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Synonym name: Phytolaccasaponin E; Phytolaccoside E
Catalogue No.: BP0560
Cas No.: 65497-07-6
Formula: C42H66O16
Mol Weight: 826.974
Botanical Source: Phytolacca americana (pokeberry), Phytolacca esculenta, Phytolacca thrysiflora and root cultures of Phytolacca acinosa
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 Esculentoside A
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
262.3600
1.4032
-.5608
.1468
.5332
.2982
Low
77.9055
6.0586
No
No
No
No
No
No
0.0
Yes
No
No
No
Esculentoside A (EsA) is a triterpene saponin natural product extracted from the root of Phytolacca esculenta. As one of the important active ingredients in traditional Chinese medicinal herbs like pokeweed, EsA has attracted much attention for its remarkable anti-inflammatory and immunomodulatory properties. In recent years, with the development of natural product pharmacology, the potential therapeutic value of EsA in inflammatory diseases, especially immune-related pathological conditions such as acute lung injury (ALI), has gradually been revealed. Through its multi-target and multi-pathway regulatory effects, it has become a hot topic in research on natural anti-inflammatory drugs and immunomodulators.
This paper systematically reviews the chemical structure and physicochemical properties of pokebroside A, plant origin and extraction methods, pharmacological activity and mechanism, druggability parameters, and pharmacokinetic characteristics, and explores its clinical application potential and future research directions, aiming to provide a theoretical basis and research reference for drug development of this natural product.
EsA has the molecular formula C_42H_66O_16 and a molecular weight of 826.9740, belonging to the triterpene saponin class. Its basic framework is a pentacyclic triterpene structure, connecting multiple glycosyl residues to form a typical saponin molecular structure. EsA's LogP value was 1.4032, indicating moderate lipid solubility, which facilitates cell membrane penetration. The polar surface area (TPSA) reaches as high as 262.36 Ų, indicating strong molecular polarity and low water solubility (0.1468), which may affect its bioavailability and in vivo distribution.
Structurally, the triterpene core ring system of EsA is stable, and the glycoside component imparts strong hydrophilicity and specific biological activity. Its molecules contain multiple hydroxyl and glycosidic bonds, making it easy to form hydrogen bonds and van der Waals forces with target proteins, enhancing binding affinity. Low blood-brain barrier penetration suggests that it mainly acts on peripheral tissues, reducing the risk of central nervous system side effects. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. Ames-induced mutagenic test results were zero, indicating that EsA has no significant genotoxicity.
Pokeweed saponin A mainly comes from Phytolacca esculenta, the active ingredient in the root of the pokeweed plant Phytolacca esculenta. Polka pokeweed is widely used in traditional Chinese medicine, with effects such as clearing heat and detoxifying, reducing swelling, and dispersing nodules. EsA, as one of its main saponin components, is abundant and biologically active.
Traditional extraction methods mostly use alcohol solvents (such as ethanol and methanol) for reflux extraction of dried Stellar chloride, followed by purification and separation using liquid-liquid partitioning, silica gel column chromatography, and high-performance liquid chromatography (HPLC). In recent years, to improve extraction efficiency and purity, ultrasound-assisted extraction, microwave-assisted extraction, and membrane separation technologies have gradually been applied to EsA extraction processes.
The extraction process typically includes:
1. Raw material drying and crushing;
2. Ethanol reflux extraction;
3. Concentrate the extract;
4. Distribute ether or chloroform to remove fat-soluble impurities;
5. Silica gel column chromatography separation;
6. HPLC purification and structural identification.
This method can obtain high-purity EsA, laying the foundation for subsequent pharmacological research and formulation development.
EsA exhibited significant anti-inflammatory effects, especially in acute inflammation models. In vitro experiments have shown that EsA can inhibit macrophage inflammation induced by lipopolysaccharide (LPS) and significantly reduce the secretion of pro-inflammatory factors such as TNF-α, IL-6, and IL-1β. In vivo studies have shown that EsA protects LPS-induced acute lung injury (ALI) models, reducing inflammatory infiltration and tissue damage in lung tissue.
EsA exerts its immunomodulatory function by modulating immune-related signaling pathways. Its targets involve various immunoregulatory factors, including TLR4, STAT3, IL2, NFKB1, TGFB1, CTLA4, STAT4, IL10, FOXP3, and IFNG. EsA can regulate the functional state of immune cells, promote immune balance, and reduce tissue damage caused by excessive immune activation.
