The Effect of Dried Ginger (Gan Jiang) on Stomach Energy Metabolism and the Related Mechanism in Rats Based on Metabonomics.

Dried ginger is a commonly used stomachic. Dried ginger is often used as a gastric protector to treat stomach-related diseases. However, the effect of dried ginger on energy metabolism in stomach tissue of rats under physiological condition has not been studied. In this study, different doses of water extract of dried ginger were given to rats for 4 weeks. The activity of Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, SDH (succinate dehydrogenase) enzyme, ATP content, mitochondrial metabolic rate and mitochondrial number in stomach tissue of rats were measured. Analysis of potential biomarkers related to the effect of dried ginger on energy metabolism in stomach tissue of rats by metabonomics, and their metabolic pathways were also analyzed. The results revealed that there was no significant difference in Na+ -K+ -ATPase in high-dose group (GJH), medium-dose group (GJM) and low-dose group (GJL) compared to the Control group. The Ca2+ -Mg2+ -ATPase activity was significantly increased in stomach tissue of GJH group and GJM group, but there were no significant changes in stomach tissue of GJL group. The SDH activity and the ATP levels were significantly increased in stomach tissue of GJH group, GJM group and GJL group. The mitochondrial metabolic rate was significantly increased in GJL group, but there was no significant change in GJM group and was inhibited in GJH group. These effects might be mediated by arginine biosynthesis, glutathione metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, arginine and proline metabolism, purine metabolism pathway.

Fucoidan from Sargassum hemiphyllum inhibits infection and inflammation of Helicobacter pylori.

Having infected by Helicobacter pylori, the infection often leads to gastritis, gastric ulcer, or even gastric cancer. The disease is typically treated with antibiotics as they used to effectively inhibit or kill H. pylori, thus reducing the incidence of gastric adenoma and cancer to significant extent. H. pylori, however, has developed drug resistance to many clinically used antibiotics over the years, highlighting the crisis of antibiotic failure during the H. pylori treatment. We report here that the fucoidan from Sargassum hemiphyllum can significantly reduce the infection of H. pylori without developing to drug resistance. Fucoidan appears to be a strong anti-inflammation agent as manifested by the RAW264.7 cell model examination. Fucoidan can prohibit H. pylori adhesion to host cells, thereby reducing the infection rate by 60%, especially in post treatment in the AGS cell model assay. Mechanistically, fucoidan intervenes the adhesion of BabA and AlpA of H. pylori significantly lowering the total count of H. pylori and the level of IL-6 and TNF-α in vivo. These results all converge on the same fact that fucoidan is an effective agent in a position to protect the stomach from the H. pylori infection by reducing both the total count and induced inflammation.

Zuojin Pill attenuates Helicobacter pylori-induced chronic atrophic gastritis in rats and improves gastric epithelial cells function in GES-1 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Zuojin pill (ZJP), a classical Chinese medicine formula, has been widely applied in Chinese clinical practice for the treatment of gastric injury such as acute gastric lesion, acute gastric mucosal injury, chronic unpredictable mild stress, gastroesophageal reflux disease, etc, thereby exerting anti-chronic atrophic gastritis (CAG) effects in traditional Chinese herbal medicine. AIM OF THE STUDY: This study was aimed to explore the therapeutic effects and molecular mechanisms of ZJP on Helicobacter pylori (H. pylori)-induced CAG based on the comprehensive approaches. MATERIALS AND METHODS: Sprague-Dawley rats were infected with H. pylori for 8 weeks to establish CAG model. Then, rats in the ZJP groups received doses of 0.63, 1.26, and 2.52 g/kg ZJP for 4 weeks. Therapeutic effects of ZJP on serum indices and the histopathology of the gastric were analyzed in vivo. Moreover, GES-1 cells were infected with H. pylori to establish gastric epithelial cell injury model in vitro. Cell viability and gastric epithelial cell morphology were detected by a high-content screening (HCS) assay. Furthermore, the relative mRNA and protein expression of JMJD2B/COX-2/VEGF axis and HMGB1/NF-κB signaling pathway in vivo and in vitro were determined by RT-PCR and Western Blotting, respectively. RESULTS: The results showed that the therapeutic effects of ZJP on CAG rats were presented in down-regulation serum biochemical indices and alleviating histological damage of gastric tissue. ZJP could dose-dependently decrease the serum IL-6, MCP-1, PGE2, TNF-α, and VEGF level and significantly improved gastric tissue inflammatory lesions. Besides, ZJP has an effect on increasing cell proliferation of GES-1 cells, ameliorating H. pylori-induced gastric epithelial cell damage. It was found that ZJP has a down-regulating effect on inflammatory reaction and could inhibit the relative mRNA and protein expression of JMJD2B/COX-2/VEGF axis and HMGB1/NF-κB signaling pathway in vivo and in vitro, including JMJD2B, COX-2, VEGF, VEGFR1, and VEGFR2, which in turn reduced the damage of gastric mucosal cells. CONCLUSIONS: The results suggested that ZJP exerts therapeutic effects on H. pylori-induced CAG by inhibiting the JMJD2B/COX-2/VEGF axis and HMGB1/NF-κB signaling pathway. These findings deeply explained why ZJP could be used to treat CAG clinically and clarified its pharmacological effect and potential mechanism in the treatment of CAG.

