Decoding the mechanism of Eleutheroside E in treating osteoporosis via network pharmacological analysis and molecular docking of osteoclast-related genes and gut microbiota.

Objective: Eleutheroside E (EE) is an anti-inflammatory natural compound derived from the edible medicinal herb Acanthopanax senticosus. This study aims to investigate the underlying mechanism of the anti-osteoporosis action of EE through network pharmacology, molecular docking and gut microbiota. Materials and methods: Network pharmacology was used to explore the potential core targets and main pathways mediated by EE in osteoporosis (OP) treatment. Molecular docking was exploited to investigate the interactions between the active anti-OP compounds in EE and the potential downstream targets. Following the multi-approach bioinformatics analysis, ovariectomy (OVX) model was also established to investigate the in vivo anti-OP effects of EE. Results: The top 10 core targets in PPI network were TP53, AKT1, JUN, CTNNB1, STAT3, HIF1A, EP300, CREB1, IL1B and ESR1. Molecular docking results that the binding energy of target proteins and the active compounds was approximately between -5.0 and -7.0 kcal/mol, which EE has the lowest docking binding energy with HIF1A. Enrichment analysis of GO and KEGG pathways of target proteins indicated that EE treatment could potentially alter numerous biological processes and cellular pathways. In vivo experiments demonstrated the protective effect of EE treatment against accelerated bone loss, where reduced serum levels of TRAP, CTX, TNF-α, LPS, and IL-6 and increased bone volume and serum levels of P1NP were observed in EE-treated mice. In addition, changes in gut microbiota were spotted by 16S rRNA gene sequencing, showing that EE treatment increased the relative abundance of Lactobacillus and decreased the relative abundance of Clostridiaceae. Conclusion: In summary, these findings suggested that the characteristics of multi-target and multi-pathway of EE against OP. In vivo, EE prevents the onset of OP by regulating gut microbiota and inflammatory response and is therefore a potential OP drug.

Protective effects of Eleutheroside E against high-altitude pulmonary edema by inhibiting NLRP3 inflammasome-mediated pyroptosis.

Eleutheroside E (EE) is a primary active component of Acanthopanax senticosus, which has been reported to inhibit the expression of inflammatory genes, but the underlying mechanisms remain elusive. High-altitude pulmonary edema (HAPE) is a severe complication of high-altitude exposure occurring after ascent above 2500 m. However, effective and safe preventative measures for HAPE still need to be improved. This study aimed to elucidate the preventative potential and underlying mechanism of EE in HAPE. Rat models of HAPE were established through hypobaric hypoxia. Mechanistically, hypobaric hypoxia aggravates oxidative stress and upregulates (pro)-inflammatory cytokines, activating NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis, eventually leading to HAPE. EE suppressed NLRP3 inflammasome-mediated pyroptosis by inhibiting the nuclear translocation of nuclear factor kappa-Β (NF-κB), thereby protecting the lung from HAPE. However, nigericin (Nig), an NLRP3 activator, partially abolished the protective effects of EE. These findings suggest EE is a promising agent for preventing HAPE induced by NLRP3 inflammasome-mediated pyroptosis.

Eleutheroside E from pre-treatment of Acanthopanax senticosus (Rupr.etMaxim.) Harms ameliorates high-altitude-induced heart injury by regulating NLRP3 inflammasome-mediated pyroptosis via NLRP3/caspase-1 pathway.

