Natural Anti-inflammatory Agent Research Articles

Preventive effects of a natural anti-inflammatory agent Salvianolic acid A on acute kidney injury in mice

Acute kidney injury (AKI) is an abrupt loss of kidney function with high mortality. Inflammatory is considered driving the progression of AKI. Salvianolic acid A (SA), one of the major ingredients of Salvia miltiorrhiza Bunge, displays plenty of biological effects. Herein, the effect of SA on lipopolysaccharide (LPS)-induced AKI in mice and further related mechanism in inflammatory cells were explored. In vivo experiments demonstrated that SA significantly ameliorated LPS-challenged AKI by preventing glomerulus atrophy and decreasing plasma creatinine and blood urea nitrogen (BUN) levels. Meanwhile, SA significantly decreased the release of serum inflammatory cytokines and blocked macrophage infiltration in damaged renal tissue. In in vitro studies, SA significantly decreased TNF-α and IL-6 release levels and altered the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in LPS-stimulated macrophages, which were consistent with the results from in vivo experiments. Furthermore, SA that bound to Toll-Like Receptor 4 (TLR4) was able to reduce endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation in response to LPS stimulation. All silence of TLR4 gene, ROS scavenger and Ca2+ chelator decreased inflammatory cytokines releases. Taken together, SA could be used as a potential therapeutic agent for preventing AKI by suppressing inflammatory responses.

Prenylated Coumarins from the Fruits of Manilkara zapota with Potential Anti-inflammatory Effects and Anti-HIV Activities.

Manilkara zapota, usually known as Sapodilla, is a fairly slow-growing evergreen tropical tree which belongs to the genus Manilkara (Sapotaceae), indigenous to Central America, southern Mexico, and the Caribbean. The ripe fruits of M. zapota have been widely consumed as an uniquely flavored tropical fruit and verified to hold a variety of health benefits. In order to investigate the potential health-promoting chemical compositions from the fruits of M. zapota cultivated in Hainan Island of China, a systematic and in-depth phytochemical study on this fruit was accordingly implemented. In our current study, three new prenylated coumarins, manizapotins A-C (1-3), together with seven known prenylated coumarins (4-10), were separated from the fruits of M. zapota. The chemical structures of new prenylated coumarins 1-3 were unambiguously established by means of comprehensive spectroscopic analyses, and the known compounds 4-10 were determined by comparing their experimental spectral data with those described data in the literature. This is the first time to discover prenylated coumarins occurring in M. zapota. The potential anti-inflammatory effects and anti-HIV (human immunodeficiency virus) activities of all these separated prenylated coumarins were assessed. Prenylated coumarins 1-10 dispalyed remarkable inhibitory effects against nitric oxide production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells with the IC50 values equivalent to that of hydrocortisone in vitro. Meanwhile, prenylated coumarins 1-10 exhibited pronounced anti-HIV-1 reverse transcriptase activities with the EC50 values in range of 0.12-8.69 μM. These results suggest that appropriate and reasonable consumption of the fruits of M. zapota might assist people to prevent and reduce the occurrence of inflammatory diseases together with the infection of HIV. Furthermore, the discovery of these prenylated coumarins from the fruits of M. zapota holding pronounced anti-inflammatory effects along with anti-HIV activities could be of great significance to the research and development of new natural anti-inflammatory and anti-HIV agents.

In vivo anti-inflammatory efficacy of the combined Bowman-Birk trypsin inhibitor and genistein isoflavone, two biological compounds from soybean.

Soybean Bowman-Birk protease inhibitor (BBI) and genistein, two biological compounds from soybean, are well-known for their anti-inflammatory, antioxidant, and anticancer activities. The aim of this study was designing a BBI-genistein conjugate and then investigating its protective effect on lipopolysaccharide (LPS)-induced inflammation in BALB/c mice, compared with the effects of combination of BBI and genistein. BBI was purified from soybean and the BBI-genistein conjugate was synthesized. The BALB/c mice were intraperitoneally treated 2 hours before LPS induction. Our results showed that treatment with the combination of BBI and genistein greatly led to more reduced serum levels of tumor necrosis factor (TNF)-α and interferon (IFN)-γ compared with the treatments of BBI alone, the BBI-genistein conjugate, and genistein alone, respectively. Moreover, the expression of TNF-α and IFN-γ in the splenocytes was significantly downregulated along with improving host survival against the LPS-induced lethal endotoxemia in the same way. Our data support a new combined therapy using BBI and genistein, as natural anti-inflammatory agents, to develop a new drug for inflammatory diseases.

