targeted liposomes, polymer nanoparticles, phospholipid complexes, etc., to improve their in vivo behavior.
• In depth elucidation of the mechanism of action At present, research mostly stays at the cellular level in vitro, and the confirmation of molecular targets is mostly speculative or based on literature reports. In the future, it is necessary to use technologies such as gene knockout/knock in, proteomics, transcriptomics, etc. to systematically identify their direct targets and elucidate their complex signaling network regulatory mechanisms in vivo.
• In vivo efficacy and safety evaluation There is an urgent need to conduct systematic in vivo pharmacological research, establish multiple tumor xenograft models, evaluate their anti-tumor effects, optimal dosing regimens, and dosages. At the same time, a comprehensive acute and chronic toxicity evaluation must be conducted, especially a detailed assessment of its hemolysis, gastrointestinal irritation, and liver and kidney toxicity.
• Study on Structure Activity Relationship By comparing the activity differences between Raddeanoside 20 and its structural analogues (such as other members of the Raddeanoside series), the key pharmacophores can be revealed, providing guidance for structural optimization. For example, the length of sugar chains, the type and connection mode of monosaccharides, and the modification of hydroxyl groups on glycosides may significantly affect their activity and drug properties.
• Combination therapy strategy Exploring the combination use of Raddeanoside 20 with existing anticancer drugs (such as cisplatin, paclitaxel, gefitinib, etc.) or immune checkpoint inhibitors (such as PD-1/PD-L1 antibodies), evaluating their synergistic and attenuated effects, is an effective way to promote its clinical translation.

Conclusion

Raddeanoside 20 is a triterpenoid saponin with a unique structure isolated from traditional Chinese medicine commonly found in silver lotus flowers. It exhibits dual pharmacological activities of inhibiting superoxide production and anti-tumor activity through multi-target and multi pathway approaches, involving the regulation of multiple key targets such as MCL1, BCL2, STAT3, MMP2, TOP1, HIF1A, etc. The preliminary pharmacological evaluation shows that it has low hERG inhibition risk and low genetic toxicity, but the extremely poor membrane permeability and oral bioavailability are major obstacles to its development as an oral drug.

Although research on Raddeanoside 20 is still in its early stages of exploration, its unique chemical framework and clear biological activity make it a highly valuable natural product for research. Future research should focus on further elucidating its mechanism of action, overcoming pharmacokinetic bottlenecks, conducting systematic in vivo efficacy and safety evaluations, and exploring its potential as a lead compound for structural optimization. With the continuous advancement of medicinal chemistry, pharmacy, and molecular biology technologies, Raddeanoside 20 is expected to find its place in the treatment of anti-tumor and oxidative stress-related diseases, providing new ideas and candidate molecules for innovative drug development. The continuous in-depth research on these natural products not only helps to reveal the scientific connotation of traditional Chinese medicine, but also provides an inexhaustible source for modern drug discovery.