Gallic acid promotes macrophage phagosome acidification and phagolysosome formation by activating NLRP3/mTOR signaling pathway.

INTRODUCTION: Gallic acid (GA) has a good therapeutic effect in bacteriological inhibition and plays a variety of functions in maintaining the stability of the immune system. The aim of the present study was to investigate the effect of GA on the bactericidal activity of macrophages against Vibrio vulnificus (Vv). METHODS: A cell counting kit-8 (CCK-8) assay was carried out to test the cytotoxicity of GA on J774A.1 cells. Concentration of proinflammatory cytokines in J774A.1 cells were evaluated by ELISA. The internalization and degradation of Vv in the phagosomes were observed by transmission electron microscopy (TEM). The phagosome acidification and phagolysosome formation were detected to evaluate the bacteria-clearing function of J774A.1 cells. The bactericidal activity of GA in vivo was also investigated by collecting the survival time of Vv infected mice and observing the inflammatory infiltration of organs. RESULTS: Our results demonstrated that GA at 50 µM significantly inhibited the proinflammatory cytokines levels, promoted phagosome acidification and phagolysosome formation in J774A.1 cells with Vv infection. This may be related to the activation of NLRP3/mTOR signaling pathway. Additionally, GA treatment improves the survival and bactericidal activity of mice infected with Vv. CONCLUSIONS: In summary, GA exerts bactericidal activity against Vv infection by regulating the formation and acidification of phagocytic lysosomes in macrophages.

Antifungal activity of compounds from Gordonia sp. WA8-44 isolated from the gut of Periplaneta americana and molecular docking studies.

Invasive fungal infections are on the rise, leading to a continuous demand for antifungal antibiotics. Rare actinomycetes have been shown to contain a variety of interesting compounds worth exploring. In this study, 15 strains of rare actinobacterium Gordonia were isolated from the gut of Periplaneta americana and screened for their anti-fungal activity against four human pathogenic fungi. Strain WA8-44 was found to exhibit significant anti-fungal activity and was selected for bioactive compound production, separation, purification, and characterization. Three anti-fungal compounds, Collismycin A, Actinomycin D, and Actinomycin X2, were isolated from the fermentation broth of Gordonia strain WA8-44. Of these, Collismycin A was isolated and purified from the secondary metabolites of Gordonia for the first time, and its anti-filamentous fungi activity was firstly identified in this study. Molecular docking was carried out to determine their hypothetical binding affinities against nine target proteins of Candida albicans. Chitin Synthase 2 was found to be the most preferred antimicrobial protein target for Collismycin A, while 1,3-Beta-Glucanase was the most preferred anti-fungal protein target for Actinomycin D and Actinomycin X2. ADMET prediction revealed that Collismycin A has favorable oral bioavailability and little toxicity, making it a potential candidate for development as an orally active medication.

[Evaluation of balanced release of complex components of Chuanping sustained tablets based on fingerprint].

To combine fingerprint and drug release rate in vitro, in order to study in vitro release of complex components of Chuanping sustained tablets, compound traditional Chinese medicine preparation. A qualitative determination of the characteristic peaks of the compound preparations were conducted by the fingerprint. The results of the dissolution rate determination under different release conditions showed that the release of three index components (methamphetamine, pseudoephedrine and scopolamine) of Chuanping sustained tablets was less affected by gastrointestinal factors, with similarity factors being more than 80 with unknown component release curves of three major characteristic peaks in the fingerprint. The qualitative determination proved that multiple components of the compound traditional Chinese medicine preparation was dissolved in vitro at similar rates, realizing the balanced release of complex components of the compound traditional Chinese medicine preparation. This study layed a theoretical and experimental basis for quality evaluation for the compound traditional Chinese medicine preparation.

[Correlation between dissolution in vitro and absorption in vivo of chuanping sustained release tablets].

OBJECTIVE: To investigate the correlation between dissolution in vitro and absorption in vivo of Chuanping sustained release tablets. METHOD: The ephedrine, pseudoephedrine were chosen as marker components, dissolution in vitro of Chuanping sustained release tablets in the different pH were tested by the rotating basket method and HPLC; urine drug levels were determined by HPLC and absorption fractions were calculated according to Wagner-Nelson's formula and deconvolution technique. RESULT: The linear regressive equation between the absorption percentage in vivo F and accumulative release percentage in vitro of Chuanping sustained release tablets was established as F(ephedrine) = 1.572 5f-20. 729 (R2 = 0.974 5); F(pseudoephedrine) = 1.237f-0.147 6 (R2 = 0.959 5). CONCLUSION: The results suggested that there was fine correlation between the absorption percentage in vivo and the accumulative release percentage in vitro of Chuanping sustained release tablets.