Comparative stomach tissue distribution profiles of four major bio-active components of Radix Astragali in normal and gastric ulcer mice

Numerous studies have demonstrated that Radix Astragali can inhibit gastric ulcers in mice. Anhydrous ethanol (0.01 mL/g) administered to mice by intragastric infusion can induce gastric ulcer injury. This study was performed to compare the stomach tissue distribution profiles of four major bioactive constituents of Radix Astragali(calycosin-7-O-ß-d-glucoside, calycosin, ononin and formononetin) after oral administration of extract of Radix Astragali (ERA)in normal and gastric ulcer mice. The abundance of Radix Astragali constituents was determined using an ultra-pressure liquid chromatograph with a photodiode array detector (UPLC-PDA), after which histograms were drawn. In comparison with normal mice, the contents of calycosin- 7-O-ß-d-glucoside, calycosin, ononin and formononetin in the stomach tissue samples of gastric ulcer mice showed significant differences at the selected time points (P < 0.05).The abundance of each of the four tested constituents in the normal groups was higher than that of the gastric ulcer groups. This study provides an empirical foundation for future studies focused on developing clinical applications of Radix Astragali

Evaluation of 28-day repeated oral dose toxicity of SUNACTIVE Zn-P240 in rats.

This study was conducted to investigate the potential toxicity of repeated oral dose of SUNACTIVE Zn-P240, a new type of zinc supplement, in Sprague-Dawley rats. SUNACTIVE Zn-P240 was administered once daily by gavage at doses of 0, 500, 1000, and 2000 mg/kg/day for each group over a 28-day period. At 2000 mg/kg/day, there were increases in serum alkaline phosphatase (ALP) and alanine aminotransferase, liver weight, histopathological changes in stomach, liver, and pancreas and decreases in body weight, food consumption, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration, total protein (TP), and albumin. At 1000 mg/kg/day, there was an increase in the serum ALP level and there were decreases in the MCV, MCH, and TP. There were no treatment-related adverse effects in the 500 mg/kg/day group. Under the present experimental conditions, the target organs in rats were determined to be the stomach, pancreas, liver, and erythrocyte and the no-observed-adverse-effect level (NOAEL) in rats was considered to be 500 mg/kg/day.

A research on the mechanism of NSAID-related gastric ulcer treated by jia wei wu qi san based on the p38mapk signal pathway.

This study aims to explore the mechanism of NSAID-related gastric ulcer treated by JIA WEI WU QI SAN. Clean-grade SD rats were randomly divided into four groups. Group A was assigned as the control group. Groups B, C and D were intragastrically administered with 2.5mg/kg of indomethacin solution QD after 48 hours. After 15 days of treatment, group B was administered with 0.9% sodium chloride, group C was given rabeprazole (2mg/kg), and group D was administered with JIA WEI WU QI SAN (2g/kg). Abdominal aorta sampling was performed, and gastric tissues were isolated on the 29th day. The protein expression of p-P38MAPK and COX-2 were detected by western blot, while the concentration of PGE2 and IL-1 were determined by ELISA. (1) The expression of IL-1ingroup B dramatically declined in group D (P<0.01). (2)The expression of PGE-2dramatically increased in group D(P<0.01). (3) The expression of COX-2 increased in group D (P<0.05). (4) The expression of p-P38MAPK decreased in group D (P<0.05). JIA WEI WU QI SAN has multiple functions, including the activation of the p-P38MAPK signaling pathway, which promote the activation of COX-2, induce the arachidonic acid to increase the level of PG, and decrease the concentration of IL-1, thereby inducing an inflammatory reaction, and promote gastric mucosa repair.

