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Capsaicin and Gastric Ulcers
Critical Reviews In Food Science and Nutrition
Abstract
In recent years, infection of the stomach with the organism Helicobacter Pylori has been found to be the main cause of gastric ulcers, one of the common ailments afflicting humans. Excessive acid secretion in the stomach, reduction in gastric mucosal blood flow, constant intake of non-steroid anti-inflammatory drugs (NSAIDS), ethanol, smoking, stress etc. are also considered responsible for ulcer formation. The prevalent notion among sections of population in this country and perhaps in others is that "red pepper" popularly known as "Chilli," a common spice consumed in excessive amounts leads to "gastric ulcers" in view of its irritant and likely acid secreting nature. Persons with ulcers are advised either to limit or avoid its use. However, investigations carried out in recent years have revealed that chilli or its active principle "capsaicin" is not the cause for ulcer formation but a "benefactor." Capsaicin does not stimulate but inhibits acid secretion, stimulates alkali, mucus secretions and particularly gastric mucosal blood flow which help in prevention and healing of ulcers. Capsaicin acts by stimulating afferent neurons in the stomach and signals for protection against injury causing agents. Epidemiologic surveys in Singapore have shown that gastric ulcers are three times more common in the "Chinese" than among Malaysians and Indians who are in the habit of consuming more chillis. Ulcers are common among people who are in the habit of taking NSAIDS and are infected with the organism "Helicobacter Pylori," responsible for excessive acid secretion and erosion of the mucosal layer. Eradication of the bacteria by antibiotic treatment and avoiding the NSAIDS eliminates ulcers and restores normal acid secretion.
... Recent studies have shown that capsaicin is also a potent gastroprotective agent (73), probably by enhancing gastric acid secretion. However, capsaicin has no role in acid secretion in GI applications, serosal application, or perfusion (73). ...
... Recent studies have shown that capsaicin is also a potent gastroprotective agent (73), probably by enhancing gastric acid secretion. However, capsaicin has no role in acid secretion in GI applications, serosal application, or perfusion (73). It has been found that very low doses of capsaicin suppress acid secretion in pylorus-ligated rats (73). ...
... However, capsaicin has no role in acid secretion in GI applications, serosal application, or perfusion (73). It has been found that very low doses of capsaicin suppress acid secretion in pylorus-ligated rats (73). Furthermore, capsaicin may also be used in diabetes, obesity, itch, gastric, and urological disorders (72). ...
Inflammation is a protective mechanism against injury or tissue damage. Depending
on the extent of inflammation, various disease conditions can be induced. The
incidence of inflammatory diseases has increased in recent years; synthetic non�steroidal anti-inflammatory drugs (NSAIDs) and steroids are usually used to treat
this condition. Synthetic NSAIDs cause side effects; thus, natural medicines may
be effective alternatives. Many natural anti-inflammatory agents and supplements
are currently available, including natural anti-inflammatory polysaccharides, green
tea, curcumin, colchicine, stingless bee honey, capsaicin, monoterpene kaempferol,
omega-3 fatty acids, certain vitamins, minerals, and others. The mechanisms of action
of these natural anti-inflammatory agents and supplements are very similar to
those of synthetic anti-inflammatory agents, exhibiting anti-inflammatory activity
mainly through inhibiting actions of pro-inflammatory cytokines including interleukins,
tumor necrosis factor-α (TNF-α), and chemokines. In addition, some natural anti�inflammatory agents inhibit the action of cyclooxygenase enzymes (mainly COX2),
inducible nitric oxide (iNOS), reactive oxygen species (ROS), and nuclear factor�kappa B (NF-κB) signaling molecules. Although the effectiveness of these natural
anti-inflammatory agents and supplements is similar to that of chemical NSAIDs
and steroids, they are safer to use. The purpose of this review is to summarize existing
research data and discuss the activity of natural anti-inflammatory agents and
supplements.
... Oral ulcers. Capsaicin in chili peppers was once proposed as a component that could cause ulcers, particularly in the gastrointestinal tract (46,47). However, later studies have found that it acted contrarily, i.e., capsaicin helps in preventing and relieving ulcers by inhibiting gastric acid secretion and stimulating mucus secretions and blood flow (47). ...
... Capsaicin in chili peppers was once proposed as a component that could cause ulcers, particularly in the gastrointestinal tract (46,47). However, later studies have found that it acted contrarily, i.e., capsaicin helps in preventing and relieving ulcers by inhibiting gastric acid secretion and stimulating mucus secretions and blood flow (47). ...
Capsaicin is a bioactive compound found prominently in Capsicum annuum L. plants and takes on a pivotal role in their characteristic spiciness. Previous studies have delved into the potential analgesic effect of capsaicin in various oral conditions, such as oral neuropathic pain, trigeminal neuralgia, oral mucositis, temporomandibular joint disorders and burning mouth syndrome. Capsaicin has also demonstrated promise in inhibiting the proliferation of different oral cancer cell lines. Its antimicrobial properties have also been shown to inhibit the growth of oral pathogens associated with dental caries, periodontitis and oral candidiasis. However, to harness its benefits effectively, more studies are required to establish optimal dosages for pain relief while minimizing adverse effects. In addition, investigation of the effect of capsaicin on nonpathogenic oral bacteria and viruses is warranted. Human-based research is crucial for elucidating the biomolecular mechanisms underlying the properties of capsaicin, potentially leading to the development of more effective interventions for oral health problems.
... This gastrointestinal disorder affect annually 10%-15% of the world's population. 1 Nowadays, the prevalence of gastric diseases is rising due to various factors, such as excessive usage of non-steroidal anti-inf lammatory drugs, alcohol, caffeine consumption, smoking, stressful life style, consumption of fatty foods, nutritional deficiencies, helicobacter pylori infection. 2,3 The basic pathophysiology of gastric ulcers results from an imbalance between some aggressive and defensive factors of the gastric mucosa. 4 Recently, the risk of developing peptic ulcer in the United States is 10% over a life time. ...
The present study was performed to evaluate the therapeutic impact of Diospyros kaki fruit aqueous extract (DKFAE) on ethanol induced peptic ulcer. The phytochemical studies of DKFAE were investigated using colorometric analysis. Gastric ulcer was induced by one dose of ethanol (5 ml/Kg, b.w) on 24 h empty stomach. Then, the plant extract (200, 400 mg/kg) was orally administrated for 2 weeks. Famotidine (FAM: 40 mg/kg, b.w.): a reference drug was also tested. The effect of mixture dose between the fruit extract and FAM (DKFAE, 50 mg/kg PC, p.o. + FAM, 50 mg/kg PC, p.o.) was also evaluated. One hour after induction of ulcer blood samples were collected, stomach acidity and volume, as well as lesion counts were measured, then stomach and intestine of scarified rats were subjected to biochemical, macroscopic and microscopic studies. Results showed that DKFAE exhibited an important antioxidant potential. In vivo, the results showed that alcohol induced gastric damage, improving oxidative stress markers level such as MDA and H2O2, gastric and intestinal calcium and free iron. The intoxication by ethanol also produce an inflammation occurred by high level of the C-reactive protein (CRP) and alkaline phosphatase (ALP) activity in plasma. In contrast, DKFAE and the mixture dose significantly protect against macroscopic and histological injuries, the secretory profile disturbances, lipid peroxidation, antioxidant enzymes activities and non enzymatic antioxidant level decrease induced by ethanol administration. More impressively, the mixture dose exerted the more excellent effect than DKFAE and famotidine each alone showing is possible synergism.
... It has been demonstrated that systemic capsaicin administration can cause the elevation of somatostatin levels [496][497][498][499]. This might hold therapeutical potential, perhaps by local instillation of capsaicin, thus obviating the risk of capsaicin side effects that accompany its systemic administration in high doses [500][501][502][503][504][505]. The interplay with SSTRs and somatostatin levels in cancers is of interest since capsaicin itself also exhibits antitumoral effects [506][507][508][509]. Another possibility is the use of nanoparticles, which are already been studied for the deployment of anti-cancer agents [510][511][512][513][514], or lipoparticles [515,516] for targeted delivery to neoplasias. ...
Somatostatin is a peptide that plays a variety of roles such as neurotransmitter and
endocrine regulator; its actions as a cell regulator in various tissues of the human body are represented
mainly by inhibitory effects, and it shows potent activity despite its physiological low concentrations.
Somatostatin binds to specific receptors, called somatostatin receptors (SSTRs), which have different
tissue distributions and associated signaling pathways. The expression of SSTRs can be altered
in various conditions, including tumors; therefore, they can be used as biomarkers for cancer cell
susceptibility to certain pharmacological agents and can provide prognostic information regarding
disease evolution. Moreover, based on the affinity of somatostatin analogs for the different types
of SSTRs, the therapeutic range includes conditions such as tumors, acromegaly, post-prandial
hypotension, hyperinsulinism, and many more. On the other hand, a number of somatostatin
antagonists may prove useful in certain medical settings, based on their differential affinity for SSTRs.
The aim of this review is to present in detail the principal characteristics of all five SSTRs and to
provide an overview of the associated therapeutic potential in neoplasias.
... Gastric ulcers are caused by a number of factors, including alcoholism, smoking, dietary inadequacies, and frequent utilization of anti-inflammatory medicines. Coffee, spicy food, and emotional stress are all things that might make the stomach secrete more acid and aggravate an ulcer that already exists (Satyanarayana, 2006). ...
This research was conducted to evaluate the nutritional content of camel milk and the difficulties that accompany them when taken with indomethacin. The results observed that camel milk is a rich source of nutritional values and antioxidants. The biological experimental was divided into six groups. The first group was control negative, and the groups G2, G3, G4, and G5 had orally one dose of indomethacin (30 mg/kg body weight) to induce ulcers. The G2 was considerably a positive control, and the groups G3, G4, and G5 had orally 5, 10, and 15 mL/kg body weight daily camel milk. The results observed that camel milk markedly raised concentrations of enzymatic antioxidants while concurrently lowering malondialdehyde levels in comparison to the positive group. However, rats taken orally 15 mL/kg camel milk showed significantly lower serum IL-6 and tumor necrosis factor-α concentration compared to 5 and 10 mL/kg camel milk. Rats given indomethacin showed a significant decrease in cyclooxygenase (COX-2) and prostaglandin E2 (PGE2) levels and also a significant increase in cytochrome P450 reductase activity. These results were based on the measurements of cyclooxygenase activity, PGE2 concentration, and cytochrome P450 reductase activity in the gastric tissues. The results from macroscopic examination and histopathological examination of gastric ulcers in normal and treated rats groups with camel milk confirmed the above results by serum and gastric tissue. Therefore, camel milk has a potent ulcer-healing impact on gastrointestinal injury caused by indomethacin. The potential cytoprotective mechanism and antioxidant characteristics of camel milk may be responsible for its antiulcer efficacy.
... Epidemiological studies have shown that the intake of spicy foods may have beneficial effects on hypertension, gastric ulcers, inflammatory bowel disease and gastrointestinal cancer [116][117][118]. And it is negatively correlated with the risk of death caused by cancer, ischemic heart disease and respiratory diseases [119]. On the contrary, it may be a risk factor for abdominal obesity [117]. ...
Transient receptor potential vanilloid 1 (TRPV1) is a transmembrane and non-selective cation channel protein, which can be activated by various physical and chemical stimuli. Recent studies have shown the strong pathogenetic associations of TRPV1 with neurodegenerative diseases (NDs), in particular Alzheimer’s disease (AD), Parkinson’s disease (PD) and multiple sclerosis (MS) via regulating neuroinflammation. Therapeutic effects of TRPV1 agonists and antagonists on the treatment of AD and PD in animal models also are emerging. We here summarize the current understanding of TRPV1’s effects and its agonists and antagonists as a therapeutic means in neurodegenerative diseases, and highlight future treatment strategies using natural TRPV1 agonists. Developing new targets and applying natural products are becoming a promising direction in the treatment of chronic disorders, especially neurodegenerative diseases.
... Buiatti et al. (1989) have recently reported that capsaicin from red pepper does not cause ulcer formation, with numerous studies resulting that eating hot pepper plays a protective role against stomach cancer. Satyanarayana (2006) has studied the effects of capsaicin and showed it inhibits acid secretion, stimulates alkali and mucus secretions, and gastric mucosal blood flow, thus preventing the formation of ulcers. Jancso, Kiraly, and Jancs o-Gábor (1977) have carried out the antiulcer activity and showed that capsaicin inhibited the growth of H. pylori and also inhibits the release of gastrin, and stimulates that of somatostatin, which decreases gastric acid secretion. ...
