Cytokine-regulatory activity and therapeutic efficacy of cinnamyl derivatives in endotoxin shock

Kurokawa, Mineo; Brown, Jacqueline; Kagawa, Yutaka; Shiraki, Kimíyasu

doi:10.1016/s0014-2999(03)02036-3

Cited by 12 publications

(14 citation statements)

References 29 publications

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“…The 7HC in kakkon-to was also demonstrated to be effective in reducing proinflammatory cytokine production in lipopolysaccharide (LPS)-exposed macrophage-like P388D1 cells [41]. This is consistent with the IL-1 -modulatory activity leading the reduction of fever in influenza virusinfected mice [40].…”

Section: Hc With Cytokine-modulatory Activitysupporting

confidence: 65%

Development of New Antiviral Agents from Natural Products~!2010-01-17~!2010-04-12~!2010-08-27~!

Kurokawa¹,

Shimizu²,

Watanabe³

et al. 2010

TOANTIMJ

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The recent great advances in medical treatment and scientific technology include the many antiviral agents that have been developed and are used for treatment of infectious diseases, but such advances have also provoked the appearance of resistant virus strains. Therefore, the development of new antiviral agents with diverse kinds of antiviral actions is required. The search for new antiviral agents focuses on not only synthetic compounds but also natural products such as traditional medicines, dietary supplements, and functional foods, including plants, insects, animal organs, and their components. Natural products have their own metabolites, and some of the metabolites may recognize the differences between viral and host metabolisms, resulting in antiviral activity. In general, they can be obtained cheaply and may be useful resources to develop new antiviral agents with different antiviral actions from those of known antiviral agents. Also, natural products and their components have been demonstrated to modify immunological activities and are candidates for biological response modifiers that are effective in alleviating symptoms and reducing mortality in virus infection. The first half of this chapter introduces natural products and purified compounds that were confirmed by in vitro experiments and animal infection models to have direct antiviral activity against herpes simplex virus type 1 (HSV-1) or influenza virus. However, even if a natural product or purified component has strong antiviral activity in vitro, if it has no therapeutic efficacy against virus infection in an animal infection model, it is merely an inhibitor and not a medicine. The search for antiviral agents should be based on the demonstration of prophylactic and/or therapeutic efficacy at the proper dosage in animals. In the second half, we introduce a Kampo medicine, Kakkon-to, which is a biological response modifier rather than a direct antiviral agent. It is the most common cold medicine used in traditional therapy and prescribed to about 20 million people annually in Japan. We also introduce the mode of immunomodulating activity of Kakkon-to on influenza virus and HSV-1 infection and its components, which can modulate cytokine production. We hope that this chapter will be useful in verifying the antiviral therapeutic efficacy of natural products against influenza infection and helpful in encouraging development of anti-influenza virus medicines from natural products.

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Section: Hc With Cytokine-modulatory Activitysupporting

confidence: 65%

Development of New Antiviral Agents from Natural Products~!2010-01-17~!2010-04-12~!2010-08-27~!

Kurokawa¹,

Shimizu²,

Watanabe³

et al. 2010

TOANTIMJ

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“…Previously, AMC was shown to inhibit transcription of IL-1 , TNF-, and IL-6 in lipopolysaccharide-treated murine macrophage-like P388D1 cells [13]. In a murine endotoxin shock model, AMC administration suppressed the rise of IL-6 and TNF-levels in serum [13], but it did not affect the basal levels of IL-1 , TNF-, and IL-6 in normal mice [13]. Thus, the differences may be due to the inducing stimuli, the target cells, and their sensitivity to AMC.…”

Section: Days After Pr Imingmentioning

confidence: 99%

“…We have been studying the roles of traditional medicines in modification of the course of viral infection by assessing antiviral activity and cytokine levels [7][8][9][10][11][12][13]. Cinnamyl derivatives and related compounds originating from herbal medicines were demonstrated to possess antipyretic activity by suppressing the rise of interleukin (IL)-1 production subsequent to the interferon (IFN)-production that was induced by influenza infection in mice [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…The cinnamyl derivatives were suggested to contribute to the modification of cytokine production and alleviation of infection without affecting basal cytokine levels. Among these compounds, 7-amino-4-methylcoumarin (AMC), a semisynthetic derivative *Address correspondence to this author at Department of Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka, Miyazaki 882-8508, Japan; Tel: +81-982-23-5574; Fax: +81-982-23-5684; E-mail: b2mk@phoenix.ac.jp of coumarin, prevented death without toxicity in an endotoxic shock model in mice and suppressed the rise in levels of systemic pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-, without affecting basal cytokine levels [13]. AMC was suggested to be a potential cytokine modulator.…”

Section: Introductionmentioning

confidence: 99%

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Cytokine-Modulatory Activity and Therapeutic Efficacy of 7-Amino-4-Methylcoumarin in Murine Collagen-Induced Arthritis

