Inhibition of endoplasmic reticulum stress alleviates secondary injury after traumatic brain injury.

Apoptosis after traumatic brain injury has been shown to be a major factor influencing prognosis and outcome. Endoplasmic reticulum stress may be involved in mitochondrial mediated neuronal apoptosis. Therefore, endoplasmic reticulum stress has become an important mechanism of secondary injury after traumatic brain injury. In this study, a rat model of traumatic brain injury was established by lateral fluid percussion injury. Fluorescence assays were used to measure reactive oxygen species content in the cerebral cortex. Western blot assays were used to determine expression of endoplasmic reticulum stress-related proteins. Hematoxylin-eosin staining was used to detect pathological changes in the cerebral cortex. Transmission electron microscopy was used to measure ultrastructural changes in the endoplasmic reticulum and mitochondria. Our results showed activation of the endoplasmic reticulum stress-related unfolded protein response. Meanwhile, both the endoplasmic reticulum stress response and mitochondrial apoptotic pathway were activated at different stages post-traumatic brain injury. Furthermore, pretreatment with the endoplasmic reticulum stress inhibitor, salubrinal (1 mg/kg), by intraperitoneal injection 30 minutes before injury significantly inhibited the endoplasmic reticulum stress response and reduced apoptosis. Moreover, salubrinal promoted recovery of mitochondrial function and inhibited activation of the mitochondrial apoptotic pathway post-traumatic brain injury. These results suggest that endoplasmic reticulum stress might be a key factor for secondary brain injury post-traumatic brain injury.

In Vitro Synergy of Biochanin A and Ciprofloxacin against Clinical Isolates of Staphylococcus aureus.

Many clinical isolates of Staphylococcus aureus (S. aureus) are resistant to numerous antimicrobials, including the fluoroquinolones (FQs). Flavonoids such as biochanin A (BCA) are compounds that are naturally present in fruits, vegetables, and plant-derived beverages. The goal of this investigation was to study the possible synergy between the antimicrobial agents BCA and ciprofloxacin (CPFX) when used in combination; CPFX was chosen as a representative FQ compound. We used S. aureus strain ATCC 25923 and 11 fluoroquinolone (FQ)-resistant methicillin-resistant S. aureus (MRSA) strains. Results from the drug susceptibility testing and checkerboard assays show that the minimum inhibitory concentration (MIC) of BCA ranged from 64 µg/mL to 512 µg/mL. When BCA was combined with CPFX, the fractional inhibitory concentration index (FICI) data showed that there was synergy in all 12 of the S. aureus strains tested. No antagonistic activity was observed in any of the strains tested. The results of time-kill tests and agar diffusion tests confirm that there was synergy between BCA and CPFX against S. aureus strains. These results suggest that BCA can be combined with FQs to produce a powerful antimicrobial agent.

Farnesol, a potential efflux pump inhibitor in Mycobacterium smegmatis.

The active multidrug efflux pump (EP) has been described as one of the mechanisms involved in the natural drug resistance of bacteria, such as mycobacteria. As a result, the development of efflux pumps inhibitors (EPIs) is an important topic. In this study, a checkerboard synergy assay indicated that farnesol both decreased the minimum inhibitory concentration (MIC) of ethidium bromide (EtBr) 8-fold against Mycobacterium smegmatis (M. smegmatis) mc²155 ATCC 700084 when incorporated at a concentration of 32 µg/mL (FICI = 0.625) and decreased MIC 4-fold at 16 µg/mL (FICI = 0.375). Farnesol also showed synergism when combined with rifampicin. A real-time 96-well plate fluorometric method was used to assess the ability of farnesol to inhibit EPs in comparison with four positive EPIs: chlorpromazine, reserpine, verapamil, and carbonyl cyanide m-chlorophenylhydrazone (CCCP). Farnesol significantly enhanced the accumulation of EtBr and decreased the efflux of EtBr in M. smegmatis; these results suggest that farnesol acts as an inhibitor of mycobacterial efflux pumps.