scholarly journals Screening and Identification of an Anti-inflammatory and Anti-adipogenic Constituent from Ligularia taquetii Nakai

2020 ◽  
Vol 15 (1) ◽  
pp. 1934578X1989950
Author(s):  
Sungchan Jang ◽  
Min-Seon Kim ◽  
Taejin Park ◽  
Ji H. Sim ◽  
Seung-Young Kim

Ligularia taquetii (H. Lev. & Vaniot) Nakai has traditionally been used to treat inflammation and skin swelling in the Jeju Island, Korea. The objective of this study was to investigate the anti-inflammatory and anti-adipogenic effects of Ligularia taquetii ethanoic extract (LTE), in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and 3T3-L1 adipocytes. Lipopolysaccharide-induced inflammation was reduced by LTE in a concentration-dependent manner, via the nuclear factor-κB signaling pathway. Ligularia taquetii ethanoic extract (100 µg/mL) inhibited the LPS-induced production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS), by 60% and 100%, respectively. In comparison, 200 and 100 µg/mL LTE suppressed the LPS-stimulated production of prostaglandin-2 (PGE2) and cyclooxygenase-2 by 50% and 80%, respectively. Ligularia taquetii ethanoic extract also inhibited the secretion of interleukin-1β and interleukin-6 at 300 and 100 μg/mL by 15% and 30%, respectively. High-performance liquid chromatography-photodiode array analysis, combined with mass analysis, revealed chlorogenic acid (CGA) as the anti-inflammatory constituent of LTE. Conversely, 25, 50, 100, and 200 μg/mL LTE lowered the lipid accumulation by 6%, 8%, 25%, and 60%, respectively, while simultaneously increasing cell viability by 7%, 14%, 34%, and 78%. The anti-adipogenic effect of LTE at 100 µg/mL was equivalent to that of CGA at 50 µg/mL. However, LTE treatment promoted cell proliferation by about 30% compared to its CGA-treated counterpart. These results suggest the potential of LTE as a new resource in the discovery of anti-inflammatory and anti-obesity drugs.

1998 ◽  
Vol 274 (1) ◽  
pp. C245-C252 ◽  
Author(s):  
Junsuke Igarashi ◽  
Masashi Nishida ◽  
Shiro Hoshida ◽  
Nobushige Yamashita ◽  
Hiroaki Kosaka ◽  
...  

The effects of nitric oxide (NO) produced by cardiac inducible NO synthase (iNOS) on myocardial injury after oxidative stress were examined. Interleukin-1β induced cultured rat neonatal cardiac myocytes to express iNOS. After induction of iNOS,l-arginine enhanced NO production in a concentration-dependent manner. Glutathione peroxidase (GPX) activity in myocytes was attenuated by elevated iNOS activity and by an NO donor, S-nitroso- N-acetyl-penicillamine (SNAP). Although NO production by iNOS did not induce myocardial injury, NO augmented release of lactate dehydrogenase from myocyte cultures after addition of H2O2(0.1 mM, 1 h). Inhibition of iNOS with Nω-nitro-l-arginine methyl ester ameliorated the effects of NO-enhancing treatments on myocardial injury and GPX activity. SNAP augmented the myocardial injury induced by H2O2. Inhibition of GPX activity with antisense oligodeoxyribonucleotide for GPX mRNA increased myocardial injury by H2O2. Results suggest that the induction of cardiac iNOS promotes myocardial injury due to oxidative stress via inactivation of the intrinsic antioxidant enzyme, GPX.


2000 ◽  
Vol 68 (12) ◽  
pp. 7087-7093 ◽  
Author(s):  
Y.-H. Li ◽  
Z.-Q. Yan ◽  
J. Skov Jensen ◽  
K. Tullus ◽  
A. Brauner

ABSTRACT Chronic lung disease (CLD) of prematurity is an inflammatory disease with a multifactorial etiology. The importance ofUreaplasma urealyticum in the development of CLD is debated, and steroids produce some improvement in neonates with this disease. In the present study, the capability of U. urealyticum to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS), and activate nuclear factor κB (NF-κB) in vitro was characterized. The effect of NO on the growth of U. urealyticum was also investigated. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (≥4 × 107 color-changing units/ml) stimulated alveolar macrophages to produce NO in a dose- and time-dependent manner (P < 0.05). This effect was further enhanced by gamma interferon (100 IU/ml; P < 0.05) but was attenuated by budesonide and dexamethasone (10−4 to 10−6 M) (P < 0.05). The mRNA and protein levels of iNOS were also induced in response to U. urealyticum and inhibited by steroids.U. urealyticum antigen triggered NF-κB activation, a possible mechanism for the induced iNOS expression, which also was inhibited by steroids. NO induced by U. urealyticum caused a sixfold reduction of its own growth after infection for 10 h. Our findings imply that U. urealyticum may be an important factor in the development of CLD. The host defense response againstU. urealyticum infection may also be influenced by NO. The down-regulatory effect of steroids on NF-κB activation, iNOS expression, and NO production might partly explain the beneficial effect of steroids in neonates with CLD.


