Echinochrome A Treatment Alleviates Fibrosis and Inflammation in Bleomycin-Induced Scleroderma

Scleroderma is an autoimmune disease caused by the abnormal regulation of extracellular matrix synthesis and is activated by non-regulated inflammatory cells and cytokines. Echinochrome A (EchA), a natural pigment isolated from sea urchins, has been demonstrated to have antioxidant activities and beneficial effects in various disease models. The present study demonstrates for the first time that EchA treatment alleviates bleomycin-induced scleroderma by normalizing dermal thickness and suppressing collagen deposition in vivo. EchA treatment reduces the number of activated myofibroblasts expressing α-SMA, vimentin, and phosphorylated Smad3 in bleomycin-induced scleroderma. In addition, it decreased the number of macrophages, including M1 and M2 types in the affected skin, suggesting the induction of an anti-inflammatory effect. Furthermore, EchA treatment markedly attenuated serum levels of inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ, in a murine scleroderma model. Taken together, these results suggest that EchA is highly useful for the treatment of scleroderma, exerting anti-fibrosis and anti-inflammatory effects.

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Toxicity and Anti-inflammatory Activities of an Extract of the Eleutherine bulbosa Rhizome on Collagen Antibody-induced Arthritis in a Mouse Model

Natural Product Communications ◽

10.1177/1934578x1801300725 ◽

2018 ◽

Vol 13 (7) ◽

pp. 1934578X1801300

Author(s):

Pham Thi Bich Hanh ◽

Do Thi Thao ◽

Nguyen Thi Nga ◽

Ngo Thi Phuong ◽

Le Ngoc Hung ◽

...

Keyword(s):

Mouse Model ◽

Ethanol Extract ◽

Serum Levels ◽

Negative Control ◽

High Dose ◽

Necrosis Factor Alpha ◽

Beneficial Effects ◽

Anti Inflammatory

As a continuation of our interest in the anti-inflammatory activities of Vietnamese plants, we searched for novel anti-inflammatory agents in Eleutherine bulbosa and evaluated the anti-inflammatory effects of an ethanol extract of the rhizome of E. bulbosa (EBE) on lipopolysaccharide-stimulated RAW 264.7 macrophages in vitro and in a collagen antibody-induced arthritic (CAIA) mouse model in vivo. Treatment of the CAIA mice with EBE decreased the incidence of arthritis, especially at a dose of 1000 mg/kg body weight. A significant ( P<0.05) decrease in the arthritis score was seen after high-dose EBE treatment between days 10 and 14 in comparison with the negative control. The serum levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-10 in the mice were measured using commercial ELISA kits. The results suggest that an ethanol extract of the E. bulbosa rhizome has beneficial effects on inflammatory cytokine regulation in an experimental CAIA model.

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Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway

Molecules ◽

10.3390/molecules26092529 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2529

Author(s):

Haeyeop Kim ◽

Woo Seok Yang ◽

Khin Myo Htwe ◽

Mi-Nam Lee ◽

Young-Dong Kim ◽

...

Keyword(s):

Ethanol Extract ◽

Serum Levels ◽

Hepatoprotective Activity ◽

Tnf Α ◽

Anti Inflammatory ◽

Related Proteins ◽

Pro Inflammatory Cytokines ◽

Inflammatory Effect

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.

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Periplaneta americana Oligosaccharides Exert Anti-Inflammatory Activity through Immunoregulation and Modulation of Gut Microbiota in Acute Colitis Mice Model

Molecules ◽

10.3390/molecules26061718 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1718

Author(s):

Kaimin Lu ◽

Jing Zhou ◽

Jie Deng ◽

Yangjun Li ◽

Chuanfang Wu ◽

...

Keyword(s):

