Capsaicin, The Vanilloid Receptor TRPV1 Agonist in Neuroprotection: Mechanisms Involved and Significance.

Hot peppers, also called chilli, chilli pepper, or paprika of the plant genus Capsicum (family Solanaceae), are one of the most used vegetables and spices worldwide. Capsaicin (8-methyl N-vanillyl-6-noneamide) is the main pungent principle of hot green and red peppers. By acting on the capsaicin receptor or transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1), capsaicin selectively stimulates and in high doses defunctionalizes capsaicin-sensitive chemonociceptors with C and Aδ afferent fibers.

Toxicokinetic Study of a Gastroprotective Dose of Capsaicin by HPLC-FLD Method.

Background: A low dose of capsaicin and its natural homologs and analogs (capsaicinoids) have shown to prevent development of gastric mucosal damage of alcohol and non-steroid anti-inflammatory drugs. Based on this experimental observation, a drug development program has been initiated to develop applicable capsaicin containing drugs to eliminate gastrointestinal damage caused by non-steroid anti-inflammatory drugs.

Methods: As a part of this program, a sensitive and selective reverse-phase high-performance liquid chromatography-based method with fluorescence detection has been developed for quantification of capsaicin and dihydrocapsaicin in experimental dog's plasma.

Membrane-bound ATP-dependent Energy Systems, as Extra- and Intracellular Key Signals for Gastrointestinal Functions and their Regulations in the Gastrointestinal Mucosa.

Aims: Our research group has carried out various biochemical examinations in rat gastric ulcer models and in human gastrointestinal resecates obtained from patient who underwent gastric intervention due to peptic ulcer disease. Biochemical methods gave excellent possibility to approach the biochemical events taking place in tissues, cellular and subcellular regulatory levels during of ulcer development and of its prevetions. This paper gives a brief summary of these biochemical examinations conducted during this study period started from the 1960's up till now.

Cellular Energetical Actions of "Chemical" and "Surgical" Vagotomy in Gastrointestinal Mucosal Damage and Protection: Similarities, Differences and Significance for Brain-Gut Function.

Background: The authors, as internists, registered significant difference in the long lasting actions of surgical and chemical (atropine treatment) vagotomy in patients with peptic ulcer during second half of the last century (efficency, gastric acid secretion, gastrointestinal side effects, briefly benefical and harmful actions were examined).

Aims: 1. Since the authors participated in the establishing of human clinical pharmacology in this field, they wanted to know more and more facts of the acute and chronic effects of surgical and chemical (atropine treatment) on the gastrointestinal mucosal biochemisms and their actions altered by bioactive compounds and scavengers regarding the development of gastric mucosal damage and protection.

A validated HPLC-FLD method for analysis of intestinal absorption and metabolism of capsaicin and dihydrocapsaicin in the rat.

A sensitive and selective reverse-phase high performance liquid chromatographic method with fluorescence detection has been developed for determination of capsaicin (8-methyl-N-vanillyl-(trans)-6-nonenamid) and dihydrocapsaicin (8-methyl-N-vanillylnonanamide) in samples generated in rat small intestine luminal perfusion experiments. The experiments were designed to study the biotransformation of capsaicinoids in the small intestine in the rat. The chromatographic separation was performed at room temperature on a ZORBAX Eclipse(®) XDB-C8 column using isocratic elution with a mobile phase consisting 0.

Capsaicin as new orally applicable gastroprotective and therapeutic drug alone or in combination with nonsteroidal anti-inflammatory drugs in healthy human subjects and in patients.

Background: Capsaicin is a specific compound acting on capsaicin-sensitive afferent nerves.

Aim: Capsaicin was used to study the different events of human gastrointestinal physiology, pathology, and clinical pharmacology, and possible therapeutic approaches to enhance gastrointestinal mucosal defense in healthy human subjects and in patients with various different gastrointestinal disorders as well as its use with nonsteroidal anti-inflammatory drugs (NSAIDs) in healthy subjects and in patients.

Materials And Methods: The observations were carried out in 198 healthy human subjects and in 178 patients with different gastrointestinal (GI) diseases (gastritis, erosions, ulcer, polyps, cancer, inflammatory bowel diseases, colorectal polyps, cancers), and in 69 patients with chronic (Helicobacter pylori positive and negative) gastritis (before and after eradication treatment).

Role of nitric oxide in the central interferon-alpha-induced inhibition of gastric acid secretion in rats.

Cytokines are known to play a key role in regulation of gastric functions. Interferon-alpha (IFN-α) has been published to impair gastric motility. Aims of this study were to clarify effect of IFN-α on gastric acid secretion (GAS) and determine role of nitric oxide (NO) in the process.

Molecular pharmacological approaches to effects of capsaicinoids and of classical antisecretory drugs on gastric basal acid secretion and on indomethacin-induced gastric mucosal damage in human healthy subjects (mini review).

