A new approach to anti-inflammatory drugs

1979 ◽  
Vol 28 (12) ◽  
pp. 1959-1961 ◽  
Author(s):  
Gerald A. Higgs ◽  
Roderick J. Flower ◽  
John R. Vane
Keyword(s):  
New Approach ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

scholarly journals N,N-Dimethylformamide Prevents LPS-Induced Preterm Birth in a Murine Model by Suppressing the Inflammatory Response

2021 ◽  
Author(s):  
Zeng-Hui Wei ◽  
Oluwabukola Salami ◽  
Jagadish Koya ◽  
Swapna Munnangi ◽  
Ryan Pekson ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Murine Model ◽  
Raw 264.7 Cells ◽  
New Approach ◽  
Affect Cell Viability ◽  
Pregnant Mice ◽  
Inflammatory Drugs ◽  
The Common ◽  
Anti Inflammatory

Abstract Preterm birth accounts for the majority of perinatal mortality worldwide and there remains no FDA-approved drug to prevent it. Recently, we discovered that the common drug excipient, N,N-dimethylacetamide (DMA), prevents inflammation–induced preterm birth in mice by inhibiting NF-κB. Since we reported this finding it has come to light that a group of widely used, structurally related aprotic solvents, including DMA, N-methyl-2-pyrrolidone (NMP) and dimethylformamide (DMF), have anti-inflammatory efficacy. We show here that DMF suppresses LPS-induced TNFα secretion from RAW 264.7 cells and IL-6 and IL-8 secretion from HTR-8 cells at concentrations that do not significantly affect cell viability. In vivo, DMF decreases LPS-induced inflammatory cell infiltration and expression of TNFα and IL-6 in the placental labyrinth, all to near baseline levels. Finally, DMF decreases the rate of preterm birth in LPS-induced pregnant mice (P<.0001) and the rate at which pups are spontaneously aborted (P<.0001). In summary, DMF, a widely used solvent structurally related to DMA and NMP, prevents LPS-induced preterm birth in a murine model without overt toxic or teratogenic effects. Re-purposing the DMA/DMF/NMP family of small molecules as anti-inflammatory drugs is a promising new approach to preventing inflammation–induced preterm birth and potentially other inflammatory disorders as well.

scholarly journals Investigation of Pharmacological Mechanism of Natural Product Using Pathway Fingerprints Similarity Based on “Drug-Target-Pathway” Heterogenous Network

2021 ◽  
Author(s):  
Feifei Guo ◽  
Chunhong Jiang ◽  
Yujie Xi ◽  
Dan Wang ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Natural Products ◽  
Heterogeneous Network ◽  
Drug Target ◽  
Computational Prediction ◽  
Experimental Result ◽  
New Approach ◽  
Pharmacological Mechanism ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Approved Drugs

Abstract Natural products from traditional medicine inherit bioactivity from their source herbs. However, the pharmacological mechanism of natural products is often unclear and studied insufficiently. Pathway fingerprint similarity based on “drug-target-pathway” heterogeneous network provides new insight into Mechanism of Action (MoA) for natural products compared with reference drugs, which are selected approved drugs with similar bioactivity. Natural products with similar pathway fingerprints may have similar MoA to approved drugs. In our study, XYPI, an andrographolide derivative, had similar anti-inflammatory activity to Glucocorticoids (GCs) and Nonsteroidal Anti-inflammatory Drugs (NSAIDs), and GCs and NSAIDs have completely different MoA. Based on similarity evaluation, XYPI has similar pathway fingerprints as NSAIDs, but has similar target profile with GCs. The expression pattern of genes in LPS-activated macrophages after XYPI treatment is similar to that after NSAID but not GC treatment, and this experimental result is consistent with the computational prediction based on pathway fingerprints. These results imply that the pathway fingerprints of drugs have potential for drug similarity evaluation. This study used XYPI as an example to propose a new approach for investigating the pharmacological mechanism of natural products using pathway fingerprint similarity based on a “drug-target-pathway” heterogeneous network.

Sign in / Sign up

Export Citation Format

Share Document