Mafenide derivatives inhibit neuroinflammation in Alzheimer's disease by regulating pyroptosis.

The main mechanism of pyroptosis is Caspase-1-mediated GSDMD cleavage, and GSDMD is also the executive protein of pyroptosis. Our previous study has shown that mafenide can inhibit pyroptosis by inhibiting the GSDMD-Asp275 site to suppress cleavage. In this study, sulfonamide was used as the parent nucleus structure to synthesize sulfa-4 and sulfa-20. Screening of drug activity in the pyroptosis model of BV2 and iBMDM cell lines revealed the efficacy of five compounds were superior to mafenide, which exerted a better inhibitory effect on the occurrence of pyroptosis. For in vivo assay, Sulfa-4 and Sulfa-22 were intervened in the neuroinflammation APP/PS1 mice. As a result, the administration of Sulfa-4 and Sulfa-22 could significantly inhibit the activation of microglia, decrease the expression of inflammatory factors in the central nervous system and simultaneously suppress the production of p30-GSDMD as well as the expression of upstream NLRP3 inflammasome and Caspase-1 protein. Immunoprecipitation and Biotin-labelled assay confirmed the targeted binding relationship of Sulfa-4 and Sulfa-22 with GSDMD protein in the iBMDM model in vitro. In this study, we investigated a new type inhibitor of GSDMD cleavage, which exerted a good inhibitory effect on pyroptosis and provided new references for the development of inflammatory drugs in the future.

Pharmacological screening of a new alpha-2 adrenergic receptor agonist, mafedine, in zebrafish.

Pharmacological agents acting at alpha-2 adrenergic receptors are widely used in physiology and neuroscience research. Mounting evidence of their potential utility in clinical and experimental psychopharmacology, necessitates new models and novel model organisms for their screening. Here, we characterize behavioral effects of mafedine (6-oxo-1-phenyl-2- (phenylamino)-1,6-dihydropyrimidine-4-sodium olate), a novel drug with alpha-2 adrenergic receptor agonistic effects, in adult zebrafish (Danio rerio) in the novel tank test of anxiety and activity. Following an acute 20-min exposure, mafedine at 60 mg/L produced a mild psychostimulant action with some anxiogenic-like effects. Repeated acute 20-min/day administration of mafedine for 7 consecutive days at 1, 5 and 10 mg/L had a similar action on fish behavior as an acute exposure to 60 mg/L. Since mafedine demonstrated robust behavioral effects in zebrafish - a sensitive vertebrate aquatic model, it is likely that it may modulate rodent and human behavior as well. Thus, further studies are needed to explore this possibility in detail, and whether it may foster clinical application of mafedine and related alpha-2 adrenergic agents.

Comparison between topical honey and mafenide acetate in treatment of auricular burn.

The auricle is a frequently injured part of the head and neck during thermal injury leading to ear deformity. The burned ear represents one of the most difficult problems for reconstructive surgeons. Mafenide acetate is a topical agent used routinely for these patients, but it has some disadvantages including painful application and allergic rash. Some authors have reported the healing effect and antibacterial activity of honey. The study reported here was undertaken to compare the effect of honey and mafenide acetate on auricular burn in rabbit. In our study, although the pathologic score of the honey group was better than that of the mafenide group both on 14 and 21 days after burning, it was not statistically significant. In the mafenide acetate group, deep complication of burn (chondritis) was significantly lower than that of the honey group. In conclusion, in contrast to healing and antibiotic activity reported for honey, it may have failure in preventing deep bacterial complications of wound (like chondritis). So in deep wounds, the use of honey as dressing is not recommended.

Inhibition of wound contraction by topical antimicrobials.

Spontaneous wound healing occurs partly by wound contraction, a process that requires intact functioning fibroblasts, and collagen production. Disruption of fibroblasts by the topical antimicrobials, silver sulfadiazine and mafenide acetate has been demonstrated in vitro. An acute rat wound model was used to show that wound contraction in vivo is significantly impeded by silver sulfadiazine and mafenide acetate.