Eleutheroside E, a major natural bioactive compound in Acanthopanax senticosus (Rupr.etMaxim.) Harms, possesses anti-oxidative, anti-fatigue, anti-inflammatory, anti-bacterial and immunoregulatory effects. High-altitude hypobaric hypoxia affects blood flow and oxygen utilisation, resulting in severe heart injury that cannot be reversed, thereby eventually causing or exacerbating high-altitude heart disease and heart failure. The purpose of this study was to determine the cardioprotective effects of eleutheroside E against high-altitude-induced heart injury (HAHI), and to study the mechanisms by which this happens. A hypobaric hypoxia chamber was used in the study to simulate hypobaric hypoxia at the high altitude of 6000 m. 42 male rats were randomly assigned to 6 equal groups and pre-treated with saline, eleutheroside E 100 mg/kg, eleutheroside E 50 mg/kg, or nigericin 4 mg/kg. Eleutheroside E exhibited significant dose-dependent effects on a rat model of HAHI by suppressing inflammation and pyroptosis. Eleutheroside E downregulated the expressions of brain natriuretic peptide (BNP), creatine kinase isoenzymes (CK-MB) and lactic dehydrogenase (LDH). Moreover, The ECG also showed eleutheroside E improved the changes in QT interval, corrected QT interval, QRS interval and heart rate. Eleutheroside E remarkably suppressed the expressions of NLRP3/caspase-1-related proteins and pro-inflammatory factors in heart tissue of the model rats. Nigericin, known as an agonist of NLRP3 inflammasome-mediated pyroptosis, reversed the effects of eleutheroside E. Eleutheroside E prevented HAHI and inhibited inflammation and pyroptosis via the NLRP3/caspase-1 signalling pathway. Taken together, eleutheroside E is a prospective, effective, safe and inexpensive agent that can be used to treat HAHI.

Effect of Eleutheroside E on an MPTP-Induced Parkinson's Disease Cell Model and Its Mechanism.

This research investigated the effects of eleutheroside E (EE) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease cell model and its mechanism. Methods: To create a cell model of Parkinson's disease, MPTP (2500 µmol/L) was administered to rat adrenal pheochromocytoma cells (PC-12) to produce an MPTP group. Selegiline (50 µmol/L) and MPTP had been administered to the positive group beforehand. The eleutheroside E group was divided into low-, medium-, and high-concentration groups, in which the cells were pretreated with eleutheroside E at concentrations of 100 µmol/L, 300 µmol/L, and 500 µmol/L. Next, MPTP was added to the cells separately. The CCK-8 method was used to measure the cell survival rate. Apart from the CCK-8 method, mitochondrial membrane potential detection, cell reactive oxygen species (ROS) detection, and other methods were also adopted to verify the effect of low, medium, and high concentrations of eleutheroside E on the MPTP-induced cell model. Western blot analysis was used to detect changes in the expression of intracellular proteins CytC, Nrf2, and NQO1 to clarify the mechanism. The results are as follows. Compared with the MPTP group, the survival rates of cells at low, medium, and high concentrations of eleutheroside E all increased. The mitochondrial membrane potential at medium and high concentrations of eleutheroside E increased. The ROS levels at medium and high concentrations of eleutheroside E decreased. Moreover, the apoptosis rate decreased and the expression levels of the intracellular proteins CytC, Nrf2, and NQO1 were upregulated. Conclusion: Eleutheroside E can improve the MPTP-induced apoptosis of PC-12 cells by increasing the mitochondrial membrane potential and reducing the level of intracellular reactive oxygen species (ROS). Moreover, the apoptosis of cells is regulated by the expression of CytC, Nrf2, and NQO1 proteins.

Safety and efficacy of a feed additive consisting of a tincture derived from the roots of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (taiga root tincture) for use in dogs, cats and horses (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a tincture from the roots of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (taiga root tincture) when used as a sensory additive in feed for dogs, cats and horses. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive is safe for dogs, cats and horses at the maximum proposed use level of 460.7, 489.5 and 140.7 mg/kg complete feed, respectively. The additive was considered safe for consumers when used at the proposed conditions of use in horses for meat production. The additive under assessment should be considered as irritant to skin and eyes, and as a skin and respiratory sensitiser. The use of the taiga root tincture as a flavour in feed for horses was not expected to pose a risk for the environment. Since the root of E. senticosus has flavouring properties and its function in feed would be essentially the same as that in food, no further demonstration of efficacy is considered necessary for the tincture under assessment.

The protective effect of Eleutheroside E against the mechanical barrier dysfunction triggered by lipopolysaccharide in IPEC-J2 cells.

