Abstract
Organosulfur compounds are bioactive components of garlic essential oil (EO), mustard oil, Ferula EOs, asafoetida, and other plant and food extracts. Traditionally, garlic (Allium sativum) is used to boost the immune system; however, the mechanisms involved in the putative immunomodulatory effects of garlic are unknown. We investigated the effects of garlic EO and 22 organosulfur compounds on human neutrophil responses. Garlic EO, allyl propyl disulfide, dipropyl disulfide, diallyl disulfide, and allyl isothiocyanate (AITC) directly activated Ca2+ flux in neutrophils, with the most potent being AITC. Although 1,3-dithiane did not activate neutrophil Ca2+ flux, this minor constituent of garlic EO stimulated neutrophil reactive oxygen species (ROS) production. In contrast, a close analog (1,4-dithiane) was unable to activate neutrophil ROS production. Although 1,3-dithiane-1-oxide also stimulated neutrophil ROS production, only traces of this oxidation product were generated after a 5 h treatment of HL60 cells with 1,3-dithiane. Evaluation of several phosphatidylinositol-3 kinase (PI3K) inhibitors with different subtype specificities (A-66, TGX 221, AS605240, and PI 3065) showed that the PI3K p110δ inhibitor PI 3065 was the most potent inhibitor of 1,3-dithiane-induced neutrophil ROS production. Furthermore, 1,3-dithiane enhanced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase 3 α/β (GSK-3α/β), and cAMP response element binding (CREB) protein in differentiated neutrophil-like HL60 cells. Density functional theory (DFT) calculations confirmed the reactivity of 1,3-dithiane vs. 1,4-dithiane, based on the frontier molecular orbital analysis. Our results demonstrate that certain organosulfur compounds can activate neutrophil functional activity and may serve as biological response modifiers by augmenting phagocyte functions.
Highlights
Garlic and onion are important in the diet and have been reported to benefit human health [1].For example, compounds in garlic and onions have been reported to exhibit antimicrobial, anticancer, anti-inflammatory, anti-asthmatic, antidiabetes, antithrombotic, and antiplatelet activities [2,3,4,5,6,7,8].Organosulfur compounds are present in many plants, and their bioactive properties have benefitted folk and traditional medicine throughout the centuries [1,9]
We evaluated the effect of garlic essential oil (EO) and pure organosulfur compounds on neutrophil functional activity
Garlic EO and twenty-two commercially available organosulfur compounds were screened for immunomodulatory activity in human neutrophils
Summary
Garlic and onion are important in the diet and have been reported to benefit human health [1]. We found that Ferula-derived EOs containing high amounts of propenyl sec-butyl disulfides stimulated Ca2+ mobilization and activated reactive oxygen species (ROS) production in human neutrophils [11]. Onion extracts and garlic EO contain many organosulfur compounds, but only a few of them have been evaluated with phagocytic cells. We evaluated the effect of garlic EO and pure organosulfur compounds on neutrophil functional activity. All of these compounds were previously reported as components of garlic EO or mustard, garlic and onion extracts. Given the critical role played by phagocytes in innate immunity against pathogens, our data support the possibility that allyl-containing organosulfur compounds and 1,3-dithiane could be effective therapeutic modulators of innate immune responses
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