scholarly journals Screening of Bufadienolides from Toad Venom Identifies Gammabufotalin as a Potential Anti-inflammatory Agent

Planta Medica ◽  
2020 ◽  
Author(s):  
Yuanru Zheng ◽  
Lijuan Deng ◽  
Huihui Cao ◽  
Nishan Xu ◽  
Dongmei Zhang ◽  
...  
Keyword(s):  
Drug Screening ◽  
Inflammatory Diseases ◽  
Primary Response ◽  
Myeloid Differentiation ◽  
Signal Pathways ◽  
Screening Model ◽  
Inflammatory Models ◽  
Alternative Drug ◽  
Toad Venom ◽  
Anti Inflammatory

AbstractToad venom (Chansu) is used in the treatment of infectious and inflammatory diseases in China and East/Southeast Asian countries. However, the anti-inflammatory components of toad venom have not yet been systematically evaluated and clearly defined. To investigate the anti-inflammatory effects of toad venom and identify new anti-inflammatory ingredients, we used zebrafish, an alternative drug screening model, to evaluate the anti-inflammatory effects of 14 bufadienolides previously isolated from toad venom. Most of the bufadienolides were found to exert significant anti-inflammatory effects on lipopolysaccharide-, CuSO4-, or tail transection-induced zebrafish inflammatory models. Moreover, gammabufotalin ( 6) inhibits lipopolysaccharide-induced inflammation by suppressing the myeloid differentiation primary response 88/nuclear factor-kappa B and STAT3 signal pathways. This study confirms the potential of zebrafish in drug screening, clarifies the anti-inflammatory effects of bufadienolides from toad venom, and indicates that gammabufotalin may be developed as a novel therapeutic agent for inflammatory diseases in the future.

scholarly journals Canscora lucidissima, a Chinese folk medicine, exerts anti-inflammatory activities by inhibiting the phosphorylation of ERK1/2 in LPS-activated macrophages

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiao-ling Fei ◽  
Xiao-yu Zhang ◽  
Rui-juan Qi ◽  
Yun-feng Huang ◽  
Yi-xin Han ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Southern China ◽  
Raw 264.7 Cells ◽  
Luciferase Reporter ◽  
Effective Treatment Option ◽  
Proinflammatory Mediators ◽  
Inflammatory Models ◽  
Inflammatory Mechanism ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Background Canscora lucidissima (Levl. & Vaniot) Hand.-Mazz. (C. lucidissima), mainly distributed in southern China, has been shown to be effective in the treatment of inflammatory diseases. However, the underlying mechanism of its anti-inflammatory effect is not fully understood. Methods In this study, we investigated the anti-inflammatory mechanism of ethanol extract of C. lucidissima (Cl-EE) in lipopolysaccharide (LPS)-induced inflammatory models. ELISA, real-time PCR, Western blot and luciferase reporter assay were used for the experiments in vitro, and ICR mouse endotoxemia model was used for in vivo test. Results Our data showed that Cl-EE reduced the production of NO by down-regulating the mRNA and protein expression of inducible nitric oxide synthase (iNOS) in LPS-activated RAW 264.7 cells. Meanwhile, it potently decreased other proinflammatory mediators, such as TNF-α, IL-6, MCP-1 and IL-1β at the transcriptional and translational levels. Further study indicated that Cl-EE did not affect NF-κB signaling pathway but significantly suppressed the phosphorylation of ERK1/2, rather than JNK or p38. In a LPS-induced endotoxemia mouse model, a single intraperitoneal injection of Cl-EE (75–300 mg/kg) could lower circulatory TNF-α, IL-6 and MCP-1 levels. Conclusions Collectively, our results indicated that Cl-EE suppressed the phosphorylation level of ERK1/2 thus reducing the transcription and translation of inflammatory genes, thereby exerted anti-inflammatory activity. This study reveals the anti-inflammatory mechanism of C. lucidissima and may provide an effective treatment option for a variety of inflammatory diseases.

scholarly journals Protective Effects of Astragaloside IV against LPS-Induced Endometritis in Mice through Inhibiting Activation of the NF-κB, p38 and JNK Signaling Pathways

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 373 ◽  
Author(s):  
Fengge Wang ◽  
Shuxiong Chen ◽  
Liang Deng ◽  
Lu Chen ◽  
Yuwen Huang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Diseases ◽  
Signal Pathways ◽  
Protective Effects ◽  
Astragaloside Iv ◽  
Active Components ◽  
Jnk Signaling ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
New Evidence

