scholarly journals Capsaicin: A Potential Therapy Adjuvant for Intestinal Bowel Disease

2019 ◽  
Vol 2 (1) ◽  
pp. 8-16 ◽  
Author(s):  
Elandia A dos Santos ◽  
Jacqueline I Alvarez-Leite
Keyword(s):  
Bowel Disease ◽  
Clinical Studies ◽  
Transient Receptor Potential ◽  
Intestinal Inflammation ◽  
Biological Effects ◽  
Experimental Studies ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Ppar Γ ◽  
Anti Inflammatory

Most of the patients with inflammatory bowel disease avoid pepper or spicy food, alleging that this condiment causes anal sensation of burning and accelerates intestinal movements. Capsaicin is the main bioactive component of peppers responsible for the pungent flavor that characterizes red peppers. Capsaicin has been related to several biological effects, including decreased body fat, antianti-inflammatory, anticarcinogenic, antioxidant activites and modulator of intestinal motility. These actions mostly are due to its role as an agonist of the transient receptor potential vanilloid 1 (TRPV1), expressed in the mesenteric nervous system and epithelial cells of the colon. Nonetheless, the anti-inflammatory action of capsaicin is also related to its role in activating the peroxisomal proliferator-activated receptor gamma (PPAR-γ). Topical capsaicin formulations are already used for pain management, but oral administration of capsaicin is rare. Here, we discuss the main actions of capsaicin that could interfere with the symptoms and severity of IBD. Although animal experiments suggest a beneficial effect of capsaicin on colitis, clinical studies exploring the potential analgesic and anti-inflammatory of capsaicin on Crohn or Ulcerative Colitis are scarce. We concluded that there is no evidence that capsaicin aggravates IBD symptoms or severity. On the opposite, experimental studies suggest that capsaicin could reduce intestinal inflammation by a mechanism that could involve not only the TRPV1 receptor but also PPAR γ. However, clinical studies are still scarce, and data regarding capsaicin concentrations, routes of administration, and long-term side-effects need to be better understood before its use.

Hydrogen sulfide modulates IL-6/STAT3 pathway and inhibits oxidative stress, inflammation, and apoptosis in rat model of methotrexate hepatotoxicity

2019 ◽  
Vol 39 (1) ◽  
pp. 77-85 ◽  
Author(s):  
AA Fouad ◽  
HM Hafez ◽  
AAH Hamouda
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Nuclear Factor Κb ◽  
Ruthenium Red ◽  
Transient Receptor Potential Vanilloid ◽  
Stat3 Pathway ◽  
Anti Inflammatory ◽  
Apoptotic Effects

Methotrexate (MTX) is a commonly used anticancer and immunosuppressive agent. However, MTX can induce hepatotoxicity due to oxidative stress, inflammation, and apoptosis. Hydrogen sulfide (H2S), the endogenous gaseous molecule, has antioxidant, anti-inflammatory, and anti-apoptotic effects. The present work explored the probable protective effect of H2S against MTX hepatotoxicity in rats and also the possible mechanisms underlying this effect. MTX was given at a single intraperitoneal (i.p.) dose of 20 mg/kg. Sodium H2S (56 µmol /kg/day, i.p.), as H2S donor, was given for 10 days, starting 6 days before MTX administration. H2S significantly reduced serum alanine aminotransferase, hepatic malondialdehyde, interleukin 6, nuclear factor κB p65, cytosolic cytochrome c, phosphorylated signal transducer and activator of transcription 3, and Bax/Bcl-2 ratio and significantly increased hepatic total antioxidant capacity and endothelial nitric oxide synthase (eNOS) in rats received MTX. In addition, H2S minimized the histopathological injury and significantly decreased the expression of STAT3 in liver tissue of MTX-challenged rats. The effects of H2S were significantly antagonized by administration of glibenclamide as KATP channel blocker, Nω-nitro-l-arginine, as eNOS inhibitor, or ruthenium red, as transient receptor potential vanilloid 1 (TRPV1) antagonist. It was concluded that H2S provided significant hepatoprotection in MTX-challenged rats through its antioxidant, anti-inflammatory, anti-apoptotic effects. These effects are most probably mediated by the ability of H2S to act as IL-6/STAT3 pathway modulator, KATP channel opener, eNOS activator, and TRPV1 agonist.

scholarly journals The Basal Pharmacology of Palmitoylethanolamide

2020 ◽  
Vol 21 (21) ◽  
pp. 7942 ◽  
Author(s):  
Linda Rankin ◽  
Christopher J. Fowler
Keyword(s):  
Transient Receptor Potential ◽  
Biological Effects ◽  
Receptor Potential ◽  
The Body ◽  
Transient Receptor Potential Vanilloid ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pharmacokinetic Properties ◽  
Endogenous Compound ◽  
Transient Receptor

