Immunomodulatory properties of various natural compounds and essential oils through modulation of human cellular immune response

doi:10.1016/j.indcrop.2015.11.088

Industrial Crops and Products

Volume 81, March 2016, Pages 117-122

https://doi.org/10.1016/j.indcrop.2015.11.088 Get rights and content

Highlights

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Immunomodulatory effect of essential oils and pure compounds were investigated.
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Foeniculum vulgare and Satureja cuneifolia oils were effective on oxidative burst.
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Mentha piperita and M. spicata oils were the most effective against TNF-α.
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Quercetin had the strongest immunomodulation in all assays applied.

Abstract

Randomly selected essential oils and some terpene and phenolic derivatives were evaluated for their ability to modulate human cellular immune responses using various inflammatory parameters including reactive oxygen species (ROS) generation from whole blood phagocytes and isolated polymorphonuclear neutrophils (PMNs), proliferation of T-cells, IL-2. and TNF-α cytokine production. The essential oils from Foeniculum vulgare, Saturea cuneifolia, and Origanum munitiflorum inhibited ROS produced from whole blood phagocytes, while thymol, carvacrol, rosmarinic acid, caffeic acid, quercetin, and kaempferol glycoside potently inhibited the ROS production from whole blood as well as from isolated PMNs, among which caffeic acid, quercetin, and kaempferol glycoside exhibited a better inhibitory effect than that of ibuprofen. The compounds rosmarinic acid, caffeic acid, quercetin, kaempferol glycoside, genistein, and apigenin (IC₅₀ 7.0 ± 0.5, <3.12, <3.12, 4.3 ± 1.0, 5.8 ± 0.5, and <3.12 μg/mL) were found to exert potent inhibition on proliferation of T-cells. On the other hand, quercetin (IC₅₀ 2.9 ± 0.3 μg/mL) and apigenin (IC₅₀ <1.0 μg/mL), were also found to be the potent inhibitor of IL-2 cytokine. The essential oils of Mentha species, and compounds quercetin and apigenin were found to potently inhibit the production of pro-inflammatory cytokine TNF-α. The results indicated that essential oils and phenolics might be considered as promising immunomodulatory agents.

Graphical abstract

Introduction

Recently, there has been a great increase of interest in phytochemicals having anti-inflammatory potential, since they are viewed as promising therapeutic agents due to their impact on the status of human health and disease prevention. Immune system is directly related to human health as its function is to prevent from foreign attacks to the body. The deregulation of immune response is strongly associated with various inflammatory or degenerative disorders including chronic and acute infections.

In inflammatory process, the various cells of the immune system including macrophages, neutrophils, and lymphocytes, releases mediators such as reactive oxygen species (ROS) and pro-inflammatory cytokines, etc. These mediators of innate immune response aid in propagation of inflammatory processes and activation of adaptive immunity. In early events of adaptive immune responses, CD4⁺ T-helper cells activate various other type of cells, i.e., synovial fibroblasts, monocytes, and B-cells by releasing various cytokines among which TNF-α, IL-1β, and IL-2 play main role in progression of inflammation and, hence, can lead to various inflammatory and autoimmune diseases including rheumatoid arthritis, ankylosing spondilytis, psoriasis, atherosclerosis, type-2 diabetes, and Alzheimer’s disease (Bradley, 2008, Lue et al., 2012).

Macrophages forming the first barrier in defense system of the body usually produce and secrete some pro-inflammatory cytokines, i.e., tumor necrosis factor (TNF)-α and interleukins (IL) which are used in determination of immune response in macrophage cell-based models (Stow et al., 2014). As one of the critical factors of immune response, TNF-α is well-known to be a fundamental mediator of various pharmacological activities including cell proliferation, cell death, and differentiation as well as initiation of inflammation and immune modulation (Al-Lamki and Mayadas, 2015).

