The chemical constituents and gastroprotective effects of Calanthe fimbriata Franch.

Calanthe fimbriata Franch. is a Tujia ethnic herb, which has traditionally been used to treat gastric ulcers, chronic hepatitis, etc. We explored the chemical constitutes, gastroprotective effects, and the active fraction of C. fimbriata, as well as elucidating the underlying mechanisms. Firstly, four in vitro antioxidant tests were applied to determine the oxidation resistance of C. fimbriata methanol extract and its fractions. The gastroprotective effects were evaluated in ethanol-induced gastric ulcer rats, gastric histopathology was visualized by H&E staining, and the acidity of gastric juice was measured by titrating with NaOH solution. The contents of malondialdehyde, catalase, superoxide dismutase, gastrin, and the activity of H+K+-ATPase were estimated using commercial kits. EtOAc fraction of C. fimbriata methanol extract (CfEF) exhibited significant gastroprotective effects by ameliorating stomach pathological changes and elevating the pH value of gastric juice. It also manifested remarkable antioxidant activities in vitro and in vivo. Using various chromatographic methods and spectroscopic techniques, 22 compounds were isolated and characterized from CfEF, in which alkaloids were the predominant components. All of these substances were derived from C. fimbriata for the first time. The results indicated that CfEF is a promising source of gastroprotective agents. The antioxidant activity of this herb, as well as prevention of gastrin secretion and inhibition of H+K+ -ATPase, was found to be the underlying mechanism of action.

Protective effect of the combination of essential oil from patchouli and tangerine peel against gastric ulcer in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential oil (EO) is the main extract of patchouli and tangerine peel with antiinflammatory, antiulcer, and other functions. However, the efficacy and mechanism of the combination of EO from patchouli and tangerine peel against gastric ulcer (GU) are unclear. AIM OF THE STUDY: This study aims to reveal the protective effect of the combination of EO from patchouli and tangerine peel against GU in rats, as well as explore the optimal ratio and possible mechanism of EO in GU treatment. MATERIALS AND METHODS: The GU model is executed via water immersion and restraint stress. The repair effect of EO in different proportions on gastric mucosa injury and the effects on serum gastrin (GAS), pepsinogen C (PGC), prostaglandin E2 (PGE2), and 5-hydroxytryptamine in GU rats were observed. The optimal ratio obtained was used in the second part to set different dose groups for further experiment. The effects of the different EO doses on gastric mucosal ulcer formation and gastric acid secretion were evaluated. The morphology of chief and parietal cells were observed via transmission electron microscopy. The contents of GAS, PGC, substance P (SP), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cholecystokinin (CCK), PGE2, and motilin (MTL) in serum in different groups were detected via enzyme-linked immunosorbent assay. Expressions of epidermal growth factor (EGF) and trefoil factor 2 (TFF2) protein in gastric tissues were detected via immunohistochemistry, and expressions of c-Jun N-terminal kinase (JNK), P53, Bcl-2-associated X protein (Bax), and Caspase-3 protein in gastric tissues were detected via western blotting. RESULTS: The EO from patchouli and tangerine peel at 1:2 ratio of compatibility significantly improved gastric mucosal injury, decreased serum GAS and PGC contents, and increased the PGE2 level in serum (p < 0.05). The mixture of EO from patchouli and tangerine peel (Mix-EO) can reduce the formation of gastric mucosal ulcers, reduce gastric mucosal injury, improve the expansion of the endoplasmic reticulum of the chief cells, repair mitochondrial damage, and inhibit the secretion of gastric acid by parietal cells. Mix-EO at 300 mg/kg can reduce the expression of serum GAS, PGC, SP, CCK, and cAMP/cGMP (p < 0.05 or 0.01); increase the expression of EGF and TFF2 protein in gastric tissues (p < 0.01); and inhibit the expression of JNK, p53, Bax, and Caspase-3 proteins (p < 0.01). CONCLUSION: The combination of EO from patchouli and tangerine peel can repair the gastric mucosal damage in GU rats and prevent the occurrence of ulcers by inhibiting the secretion of gastric acid, enhancing the defensive ability of gastric mucosa, and suppressing the apoptosis of gastric epithelial cells. Moreover, the optimal compatible ratio of patchouli and tangerine peel is 1:2.

Lactobacillus plantarum CQPC02-Fermented Soybean Milk Improves Loperamide-Induced Constipation in Mice.

