scholarly journals Anti-inflammatory effects of gallic acid in human gestational tissues in vitro

Reproduction ◽  
2020 ◽  
Vol 160 (4) ◽  
pp. 561-578 ◽  
Author(s):  
Caitlyn Nguyen-Ngo ◽  
Carlos Salomon ◽  
Andrew Lai ◽  
Jane C Willcox ◽  
Martha Lappas
Keyword(s):  
Preterm Birth ◽  
Gallic Acid ◽  
Spontaneous Preterm Birth ◽  
Cell Contractility ◽  
Proteomic Approach ◽  
Decidual Cells ◽  
Foetal Membranes ◽  
Anti Inflammatory ◽  
Gestational Tissues

Spontaneous preterm birth is the leading cause of neonatal mortality and morbidity globally. Activation of the maternal immune system leads to a downstream cascade of proinflammatory events that culminate in the activation of spontaneous uterine contractions and the rupture of the foetal membranes. Anti-inflammatory agents may be a novel therapeutic approach to prevent inflammation-induced myometrial contractions and premature rupture of foetal membranes. The polyphenol gallic acid has been previously shown to exert potent anti-inflammatory effects. Thus, this study aimed to determine the effect of gallic acid on proinflammatory and pro-labour mediators in cytokine-stimulated gestational tissues in vitro. In primary human cells isolated from myometrium and foetal membranes (decidua, and amnion mesenchymal and epithelial cells), gallic acid treatment suppressed inflammation-induced expression of proinflammatory cytokines and chemokines and extracellular matrix-degrading and matrix-remodelling enzymes. Gallic acid also significantly inhibited inflammation-induced myometrial activation as evidenced by decreased expression of contraction-associated proteins, the uterotonic PGF2α and collagen cell contractility. Using a global proteomic approach, gallic acid may differentially regulate proteins associated with collagen synthesis, cell contractility and protein synthesis in primary myometrial and decidual cells. In summary, gallic acid inhibited inflammation-induced mediators involved in active labour in primary cells isolated from myometrium and foetal membranes. These in vitro studies suggest that the polyphenol gallic acid may be able to suppress the production of proinflammatory and pro-labour mediators involved in myometrial contractions and rupture of foetal membranes. Future preclinical studies may elucidate the efficacy of gallic acid in preventing inflammation-driven preterm birth.

Targeting bromodomain-containing proteins to prevent spontaneous preterm birth

2019 ◽  
Vol 133 (23) ◽  
pp. 2379-2400 ◽  
Author(s):  
Ratana Lim ◽  
Caitlyn Nguyen-Ngo ◽  
Martha Lappas
Keyword(s):  
Preterm Birth ◽  
Preterm Labor ◽  
Selective Inhibition ◽  
Clinical Samples ◽  
Fetal Membranes ◽  
Spontaneous Preterm Birth ◽  
Protein Inhibition ◽  
Decidual Cells ◽  
Gestational Tissues ◽  
Human And Mouse

Abstract Preterm birth is a global healthcare challenge. Spontaneous preterm birth (sPTB) is commonly caused by inflammation, yet there are currently no effective therapies available. The Bromodomain and Extra-Terminal motif (BET) proteins, Bromodomain-containing protein (Brd) 2 (Brd2), Brd3 and Brd4 regulate inflammation in non-gestational tissues. The roles of Brd2–4 in human pregnancy are unknown. Using human and mouse models, the present study has identified the Brd proteins part of the process by which inflammation induces parturition. Using human clinical samples, we demonstrate that labor and infection increase the expression of Brds in the uterus and fetal membranes. In primary human myometrial, amnion and decidual cells, we found that global Brd protein inhibition, as well as selective inhibition of Brds, suppressed inflammation-induced expression of mediators involved in myometrial contractions and rupture of fetal membranes. Importantly, studies in the mouse model demonstrate that the pan-Brd inhibitor JQ1 reduced intrauterine inflammation induced by bacterial endotoxin LPS as well as decreasing the effectiveness of LPS to induce parturition. These results implicate BET proteins as novel therapeutic targets for reducing inflammation associated with spontaneous preterm labor.

