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Product name: Ginsenoside Rg5
Synonym name: Ginsenoside Rg5E
Catalogue No.: BP1651
Cas No.: 186763-78-0
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.
Description:
Ginsenoside Rg5 plays a novel role as an IGF-1R agonist, promoting therapeutic angiogenesis and improving hypertension without adverse effects in the vasculature, it can ameliorate lung inflammation possibly by inhibiting the binding of LPS to toll-like receptor (TLR)-4 on macrophages. Ginsenoside Rg5 blocks cell cycle of SK-HEP-1 cells at the Gl/S transition phase by down-regulating cyclin E-dependent kinase activity and that the down-regulation of cyclin E-dependent kinase activity is caused mainly by induced CDK2 inhibitor, p21Cip/WAF1 and decreased levels of cyclin E.
References:
Int Immunopharmacol. 2012 Jan;12(1):110-6.
Ginsenoside Rg5 ameliorates lung inflammation in mice by inhibiting the binding of LPS to toll-like receptor-4 on macrophages.
Heating and steaming processes have been applied to various natural medicines for either enhancing or altering their pharmacological activities, and the chemical compositions of the active components. While ginsenoside Rb1, which is the major constituent of raw ginseng, has been studied extensively for its anti-inflammatory effect, the biological activity of Ginsenoside Rg5, a major constituent of steamed ginseng, remains to be explored.
METHODS AND RESULTS:
Here, we isolated Rg5 and examined anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated macrophages and on LPS-induced lung inflammation. Rg5 inhibited the expression of proinflammatory cytokines, IL-1β and TNF-α, as well as inflammatory enzymes, COX-2 and iNOS in LPS-stimulated alveolar macrophages. Rg5 also reduced LPS-induced phosphorylation of IL-1 receptor-associated kinases (IRAK)-1 and IKK-β, as well as the degradation of IRAK-1 and IRAK-4. Rg5 inhibited the phosphorylation of NF-κB as well as the translocation of p65 into the nucleus. When macrophages were treated with Alexa Fluor 594-conjugated LPS in the presence of Rg5, the fluorescence intensity of LPS observed outside the cell membrane was lower than that in LPS-stimulated alveolar macrophages alone. Rg5, inhibited the levels of protein and neutrophils in bronchoalveolar lavage fluid of LPS-stimulated mice, as well as pro-inflammatory cytokines, TNF-α and IL-1β. Rg5 also inhibited iNOS and COX expressions, and NF-κB activation in LPS-stimulated lung inflammation of mice. The inhibitory effect of Rg5 (10 mg/kg) was comparable to that of dexamethasone (5 mg/kg).
CONCLUSIONS:
Based on these findings, Rg5 can ameliorate lung inflammation possibly by inhibiting the binding of LPS to toll-like receptor (TLR)-4 on macrophages.
Int Immunopharmacol. 2014 Apr;19(2):317-26.
Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses.
Neuroinflammatory responses play a crucial role in the pathogenesis of Alzheimer's disease (AD). Ginsenoside Rg5 (Rg5), an abundant natural compound in Panax ginseng, has been found to be beneficial in treating AD.
METHODS AND RESULTS:
In the present study, we demonstrated that Ginsenoside Rg5 improved cognitive dysfunction and attenuated neuroinflammatory responses in streptozotocin (STZ)-induced memory impaired rats. Cognitive deficits were ameliorated with Ginsenoside Rg5 (5, 10 and 20mg/kg) treatment in a dose-dependent manner together with decreased levels of inflammatory cytokines TNF-α and IL-1β (P<0.05) in brains of STZ rats. Acetylcholinesterase (AChE) activity was also significantly reduced by Ginsenoside Rg5 whereas choline acetyltransferase (ChAT) activity was remarkably increased in the cortex and hippocampus of STZ-induced AD rats (P<0.05). Western blot analysis also demonstrated that Ginsenoside Rg5 increased remarkably BDNF and IGF-1 expressions whereas decreased significantly Aβ deposits (P<0.05). Furthermore, it was observed that the expressions of COX-2 and iNOS were significantly up-regulated in STZ-induced AD rats and down-regulated strongly (P<0.05) by Ginsenoside Rg5 compared with control rats. These data demonstrated that STZ-induced learning and memory impairments in rats could be improved by Ginsenoside Rg5, which was associated with attenuating neuroinflammatory responses.
CONCLUSIONS:
Our findings suggested that Ginsenoside Rg5 could be a beneficial agent for the treatment of AD.
J Biol Chem. 2015 Jan 2;290(1):467-77.
Specific activation of insulin-like growth factor-1 receptor by ginsenoside Rg5 promotes angiogenesis and vasorelaxation.
Ginsenoside Rg5 is a compound newly synthesized during the steaming process of ginseng; however, its biological activity has not been elucidated with regard to endothelial function.