Endometritis, inflammation of the endometrium, is a common reproductive obstacle disease that can lead to infertility in female animals. Astragaloside IV (AS IV), one of the major and active components of the Astragalus membranaceus (Fisch.) Bunge, is known for its anti-inflammatory effects. In the present study, the effects and mechanisms of AS IV on lipopolysaccharide (LPS)-induced endometritis were investigated using a mouse model. Female mice were prepared with AS IV (0.01 mg/g) by gavage for six days before being stimulated with LPS. The results showed that the histopathological changes, levels of inflammatory cytokines (IL-1β and TNF-α), concentration of NO, and myeloperoxidase (MPO) activity in LPS-induced uteri were attenuated significantly by pretreatment with AS IV. Furthermore, LPS-induced activations of NF-κB, p38, and JNK signal pathways were suppressed by pretreatment with AS IV. In conclusion, the data provided new evidence that AS IV effectively attenuates LPS-induced endometritis through inhibition of TLR4-mediated NF-κB, p38, and JNK signaling pathways, implying that AS IV might become a promising potential anti-inflammatory agent for endometritis and other inflammatory diseases.

scholarly journals The Dual Role of Toll-like Receptor10

2021 ◽  
Author(s):  
Motahareh Dargahi ◽  
Niloufar Taheri ◽  
Zahra Mirsanei ◽  
Arezoo Rasti ◽  
Reza Jafari
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Human Cancer ◽  
Primary Response ◽  
Mitogen Activated Protein Kinase ◽  
Regulatory Function ◽  
Anti Inflammatory

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) family that identify pathogen-associated molecular patterns derived from microbes and activate immune cell response. Following TLRs ligation, different adaptor and transcription molecules such as myeloid differentiation primary response gene 88 (MyD88) and nuclear factor kappa B (NF-kB) are recruited that initiate inflammatory signaling pathways. The human Toll-like receptor 10 (hTLR10) is a novel member of the PRRs family with a regulatory function of immune responses because of unique cytoplasmic domains which lead to induction of both inflammatory and anti-inflammatory properties. Recent studies have reported the association of TLR10 polymorphisms with many inflammatory diseases and human cancer. Engagement of TLR10 on the surface of the epithelium and macrophages leads to the production of proinflammatory cytokines and chemokines, while other studies have proven an anti-inflammatory role of TLR10. Accordingly, TLR10 suppresses proinflammatory cytokine production via negative regulation of MyD88 and the Akt (protein kinase B) and MAPK (mitogen-activated protein kinase) signaling pathways. This review aimed to provide answers for these conflicting findings (Inflammatory and anti-inflammatory properties of TLR10) to further identify distinct biological functions of TLR10.

scholarly journals Smad6 Methylation Represses NFκB Activation and Periodontal Inflammation

2018 ◽  
Vol 97 (7) ◽  
pp. 810-819 ◽  
Author(s):  
T. Zhang ◽  
J. Wu ◽  
N. Ungvijanpunya ◽  
O. Jackson-Weaver ◽  
Y. Gou ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Inflammatory Diseases ◽  
Transforming Growth Factor Β ◽  
Primary Response ◽  
Tissue Homeostasis ◽  
Cytokines And Chemokines ◽  
Periodontal Inflammation ◽  
Anti Inflammatory ◽  
Protein Arginine Methyltransferase 1 ◽  
Systemic Health

The balance between pro- and anti-inflammatory signals maintains tissue homeostasis and defines the outcome of chronic inflammatory diseases such as periodontitis, a condition that afflicts the tooth-supporting tissues and exerts an impact on systemic health. The induction of tissue inflammation relies heavily on Toll-like receptor (TLR) signaling, which drives a proinflammatory pathway through recruiting myeloid differentiation primary response gene 88 (MyD88) and activating nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB). TLR-induced production of proinflammatory cytokines and chemokines is reined in by anti-inflammatory cytokines, including the transforming growth factor β (TGFβ) family of cytokines. Although Smad6 is a key mediator of TGFβ-induced anti-inflammatory signaling, the exact mechanism by which TGFβ regulates TLR proinflammatory signaling in the periodontal tissue has not been addressed to date. In this study, we demonstrate for the first time that the ability of TGFβ to inhibit TLR-NFκB signaling is mediated by protein arginine methyltransferase 1 (PRMT1)–induced Smad6 methylation. Upon methylation, Smad6 recruited MyD88 and promoted MyD88 degradation, thereby inhibiting NFκB activation. Most important, Smad6 is expressed and methylated in the gingival epithelium, and PRMT1-Smad6 signaling promotes tissue homeostasis by limiting inflammation. Consistent with this, disturbance of Smad6 methylation exacerbates inflammation and bone loss in experimental periodontitis. The dissected mechanism is therapeutically important, as it highlights the manipulation of PRMT1-Smad6 signaling as a novel promising strategy to modulate the host immune response in periodontitis.