scholarly journals Epigenetic changes in preterm birth placenta suggest a role for ADAMTS genes in spontaneous preterm birth

2018 ◽  
Vol 28 (1) ◽  
pp. 84-95 ◽  
Author(s):  
Sneha Mani ◽  
Jayashri Ghosh ◽  
Yemin Lan ◽  
Suneeta Senapati ◽  
Teri Ord ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Critical Role ◽  
Spontaneous Preterm Birth ◽  
Gene Methylation ◽  
Vitro Fertilization ◽  
Genome Wide ◽  
Common Etiology ◽  
Adamts Gene ◽  
Extravillous Trophoblasts

Abstract Preterm birth (PTB) affects approximately 1 in 10 pregnancies and contributes to approximately 50% of neonatal mortality. However, despite decades of research, little is understood about the etiology of PTB, likely due to the multifactorial nature of the disease. In this study, we examined preterm and term placentas, from unassisted conceptions and those conceived using in vitro fertilization (IVF). IVF increases the risk of PTB and causes epigenetic change in the placenta and fetus; therefore, we utilized these patients as a unique population with a potential common etiology. We investigated genome-wide DNA methylation in placentas from term IVF, preterm IVF, term control (unassisted conception) and preterm control pregnancies and discovered epigenetic dysregulation of multiple genes involved in cell migration, including members of the ADAMTS family, ADAMTS12 and ADAMTS16. These genes function in extracellular matrix regulation and tumor cell invasion, processes replicated by invasive trophoblasts (extravillous trophoblasts (EVTs)) during early placentation. Though expression was similar between term and preterm placentas, we found that both genes demonstrate high expression in first- and second-trimester placenta, specifically in EVTs and syncytiotrophoblasts. When we knocked down ADAMTS12 or ADAMTS16in vitro, there was poor EVT invasion and reduced matrix metalloproteinase activity, reinforcing their critical role in placentation. In conclusion, utilizing a population at high risk for PTB, we have identified a role for ADAMTS gene methylation in regulating early placentation and susceptibility to PTB.

scholarly journals Libidibia ferreaFruit Crude Extract and Fractions Show Anti-Inflammatory, Antioxidant, and Antinociceptive EffectIn Vivoand Increase Cell ViabilityIn Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Tamires Rocha Falcão ◽  
Aurigena Antunes de Araújo ◽  
Luiz Alberto Lira Soares ◽  
Iuri Brilhante de Farias ◽  
Wliana Alves Viturino da Silva ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Cell Viability ◽  
Gallic Acid ◽  
Cell Line ◽  
Crude Extract ◽  
Leukocyte Migration ◽  
Total Glutathione ◽  
Anti Inflammatory

Background.Libidibia ferrea(L. ferrea)is found throughout the northeastern region of Brazil, where it has been used in folk medicine with beneficial effects on many inflammatory disorders.Purpose. This study investigated the phytochemical composition of the crude extract and fractions ofL. ferreafruit and evaluated its anti-inflammatory and antinociceptive activitiesin vivoand effect on cell viabilityin vitro.Methods. Characterization of polyphenols present in crude extract (CE), hydroalcoholic fractions of 20-80% ethanol (CE20, CE40, CE60, and CE80), aqueous fraction (AqF), and ethyl acetate (EAF) fractions ofL. ferreafruit was performed by chromatographic analysis.Anti-inflammatory activity was evaluated by using a carrageenan-induced peritonitis model submitted to a leukocyte migration assay and myeloperoxidase activity (MPO) analysis. Total glutathione and malondialdehyde (MDA) levels were assessed to evaluate the oxidative stress level. Antinociceptive activity was evaluated by acetic acid-induced abdominal writhing and hot plate test.In vitrocell viability was determined by using MTT assay in a mouse embryonic fibroblast cell line (3T3 cells).Results. Chromatography revealed the presence of ellagic acid content in EAF (3.06), CE (2.96), and CE40 (2.89). Gallic acid was found in EAF (12.03), CE 20 (4.43), and CE (3.99).L. ferreacrude extract and all fractions significantly reduced leukocyte migration and MPO activity (p<0.001).L. ferreaantioxidant effect was observed through high levels of total glutathione and reduction of MDA levels (p<0.001). Acetic acid-induced nociception was significantly inhibited after administration ofL. ferreacrude extract and all fractions (p<0.001). Crude extract and all fractions significantly increased the viability of the 3T3 cell line (p<0.05).Conclusions. The appropriate extraction procedure preserves the chemical components ofL. ferreafruit, such as gallic acid and ellargic acid. Crude extract and fractions ofL. ferreafruit exhibited anti-inflammatory, antioxidant, antinociceptive activitiesin vivoand enhanced cell viabilityin vitro.