Eleutheroside E (EE) exhibits immunocompetence, antioxidant, and anti-inflammatory activity. Lipopolysaccharide (LPS) can elicit a strong immune response. In vitro experiments were used to explore whether EE protects intestinal porcine jejunum epithelial cells (IPEC-J2) barriers from LPS stress. The experiment was divided into group C (control group: complete medium), group E (group C + 0.1 mg/mL EE), group L (group C + 10 µg/mL LPS), and group EL (adding 0.1 mg/mL EE for 6 h, and then adding 10 µg/mL LPS for culture). Finally, the cell proliferation, permeability, mRNA expression of cytokines, mRNA and protein expression of tight junctions (TJs) were analyzed. The result show that, when compared to the C group, EE significantly promoted the proliferation of IPEC-J2 at 58 h and showed low permeability (P < 0.05), the anti-inflammatory cytokines IL-10 and TGF-ß mRNA expression were increased extremely significantly, the inflammatory cytokines IL-6, TNF-α, and IFN-γ mRNA expression were extremely significantly decreased (P < 0.01), the mRNA and protein expression of TJ were significantly increased in group E (P < 0.05). However, LPS showed a damaging effect. EL group compared with L group, the cell index (CI) value was higher at 58 h (P < 0.05), the permeability was significantly lower (P < 0.05), the mRNA expressions of the inflammatory cytokines were down-regulated(P < 0.01), and the TJ mRNA and protein relative expression were increased (P < 0.05). In summary, the addition of EE protects the LPS-induced increase in permeability of IPEC-J2, potentially by expressing high levels of TJ proteins and inhibiting the increase of inflammatory cytokines.

Eleutheroside E functions as anti-cervical cancer drug by inhibiting the phosphatidylinositol 3-kinase pathway and reprogramming the metabolic responses.

OBJECTIVES: Cervical cancer (CC) is the common female malignant tumour with non-negligible morbidity and mortality. Eleutheroside E (EE) has anti-oxidative stress, anti-inflammatory and anti-proliferation effects in diverse disease models. However, its anti-tumour role remains unclear. METHODS: The cell viability, apoptosis rate and protein expressions were detected by CCK-8, flow cytometry and western blot assays, respectively. The metabolic profile was performed by GC/MS analysis. Furthermore, the effect of EE on CC was verified in nude mice. KEY FINDINGS: EE notably decreased the viability and increased the cell apoptosis, which could be reversed with 740Y-P treatment. EE treatment changed the metabolic categories of SiHa cells. The fatty acids signalling pathway was the most outstanding differential pathway. Myo-inositol prominently enhanced the level of phosphorylated Akt in a dose-dependent way. Moreover, EE declined the tumour volume and weight and the proliferation, but promoted the apoptosis in vivo. EE reduced the relative expression of phosphorylated PI3K and Akt. However, all these in-vivo results were observably antagonized with myo-inositol treatment. CONCLUSIONS: EE plays an anti-tumour role in CC via inhibiting the PI3K pathway and reprogramming the metabolic responses.

Study on the technology of efficient extraction of eleutheroside E from Acanthopanax senticosus by green solvent DES.

OBJECTIVES: Acanthopanax senticosus (Rupr. & Maxim.) Harms is a medicinal and edible plant which is clinically used for the recovery and treatment of cardiovascular and central diseases. As a characteristic active pharmaceutical ingredient of Acanthopanax senticosus, eleutheroside E is the core of the therapeutic effect. Organic solvent extraction has low selectivity, low extraction rate, difficulty in separation and purification and safety risks. The purpose of this study was to extract the effective component of Acanthopanax senticosus with a new green solvent. METHODS: In this article, two kinds of deep eutectic solvents (DESs) (DES-1 and DES-2) were synthesised by heating and stirring methods. Eleutheroside E was extracted by ultrasonic extraction with two kinds of DES as extractants and quantitatively analysed by Orbitrap-tandem mass spectrometry (MS/MS). RESULTS: The main results showed that the initial polarity of the DES was similar to that of 60 to 80% ethanol and hydrogen bond donors were the main factors affecting the polarity of DES. In the test, the viscosity of DES was higher than that of ethanol, and even the addition of a small amount of water (10%) caused intermolecular hydrogen bond disruption and redistribution of the solvent, resulting in a significant decrease in solvent viscosity. The solvents in the test group were stable after standing at 5°C in the dark for 100 days. The extraction rate of eleutheroside E by DES solvent was 5-6 times higher than that by ethanol. DES-1 and DES-2 can efficiently extract eleutheroside E. CONCLUSION: This study developed a new method for the application of the green extraction of eleutheroside E with certain practical significance.