LPS로 자극된 RAW 264.7 세포에서 암대극 추출물의 항염증 효과

The Euphorbia jolkini (J11) is traditional medicinal plant, has been used for treatment diabetes, flu, toothache, etc. Recently studies shown that J11 extract has been evaluated to anti-oxidant, anti-bacterial, and anti-melanogenesis. However, Anti-inflammatory effect of J11 extract has not been reported yet. In this study, we studied the effects of J11 extract on anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. We also studied the effect of J11 extract on expression of protein in RAW 264.7 cells. The cells were treated with J11 extract, ranging between 25 and 100 μg/mL. The results indicated that J11 extract dramatically decreased nitric oxide (NO) and prostaglandin 2 (PGE₂) production in the cells without any cytotoxicity. In addition, J11 extract strongly inhibited expression of pro-inflammatory cytokines such as interleukin (IL)-6 and interleukin (IL)-1β. Moreover, western blot result showed that the J11 extract inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) expression in a does-dependent manner. Therefore, this study suggest that J11 extract may be applied for potential source as a natural anti-inflammatory agent.

Synthesis and Evaluation of Glycyrrhetic Acid-aromatic Hybrids as Antiinflammatory Agents.

Inflammation is a biological response of body tissues to harmful stimuli, so it is desirable to search for novel anti-inflammatory agents with improved pharmaceutical profiles and reduced adverse effects. This study was to explore natural anti-inflammatory agents and improve therapeutic application of glycyrrhetic acid (GA) through molecular hybridization with active aromatics. Fourteen novel GA-aromatic hybrids were synthesized and evaluated for their antiinflammatory activities by inhibiting LPS-induced nitric oxide (NO) release in RAW264.7 cells. The synthesized compounds were characterized by single-crystal X-ray diffraction, 1H NMR, 13C NMR and HRMS. The structure-activity relationship (SAR) study indicated that compounds with styryl displayed better NO inhibitory activity. Among them, compounds 2a and 3c exhibited the most promising activity with IC50 values of 9.93 μM and 12.25 μM, respectively. In addition, X-ray singlecrystal diffraction data for compounds 2e and 3c showed that the absolute configuration of GA skeleton was consistent with that of natural 18 β-glycyrrhetic acid. The results showed that GA-aromatic hybrids were a new class of anti-inflammatory agents and this study provided useful information on further optimization.

First report of spiro-compounds from marine macroalga Gracilaria salicornia: prospective natural anti-inflammatory agents attenuate 5-lipoxygenase and cyclooxygenase-2

The inflammation pathology is an orchestrated biological process and the dual inhibition of pro-inflammatory enzymes 5-lipoxygenase and cyclooxygenase-2 has been found to be an effective approach against inflammation. This study involves the characterisation of two previously undescribed spiro[5.5]undecanes, 3-(hydroxymethyl)-7-(methoxymethyl)-3,11-dimethyl-9-oxospiro[5.5]undec-4-en-10-methylbutanoate (1) and 4-ethoxy-11,11-dimethyl-7-methylene-8-(propionyloxy)spiro[5.5]undec-2-en-104,106-dihydroxytetrahydro-2H-pyran-10-carboxylate (2) with potential anti-inflammatory properties, from seaweed Gracilaria salicornia by extensive-spectroscopic-experiments. These metabolites recorded prospective bioactivities against 5-lipoxygenase (IC50 < 2.80 mM), whereas their selectivity indices were significantly greater (∼1) than ibuprofen (0.89) (p < 0.05), which attributed selective anti-inflammatory potencies of the studied spiro[5.5]undecane derivatives against inducible cyclooxygenase-2 than constitutive cyclooxygenase-1. Radical scavenging potential of spiro[5.5]undec-2-en-104,106-dihydroxytetrahydro-2H-pyran-10-carboxylate analogue (2) against oxidants, 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis-3 ethylbenzothiozoline-6-sulfonic acid were found to be greater (IC50 < 1.25 mM) than commercial standard, α-tocopherol (IC50 1.42–1.79 mM). The greater hydrogen-bonding interactions and binding affinity of 2 (−10.13 kcal/mol) with 5-LOX appropriately corroborated its prospective anti-inflammatory activity.