2003 ◽  
Vol 22 (2) ◽  
pp. 81-86 ◽  
Author(s):  
G. B. Yi ◽  
D. Mc Clendon ◽  
D. Desaiah ◽  
J. Goddard ◽  
A. Lister ◽  
...  

Massive, multiple fire ant, Solenopsis invicta, stings are often treated aggressively, particularly in the elderly, despite limited evidence of systemic toxicity due to the venom. Over 95% of the S. invicta venom is composed of piperidine alkaloid components, whose toxicity, if any, is unknown. To assess a possible pharmacological basis for systemic toxicity, an alkaloid-rich, protein-free methanol extract of the venom from whole ants was assayed for inhibitory activity on the following nitric oxide synthase (NOS) isoforms, rat cerebellar neuronal (n NOS), bovine recombinant endothelial (e NOS), and murine recombinant immunologic (i NOS). Cytosolic NOS activity was determined by measuring the conversion of [3H]arginine to [3H]citrulline in vitro. Rat n NOS activity was inhibited significantly and in a concentration-dependent manner by the alkaloid-rich venom extract. For n NOS, enzyme activity was inhibited by approximately 50% with 0.33 ± 0.06 μgg of this venom extract, and over 95% inhibition of the three isoforms, n NOS, e NOS, and i NOS, was found with doses of 60 μg in 60-μl reaction mixture. These results indicate that the alkaloid components of S. invicta venom can produce potent inhibition of all three major NOS isoforms. Isosolenopsin A ( cis-2-methyl-6-undecylpiperidine), a naturally occurring fire ant piperidine alkaloid, was synthesized and tested for inhibitory activity against the three NOS isoforms. Enzyme activities for n NOS and e NOS were over 95% inhibited with 1000 μM of isosolenopsin A, whereas the activity of i NOS was inhibited by only about 20% at the same concentration. The IC50 for each of three NOS isoforms was approximately 18 ± 3.9 μM for n NOS, 156 ± 10 μM for e NOS, and >1000 μM for i NOS, respectively. Kinetic studies showed isosolenopsin A inhibition to be noncompetitive with L-arginine ( Ki = 19 ± 2 μM). The potency of isosolenopsin A as an inhibitor of n NOS compares favorably with the inhibitory potency of widely used n NOS inhibitors. Inhibition of NOS isoforms by isosolenopsin A and structurally similar compounds may have toxicological significance with respect to adverse reactions to fire ant stings.


Author(s):  
In-Chul LEE ◽  
Jae-Sook LEE ◽  
Jeong-Hyun LEE ◽  
Yeona KIM ◽  
Wi-Young SO

Background: Kenya AA green coffee bean extracts were tested for natural ingredients used for anti-oxidative and anti-inflammatory purposes in cosmetic products Methods: Anti-oxidative activities were measured by total polyphenol, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and the 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Anti-inflammatory activities were evaluated via nitric oxide (NO) assays, and through quantification of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) protein expression by western blotting. Data analyses were performed using independent Student’s t-tests, with statistical significance set at P < 0.05. Results: Total polyphenol content of water and ethanol extract was 169.0 ± 3.1 mg and 300.34 ± 16.6 mg tannic acid/g dry weight, respectively. The DPPH and ABTS radical scavenging activities of all the extracts were significantly increased in a concentration-dependent manner. Kenya AA green coffee bean extracts were toxic at a concentration of 1,000 µg/mL in RAW 264.7 cells. Anti-inflammatory activity as determined by NO assay showed that lipopolysaccharide (LPS)-induced NO was significantly inhibited following treatment with Kenya AA green coffee bean extracts in a concentration-dependent manner. iNOS and COX-2 protein expression was also significantly inhibited following treatment. Conclusion: These results highlight the potential of Kenya AA green coffee bean extracts as a naturally active anti-inflammatory agent in cosmetic products.


2010 ◽  
Vol 38 (05) ◽  
pp. 973-983 ◽  
Author(s):  
Hee-Sung Chae ◽  
Ok-Hwa Kang ◽  
Jang-Gi Choi ◽  
You-Chang Oh ◽  
Young-Seob Lee ◽  
...  

