8.2.5 Magen-Darm-Kanal

This investigation explored the impact of dietary frankincense resin oil (FO) on growth performance parameters, intestinal histomorphology, fatty acid composition of the breast muscle, and the immune status of broilers. We allotted 400, three-day-old, male chicks (Ross 308 broiler) into four treatment groups (ten replicates/group; ten chicks/replicate). They were fed a basal diet with different concentrations of FO (0, 200, 400, and 600 mg kg). FO supplementation increased the overall body weight (BW) and body weight gain (BWG) by different amounts, linearly improving the feed conversion ratio with the in-supplementation level. Total feed intake (TFI) was not affected. Growth hormones and total serum protein levels also linearly increased with the FO level, while albumin was elevated in the FO600 group. Moreover, total globulins increased linearly in FO400 and FO600 treatment groups. Thyroxin hormone (T3 and T4) levels increased in all FO treatment groups without affecting glucose and leptin serum values. Different concentrations of FO supplementation in the diet increased the activities of Complement 3, lysozyme, and interleukin 10 levels in the serum. Dietary FO in broilers increased the total percentage of n-3 and n-6 fatty acids. It also increased the ratio of n-3 to n-6 linearly and quadratically. Additionally, FO supplementation led to the upregulation of immune clusters of differentiation 3 and 20 (CD3 and CD20) in the spleen, along with improving most of the morphometric measures of the small intestine. In conclusion, FO up to 600 mg kg as a feed additive in broiler chicken production is valuable for promoting their growth, intestinal histomorphology, and immune status along with enriching breast muscle with polyunsaturated fatty acids (PUFA).

Hemorrhoidal disease is a widespread proctologic clinical entity. Even if surgical excision is an effective treatment, it only represents the standard procedure for patients with high-grade hemorrhoids. Considering that most cases are grade I or II hemorrhoids, oral or topical therapies are widely used despite, currently, there are no satisfactory options for these kinds of treatments. The pathology involves the degeneration of the supporting tissue of the anal cushions, causing venous dilation, blood stagnation, formation of edematous venous plexus covered by mucosa and inflammation. An effective treatment must, therefore, be multi-targeted and capable of acting on all the pathological mechanisms simultaneously. During the 8th National Congress of the Italian Association of Colorectal Surgery (SICCR), some clinical evidence of hemorrhoidal disease has been discussed along with new opportunities in oral and topical treatment options. Among these, the effectiveness and the safety of two innovative products, a sublingual nanoemulsion and a liquid bandage, has been reported.

BACKGROUND: Some substances of plant origin have been reported to exert an effect in reducing intestinal neoplasm development, especially in animal models. Adenomatous polyposis coli multiple intestinal neoplasia - Apc is the most studied murine model of genetic intestinal carcinogenesis.

AIM: To assess whether an enriched nutritional formulation (silymarin, boswellic acid and curcumin) with proven and anti-carcinogenetic properties may prevent inherited intestinal cancer in animal model.

METHODS: Forty adenomatous polyposis coli multiple intestinal neoplasia - Apc mice were used for the study of cancer prevention. They were divided into two groups: 20 assumed standard and 20 enriched diet. At the 110 d animals were sacrificed. In each group, four subgroups received intraperitoneal bromodeoxyuridine injection at different times (24, 48, 72 and 96 h before the sacrifice) in order to assess epithelial turnover. Moreover, we evaluated the following parameters: Intestinal polypoid lesion number and size on autoptic tissue, dysplasia and neoplasia areas by histological examination of the whole small intestine, inflammation by histology and cytokine mRNA expression by real-time polymerase chain reaction, bromodeoxyuridine and TUNEL immuno-fluorescence for epithelial turnover and apoptosis, respectively. Additionally, we performed western blotting analysis for the expression of estrogen alpha and beta receptors, cyclin D1 and cleaved caspase 3 in normal and polypoid tissues.