Controlled-release curcumin attenuates progression of tendon ectopic calcification by regulating the differentiation of tendon stem/progenitor cells

Tendon calcification is a common but intractable problem leading to pain and activity limitation when injury or tendinopathy progresses into the late stage. This is because tendon stem/progenitor cells (TSPCs) can undergo aberrant osteogenic differentiation under inflammatory conditions. This study aims to investigate the effect of curcumin, a natural anti-inflammatory agent, on regulating the differentiation of TSPCs in tendon calcification. With inflammatory stimulation, TSPCs showed higher alkaline phosphatase activity and more frequent formation of mineralized nodules which were verified in the culture system; however, curcumin significantly alleviated these pathological changes. In in vivo function analysis, chitosan microsphere-encapsulated curcumin was delivered to injured sites of rat tendon ectopic calcification model. The inflammation in the tendon tissues of the curcumin group was significantly relieved. Controlled-release curcumin partially rescued tendon calcification and enhanced tendon regeneration in animal model. This study demonstrates that controlled-release curcumin can manipulate the fate decision of TSPCs, and that it promotes the tenogenesis and inhibits the osteogenesis of TSPCs in a pathological microenvironment, which provides a possible new therapeutic strategy for tendon disease.

Chrysin prevents cognitive and hippocampal long-term potentiation deficits and inflammation in rat with cerebral hypoperfusion and reperfusion injury

IntroductionIschemic stroke is one of the leading causes of death worldwide, and extensive efforts have focused on the neuroprotective strategies to minimize complications due to ischemia. This study aimed to examine neuroprotective potential of chrysin, as a natural potent antioxidative and anti-inflammatory agent in an animal model of bilateral common carotid artery occlusion and reperfusion (BCCAO/R). MethodsAdult male Wistar rats (250–300 g) were randomly divided into 6 groups and submitted to either sham surgery or BCCAO/R after pretreatment with chrysin (10, 30 and 100 mg/kg, once daily, for 21 consecutive days) or saline containing %5 DMSO. To make the animal model of BCCAO/R, bilateral common carotid arteries were occluded for 20 min, followed by reperfusion. Subsequently, spatial cognitive performance was evaluated in a Morris water maze (MWM), hippocampal long-term potentiation (LTP) was recorded from hippocampal dentate gyrus region, after then the hippocampal tissue content of IL-1β and TNF-α were assayed using ELISA kits. ResultsThe results showed that pretreatment with chrysin significantly prevented BCCAO/R-induced cognitive and hippocampal LTP impairments (p < 0.001). Additionally, BCCAO/R- induced elevation in hippocampal content of IL-1β and TNF-α significantly (p < 0.01, p < 0.01 respectively) while pre-treatment with chrysin restored them (p < 0.01). ConclusionOur data confirm that chrysin could prevent brain inflammation and thereby prevents cognitive and LTP impairments due to cerebral ischemia. So it could be a promising neuroprotective agent against cerebrovascular insufficiency states.

The anti-inflammatory potential of Portulaca oleracea L. (purslane) extract by partial suppression on NF-κB and MAPK activation

Portulaca oleracea L. (Purslane) has great potential as food and traditional drugs in several countries. The purpose of this study was to evaluate the anti-inflammatory effects of purslane extract on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Purslane extracts significantly reduced LPS-induced synthesis of NO in a dose-dependent manner, as well as the expression levels of iNOS and COX-2. The productions of TNF-α and IL-6 were also significantly reduced at the higher dose of 400 μg/ml. Meanwhile, the expression levels of P65, p-P65, p-MEK and p-IκB-α were inhibited dose-dependently. The nuclear translocation of P65 was partially prevented by the extract, which explained the inhibition of NF-κB pathway. In addition, three reported flavonoids, named luteolin, kaempferol and quercitrin, were identified in the extract, which might be responsible for its anti-inflammatory effects. Above all, our research has partially proved that purslane could be considered as a natural anti-inflammatory agent in further applications.

