Cannabinoids and their receptors play a significant role in the regulation of gastrointestinal (GIT) peristalsis and intestinal barrier permeability. This review critically evaluates current ...knowledge about the mechanisms of action and biological effects of endocannabinoids and phytocannabinoids on GIT functions and the potential therapeutic applications of these compounds. The results of ex vivo and in vivo preclinical data indicate that cannabinoids can both inhibit and stimulate gut peristalsis, depending on various factors. Endocannabinoids affect peristalsis in a cannabinoid (CB) receptor-specific manner; however, there is also an important interaction between them and the transient receptor potential cation channel subfamily V member 1 (TRPV1) system. Phytocannabinoids such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) impact gut motility mainly through the CB1 receptor. They were also found to improve intestinal barrier integrity, mainly through CB1 receptor stimulation but also via protein kinase A (PKA), mitogen-associated protein kinase (MAPK), and adenylyl cyclase signaling pathways, as well as by influencing the expression of tight junction (TJ) proteins. The anti-inflammatory effects of cannabinoids in GIT disorders are postulated to occur by the lowering of inflammatory factors such as myeloperoxidase (MPO) activity and regulation of cytokine levels. In conclusion, there is a prospect of utilizing cannabinoids as components of therapy for GIT disorders.
Melissa officinalis (lemon balm) has a long history of being used in traditional medicine for the treatment of gastrointestinal tract disorders in human thanks to its spasmolytic and stress reducing ...effects. These pharmacological properties have been confirmed in laboratory animals. Unfortunately, in the case of veterinary medicine, the effect of lemon balm on gut contractility has been never subjected to a detailed investigation. On the other hand, there is urgent need of new drugs that could be safely used in animals for both, causative and symptomatic treatment. In broiler chicken, one of the major health concerns includes gastrointestinal disorders with gut hypermotility. Thus, it is crucial to verify the potential utility of Melissa officinalis extract in gastrointestinal dysmotilities. The aim of the study was to analyze the effect of lemon balm extract and some of its active ingredients on chicken intestine motility. The study was performed on isolated proximal and distal jejunum preparations collected from broiler chicken which underwent routine slaughter procedure. The effect of lemon balm and 3 phenolic acids (rosmarinic, chlorogenic, and lithospermic) was verified under isometric conditions, toward spontaneous and acetylcholine (ACh)-induced smooth muscle activity. Surprisingly, M. officinalis turned out to be rather a myocontractile agent as it increased ACh-provoked contractility of proximal and distal jejunum strips and also intensified the spontaneous activity of distal jejunum. Only in the case of proximal intestine lemon balm extract diminished the force of spontaneous motoric activity up to approx. Sixty-seven percent of the control conditions. None of the tested phenolic acids displayed analog effect with the whole plant extract. In fact in the case of ACh-induced contractility, the acids had the opposite, that is, myorelaxant, effect than the extract, with a small exception of lithospermic acid in distal jejunum. Thus, it is impossible to assign one or more individual constituents to the effect of the whole Melissa officinalis extract. The obtained results do not support the use of lemon balm extract in broiler diseases which are accompanied by gut motility disturbances, including diarrhea.
