Berberine augments ATP-induced inflammasome activation in macrophages by enhancing AMPK signaling

Abstract

The isoquinoline alkaloid berberine possesses many pharmacological activities including antibacterial infection. Although the direct bactericidal effect of berberine has been documented, its influence on the antibacterial functions of macrophages is largely unknown. As inflammasome activation in macrophages is important for the defense against bacterial infection, we aimed to investigate the influence of berberine on inflammasome activation in murine macrophages. Our results showed that berberine significantly increased ATP-induced inflammasome activation as reflected by enhanced pyroptosis as well as increased release of caspase-1p10 and mature interleukin-1β (IL-1β) in macrophages. Such effects of berberine could be suppressed by AMP-activated protein kinase (AMPK) inhibitor compound C or by knockdown of AMPKα expression, indicating the involvement of AMPK signaling in this process. In line with increased IL-1β release, the ability of macrophages to kill engulfed bacteria was also intensified by berberine. This was corroborated by the in vivo finding that the peritoneal live bacterial load was decreased by berberine treatment. Moreover, berberine administration significantly improved survival of bacterial infected mice, concomitant with increased IL-1β levels and elevated neutrophil recruitment in the peritoneal cavity. Collectively, these data suggested that berberine could enhance bacterial killing by augmenting inflammasome activation in macrophages through AMPK signaling.

Berberine Inhibits Nod-Like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation and Pyroptosis in Nonalcoholic Steatohepatitis via the ROS/TXNIP Axis

“…The roles of BBR on pyroptosis may vary in different diseases. Li et al (2017) discovered that BBR significantly increased ATP-induced pyroptosis and increased the release of caspase-1, p10, and IL-1b in macrophages. A research in 2016 (Chu et al, 2016) revealed that BBR could induce pyroptosis in HepG2 cells via activating caspase-1.…”

Baicalin Inhibits NOD-Like Receptor Family, Pyrin Containing Domain 3 Inflammasome Activation in Murine Macrophages by Augmenting Protein Kinase A Signaling

“…Mouse BMDMs were differentiated as reported previously ( 21 , 39 ). Briefly, mice were sacrificed and bone marrows were collected from the femurs.…”

“…Cell death was measured by PI incorporation as described previously ( 39 , 40 ). Cells were cultured in 24-well plates and primed with 500 ng/ml LPS in Opti-MEM for 4 h. Subsequently, cells were treated with indicated concentrations of baicalin in Opti-MEM for 1 h followed by stimulation with ATP (3 mM) for 30 min or nigericin (10 µM) for 1 h. The cells were stained with PI solution (2 µg/ml PI plus 5 µg/ml Hoechst 33342) for 10 min at room temperature and observed immediately by live imaging using Zeiss Axio Observer D1 microscope equipped with a Zeiss LD Plan-Neofluar 20×/0.4 Korr M27 objective lens (Carl Zeiss MicroImaging GmbH, Göttingen, Germany).…”

The status of and trends in the pharmacology of berberine: a bibliometric review [1985–2018]

“…As the number of patients with metabolic diseases continues to rise, it is essential to find a way to treat this diseases. And current research shows that berberine can play an important role in the treatment of nonalcoholic fatty liver through its anti-inflammatory mechanisms and in metabolism by inducing the activation of the AMPK pathway [37][38][39][40]. So it can be speculated that this will be one of the focus of future development.…”