Targeting Lactate Dehydrogenase A with Catechin Resensitizes SNU620/5FU Gastric Cancer Cells to 5-Fluorouracil.

Resistance to anticancer therapeutics occurs in virtually every type of cancer and becomes a major difficulty in cancer treatment. Although 5-fluorouracil (5FU) is the first-line choice of anticancer therapy for gastric cancer, its effectiveness is limited owing to drug resistance. Recently, altered cancer metabolism, including the Warburg effect, a preference for glycolysis rather than oxidative phosphorylation for energy production, has been accepted as a pivotal mechanism regulating resistance to chemotherapy. Thus, we investigated the detailed mechanism and possible usefulness of antiglycolytic agents in ameliorating 5FU resistance using established gastric cancer cell lines, SNU620 and SNU620/5FU. SNU620/5FU, a gastric cancer cell harboring resistance to 5FU, showed much higher lactate production and expression of glycolysis-related enzymes, such as lactate dehydrogenase A (LDHA), than those of the parent SNU620 cells. To limit glycolysis, we examined catechin and its derivatives, which are known anti-inflammatory and anticancer natural products because epigallocatechin gallate has been previously reported as a suppressor of LDHA expression. Catechin, the simplest compound among them, had the highest inhibitory effect on lactate production and LDHA activity. In addition, the combination of 5FU and catechin showed additional cytotoxicity and induced reactive oxygen species (ROS)-mediated apoptosis in SNU620/5FU cells. Thus, based on these results, we suggest catechin as a candidate for the development of a novel adjuvant drug that reduces chemoresistance to 5FU by restricting LDHA.

Digestive promoting effect and mechanism of Jiao Sanxian in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiao Sanxian, a customary term for the three Traditional Chinese Medicines of charred hawthorn (Crataegi Fructus), charred malt (Hordei Fructus Germinatus) and Liu Shenqu (Massa Medicata Fermentata), is a classic prescription for the treatment of functional dyspepsia (FD). This prescription is called "Jiao Sanxian" in China because people believe that it is a miracle medicine for enhancing digestion and improving stagnation of digestive system. Even though Jiao Sanxian is widely used in clinical treatment, the underlying mechanism has not been clarified to date. AIM OF THE STUDY: The present study is aimed to explore the efficacy and mechanism of Jiao Sanxian in improving the symptoms of FD in rats by using multiple pharmacological methods. MATERIALS AND METHODS: The Sprague Dawley (SD) rats were divided into control, model, Jiao Sanxian decoction low-dosage (JSXD LD), Jiao Sanxian decoction medium-dosage (JSXD MD), and Jiao Sanxian decoction high-dosage (JSXD HD) group at random. A FD model was established with reserpine, and animals were given intragastric administration. During this period, weight and food intake of animals were recorded. Samples of rat gastric antrum, spleen, and duodenum were collected for pathological staining and immunohistochemical determination of Ghrelin protein expression after 19 days of treatment. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of related brain gut peptides in serum. Moreover, 16S rRNA sequencing was used to valuate the influence of intestinal flora structure of the cecal contents of experimental rats. And plasma metabolomics by Ultra Performance Liquid Chromatography coupled with Quadrupole-Time-of-Flight mass spectrometry (UPLC-Q/TOF-MS) were performed to further reveal the mechanism of action. RESULTS: Jiao Sanxian decoction (JSXD) group with different dosage could increase body weight and food intake, improve histopathological changes, and alter disordered brain gut peptides in FD rats. 16S rRNA sequencing results described that JSXD improved the disorder of structural composition, biodiversity and function of gut microbiota in FD rats. Metabolomics illustrated 26 metabolites with JSXD treatment underwent continuous changes, which revealed JSXD might exert digestive effect by ameliorating abnormal metabolic pathways. The most relevant metabolic pathways were arachidonic acid metabolism, pyruvate metabolism, glycerophospholipid metabolism, alanine, aspartate and glutamate metabolism. CONCLUSIONS: JSXD can improve functional dyspepsia in rats and the mechanism is related to regulate secretion of brain gut peptides, significantly improve the disorder of intestinal flora and ameliorated multi-metabolic pathways.