This study determined the ameliorative effects of the novel microorganism, Lactobacillus plantarum CQPC02 (LP-CQPC02), fermented in soybean milk, on loperamide-induced constipation in Kunming mice. High-performance liquid chromatography revealed that LP-CQPC02-fermented soybean milk (LP-CQPC02-FSM) had six types of soybean isoflavones, whereas Lactobacillus bulgaricus-fermented soybean milk (LB-FSM) and unfermented soybean milk (U-FSM) only had five types of soybean isoflavones. LP-CQPC02-FSM also contained more total and active soybean isoflavones than LB-FSM and U-FSM. Results from mouse experiments showed that the defecation factors (quantity, fecal weight and water content, gastrointestinal transit ability, and time to first black stool) in the LP-CQPC02-FSM-treated mice were better than those in the LB-FSM- and U-FSM-treated mice. The serum and small intestinal tissue experiments showed that soybean milk increased the motilin, gastrin, endothelin, acetylcholinesterase, substance P, vasoactive intestinal peptide, and glutathione levels and decreased the somatostatin, myeloperoxidase, nitric oxide, and malondialdehyde levels compared with the constipated mice in the control group. The LP-CQPC02-FSM also showed better effects than those of LB-FSM and U-FSM. Further results showed that LP-CQPC02-FSM upregulated cuprozinc-superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD), catalase (CAT), c-Kit, stem cell factor (SCF), glial cell-derived neurotrophic factor (GDNF), neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), and aquaporin-9 (AQP9) and downregulated the expression levels of transient receptor potential cation channel subfamily V member 1 (TRPV1), inducible nitric oxide synthase (iNOS), and aquaporin-3 (AQP3) in the constipated mice. LP-CQPC02-FSM increased the Bacteroides and Akkermansia abundances and decreased the Firmicutes abundance in the feces of the constipated mice and decreased the Firmicutes/Bacteroides ratio. This study confirmed that LP-CQPC02-FSM partially reversed constipation in mice.

Granularity and Laxative Effect of Ultrafine Powder of Dendrobium officinale.

Constipation is a common disorder that is a significant source of morbidity among people around the world ranging from 2% to 28%. Dendrobium officinale Kimura et Migo is a traditional herbal medicine and health food used for tonicity of the stomach and promotion of body fluid production in China. This study aimed to prepare the ultrafine powder of Dendrobium officinale (UDO) and investigate its laxative effect and potential mechanism in mice with diphenoxylate-induced constipation. Results indicated that the mean diameter (d50) of UDO obtained by ball milling was 6.56 µm. UDO (62.5, 125, and 250 mg/kg, p.o.) could significantly enhance the gastrointestinal transit ratio and promote fecal output. Moreover, UDO treatment resulted in significant increases in the serum levels of acetylcholinesterase (AChE), gastrin (Gas), motilin (MTL), and substance P (SP), and obviously decreased serum contents of somatostatin (SS). Taken together, UDO, which can be easily obtained through milling to a satisfactory particle size, exhibited obvious laxative effect in diphenoxylate-induced constipated mice, and the mechanism might be associated with elevated levels of AChE, Gas, MTL, SP, and reduced production of SS. UDO has the potential for further development into an alternative effective diet therapy for constipation.

Curcumin Ameliorates Reserpine-Induced Gastrointestinal Mucosal Lesions Through Inhibiting IκB-α/NF-κB Pathway and Regulating Expression of Vasoactive Intestinal Peptide and Gastrin in Rats.

The objective of our study was to investigate whether curcumin protects against reserpine-induced gastrointestinal mucosal lesions (GMLs) in rats and to explore the mechanism of curcumin's action. Sprague-Dawley rats were randomly divided into four groups: control group, reserpine-treated group, reserpine treatment group with curcumin at high dose (200 mg/kg), and reserpine treatment group with curcumin at low dose (100 mg/kg). Rats in reserpine-treated group were induced by intraperitoneally administered reserpine (0.5 mg/kg) for 28 days. TUNEL staining and hematoxylin and eosin staining were used to evaluate the apoptotic cells and morphologic changes. In addition, to explore the mechanism of curcumin in protecting GMLs, we used serum of experimental rats to assess the level of vasoactive intestinal peptide (VIP), gastrin, interleukin-6, interleukin-10, tumor necrosis factor-α and interferon-γ by ELISA and radioimmunoassay. The protein levels of NF-κB, p-IκB-α, IκB-α, Bcl-2, Bax, and cleaved-caspase-3 were examined by western blot analysis. Data were analyzed with SPSS 19.0 software package. Curcumin treatment prevented tissue damage and cell death in the reserpine-treated rats and effectively decreased inflammatory response and balanced the expression of VIP and gastrin in the reserpine-treated rats. NF-κB, p-IκB-α, Bax, and cleaved-caspase-3 were increased in the reserpine group, but the curcumin high-dose group inhibited them. Curcumin can target the IκB-α/NF-κB pathway to inhibit inflammatory response and regulate the level of VIP and gastrin in reserpine-induced GML rats.

