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Cassia sieberiana DC. leaves modulate LPS-induced inflammatory response in THP-1 cells and inhibit eicosanoid-metabolizing enzymes

Title
Cassia sieberiana DC. leaves modulate LPS-induced inflammatory response in THP-1 cells and inhibit eicosanoid-metabolizing enzymes
Type
Article in International Scientific Journal
Year
2021
Authors
Macedo, T
(Author)
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Ferreres, F
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David M Pereira
(Author)
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Oliveira, AP
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Gomes, NGM
(Author)
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Gil Izquierdo, A
(Author)
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Araujo, L
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Journal
Vol. 269
ISSN: 0378-8741
Publisher: Elsevier
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Publicação em ISI Web of Knowledge ISI Web of Knowledge - 0 Citations
Publicação em Scopus Scopus - 0 Citations
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Authenticus ID: P-00T-97C
Abstract (EN): Ethnopharmacological relevance: According to ethnobotanical surveys, Cassia sieberiana DC. (1825) is a particularly reputed species in African folk Medicine, namely due to the application of its leaves and roots for the treatment of diseases and symptomatology that appear to be related with an inflammatory background. In contrast with the roots of the plant, the leaves remain to be investigated, which prompted us to further detail mechanisms underlying their anti-inflammatory properties, by using in vitro models of disease. Aim of the study: Considering its use in the amelioration and treatment of conditions that frequently underlie an inflammatory response, C. sieberiana leaves extract was prioritized amongst a collection of extracts obtained from plants collected in Guinea-Bissau. As such, this work aims to deliver experimental data on the anti-inflammatory properties of C. sieberiana leaf and to establish possible associations with its chemical composition, thus providing a rationale on its use in folk Medicine. Materials and methods: The chemical profile of an hydroethanol extract obtained from the leaves of the plant was established by HPLC-DAD-ESI/MSn in order to identify bioactives. The extract and its main compound were tested towards a series of inflammatory mediators, both in enzymatic and cell-based models. The capacity to interfere with the eicosanoid-metabolizing enzymes 5-lipoxygenase (5-LOX), cyclooxygenase-1 (COX-1) and-2 (COX-2) was evaluated in cell-free systems, while the effects in interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels produced by THP-1 derived macrophages were assessed through ELISA. Results: HPLC-DAD-ESI/MSn analysis of the extract elucidated a chemical profile qualitatively characterized by a series of anthraquinones, particularly rhein derivatives, and nine flavonols, most of which 3-O-glycosylated. Considering the concentrations of the identified compounds, quercetin was detached as the main component. Effects of the hydroethanol extract obtained from C. sieberiana leaves against key enzymes of the arachidonic acid cascade were recorded, namely a concentration-dependent inhibition against 5-LOX, at concentrations ranging from 16 to 250 mu g mL(-1) and a selective inhibitory action upon COX-2 (IC50 = 3.58 mu g mL(-1)) in comparison with the isoform COX-1 (IC50 = 9.10 mu g mL(-1)). Impact on inflammatory cytokines was also noted, C. sieberiana leaf extract significantly decreasing IL-6 levels in THP-1 derived macrophages at 250 and 500 mu g mL(-1). In contrast, TNF-alpha levels were found to be increased in the same model. Quercetin appears to partially account for the observed effects, namely due to the significant inhibitory effects on the activity of the arachidonic acid metabolizing enzymes COX-2 and 5-LOX. Conclusions: The anti-inflammatory effects herein reported provide a rationale for the use of C. sieberiana leaves in African folk practices, such as in the treatment of arthritis, rheumatism and body aches. Considering the occurrence of flavonoidic and anthraquinonic constituents, as well as the observed anti-inflammatory properties of quercetin, recorded effects must be related with the presence of several bioactives.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 9
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