Capsicum annuum L., commonly known as chili pepper, is used as an important spice globally and as a crude drug in many traditional medicine systems. The fruits of C. annuum have been used as a tonic, antiseptic, and stimulating agent, to treat dys-pepsia, appetites, and flatulence, and to improve digestion and circulation. The article aims to critically review the phytochemical and pharmacological properties of C. annuum and its major compounds. Capsaicin, dihydrocapsaicin, and some caroten-oids are reported as the major active compounds with several pharmacological potentials especially as anticancer and cardioprotectant. The anticancer effect of cap-saicinoids is mainly mediated through mechanisms involving the interaction of Ca 2+-dependent activation of the MAPK pathway, suppression of NOX-dependent reac-tive oxygen species generation, and p53-mediated activation of mitochondrial apo-ptosis in cancer cells. Similarly, the cardioprotective effects of capsaicinoids are mediated through their interaction with cellular transient receptor potential vanilloid 1 channel, and restoration of calcitonin gene-related peptide via Ca 2+-dependent release of neuropeptides and suppression of bradykinin. In conclusion, this comprehensive review presents detailed information about the traditional uses, phytochem-istry, and pharmacology of major bioactive principles of C. annuum with special emphasis on anticancer, cardioprotective effects, and plausible toxic adversities along with food safety. K E Y W O R D S anticancer, capsaicinoids, Capsicum annuum, cardioprotective, pharmacology, traditional use
... Chilli pepper is commonly associated with ulcers. However, according to research of Satyanarayana (2006), is the most common ulcers in Chinese section of the population in Singapore than among the Malaysians and Indians that consuming more chillis in their diets. The author shown capsaicin has been found to inhibit the growth of Helicobacter pylori and the release of gastrin and stimulates that of somatostatin, the physiological inhibitor of acid secretion. ...
Pepper is a functional food due to is capsaicin or piperine, minerals, vitamins, phenolic acids and flavonoids. Peppers are classified according to their characteristics, such as stinging, color, size and flavor. The consumption of peppers is related pungency sensation and to the benefits to human health, as they are a source of vitamins and have nutritional and antioxidant properties that can have a significant impact on diseases. Pepper crops present problems, as pests and irrigation, which are frequently reported. The objective of this work was to report the panorama of the chili pepper sauce production process, finding regarding beneficial on properties of pepper and discuss its several forms of sold, pepper cultivation and beneficial effects and disadvantage of pepper consume.
... Arsenicum album Arsenic Oxide [32] Arsenic produce toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair [64] . Acute arsenic poisoning leads to nausea, vomiting, abdominal pain, and severe diarrhoea. ...
The Homoeopathic system follows the principle of similia similibus curantur. The concept of potentisation, molecular action of Homoeopathic drug substances, can be explained through an in-vitro study by using Staphylococcus aureus culture. Microbial culture prepared with nutrient agar medium, Hear the bacteria itself considered a whole organism. Nitric acid 1X, 2X, 3X, 4X, 5X, 6X, and 30C as taken as study sample, erythromycin 1X, 2X, 3X, 4X, 5X, 6X, and 30C used as a comparison, water plus ethanol solution used as a negative control. Nitric acid shows inhibitory effects on culture growth up to 3X. Erythromycin up to 5X. Negative control and other dilutions produce no inhibitory effects. There is no growth-stimulating effects or any other effects seen on the culture. A drug in its high concentration produces a group of symptoms during drug proving through its molecular or receptor interactions. Such drugs in their low concentrations follow the same molecular pathway or receptor pathway. We can understand the concepts much better with the action of capsaicin alkaloid on TRPV1 receptor, indications of capsicum annum homoeopathic drug from its drug proving records, Along with that, examples of homoeopathic medicine's active compounds and their molecular or receptor interactions compared with the involvement of such receptors in the disease process. Administration of specific homoeopathic medicine having an affinity towards the particular receptors or molecules involved in the disease process leads to modulation of such receptor or molecular pathway it offers the betterment of symptoms or curative effects.
... Severe cases can cause perforation and gastrointestinal bleeding (Dovjak 2017). Pathogenic factors include poor diet, physical stress, tobacco abuse, prolonged administration of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), excessive caffeine, and Helicobacter pylori infection (Satyanarayana 2006). In addition, gastric mucosal injury can be induced by excessive alcohol intake (Mousa et al. 2019). ...
Context
Zuojin Pill (ZJP) has been used to treat gastrointestinal problems in China for hundreds of years.
Objective
To discover more potential active ingredients and evaluate the gastroprotective mechanisms of ZJP.
Materials and methods
An approach involving UPLC-Q-Orbitrap HRMS and serum pharmacochemistry was established to screen the multiple chemical constituents of ZJP. Male Sprague-Dawley (SD) rats were divided into six groups: normal control, ulcer control, omeprazole (30 mg/kg), and three ZJP groups (1.0, 2.0 and 4.0 g/kg). After oral treatment with ZJP or omeprazole for 7 days, all groups except the normal control group were orally administered 5 mL/kg ethanol to induce gastric ulceration. Histopathological assessment of gastric tissue was performed by haematoxylin and eosin staining. Antioxidant parameters and inflammatory mediators were determined using ELISA Kit and immunohistochemical analysis.
Results
Ninety components were identified in ZJP. Among them, 23 prototypes were found in rat serum after oral administration of ZJP. The ulcer inhibition was over 90.0% for all the ZJP groups. Compared with the ulcer control rats, ZJP (4.0 g/kg) enhanced the antioxidant capacity of gastric tissue: superoxide dismutase (1.33-fold), catalase (2.61-fold), glutathione (2.14-fold), and reduced the malondialdehyde level (0.48-fold). Simultaneously, the ZJP meaningfully lowered the content of tumour necrosis factor-α (0.76-fold), interleukin-6 (0.66-fold), myeloperoxidase (0.21-fold), and nuclear factor kappa B (p65) (0.62-fold).
Discussion and conclusions
This study showed ZJP could mitigate ethanol-induced rat gastric ulcers, which might benefit from the synergistic actions of multiple ingredients. The findings could support the quality control and clinical trials of ZJP.
... Pungency or the hot taste of pepper fruits is a function of capsaicinoid concentration. These compounds are recognised for their therapeutic effects on gastric ulcers and rheumatoid arthritis (Sathyanarayana, 2006). Capsaicin and alkaloid content were observed to increase in fruits harvested from plants grown from seeds exposed to 100 Gy. ...
Hunger affects more than 2 billion people globally. Therefore, there is the need to improve plant species in order to increase yield and mineral contents especially β-carotene. This study was aimed at sourcing for new favourable genetic variations in the M1 generation that could be exploited in biochemical traits. Mutation was induced in Nsukka Yellow Pepper using varied doses of gamma irradiation (50, 100, 150 and 200 Gy) from 60 Co source in the Gamma Irradiation Facility, Nuclear Technology Centre, Sheda Science and Technology Complex, Abuja. The seeds were evaluated in the field during the 2016 planting season using the Completely Randomised Design in the Botanical Garden of the University of Nigeria, Nsukka. Increase in vitamin C, total carotenoid and capsaicin content were observed in fruits of the treated plants when compared with the control. The β-carotene (6.24 ± 0.06 mg/L) and iron content (5.08 ± 0.0 7 mg/L) were higher in fruits of the genotype exposed to 50 Gy. Flavonoid content was observed to decrease in fruits exposed to 50 and 150 Gy. There was reduction in the phytate content across most of the treatments when compared to the control. Gamma irradiation dosage of 50-200 Gy could be exploited in the induction of variability relevant for the improvement of biochemical traits in the pepper.
... Gastritis is a common disease that affects many people every year worldwide. A gastrointestinal mucosal injury is caused by environmental factors such as eating habits, smoking, severe stress, and heavy drinking, as well as Helicobacter pylori infections and non-steroidal anti-inflammatory drugs (NSAIDs, including indomethacin and aspirin) [1,2]. This inflammatory disease of the gastrointestinal mucosa is called gastritis, and damage to the mucous membrane progresses and can develop into chronic gastritis and gastric ulcers, which ultimately become the cause of gastric cancer [3]. ...
Gastritis is a common disease worldwide that is caused by various causes such as eating habits, smoking, severe stress, and heavy drinking, as well as Helicobacter pylori infections and non-steroidal anti-inflammatory drugs. Cinnamomum cassia is a tropical aromatic evergreen tree commonly used as a natural medicine in Asia and as a functional food ingredient. Studies have reported this species’ anti-obesity, anti-diabetic, and cardiovascular disease suppression effects. We evaluated the potential effects of C. cassia using non-steroidal anti-inflammatory drugs (NSAIDs), ethanol (EtOH), and ethanol/hydrochloric acid (HCl)-induced gastric mucosal injury models. C. cassia extracts reduced the area of gastric mucosa injury caused by indomethacin, NSAID, EtOH, and EtOH/HCl. We also applied a network pharmacology-based approach to identify the active compounds, potential targets, and pharmacological mechanisms of C. cassia against gastritis. Through a network pharmacology analysis, 10 key components were predicted as anti-gastritis effect-related compounds of C. cassia among 51 expected active compounds. The NF-κB signaling pathway, a widely known inflammatory response mechanism, comprised a major signaling pathway within the network pharmacology analysis. These results suggest that the anti-gastritis activities of C. cassia may be induced via the anti-inflammatory effects of key components, which suppress the inflammation-related genes and signaling pathways identified in this study.
... Helicobacter pylori is known to cause infection in the stomach and secrete enzymes such as phospholipase and urease, which adversely affect the protective mucosal barrier and leads to the ulcer formation (López et al. 2003). Capsicum and capsaicin were found to inhibit acid secretion and stimulate alkali and mucous secretions (Satyanarayana, 2006) and helped in healing of ulcer (Barua et al., 2014, Mozsik et al., 2005Szolcsanyi, 1990). Capsaicin also reported to regulate the release of gastrin and somatostatin, which play role in the regulation of acid secretion (Park et al., 2000). ...
... Previous studies demonstrated that capsaicin at concentrations greater that 10 µg/mL had bactericidal activity and inhibited the growth of certain bacteria among is H. pylori in vitro (Jones et al., 2006). Capsaicin administrated in a vehicle at concentration of 4 mM decreased H. pylori-induced gastric ulcer in human via topically or g.i., the reduction was related to the diminished IL-8 production and reduced NF-κB activity (Satyanarayana, 2006). ...
... mg capsaicin/day), and the findings were independent of H. pylori infection, which is a major risk factor for gastric cancer [53]. However, other factors such as sodium intake can also be attributed to the incidence of gastric cancer [22,[54][55][56]. Additionally, individuals with high capsaicin consumption levels may also consume high amounts of foods, which can cause adverse health effects. ...
The consumption of capsaicinoids, the active components in chili peppers, has been associated with both positive and negative health effects, and the level of capsaicinoid exposure may be an important determinant. Dietary capsaicinoid exposure was estimated using a previously developed database for capsaicinoid content and a 24-h dietary recall dataset obtained from the Korea National Health and Nutrition Examination Survey. The estimated consumption level was evaluated to determine its potential effects on weight reduction and gastrointestinal distress. The estimated daily mean capsaicinoid intake was 3.25 mg (2.17 mg capsaicin), and most Koreans consumed 1–30 mg of capsaicinoids (0.67–20 mg capsaicin) in a day. No adverse effect of capsaicin consumption was reported other than abdominal pain. For long-term repeated consumption, 30 mg may be the maximum tolerable dose. However, the effects on body weight or energy balance were inconsistent in 4–12 week clinical studies conducted with various capsaicin doses (2–135 mg), which was likely due to the complex interplay between capsaicin dose, study length, and participant characteristics. Therefore, the capsaicin consumption of most Koreans was below the levels that may cause adverse effects. However, more long-term studies for the dose range of 2–20 mg are required to further characterize capsaicin’s health benefits in Koreans.
... However, although studies have shown that capsaicin can aggravate certain symptoms, it does not cause gastric ulcers, and is only problematic for a select number of persons. 7 Accordingly most people could safely incorporate capsicum into their diets, at least in small amounts, to spice up their food. Even people suffering from alcohol dependency could try incorporating it in small quantities and observe how it may or may not affect their dependency. ...