Tea saponin additive to extract eleutheroside B and E from Eleutherococcus senticosus by ultrasonic mediation and its application in a semi-pilot scale.

The safety of ethanol in operations and its effects on human health are gradually being questioned. Under this premise, we attempted to use the natural surfactant tea saponin, which originates from the processing residues of camellia oil, as the additive of the extraction solvent and to extract eleutheroside B and eleutheroside E in the roots and rhizomes of E. senticosus by ultrasonic mediation. After a single-factor experiment, extraction kinetics at different powers and reaction temperatures, and Box-Behnken design optimization, the optimal conditions obtained were 0.3% tea saponin solution as the extraction solvent, 20 mL/g liquid-solid ratio, 250 W ultrasonic irradiation power (43.4 mW/g ultrasonic power density) and 40 min ultrasonic irradiation time. Under optimal conditions, satisfactory yields of eleutheroside B (1.06 ± 0.04 mg/g) and eleutheroside E (2.65 ± 0.12 mg/g) were obtained with semi pilot scale ultrasonic extraction equipment. The experiments showed that compared with the traditional thermal extraction process, the extraction time is significantly reduced at lower operating temperatures.

Eleutheroside E alleviates cerebral ischemia-reperfusion injury in a 5-hydroxytryptamine receptor 2C (Htr2c)-dependent manner in rats.

Stroke is the central disorder underlined by ischemia-reperfusion (I/R) injury. Eleutheroside E (EE) is administered as the shield in some ischemia tissues with anti-inflammatory action. However, whether EE defends I/R-induced damage in the brain remains unknown. Here, we demonstrated that EE significantly alleviated the cerebral I/R injury and reduced the apoptosis of hippocampal neuron cells in rats. During the anti-apoptosis process, EE significantly upregulated the expression of 5-hydroxytryptamine receptor 2C (Htr2c) gene. Silencing Htr2c expression dramatically weakened the protective effect of EE on I/R-induced apoptosis of rat hippocampal neuron. EE-regulated Htr2c also remarkably inhibited the expression of caspase-3, -6 and -7, thereby suggesting a plausible anti-apoptosis mechanism associated with Htr2c/caspase axis. These findings elicit the potentially clinical strategy that targets Htr2c to improve outcome of ischemia brain.

Eleutheroside E reduces intestinal fat accumulation in Caenorhabditis elegans through neuroendocrine signals.

BACKGROUND: Acanthopanax senticosus, a small woody shrub of the family Araliaceae, can be used as a functional food with multiple biological activities. Eleutheroside E (EE), an important active component of A. senticosus, has significant effects on neurological diseases. However, whether EE can regulate lipid metabolism has not been reported. The brain can mediate communication between neurons and intestinal cells through long-distance neuroendocrine signals. We speculated that EE might regulate the intestinal lipid metabolism of Caenorhabditis elegans through neuroendocrine signals. RESULTS: First, we found that EE reduced the intestinal fat content of C. elegans, without affecting development, reproduction, food intake or movement. In addition, EE significantly regulated genes and metabolites related to lipid metabolism. EE extensively affected fatty acid synthesis, ß-oxidation and lipolysis processes, and regulated the content of various fatty acid and lipid metabolism intermediates. We finally proved that EE reduced intestinal fat storage through serotonin and neuropeptide flp-7-npr-22 pathways in the nervous system. CONCLUSION: EE is expected to be a functional food that regulates lipid metabolism. © 2022 Society of Chemical Industry.

Mitigative effects of Eleutheroside E against the mechanical barrier dysfunction induced by soybean agglutinin in IPEC-J2 cell line.