Neural mechanism of gastric motility regulation by electroacupuncture at RN12 and BL21: A paraventricular hypothalamic nucleus-dorsal vagal complex-vagus nerve-gastric channel pathway.

AIM: To study the neural mechanism by which electroacupuncture (EA) at RN12 (Zhongwan) and BL21 (Weishu) regulates gastric motility. METHODS: One hundred and forty-four adult Sprague Dawley rats were studied in four separate experiments. Intragastric pressure was measured using custom-made rubber balloons, and extracellular neuron firing activity, which is sensitive to gastric distention in the dorsal vagal complex (DVC), was recorded by an electrophysiological technique. The expression levels of c-fos, motilin (MTL) and gastrin (GAS) in the paraventricular hypothalamic nucleus (PVN) were assayed by immunohistochemistry, and the expression levels of motilin receptor (MTL-R) and gastrin receptor (GAS-R) in both the PVN and the gastric antrum were assayed by western blotting. RESULTS: EA at RN12 + BL21 (gastric Shu and Mu points), BL21 (gastric Back-Shu point), RN12 (gastric Front-Mu point), resulted in increased neuron-activating frequency in the DVC (2.08 ± 0.050, 1.17 ± 0.023, 1.55 ± 0.079 vs 0.75 ± 0.046, P < 0.001) compared with a model group. The expression of c-fos (36.24 ± 1.67, 29.41 ± 2.55, 31.79 ± 3.00 vs 5.73 ± 2.18, P < 0.001), MTL (22.48 ± 2.66, 20.76 ± 2.41, 19.17 ± 1.71 vs 11.68 ± 2.52, P < 0.001), GAS (24.99 ± 2.95, 21.69 ± 3.24, 23.03 ± 3.09 vs 12.53 ± 2.15, P < 0.001), MTL-R (1.39 ± 0.05, 1.22 ± 0.05, 1.17 ± 0.12 vs 0.84 ± 0.06, P < 0.001), and GAS-R (1.07 ± 0.07, 0.91 ± 0.06, 0.78 ± 0.05 vs 0.45 ± 0.04, P < 0.001) increased in the PVN after EA compared with the model group. The expression of MTL-R (1.46 ± 0.14, 1.26 ± 0.11, 0.99 ± 0.07 vs 0.65 ± 0.03, P < 0.001), and GAS-R (1.63 ± 0.11, 1.26 ± 0.16, 1.13 ± 0.02 vs 0.80 ± 0.11, P < 0.001) increased in the gastric antrum after EA compared with the model group. Damaging the PVN resulted in reduced intragastric pressure (13.67 ± 3.72 vs 4.27 ± 1.48, P < 0.001). These data demonstrate that the signals induced by EA stimulation of acupoints RN12 and BL21 are detectable in the DVC and the PVN, and increase the levels of gastrointestinal hormones and their receptors in the PVN and gastric antrum to regulate gastric motility. CONCLUSION: EA at RN12 and BL21 regulates gastric motility, which may be achieved through the PVN-DVC-vagus-gastric neural pathway.

Identification and characterization of gastrointestinal hormone immunoreactive cells in the skin and parotoids of Chinese toad Bufo gargarizans.

