Sungeun Ahn

Ginseng saponins and the treatment of osteoporosis: mini literature review

The ginseng plant (Panax ginseng Meyer) has a large number of active ingredients including steroidal saponins with a dammarane skeleton as well as protopanaxadiol and protopanaxatriol, commonly known as ginsenosides, which have antioxidant, anticancer, antidiabetic, anti-adipocyte, and sexual enhancing effects. Though several discoveries have demonstrated that ginseng saponins (ginsenosides) as the most important therapeutic agent for the treatment of osteoporosis, yet the molecular mechanism of its active metabolites is unknown. In this review, we summarize the evidence supporting the therapeutic properties of ginsenosides both in vivo and in vitro, with an emphasis on the different molecular agents comprising receptor activator of nuclear factor kappa-B ligand, receptor activator of nuclear factor kappa-B, and matrix metallopeptidase-9, as well as the bone morphogenetic protein-2 and Smad signaling pathways.

Ginsenoside Rg5:Rk1 attenuates TNF-α/IFN-γ-induced production of thymus- and activation-regulated chemokine (TARC/CCL17) and LPS-induced NO production via downregulation of NF-κB/p38 MAPK/STAT1 signaling in human keratinocytes and macrophages

Atopic dermatitis (AD) is a chronic skin disease that affects millions of people worldwide. Keratinocytes and macrophages are two cells types that play a pivotal role in the development of AD. These cells produced different chemokines and cytokines, especially thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), as well as nitric oxide (NO) through inducible nitric oxide synthase (iNOS) and COX2 in response to stimulation by TNF-α/IFN-γ and lipopolysaccharide (LPS) respectively. These mediators are thought to be crucial regulators of the pathogenesis of AD. Although several natural compounds to treat AD have been studied, the effect of Rg5:Rk1 from Panax ginseng (P. ginseng) on AD has not yet been investigated. In this study, we evaluated the inhibitory effect of Rg5:Rk1 on TNF-α/IFN-γ stimulated keratinocytes (HaCaT cells) and LPS-stimulated macrophages (RAW 264.7 cells). Enzyme-linked immunosorbent assay (ELISA) data showed that pretreatment of HaCaT cells with Rg5:Rk1 significantly reduced the TNF-α/IFN-γ-induced increase in TARC/CCL17 expression in a dose-dependent manner. In addition, Rg5:Rk1 decreased LPS-mediated nitric oxide (NO) and reactive oxygen species (ROS) production in RAW 264.7 cells. A considerable reduction in messenger RNA (mRNA) expression of the aforementioned AD mediators was also observed. Pretreatment with Rg5:Rk1 attenuated the TNF-α/IFN-γ-induced phosphorylation of p38 MAPK, STAT1, and NF-κB/IKKβ in HaCaT cells. Together, these findings suggest that ginsenoside Rg5:Rk1 may have a potential anti-AD effect by suppressing NF-κB/p38 MAPK/STAT1 signaling.

Anticancer activity of silver nanoparticles from Panax ginseng fresh leaves in human cancer cells.

The pharmaceutical role of silver nanoparticles has been increased over the last decades, especially those synthesized through herbal medicinal plants, due to their variety of pharmacological importance. Panax ginseng Meyer (P. ginseng) has been widely used as a therapeutic herbal medicine for a long time in cancer treatment. In this study, the cytotoxic and oxidative effect of a novel silver nanoparticles synthesized from P. ginseng fresh leaves (P.g AgNPs) were evaluated in different human cancer cell lines. In addition, the effect of P.g AgNPs on cell migration, apoptosis and the determination of the mechanism involve was determinate by the use of A549 lung cancer cell line. It was found that P.g AgNPs treatment inhibited cell viability and induced oxidative stress in A549, MCF7 and HepG2 cancer cell lines. Likewise, P.g AgNPs treatment inhibited the epidermal growth factor (EGF)-enhanced migration, as well as decreased the mRNA levels and phosphorylation of EGF receptors in A549 cells. Moreover, P.g AgNPs modified the morphology of the cell nucleus and increase apoptosis percentage; this effect was linked to the stimulation of p38 MAPK/p53 pathway. Taken together, our results showed that P.g AgNPs exhibited anti-cancer activity in A549 and the regulation of EGFR/p38 MAPK/p53 pathway might be the possible mechanism of its anti-activity. Further experiments are suggested to determinate the mechanism by which P.g AgNPs induce cytotoxicity and ROS generation in MCF-7 and HepG2 cells.