... In addition to being the main component of chile peppers, capsaicin is reported to possess chemopreventive, antioxidant, anti-bacterial, anti-inflammatory and hypolipidemic effects. [12][13][14][15][16][17] Consequently, capsaicin finds use in a range of pharmaceuticals, drug delivery and medical applications such as inclusion in topical creams, liquids and patch preparations for chronic pain syndromes, dietary supplements to tackle obesity and defensive sprays. [18][19][20][21][22][23] As such, there is an analytical interest to measure capsaicinoids in a wide range of samples. ...
When you bite into a chile pepper or eat food containing chile (chilli), one might feel heat, or other associated feelings, some good such as the release of endorphins, and some bad. The heat, or pungency, and related feelings from eating chile peppers are the result of their chemical composition, i.e. the concentrations of capsaicinoids. The major components are capsaicin and dihydrocapsaicin, which occur in chiles in the ratio of 6 : 4. Other capsaicinoids occur in smaller concentrations and are known as the "minor" capsaicinoids. Wilbur L. Scoville in 1912 created an organoleptic test, now known as the Scoville scale, which asked a panel of tasters to state when an increasingly dilute solution of the chile pepper in alcohol no longer burned the mouth. Following the Scoville scale, a plethora of analytical techniques later followed. In this overview, we explore the endeavours directed to the development of electrochemical-based sensors for the determination of capsaicin and related compounds, starting from their use in hyphenated laboratory set-ups to their modern use as stand-alone electroanalytical sensors. The latter have the advantage of providing a rapid and sensitive methodology that has the potential to be translated in the field; future trends and issues to be overcome are consequently suggested.
... [4,5] The CAFs are reported to contain capsaicinoids (0.1%-2%), that are responsible for characteristic pungent taste and possess high therapeutic value in gastric ulcer and rheumatoid arthritis. [6,7] Study suggests most varieties of CAFs to comprise key capsaicinoids like capsaicin and dihydrocapsaicin (1:1); and few capsaicinoids like homodihydrocapsaicin, homocapsaicin, and nordihydrocapsaicin (ranging from 1% to 38%). [8] The crude extract of CAFs known as capsicum oleoresin contains at least 100 different volatile chemical constituents. ...
... Previous studies demonstrated that capsaicin at concentrations greater that 10 µg/mL had bactericidal activity and inhibited the growth of certain bacteria among is H. pylori in vitro (Jones et al., 2006). Capsaicin administrated in a vehicle at concentration of 4 mM decreased H. pylori-induced gastric ulcer in human via topically or g.i., the reduction was related to the diminished IL-8 production and reduced NF-κB activity (Satyanarayana, 2006). ...
The hot chili pepper industry represents one of the most important staple foods in Mexico and many Asian countries. Nowadays, large amounts of waste materials are produced from the pepper supply chain that could be used as a source to obtain nutraceuticals. Among the most common and important bioactive compounds contained in pepper residues are the capsaicinoids, which are the responsible of the pungency of the pepper. Capsaicinoids, mainly capsaicin, may ameliorate obesity, gastric disorder, diabetes, cardiovascular diseases, cancer, rhinitis, asthma, immune system diseases, and important viral diseases as the recent COVID-19. The aim of this review is to review the industrial process for the extraction of capsaicinoids ingredients from pepper residues and to examine the relation of the capsaicin and other chili pepper phytochemicals to prevent and treat chronic diseases explained through the key role of the TRPV1 receptor. The extraction and incorporation of these compounds into nutraceutical formulations depend mainly on the development of new methods to improve not only the yield of a particular compound but the validation of the bioactivity and phytochemical characterization.
... In addition, the CGRP receptor antagonist, CGRP has been demonstrated to aggravate gastric mucosal injury induced by indomethacin (indomethacin) or ethanol (72,73). Notably, the increase in the healing time of gastric ulcer by the use of acetic acid and ethanol exacerbates gastric mucosal injury during stress in CGRP gene knockout animal models (74,75 (84). Rutaecarpine has been reported to upregulate endogenous CGRP expression by activating the VR1 signaling pathway, which results in the protection of rats with acute pancreatitis (85). ...
Calcitonin gene‑related peptide (CGRP) is the predominant neurotransmitter located in sensory nerves. This peptide is extensively distributed in central and peripheral tissues. CGRP causes relaxation of cardiovascular smooth muscle cells and confers protection against ischaemic myocardium and cardiac remodeling. The pharmacological effects of nitroglycerine and rutaecarpine have been demonstrated to be associated with an increase in the synthesis and release of CGRP. In the gastrointestinal tissues, CGRP participates in the regulation of gastrointestinal function, and exerts protective effects on gastric mucosa. Rutaecarpine, capsaicin and its derivatives, such as evodiamine, decrease gastric mucosal damage induced by several factors, including increased synthesis and release of CGRP. Taken together, this review focuses on the pharmacological effects of several CGRP related canonical drugs and suggests that synthesis and secretion of CGRP exhibit significant therapeutic effects in the occurrence and development of cardiovascular and gastrointestinal diseases.
... Consumption of chili products was more common in the high risk area. Chili has been proposed as a direct irritant of the gastric mucosa but studies have been inconsistent on potential benefits or harms of its active principle capsaicin [35,36]. López-Carrillo and colleagues explored potential interactions among capsaicin, H. pylori virulent factors and genetic factors and showed that moderate to high capsaicin consumption was associated with increased risk of GC in genetically susceptible individuals (IL1B-31C allele carriers) infected with CagA positive strains [37]. ...
Background
Regional variations in gastric cancer incidence are not explained by prevalence of Helicobacter pylori, the main cause of the disease, with several areas presenting high H. pylori prevalence but low gastric cancer incidence. The IARC worldwide H. pylori prevalence surveys (ENIGMA) aim at systematically describing age and sex-specific prevalence of H. pylori infection around the world and generating hypotheses to explain regional variations in gastric cancer risk.
Methods
We selected age- and sex-stratified population samples in two areas with different gastric cancer incidence and mortality in Chile: Antofagasta (lower rate) and Valdivia (higher rate). Participants were 1–69 years old and provided interviews and blood for anti-H. pylori antibodies (IgG, VacA, CagA, others) and atrophy biomarkers (pepsinogens).
Results
H. pylori seroprevalence (Age-standardized to world population) and antibodies against CagA and VacA were similar in both sites. H. pylori seroprevalence was 20% among children <10 years old, 40% among 10–19 year olds, 60% in the 20–29 year olds and close to or above 80% in those 30+ years. The comparison of the prevalence of known and potential H. pylori cofactors in gastric carcinogenesis between the high and the low risk area showed that consumption of chili products was significantly higher in Valdivia and daily non-green vegetable consumption was more common in Antofagasta. Pepsinogen levels suggestive of gastric atrophy were significantly more common and occurred at earlier ages in Valdivia, the higher risk area. In a multivariate model combining both study sites, age, chili consumption and CagA were the main risk factors for gastric atrophy.
Conclusions
The prevalence of H. pylori infection and its virulence factors was similar in the high and the low risk area, but atrophy was more common and occurred at younger ages in the higher risk area. Dietary factors could partly explain higher rates of atrophy and gastric cancer in Valdivia.
Impact
The ENIGMA study in Chile contributes to better understanding regional variations in gastric cancer incidence and provides essential information for public health interventions.
... Alcoholism, smoking, nutritional deficiencies, and frequent ingestion of non-steroidal anti-inflammatory drugs contribute to gastric ulcers [3]. Spicy food, coffee, and emotional stress are factors that are able to increase the acid secretion of the stomach and causing the pain of an existing ulcer [4]. ...
Background: Gastric ulcer is one of the major causes of morbidity globally. It is prevalent in Nigeria and more frequent among the lowest income group; this is primarily linked to their standard of living and constant use of non-steroidal anti-inflammatory drugs. The use of camel milk in the treatment of many diseases has long been established. Objective: This study was designed to evaluate the potentials of camel milk in the treatment of gastric ulceration.
... Mhaskar et al. (2013) suggested that consumption of capsaicin-rich diets shows protective effect against Helicobacter pylori infection and H. pyloriinduced gastric ulcer. Satyanarayana (2006) has further suggested positive role of capsaicin in reduction of gastric ulcers. Several authors have discussed the gastroprotective role of capsaicin (Peng and Li 2010;Luo et al. 2011;Srinivasan 2016). ...
Capsaicinoids are a group of molecules, which impart pungency (hotness) to Capsicum fruits. The capsaicinoids are synthesized in the placenta of the Capsicum fruits. During the past few decades, there is an increasing interest in elucidation of the biosynthetic pathway of capsaicinoids. The whole genome sequencing of the highly pungent species, Capsicum chinense has revealed several important genes that are responsible for the biosynthesis of capsaicin and dihydrocapsaicin, the two major active constituents of the pungency complex, also known as capsaicinoid complex. The capsaicinoids have recently attracted a wide attention, because of its huge pharmacotherapeutic potential in treating several diseases, such as diabetes, cancer, obesity, cardiovascular, respiratory, gastric diseases and urological disorders. Further, capsaicin has been increasingly used as a molecule of choice for pain relief and many other diseases. In this chapter, we have presented briefly the sources and types of capsaicinoids, its biosynthesis, quantification of pungency and the genes responsible for its biosynthesis. Further, we have highlighted the candidate genes that are important for the biosynthesis of capsaicin and can be used for further manipulation experiments. At the end, this chapter focuses on the therapeutic potential of capsaicin in treating several diseases, such as diabetes, cancer, obesity, cardiovascular, respiratory, gastric diseases and urological disorders and its increasing role in pain relief. Finally, we have briefly discussed the mode of action of capsaicin against cancer, cardiovascular diseases, obesity management, pain relief and urological disorders.
... 20 Satynarayana observed high frequency association of capsaicin intake and peptic perforation. 21 Capsaicin is a base product of spicy and street foods. ...
Background: Presence of H. pylori infection was found associated with peptic perforation and gastric carcinoma. Present study tried to estimate the prevalence of H. pylori infection in those patients and to find out the correlates of H. pylori infection.Methods: After matching the inclusion and exclusion criteria, all cases of diagnosed peptic perforation and gastric carcinoma were taken for this prospective, single center, observational study.Results: Among the study population, gastric carcinoma was found in higher age group; whereas peptic perforation was found in lower age group; male and female ratio was 2:1 in both groups of patient. Laborer and housewives were mostly affected in both cases. Gastric carcinoma was more prevalent in urban residents, opposite was seen in peptic perforation. Most patients in two groups had no previous co-morbid condition. Use of NSAIDs was found in high frequency in both groups. Most of the patients were chronic alcoholic and chronic smoker, and most of them had history of taking spicy foods more than twice in a week.Conclusions: H. pylori infection was found in high frequency in both group of patients, and it was higher in peptic perforation. The study establishes the association of H. pylori with the gastric carcinoma and peptic perforation.
Background and Objective: Peppers are among the vegetables that provide a rich source of various bioactive compounds with potential health-improving properties. However, their occurrence and
Corticotropin-releasing factor (CRF) and capsaicin-sensitive afferent neurons with efferent-like function (CSN) make an important contribution to the regulation of the functions of the gastrointestinal tract (GIT) and gastroprotection. The aim of the review was to analyze the data of literature, including the results of our own studies on the interaction of CRF and CSN in the gastroprotection and regulation of the functions of the gastrointestinal tract, with a focus on their most studied interaction in the regulation of the motor function of the gastrointestinal tract. Based on the results obtained by the authors of the review, the contribution of CSN to the implementation of the gastroprotective effect of CRF and, conversely, the participation of CRF in the gastroprotective effect of capsacin, which activates CSN, is discussed. The contribution of glucocorticoid hormones to the implementation of the gastroprotective action of CRF and the compensatory gastroprotective role of these hormones under conditions of shutdown of CSN functioning are considered.