The skin and skin secretion of Chinese toad Bufo gargarizans have long been used in traditional Chinese medicine. However, the exact types and location of bioactive substances in Bufo gargarizans skin still have not been fully elucidated. The aim of the study was to investigate the distribution and density of six types of gastrointestinal (GI) hormone immunoreactive (IR) cells in the skin and parotoids of Bufo gargarizans. Immunohistochemistry was used for qualitative and semiquantitative analysis of GI hormone presence in the dorsal and ventral skin, and parotoids of eight adult Chinese toads. Six types of IR cells were found: serotonin (5-HT), glucagon (GLU), gastrin (GAS), somatostatin (SS), pancreatic polypeptide (PP) and neuropeptide Y(NPY) IR cells. They were mainly present in the epidermis and skin glands. 5-HT-IR cells were distributed in all layers of epidermis and glands, with higher density in the glands. Glucagon was prominently expressed in the epidermis and the bottle-shaped glands of parotoids; however, it was not present in the granular glands of skin and parotoids. The distributions of GAS and SS-IR cells were similar since they were present mainly in mucous, granular and bottle-shaped glands, while these cell types were absent in the differentiated glands of parotoids. PP-IR cells were predominant in the granular glands and the bottle-shaped glands. The expression of NPY was high in epidermal stratum granulosum and mucous glands of the dorsal skin, the bottle-shaped glands and differentiated glands of parotoids, while NPY-IR was rarely seen in the granular glands of ventral skin, and not present in the granular glands of dorsal skin and parotoids. The expression of several types of GI hormones in the skin and parotoids of Bufo gargarizans varies depending on tissue and type of glands.

Effectiveness of electroacupuncture at Zusanli (ST36) on the immunohistochemical density of enteroendocrine cells related to gastrointestinal function.

The purpose of this study was to examine the effects of electroacupuncture at Zusanli on the immunohistochemical density of enteroendocrine cells related to gastrointestinal function. The authors investigated the histochemical changes of mucous substances and immunohistochemical density of gastrin, serotonin, calcitonin gene-related peptide (CGRP), insulin, and pancreatic polypeptide (PP) secreting cells in rats. Staining density of mucous substances and the enteroendocrine cells of the gastrointestinal tract was observed with histochemical and immunohistochemical methods. Stainless steel needles with a diameter of 0.25 mm were inserted into Zusanli (St36, 5mm below the head of the fibula under the knee joint, and 2mm lateral to the anterior tubercle of the tibia) and connected to an electrical stimulator. The electroacupuncture (EA) stimulation was delivered for 30 minutes at 10 mA, 2 Hz in EA stimulation (2EA group) or 4 Hz in EA stimulation (4EA group) in each experimental group. In 4EA stimulation at the Zusanli, staining density of Alcian blue-periodic acid-Schiff on mucous substances of the stomach body was stronger than those of the 2EA and control groups. Periodic acid-Schiff staining density of pyloric mucosa in the 4EA group was stronger than that of the 2EA and control groups. The immunohistochemical staining density of gastrin, serotonin, and CGRP-secreting cells of pylorus in the 2EA and 4EA groups was stronger than that of the control group. Immunohistochemical staining density of insulin and PP secreting cells of islets of the pancreas in the 2EA and 4EA groups was stronger than that of the control group. These results suggest that EA stimulus at St36 has the potential to influence gastric mucous substances and enteroendocrine cells (gastrin, serotonin, CGRP, insulin, and PP) that subsequently modulate digestive functions.

Folic acid increases global DNA methylation and reduces inflammation to prevent Helicobacter-associated gastric cancer in mice.

BACKGROUND & AIMS: Previous studies have suggested that dietary folic acid (FA) can protect against certain types of cancers. However, the findings have varied, and the mechanisms by which FA exerts chemopreventive effects remain to be clarified. We examined the effects of FA supplementation on DNA methylation, gene expression, and gastric dysplasia in a transgenic mouse model that is etiologically and histologically well matched with human gastric cancers. METHODS: Hypergastrinemic mice infected with Helicobacter felis were studied at multiple stages of gastric dysplasia and early cancer with FA supplementation initiated both at weaning and later in life. Global DNA methylation was assessed by a methylation sensitive cytosine incorporation assay, bisulfite pyrosequencing of B1 repetitive elements, and immunohistochemistry with anti-5-methylcytosine. We also profiled gene expression in the same tissues. RESULTS: We found a decrease in global DNA methylation and tissue folate and an increase in serum homocysteine with progression of gastric dysplasia. FA supplementation prevented this loss of global DNA methylation and markedly reduced gastric dysplasia and mucosal inflammation. FA protected against the loss of global DNA methylation both in the dysplastic gastric epithelial cells and in gastric stromal myofibroblasts. In addition, FA supplementation had an anti-inflammatory effect, as indicated by expression profiling and immunohistochemistry for lymphocyte markers. CONCLUSIONS: We conclude that FA supplementation is chemopreventive in this model of Helicobacter-associated gastric cancer. The beneficial effect of FA is likely due to its ability to prevent global loss of methylation and suppress inflammation.