Palmitoylethanolamide (PEA, N-hexadecanoylethanolamide) is an endogenous compound belonging to the family of N-acylethanolamines. PEA has anti-inflammatory and analgesic properties and is very well tolerated in humans. In the present article, the basal pharmacology of PEA is reviewed. In terms of its pharmacokinetic properties, most work has been undertaken upon designing formulations for its absorption and upon characterising the enzymes involved in its metabolism, but little is known about its bioavailability, tissue distribution, and excretion pathways. PEA exerts most of its biological effects in the body secondary to the activation of peroxisome proliferator-activated receptor-α (PPAR-α), but PPAR-α-independent pathways involving other receptors (Transient Receptor Potential Vanilloid 1 (TRPV1), GPR55) have also been identified. Given the potential clinical utility of PEA, not least for the treatment of pain where there is a clear need for new well-tolerated drugs, we conclude that the gaps in our knowledge, in particular those relating to the pharmacokinetic properties of the compound, need to be filled.

Abstract 453: Ablation of TRPV1 Impairs Exendin-4 Induced Suppression in Renal Cytokine Release

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Beihua Zhong ◽  
Donna H Wang
Keyword(s):  
Transient Receptor Potential ◽  
Tissue Injury ◽  
Receptor Potential ◽  
Plasma Creatinine ◽  
Transient Receptor Potential Vanilloid ◽  
Cytokine Release ◽  
Cgrp Release ◽  
Obesity And Diabetes ◽  
Anti Inflammatory

Impairment of function and expression of the transient receptor potential vanilloid type 1 (TRPV1) occurs in obesity and diabetes, which may aggravate inflammation and tissue injury given that the TRPV1 mediated pathway has been shown to be anti-inflammatory. Glucagon-like peptide-1 (GLP-1), an incretin hormone released in response to food intake, is capable of protecting tissues from injury, but its mechanism largely unknown. We tested the hypothesis that exendin-4 (Ex4), a GLP-1 receptor agonist, suppresses hypoxia-induced cytokine release via a TRPV1 mediated pathway. Using gene-targeted TRPV1-null mutant (TRPV1 -/- ) or wild-type (WT, C57BL/6) mice, plasma creatinine or urine lactate dehydrogenase (LDH) levels were measured 40- min after ischemia plus 3-hr reperfusion (I/R). Renal I/R increased plasma creatinine and urine LDH levels with a greater magnitude in TRPV1-/- than WT mice (creatinine, uM: WT: 99.4 ± 4.4 to TRPV1: 129.7 ± 11.9, p < 0.05; LDH, mU: WT: 132.3± 39.8 to TRPV1-/-: 178.5 ± 44.4, p < 0.05). In vitro, cytokine or chemokine secretion from renal tissues incubated either with 95% O 2 -5% CO 2 or 99% nitrogen (hypoxia) was measured. TNFα, IL-6, or MCP-1 release in response to nitrogen (1 hr) was increased in both strains with a bigger magnitude in TRPV1-/- than WT mice (p<0.05). Blockade of receptors for calcitonin gene-related peptide (CGRP) with CGRP8-38 (10 -7 M) further increased hypoxia-induced MCP-1 release in WT mice (p<0.05). Ex4 suppressed nitrogen (0.5hr)-induced cytokine/chemokine release from the kidneys in WT but not TRPV1-/-mice (WT: IL-6: 0.74 ± 0.08 to 0.66 ± 0.03; TNF-a: 0.73 ± 0.07 to 0.66 ± 0.03; MCP-1: 16.1± 3.5 to 12.7 ± 1.3 pg/g/min, p < 0.05. TRPV1-/-: p>0.05 for all). Moreover, Ex4 increased CGRP release from the renal pelvis in WT ( p < 0.05) but not TRPV1 -/- mice, which can be inhibited by Ex9-39, an Ex4 antagonist. Thus, ablation of TRPV1 or blockade of CGRP receptors enhances hypoxia-induced inflammation and renal injury following I/R. Ex4 suppresses hypoxia-induced cytokine/chemokine release and enhances CGRP release from the kidney only when TRPV1 function and expression are intact, suggesting that TRPV1/CGRP may play a key role mediating Ex4-induced anti-inflammatory effects.

scholarly journals Aging reverses the role of the transient receptor potential vanilloid-1 channel in systemic inflammation from anti-inflammatory to proinflammatory