Cancer is the second most major cause of human mortality globally, and according to the International Agency for Research on Cancer (IARC), more than 19 million cancer cases are prevalent worldwide and approximately 10 million cases of death are reported in 2020. Cancer prevention and treatment is very challenging due to the involvement of multiple systems, genetic factors and pathways which manifest over a long period. The ineffectiveness and side effects of modern cancer treatment have motivated researchers to explore phytochemicals for alternative or supportive cancer therapy. The phytochemical capsaicin is a well-known naturally occurring plant secondary metabolite, which is responsible for imparting pungency or hotness in chilli peppers of the Capsicum genus. The medicinal properties of capsaicin have been explored by researchers since its discovery in the nineteenth century to the modern day. The discovery of the capsaicin receptor, transient receptor potential subfamily V type 1 (TRPV1), has shed light on the mechanisms by which capsaicin induces some of its pharmacological effects if not all. Capsaicin has been explored as an anti-cancer agent and has shown wide applications against various types of cancer because of its availability, affordability, non-toxicity and fewer side effects. This chapter highlights the in vitro and in vivo effects of capsaicin in different types of cancers, namely breast, lung, colorectal, prostate, gastric, liver, pancreatic, bladder, skin, bone, and leukemia, and helps to understand the mechanism of action of capsaicin, which elucidates the potential of capsaicin as an anti-cancer agent. Capsaicin has been reported to display a chemopreventive role by regulating the crucial stages of carcinogenesis, i.e., initiation, promotion and malignancy (metastasis). The mechanism of action of capsaicin involves inhibition of cell viability, cell cycle arrest at different phases, induction of angiogenesis, and apoptosis, via modulation of the levels of various downstream intermediaries. Newer approaches using nanotechnology are explored to improve the bioavailability of capsaicin, and synthetic non-pungent analogues are also developed to overcome the shortcomings of capsaicin. Co-treatment of capsaicin along with chemotherapy or radiation therapy are also explored. Further studies involving robust models and cancer patients may help in better understanding and utilisation of this compound.
Capsicum genus (Solanaceae) is native to the Americas. Today, it is an important agricultural crop cultivated around the world, not only due to its economic importance, but also for the nutritional value of the fruits. Among their phytochemical constituents, capsaicinoids are characteristic and responsible of the pungency of sharp-tasting cultivars. Moreover, Capsicum and capsaicinoids (mainly, capsaicin) have been largely studied because of their health benefits. Thus, this study reviews the scientific knowledge about Capsicum spp. and their phytochemicals against cancer, diabetes, gastrointestinal diseases, pain, and metabolic syndrome, as well as their antioxidant and antimicrobial activity. These bioactivities can be the basis of the formulation of functional ingredients and natural preservatives containing Capsicum extracts or isolated compounds.
Capsaicin (CAP) is a common food constituent, conferring a pungent taste to red peppers of the genus Capsicum. It has bactericidal and fungicidal activity. The study was aimed to test the hypothesis of whether oxidative stress mediates the toxicity of CAP to the baker's yeast Saccharomyces cerevisiae as a model yeast. CAP showed good antioxidant properties (1.30 and 1.10 mol Trolox equivalents/mol in the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate (ABTS) radical scavenging assay and the Ferric Reducing Antioxidant Power assay, respectively). However, its autoxidation generated hydrogen peroxide. CAP inhibited the growth of S. cerevisiae at concentrations ≥100 μM. Yeast mutants deficient in superoxide dismutase 1 or catalase T were more sensitive to CAP than wild-type yeast. CAP did not augment the ROS level in yeast cells. Standard antioxidants (N-acetylcysteine and ascorbate) did not protect significantly against CAP-induced yeast growth inhibition. Thus, oxidative stress does not mediate the CAP's inhibition of yeast growth. CAP did not decrease mitochondrial membrane potential of the yeast but induced a concentration-dependent decrease in membrane fluidity. These results indicate that the disturbance of membrane properties is the apparent cause of CAP toxicity to the yeast.
Background and Objective: The cotton leafworm, Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae), represents the worst lepidopterous pest on most vegetable crops. Moreover, its host range is extensive because it is a polyphagous and cosmopolitan pest that can cause an estimated loss of nearly 25.8 to 100% of crop production. Natural controls have replaced pesticides due to the environmental damage that chemical pesticides cause. Eggplant, tomato, okra and pepper are Egypt's most significant vegetable crops and the leaves of these plants are cheap and can act as botanical and nontoxic pesticides. Materials and Methods: Spodoptera littoralis larvae were reared in the laboratory and plant leaves of eggplant, tomato, okra and pepper were extracted in the laboratory with organic solvents. Then, these extracts were applied to the larvae. Therefore, the histological sectors in larvae bodies were prepared and the changes were observed compared with the control. Results: This study proved the efficiency of all plant leaf extracts, especially those of eggplant and tomato leaves (LC50 of 1191.9 and 1582.7 ppm, respectively). In contrast, okra and pepper leaf extracts had the highest LC50 (3904.8 and 5431.6 ppm, respectively). Also, the abnormalities in the midgut and internal tissues were evident in the larvae treated with eggplant leaf extracts, followed by tomato leaf extracts and okra leaf extracts. Larvae treated with pepper leaf extracts were as normal as the control. Conclusion: The current study opens horizons to new plant extracts that are cheap and unused plant parts and make them helpful as new and good insecticides.
The organ systems are specialized tissues that perform discrete functions. They are vital and thus have interdependencies. For instance, the heart and renal system both need and influence each other. When deficiency requirements of health and damaging factors lead to a weakened state, then the beginning of disease commences. This is at first hypofunction, then disordered circulation and communication in that tissue or organ. This further leads to inflammation, immune involvement, and eventually, fibrosis and drastic decline of function. Therapy involves addressing deficient requirements of health. More specific therapy involves supporting biochemical function, hormetic stimulation in the low-dose zone, and whole person therapy. These all help to increase adaptive responses of the body. Alternatively and often in combination, there are ways to dampen maladaptive responses and even to introduce some measure of homeostasis by external means. This is why standard medical therapy can often be successful, as it can externally create a balance or at least dampen maladaptive responses. But this may not lead to healing if the body is severely depleted and dysregulated.KeywordsDysfunctionNaturopathic treatmentDiagnosisWhole person approaches
Capsaicin (CAP) is an alkaloid isolated from pepper fruit, which possesses various pharmacological activities including antioxidant, anti-inflammatory, antibacterial and gastric mucosa protection. However, its inherent poor aqueous solubility and strong irritation impede the further clinical application. In our study, acyclic cucurbit[n]urils (ACBs, M1, M2 and M3) were rationally utilized to prepare a series of CAP inclusion complexes to improve the bioavailability and reduce stimulation. Their properties and inclusion behaviors were further investigated by multiple characterization methods, the data indicated that the inclusion complexes of ACBs/CAP were formed by a stoichiometric ratio of 2:1 with strong binding interaction. After complexation, the solubility of CAP was significantly increased by 12,076 times and its antioxidant activity also increased. Moreover, the anti-inflammatory activity and the ability to prevent gastric mucosal injury were both significantly improved, and the inhibition rate of nitric oxide (NO) and interleukin-1β (IL-1β) has been effectively improved while cytotoxicity against human normal hepatocytes cell (LO2), human lung fibroblasts cell (HLF) and the human gastric mucosal cell (GES-1) was greatly attenuated. Confocal laser scanning microscope (CLSM) images indicated that the complexes could be efficiently internalized by GES-1 cells and primarily located in cytoplasm. In vivo model of mouse, our complexes exhibited excellent biosafety. In summary, our study may provide a promising new strategy for the further clinical application of CAP.
Culinary spices and herbs have been used in food and beverages to enhance aroma, flavor, and color. They are rich in phytochemicals that provide significant antioxidant and anti-inflammatory effects. There is growing interest in identifying compounds from spices and herbs responsible for modulating oxidative and inflammatory stress to prevent diet-related diseases. This contribution will provide an overview of culinary spices and herbs, their classification , their sources or origins and more importantly, their chemical composition, antioxidant activity and their impacts on human health based on important and recent studies.
Chili pepper and its major active compound capsaicin have long been used not only a daily food additive but also medication worldwide. Like in other human organs and systems, capsaicin has multiple actions in gastrointestinal (GI) physiology and pathology. Numerous studies have revealed that capsaicin acts on GI tract in TRPV1-dependent and –independent manners, mostly depending on its consumption concentrations. In this review, we will focus on the beneficial role of capsaicin in GI tract, a less highlighted aspect, in particular how dietary capsaicin affects GI health, the mechanisms of actions and its preventive/therapeutic potentials to several GI diseases. Dietary capsaicin affects GI tract not only via TRPV1-derpendent and independent manners, but also via acute and chronic effects. Although high dose intake of dietary capsaicin is harmful to human health sometimes, current literatures suggest that appropriate dose intake is likely beneficial to GI health and is preventive/therapeutic to GI disease in most cases as well. With extensive and intensive studies on its GI actions, capsaicin, as a daily consumed food additive, has potential to become a safe drug for the treatment of several GI diseases.
The gastrointestinal tract (GIT), one of the essential organs of the human body is susceptible to various diseases. GI disorders such as constipation, diarrhea, GI reflux disease, gastric ulceration, Crohn’s disease, irritable bowel syndrome (IBS), also in addition to some other functional disorders, have become prevalent in a large part of the world population. Majority of the world’s population relies on herbal medicines nowadays for the management and treatment of GI diseases. However, the use of herbal medicines in various manifestations are traditionally derived, and further controlled trials suggest certain benefits of using ginger in nausea and vomiting, extract of licorice in peptic ulcers, Chinese herbal medicine in IBS, opium derivatives in diarrhea, and senna and ispaghula in constipation. The presence of various bioactive components in herbal preparations makes them suitable for potential therapeutic effects in GIT problems. In this chapter, we have discussed a number of single herbal formulations or herbal combinations for the treatment of different types of GIT ailments.
A highly sensitive tris(2,2'-bipyridyl)ruthenium(II) [Ru(bpy)3²⁺] electrogenerated chemiluminescence (ECL) detection method for the determination of capsaicin has been developed. In this study, capsaicin was worked as a coreactant in the oxidative-reduction pathway of the Ru(bpy)3²⁺ ECL. The oxidation of Ru(bpy)3²⁺ together with coreactant capsaicin on a bare glassy carbon electrode at an applied potential of +1.10 V vs. Ag/AgCl (3 M NaCl) led to a strong ECL emission. The Ru(bpy)3²⁺ ECL emission of capsaicin was strongly dependent upon the buffer solution pH, in which a strong ECL was obtained in alkaline buffer solution. Under the optimized conditions, the present Ru(bpy)3²⁺ ECL detection method showed a linear response to capsaicin in the linear range from 1.0 × 10⁻⁷ M to 1.0 × 10⁻⁴ M with a limit of detection of 9.4 × 10⁻⁸ M (S/N = 3). In addition, the present method can detect dihydrocapsaicin and nordihydrocapsaicin with a detection limit of 1.9 × 10⁻⁷ M and 2.2 × 10⁻⁷ M, respectively. The present ECL method shows good analytical performance for capsaicinoids in terms of linear dynamic range and detection limit compared to those obtained at other electrochemical methods even without the employment of additional modification of electrode surfaces to enhance the detection responses. In addition, no analyte preconcentration was required. The recovery tests performed for spiked capsaicin in real pepper samples were satisfactory with the recovery from 95% to 103%. To the best of our knowledge, this is the first report on the application of ECL for the quantitative determination of capsaicinoids. Since the present method is very simple, fast and sensitive, it could be applied for the determination of capsaicin in food and pharmaceuticals.
Plants, principally spices and herbs, have been given much more attention because they are considered important for flavoring and coloring foods and their use as condiments. Herbs and spices have been used for generations by humans as food and also to treat ailments since they are full of medicinal and antioxidant properties and contain bioactive compounds like tannins, alkaloids, phenolics, flavonoids, polyphenols, and vitamins, which help in healing diseases. Spices and herbs contain biomolecules that play a crucial role in healthcare and fitness levels. Spices and herbs have been considered as esoteric food adjuncts as they play numerous roles like being coloring agents, flavoring agents, preservatives, food additives, and having uses in the medicinal and pharmaceutical industries.