Anti-ulcerogenic mechanisms of the sesquiterpene lactone onopordopicrin-enriched fraction from Arctium lappa L. (Asteraceae): role of somatostatin, gastrin, and endogenous sulfhydryls and nitric oxide.

Arctium lappa L. has been used in folk medicine as a diuretic, depurative, and digestive stimulant and in dermatological conditions. The mechanisms involved in the anti-ulcerogenic activity of the sesquiterpene onopordopicrin (ONP)-enriched fraction (termed the ONP fraction), obtained from A. lappa leaves, were studied. The gastroprotective mechanism of the ONP fraction was evaluated in experimental in vivo models in rodents, mimicking this disease in humans. ONP fraction (50 mg/kg, p.o.) significantly inhibited the mucosal injury induced by ethanol/HCl solution (75%), indomethacin/bethanecol (68.9%), and stress (58.3%). When the ONP fraction was investigated in pylorus ligature, it did not induce alteration in the gastric volume but did modify the pH and total acid concentration of gastric juice. ONP fraction significantly increased serum somatostatin levels (82.1±4.1 vs. control group 12.7±4 pmol/L) and decreased serum gastrin levels (62.6±6.04 vs. control group 361.5±8.2 µU/mL). Mucus production was not significantly altered by the ONP fraction. Gastroprotection by the ONP fraction was completely inhibited by N-ethylmaleimide treatment and did not modify the effect in the animals pretreated with l-N(G)-nitroarginine methyl ester. These results suggest an antisecretory mechanism involved with the antiulcerogenic effect of the ONP fraction. However, only endogenous sulfhydryls play an important role in gastroprotection of the ONP fraction.

[Effects of transcutaneous electrical acupoint stimulation combined with general anesthesia on changes of gastric dynamics in controlled hypotension dogs].

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) combined with general anesthesia on gastric dynamics in controlled hypotension dogs, so as to provide experimental evidence for compound acupuncture anesthesia. METHODS: Eighteen male beagle dogs were randomly divided into general anesthesia group (GA group, n = 6), general anesthesia + controlled hypotension group (GA + OHT group, n = 6) and general anesthesia combined with TEAS + controlled hypotension group (TEAS group, n = 6). The latter two groups were administered with the same anesthetics [isofluane inhalation and intravenous sodium nitroprusside (SNP)] for inducing controlled hypotension (being the 40% of the baseline level). Beagles of the GA group were not treated with controlled hypotension (the initial concentration of SNP = 1 microg/kg x min(-1), and with an increase rate of 1 microg/kg x min(-1) until the controlled hypotension phase). In the TEAS group, TEAS [2 Hz/100 Hz, (4 +/- 1) mA]was applied to "Quchi" (LI 11) , "Zusanli" (ST 36), "Hegu" (LI 4), and "Sanyinjiao" (SP 6) from the beginning of the stable physiological condition phase to the end of the controlled-low mean arterial pressure (MAP) phase. Electrogastrogram (EGG) was recorded, and serum gastrin (GAS) and motilin (MTL) contents were detected by enzyme-linked immunosorbent assay. RESULTS: Compared with the basic level, the amplitude value of EGG at 60 mm after controlled hypotension in the GA + CHT group was significantly lower (P < 0.05), while the amplitude level of EGG of the TEAS group at the time-point of MAP recovery was significantly higher than those of the GA and GA + CHT groups (P < 0.05). No significant changes were found among the 3 groups in the frequency levels of EGG. At the time-points of MAP recovery and 2 h after MAP recovery, serum MTL and GAS levels in the TEAS group were close to their basic level (P > 0.05), and serum GAS level at the time-point of 2 h after MAP recovery in the TEAS group was considerably higher than those in the GA and GA + CHT groups (P < 0.05). Twenty-four, 48 and 72 h after MAP recovery, serum GAS levels in the TEAS group were moderately (24 h and 48 h ) and significantly (72 h) higher than that of the basic level. No significant differences were found between the GA and GA + CHT groups in serum MTL and GAS levels at the time-points of 2, 24, 48 and 72 h after MAP recovery (P > 0.05). CONCLUSION: TEAS combining with general anesthesia for controlled hypotension can improve the amplitude of EGG, and serum MTL and GAS contents, favoring the recovery of gastric dynamics and the functional protection of stomach.

