Inhibitory effects and molecular mechanisms of garlic organosulfur compounds on the production of inflammatory mediators

You, Sixiang; Nakanishi, Eri; Kuwata, Hiroko; Chen, Jihua; Nakasone, Yasushi; He, Xi; He, Jianhua; Liu, Xiangxin; Zhang, Shirui; Zhang, Bin; Hou, De‐Xing

doi:10.1002/mnfr.201200843

Cited by 69 publications

(61 citation statements)

References 50 publications

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“…DATS down regulated mitogen-activated protein kinase (MAPK) and NF-кB pathways. In addition, DATS activated the expression of HO-1 and NQO1 mediated by Nrf2 as well as reduced the intracellular reactive oxygen species induced by LPS, which may contribute to the suppression of inflammatory mediator production [44]. Amagase noted that the administration of S-allyl mercaptocysteine (SAMC) ameliorated hepatic inflammation induced by CCl4 by inhibiting the activity of NF-кB subunits p50 and p65, thus reducing the expression of IL-1β, IL-6, MCP-1, MIP-2, KC, COX-2 TNF-α, TGF-β1, and iNOS at both the transcriptional and translational levels [38].…”

Section: Discussionmentioning

confidence: 98%

“…Garlic extract and its constituent diallyl disulfide (DADS) were determined to promote ileal immune responses ex vivo [43]. Diallyl disulfide (DADS), diallyl trisulfide (DATS), and S-allylcysteine (SAC) were discovered to attenuate lipopolysaccharide (LPS)-induced inflammatory mediators by down-regulating the NF-кB and MAPK signaling pathways [44].…”

Section: Introductionmentioning

confidence: 99%

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Allyl methyl disulfide inhibits IL-8 and IP-10 secretion in intestinal epithelial cells via the NF-кB signaling pathway

Zhang

Wang

Zhang

et al. 2015

International Immunopharmacology

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Allyl methyl disulfide inhibits IL-8 and IP-10 secretion in intestinal epithelial cells via the NF-кB signaling pathway

Zhang

Wang

Zhang

et al. 2015

International Immunopharmacology

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“…The GO-induced reduction in the CD4 + population may indicate its balancing effect on the immune reaction; lowering B cell activation and antibody production, particularly when B cells are highly activated. This effect may be attributed to the presence of diallyl trisulfide in GO, which has been reported to exert anti-inflammatory effects and reduce lipopolysaccharide-induced IL-6, IL-12 and TNF-α (42).…”

Section: A B C D E F G H I Discussionmentioning

confidence: 99%

Modulatory effects of levamisole and garlic oil on the immune response of Wistar rats: Biochemical, immunohistochemical, molecular and immunological study

et al. 2016

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Abstract. Levamisole (LEVA) and garlic are prevalent immunomodulators in humans and animals. Therefore, the present study aimed to examine the immunomodulatory effects of LEVA and garlic oil (GO) alone or in combination on the immune response of Wistar rats. A total of 24 male Wistar rats were allocated into four equal groups: Control group, which was given ad libitum access to food and water; and groups 2-4, which were orally administered LEVA [2.5 mg/kg body weight (BW) every 2 days], GO, (5 ml/kg BW daily), or LEVA plus GO, respectively for 4 consecutive weeks. Serum immunoglobulin (Ig)G and IgM levels were measured using a radial immunodiffusion assay. Serum cytokine levels, including interferon (IFN)-γ, interleukin (IL)-5 and tumor necrosis factor (TNF)-α, were measured using enzyme-linked immunosorbent assay kits. Total blood counts were measured automatically using a cell counter. Serum lysozyme enzymatic activity was determined by measuring the diameters of the zones of clearance relative to lysozyme. Immunohistochemical detection of CD4 and CD8 was carried out using the streptavidin-biotinperoxidase method. Furthermore, the mRNA expression levels of IL-4, IL-5 and IL-12 were measured in the leukocytes and thymus gland by semi-quantitative polymerase chain reaction. The results revealed that LEVA increased serum levels of IFN-γ, IL-5 and TNF-α cytokines, whereas co-administration of LEVA and GO decreased the stimulatory action of LEVA alone. LEVA and GO alone increased the serum levels of IgG, IgM and total blood cell counts, and co-administration of GO and LEVA inhibited the effects of LEVA. At the cellular level, in the spleen, LEVA increased immunoreactivity of CD4 and CD8, whereas co-administration of GO with LEVA decreased this strong expression. At the molecular level, in leukocytes, LEVA upregulated the mRNA expression levels of IL-2, IL-4 and IL-5, whereas GO alone downregulated mRNA expression. Co-administration of GO with LEVA inhibited the LEVA-induced upregulation of IL-2, IL-4 and IL-5 mRNA expression. In the thymus, both LEVA and GO upregulated the mRNA expression levels of IL-4 and IL-5, whereas LEVA alone did not affect IL-12 mRNA expression. Co-administration of GO with LEVA inhibited LEVA-induced upregulation of IL-4 and GO-induced upregulation of IL-12 expression, and had an additive upregulatory effect on IL-5 expression. In conclusion, LEVA stimulated T-helper (Th)1 cytokines, whereas GO stimulated a Th2 response, and co-administration of GO with LEVA inhibited the stimulatory effects of LEVA and balanced the Th1/Th2 response.

