Abstract
(1) Introduction: Reactive oxygen species (ROS) and nitric oxide (NO) are key signaling molecules that play important roles in the progression of inflammatory disorders. The objective of this study was to explore the use of myrtucommuacetalone-1 (MCA-1), as a novel compound of natural origin and a potential anti-inflammatory agent. (2) Methodology: The anti-inflammatory potential of MCA-1, which was isolated from Myrthus communis Linn, was determined by assaying superoxide, hydrogen peroxide, and nitric oxide production in macrophages. Furthermore, the effects of the compound were analyzed via phosphorylation and translocation of the transcription factor NF kappa B, which is a key regulator of iNOS activation. The effect of MCA-1 on the inducible nitric oxide synthase (iNOS) enzyme was also examined using in silico docking studies. The anticancer potential for MCA-1 was evaluated with an MTT cytotoxic assay. (3) Results: In stimulated macrophages, MCA-1 inhibited superoxide production by 48%, hydrogen peroxide by 53%, and nitric oxide (NO) with an IC50 of <1 µg/mL. MCA-1 also showed a very strong binding pattern within the active site of the inducible nitric oxide synthase enzyme. Furthermore, 25 µg/mL of MCA-1 inhibited inducible nitric oxide synthase expression and abolished transcription factor (NFκB) phosphorylation and translocation to the nucleus. Cytotoxicity analyses of MCA-1 on 3T3 mouse fibroblasts, CC1 liver cell line, J774.2, macrophages and MDBK bovine kidney epithelial cell, yielded IC50 values of 6.53 ± 1.2, 4.6 ± 0.7, 5 ± 0.8, and 4.6 ± 0.7, µg/mL, respectively. (4) Conclusion: Our results suggest that MCA-1, a major phloroglucinol-type compound, shows strong anti-inflammatory activity and has a potential to be a leading therapeutic agent in the future.
Highlights
Regulation of inflammation is important because of its involvement in a number of serious chronic conditions, such as cancer, cardiovascular disease, and immune disorders
This study revealed that NFκB induced catabolic gene expression through NFκB response elements, thereby promoting the expression of major pro-inflammatory and destructive mediators, including cyclooxygenase 2 (COX2), prostaglandin E2 (PGE2), and inducible nitric oxide synthase
The present study demonstrated that myrtucommuacetalone 1 (MCA-1), isolated from Myrtus communis Linn and a phloroglucinol derivative, is an elective and potential inhibitor of nitric oxide (NO) synthesis during the oxidative burst by macrophages in vitro at a concentration of
Summary
Regulation of inflammation is important because of its involvement in a number of serious chronic conditions, such as cancer, cardiovascular disease, and immune disorders. LPS activates the nitric oxide (NO) pathway in macrophages [2] When they encounter LPS, macrophages interact with toll like receptors (TLR 4) in association with CD14, which leads to the activation of cellular kinases, resulting in NFκB activation. The inducible form of nitric oxide synthase becomes activated and causes NO generation, which in turn causes excessive vasodilation resulting in hypotension and septic shock. This may result in fatal complications in older and young people during bacterial infection, leading to sepsis [4]. We investigated the effects of myrtucommuacetalone 1 on NO induction via LPS-activated macrophages and further characterized its effects on downstream signaling pathways
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