METHODS AND RESULTS:
We found that Rg5 stimulated in vitro angiogenesis of human endothelial cells, consistent with increased neovascularization and blood perfusion in a mouse hind limb ischemia model. Rg5 also evoked vasorelaxation in aortic rings isolated from wild type and high cholesterol-fed ApoE(-/-) mice but not from endothelial nitric-oxide synthase (eNOS) knock-out mice. Angiogenic activity of Rg5 was highly associated with a specific increase in insulin-like growth factor-1 receptor (IGF-1R) phosphorylation and subsequent activation of multiple angiogenic signals, including ERK, FAK, Akt/eNOS/NO, and Gi-mediated phospholipase C/Ca(2+)/eNOS dimerization pathways. The vasodilative activity of Rg5 was mediated by the eNOS/NO/cGMP axis. IGF-1R knockdown suppressed Rg5-induced angiogenesis and vasorelaxation by inhibiting key angiogenic signaling and NO/cGMP pathways. In silico docking analysis showed that Rg5 bound with high affinity to IGF-1R at the same binding site of IGF. Rg5 blocked binding of IGF-1 to its receptor with an IC50 of ∼90 nmol/liter. However, Rg5 did not induce vascular inflammation and permeability.
CONCLUSIONS:
These data suggest that Rg5 plays a novel role as an IGF-1R agonist, promoting therapeutic angiogenesis and improving hypertension without adverse effects in the vasculature.
HPLC of Ginsenoside Rg5
HNMR of Ginsenoside Rg5
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
198.7600
3.5287
3.5289
.0208
.6205
.3916
Low
80.8545
5.8322
No
No
No
No
No
No
0.0
Yes
No
No
No
Ginsenoside Rg5, as an important active ingredient in red ginseng, has attracted widespread attention in recent years due to its remarkable biological activity and potential medicinal value. Red ginseng is a ginseng processed by steaming, widely used in traditional Chinese medicine due to its unique chemical composition and pharmacological effects. Ginsenoside Rg5, as a natural product, not only demonstrates multi-target and multi-pathway regulatory capabilities, but also exhibits good pharmacological activity in anti-tumor, anti-inflammatory, and immunomodulatory properties. Especially in research on malignant tumors such as lung cancer, ginsenoside Rg5 demonstrates unique therapeutic potential by competitively inhibiting insulin-like growth factor 1 receptor (IGF-1R) and regulating related signaling pathways.
This paper aims to systematically review the chemical structure and physicochemical properties of ginsenoside Rg5, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics. Combined with its molecular targets in diseases such as lung cancer, it explores its clinical application prospects and development trends, providing theoretical basis and reference for subsequent research and clinical translation.
Ginsenoside Rg5 belongs to the ginsenoside triterpene saponin family, with a molecular formula of C42H72O13 and a molecular weight of 767.0100. Its structural core is a tetracyclic triterpenoid backbone, connecting multiple glycogroups to form a typical glycoside structure. Rg5 is derived from the heat treatment of ginsenosides Rb1 and Rg1 during the red ginseng processing process, and it has high stability and biological activity.
In terms of physicochemical properties, the LogP value of ginsenoside Rg5 is 3.5287, indicating moderate lipid solubility that facilitates cell membrane penetration; the polar surface area (TPSA) is 198.76 Ų, indicating strong polarity that may affect water solubility and bioavailability. Low water solubility (0.0208 mg/mL) suggests limited solubility in the body. The blood-brain barrier has low permeability, indicating difficulty directly acting on the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test result was 0, indicating no significant mutagenicity and relatively high safety.
Ginsenoside Rg5 is mainly found in red ginseng (steamed ginseng). Red ginseng undergoes processes such as steaming and drying fresh ginseng, transforming the original ginsenoside structure into various specific saponin components including Rg5. The processing technology of red ginseng not only increases the content of its medicinal components but also enhances its pharmacological activity.
Common extraction methods include organic solvent extraction, ultrasound-assisted extraction, microwave-assisted extraction, and others. Ethanol or methanol is usually used as extraction solvents, and crude extracts are obtained by reflux extraction or ultrasound-assisted extraction. Subsequently, silica gel column chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC) were used for separation and purification, ultimately yielding high-purity ginsenoside Rg5. In recent years, supercritical fluid extraction technology and membrane separation technology have also been applied to improve extraction efficiency and purity, reduce the use of organic solvents, and comply with green chemistry principles.
Ginsenoside Rg5 exhibits a variety of significant pharmacological activities, covering anti-tumor, anti-inflammatory, antioxidant, and immunomodulatory aspects, and has made significant progress in research on malignant tumors such as lung cancer.
Numerous in vitro and in vivo experiments have shown that ginsenoside Rg5 significantly inhibits lung cancer cell growth by regulating signaling pathways related to apoptosis, proliferation, migration, and invasion. Its mechanism of action involves multiple key molecular pathways, including BCL2, STAT3, RELA (NF-κB p65 subunit), and members of the MAPK family (MAPK1, MAPK8). Rg5 can induce mitochondria-dependent apoptosis in lung cancer cells, regulate the expression of BCL2 family proteins, promote CASP9 activation, and thus initiate the apoptosis process.