Methods to improve efficacy of orally administered bioactive peptides using bovine colostrum as an exemplar.

BACKGROUND: Oral administration of bioactive peptides has potential clinical advantages, but its applicability is limited due to gastric and pancreatic enzyme proteolysis. OBJECTIVE: To examine whether the co-packaging of bovine colostrum (BC), a rich source of IgG, immune and growth factors, with the food additives trehalose (carbohydrate), stearine (fat), casein (protein present in BC) or soy flour (plant based with high protease inhibitory activity) enhances the stability of BC against digestion. DESIGN: Samples alone and in combination (BC+ 10% wt/wt trehalose, stearine, casein or soy) were exposed to HCl/pepsin, followed by trypsin and chymotrypsin ("CT"). Assessment of proliferation used gastric AGS cells (Alamar blue), IgG function measured bovine IgG anti-E.coli binding and ELISAs quantified growth factor constituents. In vivo bioassay assessed ability of BC alone or with soy to reduce injury caused by dextran sodium sulphate (DSS, 4% in drinking water, 7 days, test products started 2 days prior to DSS). RESULTS: Proliferative activity of BC reduced 61% following HCl/pepsin and CT exposure. This was truncated 50% if soy was co-present, and also protected against loss of total IgG, IgG E.coli binding, TGFß, lactoferrin and EGF (all P<0.01 vs BC alone). Co-packaging with trehalose was ineffective in preventing digestion whereas casein or stearine provided some intermediate protective effects. Rats given BC alone showed beneficial effects on weight gain, disease activity index, tissue histology and colonic MPO. Soy alone was ineffective. BC+ soy combination showed the greatest benefit with a dose of 7 mg/kg (6.4 BC + 0.6 soy flour) having the same degree of benefit as using 20 mg/kg BC alone. CONCLUSION: Soy, and to a lesser extent casein, enhanced the biostability of BC against digestive enzymes. Co-packaging of BC with other food products such as soy flour could result in a decreased dose being required, improving cost-effectiveness and patient compliance.

Genotoxicity of Asiasari Radix et Rhizoma (Aristolochiaceae) ethanolic extract in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herbal medicines have diverse efficacy and are increasingly used worldwide. However, some of these herbal medicines have toxicities or side effects, but the scientific understanding of traditional herbal medicine toxicity has not yet been established. Asiasari Radix et Rhizoma (ARE) is known as a herbal medicine used to relieve pain, and recent studies have shown that ARE has anticancer and antimelanogenesis efficacy. AIM OF THE STUDY: Current study was conducted to assess the potential genotoxicity of an ethanolic extract of ARE. MATERIALS AND METHODS: The genotoxixity of ARE was confirmed by the bacterial reverse mutation assay (Ames test), a mammalian chromosomal aberration test, and a micronucleus test in vivo using ICR mice and comet assay using Sprague-Dawley rats. RESULTS: ARE showed no genotoxicity in a micronucleus test up to 2000 mg/kg body weight in vivo. By contrast, the chromosomal aberration test showed that ARE induced an increase in the number of chromosomal aberrations after treatment for 6 h with a metabolic activation system and for 6 and 22 h without the metabolic activation system when compared with vehicle control. In the Ames test, all strains except TA1535, with or without a metabolic activation system, showed an increase in the number of revertant mutant colonies in the ARE-treated group. In comet assay, DNA damage was observed in the stomach when ARE was administered. CONCLUSION: ARE potentially shows genotoxicity by inducing DNA damage.

Gastroprotective Effects of Polyphenols against Various Gastro-Intestinal Disorders: A Mini-Review with Special Focus on Clinical Evidence.