Side Effects ◽

Pathogenic Bacteria ◽

Periplaneta Americana ◽

Biochemical Characterization ◽

Antioxidant Activities ◽

Inflammatory Activity ◽

Mice Model ◽

Acute Colitis ◽

Anti Inflammatory

The incidence and prevalence of inflammatory bowel disorders (IBD) are increasing around the world due to bacterial infection, abnormal immune response, etc. The conventional medicines for IBD treatment possess serious side effects. Periplaneta americana (P. americana), a traditional Chinese medicine, has been used to treat arthritis, fever, aches, inflammation, and other diseases. This study aimed to evaluate the anti-inflammatory effects of oligosaccharides from P. Americana (OPA) and its possible mechanisms in vivo. OPA were purified and biochemical characterization was analyzed by HPGPC, HPLC, FT-IR, and GC–MS. Acute colitis mice model was established, the acute toxicity and anti-inflammatory activity were tested in vivo. The results showed OPA with molecular mass of 1.0 kDa were composed of 83% glucose, 6% galactose, 11% xylose, and the backbone was (1→4)-Glcp. OPA had potent antioxidant activities in vitro and significantly alleviated the clinical symptoms of colitis, relieved colon damage without toxic side effects in vivo. OPA exhibited anti-inflammatory activity by regulating Th1/Th2, reducing oxidative stress, preserving intestinal barrier integrity, and inhibiting TLR4/MAPK/NF-κB pathway. Moreover, OPA protected gut by increasing microbial diversity and beneficial bacteria, and reducing pathogenic bacteria in feces. OPA might be the candidate of complementary and alternative medicines of IBD with low-cost and high safety.

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In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽

10.3390/biomedicines9060615 ◽

2021 ◽

Vol 9 (6) ◽

pp. 615

Author(s):

Shang-En Huang ◽

Erna Sulistyowati ◽

Yu-Ying Chao ◽

Bin-Nan Wu ◽

Zen-Kong Dai ◽

...

Keyword(s):

Articular Cartilage ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Antioxidant Properties ◽

Serum Levels ◽

Gene Expressions ◽

Tnf Α ◽

Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

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FGF1ΔHBS prevents diabetic cardiomyopathy by maintaining mitochondrial homeostasis and reducing oxidative stress via AMPK/Nur77 suppression

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00542-2 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Dezhong Wang ◽

Yuan Yin ◽

Shuyi Wang ◽

Tianyang Zhao ◽

Fanghua Gong ◽

...

Keyword(s):

Diabetic Cardiomyopathy ◽

Metabolic Regulation ◽

Cardiac Injury ◽

Serum Levels ◽

Ros Generation ◽

Dependent Manner ◽

Cardiac Tissues ◽

Beneficial Effects

AbstractAs a classically known mitogen, fibroblast growth factor 1 (FGF1) has been found to exert other pleiotropic functions such as metabolic regulation and myocardial protection. Here, we show that serum levels of FGF1 were decreased and positively correlated with fraction shortening in diabetic cardiomyopathy (DCM) patients, indicating that FGF1 is a potential therapeutic target for DCM. We found that treatment with a FGF1 variant (FGF1∆HBS) with reduced proliferative potency prevented diabetes-induced cardiac injury and remodeling and restored cardiac function. RNA-Seq results obtained from the cardiac tissues of db/db mice showed significant increase in the expression levels of anti-oxidative genes and decrease of Nur77 by FGF1∆HBS treatment. Both in vivo and in vitro studies indicate that FGF1∆HBS exerted these beneficial effects by markedly reducing mitochondrial fragmentation, reactive oxygen species (ROS) generation and cytochrome c leakage and enhancing mitochondrial respiration rate and β-oxidation in a 5’ AMP-activated protein kinase (AMPK)/Nur77-dependent manner, all of which were not observed in the AMPK null mice. The favorable metabolic activity and reduced proliferative properties of FGF1∆HBS testify to its promising potential for use in the treatment of DCM and other metabolic disorders.

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Natural feed contaminant zearalenone decreases the expressions of important pro- and anti-inflammatory mediators and mitogen-activated protein kinase/NF-κB signalling molecules in pigs

British Journal Of Nutrition ◽

10.1017/s0007114513002675 ◽

2013 ◽

Vol 111 (3) ◽

pp. 452-464 ◽

Cited By ~ 38

Author(s):

Gina Cecilia Pistol ◽

Mihail Alexandru Gras ◽

Daniela Eliza Marin ◽

Florentina Israel-Roming ◽

Mariana Stancu ◽

...

Keyword(s):

