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Papain reduces gastric acid secretion induced by histamine and other secretagogues in anesthetized rats
Abstract
We studied the effect of papain on rats' gastric acid secretion and found that: 1. Feeding of latex of unripe papaya fruit significantly reduced gastric acid secretion induced by methacholine; 2. Feeding of crystalline papain in doses of 3.2 mg/kg reduced gastric acid secretion induced by histamine, methacholine and tetragastrin; 3. The reduction of gastric acid secretion was observed as early as 2 hours after papain feeding, lasted up to 48 hours, and waned within 96 hours; 4. Intraperitoneal injection of papain had no effect on acid secretion. These results led us to believe tha the effect of papain on gastric acid secretion is a local one acting directly on the gastric mucosa, and this local effect of a single dose of papain is reversible, causing no permanent damage to the mucosa.
... In animals the local application of papaya latex and papain reduced histamine mediated gastric acid secretion (Cho & Han 1984). A five-minute digestion with papain (10mg/ml) triggers the release of intestinal surface membrane glycoproteins in the intestinal mucosa (Forstner 1971). ...
... It is known that papain supports the physiological digestion via enzymatic activity. Because it can ameliorate symptoms associated with maldigestion (Cho & Han 1984), (Forstner 1971), the high papain content of Caricol® can contribute to the observed reduction of this beneficial effect on flatulence. ...
... reduction (Cho & Han 1984). The antiulcer activity of papaya was also observed in mice (Ezike et al. 2009). ...
Objective:
Papaya (Carica papaya L.) is used as a natural remedy in abnormal digestion in tropical and industrialized countries. Besides this wide distribution little evidence has been produced with reference to its physiological effect in humans and the proof of efficacy. Former clinical observations had revealed positive effects for patients with constipation, heartburn, and symptoms of irritable bowel syndrome (IBS) after eating papaya preparations. In line with these former positive clinical observations, we studied the clinical effects of the papaya preparation Caricol® in a double blind placebo controlled study design.
Methods:
In this study the participants were volunteers, with chronic (prevailing) indigestions and dysfunctions in the gastrointestinal tract. During the trial the intake of the substance of intent and placebo was 20 ml daily for 40 days. The endpoints were the frequency of 22 symptoms recorded before and after the documented intake recorded by questionnaire.
Results:
The symptoms "Constipation", "Bloating", and "Heartburn" were defined as primary and frequency of "painful (straining) bowel movements" as secondary endpoint. The participation ended after the intake period within two days ("early returnees"). Wash out effects were observed in "late returnees", who returned with a delay of 8.6 (±5.95 days). In the verum group early returnees revealed statistically significant improvements of the symptoms "constipation" and "bloating". The analysis of "heartburn" felt short of significant improvement because of the small number of included cases with this criteria (N=13, p=0.114). None of the significant benefits were observed after the washout phase.
Conclusion:
We conclude from these results, that the papaya preparation (Caricol®) contributes to the maintenance of digestive tract physiology. It ameliorates various functional disturbances, like symptoms of IBS. The mechanism of this digestive tract physiology support is discussed.
... Animal and in vitro studies suggest that papaya has an ability to scavenge ROS and inhibit gastric secretion through histamine reduction [69][70][71] and that it also acts directly upon gastric smooth muscle to impact its motility [72]. ...
Nutritional ingredients, including various fibers, herbs, and botanicals, have been historically used for various ailments. Their enduring appeal is predicated on the desire both for more natural approaches to health and to mitigate potential side effects of more mainstream treatments. Their use in individuals experiencing upper gastrointestinal (GI) complaints is of particular interest in the scientific space as well as the consumer market but requires review to better understand their potential effectiveness. The aim of this paper is to review the published scientific literature on nutritional ingredients for the management of upper GI complaints. We selected nutritional ingredients on the basis of mentions within the published literature and familiarity with recurrent components of consumer products currently marketed. A predefined literature search was conducted in Embase, Medline, Derwent drug file, ToXfile, and PubMed databases with specific nutritional ingredients and search terms related to upper GI health along with a manual search for each ingredient. Of our literature search, 16 human clinical studies including nine ingredients met our inclusion criteria and were assessed in this review. Products of interest within these studies subsumed the categories of botanicals, including fiber and combinations, and non-botanical extracts. Although there are a few ingredients with robust scientific evidence, such as ginger and a combination of peppermint and caraway oil, there are others, such as melatonin and marine alginate, with moderate evidence, and still others with limited scientific substantiation, such as galactomannan, fenugreek, and zinc-l-carnosine. Importantly, the paucity of high-quality data for the majority of the ingredients analyzed herein suggests ample opportunity for further study. In particular, trials with appropriate controls examining dose–response using standardized extracts and testing for specific benefits would yield precise and effective data to aid those with upper GI symptoms and conditions.