scholarly journals ASSESSMENT OF PHYTOCHEMICALS AND IN VITRO ANTIOXIDANT, ANTI-INFLAMMATORY ACTIVITY OF SARCOSTEMMA BRUNONIANUM WIGHT AND ARN

2021 ◽  
pp. 64-69
Author(s):  
AMALA DIVYA S. ◽  
THAMARAIKANI V. ◽  
SEKAR T.
Keyword(s):  
Medicinal Plant ◽  
Gallic Acid ◽  
Methanol Extract ◽  
Inflammatory Activity ◽  
Total Phenolic ◽  
Pharmaceutical Drugs ◽  
Activity Maximum ◽  
Study Results ◽  
Anti Inflammatory

Objective: Sarcostemma brunonianum Wight and Arn is a potential medicinal plant belonging to Asclepiadaceae. Bioactive constituents of the plant support the application of treating various ailments in the traditional system of medicine. The study aims to determine the presence of various phytoconstituents in stem, root, and flowers. Methods: Hot percolation method was carried out to obtain crude extracts using different solvent systems from low polar-high polar solvents ranging from petroleum ether, chloroform, (mid-polar) ethyl acetate, methanol and water. Estimation of total phenols, tannins and In vitro antioxidant, anti-inflammatory activities were evaluated for the determination of potential pharmaceutical drugs. Results: The results revealed the presence of some phytoconstituents such as phenols, tannins, glycosides, gums and mucilages. Ascorbic acid, BSA, Rutin and Gallic acid were used as the reference standard. The total phenolic content was found to be high in stem methanol extract 440.84±69.99 mg/g Gallic acid equivalent, whereas the tannin content was 291.78±4.68 mg/g GAE. The result proves that the S. brunonianum stem methanol extract possesses antioxidant and anti-inflammatory activities when compared to reference standards. In vitro, Nitric oxide scavenging activity of stem showed a maximum % of inhibition in methanol stem extract (24.39µg/ml) and anti-inflammatory activity maximum inhibition was found to be (55.56 %) in stem methanol and flower(53.62 %). The IC50 (concentration required for 50% inhibition) was also calculated for the DPPH radical model. Conclusion: This study results proclaims and justifies the role of folklore medicinal plant S. brunonianum in the treatment of inflammatory-related ailments and can be recommended for an effective drug.

scholarly journals The short-chain fatty acids butyrate and propionate protect against inflammation-induced activation of mediators involved in active labor: implications for preterm birth

2020 ◽  
Vol 26 (6) ◽  
pp. 452-468 ◽  
Author(s):  
Hope Eveline Carter Moylan ◽  
Caitlyn Nguyen-Ngo ◽  
Ratana Lim ◽  
Martha Lappas
Keyword(s):  
Fatty Acids ◽  
Preterm Birth ◽  
Inflammatory Cytokines ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Fetal Membranes ◽  
Spontaneous Preterm Birth ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines ◽  
Chain Fatty Acids