To determine the anti-inflammatory and analgesic activities of methyl gallate (MG) isolated from Galla Rhois, MG was studied in vivo for its analgesic activities using the writhing response in mice. Anti-inflammatory activity of MG was evaluated for NO and IL-6 production in RAW 264.7 cells. MG inhibited LPS-induced NO and IL-6 production. Consistent with these observations, the protein and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were inhibited by MG. Moreover, MG suppressed the phosphorylation of ERK1/2 in LPS-induced RAW 264.7 cells in a dose-dependent manner. Taken together, the results of this study indicate that MG has anti-inflammatory effects.


2019 ◽  
Vol 20 (12) ◽  
pp. 2951 ◽  
Author(s):  
Fan Yao ◽  
Qiang Xue ◽  
Ke Li ◽  
Xinxin Cao ◽  
Liwei Sun ◽  
...  

We conducted this study for the first time to evaluate changes in the composition and contents of phenolic compounds and ginsenosides in ginseng shoot extracts (GSEs) prepared with different steaming times (2, 4, and 6 h) at 120 °C, as well as their antioxidant and anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages (RAW264.7 cells). The results show that total phenol and flavonoid contents were both significantly higher in steamed versus raw GSEs, and the same trend was found for 2,2′-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2′-azobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+) scavenging capacities. Among the 18 ginsenosides quantified using high-performance liquid chromatography (HPLC) with the aid of pure standards, polar ginsenosides were abundant in raw GSEs, whereas less-polar or rare ginsenosides appeared after steaming at 120 °C and increased with steaming time. Furthermore, steamed GSEs exhibited a greater ability to inhibit the production of inflammatory mediators and pro-inflammatory cytokines, such as nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in LPS-induced RAW264.7 cells at the same concentration. Relative expression levels of inducible nitric oxide synthase (iNOS), IL-6, TNF-α, and cyclooxygenase-2 (COX-2) mRNAs were attenuated by the GSEs, probably due to the enrichment of less-polar ginsenosides and enhanced antioxidant activity in steamed GSEs. These findings, combined with correlation analysis, showed that less-polar ginsenosides were major contributors to the inhibition of the overproduction of various inflammatory factors, while the inhibitory effects of total phenols and total flavonoids, and their antioxidant abilities, are also important.


Author(s):  
Pankaj Lohumi ◽  
Tirath Kumar ◽  
Lipi Nogai

Objective: The work is aimed to draw out the health beneficial properties of a weed (Parthenium hysterophorus Linn). The present work is organized to evaluate the antioxidant and anti-inflammatory activity of the ethanolic root extract of Parthenium hysterophorus Linn.Methods: In the present work the ethanolic extract was determined by using soxhlet apparatus. The antioxidant scavenging activity of this extract was determined by applying three different assay methods: (1) DPPH (1, 1-diphenyl-2-picryl hydrazyl) free radical method. (2) Nitric oxide scavenging assay and (3) Reducing power method. The anti-inflammatory activity was determined by in vivo method i.e. Carrageenan induced rat paw edema.Results: DPPH radical scavenging activities of the standard antioxidant and extracts were found to be increased in dose dependent manner. The percentage inhibition increases from 4.19% to 97.09% within the concentration range of 10µg/ml to 160µg/ml. Parthenium hysterophorus Linn effectively reduced the generation of nitric oxide radicals from sodium nitroprusside solution in a concentration dependent manner and percentage inhibition increases from 3.53% to 55.21% within the concentration range 10µg/ml to 160µg/ml. All the concentrations of extract significantly showed higher absorbance than the absorbance of control reaction (0.9705) in reducing power assay. A Higher absorbance indicates high reducing power due to the formation of reduced intermediates. Parthenium hysterophorus Linn showed highly significant anti-inflammatory activity at a dose of 200 mg/kg and the lesser effect was observed at 100 mg/kg with the percentage change in paw volume at 0 min, 30 min, 60 min, 90 min and 120 min.Conclusion: Thus, from above experimental observations, it can be stated that Parthenium is a natural antioxidant and bearing anti-inflammatory activity. 


2008 ◽  
Vol 36 (05) ◽  
pp. 913-928 ◽  
Author(s):  
Ok-Hwa Kang ◽  
Hee-Sung Chae ◽  
You-Chang Oh ◽  
Jang-Gi Choi ◽  
Young-Seob Lee ◽  
...  

