RESUMO
The process of drug discovery and drug development consumes billions of dollars to bring a new drug to the market. Drug development is time consuming and sometimes, the failure rates are high. Thus, the pharmaceutical industry is looking for a better option for new drug discovery. Drug repositioning is a good alternative technology that has demonstrated many advantages over de novo drug development, the most important one being shorter drug development timelines. In the last two decades, drug repositioning has made tremendous impact on drug development technologies. In this review, we focus on the recent advances in drug repositioning technologies and discuss the repositioned drugs used for inflammatory diseases such as sepsis, asthma, and atopic dermatitis.
RESUMO
Atopic dermatitis (AD) is a common inflammatory skin disorder mediated by inflammatory cells, such as macrophages and mast cells. Rifampicin is mainly used for the treatment of tuberculosis. Recently, it was reported that rifampicin has anti-inflammatory and immune-suppressive activities. In this study, we investigated the effect of rifampicin on atopic dermatitis in vivo and in vitro. AD was induced by treatment with 2, 4-dinitrochlorobenzene (DNCB) in NC/Nga mice. A subset of mice was then treated with rifampicin by oral administration. The severity score and scratching behavior were alleviated in the rifampicin-treated group. Serum immunoglobulin E (IgE) and interleukin-4 (IL-4) levels were also ameliorated in mice treated with rifampicin. We next examined whether rifampicin has anti-atopic activity via suppression of mast cell activation. Rifampicin suppressed the release of ß-hexosaminidase and histamine from human mast cell (HMC)-1 cultures stimulated with compound 48/80. Treatment with rifampicin also inhibited secretion of inflammatory mediators, such tumor necrosis factor-α (TNF-α) and prostaglandin D2 (PGD2), in mast cells activated by compound 48/80. The mRNA expression of cyclooxygenase 2 (COX-2) was reduced in the cells treated with rifampicin in a concentration-dependent manner. These results suggest that rifampicin can be used to treat atopic dermatitis.
RESUMO
Secondary mechanisms, including inflammation and microglia activation, serve as targets for the development and application of pharmacological strategies in the management of spinal cord injury (SCI). Tetramethylpyrazine (TMP), an active ingredient of Ligusticum wallichii (chuanxiong), has shown anti-inflammatory and neuroprotective effects against SCI. However, it remains uncertain whether the inflammation-suppressive effects of TMP play a modulatory role over microglia activation in SCI. The present study investigated the effects of TMP on microglia activation and pro-inflammatory cytokines in spinal cord compression injury in mice. For a real-time PCR measurement of pro-inflammatory cytokines, SCI was induced in mice by the clip compression method (30 g force, 1 min) and TMP (15 or 30 mg/kg, i.p.) was administered once, 30 minutes before the SCI induction. For immunohistochemistry, TMP (30 mg/kg, i.p.) treatment was given three times during the first 48 hours after the SCI. 30 mg/kg of TMP treatment reduced the up-regulation of TNF-α, IL-1ß and COX-2 mRNA in the spinal tissue at four hours after the SCI induction. TMP also significantly attenuated microglia activation and neutrophil infiltration at 48 hours after the SCI induction. In addition, iNOS expression in the spinal tissue was attenuated with TMP treatment. These results suggest that TMP plays a modulatory role in microglia activation and may protect the spinal cord from or potentially delay secondary spinal cord injury.
