Possible Contribution of Zerumbone-Induced Proteo-Stress to Its Anti-Inflammatory Functions via the Activation of Heat Shock Factor 1

Igarashi, Yoko; Ohnishi, Kohta; Irie, Kazuhiro; Murakami, Akira

doi:10.1371/journal.pone.0161282

Cited by 16 publications

(13 citation statements)

References 47 publications

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“…In addition, previous work by Igarashi et al [47] showed that zerumbone (which its structure related to radicicol and geldanamycin) in Zingiber zerumbet Smith, increased cellular protein aggregates and promoted nuclear translocation of heat shock factor 1 (HSF1), which down-regulation attenuated the suppressive effects of zerumbone on mRNA and protein expressions of pro-inflammatory genes, including inducible nitric oxide synthase and IL-1β. In this study, geldanamycin isolated from Streptomyces zerumbet; an endophyte of Zingiber zerumbet, has structure related to zerumbone from Zingiber zerumbet.…”

Section: Discussionmentioning

confidence: 99%

Streptomyces zerumbet, a Novel Species from Zingiber zerumbet (L.) Smith and Isolation of Its Bioactive Compounds

Taechowisan¹,

Puckdee²,

Phutdhawong³

2019

AiM

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Streptomyces zerumbet W14, a novel species of the endophyte genus Streptomyces was isolated from the rhizome tissue of Zingiber zerumbet (L.) Smith. Identification of strain W14 was based on its morphology, chemotaxonomy and phylogenetic analysis using 16S rDNA sequence. It was classified as the secondary meabolites of the culture extract were studied. The major active ingredients from the crude extract were purified by silica gel column chromatography and identified by spectroscopic data. The crude extract and purified compounds were tested for their biological activities on antibacterial and anti-inflammatory properties. The crude extract showed inhibition on the growth of Gram-positive bacteria with the MIC and MBC values of 8-32 µg/ml and 32-128 µg/ml, respectively. The isolated compounds were identified to be methyl 5-(hydroxymethyl)furan-2-carboxylate (1) and geldanamycin (2). Bioassay studies showed that compound 1 had antibacterial activity against Staphylococus aureus ATCC 25923 and Methicillin Resistant S. aureus strain Sp6 (clinical isolate) with the MIC and MBC values of 1 µg/ml and 16-64 µg/ml, respectively, and also showed activity against Bacillus Calmette-Guérin (vaccine strain) with MIC and MBC values of 128.00 µg/ml and 128.00 µg/ml, respectively. The compound 2 at the concentration of 1-5 µg/ml had in vitro anti-inflammatory activity on LPS-induced RAW 264.7 cells by inhibition of mRNA expression and production of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). These results suggest that compounds 1 and 2 produced by S. zerumbet W14 (an endophyte of Z. Zerumbet) have antibacterial and anti-inflammatory activities, respectively. Therefore, the future studies on these compounds could be useful for the management of bacterial infections and inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Streptomyces zerumbet, a Novel Species from Zingiber zerumbet (L.) Smith and Isolation of Its Bioactive Compounds

Taechowisan¹,

Puckdee²,

Phutdhawong³

2019

AiM

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“…We recently reported that zerumbone, a sesquiterpene present in Zingiber zerumbet Smith, induced proteo-stress and HSR for promoting HSF1 activation in hepatoma cells, which were associated with its anti-inflammatory effects. (9)(10)(11) Similarly, other recent findings indicate that the physiological functions of curcumin are partially mediated by regulation of PQC systems, (12)(13)(14)(15) and it is known to induce HSR in human leukemia cells by activating HSF1. (12) As the most abundant and essential energy carrier in cells, ATP functions to drive a variety of biochemical reactions.…”

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confidence: 79%

“…Interestingly, we recently found that proteo-stress induced by zerumbone plays an important role in its antiinflammatory functions through HSF1 activation. (11) In addition to target molecule-mediated mechanisms, xenobiotic stress-mediated mechanisms may also be described as an intrinsic property to phytochemicals, which are secondary metabolites and have no nutritional value to animals. In fact, curcumin exhibits quite a low level of bioavailability and rapid excretion from the body, (49) common characteristics of phytochemicals.…”

