scholarly journals Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

2021 ◽  
Vol 14 (12) ◽  
pp. 1252
Author(s):  
You-Cheng Lin ◽  
Chi-Chien Lin ◽  
Yi-Chia Chu ◽  
Chung-Wei Fu ◽  
Jyh-Horng Sheu

Chemical investigation of the soft coral Cespitularia sp. led to the discovery of twelve new verticillane-type diterpenes and norditerpenes: cespitulins H–O (1–8), one cyclic diterpenoidal amide cespitulactam L (9), norditerpenes cespitulin P (10), cespitulins Q and R (11 and 12), four new sesquiterpenes: cespilins A–C (13–15) and cespitulolide (16), along with twelve known metabolites. The structures of these metabolites were established by extensive spectroscopic analyses, including 2D NMR experiments. Anti-inflammatory effects of the isolated compounds were studied by evaluating the suppression of pro-inflammatory protein tumor necrosis factor-α (TNF-α) and nitric oxide (NO) overproduction, and the inhibition of the gene expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide-induced dendritic cells. A number of these metabolites were found to exhibit promising anti-inflammatory activities.


Foods ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 582 ◽  
Author(s):  
Yuan ◽  
Zhang ◽  
Shen ◽  
Jia ◽  
Xie

Phytosterols, found in many commonly consumed foods, exhibit a broad range of physiological activities including anti-inflammatory effects. In this study, the anti-inflammatory effects of ergosterol, β-sitosterol, stigmasterol, campesterol, and ergosterol acetate were investigated in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Results showed that all phytosterol compounds alleviated the inflammatory reaction in LPS-induced macrophage models; cell phagocytosis, nitric oxide (NO) production, release of tumor necrosis factor-α (TNF-α), and expression and activity of pro-inflammatory mediator cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and phosphorylated extracellular signal-regulated protein kinase (p-ERK) were all inhibited. The anti-inflammatory activity of β-sitosterol was higher than stigmasterol and campesterol, which suggests that phytosterols without a double bond on C-22 and with ethyl on C-24 were more effective. However, inconsistent results were observed upon comparison of ergosterol and ergosterol acetate (hydroxy or ester group on C-3), which suggest that additional research is still needed to ascertain the contribution of structure to their anti-inflammatory effects.


Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7642
Author(s):  
Wonmin Ko ◽  
Zhiming Liu ◽  
Kwan-Woo Kim ◽  
Linsha Dong ◽  
Hwan Lee ◽  
...  

We previously investigated the methanolic extract of Morus alba bark and characterized 11 compounds from the extract: kuwanon G (1), kuwanon E (2), kuwanon T (3), sanggenon A (4), sanggenon M (5), sanggenol A (6), mulberofuran B (7), mulberofuran G (8), moracin M (9), moracin O (10), and norartocarpanone (11). Herein, we investigated the anti-inflammatory effects of these compounds on microglial cells (BV2) and macrophages (RAW264.7). Among them, 3 and 4 markedly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide in these cells, suggesting the anti-inflammatory properties of these two compounds. These compounds inhibited the production of prostaglandin E2, interleukin-6, and tumor necrosis factor-α, and the expression of inducible nitric oxide synthase and cyclooxygenase-2 following LPS stimulation. Pretreatment with 3 and 4 inhibited the activation of the nuclear factor kappa B signaling pathway in both cell types. The compounds also induced the expression of heme oxygenase (HO)-1 through the activation of nuclear factor erythroid 2-related factor 2. Suppressing the activity of HO-1 reversed the anti-inflammatory effects caused by pretreatment with 3 and 4, suggesting that the anti-inflammatory effects were regulated by HO-1. Taken together, 3 and 4 are potential candidates for developing therapeutic and preventive agents for inflammatory diseases.


Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 871
Author(s):  
Inah Gu ◽  
Cindi Brownmiller ◽  
Nathan B. Stebbins ◽  
Andy Mauromoustakos ◽  
Luke Howard ◽  
...  

