scholarly journals Pulsed Electromagnetic Field Inhibits Synovitis via Enhancing the Efferocytosis of Macrophages

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Junjie Ouyang ◽  
Bin Zhang ◽  
Liang Kuang ◽  
Peng Yang ◽  
Xiaolan Du ◽  
...  

Synovitis plays an important role in the pathogenesis of arthritis, which is closely related to the joint swell and pain of patients. The purpose of this study was to investigate the anti-inflammatory effects of pulsed electromagnetic fields (PEMF) on synovitis and its underlying mechanisms. Destabilization of the medial meniscus (DMM) model and air pouch inflammation model were established to induce synovitis in C57BL/6 mice. The mice were then treated by PEMF (pulse waveform, 1.5 mT, 75 Hz, 10% duty cycle). The synovitis scores as well as the levels of IL-1β and TNF-α suggested that PEMF reduced the severity of synovitis in vivo. Moreover, the proportion of neutrophils in the synovial-like layer was decreased, while the proportion of macrophages increased after PEMF treatment. In addition, the phagocytosis of apoptotic neutrophils by macrophages (efferocytosis) was enhanced by PEMF. Furthermore, the data from western blot assay showed that the phosphorylation of P38 was inhibited by PEMF. In conclusion, our current data show that PEMF noninvasively exhibits the anti-inflammatory effect on synovitis via upregulation of the efferocytosis in macrophages, which may be involved in the phosphorylation of P38.

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3053
Author(s):  
Anh Thu Ha ◽  
Mi-Yeon Kim ◽  
Jae Youl Cho

Barringtonia augusta methanol extract (Ba-ME) is a folk medicine found in the wetlands of Thailand that acts through an anti-inflammatory mechanism that is not understood fully. Here, we examine how the methanol extract of Barringtonia augusta (B. augusta) can suppress the activator protein 1 (AP-1) signaling pathway and study the activities of Ba-ME in the lipopolysaccharide (LPS)-treated RAW264.7 macrophage cell line and an LPS-induced peritonitis mouse model. Non-toxic concentrations of Ba-ME downregulated the mRNA expression of cytokines, such as cyclooxygenase and chemokine ligand 12, in LPS-stimulated RAW264.7 cells. Transfection experiments with the AP-1-Luc construct, HEK293T cells, and luciferase assays were used to assess whether Ba-ME suppressed the AP-1 functional activation. A Western blot assay confirmed that C-Jun N-terminal kinase is a direct pharmacological target of Ba-ME action. The anti-inflammatory effect of Ba-ME, which functions by β-activated kinase 1 (TAK1) inhibition, was confirmed by using an overexpression strategy and a cellular thermal shift assay. In vivo experiments in a mouse model of LPS-induced peritonitis showed the anti-inflammatory effect of Ba-ME on LPS-stimulated macrophages and acute inflammatory mouse models. We conclude that Ba-ME is a promising anti-inflammatory drug targeting TAK1 in the AP-1 pathway.


Author(s):  
Chongxu Zhang ◽  
Runxia Tian ◽  
Emilee M Dreifus ◽  
Gregory Holt ◽  
Renzhi Cai ◽  
...  

AbstractGrowth hormone releasing hormone (GHRH) is a potent stimulator of GH secretion from the pituitary gland. Although GHRH is essential for the growth of immune cells, the regulatory effects of its antagonist in granulomatous disease remains unknown. Here, we report expression of GHRH receptor (R) in human tissue with sarcoidosis granuloma and demonstrate the anti-inflammatory effects of MIA602 (a GHRH antagonist) in two in vitro human granuloma models and an in vivo granuloma model. MIA602 decreases levels of IL2, IL12, and IL17A in in vitro granuloma model.We show further that the anti-inflammatory effect of MIA602 appears to be mediated by reduction in CD45++CD68+ cells in granulomatous tissue and upregulation in PD-1 expression in macrophages.In analysis of expression of proteins involved in the mitochondrial stage of apoptosis, we show that MIA602 increases the levels of caspase 3, BCL-xL/BAK dimer, and MCl-1/Bak dimer in granuloma. These findings indicate that MIA602 may not induce apoptosis.The clinical relevance of our findings further suggest that HGRH-R is potentially a target for treatment of granulomatous disease and MIA602 possibly a novel therapeutic agent for sarcoidosis.


2017 ◽  
Vol 16 (10) ◽  
pp. 2403-2410
Author(s):  
Haoran Ma ◽  
Fuqian Wang ◽  
Jie Jiang ◽  
Lu Cheng ◽  
Hong Zhang ◽  
...  

