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Implementing combination medication through crystal engineering technology receives increasing attention from researchers due to improvements in the clinical treatment effects as well as the physicochemical properties of the drug. Berberine (BER) is commonly used to treat gastroenteritis and bacterial diarrhea, with the problems of poor solubility and low oral bioavailability. Recently, it is found that gallic acid (GA) also has anti‐inflammatory and anti‐bacterial activities. Therefore, if the above‐mentioned two ingredients can be combined, it is possible to enhance the therapeutic effects and physicochemical properties of BER. Inspired by this, 8‐hydroxy‐7,8‐dihydroberberine (8H‐HBER) in this study is employed to react with gallic acid to yield BER gallate dihydrate (2BER‐2GA‐2 W). Furthermore, dissolution experiments demonstrate that the maximum apparent solubility (MAS) of 2BER‐2GA‐2 W in dilute hydrochloric acid solution medium (pH 1.2) has increased by 7 times compared to the commercial form of BER, because of avoiding the common‐ion effect. Moreover, 2BER‐2GA‐2 W has also obviously enhanced stability relative to the commercial form of BER. In addition, 2BER‐2GA‐2 W has a better inhibitory effect on Staphylococcus aureus (S. aureus) relative to the commercial form of BER. Hence, 2BER‐2GA‐2 W will be a promising solid‐state form of BER for its further development. [ABSTRACT FROM AUTHOR]

Myriocin is an inhibitor of de novo synthesis of sphingolipids and ceramides. In this research, we showed myriocin could significantly reduce Mtb burden and histopathological inflammation in mice. However, the underlying mechanism remains unclear. RNA-seq analysis revealed a significant increase in gene expression of PLIN2/CD36/CERT1 after myriocin treatment. The reduced bactericidal burden was only reversed after silencing the lipid droplets (LDs) surface protein PLIN2. This suggests that myriocin enhances the ability of macrophages to clear Mtb depending on the PLIN2 gene, which is part of the PPARγ pathway. Indeed, we observed a significant increase in the number of LDs following myriocin treatment.IMPORTANCE Mycobacterium tuberculosis has the ability to reprogram host cell lipid metabolism and alter the antimicrobial functions of infected macrophages. The sphingolipids, such as ceramides, are the primary host lipids utilized by the bacteria, making the sphingomyelinase/ceramide system critical in Mtb infections. Surprisingly, the antimicrobial effect of myriocin was found to be independent of its role in reducing ceramides, but instead, it depends on the lipid droplets surface protein PLIN2. Our findings provide a novel mechanism for how myriocin enhances Mtb clearance in macrophages.