Rapid green synthesis of silver and gold nanoparticles using Dendropanax morbifera leaf extract and their anticancer activities

Dendropanax morbifera Léveille is an oriental medicinal plant that is traditionally used in folk medicine and grows in a specific region of South Korea. We aimed to enhance the utilization of D. morbifera medicinal plants for synthesis of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs). D. morbifera leaf extract acted as both a reducing and a stabilizing agent that rapidly synthesized Dendropanax AgNPs (D-AgNPs) and Dendropanax AuNPs (D-AuNPs). The D-AgNPs and D-AuNPs were characterized by ultraviolet-visible spectroscopy, energy dispersive X-ray analysis, elemental mapping, field emission transmission electron microscopy, X-ray diffraction, and dynamic light scattering. The characterizations revealed that the D-AgNPs and D-AuNPs were in polygon and hexagon shapes with average sizes of 100–150 nm and 10–20 nm, respectively. The important outcomes were the synthesis of AgNPs and AuNPs within 1 hour and 3 minutes, respectively, avoiding the subsequent processing for removal of any toxic components or for stabilizing the nanoparticles. Additionally, D-AgNPs and D-AuNPs were examined for cytotoxicity in a human keratinocyte cell line and in A549 human lung cancer cell line. The results indicated that D-AgNPs exhibited less cytotoxicity in the human keratinocyte cell line at 100 µg/mL after 48 hours. On the other hand, D-AgNPs showed potent cytotoxicity in the lung cancer cells at the same concentration after 48 hours, whereas D-AuNPs did not exhibit cytotoxicity in both cell lines at the same concentration. However, both D-AgNPs and D-AuNPs at 50 µg/mL enhanced the cytotoxicity of ginsenoside compound K at 25 µM after 48 hours of treatment compared with CK alone. We believe that this rapid green synthesis of D-AgNPs and D-AuNPs is a valuable addition to the applications of D. morbifera medicinal plant. D-AuNPs can be used as carriers for drug delivery and in cancer therapy due to their lack of normal cell cytotoxicity.

Intracellular synthesis of gold nanoparticles with antioxidant activity by probiotic Lactobacillus kimchicus DCY51T isolated from Korean kimchi

A straightforward synthesis of gold nanoparticles (AuNps) is achieved by novel probiotic Lactobacillus kimchicus DCY51T isolated from Korean kimchi via an intracellular membrane-bound mechanism. The bioreduction of HAuCl4 into AuNps was verified by ultraviolet-visible spectrophotometry at ∼540nm. AuNps were spherical with varying sizes of 5-30nm. AuNps maintained an average crystallite size of 13nm and demonstrated long-term stability in physiological buffer and biological media. Furthermore, the protective capping layer consisted of amino acid residues and surface-bound proteins rendered them non-toxic to murine macrophage (RAW264.7) and human colorectal adenocarcinoma (HT29) cell lines. Finally, biosynthesized AuNps served as superior free radical scavengers against 2,2-diphenyl-1-picrylhydrazyl (DPPH) in contrast to their corresponding gold salt. In short, this green synthesis is cost-effective and advantageous for the development of a new class of probiotics mediated and non-toxic carriers in targeted drug delivery systems, cancer diagnostic, photothermal therapy, biosensing, and medical imaging.

Cardamom fruits as a green resource for facile synthesis of gold and silver nanoparticles and their biological applications

Abstract Gold (FA-AuNps) and silver (FA-AgNps) nanoparticles were synthesized at room temperature by aqueous extract of dried fruits of Amomum villosum, also known as Fructus Amomi (cardamom), in order to confer antioxidant, catalytic, antimicrobial activities and treatment effect against breast cancer cells. Fruit extracts served as both reducing agents and stabilizers in lieu of chemical agents. Ultra-violet visible (UV-Vis) spectroscopy, field emission transmission electron microscopy (FE-TEM), energy-dispersive X-ray (EDX) spectroscopy, elemental mapping, X-ray powder diffraction (XRD), selected area electron diffraction (SAED), dynamic light scattering (DLS) and Fourier transform infrared (FTIR) spectroscopy were employed to characterize the biosynthesized nanoparticles. Both FA-AuNps and FA-AgNps exhibited free radical scavenging activity against 2,2-diphenyl-1-picrylhydrzyl (DPPH). Additionally, biosynthesized nanoparticles successfully reduced methylene blue, a well-known redox indicator. FA-AgNps showed zones of inhibition against pathogenic Staphylococcus aureus and Escherichia coli. Finally, the biological activities and cytotoxicity of nanoparticles were subsequently investigated in vitro. FA-AuNps demonstrated a potential cytotoxic agent against breast cancer cells as evaluated by MTT assay. The study highlights a rapid synthesis of FA-AuNps and FA-AgNps by dried Fructus Amomi aqueous extract and evaluates their potential biological applications on medical platforms. Graphical Abstract

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.