Purpose: To evaluate the anti-inflammatory activity of Liquidambar formosana  Hance infructescence (Liquidambaris fructus, ELF) in vivo, and clarify its underlying mechanisms. Methods: The in vivo anti-inflammatory activity of ELF was examined by xylene-induced ear swelling test in mice as well as carrageenan-induced paw edema method in rats. The levels of inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10) in serum were measured by enzyme-linked immunosorbent assay (ELISA), while the expressions of COX-2, iNOS and NF-κB p65 in paw tissue of rats were evaluated by western blot.Results: After ELF treatment, the levels of TNF-α (p < 0.001), IL-1β (p < 0.001) and IL-6 (p < 0.001) in serum decreased and the levels of anti-inflammatory cytokine IL-10 increased (p < 0.01). In addition, ELF treatment resulted in decrease of COX-2 (p < 0.01), iNOS (p < 0.01) and NF-κB p65 (p < 0.01) expressions in Wistar rats.Conclusion: The results reveal that ELF possesses significant anti-inflammatory effect in vivo. The anti-inflammatory activity is associated with the levels of TNF-α, IL-1β, IL-6 and IL-10 in serum. Furthermore, the suppression of NF-κB p65, iNOS and COX-2 is linked to its anti-inflammatory effect. These results provide a rationale for the use of Liquidambaris fructus in inflammatory disease in traditional medicine.Keywords: Anti-inflammatory activity, Liquidambaris fructus, Cytokines, Ear swelling test, Paw edema


Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2529
Author(s):  
Haeyeop Kim ◽  
Woo Seok Yang ◽  
Khin Myo Htwe ◽  
Mi-Nam Lee ◽  
Young-Dong Kim ◽  
...  

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.


2018 ◽  
Vol 7 (2) ◽  
pp. 124-130 ◽  
Author(s):  
D. Coric ◽  
D. E. Bullard ◽  
V. V. Patel ◽  
J. T. Ryaby ◽  
B. L. Atkinson ◽  
...  

Objectives Pulsed electromagnetic field (PEMF) stimulation was evaluated after anterior cervical discectomy and fusion (ACDF) procedures in a randomized, controlled clinical study performed for United States Food and Drug Administration (FDA) approval. PEMF significantly increased fusion rates at six months, but 12-month fusion outcomes for subjects at elevated risk for pseudoarthrosis were not thoroughly reported. The objective of the current study was to evaluate the effect of PEMF treatment on subjects at increased risk for pseudoarthrosis after ACDF procedures. Methods Two evaluations were performed that compared fusion rates between PEMF stimulation and a historical control (160 subjects) from the FDA investigational device exemption (IDE) study: a post hoc (PH) analysis of high-risk subjects from the FDA study (PH PEMF); and a multicentre, open-label (OL) study consisting of 274 subjects treated with PEMF (OL PEMF). Fisher’s exact test and multivariate logistic regression was used to compare fusion rates between PEMF-treated subjects and historical controls. Results In separate comparisons of PH PEMF and OL PEMF groups to the historical control group, PEMF treatment significantly (p < 0.05, Fisher’s exact test) increased the fusion rate at six and 12 months for certain high-risk subjects who had at least one clinical risk factor of being elderly, a nicotine user, osteoporotic, or diabetic; and for those with at least one clinical risk factor and who received at least a two- or three-level arthrodesis. Conclusion Adjunctive PEMF treatment can be recommended for patients who are at high risk for pseudoarthrosis. Cite this article: D. Coric, D. E. Bullard, V. V. Patel, J. T. Ryaby, B. L. Atkinson, D. He, R. D. Guyer. Pulsed electromagnetic field stimulation may improve fusion rates in cervical arthrodesis in high-risk populations. Bone Joint Res 2018;7:124–130. DOI: 10.1302/2046-3758.72.BJR-2017-0221.R1.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rosangela Montanaro ◽  
Alessio D’Addona ◽  
Andrea Izzo ◽  
Carlo Ruosi ◽  
Vincenzo Brancaleone

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.


2021 ◽  
Vol 11 (16) ◽  
pp. 7571
Author(s):  
Yoon-Young Sung ◽  
Jae-Woo Shin ◽  
Won-Kyung Yang ◽  
Min-Jin Kim ◽  
Ja-Ik Koo ◽  
...  