Pancreatic neuroendocrine cell tumor secreting parathyroid hormone-related protein and gastrin: Report of a case.

This report presents a case of pancreatic neuroendocrine cell carcinoma with multiple liver metastases secreting gastrin and parathyroid hormone-related protein (PTHrP) related to lumbar bone fracture and hypercalcemia. A 58-year-old woman visited an affiliated hospital with a chief complaint of lumbago without any evidence of trauma. She was diagnosed with hepatic dysfunction and hypercalcemia as well as multiple lumbar compression fractures without osteolytic lesions. Abdominal computed tomography (CT) showed a hypervascular mass in the pancreatic tail and multiple liver tumors. Duodenal ulcers were found with gastrointestinal endoscopy. There was a marked increase in the serum gastrin level. She was diagnosed as gastrinoma with multiple liver metastases and was admitted to the hospital. She had an increase in serum PTHrP level without the elevation of intact parathyroid hormone at the time of admission. She underwent an extended right hepatectomy in addition to a distal pancreatectomy with a regional lymphadenectomy and splenectomy. The postoperative course was uneventful, and serum gastrin and PTHrP activities reduced to normal levels. She remained symptom-free, and serum calcium, gastrin, and PTHrP levels remain within the normal ranges 19 months after surgery without adjuvant therapy.

[Effect of method of soothing liver and regulating qi on expression of gastrin and somatostatin in hypothalamus, castric antrum of functional dyspepsia rats].

OBJECTIVE: To explore the effects of the method of soothing the liver and regulating qi on expression of gastrin and somatostatin in hypothalamus and gastric antrum of functional dyspepsia model rats. METHOD: The 32 rats were randomly divided into normal group, model group, Chaihu Shugansan group and domperidone group (n = 8). The functional dyspepsia model was established by constantly squeezing their tails and mean while saline, Chaihu Shugansan decoction and domperidone suspension were administered respectively to 4 groups by gavage. The expression of gastrin and somatostatin in hypothalamus and gastric antrum of rats by immunohistochemical were detected 3 weeks later. RESULT: The expression of GAS in the hypothalamus and gastric antrum of model group were less than those of normal group (P < 0.05, P < 0.01), while the expression of SS in the hypothalamus and gastric antrum in Model group were significantly increased than those of normal group (P < 0.01). The expression of GAS and SS in gastric antrum of Chaihu Shugansan group and domperidone group were increased and decreased respectively, and the differences were significant (P < 0.05, P < 0.01). There were no obvious difference about expression of GAS, SS in the hypothalamus between domperidone group and model group. GAS expression in hypothalamus of Chaihu Shugansan group were increased than those of normal group but there was no obvious difference in SS expression in hypothalamus between Chaihu Shugansan group and model group. CONCLUSION: The method of soothing the liver and regulating qi can increase GAS expression in central and peripheral and decrease SS expression in peripheral gastric antrum, which may be one of its therapeutic mechanisms on functional dyspepsia.

[Therapeutic and preventive effects of sulfate-chloride-sodium mineral water in experimental peptic ulcer].

Healthy animals and individuals with experimental peptic ulcer were used to evaluate effect of weakly mineralized Tselitel'nitsa water on hormonal control of metabolic and trophic reactions. The mineral water was found to activate regulation of carbohydrate metabolism by insulin and cortisol due to the formation of adaptive reactions during a course of its therapeutic intake. The mineral water promoted realization of trophic effects of gastrin and insulin in animals with peptic ulcer the size of which significantly decreased. A preventive course of therapy with the mineral water was shown to enhance resistance of experimental animals to stressful factors.

The anti-ulcerogenic effects of Curatella americana L.