The correlation diffusion of fluorophore signal decreased with increasing concentration of capsaicinoids. Ultrasensitive capsaicin sensor based on endogenous single‐molecule fluorophore enhancement and quenching interface on gold nanoislands (GNIs) was developed by correlative fluorescence fluctuation optical spectroscopy. Endogenous fluorescence of capsaicinoids was enhanced by plasmon resonance energy transfer in the proximity of GNIs. The enhanced fluorescence signals exhibited large fluctuation from the average intensity reflecting the characteristic to‐and‐fro Brownian motion of fluorophores to the proximity of GNIs. The fluctuation of fluorophores showed enhancement, quenching, and equilibrium lifetimes depending on fluorophore‐GNI distance. The correlation diffusion of fluorophore signal decreased with increasing concentration of capsaicinoids. In the cross‐correlative quantification of capsaicinoids using the GNI array chip, the method showed excellent detection limits of 290 zM for capsaicin and 467 zM for dihydrocapsaicin. This method consisting of fluorophore fluctuation analysis and correlation diffusion‐based quantification has potential application to the study of label‐free single‐molecule interactions.
In the structure of the total morbidity of the Russian Federation population in 2018, skin and subcutaneous adipose tissue diseases made about 3,5 of the total number of cases, which amounted to 8330 thousand registered cases of diseases. The purpose of the research was to analyze the expenditure of material resources allocated for drug provision of the State Budgetary Institution of Healthcare of the Republic of Crimea “Clinical Dermatovenerologic Dispensary” (SBIH RC “CDVD”) for the period from January 1, 2020 to December 31, 2020. Materials and Methods. Based on the data obtained from the Statistical Department of SBIH RC “CDVD” on the financial means expenditures on the purchase of drugs, an assessment of the budgetary funds expenditures was carried out by means of ABC/VEN analysis. Results and discussion. According to the data received, for the period from January 1, 2020 to December 31, 2020, 3 156 patients were admitted to inpatient departments. 9, 072, 064, 00 rubles were spent on the treatment of patients’ nosologies, while the list of all drugs used included 98 names. The ABC analysis showed the feasibility of spending monetary resources, which confirms the lack of “N”- category (minor) drugs among “A” – category drugs (80% of the budget). The results of VEN-analysis indicated that 50% of the drugs used are referred to “V” category, which indicates that the Healthcare Institution predominantly purchased vital drugs. Conclusion. Active implementation of the methodology of management of medical care with help of modern technologies of ABC- and VEN- analyses allows timely implementation of measures to rationalize drug procurement in inpatient and outpatient healthcare institutions, as well as the choice of drugs for inclusion into the formulary and treatment standards.
Water supply is a primary contributor to the growth and phytonutrient composition in chili peppers. Several physiological stress factors can influence phytonutrients in chili peppers, resulting in their differential synthesis. Maintaining the right and exact amount of water through a drip system can promote an effective fruit set and crop quality. Four pepper cultivars (‘Hetényi Parázs’; HET, ‘Unikal’; UNIK, ‘Unijol’; UNIJ and ‘Habanero’; HAB) were investigated under different water supply treatments: RF or rain-fed, DI or deficit irrigation, and OWS or optimum water supply. The two-year experiment was carried out in May 2018 and 2019 under open field conditions. Physiological parameters (relative chlorophyll content, chlorophyll fluorescence, and canopy temperature) were measured during the growth stage and phytonutrients (vitamin C, capsaicinoids and carotenoids) analyzed using high-performance liquid chromatography (HPLC) at harvest in September. The study revealed that, due to higher precipitation and rainfall interruption, increased water supply affected physiological response and phytonutrients in the cultivars. HAB under OWS had a lower response during the growth period when compared to HET, UNIK, and UNIJ. As water supply increased, measured individual carotenoid concentration increased in some cultivars. On the other hand, as water supply decreased, vitamin C and capsaicinoids concentration increased. Even though cultivars responded to the water supply treatments differently, HET exhibited a more uniform and stable composition in all treatments.
Citation: Agyemang Duah, S.; Souza, C.S.e; Nagy, Z.; Pék, Z.; Neményi, A.; Daood, H.G.; Vinogradov, S.; Helyes, L. Effect of Water Supply on Physiological Response and Phytonutrient Composition of Chili Peppers. Water 2021, 13, 1284. https://doi.org/10.3390/w13091284
The human diet and its nutritional content may benefit in preventing several health issues. The enrichment of natural compounds in foodstuffs, having health supporting qualities is the present-day attention of by dieticians to explore a healthy food. Capsicum spp., are amongst the enormously consumed fruits worldwide, due to their bioactive compounds, capsaicinoids. They are used as nutrition additives and possess pharmacological properties. Hence, hot pepper fruits are widely screened for their pharmaceutical uses in human beings. Capsaicin is the major and commonly occurring capsaicinoids in chilli peppers, and it imparts hot pungent flavour to chillies. It possesses several important biological functions, especially analgesic properties. Capsaicin functions as a neuropeptide-releasing agent, and selective for sensory peripheral neurons. The compound is soluble in fats and readily engrossed through the skin. When used externally, capsaicin controls peripheral nerve ache. Numerous studies have focused on phytochemicals in human diet with anti-tumourigenic or anti-mutagenic phytochemical properties. Several studies performed in animals and cell lines showed the initiation of vigorous apoptosis by capsaicin. Also, it induces cell cycle arrest, reactive oxygen species production and disrupts the loss of mitochondrial membrane integrity, thereby activating caspases activities to promote apoptosis. Further, capsaicin can induce apoptosis in cancer cell lines through increasing the expression of p53 and c-myc genes. In this chapter, scientific evidences describing the potent anticancer efficacy and the mechanisms of action of capsaicin against various types of human cancers are discussed in detail.
Manilkara hexandra (Roxb; Family:sapotaceae) is reported to exert preventive effect in several experimental ulcer models. However, there is no report of M. hexandra on gastric ulcer healing property. Thus, the present study was designed to evaluate the gastric ulcer healing activity of methanolic stem bark extract of M. hexandra (MH) and to derive a plausible molecular level of mechanism of action. MH was subjected to several phytochemical screening tests and standardized to quercetin by HPTLC. In the first pharmacological experiment, the standardized MH (50, 100 and 200 mg/kg) was carried out for ulcer healing activity against acetic acid (AA)-induced gastric ulcer in male rats. MH (100 and 200 mg/kg) ameliorated AA-induced rat gastric lesions. Further, MH (100 and 200 mg/kg) attenuated AA-induced changes in the levels of lipid peroxidation (LPO), reduced glutathione (GSH), oxidized glutathione (GSSG) and ratio of GSH/GSSG and activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) enzymes, and level of hame oxygenase-1 (HO-1) in stomach tissue. In the subsequent set of experiment, trigonelline (30 mg/kg; p.o.), a potent Nrf2 antagonist, significantly abrogated the gastric ulcer healing activity of MH (100 mg/kg) in AA challenged animals. Further, trigonelline attenuated the effects of MH (100 mg/kg) on the levels of LPO, GSH, GSSG and ratio of GSH/GSSG and activity of SOD, CAT, GPx and GR enzymes, and level of HO-1 in AA challenged rodents. These observations implicate the fact that MH could be a better therapeutic alternative in the management of gastric ulcer.
Background: Presence of H. pylori infection was found associated with peptic perforation and gastric carcinoma. Present study tried to estimate the prevalence of H. pylori infection in those patients and to find out the correlates of H. pylori infection.
Methods: After matching the inclusion and exclusion criteria, all cases of diagnosed peptic perforation and gastric carcinoma were taken for this prospective, single center, observational study.
Results: Among the study population, gastric carcinoma was found in higher age group; whereas peptic perforation was found in lower age group; male and female ratio was 2:1 in both groups of patient. Laborer and housewives were mostly affected in both cases. Gastric carcinoma was more prevalent in urban residents, opposite was seen in peptic perforation. Most patients in two groups had no previous co-morbid condition. Use of NSAIDs was found in high frequency in both groups. Most of the patients were chronic alcoholic and chronic smoker, and most of them had history of taking spicy foods more than twice in a week.
Conclusions: H. pylori infection was found in high frequency in both group of patients, and it was higher in peptic perforation. The study establishes the association of H. pylori with the gastric carcinoma and peptic perforation.
Background and aim
Herbal medicines are used to treat a broad number of maladies. However, the pharmacological profile of most remedies is poorly understood. We investigated the effect of herbal remedies from kampo, traditional Chinese medicine (TCM) and other phytotherapies on human two-pore domain potassium channels (KCNK channels; TREK-1, TASK-1 and TASK-3) as well as the human TRPV1 channel. KCNK channels are responsible for the background potassium current of excitable cells, thus essential for the maintenance of the resting membrane potential. Hence, modulators of KCNK channels are of medical significance, e.g. for the treatment of sleep disorders and pain. The transient receptor potential channel TRPV1 is a pain detector for noxious heat. Agonists of this receptor are still used for the treatment of pain in ectopic applications. Experimental procedure: We evaluated the effect of 158 herbal remedies on these channels in a heterologous expression system (Xenopus laevis oocytes) using the two-electrode voltage-clamp technique with the aim of increasing the comprehension of their pharmacological profile.
Results and conclusion
Some remedies with modulating effects were identified such as Angelica pubescens (radix), which inhibit TASK-1 and TASK-3 channels. Furthermore, the modulatory effects of the most effective remedies on the two TASK family members TASK-1 and TASK-3 correlate positively, reflecting their close relation. For the TRPV1 channel Terminalia chebula and Alchemilla xanthochlora were identified as potentiators. This study identifies a variety of herbal remedies as modulators of human K2P and TRPV1 channels and gives new insights into the pharmacological profile of these herbal remedies.
Exposure of rat stomach to 1 M NaCl reduced the transmucosal potential difference (PD) followed by an increase of luminal pH and gastric mucosal blood flow (GMBF). Desensitization of capsaicin-sensitive afferent neurons significantly mitigated the increase in GMBF without affecting PD and pH responses. Mucosal application of capsaicin increased GMBF with no effect on PD and pH. The findings suggest that capsaicin-sensitive afferent neurons may be involved in the regulatory mechanism of GMBF responses induced by a mild irritant.
The role of capsaicin-sensitive afferent nerves in gastroprotection by capsaicin was investigated in the absolute ethanol-induced gastric lesion model in rats. Capsaicin (0.1 and 0.5 mg/kg, p.o.) inhibited the lesion formation dose-dependently. The protective effect of capsaicin was attenuated by indomethacin-pretreatment and disappeared in capsaicin-sensitive nerve degenerated rats. Capsaicin did not induce the distension of gastric mucosal folds. These results suggested that stimulation of capsaicin-sensitive afferent nerves by capsaicin would enhance the prostaglandin formation, leading to an inhibition of gastric lesions.
Chemical ablation of sensory afferents produced by the treatment with the neurotoxin capsaicin worsened gastric ulcers induced by 50% ethanol in sham- and sialoadenectomized (SALX)-operated rats. Conversely, capsaicin worsened water immersion stress (WIS)-ulcers in SALX, but not those in sham-operated animals. The concomitant removal of two potent antisecretory factors, such as salivary gland containing epidermal growth factor and neuropeptides contained in the sensory afferents, is probably responsible for the enhanced vulnerability of the mucosa in WIS-ulcers.
We have examined the effect of orally administered capsaicin on gastric motility in the rat to investigate a possible relationship between motility change and cytoprotection induced by this agent. Capsaicin, given orally (l-30mg/kg), dose-dependently inhibited hemorrhagic band-like lesions induced by ethanol (60% in 150 mM HC1). This protection was significantly mitigated by desensitization of afferent neurons following capsaicin pretreatment 2 weeks before the experiment, and it was also significantly attenuated by prior administration of indomethacin, but not by spantide. Intragastric administration of capsaicin (30 mg/kg) significantly inhibited gastric motility and increased the mucosal blood flow, but had no effect on the transmucosal potential difference of the stomach. These functional changes induced by capsaicin were also less marked in the afferent neuronal desensitized rat, and they were significantly attenuated by indomethacin but not by spantide. These results suggest that the mucosal protection by intragastric capsaicin may be associated with the inhibition of gastric motility and the increase of mucosal blood flow. These responses may be induced by activation of primary afferent neurons which are probably sensitized by endogenous prostaglandins.
