Product name: (20E)-Ginsenoside F4
Synonym name: Δ20(22)-Ginsenoside Rg6; 20(E)-Ginsenoside F4
Catalogue No.: BP0656
Cas No.: 181225-33-2
Formula: C₄₂H₇₀O₁₂
Mol Weight: 767.01
Botanical Source: Ginseng Radix Et Rhizoma
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

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.




Chengdu Biopurify Phytochemicals Ltd. is a leading company in the research, development, manufacture and marketing of High Quality Phytochemicals and Extracts(especially Active Ingredients from Traditional Chinese Medicine，TCM), Natural Active Pharmaceutical Ingredients worldwide.
The main services:
A. Supply active ingredients and reference standards of TCM, from mgs to kgs scale
B. Custom extraction and purification, target Herb Active Ingredients
C. Custom synthesis and semi-synthesis for Natural Active Ingredients
D. CR(contract research), CM(contract manufacture) and PD(process development) services from lab scale, pilot scale to commercial scale(GMP is also available)
E. TCM compounds library for drug screen,more than 3000 compounds available, many of them are rare and unique.

HPLC of  (20E)-Ginsenoside F4

HNMR of  (20E)-Ginsenoside F4

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

Introduction/Overview

(20E)-Ginsenoside F4 ((20E)-Ginsenoside F4, CAS No.: 181225-33-2), as one of the important triterpene saponin natural products in ginseng, has gradually become a hot topic in pharmacological research in recent years due to its unique biological activity and potential medicinal value. Ginsenosides are the main active components in ginseng (Panax spp.), possessing a wide range of pharmacological effects, including immunomodulatory, anti-inflammatory, antitumor, and neuroprotective effects. As a representative of triterpene saponins, (20E)-ginsenoside F4 has a unique structure, molecular weight of 767.01, and high polarity (TPSA 198.76). Its immunomodulatory function is particularly prominent, involving multiple key immune signaling pathways and targets, such as TLR4, STAT3, NFKB1, and others. This article aims to systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, and druggability evaluation of (20E)-ginsenoside F4, explore its potential applications in immunoregulation and related diseases, and provide theoretical basis and research directions for its clinical translation.

Chemical structure and physicochemical properties

(20E)-ginsenoside F4 belongs to the triterpene saponin class. Its chemical structure is based on the prototype of ginsenosides—the pentacyclic triterpene skeleton—linked to multiple glycosyl residues. Its molecular formula is C42H72O13, with a molecular weight of 767.01, featuring typical triterpene saponin structural features, consisting of a hydrophobic triterpene skeleton and a hydrophilic sugar chain portion. The compound had a LogP value of 3.4907, indicating moderate lipid solubility that facilitates cell membrane penetration, but its water solubility is relatively low (0.0236), suggesting limited solubility in the aqueous phase. The polar surface area (TPSA) was 198.76, reflecting the presence of a large number of polar functional groups in its molecules, mainly derived from hydroxyl and glycosyl groups, which affect its binding ability to biological targets and pharmacokinetic properties. The blood-brain barrier has low permeability, suggesting limited distribution in 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 a low genotoxicity risk and a solid safety foundation.

Plant Origins and Extraction Methods

(20E)-ginsenoside F4 is mainly found in plants of the genus Panax in the Araliaceae family, especially in Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius). Although its content is not as abundant as mainstream ginsenosides such as Rb1 and Rg1, as a secondary saponin, its biological activity is unique and irreplaceable. Traditional extraction methods mostly rely on alcohol extraction combined with aqueous phase separation and column chromatography purification. The specific process usually includes:

1. Raw material pretreatment: Dried ginseng rhizomes are selected and ground into fine powder.
2. Solvent extraction: Using 70%-80% ethanol as the extractant, reflux or ultrasonic-assisted extraction is employed, with a typical extraction time of 2-4 hours.
3. Concentration and separation: After vacuum concentration, the extract is separated using silica gel column chromatography with water-ethanol gradient elution or reversed-phase C18 column chromatography.
4. Purification: Further purification by high-performance liquid chromatography (HPLC) yields high-purity (20E)-ginsenoside F4.
5. Identification: Use mass spectrometry (MS), nuclear magnetic resonance (NMR), and other techniques to confirm structure and purity.

In recent years, supercritical CO2 extraction, membrane separation technology, and molecular blotting technology have also been attempted to extract and purify this saponin, improving yield and purity, reducing solvent usage, and aligning with green chemistry principles.

Pharmacological activity research

The pharmacological activity of (20E)-ginsenoside F4 is mainly concentrated in immunomodulatory, showing significant bidirectional regulatory abilities in anti-inflammation, immune-enhancing, and immunosuppressive moderation. Additionally, it shows potential in anti-tumor, antioxidant, and neuroprotective properties.

Immunomodulatory effects

Numerous in vitro cell experiments and animal model studies have shown that (20E)-ginsenoside F4 can regulate immune cell function and promote immune balance. Its functions include:

• Regulating macrophage activity: By modulating the TLR4 signaling pathway, it suppresses excessive inflammatory responses and reduces the secretion of pro-inflammatory factors TNF-α and IL-6.
• Influence of T cell differentiation: Promotes FOXP3 expression in regulatory T cells (Tregs), enhances immune tolerance, regulates Th1/Th2 balance, and controls the expression of IFN-γ and IL-10.
• Regulating cytokine networks: By affecting STAT3 and STAT4 signaling pathways, it regulates the expression of key cytokines such as IL-2 and TGFB1, balancing immune activation and suppression.