Inflammation the Kingpin of Chronic Diseases Naturopathy as an alternative source of treatment: An updated overview

Inflammation involves a sequence of events which can be categorized under three phases viz. acute transient phase, delayed sub-acute phase and chronic proliferate phase. Inflammatory mediators develop due to enhanced vascular permeability and leads to local edema. It is followed by the migration of leukocytes and phagocytes from blood to vascular tissues which is the second phase, in the third phase, tissue degradation is followed by fibrosis. There is a powerful link between chronic diseases and chronic inflammatory disorders. Chronic low-level inflammation contributes to the pathogenesis of these several diseases like Heart disease, Cancer, Chronic lower respiratory disease, Stroke, Alzheimer’s, Diabetes, and Nephritis. The harmful side effects of synthetic drugs are numerous and there stands up the need of herbal drugs which are cost effective and free from side-effects. Several traditional ayurvedic phytomedicines have been used in the treatment of inflammatory disorders like Ocimum sanctum, Hypericum peroratum, Boswellic serrata, Ficus racemosa etc. which act as natural anti-inflammatory agents that can help in reducing the complications associated with chronic diseases.&#x0D; Key Words: Inflammation, Chronic-low level inflammation, Cancer, Diabetes, Phytomedicines

Electrospun Twin Fibers Encumbered with Intrinsic Antioxidant Activity as Prospective Bandage

Our investigation for the first time explores the possibility of fabrication of a Capsaicin/polyurethane-based bioactive wound dressing. A micro/nanofibrous bandage was synthesized by electrospinning polyurethane supplemented with natural anti-inflammatory agent, Capsaicin. Herein, the best concentration (3%) of Capsaicin in polyurethane to get a consistent solution was standardized in order to acquire the composite micro/nanofibrous dressing. The as-spun bandage has been investigated by scanning electron microscopy and Fourier transform infrared spectroscopy, and biocompatibility of muscle cells on the bioactive bandage was also examined. Free radical scavenging activity of the fabricated micro/nanofiber bandage was estimated using 2,2-diphenyl-1-picrylhydrazyl assay. Inclusion of Capsaicin in polyurethane transformed the morphology as well as dimension of the fibers. Anti-oxidant wound bandage with diameters around 150–500 nm was fabricated by physical unification of polyurethane with natural Capsaicin. Here, polyurethane was used as a foundation polymer, which was blended with Capsaicin to attain desirable characteristics such as better anti-oxidant activity, hydrophilicity and excellent cell attachment. The polyurethane wound bandage possesses enlarged surface, proscribed evaporation, and fluid drainage ability. These results suggest the beneficial influence of antioxidant Capsaicin on wound repairing process. Therefore, a biologically active, natural compounds such as Capsaicin is material of choice for fabrication of future wound dressings.

Retracted Article: Anti-inflammatory potency of Locusta migratoria manilensis cyclopeptides in mast cells and macrophages.

Locusts are esteemed as a traditional Chinese medicine, as well as tonic foods in Asian countries. While searching for natural anti-inflammatory agents in natural products, we isolated four novel locust cyclopeptides (LCPs) and the results show that [cyclo-(Trp-Leu-His-Thr)]∼LCP-3 has potent anti-inflammatory potency in RAW264.7 and HMC-1 cells under LPS (lipopolysaccharide) stimuli. Furthermore, mechanistic studies show that LCP-3 attenuates pro-inflammatory cytokine (TNF-α, IL-6, IL-1β, NO and PGE2) expression. Moreover, LCP-3 attenuates inflammatory damage associated with the direct inhibition of iNOS and COX-2 expression. LCP-3 also regulates the MAPK, PI3K/AKT and NF-κB pathways to attenuate LPS-induced damage. Of note, our study first reports the anti-inflammatory potency of LCPs and elucidates their underlying molecular mechanisms.

