Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from Myrtus Communis on Inflammatory Response in Mouse Macrophages

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 IC 50 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 IC 50 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.

The therapeutic value of Myrtus communis L.: an updated review

“… Pharmacological effects Activity model Plant part used References Anti-inflammatory Lipopolysaccharide (LPS)-stimulated macrophages in vitro model Seeds Cruciani et al 2019 , Soomro et al 2019 , Dragomanova et al 2019 , Alem et al 2008 , Maxia et al 2011 , Rossi et al 2009 , Raoof et al 2019 . Analgesic effects Mouse model Aerial part Koeberle et al 2009 Antimicrobial effects P. aeruginosa , S. shigie , S. aureus , S. typhi , E. coli , K. aerogenes , P. vulgaris , and P. mirabilis Leaves, seeds Barboni et al 2010 , Feuillolay et al 2016 , Teimoory et al 2013 , Rasaie et al 2017 , Appendino et al 2006 , Harassi et al 2019 , Rahimvand et al 2018 , Fani et al 2014 , Ben et al 2014 , Javadi et al 2017 , Cruciani et al 2019 , Beni et al 2017 , Flaminia et al 2004 , Cannas et al 2013 , Mert et al 2008 , Aleksic et al 2014 , Fadil et al 2018 , Masoudi et al 2017 , Cannas et al 2014 ,Barac et al 2018 , Mahdi et al 2006 , Mehrabani et al 2013 , Penauelas et al 2001 Antidiabetic effects Mouse model Berry, leaves <...…”

“…M. communis essential oil was assessed for anti-inflammatory property using lipopolysaccharide (LPS)-stimulated macrophages in vitro model; oils significantly inhibited the production of NO without altering the viability of the cell at 0.64 mg/ml concentrations (Cruciani et al 2019 ). The aqueous extracts (0.03, 0.015, 0.005 g/kg) and ethanolic (0.05 g/kg) possessed anti-inflammatory action against prolonged inflammation (Soomro et al 2019 ). M. communis essential oil anti-inflammatory activity was assessed by mice with ear edema induced by croton oil and myeloperoxidase activity, and in rats’ models, granuloma induced by cotton pellet and serum TNF-α as well as IL-6 (Feisst et al 2005 ).…”

<em>Myrtus communis </em>Leaves: Source of Bioactives, Traditional Use and their Biological Properties

“…The compound was less toxic towards the various cell lines of MDBK kidney cells, liver cells, 3T3NIH mouse fibroblasts, and J774.2 macrophages compared to cyclohexamide. By abolishing the phosphorylation of the transcription factor (NFkB) and its nuclear translocation, MCA-1 inhibited the expression of inducible nitric oxide synthase (73) The folkloric use of Myrtus communis L. for the treatment of diarrhea and dysentery has been supported by scientific data, according to Mekonnen Sisay et al In his study the acclaimed traditional use of 80ME and solvent fractions of Myrtus communis L. leaves were assessed for their ability to treat diarrhea in a model using castor oil-induced diarrheal mice. The 80ME, chloroform and methanol fractions significantly delayed the onset of diarrhea.…”

Free Radical Scavenging, Metal chelating and Antiperoxidative Activities of M. communis Berries Methanol extract and its Fractions

“…It is also used in the production of liqueurs, for which the berries or a mixture of leaves and berries is macerated in alcohol for a prescribed amount of time (Pereira et al, 2017). Fruit has carminative properties and have been used traditionally for the treatment of diarrhoea (Benchikh et al, 2016 a,b), hemorrhoids (Mahboubi et al, 2017;Malekuti et al, 2019), inflammation (Amira et al, 2012;Soomro et al, 2019), hepatotoxicity (Kumar et al, 2011;Hanaa et al, 2020), burns (Ozcan et al, 2019), pancreatitis (Ozbeyli et al, 2019) and skin diseases (Baharvand-Ahmadi et al, 2015).…”