Abstract
Sambucus ebulus L. (SE) fruits are used for their immunostimulation, hematopoietic and antiviral potential. Recently, we focused on analyzing the mechanism underlying SE fruit aqueous extract’s (FAE) immunomodulation and anti-inflammatory activities, with attention to its endoplasmic reticulum (ER) stress-reducing potential. J774A.1 macrophages were treated with SE FAE alone or in conditions of lipopolysaccharides (LPS) stimulation. Using GC–MS and LC–MS/MS, its phytochemical composition was analyzed. To measure transcription and protein levels, we used qPCR and Western blot, respectively. The prevailing phytochemicals in SE FAE were hydroxycinnamic acids, proanthocyanidins and anthocyanins. The content of some amino acids, organic acids, alcohols, fatty acids and esters were newly reported. Extracts exerted an immunostimulation potential by stimulating IL-6, TNFα, Ccl2, COX2 and iNOS transcription, without inducing ER stress. SE FAE suppressed the LPS-induced transcription of inflammation related genes (IL-1β, IL-6, TNFα, Ccl2, Icam-1, Fabp4, COX2, iNOS, Noxo1, IL-1ra, Sirt-1) and reduced the protein levels of iNOS, peIF2α, ATF6α and CHOP. The effects were comparable to that of salicylic acid. SE suppresses LPS-stimulated inflammatory markers on the transcription and translation levels. Targeting ER stress is possibly another mechanism underlying its anti-inflammatory potential. These findings reveal the potential of SE fruits as a beneficial therapeutic of inflammation and ER stress-related pathological conditions.
Highlights
Traditional medicine is a good source of knowledge about therapeutics, which are researched and successfully implicated in modern pharmaceutical preparations
Among the phytochemical compounds identified in the tested Sambucus ebulus L. (SE) fruit aqueous extract (FAE) 15 amino acids (AAs), 10 organic acids (OAs), 36 sugar acids and alcohols, 25 mono, di- and trisaccharides, 13 fatty acids and their esters (Table 1), and 38 phenolic compounds were detected and quantified (Table 2)
In our previous study we found that SE FAE reduces LPS activated mRNA expression of NFκB, which correlated with decreased transcription levels of glutamate–cysteine ligase and glutathione peroxidase enzymes [18]
Summary
Traditional medicine is a good source of knowledge about therapeutics, which are researched and successfully implicated in modern pharmaceutical preparations. Jam, tea or decoction of SE fruits are used as immunostimulating and hematopoietic herbal preparations, as well as for the treatment of rheumatoid arthritis and gastrointestinal disorders [1,2,6]. The number of modern studies focusing on SE biological activities are growing, but there is still insufficient knowledge regarding molecular mechanisms of action of fresh or dry fruits and various fruit extracts. Ripe fruits are used in traditional medicine recipes and the chemical content varies depending on the types of the extract [3,7]. Data from phytochemical analyses in the literature reveal that SE fruits are high in polyphenolics, especially anthocyanins and proantchocyanidins, phenolic acids, hydroxycinnamic acids, flavonol glycosides, as well as organic acids, tannins, pectins, resins, vitamin C, volatile substances (eugenol, valeric acid, citronellal etc.), amino acids (including some essential ones), and plant sterols [3,7,8,9,10,11,12,13,14,15,16]
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