Soybean agglutinin (SBA) is an anti-nutritional factor which decreases the mechanical barrier function in intestinal porcine jejunum epithelial cells (IPEC-J2). Eleutheroside E (EE) is a key part of Acanthopanax senticosus to exert pharmacological effects. This study aims to investigate the effects of EE on the barrier function in IPEC-J2 cells and to determine the ability of EE to enhance the protective effect of barrier function against SBA exposure. The IPEC-J2 cells were cultured in mediums with concentration of 0.1 mg/ml EE, 0.5 ml/ml SBA and 0.1 mg/ml EE pre-treated then treated with 0.5 mg/ml SBA. Then, the transepithelial electric resistance (TEER) value, inflammatory cytokines mRNA expression, tight junction mRNA and protein expression were tested by epithelial Voltohm meter, q-PCR and Western blot method respectively. The results showed that cells treated with 0.1 mg/ml EE had lower permeability (p < 0.05) while 0.5 mg/ml SBA treatment had higher permeability through tested TEER, and higher tight junction proteins (Claudin-3 and ZO-1) expressions and genes (Claudin-3, Occludin and ZO-1) expressions (p < 0.05) in 0.1 mg/ml EE group. IPEC-J2 cells pre-treated with 0.1 mg/ml EE could significantly improve the inflammatory response caused by 0.5 mg/ml SBA by up-regulation for IL-10, TGF-ß, and down-regulation gene expression of IL-6, TNF-α and IFN-γ (p < 0.05). In conclusion, 0.1 mg/ml EE can improve the mechanical barrier function and could protect the effects while 0.5 mg/ml of SBA-induced barrier dysfunction in IPEC-J2.

Development and application of a rapid HPLC method for simultaneous determination of hyperoside, isoquercitrin and eleutheroside E in Apocynum venetum L. and Eleutherococcus senticosus.

Apocynum venetum L. and Eleutherococcus senticosus have been used for hundreds of years to treat hypertension in China. In previous research, there was not a suitable quality control of method for the formulas of Apocynum venetum L. and Eleutherococcus senticosus. It is urgent and essential to develop modern analytical methods for Apocynum venetum L. and Eleutherococcus senticosus to ensure the quality of the formulas. A rapid approach for simultaneous determination of hyperoside, isoquercitrin and eleutheroside E in Apocynum venetum L. and Eleutherococcus senticosus by high-performance liquid chromatography with a diode array detector was described and validated. The full method validation, including the linearity, limits of detection and quantification, precision, repeatability, stability and recovery, was examined. All target components, including isomers of hyperoside and isoquercitrin, were baseline separated in 35 min. The developed method was sensitive, reliable and feasible. With this method, the optimal decoction conditions of Apocynum venetum L. and Eleutherococcus senticosus were selected, and their quality analysis was carried out. Furthermore, an herbal compatibility study of Apocynum venetum L. and Eleutherococcus senticosus based on detecting variations in the content of their active ingredients was performed by the developed HPLC method. It could be an alternative for the quantitative analysis of herbs that contain hyperoside, isoquercitrin or (and) eleutheroside E in the future.

Eleutheroside E decreases oxidative stress and NF-κB activation and reprograms the metabolic response against hypoxia-reoxygenation injury in H9c2 cells.

Ischemia-reperfusion (I/R) injury causes cardiac dysfunction through several mechanisms including oxidative stress and pro-inflammation. Eleutheroside E (EE) has protective effects in ischemia tissue and anti-inflammatory action. However, the effect of EE on I/R-injured cardiomyocytes is unknown. In this study, we used in vitro H9c2 cell model to investigate the favorable role of EE on myocardial I/R injury. We found that EE administration attenuated the cardiomyocyte apoptosis induced by hypoxia-reoxygenation (H/R) injury. Further, pre-treatment with EE dramatically inhibited mitochondrial oxidative stress, IκBα phosphorylation and nuclear factor kappa B (NF-κB) subunit p65 translocation into nuclei. EE might suppress the MAPK signaling pathway to inhibit the H/R-induced NF-κB activation. Moreover, we had analyzed the metabolomic profile of H/R-injured and H/R + 100 EE-treated H9c2 cells and found that the abundance of most metabolites changed by H/R could be re-modulated by EE treatment. Pathway analysis highlighted the inhibition of fatty acid biosynthesis and alternation of arginine and proline metabolism as two potential links to the favorable effect of EE on H/R-injured cardiomyocytes. The further demonstration showed that nitric oxide (NO), a product that is solely catabolized by l-arginine and has profound anti-oxidative stress activity during H/R in cardiomyocytes, was augmented by EE. Altogether, our results provide evidence that EE may be a potential drug for myocardial I/R injury by reducing oxidative stress, NF-κB activation, and metabolic reprogramming.