ETHNOPHARMACOLOGICAL RELEVANCE: Curatella americana L. (Dilleneaceae) is a medicinal plant very frequently cited as acting against gastrointestinal disorders in ethnopharmacological inventories of the Cerrado region of Brazil. AIM OF THE STUDY: The ethanolic extract (CEB) and infusion (BI) of Curatella americana bark were investigated for their ability to prevent and heal ulceration of the gastric mucosa. MATERIALS AND METHODS: The preventive and healing actions of Curatella americana were evaluated in experimental in vivo models in rodents that simulated this disease in human gastric mucosa. RESULTS: CEB significantly decreased the severity of gastric damage formation induced by the combination of several gastroprotective models (HCl/ethanol, indomethacin/bethanecol, absolute ethanol, stress and pylorus ligature). But, unlike CEB, the BI did not exert gastroprotective effect. The gastroprotective action of CEB involved antisecretory action, augmentation of gastric mucus (48%) and participation of endogenous sulfhydryl compounds that increase efficacy of barrier mucosa against injurious agents. CEB also presents effective healing action in chronic gastric disease (1.90+/-0.55 vs. 6.86+/-0.46 mm2)in the control) and its action mechanisms consisted of increasing the PGE2 (40%) and somatostatin levels (269%) while decreasing the gastrin level in rat plasma (79%). CONCLUSIONS: The gastroprotective effect and healing action of Curatella americana involved modulation of PGE2, somatostatin and gastrin levels, probably due to the presence of oligomeric and polymeric proanthocyanidins in the bark.

Activation of the calcium sensing receptor stimulates gastrin and gastric acid secretion in healthy participants.

UNLABELLED: In 17 adults on a fixed metabolic diet, an 11-day course of cinacalcet increased serum gastrin and basal gastric acid output, but not maximal gastric acid output, compared with a placebo. These findings indicate that the calcium sensor receptor plays a role in the regulation of gastric acid. INTRODUCTION: Gastric acid secretion is a complex process regulated by neuronal and hormonal pathways. Ex vivo studies in human gastric tissues indicate that the calcium sensing receptor (CaR), expressed on the surface of G and parietal cells, may be involved in this regulation. We sought to determine whether cinacalcet, a CaR allosteric agonist, increases serum gastrin and gastric acid secretion. METHODS: Seventeen healthy adults with normal gastric acid output were placed on an 18-day metabolic diet. On day 8 (baseline), participants were given cinacalcet (15 then 30 mg/day) or placebo for 11 days. Changes in gastric acid output, serum gastrin, and other measures were compared in the two groups. RESULTS: Changes in serum gastrin and basal acid output (adjusted for baseline body weight) were significantly more positive in the cinacalcet group compared with placebo (P = 0.004 and P = 0.039 respectively). Change in maximal acid output was similar in the two groups (P = 0.995). As expected, cinacalcet produced significant decreases in serum PTH (P < 0.001) and ionized calcium levels (P = 0.032), and increases in serum phosphorus levels (P = 0.001) and urinary calcium (P = 0.023). CONCLUSIONS: This study provides in vivo evidence that activation of the CaR increases serum gastrin levels and basal gastric acid secretion in healthy adults.

Effects of a bicarbonate-alkaline mineral water on digestive motility in experimental models of functional and inflammatory gastrointestinal disorders.

This study investigates the effects of Uliveto, a bicarbonate-alkaline mineral water, in experimental models of diarrhea, constipation and colitis. Rats were allowed to drink Uliveto or oligomineral water (control) for 30 days. Diarrhea and constipation were evoked by 16,16-dimethyl-prostaglandin E(2) (dmPGE(2)) or loperamide, respectively. Colitis was induced by 2,4-dinitrobenzenesulfonic acid (DNBS) or acetic acid. Gastric emptying, small-intestinal and colonic transit were evaluated. dmPGE(2)-induced diarrhea reduced gastric emptying and increased small-intestinal and colonic transit. In this setting, Uliveto water enhanced gastric emptying, and this effect was prevented by L-365,260 (gastrin receptor antagonist). Loperamide-induced constipation reduced gastric emptying, small-intestinal and colonic transit, and these effects were prevented by Uliveto water. L-365,260 counteracted the effects of Uliveto on gastric emptying, while alosetron (serotonin 5-HT(3) receptor antagonist) blunted the effect of Uliveto on colonic transit. Gastric emptying, small-intestinal and colonic transit were reduced in DNBS-induced colitis, and Uliveto water enhanced gastric emptying and normalized small-intestinal and colonic transit. Gastric emptying, small-intestinal and colonic transit were also reduced in acetic acid-induced colitis, and Uliveto increased both gastric emptying and small-intestinal transit. In conclusion, Uliveto water exerts beneficial effects on gastrointestinal motility in the presence of bowel motor dysfunctions. The effects of Uliveto water on gastric emptying depend on gastrin-mediated mechanisms, whereas the activation of serotonergic pathways accounts for the modulation of colonic functions.

Supplemental sodium butyrate stimulates different gastric cells in weaned pigs.