... In a study on rats, feeding with crystallized papain reduced gastric acid secretion induced by methacholine, histamine and tetragastrin already after 2 h of administration, lasting up to 48 h, but the effect disappeared in 96 h. 18 In rat uterine preparations, papain showed an effect already at a concentration of 2.5 µg mL −1 , but the maximal effect was seen at a final concentration of 10-12.5 µg mL −1 in the organ bath. 13 In our experiments, the lowest tested concentration was 12.5 µg mL −1 . ...
Background
Papaya is a traditional remedy for gastrointestinal complaints in the folk medicine. On this basis, papain, a cysteine protease of the fruit, is sold as a nutritional supplement, although scientific data on its effects in the gastrointestinal tract are lacking. We aimed to explore the effect of papain on gastric motility in vitro.
Methods
Guinea pig antrum and corpus strips were mounted in organ bath.
Key results
Papain reversibly increased the amplitude of ongoing phasic contractions in both circular and longitudinal antrum strips without having an effect on the frequency or on the muscle tone. All three tested doses of papain (end cc.: 12.5 mg L⁻¹, 50 mg L⁻¹, 100 mg L⁻¹) were similarly effective. Contrarily, in the corpus circular and longitudinal muscle strips, papain caused a dose‐dependent relaxation, which was preceded by a transient contraction in most tissues. The effect was resistant to tetrodotoxin (1 µM), but diminished by the cysteine protease inhibitor E64 (4.5 µM) in both regions. In the corpus, L‐NAME (100 µM) and the protease‐activated receptor (PAR)‐1 antagonist SCH79797 (5 µM) or the PAR‐2 antagonist GB 83 (3 µM) did not change the effect of papain significantly. This demonstrates that the effects of papain are not neurally mediated and nitrergic pathways are not involved in the mechanism. The effects are linked to the enzymatic activity, but not executed via PAR‐1 or 2.
Conclusions and inferences
Papain alters gastric motility in a region‐specific manner, which could at least partly explain its claimed beneficial effects in functional gastrointestinal disorders.
... Papaya contains a variety of enzymes, such as papain, chymopapain, and lysozyme, Vitamin C, antioxidants, bioflavonoids, and minerals, which are responsible for a beneficial nutritive effect [14][15][16][17]. Clinical observations showed that in patients with gastrointestinal disease papaya interacted with reactive oxygen species and reduced the secretion of gastric acid caused by histamine [17,18]. Oat from Avena Sativa L. comprises fatty acids, antioxidants, vitamins (E and B), minerals, and cell wall polysaccharides such as starch and β-glucan. ...
Gastritis is an inflammatory disease leading to abdominal pain, nausea, and diarrhea. While therapy depends on etiology, adhesive agents protecting the gastric tissue represent a promising treatment option. Caricol®-Gastro is an organic product that significantly decreased gastritic abdominal pain in a recent clinical study. To investigate whether this beneficial effect can be attributed to the formation of a protective layer covering the gastric mucosa after oral application, several methods were used to determine adhesion. These include macro-rheological measurements and gastric mucin interactions, which were correlated to network formation, examined by Cryo-scanning electron microscopy technique, wettability via sessile drop method on human gastric adenocarcinoma cell layers, and ex vivo adhesion studies on gastric porcine tissue with the falling liquid film technique considering physiological conditions and Franz diffusion cells for quantification. The results showed that Caricol®-Gastro formed a stable viscoelastic network with shear thinning properties. It exhibited high wettability and spreadability and adhered to the excised gastric mucosa. We found that oat flour, as the main ingredient of Caricol®-Gastro, supports the gel network regarding viscoelasticity and, to a lesser extent, adhesion in a concentration dependent manner. Moreover, our data highlight that a variety of coordinated methods are required to investigate gastric adhesion.
... In patients with gastrointestinal disease papaya is known to interfere with reactive oxygen species (Osato et al. 1993). Papaya latex and cristallin papain (3.2 mg/kg) reduces the histamin triggered secretion of gastric acid (Cho & Han 1984). ...
Objective:
Papaya and oats are natural food and used in traditional medicine in many parts of the world. Papaya has a high content of enzymes supporting digestive function. Oats are a source of minerals, beta-glucan fibres, immunmodulatory and antiinflammatory probiotic substances. Caricol®-Gastro combines both constituents, it was designed as vegan organic preparation for intestinal inflammatory diseases. We performed a randomized, double blind placebo controlled clinical trial to investigate the potential of Caricol®-Gastro as add on therapy in patients with diagnosed chronic gastritis.
Methods:
60 Patients with endoscopically confirmed mild chronic disease were recruited. A structured interview documented the baseline data. Then the patients were allocated to the verum or placebo group by handing out a numbered study package with the study substance for the daily intake at home. A single dose was 20 g, taken twice per day. After 30 days the participants were interviewed again.
Results:
After the intake phase the disease related symptoms were found improved in both groups, indicating a strong placebo effect. However, the pain load reduction in the Caricol®-Gastro group was significantly larger (p=0.048).