For centuries, various species from the genus
have been utilized in traditional medicine worldwide. A number of ethnopharmacological reports have pointed out that
plants can be applied to diminish ...digestive problems. Among them,
(L.) Scop. (Asteraceae) stands out as a promising herbal drug candidate because its constituents exhibit antimicrobial and antioxidant potential, as evidenced by ethnopharmacological reports. As a result, the species is particularly intriguing as an adjunctive therapy for functional gastrointestinal and motility disorders. Our research goal was to verify how the extracts, fractions, and main flavonoids of
affect colon contractility under ex vivo conditions. An alternative model with porcine-isolated colon specimens was used to identify the effects of
preparations and their primary flavonoids. LC-ESI-MS was utilized to evaluate the impacts of methanol (CP1), methanolic 50% (CP2), and aqueous (CP3) extracts as well as diethyl ether (CP4), ethyl acetate (CP5), and
-butanol (CP6) fractions. Additionally, the impacts of four flavonoids, apigenin (API), luteolin (LUT), apigenin 7-
-glucuronide (A7GLC), and chrysoeriol (CHRY), on spontaneous and acetylcholine-induced motility were assessed under isometric conditions. The results showed that
extracts, fractions, and their flavonoids exhibit potent motility-regulating effects on colonic smooth muscle. The motility-regulating effect was observed on spontaneous and acetylcholine-induced contractility. All extracts and fractions exhibited an enhancement of the spontaneous contractility of colonic smooth muscle. For acetylcholine-induced activity, CP1, CP2, and CP4 caused a spasmolytic effect, and CP5 and CP6 had a spasmodic effect. LUT and CHRY showed a spasmolytic effect in the case of spontaneous and acetylcholine-induced activity. In contrast, API and A7GLC showed a contractile effect in the case of spontaneous and pharmacologically induced activity. Considering the results obtained from the study,
could potentially provide benefits in the treatment of functional gastrointestinal disorders characterized by hypomotility and hypermotility.
The presence of deoxynivalenol (DON) in feed may increase intestinal barrier permeability. Disturbance of the intestinal barrier integrity may affect the absorption of antibiotics used in animals. ...Since the bioavailability of orally administered antibiotics significantly affects their efficacy and safety, it was decided to evaluate how DON influences the absorption of the most commonly used antibiotics in pigs, i.e., amoxicillin (AMX) and doxycycline (DOX). The studies were conducted using jejunal explants from adult pigs. Explants were incubated in Ussing chambers, in which a buffer containing DON (30 µg/mL), AMX (50 µg/mL), DOX (30 µg/mL), a combination of AMX + DON, or a combination of DOX + DON was used. Changes in transepithelial electrical resistance (TEER), the flux of transcellular and intracellular transport markers, and the flux of antibiotics across explants were measured. DON increased the permeability of small intestine explants, expressed by a reduction in TEER and an intensification of transcellular marker transport. DON did not affect AMX transport, but it accelerated DOX transport by approximately five times. The results suggest that DON inhibits the efflux transport of DOX to the intestinal lumen, and thus significantly changes its absorption from the gastrointestinal tract.
Due to the growing interest in the use of cannabinoids in supportive therapies, they are increasingly used together with anti-inflammatory drugs. Cannabinoids inhibit gastrointestinal motility, while ...steroidal and nonsteroidal anti-inflammatory drugs influence motility in other ways. The aim of the research was to study the interactions between cannabidiol (CBD) and these two classes of anti-inflammatory drugs in the context of gastrointestinal motility. Dexamethasone (DEX) was selected as a steroidal drug and diclofenac (DCF) as a nonsteroidal counterpart.
The experiments were performed on isolated rat colon strips in isometric conditions. The contractile response to acetylcholine (ACh) (1 μM) was measured with no substance applied as a control value and was measured after application of CBD (80 μM), DEX (100 μM), DCF (100 μM), or a combination of these substances.
Cannabidiol strongly inhibited intestinal motility mediated by ACh application, DCF inhibited it non-significantly, while DEX intensified it. When CBD was co-administered with DEX, the combination inhibited intestinal motility non-significantly relative to the ACh-only control. Co-administration of CBD with DCF inhibited motility more than when these substances were administered separately.
Inhibition of the intestinal response to ACh is likely due to the synergistic effect of CBD and endogenous cannabinoids. Dexamethasone lessened the inhibitory effect of CBD, likely because of diminished availability of the arachidonic acid necessary for endogenous cannabinoid synthesis. However, diclofenac may increase endogenous cannabinoid synthesis, because of the greater availability of arachidonic acid caused by DCF blocking the cyclooxygenation pathway.
