scholarly journals Sweroside Alleviated LPS-Induced Inflammation via SIRT1 Mediating NF-κB and FOXO1 Signaling Pathways in RAW264.7 Cells

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 872 ◽  
Author(s):  
Rui Wang ◽  
Zhaoyue Dong ◽  
Xiaozhong Lan ◽  
Zhihua Liao ◽  
Min Chen

Pterocephalus hookeri was used as a traditional Chinese medicine for the treatment of rheumatoid arthritis. Sweroside was a main iridoid isolated from P. hookeri. The present study aimed to investigate the anti-inflammatory effect mechanism of sweroside. In RAW264.7 cells induced by lipopolysaccharide (LPS), the abnormal proliferation, the NO content increase, and the downregulated Sirtuin1 (SIRT1) expression were observed. Sweroside could alleviate the inflammation by inhibiting cell proliferation through arresting the cell cycle at the G0/G1 phase, by suppressing pro-inflammatory cytokines and by promoting anti-inflammatory cytokines in LPS-induced RAW264.7 cells. Further mechanism research indicated that sweroside could activate the SIRT1, then suppress the nuclear factor-kappa B (NF-κB) and promote the Forkhead transcription factor O1 (FOXO1) signaling pathways. The present study indicated that sweroside may be the main anti-inflammatory constituent of P. hookeri and a promising candidate for anti-inflammation therapy.

2021 ◽  
Vol 43 (1) ◽  
pp. 93-106
Author(s):  
Orapin Insuan ◽  
Phornphimon Janchai ◽  
Benchaluk Thongchuai ◽  
Rujirek Chaiwongsa ◽  
Supaporn Khamchun ◽  
...  

Bromelain is a mixture of proteolytic enzymes derived from pineapple (Ananas comosus) fruit and stem possessing several beneficial properties, particularly anti-inflammatory activity. However, the molecular mechanisms underlying the anti-inflammatory effects of bromelain are unclear. This study investigated the anti-inflammatory effects and inhibitory molecular mechanisms of crude and purified rhizome bromelains on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells. RAW264.7 cells were pre-treated with various concentrations of crude bromelain (CB) or purified bromelain (PB), and then treated with LPS. The production levels of pro-inflammatory cytokines and mediators, including nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)-α were determined by Griess and ELISA assays. The expressions of inducible nitric oxide synthetase (iNOS), cyclooxygenase (COX)-2, nuclear factor kappa B (NF-κB), and mitogen-activated protein kinases (MAPKs)-signaling pathway-related proteins were examined by western blot analysis. The pre-treatment of bromelain dose-dependently reduced LPS-induced pro-inflammatory cytokines and mediators, which correlated with downregulation of iNOS and COX-2 expressions. The inhibitory potency of PB was stronger than that of CB. PB also suppressed phosphorylated NF-κB (p65), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha, extracellular signal-regulated kinases, c-Jun amino-terminal kinases, and p38 proteins in LPS-treated cells. PB then exhibited potent anti-inflammatory effects on LPS-induced inflammatory responses in RAW264.7 cells by inhibiting the NF-κB and MAPKs-signaling pathways.


2021 ◽  
Vol 22 (2) ◽  
pp. 762
Author(s):  
Gi Ho Lee ◽  
Ji Yeon Kim ◽  
Sun Woo Jin ◽  
Thi Hoa Pham ◽  
Jin Song Park ◽  
...  

Inflammatory diseases are caused by excessive inflammation from pro-inflammatory mediators and cytokines produced by macrophages. The Nrf2 signaling pathway protects against inflammatory diseases by inhibiting excessive inflammation via the regulation of antioxidant enzymes, including HO-1 and NQO1. We investigated the anti-inflammatory effect of impressic acid (IPA) isolated from Acanthopanax koreanum on the lipopolysaccharide (LPS)-induced inflammation and the underlying molecular mechanisms in RAW264.7 cells. IPA attenuated the LPS-induced production of pro-inflammatory cytokines and reactive oxygen species, and the activation of the NF-κB signaling pathway. IPA also increased the protein levels of Nrf2, HO-1, and NQO1 by phosphorylating CaMKKβ, AMPK, and GSK3β. Furthermore, ML385, an Nrf2 inhibitor, reversed the inhibitory effect of IPA on LPS-induced production of pro-inflammatory cytokines in RAW264.7 cells. Therefore, IPA exerts an anti-inflammatory effect via the AMPK/GSK3β/Nrf2 signaling pathway in macrophages. Taken together, the findings suggest that IPA has preventive potential for inflammation-related diseases.


2007 ◽  
Vol 112 (11) ◽  
pp. 543-555 ◽  
Author(s):  
Kenneth R. Wilund

Engaging in regular physical activity reduces the risk of developing CVD (cardiovascular disease), but it is not certain to what degree this may be due to the anti-inflammatory effects of exercise. Following acute exercise, there is a transient increase in circulating levels of anti-inflammatory cytokines, whereas chronic exercise reduces basal levels of pro-inflammatory cytokines. Exercise training also induces the expression of antioxidant and anti-inflammatory mediators in the vascular wall that may directly inhibit the development of atherosclerosis. Limited studies in humans and more comprehensive assessments in animal models have confirmed that exercise is atheroprotective and helped identify a number of the mechanisms to explain these effects. This review explores the relationship between systemic and vascular wall inflammation and the role that the anti-inflammatory effects of exercise have on the development and progression of CVD.