Polyphenols are classified as an organic chemical with phenolic units that display an array of biological functions. However, polyphenols have very low bioavailability and stability, which make polyphenols a less bioactive compound. Many researchers have indicated that several factors might affect the efficiency and the metabolism (biotransformation) of various polyphenols, which include the gut microbiota, structure, and physical properties as well as its interactions with other dietary nutrients (macromolecules). Hence, this mini-review covers the two-way interaction between polyphenols and gut microbiota (interplay) and how polyphenols are metabolized (biotransformation) to produce various polyphenolic metabolites. Moreover, the protective effects of numerous polyphenols and their metabolites against various gastrointestinal disorders/diseases including gastritis, gastric cancer, colorectal cancer, inflammatory bowel disease (IBD) like ulcerative colitis (UC), Crohn's disease (CD), and irritable bowel syndrome (IBS) like celiac disease (CED) are discussed. For this review, the authors chose only a few popular polyphenols (green tea polyphenol, curcumin, resveratrol, quercetin), and a discussion of their proposed mechanism underpinning the gastroprotection was elaborated with a special focus on clinical evidence. Overall, this contribution would help the general population and science community to identify a potent polyphenol with strong antioxidant, anti-inflammatory, anti-cancer, prebiotic, and immunomodulatory properties to combat various gut-related diseases or disorders (complementary therapy) along with modified lifestyle pattern and standard gastroprotective drugs. However, the data from clinical trials are much limited and hence many large-scale clinical trials should be performed (with different form/metabolites and dose) to confirm the gastroprotective activity of the above-mentioned polyphenols and their metabolites before recommendation.

Region-specific effects of the cysteine protease papain on gastric motility.

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.

Taxifolin and gastro-adhesive microparticles containing taxifolin promotes gastric healing in vivo, inhibits Helicobacter pylori in vitro and proton pump reversibly in silico.

Taxifolin (3,5,7,3,4-pentahydroxy flavanone or dihydroquercetin, Tax) was identified as a gastroprotective compound and a gastroadhesive formulation was recently developed to prolong its residence time and release in the stomach. So, the gastric healing effectiveness of Tax and gastro-mucoadhesive microparticles containing Tax (MPTax) against the acetic acid induced-gastric ulcer in rats was investigated in this study. Moreover, the interactions between Tax and H+/K+-ATPase were investigated in silico, and its anti- H. pylori activity was determined in vitro. The oral treatment with MPTax (81.37 mg/kg, containing 12.29% of Tax) twice a day for seven days reduced the ulcer area by 63%, compared to vehicle-treated group (Veh: 91.9 ± 10.3 mm2). Tax (10 mg/kg, p.o) reduced the ulcer by 40% but with a p = 0.07 versus Veh group. Histological analysis confirmed these effects. Tax and MPTax increased the gastric mucin amount, reduced the myeloperoxidase activity, and increased the glutathione reduced content at ulcer site. However, only MPTax decreased the lipoperoxide accumulation at ulcer site. Besides, Tax and MPTax normalize the catalase and glutathione S-transferase activity. Tax showed reversible interaction with H+/K+-ATPase in silico and its anti-H. pylori effects was confirmed (MIC = 625 µg/mL). These results suggest that the antiulcer property of Tax involves the strengthening of the gastric protective factors in parallel to its inhibitory interaction with H+/K+-ATPase and H. pylori. Considering that ulcer healing action displayed by Tax was favored by gastroadhesive microparticles, this approach seems to be promising for its oral delivery to treat acid-peptic diseases.

Ameliorative activity of aqueous leaf extract from Madhuca longifolia against diclofenac-administered toxicity on rat stomach and intestine.

Madhuca longifolia, a tropical tree used as medicine and food, is known to have a beneficial effect against stomach gastric toxicity. Madhuca longifolia is used in treating cough, skin disease and nerve disorders. Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with overdosage and prolonged use, is known to cause gastric toxicity. Silymarin (SLY), a polyphenolic antioxidant flavonoid, is a derivative of Silybum marianum extracted from milk thistle seeds and fruits, has been widely used in the treatment of gastric ulcer. SLY was used as the standard drug to compare the effects with the Madhuca longifolia aqueous leaf extract treatment. The aim of the current study is to understand the effect of Madhuca longifolia aq. leaf extract on rat stomach and intestine against diclofenac-administered toxicity. Rats (n = 30) were divided into Group I normal control, Group II treated with diclofenac, Group III treated with diclofenac and Madhuca longifolia leaf extract, Group IV treated with diclofenac and silymarin, and Group V was treated with Madhuca longifolia leaf extract alone. After the study duration, rats were euthanized and tissue samples were analyzed for antioxidant, cytokine, protein expression levels and histopathological changes. Diclofenac treated rats had significant (p < 0.05) changes in levels of antioxidants, cytokines, protein expression and pathological changes as compared to rats treated with Madhuca longifolia. This study demonstrated that Madhuca longifolia leaf extract had gastroprotective activity in rats treated with diclofenac.