A review on the immunomodulatory activity of Acanthopanax senticosus and its active components.

Acanthopanacis Senticosi Radix et Rhizoma seu Caulis, the dried root and rhizome or stem of Acanthopanax senticosus, is commonly known as Siberian ginseng or Ciwujia in Chinese. It is used all over the world as an adaptogen to enhance physical and mental performance for the sake of normal physiological functioning of human bodies under stress. In the theory of traditional Chinese medicine, Ciwujia can strengthen the spleen that is an essential organ for immunological response. Its traditional applications include inflammation, fatigue and cancer in which the immune-regulating function is always involved. In this article, the immunomodulatory activities of Ciwujia extracts, fractions and pure compounds were extensively reviewed first. Then, the possibility of upgrading the chemical markers to bioactive markers was explored. Finally, the potency of aqueous extract and ethanol extract in regulating cytokines production from human peripheral blood mononuclear cells was compared. We conclude that although various phytochemicals such as isofraxidin, syringin and eleutheroside E from Ciwujia have been shown to modulate immunological functions, the aqueous extract of Ciwujia as a whole possesses the most potent efficacy. Therefore, aqueous (rather than ethanol) extract of Ciwujia should be used in order to benefit from its immunomodulatory properties.

Natural medicines for the treatment of fatigue: Bioactive components, pharmacology, and mechanisms.

It is a common phenomenon that people are in a sub-health condition and facing "unexplained fatigue", which seriously affects their health, work efficiency and quality of life. Meanwhile, fatigue is also a common symptom of many serious diseases such as HIV/AIDS, cancer, and schizophrenia. However, there are still no official recommendations for the treatment of various forms of fatigue. Some traditional natural medicines are often used as health care products, such as ginseng, Cordyceps militaris (L.ex Fr.Link) and Rhodiola rosea L., and these have been reported to have specific anti-fatigue effects with small toxic and side effects and rich pharmacological activities. It may be promising treatment strategy for sub-health. In this review, we first outline the generation of fatigue. Furthermore, we put emphasis on the anti-fatigue mechanism, bioactive components, and clinic trials of natural medicines, which will contribute to the development of potential anti-fatigue agents and open up novel treatments for sub-health.

HPTLC-profiling of eleutherosides, mechanism of antioxidative action of eleutheroside E1, the PAMPA test with LC/MS detection and the structure-activity relationship.

Human body is constantly generating free radicals, which causes oxidative stress. Despite naturally occurring antioxidant systems in human body, free radicals cause lipid, proteins and DNA oxidation. New antioxidants are still urgent as well as their mechanisms of action should be explained. In this study, we investigated the mechanism by which eleutherosides B, E and E1 may act as antioxidants, identified eleutherosides in Eleutherococcus lasiogyne and Eleutherococcus giraldii, and explained in vitro the absorption of eleutheroside E1 based on passive transport. The DPPH∗ and DB-HPTLC tests were used to assess the antioxidant activity. Of the three eleutherosides, only eleutheroside E1 exhibited a strong anti-DPPH∗ activity (EC50 37.03 µg/mL; 63 mMol) compared to the raw extracts (EC50 170 and 180 µg/mL for E. lasiogyne and E. giraldii). This activity was also confirmed by the DB-HPTLC autography technique. According to Zaluski's hypothesis, the antioxidant mechanism of eleutheroside E1 is based on the complexation of DPPH∗ molecule with its aryl radical. During this reaction, the aryl radical of eleutheroside E1 (E1∗) and DPPHH are created. Next, the aryl radical (E1∗) is complexed with another DPPH∗ molecule. Additionally, the aryl radical can be stabilized by the presence of the methoxy groups in the aromatic ring, which increases its antioxidative action. The HPTLC-identification of extracts showed the presence of eleutherosides B, E and E1 in both species. The PAMPA test coupled with LC/MS detection showed a low permeability of eleutheroside E1 across artificial membrane. Because eleutherosides belong to the polyphenols, the TPC and TFC were quantified. The TPC and TFC varied from 51.4 to 49.3 mg/g dry extract for TPC, and from 5.73 to 4.91 mg/g dry extract for TFC, for E. giraldii and E. lasiogyne, respectively. In conclusion, eleutheroside E1 in its pure form could be a chemopreventive ingredient of new pharmacological or dietary products, stimulating the GALT. These findings can explain partially the adaptogenic activity of eleutheroside E1 on the GALT, which has been still unknown.