Kurokawa¹,

Imakita²,

Shiraki³

2010

Open Bioact Compd J

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7-Amino-4-methylcoumarin (AMC) was previously shown to suppress pro-inflammatory cytokine production and prevent death in an endotoxic shock model in mice. In the present study, we investigated the effectiveness of AMC as a potential cytokine modulator in alleviating autoimmune diseases. We examined the efficacy and cytokine-modulatory activity of AMC in collagen-induced arthritis (CIA) in mice. Mice were immunized with type II collagen. AMC at 0, 3, or 30 mg/kg was administered orally to the immunized mice once daily for three weeks before and/or three times daily for two weeks after the onset of CIA. The development of arthritis of the paws and cytokine levels in serum were examined. AMC significantly reduced the incidence and severity of CIA prophylactically and therapeutically, and suppressed the rise of systemic interleukin-6 and interferon-levels to the basal levels in the early phase of CIA. AMC also significantly suppressed the level of tumor necrosis factor-in the severe phase of CIA. However, the levels of interleukin-10 and anti-collagen antibody were not affected by AMC. In the early phase of CIA, the suppression of interleukin-6 and interferon-levels by AMC correlated with the amelioration of symptoms of CIA in a dose-dependent manner. AMC may inhibit the onset of cytokine-mediated disease rather than suppressing disease progression without toxicity or affecting anti-collagen antibody production. AMC was significantly effective against CIA in mice and confirmed to possess cytokine-modulatory activity in vivo. The results suggest that AMC is a potential therapeutic agent for autoimmune diseases.

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“…Two hundred microliters of bronchoalveolar lavage cell suspension (2.5 Â 10 5 cells/ml) was seeded on each well in a 96-well microtiter plate and incubated at 378C for 24 hr in a humidified air with 5% CO 2 . After incubation, the culture medium was removed by aspiration and replaced in fresh RPMI medium with or without 100 ng/ml of lipopolysaccharide (W E. coli O127: B8, Difco, Detroit, MI; LPS) [Kurokawa et al, 2003]. Following 24 hr further incubation, the culture supernatant was harvested from each well and the amount of TNF-a was measured by ELISA.…”

Section: Assay Of Tnf-a Production From Bronchoalveolar Lavage Cellsmentioning

confidence: 99%

Functional disorder of primary immunity responding to respiratory syncytial virus infection in offspring mice exposed to a flame retardant, decabrominated diphenyl ether, perinatally

Watanabe

Shimizu

Sawamura

et al. 2010

Journal of Medical Virology

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Perinatal exposure to a representative flame retardant, decabrominated diphenyl ether (DBDE), was shown previously to increase viral titers in the lungs of respiratory syncytial virus (RSV)-infected offspring on day 5 post-infection, resulting in exacerbation of pneumonia. In this study, the significant increase of pulmonary viral titers was confirmed even on day 1 post-infection and the effect on the primary immune response to RSV infection were examined to assess a mode of DBDE action on developmental immunotoxicity. On day 1 after infection, the secretion of both TNF-alpha and IL-6 decreased significantly in the bronchoalveolar lavage fluid prepared from RSV-infected offspring exposed to DBDE perinatally, but IL-1beta increased. However, in ex vivo lipopolysaccharide stimulation test, the productivity of TNF-alpha in the bronchoalveolar lavage cells, which are mainly primary immune cells responding to RSV infection, prepared from offspring mice exposed to DBDE perinatally was not lower than that in the control. The primary immune cells retained normally the ability of cytokine production after the DBDE exposure. Gene expressions of innate pattern recognition receptors (Toll-like receptor 3 and 4, melanoma differentiation-associated gene-5, and retinoic acid-inducible gene I) in lung tissues were not affected by DBDE exposure. Because the levels of TNF-alpha, IL-6, and IL-1beta are known to be elevated in the lungs of RSV-infected mice, these irregular productions due to perinatal DBDE exposure indicate a disorder of the primary immune response to RSV infection. Thus, perinatal exposure to DBDE was suggested to cause a functional disorder of primary immunity responding to RSV infection.

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Cytokine-regulatory activity and therapeutic efficacy of cinnamyl derivatives in endotoxin shock

Cited by 12 publications

References 29 publications

Development of New Antiviral Agents from Natural Products~!2010-01-17~!2010-04-12~!2010-08-27~!

Development of New Antiviral Agents from Natural Products~!2010-01-17~!2010-04-12~!2010-08-27~!

Cytokine-Modulatory Activity and Therapeutic Efficacy of 7-Amino-4-Methylcoumarin in Murine Collagen-Induced Arthritis

Functional disorder of primary immunity responding to respiratory syncytial virus infection in offspring mice exposed to a flame retardant, decabrominated diphenyl ether, perinatally

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