Immune Response ◽

Protein Kinase ◽

Matrix Metalloproteinases ◽

Inflammatory Mediators ◽

Interferon Γ ◽

Mitogen Activated Protein Kinase ◽

Economic Point ◽

Mitogen Activated Protein ◽

Anti Inflammatory

Zearalenone (ZEA) is an oestrogenic mycotoxin produced byFusariumspecies, considered to be a risk factor from both public health and agricultural perspectives. In the presentin vivostudy, a feeding trial was conducted to evaluate thein vivoeffect of a ZEA-contaminated diet on immune response in young pigs. The effect of ZEA on pro-inflammatory (TNF-α, IL-8, IL-6, IL-1β and interferon-γ) and anti-inflammatory (IL-10 and IL-4) cytokines and other molecules involved in inflammatory processes (matrix metalloproteinases (MMP)/tissue inhibitors of matrix metalloproteinases (TIMP), nuclear receptors: PPARγ and NF-κB1, mitogen-activated protein kinases (MAPK): mitogen-activated protein kinase kinase kinase 7 (TAK1)/mitogen-activated protein kinase 14 (p38α)/mitogen-activated protein kinase 8 (JNK1)/ mitogen-activated protein kinase 9 (JNK2)) in the liver of piglets was investigated. The present results showed that a concentration of 316 parts per billion ZEA leads to a significant decrease in the levels of pro- and anti-inflammatory cytokines at both gene expression and protein levels, correlated with a decrease in the levels of other inflammatory mediators, MMP and TIMP. The results also showed that dietary ZEA induces a dramatic reduction in the expressions ofNF-κB1andTAK1/p38αMAPK genes in the liver of the experimentally intoxicated piglets, and has no effect on the expression ofPPARγmRNA. The present results suggest that the toxic action of ZEA begins in the upstream of the MAPK signalling pathway by the inhibition of TAK1, a MAPK/NF-κB activator. In conclusion, the present study shows that ZEA alters several important parameters of the hepatic cellular immune response. From an economic point of view, these data suggest that, in pigs, ZEA is not only a powerful oestrogenic mycotoxin but also a potential hepatotoxin when administered through the oral route. Therefore, the present results represent additional data from cellular and molecular levels that could be taken into account in the determination of the regulation limit of the tolerance to ZEA.

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Cyclosporine increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00543.2007 ◽

2008 ◽

Vol 294 (3) ◽

pp. R811-R818 ◽

Cited By ~ 31

Author(s):

Chao-Hung Wang ◽

Wen-Jin Cherng ◽

Ning-I Yang ◽

Chia-Ming Hsu ◽

Chi-Hsiao Yeh ◽

...

Keyword(s):

Critical Role ◽

Serum Levels ◽

Blood Levels ◽

Short Term ◽

Endothelial Progenitor ◽

Beneficial Effects ◽

Dpp Iv ◽

Before And After ◽

Cell Mobilization

Cyclosporin A (CsA) improves the success rate of transplantation. The CD26/dipeptidylpeptidase IV (DPP IV) system plays a critical role in mobilizing endothelial progenitor cells (EPCs) from bone marrow. This study investigated whether CsA manipulates CD26/DPP IV activity and increases EPC mobilization. C57BL/6 mice were divided into control and CsA-treated groups. Before and after hindlimb ischemia was induced, circulating EPC number and serum levels of different cytokines were measured. Compared with the controls, CsA treatment significantly increased the blood levels of stroma-derived factor-1α and stem cell factor after ischemic stress ( P < 0.001). The CsA group displayed a significant increase in the number of circulating EPCs (sca-1+KDR+ and c-kit+CD31+ EPCs, both P < 0.05). In vivo, CsA caused a significant increase in the numbers of EPCs incorporated into the Matrigel and ischemic limbs ( P < 0.05). In the peripheral blood, CsA significantly decreased CD26+ cell numbers and attenuated the plasma CD26/DPP IV activity ( P < 0.001). Furthermore, short-term CsA treatment significantly improved the perfusion of ischemic limbs and decreased the spontaneous digital amputation rate. In summary, CsA manipulates the mobilization of EPCs into the circulation via the CD26/DPP IV system. Short-term CsA treatment has beneficial effects on angiogenesis of ischemic tissues.

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Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor

Mediators of Inflammation ◽

10.1155/2019/3041438 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Mohamed A. Morsy ◽

Snehal S. Patel ◽

Azza A. K. El-Sheikh ◽

Jignasa K. Savjani ◽

Anroop B. Nair ◽

...

Keyword(s):

Side Effects ◽

Glucocorticoid Receptor ◽

Tumor Necrosis ◽

Serum Levels ◽

Withaferin A ◽

Boswellic Acid ◽

Cotton Pellet ◽

Anti Inflammatory ◽

Necrosis Factor

Despite the usefulness of glucocorticoids, they may cause hazardous side effects that limit their use. Searching for compounds that are as equally efficient as glucocorticoids, but with less side effects, the current study compared plant steroids, namely, glycyrrhetinic acid, guggulsterone, boswellic acid, withaferin A, and diosgenin with the classical glucocorticoid, fluticasone. This was approached both in silico using molecular docking against glucocorticoid receptor (GR) and in vivo in two different animal models. All tested compounds interacted with GR, but only boswellic acid and withaferin A showed docking results comparable to fluticasone, as well as similar in vivo anti-inflammatory effects, by significantly decreasing serum levels of interleukin-6 and tumor necrosis factor-α in cotton pellet-induced granuloma in rats. In addition, both compounds significantly decreased the percent of change in ear weight in croton oil-induced ear edema in mice and the granuloma weight in cotton pellet-induced granuloma in rats, to levels comparable to that of fluticasone. Both boswellic acid and withaferin A had no effect on adrenal index, but only withaferin A significantly increased the thymus index. In conclusion, boswellic acid may have comparable anti-inflammatory effects to fluticasone with fewer side effects.