Anti-inflammatory and antioxidant

(20E)-ginsenoside F4 can inhibit NFKB1 activation, reduce the production of inflammatory mediators, and alleviate tissue inflammatory damage. Its antioxidant effects eliminate free radicals, reduce oxidative stress, and protect cells from damage.

Anti-tumor

Some studies have shown that this saponin inhibits tumor cell proliferation and induces apoptosis, possibly related to its regulation of the immune microenvironment and its direct action on tumor cell signaling pathways.

Mechanism of action and molecular targets

The immunoregulatory mechanism of (20E)-ginsenoside F4 involves multiple signaling pathways and key molecular targets:

• TLR4 (Toll-like receptor 4): As an innate immune recognition receptor, TLR4 mediates inflammatory responses. This saponin reduces downstream NFKB1 activation and lowers inflammatory factor expression by inhibiting TLR4-mediated signaling.
• STAT3 and STAT4 (signal transduction and transcription activators): regulate the differentiation and function of immune cells. Ginsenoside F4 regulates the phosphorylation status of STAT3/4, affecting T cell subsets and cytokine expression.
• NFKB1 (nuclear factor κB subunit): a key transcription factor for inflammatory responses. This compound inhibits NFKB1 nuclear translocation, reducing inflammatory responses.
• Cytokines such as IL2, IL10, IFNG, TGFB1: By regulating the expression of these cytokines, immune activation and suppression are regulated to maintain immune homeostasis.
• CTLA4 (cytotoxic T lymphocyte-associated antigen 4) and FOXP3: promote the function of regulatory T cells, enhance immune tolerance, and prevent autoimmune responses.

The synergistic regulation of these targets enables (20E)-ginsenoside F4 to exhibit complex and delicate regulatory capabilities in immune regulation, enhancing immune defense while suppressing excessive inflammation, demonstrating its bidirectional regulatory properties.

Druggability evaluation and pharmacokinetics

Analysis of drug-dosable parameters

(20E)-ginsenoside F4 has a relatively large molecular weight (767.01), a high TPSA (198.76), and low water solubility (0.0236), which poses challenges for oral absorption and bioavailability. The LogP value is 3.49, indicating a certain degree of lipid solubility, which is beneficial for cell membrane penetration, but overall polarity is strong, which may limit its passive diffusion. The low permeability of the blood-brain barrier suggests its limited distribution in the central nervous system, which may reduce CNS-related side effects. Negative hERG channel inhibition and Ames test negative indicate low cardiotoxicity and genotoxicity risks and good safety.

Pharmacokinetic characteristics

Currently, there is limited systematic pharmacokinetic research on (20E)-ginsenoside F4, but considering the general characteristics of ginsenoside compounds, it is inferred that it has poor oral absorption and limited bioavailability, mainly affecting plasma concentrations through intestinal metabolism and first-pass effects in the liver. Its metabolites may be more easily absorbed active metabolites through glycoside hydrolysis mediated by the gut microbiota. The main excretory routes are bile and urine.

In the future, systematic in vivo pharmacokinetic studies are needed to clarify its absorption, distribution, metabolism, and excretion (ADME) characteristics, providing a basis for dosage formulation design and clinical application.

Prospects and outlooks for clinical applications

(20E)-ginsenoside F4 has significant immunomodulatory effects and holds potential clinical value in various immune-related diseases. Including but not limited to:

• Autoimmune diseases: such as rheumatoid arthritis and systemic lupus erythematosus, which reduce autoimmune responses by regulating T cell subsets and suppressing inflammatory mediators.
• Inflammatory diseases: such as inflammatory bowel disease and chronic obstructive pulmonary disease, which suppress excessive inflammation and promote tissue repair.
• Tumor adjuvant therapy: Enhances the body's immune surveillance function, improves the tumor immune microenvironment, and improves the effectiveness of immunotherapy.
• Immunodeficiency: Immune dysfunction caused by post-infection immunosuppression or chemotherapy or radiotherapy promotes immune recovery.

Moreover, given its good safety, future methods such as structural modification and nanocarrier technology can improve its pharmacokinetic properties, enhance bioavailability and targeting, and promote clinical translation.

Conclusion

(20E)-ginsenoside F4, as a triterpene saponin with a unique structure and multi-target immunomodulatory effects, shows broad prospects for pharmacological research and clinical applications. By regulating key immune signaling pathways such as TLR4, STAT3, and NFKB1, it achieves fine regulation of the immune system, combining anti-inflammatory, immunobalance, and anti-tumor potential. Although its pharmacokinetics and clinical research are still in its early stages, due to its good safety and significant bioactivity, (20E)-ginsenoside F4 is expected to become an important candidate molecule in natural product drug development. Future research should focus on systematic pharmacokinetic evaluation, in-depth analysis of mechanisms of action, and expansion of clinical indications, aiming to achieve successful translation from laboratory to clinical practice and promote innovation in the application of natural products in modern medicine.