Some studies have shown that EsA has antioxidant activity, can eliminate excess reactive oxygen species (ROS), and reduce cellular damage caused by oxidative stress. Additionally, EsA protects against apoptosis and necrosis processes, helping to maintain tissue homeostasis.
The anti-inflammatory and immunomodulatory effects of EsA are mainly achieved by inhibiting nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. In LPS-induced inflammatory responses, EsA can block TLR4-mediated signaling, inhibit downstream NF-κB activation, and reduce the transcription and release of pro-inflammatory factors.
The specific mechanisms include:
- Inhibits the phosphorylation and degradation of IκBα, preventing NF-κB from entering the nucleus;
- Inhibits phosphorylation of MAPK family members (such as p38, ERK, JNK), reducing amplification of inflammatory signals;
- Regulates the STAT3 and STAT4 signaling pathways, affecting immune cell proliferation and differentiation;
- Promotes expression of the anti-inflammatory factor IL-10 and the regulatory T cell marker FOXP3, enhancing immune tolerance;
- Inhibits overexpression of pro-inflammatory cytokines IFN-γ and IL-2, alleviating immune-mediated inflammatory responses.
Additionally, EsA may participate in the regulation of the immune microenvironment by regulating immunosuppressive molecules such as TGFB1 and CTLA4, promoting the transition of inflammation into the repair phase.
EsA has a large molecular weight (826.9740) and TPSA is high (262.36 Ų), indicating strong polarity that may affect oral absorption and cell membrane penetration. The LogP is 1.4032, indicating moderate lipid solubility, which is beneficial for distribution in vivo. Low water solubility (0.1468), which may limit its bioavailability.
The low penetration of the blood-brain barrier suggests that EsA mainly acts on peripheral tissues, reducing the risk of central nervous system side effects. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test is non-mutagenic and relatively safe.
Currently, there is limited research on the systemic pharmacokinetics of EsA. Preliminary data indicate that EsA is slowly absorbed orally and has limited bioavailability, possibly due to its high polarity and molecular weight. Its distribution in vivo is mainly concentrated in tissues rich in immune cells, such as the liver and lungs. The metabolic pathway is not fully understood, but it is presumed that glycoside hydrolysis and oxidative metabolism mainly occur through the hepatic enzyme system. Excretion routes may mainly be bile and urine.
In the future, systematic research on pharmacokinetics and pharmacodynamics should be conducted to optimize dosing regimens and dosage form designs to enhance their clinical application potential.
As a natural triterpene saponin, EsA shows broad application prospects in the treatment of inflammatory diseases due to its remarkable anti-inflammatory and immunomodulatory activities. Especially in acute lung injury, chronic inflammatory diseases, autoimmune diseases, and immune function regulation, EsA has potential drug development value.
The key to future clinical applications lies in:
- Optimized extraction and purification processes to ensure stable drug quality;
- Enhance oral bioavailability and in vivo stability through structural modification or formulation innovation;
- In-depth study of its mechanisms of action to identify key molecular targets and signaling pathways;
- Conduct systematic safety evaluations and preclinical pharmacokinetic studies;
- Design reasonable clinical trials to verify efficacy and safety.
Moreover, the combined application of EsA with existing anti-inflammatory drugs and its multi-target role in immunomodulatory also provide opportunities for developing new indications. With advances in natural product pharmacology and modern drug development technologies, EsA is expected to become an important candidate for novel anti-inflammatory immunomodulatory drugs.
Esculentoside A, as the main triterpene saponin in the root of Esculentoside pokeweed, has significant anti-inflammatory and immunomodulatory activities. By inhibiting key inflammatory signaling pathways such as NF-κB and MAPK, it regulates various immune-related targets, reduces inflammatory responses, and protects tissue function. Although its druggability faces certain challenges, its good safety and multi-target mechanism provide a solid foundation for drug development.
In the future, in-depth research into the pharmacokinetics and clinical efficacy of EsA should be strengthened, combined with modern drug design technologies to promote its translation into clinical application. As an important subject of natural product pharmacology research, EsA not only enriches the resource library of natural anti-inflammatory drugs but also provides a valuable example for exploring novel immunomodulatory strategies.
Shenshuai
Wenjing
Hedandan