The effect of capsaicin-sensitive nerve degeneration (capsaicin-treatment) was investigated on the antral ulcer induction by the combined administration of 2-deoxy-D-glucose (2-DG; 200 mg/kg, i.v.), aspirin (200 mg/kg, p.o.) and 1% ammonia solution (10 ml/kg, p.o.) in male Sprague-Dawley rats. On the 2nd day after ulcer induction, erosive lesions were seen in the corpus, and ulcers penetrating into the muscularis mucosae were also seen in the antrum. In the capsaicin-treated rats, the antral ulcer was significantly aggravated as compared with that in capsaicin non-treated rats, although no difference was noted in the formation of corpus lesions between capsaicin-treated rats and non-treated rats. Acid output was investigated in pylorus ligated rats. 2-DG significantly increased the acid output. A significant increase in acid output was also observed in capsaicin-treated rats, and this increase tended to be augmented by the additional treatment with 2-DG. Atropine sulfate inhibited the significant increase in acid output of the capsaicin-treated rats. In all rats, both capsaicin-treated and pylorus-ligated, 2-DG induced antral ulcers that penetrated into the muscularis mucosae. From the above results, it was suggested that capsaicin-sensitive nerve degeneration modifies the gastroprotective ability in the antral mucosa to a greater extent than in the fundic mucosa, and this aggravation may be caused by activation of the vagus nerve, although the role of acid is not completely excluded.
Effects of chemical ablation of capsaicin-sensitive sensory nerves on functional and mucosal ulcerogenic responses to 2-deoxy-D-glucose (2DG) were investigated in the rat stomach, in comparison with those of indomethacin, a prostaglandin (PG) biosynthesis inhibitor. Intravenous injection of 2DG (200 mg/kg) followed by infusion of this agent (100 mg/kg/hr, i.v.) significantly increased gastric acid secretion and motility, but rarely induced macroscopic damage in the gastric mucosa of normal conscious rats. Chemical ablation of capsaicin-sensitive sensory nerves or pretreatment with indomethacin (5 mg/kg, s.c.) did not significantly affect the acid secretory and motility responses to 2DG, but induced severe hemorrhagic lesions in the stomach within 4 hr. Gastric mucosal blood flow (GMBF) determined by laser Doppler flowmetry under anesthetized conditions did not consistently change during 2DG treatment in any of these three groups, but the rise in GMBF in response to mucosal acidification (0.2 N HCl) was significantly inhibited in the animals pretreated with indomethacin or following chemical deafferentation. We conclude that functional ablation of capsaicin-sensitive sensory neurons, similar to the PG deficiency, increases the gastric mucosal vulnerability during 2DG infusion (acid hypersecretion and hypermotility due to vagal excitation), resulting in hemorrhagic lesions, and that the mechanism may be accounted for at least partly by the impairment of gastric mucosal blood flow response to mucosal acidification.
Calcitonin gene-related peptide (CGRP) is a polypeptide produced by alternative processing of calcitonin gene transcripts1. CGRP-like immunoreactivity (li) is widely distributed in the rat gastrointestinal tract2 and high concentrations of CGRP-li have been found in the rat stomach and duodenum2. The absence of CGRP-li in endocrine cells3 at these levels suggests that it is more important as a neuropeptide than as a circulating hormone. Exogenous CGRP was reported to inhibit gastric acid secretion4, increase gastric blood flow5,6, induce a relaxation of duodenal smooth muscle7, act as a potent antiulcer against experimentally-induced gastroduodenal ulcers8. All these effects have been shown to be protective in duodenal ulcers.
This study investigated the relationship between adrenals and capsaicin-sensitive fibers on the integrity of gastric mucosal injury by indomethacin.
Adrenalectomy, but not hypophysectomy, enhanced the degree of gastric ulcers induced by indomethacin. Systemic capsaicin pretreatment, which selectively induced degeneration of primary sensory neurons, produced aggravation of indomethacin-induced gastric ulcers in sham- and hypophysectomized-operated but not in adrenalectomized rats.
Removal of the celiac ganglion complex increased gastric ulcers induced by indomethacin in adrenalectomized rats but not in sham-operated animals.
The protetctive effects of exogenous administration of deoxycorticosteron acetate or triamcinolon, but not od adrenaline, toward gastric ulcers induced by indomethacin were decreased by systemic capsaicin pretreatment.
These findings provide evidence of the local involvement of adrenal glands in the cpsaicin-sensitive "gastric defence mechanism" against ulcers induced by indomethacin.
More than 90% of 75 clinical isolates of Helicobacter pylori strains had the vacuolating cytotoxin gene vacA as demonstrated by polymerase chain reaction (PCR). A PCR restriction fragment-length polymorphism (RFLP) analysis revealed various gene subtypes, and some of the RFLPs correlated significantly with gastric cancer or duodenal ulcer. These findings suggest that specific types of H. pylori have factors that cause gastric cancer or duodenal ulcer.
FRG-8813 ((+/-)-2-(furfurylsulfinyl)-N-[4- [4-(piperidinomethyl)-2-pyridyl] oxy-(Z)-2-butenyl]acetamide) is a novel histamine H-2-receptor antagonist with gastric antisecretory and gastroprotective activities. The present study was designed to investigate the property of gastroprotective action. The oral ED(50) values for inhibition of mucosal lesions against 1% NH3-, 60% ethanol in 0.15 N HCl-, 100% ethanol-, 0.6 N HCl- and sodium taurocholate in 0.4 N HCl-induced damage were 3.3, 11.1, 14.9, 23.3 and 23.1 mg/kg, respectively. FRG-8813 was gastroprotective despite pretreatment with omeprazole, suggesting that the protective effect is independent of its antisecretory activity. It is unlikely that FRG-8813 works as a mild irritant because it showed a gastroprotective effect after intraperitoneal injection, but oral administration itself did not influence the rat gastric mucosa. Although pretreatment with indomethacin or N-ethyl-maleimide did not affect the gastroprotection of FRG-8813, chemical deafferentation induced by capsaicin abolished the gastroprotection. Furthermore, prior administration of tetrodotoxin, the calcitonin generated peptide (CGRP) antagonist hCGRP(8-37) or N-G-nitro-L-arginine attenuated the gastroprotection of FRG-8813 as well as that of capsaicin. In contrast to capsaicin, repeated administration of FRG-8813 neither enhanced the susceptibility of the mucosa to damage nor affected the gastroprotective action of short-term treatment. In conclusion, these results suggest that FRG-8813 has gastroprotective activity independently of acid antisecretory activity and that capsaicin-sensitive nerves may be partially or fully involved in the gastroprotective mechanisms of FRG-8813.
Activation of medullary thyrotropin-releasing hormone (TRH), at a dose subthreshold to increase gastric acid secretion, protects the gastric mucosa against ethanol injury through vagal cholinergic pathways in urethane-anaesthetized rats. Peripheral mediators involve the efferent function of capsaicin-sensitive splanchnic afferents leading to calcitonin gene-related peptide (CGRP)- and nitric oxide (NO)-dependent gastric vasodilatory mechanisms. In addition, gastric prostaglandins participate in gastric protection through mechanisms independent of the stimulation of gastric mucosal blood flow and mucus secretion. Medullary TRH has physiological relevance in the vagal-dependent adaptive gastric protection induced by mild (acid or ethanol), followed by strong, irritants. Additional neuropeptides, namely peptide YY (PYY), somatostatin analogues, CGRP and adrenomedullin, also act in the brainstem to induce a vagal-dependent gastric protection against ethanol through interactions with their specific receptors in the medulla. Central PYY and adrenomedullin act through vagal cholinergic prostaglandins and NO pathways, while somatostatin analogue acts through vagal non-adrenergic, non-cholinergic vasoactive intestinal peptide and NO mechanisms. Although their biological relevance is still to be established, these peptides provide additional tools to investigate the multiple vagal-dependent mechanisms which increase the resistance of the gastric mucosa to injury.
Capsaicin, the principal pungent constituent of red and chili peppers, has numerous pharmacological and physiological effects. This hot stuff currently is being utilized for the management of some painful conditions. In consideration of the frequent consumption of Capsaicin as a food additive and its current clinical applications, it is important to precisely assess the safety of this compound. Capsaicin has been tested for genotoxicity and carcinogenicity, but results remain conflicting. Thus, while certain groups have reported mutagenic and tumor-initiating or tumor-promoting effects of capsaicin, others have found just the opposite effects. Capsaicin appears to be a double-edged sword, and the opposing dual roles this molecule plays in experimental carcinogenesis and mutagenesis are the subject of this review.
Local capsaicin-sensitive sensory afferent neurons may regulate the ability of the gastric mucosa to withstand challenge. Since opioids can modulate the activity of afferent neurones by actions at peripheral sites, the effects of morphine on gastric mucosal damage has been investigated in the rat. Morphine (3–9 mg · kg−1 i.v.) dose-dependently augmented the damage induced by a 5-min intragastric challenge with ethanol (25%–100%), as assessed by macroscopic and histological evaluation. These effects of morphine were significantly inhibited by the opioid antagonists naloxone and the peripherally acting N-methylnalorphine. Pretreatment of rats with capsaicin 2 weeks before the study to induce functional ablation of primary afferent neurons likewise significantly augmented the damage induced by ethanol. Both morphine administration and capsaicin pretreatment substantially augmented histologically assessed damage to the glandular mucosa and enhanced deep hemorrhagic damage following challenge with the low ethanol concentrations, with the appearance of macroscopically distinct antral damage. The enhanced damage induced by 50% ethanol in capsaicin-pretreated rats was not further enhanced by morphine administration, suggesting actions on a common mechanism. These findings support a pathophysiological role for activation of local opioid-sensitive afferent neurons in the modulation of mucosal injury following challenge.
Disruption of the gastric mucosal barrier with resultant increased acid back-diffusion leads to a marked increase in gastric mucosal blood flow (GMBF). This increase in GMBF is blocked by ablation of capsaicin-sensitive sensory neurons. The gastric arterioles are densely innervated by afferent neurons containing vasodilator peptides, calcitonin gene-related peptide (CGRP) being the most potent of these. We investigated (a) whether CGRP is the vasodilator mediator released by acid stimulation of capsaicin-sensitive sensory neurons and (b) whether the resultant hyperemia protects against the acid-induced mucosal injury. When the stomach was perfused with 0.15N HCl plus 15% ethanol, GMBF significantly increased by 70%. This hyperemic response was completely blocked by intra-arterial infusion of human CGRP8–37 (500 pmol/min), a CGRP-receptor antagonist, close to the stomach. With the blockade of the hyperemic response to acid back-diffusion, gross and histological mucosal damage were significantly aggravated. It is concluded that CGRP mediates the gastric hyperemic response to acid back-diffusion and that this gastric hyperemic response is an important protective factor against acid-induced injury.
In an earlier study1 we observed that alcohol-induced gastric damage in the rat was exacerbated by truncal vagotomy. We further noted that the mild irritant, 30% ethanol, which significantly reduced the magnitude of injury when mucosa was subsequently exposed to 100% alcohol, was no longer capable of eliciting this protective effect under conditions of vagal denervation. These observations suggested that vagal integrity played an important role in mucosal defense and was necessary for adaptive cytoprotection to occur, at least under conditions of injury induced by alcohol. While the mechanism(s) responsible for these findings has remained elusive, the possibility that capsaicin-sensitive fibers may play a role in mediating these vagotomy effects must be considered. This contention is based on the fact that as many as 80% of fibers comprising the gastric vagus are afferent in nature, being composed of unmyelinated and thinly myelinated afferent neurons2, and capsaicin, the pungent ingredient of red peppers, is able to impede the conducting activity of such primary afferent neurons when administered in high doses3,4,5. Further, functional ablation of capsaicin-sensitive fibers has been shown to enhance gastric injury and ulcer formation in a number of experimental models including those in which gastric damage was induced by pylorus ligation6, acid distension of the stomach6, and in response to various noxious agents such as indomethacin7 and ethanol7.
The dose-response effects of capsaicin on various gastric functions were investigated in the rat and correlated with the cytoprotective action of this agent. Oral administration of capsaicin induced a concentration-dependent reduction in the severity of gastric lesions induced by acidified ethanol (60% in 150 mM HCl, p.o.), and a significant effect was obtained at the concentration of 0.6 mg ml-1 or greater. This protection was significantly attenuated by chemical deafferentation or pretreatment with indomethacin (5 mg kg-1, s.c.). Capsaicin, given intragastrically or applied topically to the mucosa, produced significant changes in various gastric functions at different dose levels; inhibition of gastric motility (>0.6 mg ml-1), increase of mucosal blood flow (>0.03 mg ml-1) and stimulation of HCO3- secretion (>0.3 mg ml-1), but did not affect acid secretion. These effects, similar to the cytoprotection, were significantly mitigated by either chemical deafferentation or indomethacin pretreatment, yet their dose-response relationships showed that the effective dose range for cytoprotection was close to that for motility inhibition but much higher than that for the mucosal blood flow response. These data suggest that the cytoprotective action of capsaicin may be functionally associated with gastric motility inhibition rather than increase of mucosal blood flow.
