Extract From Plectranthus amboinicus Inhibit Maturation and Release of Interleukin 1β Through Inhibition of NF-κB Nuclear Translocation and NLRP3 Inflammasome Activation

Abstract

Uncontrolled inflammation may produce massive inflammatory cytokines, in which interleukin 1β (IL-1β) plays a key role, resulting in tissue damage and serious disorders. The activation of NLRP3 inflammasome is one of the major mechanisms in maturation and release of IL-1β. Plectranthus amboinicus is a perennial herb. Several pharmacological activities of natural components and crude extracts from P. amboinicus have been reported including anti-inflammation; however, the underlying mechanism is not clear. Phorbol-12-myristate 13-acetate-differentiated THP-1 monocytic leukemia cells were used as a reliable model in this study to examine the effect on inflammasome signaling pathway by PA-F4, an extract from Plectranthus amboinicus . PA-F4 inhibited ATP-induced release of caspase-1, IL-1β, and IL-18 from lipopolysaccharides (LPS)-primed cells. PA-F4 induced a concentration-dependent inhibition of both ASC dimerization and oligomerization in cells under LPS priming plus ATP stimulation. Co-immunoprecipitation of NLRP3 and ASC demonstrated that PA-F4 significantly blunted the interaction between NLRP3 and ASC. Furthermore, PA-F4 completely abolished ATP-induced K + efflux reaction in LPS-primed cells. Taken together, PA-F4 displayed an inhibitory activity on NLRP3 inflammasome activation. Moreover, PA-F4 also inhibited LPS-induced p65 NF-κB activation, suggesting an inhibitory activity on LPS priming step. Further identification showed that rosmarinic acid, cirsimaritin, salvigenin, and carvacrol, four constituents in PA-F4, inhibited LPS-induced IL-6 release. In contrast, rosmarinic acid, cirsimaritin and carvacrol but not salvigenin inhibited ATP-induced caspase-1 release from LPS-primed cells. In conclusion, PA-F4 displayed an inhibitory activity on activation of NLRP3 inflammasome. PA-F4 inhibited LPS priming step through block of p65 NF-κB activation. It also inhibited ATP-induced signaling pathways in LPS-primed cells including the inhibition of both ASC dimerization and oligomerization, K + efflux reaction, and the release reaction of caspase-1, IL-1β, and IL-18. Rosmarinic acid, cirsimaritin, salvigenin, and carvacrol could partly explain PA-F4-mediated inhibitory activity on blocking the activation of NLRP3 inflammasome.

Biotechnologically Produced Lavandula angustifolia Mill. Extract Rich in Rosmarinic Acid Resolves Psoriasis-Related Inflammation Through Janus Kinase/Signal Transducer and Activator of Transcription Signaling

“…Significant pharmacological attention has been attracted toward RA as a result of its bioactive properties and, hence, therapeutic potential ( Nunes et al, 2017 ; Luo et al, 2020 ). Among the wide range of its beneficial biological actions are antioxidant, anti-inflammatory ( Chen et al, 2018 ; Joardar et al, 2019 ; Leu et al, 2019 ) anti-allergic ( Liang et al, 2016 ), anti-fibrotic ( Domitrovic et al, 2014 ; Joardar et al, 2019 ), neuroprotective ( Shang et al, 2016 ) and anti-adipogenic ( Vasileva et al, 2021 ). Apart from its potential medical applications, RA is also a preferred natural antioxidant and preservative in food and cosmetic industries ( Kovatcheva-Apostolova et al, 2008 ; Shen et al, 2017 ; Chaiyana et al, 2019 ; Choi et al, 2019 ).…”

Chalcones Display Anti-NLRP3 Inflammasome Activity in Macrophages through Inhibition of Both Priming and Activation Steps—Structure-Activity-Relationship and Mechanism Studies

“…The results suggest that 11Cha1 displays an inhibitory activity on the inflammasome activation. Upon NLRP3 inflammasome activation, autoproteolysis of pro-caspase-1 produced large (p20) and small (p10) cleavage fragments of the catalytically active enzymes, leading to the cleavage of pro-IL-1β and pro-IL-18 into their secreted active forms [9,21,22]. The detection of release reaction in the medium using ELISA system demonstrated that 11Cha1, by itself without cytotoxic effect (Supplementary Materials Figure S1), caused a concentration-dependent inhibition of ATP-induced caspase-1 activation and the release of IL-1β and IL-18 in LPS-primed macrophages with IC 50 values of 1.5 ± 0.1, 4.9 ± 1.8, and 3.2 ± 0.5 µM, respectively (Figure 2A).…”

Dihydrolipoic acid protects against lipopolysaccharide-induced behavioral deficits and neuroinflammation via regulation of Nrf2/HO-1/NLRP3 signaling in rat

“…The nod-like receptor pyrin-containing pyrin domain 3 (NLRP3) inflammasome is one of the most widely studied inflammasomes [4]. After NLRP3 inflammasome is assembled and activated, it activates caspase-1 by proteolytic cleavage, which in turn, converts pro-IL-1β into bioactive IL-1β, leading to inflammatory responses in bodies [5,6]. Reactive oxygen species (ROS) is a normal metabolic product of redox reactions.…”