Soft Coral Dendronephthya puetteri Extract Ameliorates Inflammations by Suppressing Inflammatory Mediators and Oxidative Stress in LPS-Stimulated Zebrafish.

Marine-derived extract and/or bioactive compounds have attracted increasing demand due to their unique and potential uses as cures for various inflammation-based diseases. Several studies revealed anti-inflammatory candidates found in soft corals. However, the effects of soft corals on inflammation in an in vivo model remain to be determined. Therefore, the extract of soft coral Dendronephthya puetteri (DPE) was investigated for an in vivo anti-inflammatory effect in a lipopolysaccharide (LPS)-stimulated zebrafish model to determine its potential use as a natural anti-inflammatory agent. We also investigated whether DPE has toxic effects in a zebrafish model. No significant changes were observed in terms of survival, heart beat rate, or developmental abnormalities in the zebrafish embryos exposed to a concentration below 100 µg/mL of DPE. Treating the zebrafish model with LPS-treatment significantly increased the ROS, NO generation, and cell death. However, DPE inhibited this LPS-stimulated ROS, NO generation, and cell death in a dose-dependent manner. In addition, DPE significantly reduced the mRNA expression of both iNOS and COX-2 and markedly suppressed the expression levels of the proinflammatory cytokines, TNF-α and IL-6, in an LPS-stimulated zebrafish model. These findings demonstrate that DPE has profound anti-inflammatory effect in vivo, suggesting that DPE might be a strong natural anti-inflammatory agent.

LPS 자극 RAW 264.7 세포에서 제주산 올리브 추출물의 항염 활성

Lipopolysaccharide (LPS)-induced activation of murine RAW 264.7 cells results in the production of pro-inflammatory cytokines including PGE2, IL-6, TNF-α, and IL-1β. In this study, we investigated the anti-inflammatory effects of the Olea europaea extract from Jeju island using LPS which induces an inflammatory response. To examine the potential anti-inflammatory properties of the Olea europaea extract, we measured the amount of nitric oxide (NO), prostaglandin E2(PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β on RAW 264.7 cells after the Olea europaea extract treatment. The Olea europaea extracts showed higher anti-inflammatory activity by inhibiting the production of PGE2, NO, TNF-α, IL-6, and IL-1β induced by LPS stimulation in RAW 264.7 cells. Also, Olea europaea extracts decreased mRNA expression of iNOS, and COX-2. There was no cytotoxicity in the macrophage proliferation treated with the Olea europaea extract compared to the control in the LDH assay. These results suggest that the Olea europaea extract may exert significant effects on inflammatory factors and be a potential source as a new natural anti-inflammatory agent. Further investigations will focus on cell-based in vitro assays and in chemically identifying the major active components mediating the anti-aging and anti-inflammation responses.

Chemical components and bioactivity evaluation of extracts from pear (Pyrus UssuriensisMaxim) fruit

In order to discover the bioactive metabolites of Pyrus ussuriensis Maxim, the systematic chemical and pharmacological investigations were performed. The ethyl acetate extract of the plant displayed activities against ear edema in mice, with an inhibition rate of 17.1%, at a dose of 400mg/kg in vivo. Meanwhile, the ethyl acetate extract showed the best apophlegmatic (inhibition: 49.9%) and antitussive effects (inhibition: 34%) at 800mg/kg in vivo tests, and inhibition of NO production (IC50=0.06 μg/mL). Subsequently, twelve compounds were isolated from the ethyl acetate extract and identified as friedelin (1), daucosterol (2), β-sitosterol (3), betulinic acid (4), oleanolic acid (5), ursolic acid (6), 2-O-buty-1-O’-(2-ethylhexyl) benzene-1,8-dicarboxylate (7), Narcissin (8), 3-hydroxy-3-carboxyl-glutaric acid dimethyl ester (9), 2-hydroxyl -butanediol icacid-4-methyleste (10), myristic acid (11), and (Z)-11-hexadecen-1-ol acetate (12). Among them, compounds 1, 2, 4, 5, 6, and 11 exhibited moderate indirect inhibitory effects on lipopolysaccharide-induced NO and TNF-α production. Practical applications Pyrus ussuriensis Maxim is an edible and medical fruit with many functional properties. Unfortunately, few literatures about bioactive components of this fruit have been investigated. The result indicated that P. ussuriensis have obvious anti-inflammatory, antitussive, and apophlegmatic activities, which were associated with the folk uses of this fruit. Furthermore, this work also suggests a potential use of P. ussuriensis as an important source of natural anti-inflammatory agents and they may also be considered as a functional food.