Cannabis roots: Pharmacological and toxicological studies in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: There are many studies and therapeutic properties attributed to the flowers and leaves of the Cannabis species, but even with few pharmacological studies, Cannabis sativa L. (Cannabaceae) roots presents several therapeutic indications in folk medicine. AIM OF THE STUDY: This study aimed to evaluate the anti-inflammatory and spasmolytic effects as well as the toxicological profile of the aqueous extract of Cannabis sativa roots (CsAqEx) in mice. MATERIALS AND METHODS: We assessed the anti-inflammatory effect with carrageenan-induced leukocyte migration assay, and carrageenan and histamine-induced paw edema methods; The spasmolytic effect was assessed through in vitro assays with isolated mice trachea. To assess motor coordination and mobility, mice went through the rotarod and open field tests, respectively. For the single-dose toxicity study, we administered CsAqEx at the dose of 1000 mg/kg by gavage. In a repeated dose toxicity study, animals received CsAqEx at doses of 25 mg or 100 mg/kg for 28 days. RESULTS: The CsAqEx inhibited the migration of leukocytes at the doses of 25, 50, and 100 mg/kg. The CsAqEx showed anti-inflammatory activity after the intraplantar injection of carrageenan, presenting a reduction in edema formation at all tested doses (12.5, 25, 50 and 100 mg/kg). The dose of 12.5 mg/kg of CsAqEx prevented edema formation after intraplantar injection of histamine. In an organ bath, 729 µg/mL of CsAqEx did not promote spasmolytic effect on isolated mice tracheal rings contracted by carbachol (CCh) or potassium chloride (KCl). We did not observe clinical signs of toxicity in the animals after acute treatment with CsAqEx, which suggested that the median lethal dose (LD50) is greater than 1000 mg/kg. Repeated dose exposure to the CsAqEx did not produce significant changes in hematological, biochemical, or organ histology parameters. CONCLUSIONS: The results suggest that the anti-inflammatory effect of CsAqEx is related to the reduction of vascular extravasation and migration of inflammatory cells, without effects on the central nervous system. Moreover, there was no spasmolytic effect on airway smooth muscle and no toxicity was observed on mice.

Effect of the proportion of curcuminoids on the gastroprotective action of Curcuma longa L. in rats.

The gastroprotective effect of a turmeric acetone extract (TAE) (Curcuma longa L. [Zingiberaceae]) was evaluated and compared against its major curcuminoids; curcumin (CUR), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC). Additionally, to demonstrate the importance of the metabolites' ratio in the extract on the synergistic effect, different mixtures were evaluated. An ethanol-induced gastric injury model was used to evaluate the gastroprotection activity in Wistar rats. The pharmacologic interaction analysis was performed using the Combination Index (CI)-Isobologram Equation method. The CI calculated at 0.5 of affected fraction (fa) for the TAE indicated a synergistic interaction between its components. However, when the proportion of curcuminoids changed from 3.7:1:10 in TAE to a 1:1:1 ratio, the CI implied an antagonistic effect. The binary combinations of curcuminoids (1:1) also showed an antagonistic interaction. The results of this work suggest that the proportion of curcuminoids in the TAE is crucial for the gastroprotective effect against ethanol-induced damage.

Effects of the herbal preparation STW 5-II on in vitro muscle activity in the guinea pig stomach.