Abstract Spontaneous preterm birth is a global health issue affecting up to 20% of pregnancies and leaves a legacy of neurodevelopmental complications. Inflammation has been implicated in a significant proportion of preterm births, where pro-inflammatory insults trigger production of additional pro-inflammatory and pro-labor mediators. Thus, novel therapeutics that can target inflammation may be a novel avenue for preventing preterm birth and improving adverse fetal outcomes. Short-chain fatty acids (SCFAs), such as butyrate and propionate, are dietary metabolites produced by bacterial fermentation of fiber in the gut. SCFAs are known to possess anti-inflammatory properties and have been found to function through G-coupled-receptors and histone deacetylases. Therefore, this study aimed to investigate the effect of SCFAs on pro-inflammatory and pro-labor mediators in an in vitro model of preterm birth. Primary human cells isolated from myometrium and fetal membranes (decidua, amnion mesenchymal and amnion epithelial cells) were stimulated with the pro-inflammatory cytokines tumor necrosis factor alpha (TNF) or interleukin 1B (IL1B). The SCFAs butyrate and propionate suppressed inflammation-induced expression of pro-inflammatory cytokines and chemokines, adhesion molecules, the uterotonic prostaglandin PGF2alpha and enzymes involved in remodeling of myometrium and degradation of the fetal membranes. Notably, propionate and butyrate also suppressed inflammation-induced prostaglandin signaling and myometrial cell contraction. These effects appear to be mediated through suppression of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation. These results suggest that the SCFAs may be able to prevent myometrial contractions and rupture of membranes. Further in vivo studies are warranted to identify the efficacy of SCFAs as a novel anti-inflammatory therapeutic to prevent inflammation-induced spontaneous preterm birth.

Chemical Composition, Antioxidant, and Anti-inflammatory Activities of Whole Parts of Onobrychis crista-galli (L.) Lam

2020 ◽  
Vol 10 (5) ◽  
pp. 642-654
Author(s):  
Wassila Benchadi ◽  
Hamada Haba ◽  
Emerson Ferreira Queiroz ◽  
Laurence Marcourt ◽  
Jean-Luc Wolfender ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Linoleic Acid ◽  
Ethyl Acetate ◽  
Gallic Acid ◽  
Ethyl Acetate Extract ◽  
Fresh Weight ◽  
Anti Inflammatory ◽  
First Time ◽  
Β Carotene

Objective: The aim of the present study is to examine the phytochemical components and the biological activities of the whole parts of Onobrychis crista-galli (L.) Lam. growing in Algeria. Methods: The structures of the isolated compounds 1-15 were elucidated using different spectroscopic methods and by comparison with literature data. The biological evaluation of the plant was determined by the in vitro antioxidant and anti-inflammatory activities. The antioxidant activity of various extracts (petroleum ether, ethyl acetate, and n-butanol) and some isolated flavonoids was assessed by using five different test systems, namely, 1,1-diphenyl-2-picryl-hydrazil (DPPH), 2,2’- azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), cupric reducing antioxidant capacity (CUPRAC), superoxide alkaline DMSO, and β-carotene/linoleic acid tests. In addition, the total phenolic and flavonoid contents of the extracts were determined as gallic acid and quercetin equivalents, respectively. In vitro anti-inflammatory activity by protein denaturation was measured for all extracts. Results: Phytochemical investigation of the ethyl acetate and n-butanol extracts of Onobrychis crista- galli led to the isolation for the first time of fifteen known compounds. The present study reports for the first time the isolation and identification of fifteen known compounds from this species. The ethyl acetate extract had rich phenolic content indicating (31.09 ± 0.40 mg gallic acid equivalents/g of fresh weight), while n-butanol extract displayed a high content in flavonoid compounds (60.70±0.7 mg quercetin equivalents/ g of fresh weight). This investigation indicated that the ethyl acetate extract of O. crista-galli showed the highest antioxidant activity (IC50= 17.13±0.51 μg/mL, DPPH), (IC50= 82.99±2.50 μg/mL, ABTS), and (A0.50= 94.67±0.41 μg/mL, CUPRAC), (IC50= 97.09±2.20 μg/mL, DMSO), (IC50: 36.73±1.17 μg/mL, β-carotene/linoleic acid). Furthermore, the compound luteolin 5-methyl ether (14) exhibited a good antioxidant activity in DPPH (IC50= 06.05 ± 0.15 μg /mL) and CUPRAC (A0.5= 12.57 ± 0.34 μg /mL) assays. Moreover, the ethyl acetate and nbutanol extracts of O. crista-galli evidenced a good to moderate in vitro anti-inflammatory activity. Conclusion: The extracts of the whole plant of O. crista-galli (L.) Lam. showed potent antioxidant and anti-inflammatory activities.

