Effects of Cinnamaldehyde on PGE&lt;sub&gt;2&lt;/sub&gt; Release and TRPV4 Expression in Mouse Cerebral Microvascular Endothelial Cells Induced by Interleukin-1&amp;beta;

Ma, Yongfu; Huo, Hai-Ru; Li, Cang-Hai; Zhao, Baosheng; Li, Lanfang; Shi, Feng; Guo, Shubin; Ting-liang, Jiang

doi:10.1248/bpb.31.426

Cited by 30 publications

(18 citation statements)

References 25 publications

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“…For example, mammalian TRPV4 can rescue mechanosensitive defects observed in C.elegans OSM-9 mutants [5]. In higher organisms TRPV4 is endogenously expressed in nociceptive dorsal root ganglion (DRG) neurons but also in many non-neuronal tissues and cells such as skin, kidney corneal epithelial cells [6], cerebral microvascular endothelial cells [7], cortical astrocytes [8], tracheal epithelial cells [9], keratinocyte cell lines [10] and in other cells. The widespread distribution of TRPV4 is indicative of its involvement in various physiological functions.…”

Section: Introductionmentioning

confidence: 99%

Importance of Non-Selective Cation Channel TRPV4 Interaction with Cytoskeleton and Their Reciprocal Regulations in Cultured Cells

et al. 2010

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BackgroundTRPV4 and the cellular cytoskeleton have each been reported to influence cellular mechanosensitive processes as well as the development of mechanical hyperalgesia. If and how TRPV4 interacts with the microtubule and actin cytoskeleton at a molecular and functional level is not known.Methodology and Principal FindingsWe investigated the interaction of TRPV4 with cytoskeletal components biochemically, cell biologically by observing morphological changes of DRG-neurons and DRG-neuron-derived F-11 cells, as well as functionally with calcium imaging. We find that TRPV4 physically interacts with tubulin, actin and neurofilament proteins as well as the nociceptive molecules PKCε and CamKII. The C-terminus of TRPV4 is sufficient for the direct interaction with tubulin and actin, both with their soluble and their polymeric forms. Actin and tubulin compete for binding. The interaction with TRPV4 stabilizes microtubules even under depolymerizing conditions in vitro. Accordingly, in cellular systems TRPV4 colocalizes with actin and microtubules enriched structures at submembranous regions. Both expression and activation of TRPV4 induces striking morphological changes affecting lamellipodial, filopodial, growth cone, and neurite structures in non-neuronal cells, in DRG-neuron derived F11 cells, and also in IB4-positive DRG neurons. The functional interaction of TRPV4 and the cytoskeleton is mutual as Taxol, a microtubule stabilizer, reduces the Ca2+-influx via TRPV4.Conclusions and SignificanceTRPV4 acts as a regulator for both, the microtubule and the actin. In turn, we describe that microtubule dynamics are an important regulator of TRPV4 activity. TRPV4 forms a supra-molecular complex containing cytoskeletal proteins and regulatory kinases. Thereby it can integrate signaling of various intracellular second messengers and signaling cascades, as well as cytoskeletal dynamics. This study points out the existence of cross-talks between non-selective cation channels and cytoskeleton at multiple levels. These cross talks may help us to understand the molecular basis of the Taxol-induced neuropathic pain development commonly observed in cancer patients.

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Section: Introductionmentioning

confidence: 99%

Importance of Non-Selective Cation Channel TRPV4 Interaction with Cytoskeleton and Their Reciprocal Regulations in Cultured Cells

et al. 2010

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“…Cinnamaldehyde, one of the main constituents of C. cassia , is an aromatic aldehyde which has been reported to have multiple potential therapeutic activities 6. Ma et al found that cinnamaldehyde could decrease production of prostaglandin E 2 stimulated by interleukin-1β and could downregulate the expression of transient receptor potential vanilloid subtype 4 in the cerebral microvascular endothelial cells of the mouse, which may contribute to its antipyretic effects 7. Chao et al has reported that cinnamaldehyde has antioxidant and anti-inflammatory properties.…”