THE EFFECT OF COENZYME Q10 AND/OR SILYMARIN ON RENALASE GENE EXPRESSION OF CARDIORENAL SYNDROME IN ADULT MALE ALBINO RATS

Background: Therapeutic strategies in cardiorenal syndrome (CRS) should be directed to the cardio-renal connectors like renalase. Coenzyme Q10 (CoQ10) and silymarin are natural anti-oxidant and anti-inflammatory agents. Objectives: Assessing the effect of CoQ10 and/or Silymarin on renalase gene expression in CRS induced by high fructose diet (HFD) in male rats. Patients and Methods: Fifty adult male albino rats of local strain were divided into 5 equal groups and subjected to the following regimens for 8 weeks: Group I: Supplemented orally with 1 ml of 2% aqueous solution of tween 80. Group II: Received HFD in the form of 30% fructose in drinking water. Group III: Received HFD and CoQ10 orally at a dose of 20 mg/kg/day dissolved in 2% tween-80 aqueous solution. Group IV: Received HFD and Silymarin orally at a dose of 200 mg/kg/day dissolved in 2% tween-80 aqueous solution. Group V: Received HFD and both CoQ10 and silymarin in the same regimen as described before. Results: CoQ10 and/or Silymarin significantly decreased plasma lipid profile, cardiac troponin-I, creatinine, malondialdehyde (MDA) & tumor necrosis factor alpha (TNF- α) levels when compared to HFD group. On the other hand, CoQ10 and/or silymarin caused significant increase in plasma catalase level & renalase gene expression in kidney tissue when compared to HFD group. They also improved HFD -induced cardiac and renal fibrosis. Conclusion: CoQ10 and Silymarin induced improvement in HFD-induced CRS as they possessed cardio-protective, reno-protective, hypo-lipidimic, anti-oxidant, anti-inflammatory and anti-fibrotic activities, as well as increased renalase expression.

Is Curcumin a Possibility to Treat Inflammatory Bowel Diseases?

The inflammatory bowel diseases (IBDs) are mainly represented by Crohn's disease and Ulcerative colitis that are characterized by chronic and relapsing inflammatory processes of the gastrointestinal system. Curcuma longa L. is a plant with several medicinal properties, including anti-inflammatory effects, and curcumin is the most important compound derived from its rhizomes. As curcumin has remarkable anti-inflammatory actions, the aim of this work is to review the potential use of this compound in IBD patients. We consulted MEDLINE (PubMed/PMC), and the literature search was performed with the following combinations of terms "Inflammatory Bowel Diseases" and "Curcumin," "Crohn's Disease" and "Curcumin," "Ulcerative colitis" and "Curcumin." The inclusion criteria were articles that showed original studies with human models and the exclusion criteria were not full-text articles, articles not in English, poster presentations, letters, editorials, and articles not available. Curcumin interacts with receptors, growth and transcription factors, cytokines, enzymes, and genes leading to inhibitory effects on cyclooxygenase-1, tumor necrosis factor-α, interferon-γ, inducible nitric oxide synthase, transcriptional nuclear factor kappa B, and many other molecules associated with inflammatory processes. These molecules are critical factors in the positive regulation of inflammatory cytokines in inflammatory diseases, suggesting that curcumin may be considered as a new therapeutic agent for patients with IBD. Curcumin is a natural anti-inflammatory agent that represents an attractive, safe and inexpensive alternative for the treatment of IBD. Nevertheless, it is necessary to know the efficient and safe dose and consider its poor absorption.