RESULTS: Compared to standard, enriched diet reduced the total number (203 416) and the mean ± SD/animal (12.6 ± 5.0 26.0 ± 8.8; < 0.001) of polypoid lesions. In enriched diet group a reduction in polyp size was observed ( < 0.001). Histological inflammation and pro-inflammatory cytokine expression were similar in both groups. Areas of low-grade dysplasia ( < 0.001) and intestinal carcinoma (IC; < 0.001) were significantly decreased in enriched diet group. IC was observed in 100% in standard and 85% in enriched formulation assuming animals. Enriched diet showed a faster epithelial migration and an increased apoptosis in normal mucosa and low-grade dysplasia areas ( < 0.001). At western blotting, estrogen receptor beta protein was well expressed in normal mucosa of enriched and standard groups, with a more marked trend associated to the first one. Estrogen receptor alpha was similarly expressed in normal and polypoid mucosa of standard and enriched diet group. Cleaved caspase 3 showed in normal mucosa a stronger signal in enriched than in standard diet. Cyclin D1 was more expressed in standard than enriched diet group of both normal and polypoid tissue.

CONCLUSION: Our results are suggestive of a chemo-preventive synergic effect of the components (silymarin, boswellic acid and curcumin) of an enriched formulation in inherited IC. This effect may be mediated by the reduction of epithelial proliferation, the increase of apoptosis and the acceleration of villous cell renewal due to dietary formulation intake.

Abdominal pain is a frequent symptom of irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBDs). Although the knowledge of these pathologies is progressing, new therapeutic strategies continue to be investigated. In the present study, the effect of a system of molecules of natural origin (a medical device according to EU Directive 93/42/EC, engineered starting from resins, polysaccharides and and polyphenols) was evaluated against the intestinal damage and visceral pain development in DNBS-induced colitis model in rats. The system (250 and 500 mg kg) was orally administered once daily, starting three days before the injection of 2,4-dinitrobenzenesulfonic acid (DNBS) and for 14 days thereafter. The viscero-motor response (VMR) to colon-rectal balloon distension (CRD) was used as measure of visceral sensitivity. The product significantly reduced the VMR of DNBS-treated animals. Its effect on pain threshold was better than dexamethasone and mesalazine, and not lower than amitriptyline and otilonium bromide. At microscopic and macroscopic level, the tested system was more effective in protecting the intestinal mucosa than dexamethasone and mesalazine, promoting the healing of tissue lesions. Therefore, we suggest that the described system of molecules of natural origin may represent a therapeutic option to manage painful bowel diseases.

The oral epithelium represents a major interface between an organism and its external environment. Improving this barrier at the molecular level can provide an organism added protection from microbial-based diseases. Barrier function of the Gie-3B11-human-gingival-epithelial-cell-culture model is enhanced by the micronutrients zinc, quercetin, retinoic acid, and acetyl-11-keto-β-boswellic acid, as observed by a concentration-dependent increase in transepithelial electrical resistance and a decrease in transepithelial C-d-mannitol permeability. With this improvement of tight-junction (TJ)-barrier function (reduced leak) comes a pattern of micronutrient-induced changes in TJ claudin abundance that is specific to each individual micronutrient, along with changes in claudin subcellular localization. These micronutrients were effective not only when administered to both cell surfaces simultaneously but also when administered to the apical surface alone, the surface to which the micronutrients would be presented in routine clinical use. The biomedical implications of micronutrient enhancement of the oral-epithelial barrier are discussed.

The use of herbal therapy for inflammatory bowel disease is increasing worldwide. The aim of this study was to review the available literature on the efficacy of herbal therapy in experimental colitis. All relevant studies published in Medline and Embase up to June 2015 have been reviewed. The results of bowel histology and serum parameters have been recorded. A satisfactory number of published experimental studies, and a quite large one of both herbal and plant products tested in different studies have been reported. The results showed that in the majority of the studies, herbal therapy reduced the inflammatory activity of experimental colitis and diminished the levels of many inflammatory indices, including serum cytokines and indices of oxidative stress. The most promising plant and herbal products were tormentil extracts, wormwoodherb, Aloe vera, germinated barley foodstuff, curcumin, Boswellia serrata, Panax notoginseng, Ixeris dentata, green tea, Cordia dichotoma, Plantago lanceolata, Iridoidglycosides, and mastic gum. Herbal therapies exert their therapeutic benefit via various mechanisms, including immune regulation, anti-oxidant activity, inhibition of leukotriene B4 and nuclear factor-κB, and antiplatelet activity. Large, double-blind clinical studies assessing these natural substances should be urgently conducted.

