Mechanistic insight into the attenuation of gouty inflammation by Taiwanese green propolis via inhibition of the NLRP3 inflammasome

Abstract

Dysregulation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3)inflammasome is involved in many chronic inflammatory diseases, including gouty arthritis. Activation of the NLRP3 inflammasome requires priming and activation signals: the priming signal controls the expression of NLRP3 and interleukin (IL)-1β precursor (proIL-1β), while the activation signal leads to the assembly of the NLRP3 inflammasome and to caspase-1 activation. Here, we reported the effects of the alcoholic extract of Taiwanese green propolis (TGP) on the NLRP3 inflammasome in vitro and in vivo. TGP inhibited proIL-1β expression by reducing nuclear factor kappa B activation and reactive oxygen species (ROS) production in lipopolysaccharide-activated macrophages. Additionally, TGP also suppressed the activation signal by reducing mitochondrial damage, ROS production, lysosomal rupture, c-Jun N-terminal kinases 1/2 phosphorylation and apoptosis-associated speck-like protein oligomerization. Furthermore, we found that TGP inhibited the NLRP3 inflammasome partially via autophagy induction. In the in vivo mouse model of uric acid crystal-induced peritonitis, TGP attenuated the peritoneal recruitment of neutrophils, and the levels of IL-1β, active caspase-1, IL-6 and monocyte chemoattractant protein-1 in lavage fluids. As a proof of principle, in this study, we purified a known compound, propolin G, from TGP and identified this compound as a potential inhibitor of the NLRP3 inflammasome. Our results indicated that TGP might be useful for ameliorating gouty inflammation via inhibition of the NLRP3 inflammasome.

Scavenging Intracellular ROS Attenuates p-Cresyl Sulfate-Triggered Osteogenesis through MAPK Signaling Pathway and NF-κB Activation in Human Arterial Smooth Muscle Cells

“…Intracellular ROS production was measured by detecting the fluorescence intensity of 2 , 7 -dichlorofluorescein, the oxidation product of 2 , 7 -dichlorofluorescein diacetate (Molecular Probes, Eugene, OR, USA) as described previously [24,25]. In brief, 12-well plates (8 × 10 4 cells/well) with 0.1 mL of culture medium were grown overnight at 37 • C in a 5% CO 2 incubator.…”

Synthetic 4-Hydroxy Auxarconjugatin B, a Novel Autophagy Inducer, Attenuates Gouty Inflammation by Inhibiting the NLRP3 Inflammasome

“…However, little is known about the effects of 4-HAB on the NLRP3 inflammasome and the underlying molecular mechanism of these effects. As part of our efforts is to identify novel NLRP3 inflammasome inhibitors [11][12][13][14][15] and based on the known anti-inflammatory effects of 4-HAB, we hypothesized that 4-HAB can inhibit the NLRP3 inflammasome.…”

Therapeutic Targeting of Aristolochic Acid Induced Uremic Toxin Retention, SMAD 2/3 and JNK/ERK Pathways in Tubulointerstitial Fibrosis: Nephroprotective Role of Propolis in Chronic Kidney Disease

“…There is a clear need for safe and effective therapeutic regimens focusing on TIF to timely preserve renal function in patients with AAs intoxication, preventing from ESKD and fatal urothelial cancer in clinical medicine. PE, a potent natural antioxidant with multi-components, serves as a multi-targeted regimen in inflammation [ 12 ], diabetes [ 13 ], and cancers [ 15 ]. Our recent study unraveled that the scavenging of ROS by antioxidants ameliorates obesity-related kidney fibrosis [ 16 ].…”

“…All animals were randomly divided into four groups of six mice each: vehicle-treated control group (normal renal function), PE-treated group (normal renal function), AAN group and PE-treated AAN group. PE was collected in Taiwan using propolis collectors as described previously [ 12 ]. The dosage and experimental administration were presented here: Group I (control; IP injection of vehicle (DMSO, Sigma Aldrich, China) once every 3 days for 6 weeks and orally administered with vehicle (distilled water, 200 μL) everyday, 12 weeks; n = 6).…”

“…Propolis, a natural product rich in prenylated flavonoids, has been reported to exert versatile biological activities in our prior research, including anti-inflammasome [ 12 ], anti-oxidant [ 12 ], anti-diabetes [ 13 , 14 ] and anti-cancer properties [ 15 ]. Our recent rodent model of metabolic endotoxemia with obesity demonstrated that elimination of reactive oxygen species (ROS) using antioxidant therapy ameliorates kidney fibrosis as well as inflammation [ 16 ].…”