The age-related changes of calcitonin gene-related peptide (CGRP) were studied in 2, 14 and 18-month old Wistar rats. The release of CGRP from peripheral and central endings of sensory nerves was investigated in isolated perfused mesenteric arterial beds and incubated spinal cord slices. The basal and stimulated (by capsaicin, 10 -7 - 3 x 10 -6 mol/L for arterial beds, and 10 -7 - 10 -6 mol/L for spinal cord) CGRP release in both tissues were decreased significantly in 14 and 18 month-old rats. Immunohistochemistry study showed an attenuation of CGRP content and innervation in peripheral vasculature of aged rats. By using semi-quantitative RT-PCR, it was found that a 29% elevation of CGRP mRNA level in spinal dorsal root ganglions, where CGRP was synthesized, in 18 month-old rats compared with 2 month ones, suggesting that age related changes of CGRP may occur at some stages other than mRNA level. The data suggest that the age-related changes of CGRP may induce the functional impairment of peripheral vasodilation and nervous system which may play an important role in pathogenesis of aging-related disease, especially in vascular disorders such as hypertension.
Background: Phospholipase A2 is a key enzyme in the release of arachidonic acid, subsequent production of eicosanoids, leukotriens and platelet-activating factor which play an important role in a variety of biological processes. Experimental and clinical evidences suggest that phospholipase A2 may serve a primary regulatory role in the development of many organ disorders. Method: We investigated the phospholipase A2 activity and content of phospholipids in the gastric mucosa of rats in which gastric lesions were induced by indomethacin (intraperitoneally, i. p. 20 mg.kg-1). We focused attention on the relationship between damage of gastric mucosa, content of phospholipids and activity of phospholipase A2. The experiments were made on the rats fasted for 24 hours. Gastric lesions, phospholipids content and phospholipase A2 activity were investigated 4 hours after indomethacin administration. To influence the damage of gastric mucosa 30 minutes before indomethacine the following substances were administered: dopamine (1 mg.kg-1), L-DOPA, (0.25 mg.kg-1), pentoxifylline (50 mg.kg-1), prostaglandine I2 (5 μg.kg-1) and allopurinol (50 mg.kg-1). Results: We found that all substances used reduce the disposition for development of gastric lesions after indomethacin. Indomethacin significantly decreases phospholipase A2 activity and increases phospholipids content. Combination of indomethacin with dopamine, L-DOPA, prostaglandine I2, pentoxifylline or allopurinol prevents decrease of phospholipase A2 activity and prevents the rise of phospholipids content caused by indomethacin. Conclusion: Indomethacin-induced gastric lesions are associated with decrease of phospholipase A2 activity. Substances which diminish the development of gastric lesions after indomethacin (dopamine, L- DOPA, prostaglandine I2 pentoxifylline, and allopurinol), are associated with changes of phospholipase A2 activity (prevent decrease) and phospholipids content (prevent increase) in the gastric mucosa.
AIM: To study the effect of Helicobacter pylori (H. pylori) infection on gastric epithelial proliferation in the progression from normal mucosa to gastric carcinoma.
METHODS: Gastric biopsy specimens from normal controls (n = 11), superficial gastritis (n = 32), atrophic gastritis with intestinal metaplasia (n = 83), dysplasia (n = 25) and gastric carcinoma (n = 10) were studied by immunohistochemical stianing of proliferating cell nuclear antigen (PCNA).
RESULTS: The gastric epithelial proliferation, expressed as PCNA labeling index (LI)%, was progressively increased in successive stages from normal mucosa to gastric carcinoma regardless of H. pylori status. There was significant difference in PCNA LI% among all groups (P 0.05).
CONCLUSION: H. pylori infection causes increased gastric epithelial proliferation in the stages of superficial and mild atrophic gastritis and may play a part in triggering gastric carcinogenesis.
This study investigated the role of nitric oxide on the oxidative damage in gastric mucosa of rats which received ischemia/reperfusion and its relation to mucus. Nitric oxide synthesis modulators such as L-arginine and N(G)-nitro-L-arginine methyl ester, and sodium nitroprusside, a nitric oxide donor, were injected intraperitoneally to the rats 30 min prior to ischemia/reperfusion which was induced by clamping the celiac artery and the superior mesenteric artery for 30 min and reperfusion for 1 h. Lipid peroxide production, the contents of glutathione and mucus, and glutathione peroxidase activities of gastric mucosa were determined. Histological observation of gastric mucosa was performed by using hematoxylin-eosin staining and scanning electron microscopy. The result showed that ischemia/reperfusion increased lipid peroxide production and decreased the contents of glutathione and mucus as well as glutathione peroxidase activities of gastric mucosa. Ischemia/reperfusion induced gastric erosion and gross epithelial disruption of gastric mucosa. Pretreatment of L-arginine, a substrate for nitric oxide synthase, and sodium nitroprusside prevented ischemia/reperfusion-induced alterations of gastric mucosa. However, N(G)-nitro- L-arginine methyl ester, a nitric oxide synthase inhibitor, deteriorated oxidative damage induced by ischemia/reperfusion. In conclusion, nitric oxide has an antioxidant defensive role on gastric mucosa by maintaining mucus, glutathione, and glutathione peroxidase of gastric mucosa.
Conflicting data have been reported on the effect of nicotine on gastric mucosal damage. To elucidate the effect of chronic intermittent nicotine on gastric mucosal damage, intragastric nicotine (5 mg/kg, 10 mg/kg) was administered twice per day for 9 days. Gastric mucosal damage was created by s.c. injection of a large dose (1.2 mg/kg) of pentagastrin followed by pylorus ligation for 6 hours. Nicotine treated rats showed reduced gastric mucosal damage about 50% of the control. To examine the mechanism of the protective effect of nicotine, gastric perfusion experiments were done. Basal acid secretion was not affected by intragastric or intravenous nicotine. However, pentagastrin-stimulated acid secretion markedly inhibited by a bolus injection of nicotine, and this response was dose-related. These data indicates that chronic intermittent administration of nicotine protects gastric mucosa against gastrin-induced gastric mucosal damage, and nicotine-induced inhibition of gastrin-stimulated acid secretion has an important role for the protective effect of nicotine. Considering reports concerning nicotine's aggrevating effect on the gastric mucosal damage, it is suggested that the methods of administration of nicotine may be an important decisive factor of the divergent action of nicotine on the gastric mucosa.
This chapter discusses studies carried out to research impaired defense mechanism to peptic ulcer in the capsaicin-desensitized rat. It has been shown that capsaicin, the pungent principle of different red peppers is a selective sensory neuron blocking agent, which at first stimulates and then after larger doses desensitizes polymodal nociceptors, warm sensors, and some interoceptors resembling in some aspects polymodal nociceptors. In the exteroceptive skin and mucous membrane areas, these capsaicin-sensitive nociceptors mediate chemogenic pain sensation and are responsible for the phenomena of antidromic vasodilatation and neurogenic inflammation. Indirect and direct evidence suggest that there are mucosal sensory receptors in the stomach which can be excited by capsaicin.
The effect of capsaicin, a pungent principle of capsicum fruit, on lipid peroxide formation in cardiac and skeletal muscles as well as on plasma enzyme activities that indicated tissue damaged induced by acute exhaustive exercise in rats was investigated. Lipid peroxide levels in muscles and plasma enzyme activities were determined at various time intervals after 60 min swimming with 3% BW resistance. The maximum inhibitory effect of capsaicin on lipid peroxide levels in cardiac and skeletal muscles occurred at 24 h after exercise. The results also corresponded to the decrease in plasma enzyme activities of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH). There was no statistical change in the activity of plasma aspartate aminotransferase (AST) at various time intervals after exhaustive exercise in the capsaicin-treated group compared to control. The mechanism by which capsaicin inhibits lipid peroxide formation by increasing antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in skeletal muscle, but not in cardiac muscle, subsequently prevents free radical formation during exercise.
Methods for proper measurement of gastric mucosal blood flow (MBF) in animal experiments or in clinical studies are critically reviewed. It can be stated that none of the techniques hitherto published fulfil all the criteria for proper measurement of the mucosal blood flow and concomitant acid production in the stomach. Some give an estimate of local blood flow changes (e.g. H 2 gas clearance, laser Doppler flowmetry) in man without the possibility of simultaneous acid measurement. The 99m Tc-MAP clearance technique developed by the authors reflects changes in both parameters and may also be used in clinical studies, when limitations of the method are taken into consideration. As a rule we assume that acid production and mucosal blood flow may change independently. The effects of various bioactive substances and drugs on both parameters are analysed. It seems that many contradictory findings have arisen because of differences in technique and experimental animals used.
Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) account for nearly all gastroduodenal ulcers and serious ulcer complications. 1–4 Endoscopic and epidemiological data are conflicting about whether H pylori infection increases the risks in NSAID users, has no effect, or is protective. 5–10 Eradication of H pylori substantially decreases the rate of recurrence of gastric and duodenal ulcers in patients not taking NSAIDs, 11 but whether this effect occurs in patients on NSAIDs is unclear. In NSAID users, dyspepsia correlates poorly with ulceration but is common in patients infected with H pylori. 12,13 In a randomised controlled trial we investigated the hypothesis that H pylori eradication would decrease dyspepsia in patients taking NSAIDs but would have no effect on ulcer recurrence. Methods We did the HELP NSAIDs (Heliobacter Eradication for Lesion Prevention with NSAIDs) study in primary-care and secondary-care centres in Hungary, Poland, South Africa, Spain, and the UK. The study was approved by the ethics committees of the part-icipating centres and all patients gave written, informed consent. Patients We enrolled men and women aged 18–85 years, who required continuous NSAID treatment and who had H pylori infection of the gastric mucosa. Patients were eligible if they had a gastric or duodenal ulcer at the start of the study, had had an endoscopically confirmed ulcer in the previous 5 years, or had moderate or severe NSAID-associated dyspepsia alone or in combination with ulcers. Patients could be taking any NSAID available for prescription in the participating country (with the exception of phenylbutazone, azapropazone, and ketorolac, which are used for special purposes) for treatment of any musculoskeletal disease at more than a minimum dose (diclofenac 50 mg; ibuprofen 1200 mg; naproxen 500 mg; indometacin 50 mg) on at least 5 days per week. We defined an ulcer as a break of at least 3 mm diameter in the gastric or duodenal mucosa with definite depth. Our main exclusion criteria were: a previous attempt to eradicate H pylori infection; treatment in the month before enrolment with antibiotics, bismuth compounds, or steroids in a dose equivalent to more than 10 mg prednisolone daily; use of drugs, including methotrexate, that could interact with trial drugs; current erosive gastro-oesophageal reflux disease; pyloric stenosis; or substantial bleeding in the upper gastrointestinal tract. Methods We asked patients about history of peptic ulcers, likelihood of current ulceration, and current symptoms. If H pylori status was unknown, we did serological testing with ELISA. Suitable patients underwent endoscopy and all patients (n=285) who were Summary Background The effect of Helicobacter pylori in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) is unclear. We investigated the effects of H pylori eradication in patients with current or previous peptic ulceration, dyspepsia, or both who continued to use NSAIDs.
Capsaicin, the principal pungent ingredient of hot chili peppers, has anti-inflammatory and analgesic properties and is currently used as a topical cream for the management of various neuropathic conditions. In the present study, topical application of capsaicin onto dorsal skin of female ICR mice strongly suppressed phorbol ester-stimulated activation of NF-κB via blockade of IκB-α degradation with subsequent inhibition of nuclear translocation of the functionally active NF-κB subunit, p65. Likewise, phorbol ester-induced activation of activator protein-1 (AP-1) was abolished by capsaicin pretreatment. Since altered transactivation of NF-κB and AP-1 has been implicated for neoplastic transformation and progression, the suppression of these transcription factors by capsaicin may account for its previously reported chemopreventive effects on mouse skin tumorigenesis as well as inflammation.