OBJECTIVES: The purpose of this study was to assess the gastroprotective properties of alpha-boswellic acid (α-BA), a pentacyclic triterpene compound from extracts of Frankincense.

METHODS: The gastroprotection of α-BA was assessed with ethanol-induced gastric lesions model, by histopathological assessment and measuring gastric juice acidity (pH), gastric wall mucus (GWM), prostaglandins E2 (PGE-2), membrane lipids peroxidation (MDA), superoxide dismutase (SOD) activity, catalase (CAT) activity and amount of nitric oxide (NO). The gastroprotective effects of α-BA through the nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) anti-oxidative pathway were presented and measured by immunohistochemistry and Western blot.

KEY FINDINGS: The results showed that α-BA reduced injuries associated with the administration of ethanol, gastric juice acidity and the formation of MDA and increased CAT activity and SOD activity and the level of NO and PGE-2 in a dose-depended manner. The expression of both Nrf2 and HO-1 was significantly increased in the group treated with 200 mg/kg α-BA, which suggested that activation of the Nrf2/HO-1 pathway might be critical in α-BA's prevention of gastric ulcers.

CONCLUSIONS: These findings demonstrate that α-BA decreases oxidative stress and that the Nrf2/HO-1 pathway might play a role in the gastroprotective action of α-BA in ethanol-induced gastric injury in rats.

Eight new cembranoids, boscartins A-H (1, 2, and 4-9), and the known incensole oxide were isolated from the gum resin of Boswellia carterii. The absolute configurations of 1, 2, 4, and incensole oxide were unequivocally resolved using single-crystal X-ray diffraction analysis with Cu Kα radiation, and the absolute configuration of 5 was resolved via electronic circular dichroism data. The antiulcerative colitis activities of the compounds were evaluated in an in vitro x-box-binding protein 1 (XBP 1) transcriptional activity assay using dual luciferase reporter detection. At 10 μM, compounds 1, 5, 6, and 7 significantly activated XBP 1 transcription with EC50 values of 0.34, 1.14, 0.88, and 0.42 μM, respectively, compared with the pGL3-basic vector control.

Currently available anti-ulcer drugs suffer from serious side effects which limited their uses and prompted the need to search for a safe and efficient new anti-ulcer agent. Boswellia gum resin (BR) emerged as a safe, efficient, natural, and economic potential cytoprotective agent. Thus, it is of medical importance to develop gastroretentive (GR) formulations of BR to enhance its bioavailability and anti-ulcer efficacy. Early attempts involved the use of organic solvents and non-applicability to large-scale production. In this study, different tablet formulations were prepared by simple direct compression combining floating and bioadhesion mechanisms employing hydroxypropyl methylcellulose (HPMC), sodium carboxymethyl cellulose (SCMC), pectin (PC), and/or carbopol (CP) as bioadhesive polymers and sodium bicarbonate (SB) as a gas former. The prepared tablets were subjected for assessment of swelling, floating, bioadhesion, and drug release in 0.1 N HCl. The optimized GR formulation was examined for its protective effect on the gastric ulcer induced by indomethacin in albino rabbits compared with lactose tablets. The obtained results disclosed that swelling, floating, bioadhesion, and drug release of the GR tablets of BR depend mainly on the nature of the matrix and the ratio of polymer combinations. Moreover, a combination of SCMC-CP in a ratio of 2:1 (SCP21) exhibited desirable floating, bioadhesion, swelling, and extended drug release. Also, a 6-h pretreatment with SCP21 tablets decreased the severity of inflammation and number of bleeding spots among ulcer-induced rabbits in comparison to those treated with lactose tablets.