The extract of Angelicae Dahuricae Radix has traditionally been used as an anti-noceptive remedy in China. In this study, the methanol extract of Angelicae Dahuricae Radix (MEAD) was evaluated to determine if it has anti-noceptive and anti-inflammatory action. The anti-nociceptive activities of MEAD were evaluated by determining the writhing response and sleeping time, as well as by a formalin test. In addition, the anti-inflammatory activities of MEAD were evaluated by a vascular permeability test as well as by measuring the carrageenan-induced paw edema and conducting a myeloperoxidase (MPO) assay. MEAD (600 and 1200 mg/kg) exhibited anti-inflammatory effects on acetic acid-induced vascular permeability, carrageenan-induced paw edema, and MPO activity. Moreover, the results of the formalin test, the acetic acid-induced writhing response and the pentobarbital-induced sleeping time indicated that MEAD had anti-nociceptive effects that occurred in a concentration-dependent manner. To determine the mechanism by which MEAD exerted its effects on the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) by treated murine macrophage RAW 264.7 cells was evaluated. Similar to the in vivo activities, both the iNOS expression and NO production were significantly suppressed by MEAD in a dose-dependent manner. Furthermore, MEAD inhibited the activating phosphorylation of ERK1/2. These results provide a scientific basis that explains the mechanism by which Angelicae Dahuricae Radix relieves inflammatory pain.


Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5351
Author(s):  
Jin-Kyu Kang ◽  
You-Chul Chung ◽  
Chang-Gu Hyun

Persistent inflammatory reactions promote mucosal damage and cause dysfunction, such as pain, swelling, seizures, and fever. Therefore, in this study, in order to explore the anti-inflammatory effect of 6-methylcoumarin (6-MC) and suggest its availability, macrophages were stimulated with lipopolysaccharide (LPS) to conduct an in vitro experiment. The effects of 6-MC on the production and levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α) and inflammatory mediators (nitric oxide (NO), prostaglandin E2 (PGE2)) in LPS-stimulated RAW 264.7 cells were examined. The results showed that 6-MC reduced the levels of NO and PGE2 without being cytotoxic. In addition, it was demonstrated that the increase in the expression of pro-inflammatory cytokines caused by LPS stimulation, was decreased in a concentration-dependent manner with 6-MC treatment. Moreover, Western blot results showed that the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which increased with LPS treatment, were decreased by 6-MC treatment. Mechanistic studies revealed that 6-MC reduced the phosphorylation of the mitogen-activated protein kinase (MAPK) family and IκBα in the MAPK and nuclear factor-kappa B (NF-κB) pathways, respectively. These results suggest that 6-MC is a potential therapeutic agent for inflammatory diseases that inhibits inflammation via the MAPK and NF-κB pathways.


2020 ◽  
Vol 15 (4) ◽  
pp. 1934578X2092048 ◽  
Author(s):  
Hyun-Kyu Kang ◽  
Chang-Gu Hyun

Recently, additional therapeutic potentials of classical antibiotics are gaining considerable attention. The discovery of penicillin in the 1920s had a major impact on the history of human health. Penicillin has been used for the treatment for fatal microbial infections in humans and has led to the discovery of several new antibiotics. d-(+)-Cycloserine (DCS) is an antibiotic isolated from Streptomyces orchidaceous and is used in conjunction with other drugs in the treatment of tuberculosis. However, there have been no studies on the anti-inflammatory effects of DCS in RAW 264.7 macrophage cell line. To investigate the anti-inflammatory effects of DCS, we examined the ability of DCS to inhibit the inflammatory responses in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in this study. Cell viability was analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were pretreated with various concentrations (2, 4, and 6 mM) of DCS, then treated with 1 μg/mL LPS to detect its anti-inflammatory effects. d-(+)-Cycloserine inhibited the production of nitric oxide (NO) in a concentration-dependent manner, and to some extent, inhibited the production of prostaglandin E2. Consistent with these findings, DCS suppressed the expression of pro-inflammatory cytokines such as interleukin (IL)-1β and IL-6. However, it had no effect on the expression of tumor necrosis factor-α. Western blot analysis demonstrated that DCS inhibited inducible nitric oxide synthase and suppressed cyclooxygenase type-2 (COX-2) expression. In addition, investigation of its effects on nuclear factor kappa B signaling showed that DCS inhibited phosphorylation of inhibitory kappa B-α (IκB-α) and increased intracellular IκB-α in a concentration-dependent manner. Furthermore, DCS inhibited the phosphorylation of LPS-induced extracellular signal-regulated kinase, however it did not affect phosphorylation of c-jun N-terminal kinase and p38. Further studies confirmed that the inhibition of phosphorylation of IκB-α was mediated through the inhibition of phosphoinositide 3-kinase/Akt (PI3K/Akt) pathway. To determine the applicability of DCS to the skin, cytotoxicity on HaCaT keratinocytes was measured following treatment with various concentrations (2, 4, 6, 8, and 10 mM) of DCS using MTT assay. These results suggest that DCS may be used as a potential drug for the treatment of inflammatory diseases.


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