The Quassinoid Isobrucein B Reduces Inflammatory Hyperalgesia and Cytokine Production by Post-transcriptional Modulation

Abstract

Isobrucein B (1) is a quassinoid isolated from the Amazonian medicinal plant Picrolemma sprucei. Herein we investigate the anti-inflammatory and antihyperalgesic effects of this quassinoid. Isobrucein B (1) (0.5-5 mg/kg) inhibited carrageenan-induced inflammatory hyperalgesia in mice in a dose-dependent manner. Reduced hyperalgesia was associated with reduction in both neutrophil migration and pronociceptive cytokine production. Pretreatment with 1 inhibited in vitro production/release of cytokines TNF, IL-1β, and KC/CXCL1 by lipopolysaccharide-stimulated macrophages. To investigate its molecular mechanism, RAW 264.7 macrophages with a luciferase reporter gene controlled by the NF-κB promoter were used (RAW 264.7-Luc). Quassinoid 1 reduced the luminescence emission by RAW 264.7-Luc stimulated by different compounds. Unexpectedly, NF-κB translocation to macrophage nuclei was not inhibited by 1 when evaluated by Western blotting and immunofluorescence. Furthermore, quassinoid 1 did not change the levels of TNF mRNA transcription in stimulated macrophages, suggesting post-transcriptional modulation. In addition, constitutive expression of luciferase in RAW 264.7 cells transiently transfected with a plasmid containing a universal promoter was inhibited by 1. Thus, isobrucein B (1) displays anti-inflammatory and antihyperalgesic activities by nonselective post-transcriptional modulation, resulting in decreased production/release of pro-inflammatory cytokines and neutrophil migration.

Eurycomalactone Inhibits Expression of Endothelial Adhesion Molecules at a Post-Transcriptional Level

“… 23 − 25 Silva et al quite recently reported that the quassinoid isobrucein B isolated from the Amazonian medicinal plant Picrolemma sprucei exerted in vivo and in vitro anti-inflammatory activity. 26 They showed that isobrucein B inhibits the release of pro-inflammatory cytokines in LPS-activated primary murine peritoneal macrophages in a concentration-dependent manner within a similar concentration range to that used in our study (0.1–10 μM). Interestingly, isobrucein B was unable to interfere with the NF-κB signaling pathway in LPS-activated RAW264.7 macrophages; the mRNA levels of the NF-κB target gene TNF also remained unaffected.…”

“… 15 These data suggest that 1 might act at a post-transcriptional level as reported earlier for quassinoids. 10 , 16 …”

Chemical Characterization and Antioxidant, Antimicrobial, and Anti-Inflammatory Activities of South Brazilian Organic Propolis

“…RAW 264.7 macrophages were cultured and plated in 24-well plates, treated with EEP (0.1, 1, and 10 μg/mL) for 30 min and stimulated with lipopolysaccharide (LPS) (100 ng/mL) for 4 h. After that, luciferase assay reagent was added and luminescence emission was measured using a microplate reader (FlexStation 3, Molecular Devices, Sunnyvale, CA, USA) [25,26]. The results were expressed as mean ± SD of relative luminescence units (%).…”

The protein synthesis inhibitor brusatol normalizes high‐fat diet‐induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination

“…Brusatol is a member of quassinoids, group of chemical compounds related to triterpenoids, which can be isolated from evergreen tropical plants of the family Simaroubaceae (genera Brucea, grown in Southeast Asia, and Picrolemma, grown in Brazil) (6,7). Brusatol and structurally related natural compounds (bruceins, isobruceins, bruceantin, bruceoside, and others) are capable of inducing a variety of biologic effects, including antimalarial, antitrypanosomal, amoebicidal, antiinflammatory, and antineoplastic activities.…”

“…Brusatol and structurally related natural compounds (bruceins, isobruceins, bruceantin, bruceoside, and others) are capable of inducing a variety of biologic effects, including antimalarial, antitrypanosomal, amoebicidal, antiinflammatory, and antineoplastic activities. Extracts and other preparations obtained from Simaroubaceae plants are used in traditional herbal medicine to treat fever, malaria, gastropathies, and amebic dysentery (7)(8)(9)(10)(11).…”