Cell Cycle ◽  
2012 ◽  
Vol 11 (2) ◽  
pp. 343-349 ◽  
Author(s):  
Samuel P. Wanner ◽  
Andras Garami ◽  
Eszter Pakai ◽  
Daniela L. Oliveira ◽  
Narender R. Gavva ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Anti Inflammatory ◽  
Transient Receptor

scholarly journals Quinoline as TRPV1 Antagonists: A New Approach against Inflammation

2019 ◽  
Vol 9 (4-s) ◽  
pp. 782-788
Author(s):  
Megha P. Ambatkar ◽  
Pramod B. Khedekar
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
The Novel ◽  
Quinoline Ring ◽  
First Response ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Transient Receptor ◽  
Acute And Chronic Inflammation

Inflammation is the first response of the immune system to harmful stimuli such as infection or irritation, consists of a cascade of biochemical events that propagates and matures the inflammatory response. Number of anti-inflammatory drugs are available for treatment of acute and chronic inflammation. Many anti-inflammatory drugs cause adverse side effects. The quinoline class of compounds are important for searching the safe and effective anti-inflammatory drugs. These drugs are classified based on the number of substituents present on the quinoline ring or compounds containing a quinoline ring fused to other heterocyclic compounds. Quinolines have the ability to target several causes of inflammation includes transient receptor potential vanilloid 1 receptor. The TRPV1 receptor, first cloned and characterized in 1997, is a non-selective cation channel expressed in primary sensory neurons, and is a key pain sensor and integrator. This review provides the discovery of various quinoline derivatives as transient receptor potential vanilloid 1 (TRPV1) antagonists. Overall, the quinoline moiety will be used as a new template for designing and identifying the novel anti-inflammatory drugs in future. Keywords: Quinoline, Inflammation, Transient receptor Potential Vanilloid 1, Antagonists.

scholarly journals Role of TRPV1 and TRPA1 Ion Channels in Inflammatory Bowel Diseases: Potential Therapeutic Targets?

2019 ◽  
Vol 12 (2) ◽  
pp. 48 ◽  
Author(s):  
Kata Csekő ◽  
Bram Beckers ◽  
Daniel Keszthelyi ◽  
Zsuzsanna Helyes
Keyword(s):  
Ion Channels ◽  
Inflammatory Bowel Diseases ◽  
Transient Receptor Potential ◽  
Intestinal Inflammation ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
High Morbidity ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Transient Receptor

Inflammatory bowel diseases (IBD) have long been recognized to be accompanied by pain resulting in high morbidity. Transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) ion channels located predominantly on the capsaicin-sensitive sensory neurons play a complex role in hyperalgesia and neurogenic inflammation. This review provides an overview of their expression and role in intestinal inflammation, in particular colitis, that appears to be virtually inconsistent based on the thorough investigations of the last twenty years. However, preclinical results with pharmacological interventions, as well as scarcely available human studies, more convincingly point out the potential therapeutic value of TRPV1 and TRPA1 antagonists in colitis and visceral hypersensitivity providing future therapeutical perspectives through a complex, unique mechanism of action for drug development in IBD.

scholarly journals A Glucuronic Acid-Palmitoylethanolamide Conjugate (GLUPEA) Is an Innovative Drug Delivery System and a Potential Bioregulator

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 450
Author(s):  
Emiliano Manzo ◽  
Aniello Schiano Moriello ◽  
Francesco Tinto ◽  
Roberta Verde ◽  
Marco Allarà ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Glucuronic Acid ◽  
Drug Carrier ◽  
Receptor Potential ◽  
Lipid Mediator ◽  
Transient Receptor Potential Vanilloid ◽  
Innovative Drug ◽  
Anti Inflammatory

Palmitoylethanolamide (PEA) is an endogenous anti-inflammatory lipid mediator and a widely used nutraceutical. In this study, we designed, realized, and tested a drug-carrier conjugate between PEA (the active drug) and glucuronic acid (the carrier). The conjugate, named GLUPEA, was characterized for its capability of increasing PEA levels and exerting anti-inflammatory activity both in vitro and in vivo. GLUPEA treatment, compared to the same concentration of PEA, resulted in higher cellular amounts of PEA and the endocannabinoid 2-arachidonoyl glycerol (2-AG), and increased 2-AG-induced transient receptor potential vanilloid type 1 (TRPV1) channel desensitization to capsaicin. GLUPEA inhibited pro-inflammatory monocyte chemoattractant protein 2 (MCP-2) release from stimulated keratinocytes, and it was almost as efficacious as ultra-micronized PEA at reducing colitis in dinitrobenzene sulfonic acid (DNBS)-injected mice when using the same dose. GLUPEA is a novel pro-drug able to efficiently mimic the anti-inflammatory and endocannabinoid enhancing actions of PEA.

Sign in / Sign up

Export Citation Format

Share Document