Currently, many children undergo precocious puberty, resulting in short stature due to premature closure of the growth plate. Pulsed electromagnetic field (PEMF) stimulation induces cell proliferation of articular chondrocytes. We developed a method for growth promotion using equipment with PEMF. In this study, we aimed to evaluate the effects of PEMF on the growth rate of growth plates using an animal model. An experimental study was conducted on 16 3-week-old rats to validate the effects of the growth care device on growth and development by PEMF stimulation at 28 Hz and 20 Gauss. The tibia bones of the groups with and without PEMF administration were dissected after 10 days, and then, the length of the growth plate of the knee and levels of insulin-like growth factor (IGF)-1 hormone in serum were measured. The length of the growth plate on the tibia bone and the levels of circulating IGF-1 were significantly increased by 25.6% and 13.6%, respectively, in the experimental group to which PEMF was applied compared to those of the control group, without any side effects. These results suggest that PEMF can safely stimulate growth of the growth plate in a non-invasive manner to promote bone growth.


2021 ◽  
Author(s):  
Reinier Gesto-Borroto ◽  
Gabriela Meneses ◽  
Alejandro Espinosa-Cerón ◽  
Guillermo Granados ◽  
Jacquelynne Cervantes-Torres ◽  
...  

Abstract The genus Galphimia is widely distributed in Mexico, and is represented by 22 species, including medicinal species. The sedative and anti-inflammatory effects of galphimines produced by the species Galphimia glauca have been documented. Formerly, molecular studies using DNA barcodes demonstrated that nine populations botanically classified as Galphimia glauca belong to four different species of the genus Galphimia, and that only one exhibited the sedative properties; however, all the collected species showed anti-inflammatory activity. Other bioactive compounds like quercetin, galphins, galphimidins and glaucacetalins have been identified from methanolic extracts of plants botanically classified as Galphimia glauca. The aim of this work was to determine the anti-inflammatory activity of methanolic extracts of nine collected Galphimia spp. populations grown in Mexico. The possible modes of action were analyzed by evaluating the inhibition of LPS-induced inflammation processes both in vitro and in vivo. The nine populations were evaluated by an in vitro model using RAW 264.7 murine macrophage cells, and two populations (a galphimine-producing and a non-galphimine-producing population) were selected for the in vivo experiments of systemic inflammation and neuroinflammation in mice. Results suggest that an anti-inflammatory in vitro effect was present in all the studied populations, evidenced by the inhibition of nitrite production. An inhibitory systemic inflammation in mice was exerted by the two analyzed populations. In the neuroinflammation model, the anti-inflammatory effect was demonstrated in methanolic extract of the non-galphimine-producing population. For the populations of Galphimia spp. studied herein, the anti-inflammatory effect could not be correlated to the presence of galphimines.


2014 ◽  
Vol 32 (5) ◽  
pp. 677-685 ◽  
Author(s):  
F. Veronesi ◽  
P. Torricelli ◽  
G. Giavaresi ◽  
M. Sartori ◽  
F. Cavani ◽  
...  

Author(s):  
Boussoualim Naouel ◽  
Trabsa Hayat ◽  
Krache Imane ◽  
Ouhida Soraya ◽  
Arrar Lekhmissi ◽  
...  

Background: Anchusa azurea Mill. (AA) is a medicinal plant largely used traditionally in folk medicine in Algeria, it is locally named: hamham. It is effective in the treatment of various diseases. Objectives: The aim of the present study is to determine the antioxidant, anti-inflammatory and anti-hemolytic effects of phenolic fractions from Anchusa azurea Mill. Methods: In this study, various extracts from Anchusa azurea Mill. (AA) using solvents with increasing polarity were prepared. The quantification of polyphenols and flavonoids was determined. The anti-radical activity of the different extracts was evaluated using DPPH and by measuring the inhibition of the oxidative degradation of β-carotene. The In vitro antihemolytic effect of the plant extracts is determined (CrE, ChE, AcE and AqE). For each extract, four concentrations were tested: 10.59, 21.18, 42.37, 84.74 µg/ml. Vitamin C is used as a standard. Free-radical attack was measured by measuring the HT50 (Half-Hemolysis Time). The anti-inflammatory effect using PMA on mice of the methanolic extract (CrE) was evaluated. Results: The quantification of polyphenols and flavonoids showed that ethyl acetate extract (AcE) contains a higher amount of polyphenols. However, chloroform extract (ChE) presents a higher amount of flavonoids. AcE showed an important scavenging activity using the DPPH radical (IC50= 68.35 µg/ml). The results showed that AcE also exhibited very great inhibition on the oxidation of β-carotene/linoleic acid (84.33%). All extracts increased the HT50 values (Half-Hemolysis Time) in a dose-dependent manner. The three highest concentrations (21.18, 42.37 and 84.74 µg / ml) of ChE caused a very significant delay (p ≤ 0.001) of hemolysis compared to the negative control and the positive control "VIT C". The anti-inflammatory effect using PMA on mice showed that the methanolic extract (CrE) of AA reduced the weight of the ear edema. Conclusions: This plant has a strong pharmacological power, which supports its traditional medicinal use.


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