Additionally, Rg5 inhibits the activity of the STAT3 signaling pathway, reducing tumor cell proliferation and immune evasion. By inhibiting RELA's DNA-binding activity, it reduces COX-2 mRNA expression, alleviates tumor-related inflammatory responses, and further suppresses tumor progression. Rg5 also regulates PIK3CG in the PI3K/AKT pathway, affecting cell metabolism and survival, thereby enhancing antitumor effects.
Ginsenoside Rg5 exerts significant anti-inflammatory effects by inhibiting the NF-κB signaling pathway and reducing the expression of inflammatory mediators such as COX-2. It directly inhibits the DNA-binding activity of the NF-κB p65 subunit, blocking the transduction of inflammatory signals and reducing tissue inflammatory damage. Additionally, Rg5 regulates PPARG expression, participating in immune cell metabolism and functional regulation, and promoting immune homeostasis.
Rg5 also exhibits antioxidant activity, capable of scavenging free radicals and reducing cellular damage caused by oxidative stress. Its effects on neurological diseases are still in the preliminary research stage, as the low permeability of the blood-brain barrier may limit the direct effects of the central nervous system.
The pharmacological mechanism of ginsenoside Rg5 is complex, involving coordinated regulation of multiple targets and pathways, mainly focusing on the IGF-1R signaling pathway and its downstream effector molecules.
Ginsenoside Rg5, as a competitive agonist of IGF-1R, can compete for IGF-1R binding sites, blocking the binding of IGF-1 and IGF-1R, with an IC50 of about 90 nM. This competitive binding inhibits IGF-1R activation, blocking its downstream signaling and thereby affecting cell proliferation, differentiation, and survival. IGF-1R is highly expressed in various tumor cells and is a key driver of tumor development. Rg5 exerts antitumor effects by inhibiting this receptor.
Rg5 reduces COX-2 mRNA expression by inhibiting the DNA binding activity of the NF-κB p65 subunit, thereby alleviating inflammatory responses. As a core transcription factor for inflammation and tumorigenesis, NF-κB's inhibition of its activity helps control inflammatory states in the tumor microenvironment and blocks pro-tumor signaling.
The synergistic effects of these targets form a complex and effective antitumor and anti-inflammatory mechanism of Rg5.
The druggability evaluation of ginsenoside Rg5 shows that it has certain advantages and challenges. Its large molecular weight (767.01 Da) and high polar surface area (TPSA 198.76) limit its oral absorption and bioavailability. A moderate LogP value (3.53) favors cell membrane permeability, but low water solubility (0.0208 mg/mL) limits its dissolution and distribution in vivo.
The low permeability of the blood-brain barrier suggests it is difficult to act directly on the central nervous system, which may limit its application in neurological diseases. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity and good safety. The Ames test is non-mutagenic, further supporting its safety.
Pharmacokinetics, existing studies show that Rg5 metabolism in the body is quite complex, mainly through hepatic metabolic enzyme systems, with some metabolites possibly bioactive. Its half-life is moderate, with its distribution mainly concentrated in organs such as the liver, lungs, and kidneys. Due to its low water solubility, Rg5's oral bioavailability is limited and its efficacy is enhanced through formulation improvements or optimization of administration routes.
As a natural product, ginsenoside Rg5 demonstrates broad clinical application potential due to its multi-target and multi-mechanism anti-tumor and anti-inflammatory activities. Especially in lung cancer treatment, Rg5 can effectively suppress tumor cell proliferation and migration by inhibiting the IGF-1R signaling pathway and related molecular targets, promoting tumor cell apoptosis, and has the potential to be an adjunct or combination therapy drug.
The key to future clinical applications lies in improving the bioavailability and targeting of Rg5. The development of novel drug delivery systems such as nanocarriers, liposomes, and solid dispersions is expected to address their poor water solubility and insufficient oral absorption. Moreover, in-depth analysis of its metabolic pathways and metabolite activity will help optimize dosage and administration regimens.
At the same time, Rg5's role in immune regulation and anti-inflammation offers new ideas for its application in chronic inflammatory diseases, autoimmune diseases, and other fields. In the future, more preclinical and clinical studies are needed to systematically evaluate their safety, efficacy, and pharmacokinetic characteristics, and promote their clinical translation.
Ginsenoside Rg5, as an important active ingredient in red ginseng, demonstrates excellent antitumor and anti-inflammatory potential due to its unique chemical structure and multi-target pharmacological effects. By competitively inhibiting IGF-1R and regulating signaling pathways such as NF-κB, it exerts multi-layered biological effects, especially showing significant value in lung cancer treatment.
Although there are certain challenges in druggability, with continuous advances in extraction and purification technologies and drug delivery systems, Rg5 has broad clinical development prospects. Future research should focus on mechanism analysis, pharmacokinetic optimization, and safety evaluation to promote clinical application and support the development and innovation of natural product drugs.
Shenshuai
Wenjing
Hedandan