Section: Discussionmentioning

confidence: 99%

Curcumin may induce lipolysis via proteo-stress in Huh7 human hepatoma cells

Valentine

Ohnishi

Irie

et al. 2019

J. Clin. Biochem. Nutr.

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“…As expected, treatment of RAW264.7 macrophage with zerumbone led to marked nuclear translocation of HSF1 for HSP70 protein expression. ( 90 ) Interestingly, pretreatment with N -acetyl- l -cysteine (competitive nucleophile that reacts with zerumbone) or 4-phenylbutyric acid (chemical chaperone ( 91 ) ) reduced the suppressive effects of zerumbone on LPS-induced inducible nitric oxide synthase and COX-2 expression. Similarly, the suppressive effects of zerumbone on LPS-induced pro-inflammatory gene expressions were significantly diminished in HSF1-downregulated cells.…”

Section: Unique Role Of Proteo-stress In Anti-inflammatory Functionsmentioning

confidence: 99%

Non-specific protein modifications may be novel mechanism underlying bioactive phytochemicals

Murakami

2018

J. Clin. Biochem. Nutr.

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In a variety of experimental models, dietary phytochemicals have been demonstrated to exhibit pronounced and versatile bioactivities. Importantly, the possibility of such phytochemicals for human application has been supported in part by epidemiological surveys, which have demonstrated that frequent ingestion of vegetables and fruits containing abundant phytochemicals lowers the risk of onset of various diseases. However, the action mechanisms underlying those dietary phytochemical activities remain to be fully elucidated. For example, even though the anti-oxidant effects of natural polyphenols have long received widespread attention from food scientists, their roles in and contribution to those bioactivities remain controversial because of their poor bioavailability, resulting in extremely low concentrations in the bloodstream. Meanwhile, another important question is why phytochemicals have beneficial effects for animals, including humans, since they are biosynthesized by plants as compounds necessary for adaptation to environmental stress. In regard to that fundamental question, we recently reported novel and unique mechanisms of action of zerumbone, a sesquiterpene with anti-inflammatory and chemopreventive properties. This agent was found to partially exhibit bioactivity through its non-specific interactions with cellular proteins. More strikingly, a non-specific protein binding action of zerumbone was revealed to partially contribute to its anti-inflammatory functions via activation of heat shock factor 1. The present review article highlights and introduces our recent findings regarding the proteo-stress-mediated mechanisms of this phytochemical, along with the concept of hormesis.

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Possible Contribution of Zerumbone-Induced Proteo-Stress to Its Anti-Inflammatory Functions via the Activation of Heat Shock Factor 1

Cited by 16 publications

References 47 publications

<i>Streptomyces zerumbet</i>, a Novel Species from <i>Zingiber zerumbet</i> (L.) Smith and Isolation of Its Bioactive Compounds

<i>Streptomyces zerumbet</i>, a Novel Species from <i>Zingiber zerumbet</i> (L.) Smith and Isolation of Its Bioactive Compounds

Curcumin may induce lipolysis via proteo-stress in Huh7 human hepatoma cells

Non-specific protein modifications may be novel mechanism underlying bioactive phytochemicals

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Possible Contribution of Zerumbone-Induced Proteo-Stress to Its Anti-Inflammatory Functions via the Activation of Heat Shock Factor 1

Cited by 16 publications

References 47 publications

&lt;i&gt;Streptomyces zerumbet&lt;/i&gt;, a Novel Species from &lt;i&gt;Zingiber zerumbet&lt;/i&gt; (L.) Smith and Isolation of Its Bioactive Compounds

&lt;i&gt;Streptomyces zerumbet&lt;/i&gt;, a Novel Species from &lt;i&gt;Zingiber zerumbet&lt;/i&gt; (L.) Smith and Isolation of Its Bioactive Compounds

Curcumin may induce lipolysis via proteo-stress in Huh7 human hepatoma cells

Non-specific protein modifications may be novel mechanism underlying bioactive phytochemicals

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<i>Streptomyces zerumbet</i>, a Novel Species from <i>Zingiber zerumbet</i> (L.) Smith and Isolation of Its Bioactive Compounds

<i>Streptomyces zerumbet</i>, a Novel Species from <i>Zingiber zerumbet</i> (L.) Smith and Isolation of Its Bioactive Compounds