2018 ◽  
Vol 11 (4) ◽  
pp. 1755-1761
Author(s):  
Eun-Jin Yang ◽  
Sungchan Jang ◽  
Kwang Hee Hyun ◽  
Eun-Young Jung ◽  
Seung-Young Kim ◽  
...  

The anti-inflammatory activity and non-toxicity of Sonchus oleraceus extract (J6) were tested by measuring its effect on the levels of nitric oxide (NO), prostaglandin E2 (PGE2), and the pro-inflammatory cytokines, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We treated the RAW264.7 cells with various concentrations (50, 100, or 200 μg/mL) of J6. Our results showed that J6 inhibited the production of NO, PGE2, and pro-inflammatory cytokines in a concentration-dependent manner, without compromising cell viability. In addition, we provided supporting evidence that the inhibitory activity of J6 on the production of NO and PGE2 occurred via the downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. Our findings suggest that J6 is a new source for anti-inflammatory drugs and ingredients for healthcare products that include functional cosmetics.


2021 ◽  
Vol 11 ◽  
Author(s):  
Mariaelena Filippelli ◽  
Giuseppe Campagna ◽  
Pasquale Vito ◽  
Tiziana Zotti ◽  
Luca Ventre ◽  
...  

Purpose: To determine the levels of pro-inflammatory cytokines and soluble mediators (TNF-α, IL6, IL2, and PDGF-AB) in 28 vitreous biopsies taken from patients with proliferative diabetic retinopathy (PDR) and treated with increasing doses of curcumin (0. 5 and 1 μM), with or without homotaurine (100 μM) and vitamin D3 (50 nM).Materials and Methods: ELISA tests were performed on the supernatants from 28 vitreous biopsies that were incubated with bioactive molecules at 37°C for 20 h. The concentration of the soluble mediators was calculated from a calibration curve and expressed in pg/mL. Shapiro-Wilk test was used to verify the normality of distribution of the residuals. Continuous variables among groups were compared using the General Linear Model (GLM). Homoscedasticity was verified using Levene and Brown-Forsythe tests. Post-hoc analysis was also performed with the Tukey test. A p ≤ 0.05 was considered statistically significant.Results: The post-hoc analysis revealed statistically detectable changes in the concentrations of TNF-α, IL2, and PDGF-AB in response to the treatment with curcumin, homotaurine, and vitamin D3. Specifically, the p-values for between group comparisons are as follows: TNF-α: (untreated vs. curcumin 0.5 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.008, (curcumin 0.5 μM vs. curcumin 0.5 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.0004, (curcumin 0.5 μM vs. curcumin 1 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.02, (curcumin 1 μM vs. curcumin 0.5 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.025, and (homotaurine 100 μM + vitamin D3 50 nM vs. curcumin 0.5 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.009; IL2: (untreated vs. curcumin 0.5 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.0023, and (curcumin 0.5 μM vs. curcumin 0.5 μM+ homotaurine 100 μM + vitamin D3 50 nM) p = 0.0028; PDGF-AB: (untreated vs. curcumin 0.5 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.04, (untreated vs. curcumin 1 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.0006, (curcumin 0.5 μM vs. curcumin 1 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.006, and (homotaurine 100 μM + vitamin D3 50 nM vs. curcumin 1 μM + homotaurine 100 μM + vitamin D3 50 nM) p = 0.022. IL6 levels were not significantly affected by any treatment.Conclusions: Pro-inflammatory cytokines are associated with inflammation and angiogenesis, although there is a discrete variability in the doses of the mediators investigated among the different vitreous samples. Curcumin, homotaurine, and vitamin D3 individually have a slightly appreciable anti-inflammatory effect. However, when used in combination, these substances are able to modify the average levels of the soluble mediators of inflammation and retinal damage. Multi-target treatment may provide a therapeutic strategy for diabetic retinopathy in the future.Clinical Trial Registration : The trial was registered at clinical trials.gov as NCT04378972 on 06 May 2020 (“retrospectively registered”) https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid = S0009UI8&selectaction = Edit&uid = U0003RKC&ts = 2&cx = dstm4o.


Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2802
Author(s):  
So Ra Kim ◽  
Eun Jung Park ◽  
Theodomir Dusabimana ◽  
Jihyun Je ◽  
Kyuho Jeong ◽  
...  