Essential oils with a wide range of applications in the pharmaceutical, food, and cosmetic industries have gained a great popularity due to their various pharmacological effects desired for human health and many studies dealing with immunomodulatory effect of essential oils have been reported up to date (Saad et al., 2013). Moreover, monoterpenes, present commonly in the chemical compositions of essential oils, have exerted strong immunobiological properties through TNF-α, ILs, tromboxanes, and leukotrienes (De Cássia Da Silveira E Sá et al., 2013). In our previous research (Orhan et al., 2011), we reported a strong antimicrobial activity of several essential oils and their common pure components against 10 isolated strains of Klebsiella pneumoniae producing extended-spectrum beta-lactamase (ESBL) enzyme, which is responsible for resistance against antibiotics by these strains. Consequently, the positive results obtained from that study with some selected essential oils (Foeniculum vulgare, Satureja cuneifolia, Mentha × piperita, Mentha spicata, Origanum onites, Origanum munitiflorum, Origanum majorana, and Origanum vulgare var. hirtum) and several compounds, some of which are generally found in essential oils (citronellol, thymol, vanillin, iso-borneol, menthol, borneol, carvacrol, and menthofurane) prompted us to investigate their immunomodulatory activity. Furthermore immunomodulatory properties of various other natural compounds of polyphenolic origin, i.e., rosmarinic, quinic, and caffeic acids, quercetin, kaempferol-3-O-β-d-galactoside, silibinin, genistein, and apigenin were also assessed in this study.

Section snippets

Plant materials

F. vulgare, S. cuneifolia, M. × piperita, M. spicata, O. onites, O. munitiflorum, O. majorana, and O. vulgare var. hirtum were cultivated in the experimental farm belonging to Faculty of Agriculture, Selcuk University, in ecological conditions of Konya province (Turkey) with a cold semi-arid steppe climate and less rainfalls (rain index 18.08), where the average temperature is around 11.3 °C. The city of Konya is located at between 36.5–39.58 north latitude and 31.5–34.58 east longitude and is the

Results

Immunomodulatory activities of various samples were determined by evaluating their effect on oxidative burst produced by reactive oxygen species (ROS), PHA-stimulated T-cell proliferation and on production of pro-inflammatory cytokines; IL-2 and TNF-α.

Discussion

Up to date, many studies have mentioned about immunomodulatory effect of essential oils and natural compounds of various chemical classes to some extent, most of which have left with unclear mechanisms of action. In consistency with our current data, the essential oil of Mentha × piperita did not affect the oxidative burst on PMNs and IL production (Cosentino et al., 2009). Nevertheless, the essential oils of M. × piperita and M. spicata were rather effective on TNF-α inhibition. Among the

Conclusion

A number of selected essential oils, terpene and aromatic components widely present in essential oils as well as some polyphenolic compounds were monitored in this study for their effect on ROS production via oxidative burst, T-lymphocyte proliferation, and inhibition of two cytokines (IL-2 and TNF-α), which take a chief part in modulation of immune response. Accordingly, our results have provided the evidence of a health-regulating effect of these essential oils with vegetable and spice use as

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Immunomodulatory properties of various natural compounds and essential oils through modulation of human cellular immune response

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Plant materials

Results

Discussion

Conclusion

Suppression of tumor necrosis factor-alpha-induced neutrophil adherence responses by essential oils

Med. Inflamm.

TNF receptors: signaling pathways and contribution to renal dysfunction

Kidney Int.

TNF-mediated inflammatory disease

J. Pathol.

Potentiation of macrophage activity by thymol through augmenting phagocytosis

Int. Immunopharmacol.

Inhibition of lipopolysaccharide-induced interleukin-1β and tumor necrosis factor-α production by menthone through nuclear factor-κB signaling pathway in HaCat cells

Chin. J. Physiol.

Immunomodulatory activities of common vegetables and spices of Umbelliferae and its related coumarins and flavonoids

Food Chem.

Antioxidant properties and in vitro immunomodulatory effects of peppermint (Mentha × piperita L.) essential oils in human leukocytes

J. Pharm. Sci. Res.

A review on anti-inflammatory activity of monoterpenes

Molecules

Immunomodulatory and antioxidant actions of dietary flavonoids

Int. J. Pharm. Pharm. Sci.

Carvacrol attenuates mechanical hypernociception and inflammatory response

Naunyn-Schmiedeberg’s Arch. Pharmacol.