Curcumin acts via transient receptor potential vanilloid‐1 receptors to inhibit gut nociception and reverses visceral hyperalgesia

Zhi, Lin; Dong, Li; Kong, Defu; Sun, Binbin; Sun, Qiang; Grundy, David; Zhang, G.; Rong, Weifang

doi:10.1111/nmo.12145

Cited by 35 publications

(29 citation statements)

References 49 publications

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“…Oral gavage with curcumin during adult chronic stress suppressed the VMR to CRD by reducing the transcription of BDNF mRNA and protein expression. Curcumin is a naturally occurring p300 histone acyl transferase inhibitor that has anti‐nociceptive effects in a number of rodent pain models, in some reports due to down‐regulation of specific pro‐nociceptive genes. These findings are consistent with our finding that curcumin down‐regulates spinal cord BDNF expression and reduces colonic hypersensitivity in stressed female CPS rats.…”

Section: Discussionmentioning

confidence: 99%

Chronic prenatal stress epigenetically modifies spinal cordBDNFexpression to induce sex‐specific visceral hypersensitivity in offspring

Winston

Sarna

2014

Neurogastroenterology Motil

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Background Irritable bowel syndrome (IBS) is a heterogeneous disorder with abdomen pain as one of the primary symptoms. The etiology of IBS remains unknown. Epidemiological studies found that a subset of these patients have a history of adverse early-life events. We tested the hypothesis that chronic prenatal stress (CPS) epigenetically enhances brain-derived neurotrophic factor (BDNF) in spinal cord to aggravate colon sensitivity to colorectal distension (CRD) differentially in male and female offspring. Methods We used heterotypic intermittent chronic stress (HeICS) protocols in pregnant dams from E11 until delivery. Results CPS induced significant visceral hypersensitivity (VHS) to CRD in male and female offspring. A second exposure to HeICS in adult offspring exacerbated VHS greater in female offspring that persisted longer than in male offspring. CPS upregulated BDNF expression in the lumbar-sacral dorsal horn that correlated with the exacerbation of VHS in female, but not in male offspring. The upregulation of BDNF was due to a significant increase in RNA Pol II binding, histone H3 acetylation and significant decrease in histone deacetylase 1 association with the core promoter of BDNF in female offspring. Other chronic prenatal and neonatal stress protocols were less effective than HeICS. Conclusion & Inferences The development of visceral hypersensitivity, which contributes to the symptom of intermittent abdominal pain, is a two-step process, chronic in utero stress followed by chronic stress in adult-life. This two-step process induces aggravated and persistent colon hypersensitivity in female than in male offspring. Our preclinical model explains several clinical features in IBS patients.

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Section: Discussionmentioning

confidence: 99%

Chronic prenatal stress epigenetically modifies spinal cordBDNFexpression to induce sex‐specific visceral hypersensitivity in offspring

Winston

Sarna

2014

Neurogastroenterology Motil

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“…125 Another in vivo study showed a remarkable decrease by curcumin in visceromotor response to colorectal distension in rats. 126 Ex vivo assessments on TNBS-treated jejunum confirmed the peripheral effect of curcumin on mesenteric afferent nerves. It was also demonstrated that curcumin, at least in part, interacts with TRPV1.…”

Section: Curcuminmentioning

confidence: 98%

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

Farzaei

Bahramsoltani

Abdollahi

et al. 2016

J Neurogastroenterol Motil

142

122

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Irritable bowel syndrome (IBS) is the most common disorder referred to gastroenterologists and is characterized by altered bowel habits, abdominal pain, and bloating. Visceral hypersensitivity (VH) is a multifactorial process that may occur within the peripheral or central nervous systems and plays a principal role in the etiology of IBS symptoms. The pharmacological studies on selective drugs based on targeting specific ligands can provide novel therapies for modulation of persistent visceral hyperalgesia. The current paper reviews the cellular and molecular mechanisms underlying therapeutic targeting for providing future drugs to protect or treat visceroperception and pain sensitization in IBS patients. There are a wide range of mediators and receptors participating in visceral pain perception amongst which substances targeting afferent receptors are attractive sources of novel drugs. Novel therapeutic targets for the management of VH include compounds which alter gut-brain pathways and local neuroimmune pathways. Molecular mediators and receptors participating in pain perception and visceroperception include histamine-1 receptors, serotonin (5-hydrodytryptamine) receptors, transient receptor potential vanilloid type I, tachykinins ligands, opioid receptors, voltage-gated channels, tyrosine receptor kinase receptors, protease-activated receptors, adrenergic system ligands, cannabinoid receptors, sex hormones, and glutamate receptors which are discussed in the current review. Moreover, several plant-derived natural compounds with potential to alleviate VH in IBS have been highlighted. VH has an important role in the pathology and severity of complications in IBS. Therefore, managing VH can remarkably modulate the symptoms of IBS. More preclinical and clinical investigations are needed to provide efficacious and targeted medicines for the management of VH. (J Neurogastroenterol Motil 2016;22:558-574)

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“…The authors further postulated that the curcumin-induced browning of WAT is mediated by the upregulation of β3-adrenergic receptor expression and elevation of plasma levels of norepinephrine by curcumin [40]. Not surprisingly, curcumin appears to act through the transient receptor potential vanilloid receptor 1 (TRPV1) receptors located in the intestinal jejunum and thus may have downstream effects on both WAT and BAT through direct modulation of the sympathetic nervous system [41]. …”

Section: Phytochemicals In Obesitymentioning

confidence: 99%

Phytochemicals as novel agents for the induction of browning in white adipose tissue

et al. 2016

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Obesity and its associated metabolic syndrome continue to be a health epidemic in westernized societies and is catching up in the developing world. Despite such increases, little headway has been made to reverse adverse weight gain in the global population. Few medical options exist for the treatment of obesity which points to the necessity for exploration of anti-obesity therapies including pharmaceutical and nutraceutical compounds. Defects in brown adipose tissue, a major energy dissipating organ, has been identified in the obese and is hypothesized to contribute to the overall metabolic deficit observed in obesity. Not surprisingly, considerable attention has been placed on the discovery of methods to activate brown adipose tissue. A variety of plant-derived, natural compounds have shown promise to regulate brown adipose tissue activity and enhance the lipolytic and catabolic potential of white adipose tissue. Through activation of the sympathetic nervous system, thyroid hormone signaling, and transcriptional regulation of metabolism, natural compounds such as capsaicin and resveratrol may provide a relatively safe and effective option to upregulate energy expenditure. Through utilizing the energy dissipating potential of such nutraceutical compounds, the possibility exists to provide a therapeutic solution to correct the energy imbalance that underlines obesity.

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Curcumin acts via transient receptor potential vanilloid‐1 receptors to inhibit gut nociception and reverses visceral hyperalgesia

Abstract: Our results provide strong evidence that curcumin inhibit visceral nociception via antagonizing TRPV1 and may be a promising lead for the treatment of functional gastrointestinal diseases.

Cited by 35 publications

References 49 publications

Chronic prenatal stress epigenetically modifies spinal cordBDNFexpression to induce sex‐specific visceral hypersensitivity in offspring

Chronic prenatal stress epigenetically modifies spinal cordBDNFexpression to induce sex‐specific visceral hypersensitivity in offspring

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

Phytochemicals as novel agents for the induction of browning in white adipose tissue

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