Endotoxin-induced acute liver injury is mediated by an excessive inflammatory response, hepatocellular oxidative stress, and apoptosis. Traditional medicinal plants have been used to treat various disorders. Platycodon grandifloras (PG) has been shown to be beneficial in relieving cough and asthma and to have anti-tumor, anti-inflammatory, anti-diabetic activities. The pharmacological action of PG is mainly due to saponins, flavonoids, phenolic, and other compounds. However, raw PG exhibits some side effects at high doses. Here, we extracted raw PG with varying fermentation methods and examined its anti-inflammatory effect and associated signaling kinases in Raw264.7 cells. Then, we investigated the effect of fermented black PG (FBPG) on endotoxin-induced liver injury. Mice were administered FBPG orally at 1 h before the lipopolysaccharide and D-galactosamine (LPS/GalN) injection and sacrificed after 5 h. Black PG (BPG) and FBPG showed a significant reduction in pro-inflammatory cytokines and extracellular nitric oxide (NO); p-38 and ERK signaling was involved in reducing inducible NO synthase in Raw264.7 cells. Consistently, FBPG attenuates LPS/GalN-induced liver injury; plasma ALT and AST, hepatic necrosis, pro-inflammatory cytokines, apoptosis, and lipid peroxidation were all reduced. In conclusion, PG extracts, particularly FBPG, play anti-inflammatory, antioxidant, and anti-apoptotic roles, alleviating endotoxin-induced acute liver injury. Processing raw PG into FBPG extract may be clinically useful by improving the pharmacologically active ingredients and reducing the required dosage.


Author(s):  
Nithya Sermugapandian ◽  
Rubini R ◽  
Martina V

 Objective: In this study, we evaluated the anti-inflammatory effect of Elettaria cardamom oil and the underlying mechanism using in vivo models of inflammation.Methods: Male Sprague–Dawley rats, 4-6 weeks old, weighing 120-130 gms are used for the study. The anti-inflammatory study of E. cardamom oil was studied by injecting 0.1 ml of 1% carrageenan to the subplantar region of the right hind paw of rats. The development of acute inflammation was measured at the end of every 1st, 2nd, 3rd, 4th, 5th, and 6th h using plethysmometer.Results: As results from the above study, E. cardamom oil at a dose of 0.175 ml/kg was less significant than that of E. cardamom oil at a dose of 0.280 ml/kg when given orally. A p<0.05 shows a significant decrease in paw edema. It also reduced the levels of pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL) 1, and IL 6 levels in the serum. The histopathology results also showed a significant reduction of congested blood vessels with no marked impression for inflammation.Conclusion: E. cardamom oil possesses anti-inflammatory activity in dose-dependent manner as they inhibit the levels of pro-inflammatory cytokines.


2017 ◽  
Vol 15 (3) ◽  
pp. 143-151 ◽  
Author(s):  
Rui Fei ◽  
Huan Zhang ◽  
Sheng Zhong ◽  
Baigong Xue ◽  
Yuanqi Gao ◽  
...  

Serine protease inhibitors (serpins) are a superfamily of proteins involved in many important biological processes, including inflammation. Serpins dysfunction-related diseases are mainly treated by augmentation therapy using serpins purified from human plasma. Pnserpin from hyperthermophilic archaeon Pyrobaculum neutrophilum showed protease inhibition activity and high stability. In this study, we examined the anti-inflammatory activity of Pnserpin using xylene-induced acute inflammatory model of mouse ear swelling and lipopolysaccharide (LPS)-induced murine RAW 264.7 macrophages cellular model. The inhibition of mouse ear swelling and the production of pro-inflammatory cytokines in mouse serum or in macrophages cell were used to evaluate the anti-inflammatory effect of Pnserpin. Our results showed that Pnserpin could inhibit the xylene-induced mouse ear swelling and suppress the production of pro-inflammatory cytokines in mouse serum and in LPS-induced RAW264.7 cells. This study indicated that Pnserpin might have anti-inflammatory effect in vivo and in vitro.


2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110209
Author(s):  
Yun Sil Kang ◽  
You Chul Chung ◽  
Jung No Lee ◽  
Bong Seok Kim ◽  
Chang-Gu Hyun

Coumarin derivatives, such as esculetin, have various physiological functions, including antioxidant, anti-inflammatory, antibacterial, antiviral, and anti-cancer. 6,7-Dihydroxy-4-methylcoumarin (6,7-DH-4MC) is a derivative of esculetin, and its anti-inflammatory effect and mechanism in macrophages have not been studied. In this study, the anti-inflammatory activity of 6,7-DH-4MC was evaluated by measuring the expression of inflammatory factors (NO and PGE2) and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in LPS-stimulated RAW 264.7 macrophages. The results revealed that 6,7-DH-4MC significantly reduced NO levels and PGE2 expression without inducing cytotoxicity; it was confirmed that the inhibition of NO and PGE2 expression was related to iNOS and COX-2 downregulation in response to 6,7-DH-4MC treatment. Moreover, 6,7-DH-4MC decreased the levels of pro-inflammatory cytokines, such as IL-1β and IL-6, in a dose-dependent manner. Mechanistic studies revealed reduced phosphorylation of ERK and p38-MAPK upon 6,7-DH-4MC treatment. Furthermore, the degradation of IκB-α and phosphorylation of NF-κB in cells treated with LPS were interrupted by 6,7-DH-4MC treatment. These results suggest that 6,7-DH-4MC is a potential therapeutic agent for inflammatory diseases. To the best of our knowledge, this is the first report demonstrating the anti-inflammatory effects of 6,7-DH-4MC in RAW 264.7 cells via MAPK and NF-κB signaling pathways.


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