scholarly journals Quantitative Analysis and In vitro Anti-inflammatory effects of gallic acid, ellagic acid, and quercetin from radix sanguisorbae

2016 ◽  
Vol 12 (46) ◽  
pp. 104 ◽  
Author(s):  
Hyeun-Kyoo Shin ◽  
Chang-Seob Seo ◽  
Soo-Jin Jeong ◽  
Sae-Rom Yoo ◽  
Na-Ri Lee
Keyword(s):  
Quantitative Analysis ◽  
Gallic Acid ◽  
Ellagic Acid ◽  
Anti Inflammatory

scholarly journals IL-37 Exerts Anti-Inflammatory Effects in Fetal Membranes of Spontaneous Preterm Birth via the NF-κB and IL-6/STAT3 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Lulu Wang ◽  
Zheng Liu ◽  
Dongni Huang ◽  
Yuxin Ran ◽  
Hanwen Zhang ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Signaling Pathway ◽  
Biological Effects ◽  
Clinical Samples ◽  
Fetal Membranes ◽  
Spontaneous Preterm Birth ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Anti Inflammatory

Spontaneous preterm birth (sPTB), defined as delivery before 37 weeks of gestation, is thought to be a multifactorial syndrome. However, the inflammatory imbalance at the maternal-fetal interface promotes excessive secretion of inflammatory factors and induces apoptosis and degradation of the extracellular matrix (ECM), which can subsequently lead to preterm birth. As an anti-inflammatory molecule in the IL-1 family, interleukin-37 (IL-37) mainly plays an inhibiting role in a variety of inflammatory diseases. However, as a typical inflammatory disease, no previous studies have been carried out to explore the role of IL-37 in sPTB. In this study, a series of molecular biological experiments were performed in clinical samples and human amniotic epithelial cell line (Wistar Institute Susan Hayflick (WISH)) to investigate the deficiency role of IL-37 and the potential mechanism. Firstly, the results indicated that the expression of IL-37 in human peripheral plasma and fetal membranes was significantly decreased in the sPTB group. Afterward, it is proved that IL-37 could significantly suppress the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in WISH cells. Simultaneously, once silence IL-37, LPS-induced apoptosis and activity of matrix metalloproteinases (MMPs) 2 and 9 were significantly increased. In addition, the western blot data showed that IL-37 performed its biological effects by inhibiting the NF-κB and IL-6/STAT3 pathway. In conclusion, our results suggest that IL-37 limits excessive inflammation and subsequently inhibits ECM remodeling and apoptosis through the NF-κB and IL-6/STAT3 signaling pathway in the fetal membranes.

168: Impaired anti-inflammatory response in women with a prior spontaneous preterm birth

2008 ◽  
Vol 199 (6) ◽  
pp. S59
Author(s):  
Luisa Wetta ◽  
Alice Goepfert ◽  
Elena Lobashevskaya ◽  
Suzanne Cliver ◽  
Joseph Biggio ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Inflammatory Response ◽  
Spontaneous Preterm Birth ◽  
Anti Inflammatory
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