Anti-Inflammatory Effect of Ginsenoside Rh<sub>2</sub>-Mix on Lipopolysaccharide-Stimulated RAW 264.7 Murine Macrophage Cells

Baatar, Delgerzul; Ṣiddiqi, Muḥammad Zubair; Im, Wan Taek; Khaliq, Nisar Ul; Hwang, Seong Gu

doi:10.1089/jmf.2018.4180

Cited by 37 publications

(23 citation statements)

References 46 publications

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“…The overproduction of NO is positively linked with excess iNOS expression. Thus, the release of NO was reduced as iNOS expression was blocked [42]. Accordingly, selective inhibitors of iNOS in inflammatory macrophages are considered to be effective therapeutics for inflammatory diseases [43].…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Activity of Populus deltoides Leaf Extract via Modulating NF-κB and p38/JNK Pathways

Jeong

Lee

2018

IJMS

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Populus deltoides, known as eastern cottonwood, has been commonly used as a medicinal plant. The aim of the present study was to investigate the mechanism underlying the anti-inflammatory activity of P. deltoides leaf extract (PLE). PLE effectively inhibited the expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, but not that of cyclooxygenase-2 (COX-2) and prostaglandin E2. Proinflammatory tumor necrosis factor alpha (TNF-α) levels were also reduced by the extract. PLE inhibited the phosphorylation of nuclear factor-kappa B (NF-κB) and inhibitor of Kappa Bα (IκBα), and blunted LPS-triggered enhanced nuclear translocation of NF-κB p65. In mitogen-activated protein kinase (MAPK) signaling, PLE effectively decreased the phosphorylation of p38 and c-Jun N-terminal protein kinase (JNK), but not of extracellular signal-regulated kinase 1/2 (ERK1/2). Taken together, these results suggest that anti-inflammatory activity of P. deltoides leaf extract might be driven by iNOS and NO inhibition mediated by modulation of the NF-κB and p38/JNK signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Activity of Populus deltoides Leaf Extract via Modulating NF-κB and p38/JNK Pathways

Jeong

Lee

2018

IJMS

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“…Natural products (especially secondary metabolites of herbal medicinal plants) play therapeutic roles in treating numerous human diseases. Among these natural products, the biologically active compounds of Panax ginseng are famous around the world because of their strong pharmacological effects against numerous human diseases [1][2][3][4][5][6]. Historically, to produce biologically active minor ginsenosides, the ginseng plant was treated with heat or steam and was commonly known as red or black ginseng.…”

Section: Introductionmentioning

confidence: 99%

“…More than 80% of ginseng extract is composed of the major ginsenosides Rb1, Rc Rd, Re, and Rg1, which are categorized as protopanaxadiol (PPD)-and protopanaxatriol (PPT)-type ginsenosides based on the structure of the aglycon [9,10]. However, these major ginsenosides can be transformed into pharmacologically active minor ginsenosides, such as Rg3(S), F2, C-K, CM-c1, and Rh2, by microorganisms or recombinant enzymes [4,[6][7][8]. Minor ginsenosides exhibit various antitumor, antistress, anti-inflammatory, anticancer, immunomodulatory, anti-atherosclerotic, anti-allergic, anti-osteoporosis, antiproliferation, antidiabetic, antigenotoxic, and antihypertensive properties [1][2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Exploration and Characterization of Novel Glycoside Hydrolases from the Whole Genome of Lactobacillus ginsenosidimutans and Enriched Production of Minor Ginsenoside Rg3(S) by a Recombinant Enzymatic Process

et al. 2020

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Background: Several studies have reported that ginsenoside Rg3(S) is effective in treating metastatic diseases, obesity, and various cancers, however, its presence in white ginseng cannot be estimated, and only a limited amount is present in red ginseng. Therefore, the use of recombinant glycosidases from a Generally Recognized As Safe (GRAS) host strain is a promising approach to enhance production of Rg3(S), which may improve nutritional activity, human health, and quality of life. Method: Lactobacillus ginsenosidimutans EMML 3041T, which was isolated from Korean fermented pickle (kimchi), presents ginsenoside-converting abilities. The strain was used to enrich the production of Rg3(S) by fermenting protopanaxadiol (PPD)-mix-type major ginsenosides (Rb1, Rb2, Rc, and Rd) in four different types of food-grade media (1, MRS; 2, Basel Food-Grade medium; 3, Basel Food-Grade medium-I, and 4, Basel Food-Grade medium-II). Due to its tendency to produce Rg3(S), the presence of glycoside hydrolase in Lactobacillus ginsenosidimutans was proposed, the whole genome was sequenced, and the probable glycoside hydrolase gene for ginsenoside conversion was cloned. Results: The L. ginsenosidimutans EMML 3041T strain was whole genome sequenced to identify the target genes. After genome sequencing, 12 sets of glycoside hydrolases were identified, of which seven sets (α,β-glucosidase and α,β-galactosidase) were cloned in Escherichia coli BL21 (DE3) using the pGEX4T-1 vector system. Among the sets of clones, only one clone (BglL.gin-952) showed ginsenoside-transforming abilities. The recombinant BglL.gin-952 comprised 952 amino acid residues and belonged to glycoside hydrolase family 3. The enzyme exhibited optimal activity at 55 °C and a pH of 7.5 and showed a promising conversion ability of major ginsenoside Rb1→Rd→Rg3(S). The recombinant enzyme (GST-BglL.gin-952) was used to mass produce Rg3(S) from major ginsenoside Rb1. Scale-up of production using 50 g of Rb1 resulted in 30 g of Rg3(S) with 74.3% chromatography purity. Conclusion: Our preliminary data demonstrated that this enzyme would be beneficial in the preparation of pharmacologically active minor ginsenoside Rg3(S) in the functional food and pharmaceutical industries.

