Product name: Ginsenoside Rg4
Synonym name: 20(Z)-Ginsenoside F4
Catalogue No.: BP1650
Cas No.: 126223-28-7
Formula: C42H70O12
Mol Weight: 767.01
Botanical Source:
Physical Description: Powder
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.
We provide solution to improve the water-solubility of compounds, thereby facilitating the variety of activity tests and clinic uses.
For Reference Standard and R&D, Not for Human Use Directly.
HPLC of Ginsenoside Rg4
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
Ginsenoside Rg4, as one of the important proto-ginsenotriol saponins in ginseng, has attracted widespread attention in the field of natural product pharmacology in recent years. Its unique chemical structure endows it with remarkable biological activity, especially showing excellent potential in regulating cellular signaling pathways, anti-inflammatory, and antioxidant properties. Ginsenoside Rg4 not only exhibits good oral bioactivity, but also demonstrates significant therapeutic effects on various disease models, especially inflammation, infection, and metabolic diseases such as sepsis and pulmonary inflammation. In addition, research on the molecular targets related to ginsenoside Rg4 for breast cancer and other tumor diseases provides a theoretical basis for its development as a potential anticancer drug. This paper aims to systematically review the chemical structure, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of ginsenoside Rg4, aiming to provide reference for in-depth research and drug development of this natural product.
The molecular formula of ginsenoside Rg4 is C42H72O13, with a molecular weight of 767.0100, making it a genoside of the original ginsenotriol type. Its core structure is composed of a tetracyclic triterpene bone structure, connecting multiple sugar groups, giving it high polarity and a complex three-dimensional structure. The LogP value of Rg4 is 3.4885, indicating moderate lipid solubility, which facilitates cell membrane penetration and oral absorption. Its topological pole surface area (TPSA) is 198.7600, indicating high polarity, which may affect transmembrane transport and bioavailability. Its water solubility is relatively low (0.0246), which to some extent limits its solubility and biological distribution in the aqueous phase. Low blood-brain barrier permeability indicates limited distribution in the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames-induced mutagenic test result was 0.0, indicating a low genotoxicity risk and a solid safety foundation.
Ginsenoside Rg4 is mainly found in the roots of ginseng (Panax ginseng C.A. Meyer) and its processed products. As a traditional Chinese medicinal herb, ginseng has complex saponin components and relatively low Rg4 content, requiring specialized extraction and separation techniques. Common extraction methods include:
Solvent extraction method: Using organic solvents such as ethanol or methanol to extract dried ginseng powder by reflux, then removing impurities through concentration and liquid-liquid distribution.
Column chromatography separation: Using silica gel or C18 reversed phase columns for chromatographic separation, combined with gradient elution technology, can effectively separate and purify Rg4.
Supercritical CO2 Extraction: Utilizes the high permeability and selectivity of supercritical fluids, resulting in high extraction efficiency and environmental friendliness.
Enzymatic conversion: Through enzymes such as β-glucosidase, other ginsenosides are converted into Rg4, increasing yield.
In recent years, with technological advancements, combining high-performance liquid chromatography (HPLC) and mass spectrometry (MS) analytical methods has enabled rapid qualitative and quantitative detection of Rg4, providing technical support for its extraction and purification.
Ginsenoside Rg4 exhibits significant pharmacological activity across various biological functions, mainly including anti-inflammatory, antioxidant, immunomodulatory, and antitumor effects.
Multiple in vivo and in vitro studies have shown that Rg4 can significantly inhibit the release of inflammatory mediators and reduce the expression levels of inflammatory cytokines such as TNF-α, IL-6, and IL-1β. It regulates the PI3K/AKT/GSK-3β signaling pathway, inhibiting NF-κB activation and thereby reducing inflammatory responses. In sepsis and pulmonary inflammation models, Rg4 significantly reduces inflammatory infiltration and oxidative stress in lung tissue, improves tissue damage, and suggests its therapeutic potential in acute inflammatory diseases.
Rg4 can effectively scavenge reactive oxygen species (ROS), reducing cellular damage caused by oxidative stress. Research shows that Rg4 enhances cellular antioxidant capacity by activating intracellular antioxidant enzyme systems such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), protecting cells from oxidative damage.