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2,5-disubstituted-4-thiazolidinones: Synthesis, anti-inflammatory, free radical scavenging potentials and structural insights through molecular docking

Letters in Organic Chemistry ◽

10.2174/1570178618666210706111055 ◽

2021 ◽

Vol 18 ◽

Author(s):

Jagseer Singh ◽

Pooja A Chawla ◽

Rohit Bhatia ◽

Shamsher Singh

Keyword(s):

Free Radicals ◽

Antioxidant Activities ◽

Radical Scavenging ◽

Assay Method ◽

Acidic Group ◽

Active Compounds ◽

Cox 2 ◽

Anti Inflammatory

: The present work reports synthesis and screening of fifteen 2,5-disubstituted-4-thiazolidinones with different substitutions of varied arylidene groups at imino. The structures of the compounds were confirmed by spectral characterization. The compounds were subjected to in vivo anti-inflammatory and in vitro antioxidant activities. The derivatives possessed remarkable activities quite close to standard drugs used. Unlike conventional non-selective NSAIDs, the synthesized compounds did not contain any acidic group, thereby ensuring a complete cure from ulcers. To further substantiate the claim for safer derivatives, the active compounds were docked against the cyclooxygenase (COX)-2 enzyme. It was found that 4-fluorophenylimino substituent at 2- position and 3-nitro moiety on a 5-benzylidene nucleus of the 4-thiazolidinone derivative fitted in the COX-2 binding pocket. The compounds exhibited remarkable activity in scavenging free radicals, as depicted by the DPPH assay method. The structure-activity relationship was also established in the present work with respect to the nature and position of the substituents. The active compounds were evaluated for drug-like nature under Lipinski’s rule of five, and the toxicity behaviour of active compounds was predicted using ADMETlab software. The compounds have the potential to target degenerative disorders associated with inflammation and the generation of free radicals.

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Identification of a Kavain Analog with Efficient Anti-inflammatory Effects

Scientific Reports ◽

10.1038/s41598-019-49383-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Olivier Huck ◽

Xiaxian Han ◽

Hannah Mulhall ◽

Iryna Gumenchuk ◽

Bin Cai ◽

...

Keyword(s):

Joint Destruction ◽

Cell Types ◽

Interferon Γ ◽

Piper Methysticum ◽

Tnf Α ◽

Osteoclast Activation ◽

Anti Inflammatory ◽

Soft Tissue Inflammation

Abstract Kavain, a compound derived from Piper methysticum, has demonstrated anti-inflammatory properties. To optimize its drug properties, identification and development of new kavain-derived compounds was undertaken. A focused library of analogs was synthesized and their effects on Porphyromonas gingivalis (P. gingivalis) elicited inflammation were evaluated in vitro and in vivo. The library contained cyclohexenones (5,5-dimethyl substituted cyclohexenones) substituted with a benzoate derivative at the 3-position of the cyclohexanone. The most promising analog identifed was a methylated derivative of kavain, Kava-205Me (5,5-dimethyl-3-oxocyclohex-1-en-1-yl 4-methylbenzoate.) In an in vitro assay of anti-inflammatory effects, murine macrophages (BMM) and THP-1 cells were infected with P. gingivalis (MOI = 20:1) and a panel of cytokines were measured. Both cell types treated with Kava-205Me (10 to 200 μg/ml) showed significantly and dose-dependently reduced TNF-α secretion induced by P. gingivalis. In BMM, Kava-205Me also reduced secretion of other cytokines involved in the early phase of inflammation, including IL-12, eotaxin, RANTES, IL-10 and interferon-γ (p < 0.05). In vivo, in an acute model of P. gingivalis-induced calvarial destruction, administration of Kava-205Me significantly improved the rate of healing associated with reduced soft tissue inflammation and osteoclast activation. In an infective arthritis murine model induced by injection of collagen-antibody (ArthriomAb) + P. gingivalis, administration of Kava-205Me was able to reduce efficiently paw swelling and joint destruction. These results highlight the strong anti-inflammatory properties of Kava-205Me and strengthen the interest of testing such compounds in the management of P. gingivalis elicited inflammation, especially in the management of periodontitis.

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