Stimulative Effect of Ginsenosides Rg5:Rk1 on Murine Osteoblastic MC3T3‐E1 Cells

Panax ginseng C.A. Meyer (P. ginseng), hereafter referred to as P. ginseng, is known to exert a wide range of pharmacological effects both in vitro and in vivo; however, few studies have investigated the effects of ginseng on bone metabolism. We therefore investigated the potential antiosteoporotic properties of ginseng on the growth and differentiation of murine MC3T3‐E1 cells. Rg5:Rk1 is a mixture of protopanaxadiol‐type ginsenosides, isolated from fresh P. ginseng root, via a repetitive steaming and drying process. In this study, we examined the stimulatory effects of Rg5:Rk1 on the differentiation and mineralization of MC3T3‐E1 cells. Undifferentiated cells were treated with a range of concentrations of Rg5:Rk1 (1–50 µg/mL), and cell viability was measured with the 3‐(4,5‐dimethyl‐thiazol‐2yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. Treatment with Rg5:Rk1 significantly increased cell viability in a dose‐dependent manner. To investigate the possible mechanisms by which Rg5:Rk1 affects the early differentiation phase of MC3T3‐E1 cells, the cells were treated with Rg5:Rk1 for 14–24 days before assessing the levels of multiple osteoblastic markers. The markers examined included alkaline phosphatase (ALP) activity type I collagen content (Coll‐I), calcium deposition (by Alizarin Red S staining), extracellular mRNA expression of bone morphogenetic protein‐2 (BMP‐2), and the level of Runt‐related transcription factor 2 (Runx2). Rg5:Rk1 treatment also increased the activities of proteins associated with osteoblast growth and differentiation in a dose‐dependent manner. Overall, we found that the Rg5:Rk1 mixture of ginsenosides improved the osteoblastic function of MC3T3‐E1 cells by increasing their proliferative capacity. This improvement is due to the action of Rg5:Rk1 on BMP‐2, which is mediated by Runx2‐dependent pathways. Copyright

Ginsenoside Rh1 induces mouse osteoblast growth and differentiation through the bone morphogenetic protein 2/runt-related gene 2 signalling pathway.

This study aimed to investigate the stimulative and pharmacological effects of ginsenoside Rh1 (hereinafter referred to as: Rh1) on differentiation and mineralization of osteoblast and its possible mechanism of action on the expression of bone morphogenetic protein 2 (BMP‐2)/Runt‐related gene 2 (Runx2) signalling pathways using mouse preosteoblastic MC3T3‐E1 cell line as in‐vitro model.

Biological synthesis of gold and silver chloride nanoparticles by Glycyrrhiza uralensis and in vitro applications

Abstract The current study highlights the rapid biosynthesis of gold nanoparticles (Gu–AuNps) and silver chloride nanoparticles (Gu–AgClNps) by aqueous root extract of Glycyrrhiza uralensis, a medicinal plant. G. uralensis has been reported for anticancer and hepatoprotective effects. The reduction of chloroauric acid and silver nitrate by the Glycyrrhiza root extract prompted the formation of Gu–AuNps and Gu–AgClNps within 4 and 40 min at 80 °C, respectively. The complete reaction did not require supplemental reducing and stabilizing agents, which demonstrated green synthesis. Field emission transmission electron microscopy (FE-TEM) revealed the spherical shape of Gu–AuNps and Gu–AgClNps. X-ray diffraction (XRD) showed face-centred cubic structure of Gu–AuNps and Gu–AgClNps with average crystallite size 12.25 nm and 8.01 nm, respectively. The biosynthesized Gu–AgClNps served as competent antimicrobial agent against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella enterica. Additionally, Gu–AuNps and Gu–AgClNps were analyzed for their catalytic ability to reduce methylene blue as model test pollutant. Likewise, both nanoparticles possessed free radical scavenging activity against 2,2-diphenyl-1-picrylhydrzyl (DPPH). Moreover, in vitro cytotoxicity in murine macrophage (RAW264.7) and human breast cancer (MCF7) cells were evaluated. Thus, the study proposes a green synthesis of Gu–AuNps and Gu–AgClNps by G. uralensis extract and in vitro biological applications.