Aminosalicylates, corticosteroids and immunosuppressants are currently the therapeutic choices in inflammatory bowel diseases (IBD), however, with limited remission and often serious side effects. Meanwhile complementary and alternative medicine (CAM) use is increasing, particularly herbal medicine. Boswellia serrata is a traditional Ayurvedic remedy with anti-inflammatory properties, of interest for its usefulness in IBDs. The mechanism of this pharmacological potential of Boswellia serrata was investigated in colonic epithelial cell monolayers exposed to H2O2 or INF-γ+TNF-α, chosen as in vitro experimental model of intestinal inflammation. The barrier function was evaluated by the transepithelial electrical resistance (TEER) and paracellular permeability assay, and by the tight junction proteins (zonula occludens-1, ZO-1 and occludin) immunofluorescence. The expression of phosphorylated NF-κB and reactive oxygen species (ROS) generation were determined by immunoblot and cytofluorimetric assay, respectively. Boswellia serrata oleo-gum extract (BSE) and its pure derivative acetyl-11-keto-β-boswellic acid (AKBA), were tested at 0.1-10 μg/ml and 0.027 μg/ml, respectively. BSE and AKBA safety was demonstrated by no alteration of intestinal cell viability and barrier function and integrity biomarkers. H2O2 or INF-γ+TNF-α treatment of Caco-2 cell monolayers significantly reduced TEER, increased paracellular permeability and caused the disassembly of tight junction proteins occludin and ZO-1. BSE and AKBA pretreatment significantly prevented functional and morphological alterations and also the NF-κB phosphorylation induced by the inflammatory stimuli. At the same concentrations BSE and AKBA counteracted the increase of ROS caused by H2O2 exposure. Data showed the positive correlation of the antioxidant activity with the mechanism involved in the physiologic maintenance of the integrity and function of the intestinal epithelium. This study elucidates the pharmacological mechanisms mediated by BSE, in protecting intestinal epithelial barrier from inflammatory damage and supports its use as safe adjuvant in patients affected by IBD.

(BC) Birdwood oleogum resin is an ancient remedy of inflammation processes known since Ancient Egyptian time. Of boswellic acids, 3-acetyl-11-keto-β-boswellic acid (AKBA) is the most potent anti-inflammatory active principle. Liquisolid systems of the biologically active fraction of BC oleogum resin were prepared for improving dissolution properties using low dose oral delivery to achieve enhanced anti-inflammatory activity, in comparison with the standard oral anti-inflammatory; Indomethacin. AKBA was assayed, employing an accurate and sensitive HPLC method. Detection was carried out at 210 nm using UV/Vis detector. A solubility study for the bioactive fraction was conducted. Microcrystalline cellulose and Aeroperl®300 Pharma were used as carrier and coating materials. Angle of slide, liquid load factor and Carr's flow index were estimated. Six systems were prepared using polyethylene glycol 400, solvent and two drug loading concentrations; 20 and 40 %. For each concentration, three carrier: coat ratios were dispensed; 20:1, 10:1, and 5:1. Dissolution study was performed and two systems were selected for characterization and in vivo evaluation by investigating upper GIT ulcerogenic effect and anti-inflammatory efficacy in rats. Results indicate absence of ulcers and significantly higher and prolonged anti-inflammatory efficacy for formulations F1 and F2, with carrier: coat ratio, 5:1 and drug loads of 20 and 40 %, respectively, compared with standard oral indomethacin. We conclude higher efficacy of BC bioactive fraction liquisolids compared with Indomethacin with greater safety on GIT, longer duration of action and hence better patient compliance.

CONTEXT: The water extract of Boswellia sacra Flueck. (Burseraceae) is used in the treatment of gastric and hepatic disorders in the Arab countries.

OBJECTIVE: The effect of Boswellia sacra water extract on gastric secretion and experimentally induced gastric ulcers in rats was studied.

MATERIALS AND METHODS: Acetic acid-induced chronic gastric ulcers, pylorus ligation, aspirin-induced, ethanol-induced, and restraint plus cold stress-induced gastric ulcer models were employed. The effect on normal rats was also studied. The water extract of B. sacra was administered orally at doses of 2 and 5 ml/kg once daily ranging from single dose to 30 d treatment depending on the model. The extract was subjected to GC-MS analysis to determine the presence of various phytoconstituents.