BACKGROUND: STW 5 is a combination of nine medicinal herbal extracts and used to treat functional gastrointestinal disorders including functional dyspepsia. It has a region-specific effect by relaxing the proximal and contracting the distal stomach. The research combination STW 5-II (Iberogast® Advance) lacks three herbal extracts but seems clinically as effective as STW 5. However, the action of STW 5-II on gastric motility is unknown. METHODS: In vitro circular and longitudinal muscle tone and contractility were recorded from guinea pig gastric fundus and antrum with isometric force transducers. KEY RESULTS: STW 5-II decreased concentration-dependently (64-512 µg/ml) the tone of circular and longitudinal muscle strips from the fundus. In contrast, STW 5-II increased concentration-dependently contraction amplitude in antral circular and longitudinal muscle. The effects were region-dependent but comparable in the two muscle layers. Application of 512 µg STW 5 or STW 5-II revealed comparable effects in the fundus and antrum circular and longitudinal muscle strips. CONCLUSIONS AND INTERFERENCES: STW 5-II had a region-specific effect and relaxed the proximal stomach but increased the contractility in the antrum. It was as effective as STW 5 which may explain its comparable clinical effects in treating functional dyspepsia. Impaired accommodation may be normalized through relaxation of the fundus, while the motility-promoting effects leading to an increase in antral motility may activate the gastric pump.

Mitochondria metabonomics of Huangqi Jianzhong Tang against chronic atrophic gastritis.

Huangqi Jianzhong Tang (HQJZ) is a representative prescription used for clinical treatment of chronic atrophic gastritis (CAG) in Chinese medicine. Our previous study had revealed that energy regulation was one of the important mechanisms of HQJZ action against CAG. In this study, ultra-high-performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry (UHPLC-Q-Exactive MS) based metabonomics was used to find the potential mitochondrial biomarkers and metabolic pathways of HQJZ in CAG rats, which focused on a specific organelle (mitochondria) isolated from gastric tissue samples. A total of 16 biomarkers from CAG tissues were identified with 11 of these significantly regulated by HQJZ treatment. These biomarkers was mainly involved in glycine, serine, and threonine metabolism; aminoacyl-tRNA biosynthesis metabolism; and taurine and hypotaurine metabolism. Our results show that HQJZ could protect from CAG by altering the mitochondrial function. These findings deepen our understanding of the mitochondrial metabolic changes that occur with CAG and shine a light on the mechanism of HQJZ.

Effect of Auricularia auricula fermentation broth on the liver and stomach of mice with acute alcoholism.

In this paper, the protective effect of Auricularia auricula (A. auricula) fermentation broth on the liver and stomach of mice with acute alcoholism was studied. The A. auricula fermentation broth was prepared by adding Bacillus subtilis, lactic acid bacteria, and Saccharomyces cerevisiae to A. auricula solution. The changes of physical and chemical indexes during the fermentation of A. auricula were monitored, and the results showed the content of polysaccharides and protein in the two kinds of fermentation broth after the fermentation was completed. Furthermore, the characteristic structures of active substances such as proteins, polysaccharides and phenolics were found in the A. auricula fermentation by structural analysis. Antioxidant activity test results showed that the A. auricula fermentation broth had a strong ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals. Cell experiments showed that the fermentation broth of A. auricula could significantly enhance the activity of NRK cells and protect NRK cells from H2O2 damage. Animal experiments showed that the A. auricula fermentation broth had protective effects on the liver and stomach of mice with acute alcoholism, and significantly reduced the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC) and triglycerides (TG) in serum. These results indicated that the A. auricula fermentation broth had protective effects on the liver and stomach of mice with acute alcoholism, and could be used as a potential functional food to prevent liver and stomach damage caused by acute alcoholism.

Long-term consumption of recycled cooking oil induces cell death and tissue damage.

Recycled cooking oil (RCO) is widely used in many small restaurants. However, the health risk posed by long-term consumption of RCO is unclear. In this study, C57 mice were treated with RCO for 34 weeks. Organ coefficients of the liver, stomach, and kidney were found to be decreased. H&E staining revealed overt lesions in the pancreas, liver, kidney, esophagus, duodenum, and ileum of RCO-treated mice. Immunohistochemistry showed significant DNA damage in the duodenum and ileum and apoptosis in the lungs of the RCO-treated mice. Immunoblotting showed elevated levels of γ-H2AX, Bcl-2/Bax, TNFα, cleaved Caspase-3 and poly ADP-ribose polymerase (PARP). Increased levels of lactate dehydrogenase (LDH) and decreased levels of succinate dehydrogenase (SDH) were also detected. These findings suggest that long-term consumption of RCO produces various toxicities in mice with important implications for humans. DNA damage followed by mitochondria-associated apoptosis, and necrosis is likely to contribute to the toxicities.