Discussion:
Due to the inherent biological activities of ingredients of papaya and of oats and their known effects (anti-inflammatory, epithelial integrity), the observed beneficial effects may be owed to the constituents synergisms to reduce chronic inflammation. We conclude, that the regular intake is a safe add on therapeutic option for patients with chronic gastritis to support standard medical care.
... The cysteine proteinases from V. cundinamarcensis share structural similarities with cysteine proteolytic enzymes from different plants. Commercial papain, a mixture of proteolytic enzymes, protects against ulcer provoked by histamine [27] and reduces acid secretion induced by the paracrine induction [28] in rats. In this work, we demonstrated that P1G10 significantly reduces gastric acidity in animals submitted to pyloric ligation (Table 1). ...
Objectives
The aim of this study was to extend our knowledge about the mechanism involved in the gastroprotective effect of P1G10, a proteolytic fraction rich in cysteine proteinases from Vasconcellea cundinamarcensis (syn. Carica candamarcensis) latex, which demonstrated gastric healing and protection activities in rats.Methods
Wistar rats were submitted to gastric lesions by indomethacin and treated with P1G10 (10 mg/kg). Free thiol groups and prostaglandin E2 content were measured in gastric mucosal and gastrin levels in blood samples. To evaluate the participation of nitric oxide (NO) or proteolytic activity of P1G10 on its gastroprotective effect, animals were treated with an inhibitor of NO production (L-NAME) or the fraction inhibited by iodoacetamide, respectively. Gastric secretion study (acidity and pepsin activity) was also performed.Key findingsP1G10 (10 mg/kg) inhibited the occurrence of gastric lesions by indomethacin, restored the free thiol groups content on gastric mucosa and increased moderately prostaglandin E2 levels (34%). Furthermore, the treatment decreased the gastrin levels (95%), suggesting a possible modulation of secretory activity. This effect was accordant with attenuation of gastric acidity (42%) and pepsin activity (69%) seen in animals subjected to pyloric ligation. The inhibition of NO production or the proteolytic activity of P1G10 does not affect the gastroprotective effect.Conclusions
These results can explain the gastroprotective activity of P1G10 and serve a basis for further studies of this active principle.
Carica papaya has been investigated in treatments of ulcers and wounds especially in developing countries. This study was aimed at investigating the wound healing efficiency of powdered Carica papaya leave. Wistar rats were divided into 3 groups: Group 1(control): Treated with normal saline. Group 2 (control check): Treated with propylene glycol alone, Group 3 (experimental): Treated with powdered Carica papaya leave. Wound was inflicted and dressed with normal saline; propylene glycol and powdered Carica papaya leave respectively. The efficacy of treatment was assessed by the rate of wound closure, Wound contraction, fibroblast cell count and histology of granulation tissue. The result showed an insignificant difference in wound contraction (P> 0.05). Significant difference in wound closure was observed with group 3 been the fastest (P< 0.05). Fibroblast cell count showed statistical significant difference among the groups and across days (P< 0.05). Scar tissue also showed significant difference in fibroblast cell counts (P< 0.05). In conclusion, our study gave scientific background for the use powdered Carica papaya leave as a potential wound healing agent which is potent and faster in wound healing as against papaya extracts and normal saline among Wistar rats. It has also documented that propylene glycol has an enhancing therapeutic property in the wound healing process among Wistar rats.
Chewing gum alleviates symptoms of gastro-esophageal reflux (GER) following a refluxogenic meal. GutsyGumtm, a chewing gum developed to alleviate the symptoms of GER contains calcium carbonate, with a proprietary blend of licorice extract, papain, and apple cider vinegar (GiGs®). The efficacy of GutsyGumtm was determined in alleviating the symptoms of GER after a refluxogenic meal compared to placebo gum. This double-blind, placebo-controlled-crossover trial with a one-week washout between treatments had 24 participants with a history of GER consume a refluxogenic meal and then chew GutsyGumtm or placebo gum. Participants completed GER symptom questionnaires, consisting of symptom based 10 cm Visual Analogue Scales, immediately following the meal and then at regular intervals out to four hours postmeal. Adjusted mean ± SEM heartburn score (15-min postmeal to 240 min) was significantly lower in GutsyGumtm than in placebo gum treatment (0.81 ± 0.20 vs. 1.45 ± 0.20 cm; p = 0.034). Mean acid reflux score was significantly lower in GutsyGumtm than in placebo treatment (0.72 ± 0.19 vs. 1.46 ± 0.19 cm; p = 0.013). There were no significant differences for any of the secondary outcomes. However, pain approached significance with less pain reported in GutsyGumtm versus placebo treatment (0.4 ± 0.2 vs. 0.9 ± 0.2 cm; p = 0.081). Although nausea (p = 0.114) and belching (p = 0.154) were lower following GutsyGumtm, the difference was not statistically significant. GutsyGumtm is more effective than a placebo gum in alleviating primary symptoms of heartburn and acid reflux (Clinical Trial Registration: ACTRN12612000973819).
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