RESULTS: Boswellia sacra water extract (5 ml/kg, p.o (per os)) aggravated acetic acid-induced chronic ulcers, wherein an increase in ulcer index (p < 0.01) and ulcer score (p < 0.05) was observed. In pylorus-ligated rats, the extract increased gastric content volume (p < 0.01), free acidity (p < 0.01), total acidity (p < 0.01), ulcer index (p < 0.01), and pepsin activity (p < 0.05). There was no significant effect on the development of ethanol-induced and aspirin-induced ulcers while an increase in the development of stress-induced ulcers was observed (p < 0.01). The extract did not produce any ulcers when administered to normal rats. The dose of 2 ml/kg was less proulcerogenic compared with 5 ml/kg. The GC-MS analysis revealed the presence of several phytoconstituents that included menthol, 3-cyclohexen-1-ol, and octanoic acid.

CONCLUSION: Boswellia sacra water extract has proulcerogenic activity due to its gastric hypersecretory effect.

AIM OF THE STUDY: To evaluate the antioxidant effect of an extract of the plant Boswellia serrata in an experimental model of acute ulcerative colitis induced by administration of acetic acid (AA) in rats.

MATERIALS AND METHODS: The extract of B. serrata (34.2 mg/kg/day) was administered orally by gavage for 2 days before and after induction of colitis with AA diluted to 4 % and in a volume of 4 ml.

RESULTS: The anal sphincter pressure in the groups treated with B. serrata showed a significant increase compared to the colitis group (P < 0.001). Histological analysis of treated animals showed less edema with preservation of mucosal crypts. Lipid peroxidation showed a significant decrease in the treated groups compared to the colitis group (P < 0.001). The superoxide dismutase (SOD) enzyme activity showed a significant reduction in the treated groups compared to the colitis group (P < 0.001), the glutathione peroxidase (GPx) significantly increased in the treated groups compared to colitis group (P < 0.05), and the same was the result for enzyme activity glutathione (GSH; P < 0.05).

CONCLUSIONS: The extract of B. serrata has active antioxidant substances that exert protective effects in acute experimental colitis.

The methanolic extracts of 20 medicinal plants from the island Soqotra/Yemen were screened with respect to their inhibitory potency against angiotensin converting enzyme (ACE), neutral endopeptidase (NEP) and aminopeptidase N (APN). Eight extracts did not show significant inhibitory activity against the enzymes tested, only Kalanchoe farinacea, Boswellia elongata and Cissus hamaderohensis inhibited all three enzymes. The most active extract was prepared from Kalanchoe farinacea characterized by low IC50 values especially for NEP and APN.

Clinical studies suggest that the Ayurvedic plant Boswellia serrata may be effective in reducing diarrhoea in patients with inflammatory bowel disease. In the present study, we evaluated the effect of a Boswellia serrata gum resin extract (BSE) on intestinal motility and diarrhoea in rodents. BSE depressed electrically-, acetylcholine-, and barium chloride-induced contractions in the isolated guinea-pig ileum, being more potent in inhibiting the contractions induced by acetylcholine and barium chloride. The inhibitory effect of BSE on acetylcholine-induced contractions was reduced by the L-type Ca(2+) channel blockers verapamil and nifedipine, but not by the sarcoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid, by the phosphodiesterase type IV inhibitor rolipram or by the lipoxygenase inhibitor zileuton. 3-acetyl-11-keto-beta-boswellic acid, one of the main active ingredients of B. serrata, inhibited acetylcholine-induced contractions. BSE inhibited upper gastrointestinal transit in croton oil-treated mice as well as castor oil-induced diarrhoea. However, BSE did not affect intestinal motility in control mice, both in the small and in the large intestine. It is concluded that BSE directly inhibits intestinal motility with a mechanism involving L-type Ca(2+) channels. BSE prevents diarrhoea and normalizes intestinal motility in pathophysiological states without slowing the rate of transit in control animals. These results could explain, at least in part, the clinical efficacy of this Ayurvedic remedy in reducing diarrhoea in patients with inflammatory bowel disease.