BACKGROUND
It remains controversial whether or not Helicobacter pyloriinfection causes altered gastric acid secretion. A novel test for evaluating gastric acid secretion (endoscopic gastrin test; EGT) has recently been developed.AIMTo investigate by EGT the effects of H pylorieradication on the state of gastric acid secretion in patients with peptic ulcer.METHODS
Twenty six patients with duodenal ulcer and 33 with gastric ulcer, for all of whomH pylori infection had been documented, were studied by EGT, histological examination of gastric mucosa, and measurement of plasma gastrin levels before and one and seven months after H pylori eradication.RESULTSIn patients with duodenal ulcer, the mean EGT value beforeH pylori eradication was higher than that inH pylori negative controls, but it had decreased significantly seven months after the treatment. In contrast, the mean EGT value of patients with gastric ulcer beforeH pylori eradication was lower than that inH pylori negative controls, but it had increased one month after the treatment; this was followed by a slight decrease at seven months. In both groups, mean EGT values seven months after the treatment were not significantly different from the mean control value.CONCLUSIONS
The reduced acid secretion in gastric ulcer patients and gastric acid hypersecretion in duodenal ulcer patients were both normalised after the clearance of H pylori.
The present study was undertaken to investigate how the activation of gastric mechanoreceptors by distension of the stomach in conscious gastric fistula rats influences gastric emptying; and the roles of capsaicin sensitive vagal afferent fibres and the 5-HT3, GRP and CCK-A receptors involved in mediating these responses. To activate mechanoreceptors by non-nutrient dependent pathways, methylcellulose in saline was used to distend the stomach (5 cm H2O) and the subsequent emptying of saline was examined immediately, and at 3, 5 and 10 min following distension. Prior distension delayed the subsequent emptying of saline instilled into the stomach compared with non-distended controls (2.28±0.09 ml/5 min; P
Nitric oxide is a messenger molecule, mediating the effect of endothelium-derived relaxing factor in blood vessels and the cytotoxic actions of macrophages, and playing a part in neuronal communication in the brain. Cloning of a complementary DNA for brain nitric oxide synthase reveals recognition sites for NADPH, FAD, flavin mononucleotide and calmodulin as well as phosphorylation sites, indicating that the synthase is regulated by many different factors. The only known mammalian enzyme with close homology is cytochrome P-450 reductase.
The mechanism of inhibition of Ca2+ - triggered phospholipase A2 (PLA2) activity and respiratory burst in macrophages by capsaicin is assessed. In the present study, it has been shown that capsaicin inhibits calcium-ionophore stimulated pro-inflammatory responses in macrophages such as generation of superoxide anion, PLA2 activity (IC50 = 20uM) and membrane lipid peroxidation (IC50 = 10 uM). Both capsaicin and PLA2 antagonists altered the kinetics of respiratory burst in a time and dose dependent manner. Arachidonic acid, linoleic acid and SDS restored capsaicin inhibited respiratory burst. Capsaicin and known PLA2 inhibitors, dexamethasone and indomethacin, inhibited Ca2+-dependent PLA2 activity in vitro from macrophages. Inhibition of PLA2 activity by capsaicin is independent of Ca2+ and substrate concentration. Fluorescence studies suggest that capsaicin interacts directly with partially purified macrophage PLA2. Finally, the antioxidant property of capsaicin was comparable to that of butylated hydroxy toludine (BHT). Taken together these results show that capsaicin an antiinflammatory agent with potential clinical application.
This review of the past year's literature focuses on progress in the elucidation of the pathways and mechanisms controlling gastric exocrine (ie, acid and pepsin) and endocrine (ie, gastrin, histamine, and somatostatin) secretion at the central, peripheral, and intracellular levels by neural, hormonal, and paracrine agents. Molecular biological techniques continue to further our knowledge into the function of receptors regulating gastric secretion and the transduction pathways to which they are coupled. Techniques for purification and enrichment of fundic enterochromaffin-like cells have proven useful tools with which to examine the mechanisms regulating histamine secretion. Somatostatin, acting as a paracrine agent, is the main inhibitor of exocrine and endocrine secretion by the stomach and additional evidence is provided that the hypergastrinemia induced by Helicobacter pylori is mediated via a decrease in somatostatin secretion. The role of trefoil peptides and nitric oxide in the regulation of gastric secretion remains to be determined.
(C) Lippincott-Raven Publishers.
Gastric secretion is finely regulated by neural, hormonal, and paracrine pathways. During ingestion of a meal, the pathways can be activated by stimuli originating in the brain or stimuli originating in the stomach, such as mechanical stimulation (eg, distension) or chemical stimulation (eg, protein). The main secretagogues active at the level of the parietal cell are acetylcholine (neurotransmitter), gastrin (hormone), and histamine (paracrine agent); the main inhibitor is somatostatin (paracrine agent). The release of these four agents by neural, hormonal, and paracrine mechanisms and the interactions among them determine the rate of acid secretion in response to physiological stimuli. The two main intracellular signaling pathways involve cyclic adenosine monophosphate and calcium. A third pathway, involving accumulation of guanosine 3',5'-cyclic monophosphate, is receiving increased attention. Progress has been made in characterizing the intracellular events that occur between generation of second messengers and incorporation of tubulovesicle-rich H+K+-ATPase into the apical membrane of the parietal cell and exocytosis of pepsinogen from the chief cell.
(C) Lippincott-Raven Publishers.
Thirty-eight healthy subjects who had normal index endoscopies were re-endoscoped following ingestion of 20 g of chilli powder with 400 ml of water, 600 mg aspirin BP with 400 ml of water or 400 ml of water only. There were good correlations between endoscopic scores given by two endoscopists who independently recorded their findings, as well as with scores given by a third observer viewing photographs taken at endoscopy. There were statistically significant differences between the aspirin group and the other two groups but not between the chilli and the control groups. Chilli ingestion, therefore, does not lead to macroscopic gastroduodenal mucosal damage.
Exposure of rats to formalin and nitrogen dioxide vapour caused a significant increase in values of the lung wet wt/dry wt ratio (oedema formation) and lipid peroxidation. These effects were not observed in rats treated with short-term capsaicin, either before or after exposure to the two gases. This protective action of short-term capsaicin treatment can possibly be linked with the strengthening of the pulmonary antioxidant enzyme defence system by capsaicin.
Leptin, the product of the ob gene, plays a key role in the regulation of food intake via a cross-talk between hypothalamic leptin receptors and neuropeptides that affect feeding behaviour. Recent studies have shown a synergistic interaction between leptin and cholecystokinin (CCK) leading to suppression of food intake, which involves CCK-1 receptors and capsaicin-sensitive vagal fibres. In this study, we have investigated the presence of leptin receptors in afferent and efferent neurons of the vagus nerve. By using reverse transcription-polymerase chain reaction, mRNAs encoding long (Ob-Rb) and short (Ob-Ra) leptin receptor isoforms were detected in the rat nodose ganglion, which contains the cell bodies of the vagal afferent neurons. Western blot analysis confirmed the presence of leptin receptor-immunoreactive proteins in extracts from the vagal trunk. Immunohistochemistry showed the presence of leptin receptors and the leptin-induced transcription factor STAT3 in the cytoplasm of nodose ganglion cells. In cervical vagal segments, levels of leptin receptor protein displayed physiological regulation, with decreased amounts after feeding and increased levels after food restriction. In addition, leptin receptor and STAT3 immunoreactivities were detected in neurons of the nucleus of tractus solitarius (NTS) and the dorsal motor nucleus of the vagus nerve (DMNX) by immunofluorescence histochemistry. Furthermore, direct double-labelling demonstrated colocalization of Ob-Rb and STAT3 immunoreactivities in cholinergic vagal efferent cell bodies of the DMNX. It is speculated that vagal leptin receptors, apart from being activated by adipocyte-derived leptin, may also be influenced by leptin produced by the stomach. This may explain the synergistic action of leptin and CCK on neuronal activity in the NTS and on food intake.
Activation of medullary thyrotropin-releasing hormone (TRH), at a dose subthreshold to increase gastric acid secretion, protects the gastric mucosa against ethanol injury through vagal cholinergic pathways in urethane-anaesthetized rats. Peripheral mediators involve the efferent function of capsaicin-sensitive splanchnic afferents leading to calcitonin gene-related peptide (CGRP)- and nitric oxide (NO)-dependent gastric vasodilatory mechanisms. In addition, gastric prostaglandins participate in gastric protection through mechanisms independent of the stimulation of gastric mucosal blood flow and mucus secretion. Medullary TRH has physiological relevance in the vagal-dependent adaptive gastric protection induced by mild (acid or ethanol), followed by strong, irritants. Additional neuropeptides, namely peptide YY (PYY), somatostatin analogues, CGRP and adrenomedullin, also act in the brainstem to induce a vagal-dependent gastric protection against ethanol through interactions with their specific receptors in the medulla. Central PYY and adrenomedullin act through vagal cholinergic prostaglandins and NO pathways, while somatostatin analogue acts through vagal non-adrenergic, non-cholinergic vasoactive intestinal peptide and NO mechanisms. Although their biological relevance is still to be established, these peptides provide additional tools to investigate the multiple vagal-dependent mechanisms which increase the resistance of the gastric mucosa to injury.
Pretreatment with capsaicin tends to normalize pulmonary lipid peroxidation changes induced by exposure to sulfur dioxide, formalin or nitrogen dioxide gases. This protective effect of capsaicin pretreatment appears to be due to the stabilization of the rat lung membrane lipid system.
A case-control study was conducted in high- and low-risk areas of Italy to evaluate reasons for the striking geographic variation in gastric cancer (GC) mortality within the country. Personal interviews with 1,016 histologically confirmed GC cases and 1,159 population controls of similar age and sex revealed that the patients were more often of lower social class and resident in rural areas and more frequently reported a familial history of gastric (but not other) cancer. After adjusting for these effects, case-control differences were found for several dietary variables, assessed by asking about the usual frequency of consumption of 146 food items and beverages. A significant trend of increasing GC risk was found with increasing consumption of traditional soups, meat, salted/ dried fish and a combination of cold cuts and seasoned cheeses. The habit of adding salt and the preference for salty foods were associated with elevated GC risk, while more frequently storing foods in the refrigerator, the availability of a freezer and use of frozen foods lowered risk. Reduced GC risk were associated with increasing intake of raw vegetables, fresh fruit and citrus fruits. Lowered risk was also related to consumption of spices, olive oil and garlic. Neither cigarette smoking nor alcoholic beverage drinking were significantly related to GC risk. The case-control differences tended to be consistent across geographic areas, despite marked regional variations in intake levels of certain foods. The high-risk areas tended to show higher consumption of food associated with elevated risk (traditional soups, cold cuts) and lower consumption of foods associated with reduced risks (raw vegetables, citrus fruits, garlic). Our findings indicate that dietary factors contribute to the regional variation of stomach cancer occurrence in Italy, and offer clues for further etiologic and prevention research.
Previous work from this laboratory has already indicated that capsaicin, stabilizes the rat lung membrane lipid system on long-term treatment. This stabilization of the membrane is further supported by our present findings that capsaicin pretreatment causes significant inhibition of various chemically induced lipid peroxidative changes at both cellular and subcellular levels. Both in vivo and in vitro studies, using whole lung and liver tissue slices and mitochondrial and microsomal fractions, have shown that capsaicin pretreatment inhibits peroxidative changes at both cellular and subcellular levels. Both in vivo and in vitro studies, using whole lung and liver tissue slices and mitochondrial and microsomal fractions, have shown that capsaicin pretreatment inhibits peroxidative changes induced by different chemical irritants such as chloroform, dichloromethane, carbon tetrachloride as well as ferrous sulphate.
Ultraviolet-radiation has been reported to cause lipid peroxidation in the liposomal membrane. In the present study, treatment with capsaicin, (8-methyl-n-vanillyl-6-nonenamide), the pungent principle of red hot pepper, was shown to modify UV-induced lipid peroxidation in the liposomal membrane. Treatment with low doses of capsaicin (less than 0.1 μg/mL of phosphatidyl choline liposome) produced a significant increase in UV-induced lipid peroxidation, while high doses (0.1–0.5 μg/mL of PC liposome) caused a significant decrease of UV-induced peroxidation. These pro-oxidant and antioxidant activities of capsaicin over UV-induced liposomal lipid peroxidation were also comparable to experiments modulated with standard pro-oxidant ferrous sulphate and antioxidant sodium azide. The observed dual nature of capsaisin's action on the UV-induced lipid peroxidation of the liposomal membrane may be attributed to the previously reported “activation” followed by “desensitization” action of capsaicin on other membrane lipid systems.