Diallyl disulfide

Diallyl-disulfide, an organosulfur compound of garlic, attenuates airway inflammation via activation of the Nrf-2/HO-1 pathway and NF-kappaB suppression.[Pubmed: 24051194]

Food Chem Toxicol. 2013 Dec;62:506-13.

Diallyl disulfide (DADS) is a major organosulfur compound found in garlic oil that is widely used as a flavoring agent.
METHODS AND RESULTS:
In this study, we evaluated the effects of DADS on airway inflammation using an ovalbumin-induced model of allergic asthma and RAW264.7 cells. DADS decreased nitric oxide production with a reduction in the levels of interleukins (IL)-1β and IL-6 in RAW264.7 cells stimulated with LPS. DADS also reduced the expression of proinflammatory proteins including inducible nitric oxide synthase (iNOS), nuclear factor (NF)-κB, and matrix metalloproteinase (MMP)-9, and it enhanced the expression of antioxidant proteins including Nrf-2 and hemeoxygenase (HO)-1. In in vivo experiments, DADS decreased the inflammatory cell count in the bronchoalveolar lavage fluid (BALF) with IL-4, IL-5, IL-13, and immunoglobulin (Ig) E. These results were consistent with the histological analysis. DADS attenuated the airway inflammation and mucus hypersecretion induced by OVA challenge. In addition, DADS induced the activation of Nrf-2 and the expression of HO-1. In contrast, DADS reduced the activation of NF-κB, iNOS and MMP-9.
CONCLUSIONS:
In conclusion, DADS reduced the airway inflammation via regulation of Nrf-2/HO-1 and NF-κB. These results suggest that DADS might represent a useful new oral therapy to treat allergic asthma.

Induction of cytochrome P450 3A1 expression by diallyl disulfide: protective effects against cyclophosphamide-induced embryo-fetal developmental toxicity.[Pubmed: 24769015]

Food Chem Toxicol. 2014 Jul;69:312-9.

The protective effects of Diallyl disulfide (DADS) on cyclophosphamide (CP)-induced developmental toxicity and the possible mechanisms involved in this protection were investigated in rats.
METHODS AND RESULTS:
In order to study the mechanisms involved in the protection, we examined the effects of DADS on the expression of cytochrome P450 (CYP) 3A1 in the maternal liver and placenta and oxidative stress in the maternal hepatic tissues caused by CP. CP caused severe embryo-fetal developmental toxicity and hepatic oxidative stress. In contrast, DADS treatment significantly attenuated CP-induced developmental toxicity and oxidative damage in the maternal liver. DADS also significantly increased expression of CYP3A1 in the maternal liver and placenta.
CONCLUSIONS:
These results indicate that the protective effects of DADS against CP-induced developmental toxicity may be due to its ability to promote detoxification of CP, primarily by inducing CYP3A1 expression in the maternal liver and placenta, and its potent antioxidant effects.

The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats.[Pubmed: 24246655]

Food Chem Toxicol. 2014 Jan;63:174-85.

METHODS AND RESULTS:
This study investigated the potential effect of Diallyl disulfide (DADS) against carbon tetrachloride (CCl4)-induced oxidative hepatic damage and inflammatory response in rat liver. Diallyl disulfide at doses of 50 and 100 mg/kg/day was administered orally once daily for 5 days, prior to CCl4 administration. Pretreatment with Diallyl disulfide attenuated CCl4-induced elevated serum transaminase activities and histopathological alterations in liver. It prevented the hepatocellular apoptotic changes with induction of Bcl-2-associated X (Bax), cytochrome c, and caspase-3 caused by CCl4. An increase in the nuclear translocation of nuclear factor-kappaB (NF-κB) and phosphorylation of I kappaB alpha (IκBα) was observed in the livers of CCl4-treated rats that coincided with induction of inflammatory mediators or cytokines. In contrast, Diallyl disulfide inhibited NF-κB translocation and IκBα phosphorylation, and that subsequently decreased inflammatory mediators. Furthermore, Diallyl disulfide prevented CCl4-induced depletion of cytosolic nuclear factor E2-related factor 2 (Nrf2) and suppression of nuclear translocation of Nrf2, which, in turn, up-regulated phase II/antioxidant enzyme activities. Taken together, these results demonstrate that Diallyl disulfide increases the expression of phase II/antioxidant enzymes and simultaneously decreases the expression of inflammatory mediators in CCl4-induced liver injury.
CONCLUSIONS:
These findings indicate that Diallyl disulfide induces antioxidant defense mechanism by activating Nrf2 pathway and reduces inflammatory response by inhibiting NF-κB activation.

Diallyl disulfide inhibits TNFα-induced CCL2 release by MDA-MB-231 cells.[Pubmed: 24922637]

Diallyl disulfide suppresses proliferation and induces apoptosis in human gastric cancer through Wnt-1 signaling pathway by up-regulation of miR-200b and miR-22.[Pubmed: 23851184]

Cancer Lett. 2013 Oct 28;340(1):72-81.

The purpose of this study was to identify a mechanism related to miRNA pathway which plays a role in the anti-tumor effects of Diallyl disulfide.
METHODS AND RESULTS:
Alterations in miRNA expression were observed in Diallyl disulfide-treated MGC-803 cells, including up-regulation of miR-200b and miR-22 expression. Furthermore, Wnt-1 was identified as a target of both miR-200b and miR-22. MiR-200b and miR-22 not only synergistically inhibited gastric cancer growth, but also enhanced the antitumor effect of Diallyl disulfide both in vitro and in vivo.
CONCLUSIONS:
It indicated that miR-200b and miR-22 may serve as potential gene therapy and enhance Diallyl disulfide antitumor effects.

Anticancer Res. 2014 Jun;34(6):2763-70.

Monocyte chemotactic protein-1 (MCP-1/CCL2) is released by tumor tissues, serving as a potent chemokine enabling directional homing of mononuclear cells to tumor tissue, which subsequently differentiate into tumor-associated macrophages (TAMs) via TGFβ1 signaling. TAMs readily invade tumor tissue and continue to synthesize pro-oncogenic proteins including tumor growth factors, matrix proteases (metastasis), angiogenic factors (neovascularization) and CCL2. Substances, which can attenuate or block the initial release of CCL2 have been shown to prevent cancer-associated inflammative pro-oncogenic processes.
METHODS AND RESULTS:
In the current study, we investigated the effects of the organosulfur compound Diallyl disulfide (DADS), a natural constituent of Allium sativum (garlic) on suppression of TNFα-induced release of CCL2 from triple-negative human breast tumor (MDA-MB-231) cells. Using an initial adipokine/chemokine protein panel microarray, the data show a predominant expression profile in resting/untreated MDA-MB-231 cells for sustained release of IL6, IL8, plasminogen Activator Inhibitor 1 and TIMP1/2. Treatment with TNFα (40 ng/ml) had no effect on many of these molecules, with a single major elevation in release of CCL2 (~1,300-fold up-regulation). TNFα-induced CCL2 release was reversed by a sub-lethal concentration of DADS (100 μM), evident in antibody based assays.
CONCLUSIONS:
These findings provide evidence to support another avenue of anticancer/chemopreventative properties attributable to garlic constituents through immunomodulation.