Green synthesis of multifunctional silver and gold nanoparticles from the oriental herbal adaptogen: Siberian ginseng.

Pharmacologically active stem of the oriental herbal adaptogen, Siberian ginseng, was employed for the ecofriendly synthesis of Siberian ginseng silver nanoparticles (Sg-AgNPs) and Siberian ginseng gold nanoparticles (Sg-AuNPs). First, for metabolic characterization of the sample, liquid chromatography-tandem mass spectrometry analysis (indicated the presence of eleutherosides A and E), total phenol content, and total reducing sugar were analyzed. Second, the water extract of the sample mediated the biological synthesis of both Sg-AgNPs and Sg-AuNPs that were crystalline face-centered cubical structures with a Z-average hydrodynamic diameter of 126 and 189 nm, respectively. Moreover, Fourier transform infrared analysis indicated that proteins and aromatic hydrocarbons play a key role in the formation and stabilization of Sg-AgNPs, whereas phenolic compounds accounted for the synthesis and stability of Sg-AuNPs. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay determined that Sg-AgNPs conferred strong cytotoxicity against MCF7 (human breast cancer cell line) and was only slightly toxic to HaCaT (human keratinocyte cell line) at 10 µg⋅mL(-1). However, Sg-AuNPs did not display cytotoxic effects against both of the cell lines. The disc diffusion assay indicated a dose-dependent increase in the zone of inhibition of Staphylococcus aureus (ATCC 6538), Bacillus anthracis (NCTC 10340), Vibrio parahaemolyticus (ATCC 33844), and Escherichia coli (BL21) treated with Sg-AgNPs, whereas Sg-AuNPs did not show inhibitory activity. In addition, the 2,2-diphenyl-1-picrylhydrazyl assay demonstrated that both Sg-AgNPs and Sg-AuNPs possess strong antioxidant activity. To the best of our knowledge, this is the first report unraveling the potential of Eleutherococcus senticosus for silver and gold nanoparticle synthesis along with its biological applications, which in turn would promote widespread usage of the endemic Siberian ginseng.

Antiedema effects of Siberian ginseng in humans and its molecular mechanism of lymphatic vascular function in vitro.

The lymphatic system in the skin plays a major role in tissue fluid homeostasis, in the afferent phase of the immune response, and in tumor metastasis. Although lymphangiogenic factors involved in embryonic development and the metastatic spread of tumor cells have been well studied, little is known about small-molecule compounds that activate lymphatic function, especially under physiological conditions. We hypothesized that the identification of a lymphatic-activating compound could provide a method for improving edema. Here, we show that Siberian ginseng (Eleutherococcus senticosus) and its component eleutheroside E induce phosphorylation of the endothelial-specific receptor Tie2 in vitro. The activation of Tie2 on lymphatic endothelial cells (LECs) is known to stabilize lymphatic vessels, so we examined the effects of Siberian ginseng on LECs. We found that Siberian ginseng induces the migration and cord formation of LECs. Permeability assays demonstrated that it stabilizes LECs by promoting the intercellular localization of vascular endothelial cadherin, which is an endothelium-specific cell-cell adhesion molecule involved in endothelial barrier function, and it induces the phosphorylation of endothelial nitric oxide synthase by LECs. These effects appear to be mediated by the activation of Tie2 in LECs. Finally, we investigated whether the consumption of Siberian ginseng powder improves edema in a 2-way, randomized, crossover study in 50 healthy female volunteers. Edema of the lower limbs was significantly attenuated at 2 and 4hours after ingestion as compared with the control group. Thus, we demonstrate that Siberian ginseng exerts its potent antiedema activity mainly by promoting lymphatic function.