scholarly journals Anti-Inflammatory Effects of an Extract of Polygonum hydropiper Stalks on 2,4,6-Trinitrobenzenesulphonic Acid-Induced Intestinal Inflammation in Rats by Inhibiting the NF-κB Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Wei Zhang ◽  
Yingni Pan ◽  
Shouhe Qu ◽  
Dongmei Wang ◽  
Song Cheng ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Oral Administration ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Underlying Mechanism ◽  
Signal Pathways ◽  
High Dose ◽  
Polygonum Hydropiper ◽  
Cox 2 ◽  
Anti Inflammatory

The stalks of Polygonum hydropiper L. (PHL) have been traditionally used in clinical practice for thousands of years in China to treat various inflammatory diseases. However, little research has been conducted to investigate the anti-inflammatory effects of PHL on TNBS-induced intestinal inflammation in rats. The aim of the present study was to investigate the anti-inflammatory effects and to explain the underlying mechanism of PHL on TNBS-induced intestinal inflammation in rats. PHL (125, 250, and 500 mg/kg) was given for 7 consecutive days to rats with intestinal inflammation induced by TNBS. Oral administration of an aqueous extract of a high dose of PHL (H-PHL) significantly improved TNBS-induced symptoms such as the macroscopic score and histological examination. H-PHL treatment significantly ameliorated the activity of MPO and improved the GSH content. In addition, there was a downregulation of the TNBS-induced increase in the activity of iNOS and levels of Cox-2, TNF-α, and IL-1β while the protein expression of NF-κB was significantly unregulated after administration of H-PHL. The present findings suggested that H-PHL has a protective effect on experimental intestinal inflammation in rats and its anti-inflammatory effects are closely related to inhibition of NF-κB signal pathways.

scholarly journals Tripterygium wilfordiiGlycosides Upregulate the New Anti-Inflammatory Cytokine IL-37 through ERK1/2 and p38 MAPK Signal Pathways

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Sen Wang ◽  
Rumeng Li ◽  
Suhui He ◽  
Lingge He ◽  
Hang Zhao ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Inflammatory Diseases ◽  
Signal Pathways ◽  
Tripterygium Wilfordii ◽  
Inflammatory Mechanism ◽  
Autoimmune And Inflammatory Diseases ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

As a Chinese traditional patent medicine,Tripterygium wilfordiiglycosides (TWG) have been approved by the China State Food and Drug Administration (Z32021007) for autoimmune and inflammatory diseases. Application of TWG leads to significant decrease of the inflammatory cytokines, such as IL-6, IL-1β, and TNF-α. However, little is known whether TWG could regulate the anti-inflammatory cytokines and what the mechanism is. Here, we found that TWG could induce the upregulation of IL-37 which is a new anti-inflammatory cytokine. Furthermore, the inhibitors of ERK1/2 and/or p38 MAPK pathways suppressed IL-37 expression induced by TWG, indicating that the two pathways took part in this process. In conclusion, TWG could upregulate the anti-inflammatory cytokine IL-37 and ERK1/2 and p38 MAPK signal pathways were involved in the upregulation of IL-37 induced by TWG. The results showed that TWG had a potent activity on promoting the expression of IL-37, a new anti-inflammatory cytokine, which help further understanding the anti-inflammatory mechanism for the clinical application of TWG in therapy of diseases.

Heparin and proteoglycans as anti-inflammatory drugs

1996 ◽  
Vol 16 (01) ◽  
pp. 56-59
Author(s):  
D. J. Tyrrell ◽  
C. P. Page
Keyword(s):  
Inflammatory Diseases ◽  
Therapeutic Applications ◽  
Wide Range ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

SummaryEvidence continues to accumulate that the pleiotropic nature of heparin (beyond its anticoagulant potency) includes anti-inflammatory activities at a number of levels. It is clear that drugs exploiting these anti-inflammatory activities of heparin may offer exciting new therapeutic applications to the treatment of a wide range of inflammatory diseases.

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