Background: Actions of various drugs have been tested on the gastric acid basal secretion and on the drug (Indomethacin)- induced gastric mucosal damage; however their physiological and pharmacological mechanisms have not been compared.

Aims: The effects of capsaicinoids, atropine, cimetidine, omeprazole, famotidine and ranitidine were studied on gastric basal acid output, whereas the gastric mucosal preventive effects of capsaicinoids (capsaicin), atropine and cimetidine were tested on the indomethacin-induced gastric mucosal microbleedings in human healthy subjects. Results were presented by molecular pharmacological method; affinity (pD) and intrinsic activity (α-values) were calculated.

Capsaicin-sensitive afferentation represents an indifferent defensive pathway from eradication in patients with H. pylori gastritis.

Aim: To study the role of capsaicin-sensitive afferent nerves in Helicobacter pylori (H. pylori) positive chronic gastritis before and after eradication.

Methods: Gastric biopsy samples were obtained from corpus and antrum mucosa of 20 healthy human subjects and 18 patients with H.

Approaches to gastrointestinal cytoprotection: from isolated cells, via animal experiments to healthy human subjects and patients with different gastrointestinal disorders.

Our clinical observations proved that the the duodenal ulcer in patients healed without any inhibition of gastric acid secretion (1965), and the healing rates of atropine vs cimetidine vs Carbenoxolone were equal and superior to that of placebo in randomized, prospective and multiclinical study of DU patients (1978). The phenomenon of gastric cytoprotection was defined by André Robert in rats (1979). The essential point of this phenomenon is that the prostaglandins prevent the chemical-induced gastric mucosal damage without affecting gastric acid secretion, this being originally suggested as a reaction specific to prostaglandins.

Serum prohepcidin levels in chronic inflammatory bowel diseases.

Background And Aims: One of the major symptoms of chronic inflammatory bowel diseases is anemia. The two most common diseases are Crohn's disease and ulcerative colitis. Anemia may develop due to intestinal bleeding, iron absorption disturbances, or high levels of inflammatory cytokines.

Gastric cytoprotection 30 years after its discovery by André Robert: a personal perspective.

It is generally accepted that the development of gastric mucosal injury and protection is a consequence of an imbalance between the existing aggressive and defensive factors in the gastric mucosa. The excess secretion of gastric acid and increased production of pepsin have been considered as the main etiological factors in the development of peptic ulcer diseases in humans. André Robert and his coworkers (Kalamazoo, Michigan, USA) identified a new pathway for the gastric mucosal protection against the gastric mucosal damage injury (e.

Production of orally applicable new drug or drug combinations from natural origin capsaicinoids for human medical therapy.

It is well known that the capsaicin stimulates (in small doses) or impairs (in high doses) the capsaicin-sensitive afferent nerves and the final effects of capsaicin depend on its applied doses. The effects of capsaicin were analyzed on the gastrointestinal mucosal protection and injury in animal experiments and in human beings (from 1980 up to now). From 2005 to 2008 an interdisciplinary group (21 researchers) participated in the production of orally applicable drug or drug combinations from capsaicin for human medical therapy of patients suffering from cardiovascular, degenerative joint and locomotor diseases, who received in their treatments non-steroidal anti-inflammatory compounds (NSAIDs).

Interdisciplinary review for correlation between the plant origin capsaicinoids, non-steroidal antiinflammatory drugs, gastrointestinal mucosal damage and prevention in animals and human beings.

Background: The plant origin capsaicinoids (capsaicin, dihydrocapsaicin, norcapsaicin, dihydrocapsaicin, homocapsaicin, homodihydrocapsaicin) are well known and used as nutritional additive agents in the every day nutritional practice from the last 9,500 years; however, we had have a very little scientifically based knowledge on their chemistry, physiology and pharmacology in animal observations, and in humans up to the mid-twentieth century. Our knowledge about their chemistry, physiology, pharmacology entered to be scientifically based evidence from the year 1980, dominantly in animal observations. The human observations with capsaicin (capsaicinoids), in terms of good clinical practice, have been started only in the last 10-year period (from 1997) in randomized, prospective, multiclinical studies.

No association of the cytotoxic T-lymphocyte associated gene CTLA4 +49A/G polymorphisms with Crohn's disease and ulcerative colitis in Hungarian population samples.

Aim: The goal of the current work was to analyse the prevalence of the +49A/G variant of the cytotoxic T-lymphocyte antigen 4 gene (CTLA4) in Hungarian patients with Crohnos disease (CD) and ulcerative colitis (UC).

Methods: A total of 130 unrelated subjects with CD and 150 with UC, and 170 matched controls were genotyped for the single nucleotide polymorphism (SNP). The genotypes were determined by using PCR/RFLP test.