Sodium butyrate (SB) is used as an acidifier in animal feed. We hypothesized that supplemental SB impacts gastric morphology and function, depending on the period of SB provision. The effect of SB on the oxyntic and pyloric mucosa was studied in 4 groups of 8 pigs, each supplemented with SB either during the suckling period (d 4-28 of age), after weaning (d 29 to 39-40 of age) or both, or never. We assessed the number of parietal cells immunostained for H+/K+-ATPase, gastric endocrine cells immunostained for chromogranin A and somatostatin (SST) in the oxyntic mucosa, and gastrin-secreting cells in the pyloric mucosa. Gastric muscularis and mucosa thickness were measured. Expressions of the H+/K+-ATPase and SST type 2 receptor (SSTR2) genes in the oxyntic mucosa and of the gastrin gene in the pyloric mucosa were evaluated by real-time RT-PCR. SB increased the number of parietal cells per gland regardless of the period of administration (P < 0.05). SB addition after, but not before, weaning increased the number of enteroendocrine and SST-positive cells (P < 0.01) and tended to increase gastrin mRNA (P = 0.09). There was an interaction between the 2 periods of SB treatment for the expression of H/K-ATPase and SSTR2 genes (P < 0.05). Butyrate intake after weaning increased gastric mucosa thickness (P < 0.05) but not muscularis. SB used orally at a low dose affected gastric morphology and function, presumably in relationship with its action on mucosal maturation and differentiation.

Regulative effects of essential oil from Atractylodes lancea on delayed gastric emptying in stress-induced rats.

Gastric motor dysfunction induced by psychological stress results in many symptoms of functional dyspepsia (FD). There are a number of herbal medicines that are reported to improve gastrointestinal motor. However, the mechanisms of considerable herbal medicines are not explicit. In the present study, the effects of an essential oil (EO) extracted from Atractylodes lancea on delayed gastric emptying, gastrointestinal hormone and hypothalamic corticotropin-releasing factor (CRF) abnormalities induced by restraint stress in rats were investigated and the mechanism of the EO is also explored. Oral administration of EO for 7 days did not affect normal gastric emptying, but accelerated delayed gastric emptying induced by restraint stress in rats. The EO significantly increased the levels of motilin (MTL) and gastrin (GAS) and decreased the levels of somatostatin (SS) and CRF. The EO did not modify gastric emptying in vagotomized rats that underwent restraint stress, but antagonized delayed gastric emptying induced by intracisternal injection of CRF. These results suggest that the regulative effects of the EO on delayed gastric emptying are preformed mainly via inhibition of the release of central CRF and activation of vagal pathway, which are also involved in the release of gastrointestinal hormones such as MTL, GAS and SS.

A continuous dietary supply of free calcium formate negatively affects the parietal cell population and gastric RNA expression for H+/K+-ATPase in weaning pigs.

Baby formula acidification can be used to reduce diarrhea. Calcium formate is a dietary acidifier frequently used in animal weaning diets; it is also a source of available calcium. Gastric acidification reduces gastrin release and hydrochloric acid (HCl) secretion. To study the medium-term effects on fundic gastric mucosa, we fed weaning pigs control diets or diets supplemented with free or fat-protected calcium formate. We evaluated the following: 1) the number of HCl-secreting parietal cells, by immunohistochemistry using an antibody against H(+)/K(+)-ATPase; 2) the number of enteroendocrine cells immunohistochemically stained with chromogranin A (CGA), somatostatin, and histamine (HIS); and 3) the expression of the H(+)/K(+)-ATPase gene, by real-time RT-PCR in the oxyntic mucosa. Cells co-staining for CGA and HIS were defined as enterochromaffin-like (ECL) cells. Pigs fed calcium formate had fewer parietal cells and a lower expression of the H(+)/K(+)-ATPase gene than the controls (P < 0.05). This reduction did not occur in pigs fed fat-protected calcium formate. Somatostatin immune-reactive cells were also more numerous in pigs fed free calcium formate than in controls (P < 0.05). The number of ECL cells was not affected. Using covariance analysis, the number of parietal cells explained part of the differences in the expression of H(+)/K(+)-ATPase gene (positive correlation, r = 0.385, P < 0.01), and excluded the statistical significance of the diet. In the future, the effects on the oxyntic mucosa should be checked when the diet supplemented with calcium formate is discontinued. Furthermore, a reduction in the number of parietal cells could impair the absorption of vitamin B-12 due to a reduced secretion of the intrinsic factor by these cells.