Berries are a rich source of phytochemicals, especially phenolics well known for protective activity against many chronic diseases. Berries also contain a complex mixture of volatile compounds that are responsible for the unique aromas of berries. However, there is very limited information on the composition and potential health benefits of berry volatiles. In this study, we isolated phenolic and volatile fractions from six common berries and characterized them by HPLC/HPLC-MS and GC/GC-MS, respectively. Berry phenolic and volatile fractions were evaluated for an anti-inflammatory effect using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells by measuring levels of pro-inflammatory cytokines and the nuclear factor-kappa B (NF-κB) signaling pathway. Results showed that LPS-induced excessive production of nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which were inhibited by berry phenolic and volatile extracts. Moreover, berry phenolic and volatile extracts reduced the nuclear translocation of NF-κB by blocking the phosphorylation of p65 and degradation of IκBα. These findings showed that berry volatiles from six berries had comparable anti-inflammatory effects to berry phenolics through the suppression of pro-inflammatory mediators and cytokines expression via NF-κB down-regulation, despite being present in the fruit at a lower concentration.


Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2367 ◽  
Author(s):  
Chi-Su Yoon ◽  
Dong-Cheol Kim ◽  
Jin-Soo Park ◽  
Kwan-Woo Kim ◽  
Youn-Chul Kim ◽  
...  

Nardostachys jatamansi contains various types of sesquiterpenoids that may play an important role in the potency of plant’s anti-inflammatory effects, depending on their structure. In this study, five new sesquiterpenoids, namely kanshone L (1), kanshone M (2), 7-methoxydesoxo-narchinol (3), kanshone N (4), and nardosdaucanol (5), were isolated along with four known terpenoids (kanshone D (6), nardosinanone G (7), narchinol A (8), and nardoaristolone B (9)) from the rhizomes and roots of Nardostachys jatamansi. Their structures were determined by analyzing 1D and 2D NMR and MS data. Among the nine sesquiterpenoids, compounds 3, 4, and 8 were shown to possess dose-dependent inhibitory effects against lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in BV2 microglial cells. Furthermore, compounds 3, 4, and 8 exhibited anti-neuroinflammatory effects by inhibiting the production of pro-inflammatory mediators, including prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) proteins, as well as pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-12 and tumor necrosis factor-α (TNF-α), in LPS-stimulated BV2 microglial cells. Moreover, these compounds were shown to inhibit the activation of the NF-κB signaling pathway in LPS-stimulated BV2 microglial cells by suppressing the phosphorylation of IκB-α and blocking NF-κB translocation. In conclusion, five new and four known sesquiterpenoids were isolated from Nardostachys jatamansi, and compounds 3, 4, and 8 exhibited anti-neuroinflammatory effects in LPS-stimulated BV2 microglial cells through inhibiting of NF-κB signaling pathway.


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.


2021 ◽  
Author(s):  
Orlando Vieira Sousa ◽  
Guilherme C. Gonçalves ◽  
Lucas S. Queiroz ◽  
Everton A. Ferreira ◽  
Bruna C. S. Santos ◽  
...  

Abstract Centaurea benedicta L., commonly known as “cardo santo,” is used as a tonic, antidepressant, anti-inflammatory, antibacterial, and antiseptic in traditional medicine. This study evaluated the topical anti-inflammatory potential of an extract (ECB) and cnicin (CNI) from C. benedicta leaves in a mouse model. Activity was assessed using the ear edema method with croton oil, phenol, capsaicin, and histamine as phlogistic agents. Myeloperoxidase (MPO), N-acetyl-β-D-glucosaminidase (NAG), nitric oxide (NO), t umor necrosis factor α (TNF-α), interleukin 6 (IL-6), and histopathology were assessed as markers of edema/inflammation. Interaction profiles between CNI and cyclooxygenase-1 and -2, induced nitric oxide synthase, and glucocorticoid receptor were examined with molecular docking. Twenty-four h after induction of inflammation, ECB and CNI treatments decreased the thickness and weight of ears by 39.59%– 94.72%. MPO, NAG, NO, TNF-α, and IL-6 levels were also reduced. Histopathological, treatments reduced edema thickness, leukocytes, and vasodilation. Inflammation induced by phenol and histamine was inhibited by ECB and CNI, and ECB suppressed capsaicin-induced inflammation. CNI interacts with cyclooxygenase-1 and nitric oxide synthase through conventional hydrogen bonds, indicating inhibition of these enzymes. ECB and its compound cnicin reduce chemically-induced inflammation in mice suggesting new possibilities for the treatment of diseases associated with dermal inflammatory processes.


Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3093 ◽  
Author(s):  
Jingyi Hou ◽  
Yu Gu ◽  
Shuai Zhao ◽  
Mengqi Huo ◽  
Shifeng Wang ◽  
...  

Aurantio-obtusin, an anthraquinone compound, isolated from dried seeds of Cassia obtusifolia L. (syn. Senna obtusifolia; Fabaceae) and Cassia tora L. (syn. Senna tora). Although the biological activities of Semen Cassiae have been reported, the anti-inflammatory mechanism of aurantio-obtusin, its main compound, on RAW264.7 cells, remained unknown. We investigated the anti-inflammatory effect of aurantio-obtusin on lipopolysaccharide- (LPS)-induced RAW264.7 cells in vitro and elucidated the possible underlying molecular mechanisms. Nitric oxide production (NO) and prostaglandin E2 (PGE2) were measured by the Griess colorimetric method and enzyme-linked immunosorbent assay (ELISA), respectively. Protein expression levels of cyclooxygenase 2 (COX-2) were monitored by cell-based ELISA. Interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) synthesis were analyzed using ELISA. The mRNA expression of nitric oxide synthase (iNOS), COX-2, and the critical pro-inflammatory cytokines (IL-6 and TNF-α) were detected by quantitative real-time PCR. Aurantio-obtusin significantly decreased the production of NO, PGE2, and inhibited the protein expression of COX-2, TNF-α and IL-6, which were similar to those gene expression of iNOS, COX-2, TNF-α and IL-6 (p < 0.01). Consistent with the pro-inflammatory gene expression, the Aurantio-obtusin efficiently reduced the LPS-induced activation of nuclear factor-κB in RAW264.7 cells. These results suggested that aurantio-obtusin may function as a therapeutic agent and can be considered in the further development of treatments for a variety of inflammatory diseases. Further studies may provide scientific evidence for the use of aurantio-obstusin as a new therapeutic agent for inflammation-related diseases.


Marine Drugs ◽  
2020 ◽  
Vol 18 (6) ◽  
pp. 283
Author(s):  
M. Cecilia Montero ◽  
Miguel del Campo ◽  
M. Bono ◽  
M. Valeska Simon ◽  
Julia Guerrero ◽  
...  

(1) Background: Neosaxitoxin (NeoSTX) has been used as a local anesthetic, but its anti-inflammatory effects have not been well defined. In the present study, we investigate the effects of NeoSTX on lipopolysaccharide (LPS)-activated macrophages. (2) Methods: Raw 264.7 and equine PBMC cells were incubated with or without 100 ng/mL LPS in the presence or absence of NeoSTX (1µM). The expression of inflammatory mediators was assessed: nitric oxide (NO) content using the Griess assay, TNF-α content using the ELISA assay, and mRNA of inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) using a real-time polymerase chain reaction. (3) Results: NeoSTX (1 μM) significantly inhibited the release of NO, TNF-α, and expression of iNOS, IL-1β, and TNF-α in LPS-activated macrophages of both species studied. Furthermore, our study shows that the LPS-induced release of inflammatory mediators was suppressed by NeoSTX. Additionally, NeoSTX deactivated polarized macrophages to M1 by LPS without compromising its polarization towards M2. (4) Conclusions: NeoSTX inhibits LPS-induced release of inflammatory mediators from macrophages, and these effects may be mediated by the blockade of voltage-gated sodium channels (VGSC).


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