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“…Ginsenosides, the main active components of Panax ginseng Mayer ( P. ginseng ), are mainly classified into protopanaxadiol (PPD; Rb1, Rb2, Rb3, Rc, Rd, Rg3, and Rh2)- and protopanaxatriol (PPT; Re, Rg1, Rg2, and Rh1)-type saponins [ 12 ]. They have been shown to have various pharmacological effects, including anticancer and anti-inflammatory effects, and beneficial effects against cardiovascular diseases and immunodeficiency [ 13 , 14 , 15 , 16 ]. Among them, Rg1 attenuates hepatocellular apoptosis and inflammatory response in ischemia–reperfusion injury mouse models [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Minor Ginsenoside Rg2 and Rh1 Attenuates LPS-Induced Acute Liver and Kidney Damages via Downregulating Activation of TLR4-STAT1 and Inflammatory Cytokine Production in Macrophages

Huynh

Baek

Sim

et al. 2020

IJMS

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Ginsenosides have been reported to have various biological effects, such as immune regulation and anticancer activity. In this study, we investigated the anti-inflammatory role of a combination of Rg2 and Rh1, which are minor ginsenosides, in lipopolysaccharide (LPS)-stimulated inflammation. In vitro experiments were performed using the RAW264.7 cell line, and an in vivo model of inflammation was established using LPS-treated ICR mice. We employed Griess assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, quantitative reverse transcriptase-polymerase chain reaction, western blotting, immunofluorescence staining, and hematoxylin and eosin staining to evaluate the effect of Rg2 and Rh1. We found that Rg2 and Rh1 significantly decreased LPS-induced major inflammatory mediator production, inducible-nitric oxide synthase expression, and nitric oxide production in macrophages. Moreover, Rg2 and Rh1 combination treatment inhibited the binding of LPS to toll-like receptor 4 (TLR4) on peritoneal macrophages. Therefore, the combination of ginsenoside Rg2 and Rh1 suppressed inflammation by abolishing the binding of LPS to TLR4, thereby inhibiting the TLR4-mediated signaling pathway. The combined ginsenoside synergistically blocked LPS-mediated PKCδ translocation to the plasma membrane, resulting in p38-STAT1 activation and NF-κB translocation. In addition, mRNA levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IFN-β, were significantly decreased by combined ginsenoside treatment. Notably, the 20 mg/kg ginsenoside treatment significantly reduced LPS-induced acute tissue inflammation levels in vivo, as indicated by the tissue histological damage scores and the levels of biochemical markers for liver and kidney function from mouse serum. These results suggest that the minor ginsenosides Rg2 and Rh1 may play a key role in prevention of LPS-induced acute inflammation and tissue damage.

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Anti-Inflammatory Effect of Ginsenoside Rh₂-Mix on Lipopolysaccharide-Stimulated RAW 264.7 Murine Macrophage Cells

Cited by 37 publications

References 46 publications

Anti-Inflammatory Activity of Populus deltoides Leaf Extract via Modulating NF-κB and p38/JNK Pathways

Anti-Inflammatory Activity of Populus deltoides Leaf Extract via Modulating NF-κB and p38/JNK Pathways

Exploration and Characterization of Novel Glycoside Hydrolases from the Whole Genome of Lactobacillus ginsenosidimutans and Enriched Production of Minor Ginsenoside Rg3(S) by a Recombinant Enzymatic Process

Minor Ginsenoside Rg2 and Rh1 Attenuates LPS-Induced Acute Liver and Kidney Damages via Downregulating Activation of TLR4-STAT1 and Inflammatory Cytokine Production in Macrophages

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Anti-Inflammatory Effect of Ginsenoside Rh2-Mix on Lipopolysaccharide-Stimulated RAW 264.7 Murine Macrophage Cells

Cited by 37 publications

References 46 publications

Anti-Inflammatory Activity of Populus deltoides Leaf Extract via Modulating NF-κB and p38/JNK Pathways

Anti-Inflammatory Activity of Populus deltoides Leaf Extract via Modulating NF-κB and p38/JNK Pathways

Exploration and Characterization of Novel Glycoside Hydrolases from the Whole Genome of Lactobacillus ginsenosidimutans and Enriched Production of Minor Ginsenoside Rg3(S) by a Recombinant Enzymatic Process

Minor Ginsenoside Rg2 and Rh1 Attenuates LPS-Induced Acute Liver and Kidney Damages via Downregulating Activation of TLR4-STAT1 and Inflammatory Cytokine Production in Macrophages

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Anti-Inflammatory Effect of Ginsenoside Rh₂-Mix on Lipopolysaccharide-Stimulated RAW 264.7 Murine Macrophage Cells