Section: Introductionmentioning

confidence: 99%

Vasodilatory effects of cinnamaldehyde and its mechanism of action in the rat aorta

Xue

Shi²,

Murad³

et al. 2011

VHRM

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The vasodilatory effect of cinnamaldehyde was investigated for its mechanism of action using isolated rings of rat aorta. Cinnamaldehyde relaxed aortic rings precontracted with phenylephrine in a dose-dependent manner, was not affected by either the presence or removal of the endothelium. Pretreatment with NG-nitro-L-arginine methyl ester and 1H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one could not block vasodilation by cinnamaldehyde, indicating that nitric oxide signaling is not involved. Potassium channel blockers, such as glibenclamide, tetraethylammonium, and BaCl2, had no effect on the relaxation produced by cinnamaldehyde. In addition, treatment with either indomethacin or propranolol did not affect cinnamaldehyde-induced vasodilatation. On the other hand, pretreatment of endothelium-denuded rings with cinnamaldehyde significantly inhibited vasoconstriction induced by endogenous vasoconstrictors, including angiotensin II, 5-hydroxytryptamine, dopamine, endothelin-1, and phenylephrine. In a Ca2+-free experimental setting, this natural vasodilator not only blocked Ca2+ influx-dependent vasoconstriction by either phenylephrine or KCl, but also inhibited phenylephrine-induced tonic contraction, which relies on intracellular Ca2+ release. This study shows that endothelium-independent, Ca2+ influx and/or an inhibitory release mechanism contributes to the vasodilatory effect of cinnamaldehyde.

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“…A significant reduction in nasal congestion from seasonal allergies found in a past clinical trial utilizing DF can now be partially explained from the favorable impact on PGE2 in this study [6]. It is also of interest that a traditional Chinese medicine (Guizhi-Tang or GZT) utilized to treat the common cold, pyrexia, and influenza is thought to favorably impact several immune pathways including the fairly recent finding of a reduction in PGE2 [20]. This medicine also contains a plethora of diverse compounds [21].…”

Section: Discussionmentioning

confidence: 59%

A Dried Yeast Fermentate Prevents and Reduces Inflammation in Two Separate Experimental Immune Models

Evans

Reeves²,

Robinson³

2012

Evidence-Based Complementary and Alternative Medicine

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Diverse and significant benefits against cold/flu symptoms and seasonal allergies have been observed with a dried fermentate (DF) derived from Saccharomyces cerevisiae (EpiCor) in multiple published randomized trials. To determine if DF may influence other immune conditions, two separate animal studies were conducted. Study 1 examined the ability of DF to prevent or reduce inflammation when given orally for 14 days to rats prior to receiving 1% carrageenan (localized inflammation model). DF significantly (P < 0.05) reduced swelling at all time points (1, 2, 3, 6, 12, and 24 hours) versus the control. Edema severity and PGE2 levels were reduced by approximately 50% and 25% (P < 0.05), respectively. Study 2 examined the ability of DF to treat established inflammation induced by type-2 collagen in mice over 4 weeks (autoimmune arthritis model). Significantly reduced arthritis scores, antibody response to type-2 collagen, and interferon-gamma levels were observed compared to controls (all parameters P < 0.05). DF favorably impacts multiple acute and potentially chronic immunologic inflammatory control mechanisms and should be further tested in clinical trials.

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Effects of Cinnamaldehyde on PGE<sub>2</sub> Release and TRPV4 Expression in Mouse Cerebral Microvascular Endothelial Cells Induced by Interleukin-1β

Cited by 30 publications

References 25 publications

Importance of Non-Selective Cation Channel TRPV4 Interaction with Cytoskeleton and Their Reciprocal Regulations in Cultured Cells

Importance of Non-Selective Cation Channel TRPV4 Interaction with Cytoskeleton and Their Reciprocal Regulations in Cultured Cells

Vasodilatory effects of cinnamaldehyde and its mechanism of action in the rat aorta

A Dried Yeast Fermentate Prevents and Reduces Inflammation in Two Separate Experimental Immune Models

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