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“…Allyl sulfides have many biological functions, including suppression of inflammation, upregulation of detoxification, enhancement of histone acetylation, generation (or reduction) of reactive oxygen species (ROS), and induction of endoplasmic reticulum (ER) stress (17,18). There have been many reports of anticancer effects of these compounds against a variety of cancers, including prostate, lung, breast, and colon cancer cells (19)(20)(21)(22). In addition, DAT directly produces ROS through the homolytic cleavage of intramolecular trisulfide bonds, and DAT-mediated ROS induces oxidative and ER stress, causing apoptosis of various cancer cell types (20)(21)(22)(23).…”

Section: Diallyl Trisulfide Induces Apoptosis By Suppressing Nf-κb Simentioning

confidence: 99%

Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma

Shigemi

Furukawa

Hosokawa

et al. 2015

International Journal of Oncology

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Abstract. The allyl sulfides, including diallyl sulfide (DAS), diallyl disulfide (DAD), and diallyl trisulfide (DAT), contained in garlic and members of the Allium family, have a variety of pharmacological activities. Therefore, allyl sulfides have been evaluated as potential novel chemotherapeutic agents. Here, we found that DAT inhibited nuclear factor-κB (NF-κB) signaling and induced apoptosis in primary effusion lymphoma (PEL), a subtype of non-Hodgkin's B-cell lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV). We examined the cytotoxic effects of DAS, DAD and DAT on PEL cells. DAT significantly reduced the viability of PEL cells compared with uninfected B-lymphoma cells, and induced the apoptosis of PEL cells by activating caspase-9. DAT induced stabilization of IκBα, and suppressed NF-κB transcriptional activity in PEL cells. We examined the mechanism underlying DAT-mediated IκBα stabilization. The results indicated that DAT stabilized IκBα by inhibiting the phosphorylation of IκBα by the IκB kinase (IKK) complex. Furthermore, DAT induced proteasomal degradation of TRAF6, and DAT suppressed IKKβ-phosphorylation through downregulation of TRAF6. It is known that activation of NF-κB is essential for survival of PEL cells. In fact, the NF-κB inhibitor BAY11-7082 induced apoptosis in PEL cells. In addition, DAT suppressed the production of progeny virus from PEL cells. The administration of DAT suppressed the development of PEL cells and ascites in SCID mice xenografted with PEL cells. These findings provide evidence that DAT has antitumor activity against PEL cells in vitro and in vivo, suggesting it to be a novel therapeutic agent for the treatment of PEL. IntroductionPrimary effusion lymphoma (PEL, also termed body-cavitybased lymphoma) is a malignant B-cell lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV, also named HHV-8) in immunosuppressed individuals, such as AIDS patients or those that have undergone organ transplantation (1,2). PEL is a subtype of non-Hodgkin's lymphoma and is characterized by lymphomatous effusions of pleural and abdominal cavities. KSHV is a rhadinovirus of the γ-herpesvirus subfamily and is closely related to herpesvirus Saimiri and Epstein-Barr virus (EBV). KSHV is the causative agent of Kaposi's sarcoma and AIDS-related lymphoproliferative disorders, such as PEL and multicentric Castleman's disease (3). Similar to other herpesviruses, KSHV has two life cycles (latency and lytic replication). The KSHV genome circularizes and forms a double-stranded DNA, the episome, in the nucleus of PEL cells during latent infection. To establish a latent infection, KSHV expresses several viral genes, including latency-associated nuclear antigen (LANA), v-FLIP, v-cyclin, kaposin and microRNAs, in PEL cells. LANA is required for the replication and maintenance of viral DNA, and contributes to KSHV-associated oncogenesis through interaction with cellular molecules, such as p53, Rb and GSK-3. These viral proteins and RNA manipulate cellular signaling pathways, includ...

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Inhibitory effects and molecular mechanisms of garlic organosulfur compounds on the production of inflammatory mediators

Abstract: DATS as a potential inhibitor revealed antiinflammatory effect in both cell and animal models by downregulating AKT1/TGF-β-activated kinase-mediated NFκB and MAPK signaling pathways.

Cited by 69 publications

References 50 publications

Allyl methyl disulfide inhibits IL-8 and IP-10 secretion in intestinal epithelial cells via the NF-кB signaling pathway

Allyl methyl disulfide inhibits IL-8 and IP-10 secretion in intestinal epithelial cells via the NF-кB signaling pathway

Modulatory effects of levamisole and garlic oil on the immune response of Wistar rats: Biochemical, immunohistochemical, molecular and immunological study

Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma

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