Compound K Inhibits the Lipopolysaccharide-Induced Inflammatory Responses in Raw 264.7 Cell Line and Zebrafish

Compound K, a major metabolite of ginsenosides Rb1, which is produced by human intestinal bacteria after oral administration, is one of the main pharmacologic compounds found in ginseng. In our previous study, we demonstrated that compound K inhibited the production of nitric oxide (NO) and prostaglandin E2 in lipopolysaccharide (LPS)-treated RAW264.7 cells. However, the mechanisms by which compound K may be effective against inflammation remain unknown. In the present study, compound K significantly inhibited LPS-induced NO production by suppression of inducible NO synthase (iNOS) in LPS-treated RAW264.7 cells. Compound K also inhibited LPS-induced cyclooxygenase-2 (COX-2) expression at both the mRNA and protein levels. It effectively suppressed both the release and mRNA expression levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and IL-6. The anti-inflammatory effects of compound K appeared to occur via inhibition of LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) and inhibition of NF-κB translocation from the cytosol to the nucleus by suppressing phosphorylation of inhibitory kappa B-α (IκB-α). Furthermore, we showed that compound K inhibited LPS-induced NO generation in an experimental zebrafish model. Considering these results, compound K could potentially be developed as a natural anti-inflammatory agent.

Negative effects of a high tumour necrosis factor-\u03b1 concentration on human gingival mesenchymal stem cell trophism: the use of natural compounds as modulatory agents

BackgroundAdult mesenchymal stem cells (MSCs) play a crucial role in the maintenance of tissue homeostasis and in regenerative processes. Among the different MSC types, the gingiva-derived mesenchymal stem cells (GMSCs) have arisen as a promising tool to promote the repair of damaged tissues secreting trophic mediators that affect different types of cells involved in regenerative processes. Tumour necrosis factor (TNF)-α is one of the key mediators of inflammation that could affect tissue regenerative processes and modify the MSC properties in in-vitro applications. To date, no data have been reported on the effects of TNF-α on GMSC trophic activities and how its modulation with anti-inflammatory agents from natural sources could modulate the GMSC properties.MethodsGMSCs were isolated and characterized from healthy subjects. The effects of TNF-α were evaluated on GMSCs and on the well-being of endothelial cells. The secretion of cytokines was measured and related to the modification of GMSC-endothelial cell communication using a conditioned-medium method. The ability to modify the inflammatory response was evaluated in the presence of Ribes nigrum bud extract (RBE).ResultsTNF-α differently affected GMSC proliferation and the expression of inflammatory-related proteins (interleukin (IL)-6, IL-10, transforming growth factor (TGF)-β, and cyclooxygenase (COX)-2) dependent on its concentration. A high TNF-α concentration decreased the GMSC viability and impaired the positive cross-talk between GMSCs and endothelial cells, probably by enhancing the amount of pro-inflammatory cytokines in the GMSC secretome. RBE restored the beneficial effects of GMSCs on endothelial viability and motility under inflammatory conditions.ConclusionsA high TNF-α concentration decreased the well-being of GMSCs, modifying their trophic activities and decreasing endothelial cell healing. These data highlight the importance of controlling TNF-α concentrations to maintain the trophic activity of GMSCs. Furthermore, the use of natural anti-inflammatory agents restored the regenerative properties of GMSCs on endothelial cells, opening the way to the use and development of natural extracts in wound healing, periodontal regeneration, and tissue-engineering applications that use MSCs.

The crucial roles of inflammatory mediators in inflammation: A review.

The inflammatory response is a crucial aspect of the tissues’ responses to deleterious inflammogens. This complex response involves leukocytes cells such as macrophages, neutrophils, and lymphocytes, also known as inflammatory cells. In response to the inflammatory process, these cells release specialized substances which include vasoactive amines and peptides, eicosanoids, proinflammatory cytokines, and acute-phase proteins, which mediate the inflammatory process by preventing further tissue damage and ultimately resulting in healing and restoration of tissue function. This review discusses the role of the inflammatory cells as well as their by-products in the mediation of inflammatory process. A brief insight into the role of natural anti-inflammatory agents is also discussed. The significance of this study is to explore further and understand the potential mechanism of inflammatory processes to take full advantage of vast and advanced anti-inflammatory therapies. This review aimed to reemphasize the importance on the knowledge of inflammatory processes with the addition of newest and current issues pertaining to this phenomenon.