Plasma carnitine ester profiles in Crohn's disease patients characterized for SLC22A4 C1672T and SLC22A5 G-207C genotypes.

Crohn's disease (CD) is a chronic inflammatory bowel disorder caused by environmental and genetic factors. The purpose of this study was to analyse the possible influence of functional variants of genes of OCTN cation transporters on the carnitine ester profile of patients with CD. Genotyping for SLC22A4 1672C --> T, SLC22A5-207G --> C mutations and three common NOD2 variants (R702W, G908R and 1007finsC) were performed in 100 adult CD patients and in ninety-four healthy controls by direct sequencing.

Molecular pharmacological approach to drug actions on the afferent and efferent fibres of the vagal nerve involved in gastric mucosal protection in rats.

Background: Gastric mucosal protection is associated with the actions of anti-ulcer drugs or agents affecting on the afferent and/or efferent nerve fibres of the vagal nerve.

Aims: 1. To identify the dose-response curves of drugs (compounds) on the afferent vanilloid-receptor (capsaicin or resiniferatoxin-sensitive) and on efferent secretion (atropine, pirenzepine, cimetidine, ranitidine, famotidine, omeprazole, esomeprazole) basal gastric acid and stimulated gastric secretion in relation to the chemically-induced gastric mucosal damage in rats; 2.

Prevalence of SLC22A4, SLC22A5 and CARD15 gene mutations in Hungarian pediatric patients with Crohn's disease.

Aim: To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn's disease (CD).

Methods: A cohort of 19 unrelated pediatric and 55 unrelated adult patients with Crohn's disease and 49 healthy controls were studied. Genotyping of the three common CD-associated CARD15 variants (Arg702Trp, Gly908Arg and 1007finsC changes) with the SLC22A4 1672C-->T, and SLC22A5 -207G-->C mutations was performed by direct sequencing of the specific regions of these genes.

[Immunology of HCV infection: the causes of impaired cellular immune response and the effect of antiviral treatment].

Background: The outcome of HCV infection and the response to antiviral treatment depend on both viral and host factors. Host immune response contributes not only to viral control, clinical recovery and protective immunity, but also to chronic hepatitis and liver cirrhosis. Establishing immunological status and identifying pretreatment immunological factors associated with better response to therapy might be of importance in the understanding of the successful immune response and in the future of combination therapy to HCV infection.

Capsaicin and glucose absorption and utilization in healthy human subjects.

Although many animal experiments (under different experimental circumstances) have been performed, however, to date there have been no human studies of the role of capsaicin-sensitive afferent nerves in carbohydrate metabolism. The glucose loading test (administration of 75 g orally given glucose) was evaluated in 14 human healthy subjects by the simultaneous measurement of plasma level of glucose, C-peptide and glucagon every 15 min for 4 h without and with (ED50) oral application of capsaicin. The plasma level of glucose increased significantly from 30 to 150 min, and the plasma glucagon level increased from 90 to 180 min after the glucose loading when capsaicin administered.

Effect of special Hungarian probiotic kefir on faecal microflora.

Aim: To investigate the effect of a four-week consumption of a special Hungarian probiotic agent (Biofir) on the faecal microflora in human healthy subjects.

Methods: The effect of Biofir with 10(6)/cm3 initial germs on the faecal microflora was studied in 120 healthy volunteers (71 females, 49 males). The traditional Russian type kefir was used as control.

Changes of plasma fasting carnitine ester profile in patients with ulcerative colitis.

Aim: To determine the plasma carnitine ester profile in adult patients with ulcerative culitis (UC) and compared with healthy control subjects.

Method: Using ESI triple quadrupole tandem mass spectrometry, the carnitine ester profile was measured in 44 patients with UC and 44 age- and sex-matched healthy controls.

Results: There was no significant difference in the fasting free carnitine level between the patients with UC and the healthy controls.

Involvement of serum retinoids and Leiden mutation in patients with esophageal, gastric, liver, pancreatic, and colorectal cancers in Hungary.

Aim: To analyze the serum levels of retinoids and Leiden mutation in patients with esophageal, gastric, liver, pancreatic, and colorectal cancers.

Methods: The changes in serum levels of retinoids (vitamin A, alpha- and beta-carotene, alpha- and beta-cryptoxanthin, zeaxanthin, lutein) and Leiden mutation were measured by high liquid performance chromatography (HPLC) and polymerase chain reaction (PCR) in 107 patients (70 males/37 females) with esophageal (0/8), gastric (16/5), liver (8/7), pancreatic (6/4), and colorectal (30/21 including 9 patients suffering from in situ colon cancer) cancer. Fifty-seven healthy subjects (in matched groups) for controls of serum retinoids and 600 healthy blood donors for Leiden mutation were used.