Ginsenoside Rg4 can regulate immune cell function, promote the activity of macrophages and lymphocytes, and enhance the body's immune defense capabilities. At the same time, Rg4 exhibits a bidirectional regulatory effect in regulating immune balance, both suppressing excessive inflammatory responses and enhancing the immune system's defense functions.
For tumor cells such as breast cancer, Rg4 exhibits effects in inhibiting cell proliferation, inducing apoptosis, and inhibiting migration and invasion. Its antitumor effects are related to regulating multiple signaling pathways, including activating AMPK, inhibiting the STAT3 signaling pathway, regulating the expression of BCL2 family proteins, and affecting the balance of tumor cell survival and apoptosis. Additionally, Rg4 can affect tumor-associated transporters such as ABCB1 and ABCG2, potentially reversing tumor resistance.
The pharmacological effects of ginsenoside Rg4 involve multiple cellular signaling pathways and key molecular targets, with the specific mechanisms as follows:
Rg4 can activate PI3K (phosphatidylinositol 3-kinase) and downstream AKT (protein kinase B), promoting cell survival and anti-inflammatory responses. AKT activation further inhibits GSK-3β (glycogen synthase kinase 3β), regulates cellular metabolism and inflammatory responses, and reduces tissue damage.
By activating the Nrf2 (nuclear factor red blood cell 2-related factor 2) signaling pathway, Rg4 promotes antioxidant enzyme expression, clears ROS, and protects cells from oxidative damage.
The multiple regulation of these targets gives Rg4 the advantage of multi-target synergistic action in anti-tumor therapy.
The druggability parameters of ginsenoside Rg4 indicate that it has certain potential for drug development. A large molecular weight (767.0100) and a higher TPSA value suggest that oral absorption may be limited, but its moderate LogP value favors cell membrane penetration. Low water solubility is a major challenge in formulation development, requiring improved solubility and bioavailability through technologies such as nanocarriers, liposomes, or solid dispersions.
Low blood-brain barrier permeability indicates that Rg4's role in the central nervous system is limited, but it also reduces the risk of possible CNS toxicity. hERG channels have no inhibitory effect, indicating good cardiac safety. A negative Ames test indicates low genotoxicity risk and relatively high safety.
Pharmacokinetics, existing studies show that Rg4 can reach effective concentrations in plasma after oral administration and has a certain biological half-life, but its metabolic pathways are not yet fully elucidated. In the future, further research on in vivo pharmacokinetics and metabolic kinetics is needed to clarify their absorption, distribution, metabolism, and excretion characteristics, providing a basis for clinical application.
Based on the multiple pharmacological activities of ginsenoside Rg4, it shows broad application prospects in inflammation, infection, metabolic diseases, and tumor treatment. Especially in acute inflammatory diseases such as sepsis and pulmonary inflammation, Rg4 has potential clinical therapeutic value by regulating immune responses and oxidative stress, reducing tissue damage.
In tumor treatment, Rg4's multi-target mechanism provides a theoretical basis for its use as an adjunct anticancer drug, especially showing promising prospects for breast cancer treatment. In the future, combined chemotherapy strategies are expected to improve efficacy and overcome drug resistance.
However, Rg4's low water solubility and large molecular weight limit its drug development process, requiring improvements in bioavailability through pharmacoformulation. At the same time, preclinical safety evaluation and systematic clinical trials still need to be strengthened to verify efficacy and safety.
Future research should focus on:
Ginsenoside Rg4, as a natural product with multiple biological activities, demonstrates broad application potential in anti-inflammation, antioxidant, immunomodulatory, and anti-tumor areas due to its unique chemical structure and rich pharmacological functions. Its mechanism of action involves multiple key cellular signaling pathways and molecular targets, demonstrating the advantages of multi-target and multi-mechanism collaborative therapy from natural products. Despite challenges such as poor water solubility and limited bioavailability, Rg4 is expected to become an innovative drug candidate in the fields of inflammatory disease and tumor treatment as formulation technology and pharmacological research continue to advance. In the future, through systematic pharmacokinetic studies and clinical validation, it is hoped that ginsenoside Rg4 can successfully transform from a natural product into a clinical drug, contributing new therapeutic approaches to human health.