Abstract
After the European Union ban of antibiotic growth promoters, works on different methods of improving gut health have intensified. The poultry industry is struggling with problems that were ...previously controlled by antibiotic growth promoters, therefore the search for optimal solutions continues. Simultaneously, there is also increasing social pressure to minimize the use of antibiotics and replace them with alternative feed additives. A variety of available alternatives is considered safe by consumers, among which phytogenics play a significant role. However, there are still some limitations that need to be considered. The most questionable are the issues related to bioavailability, metabolism of plant derivatives in birds, and the difficulty of standardizing commercial products. There is still a need for more evidence-based recommendations for the use of phytogenics in livestock. On the other hand, a positive influence of phytogenic compounds on the health of poultry
has been previously described by many researchers and practical application of these compounds has auspicious perspectives in poultry production. Supplementation with phytogenic feed additives has been shown to protect birds from various environmental threats leading to impaired intestinal barrier function. Phytogenic feed additives have the potential to improve the overall structure of intestinal mucosa as well as gut barrier function on a molecular level. Recognition of the phytogenicsʼ effect on the components of the intestinal barrier may enable the selection of the most suitable ones to alleviate negative effects of different agents. This review aims to summarize current knowledge of the influence of various phytogenic constituents on the intestinal barrier and health of poultry.
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•Plant secondary metabolites (PSM) are often applied phytogenic feed additives.•The effects of PSM and plants extracts on ruminants gut motility are summarized.•Essential oils, ...tannins and saponins are the object of the review.•The review reveals the predominant myorelaxant effect of analyzed PSM.•The effect of PSM on gut motility must be realized while introducing feed additives.
The increasing requirement for implementing new feed additives in livestock, especially ruminants, results predominantly from two issues: the urgent need of reduction of greenhouse gas emissions and the necessity of finding replacements of antibiotics which must not be preventively used in animals feeding. A group of additives that has gained a progressive interest in recent years consists of plant secondary metabolites and plant-derived extracts. There is extensive knowledge of the effects of phytogenic feed additives on rumen microbial fermentation, rumen methanogenesis and ruminant performance. However, there is little information about their systemic effects. In case of ruminants, the possible impact of employed additives on gut motility should be carefully analyzed due to the special anatomical and physiological features. Therefore, the aim of this review is to present available data on the effects of plant extracts and individual secondary plant metabolites which can be potentially used as feed additives on gastrointestinal motility. The review describes the impact of essential oils, tannins and saponins on gut smooth muscle activity in laboratory animals and livestock, particularly ruminants, under in vivo and in vitro conditions The analysis of gathered data allows to generalize that most essential oils, tannins and saponins which are under consideration as phytogenic feed additives generate myorelaxant effects towards gastrointestinal tissues. Significant antispasmodic effects of plant secondary metabolites can reduce the gastrointestinal smooth muscle basal tone and cause an impaired response of rumen and abomasal muscles to acetylcholine which reflect hypotony and subsequently predispose the animals to some gut disturbances, like abomasal displacement or rotation, and or indigestion. On the other hand, the revealed ability of various plant extracts to reduce acetylcholine-induced contraction could be used to contract gastrointestinal muscle spasm and consequently become beneficial in animals with diarrhea symptoms. Noteworthy, essential oils of numerous plants turned out to act spasmogenic if used in low doses and spasmolytic whenever tested in higher concentrations. This dual character of essential oils should be further analyzed and possible used to treat or prevent hypo- and hypermotility disorders.
Bearing in mind, the process of gut microorganisms’ adaptation and their ability to decompose or neutralize various substances, including plant secondary metabolites, the effects of plant-derives substances on gastrointestinal motoric activity are especially expected in a short time after the introduction of a new phytocompound or plant extract to animal feed.
The application of pyriproxyfen (PPF) to drinking water and constant exposure of the whole population to this insecticide is an unprecedented action on a world scale and presents a new and serious ...challenge for toxicology. The aim of the study was to evaluate the potential effect of PPF on the intestine muscle activity. The experiments were performed on isolated duodenum and jejunum strips of rat, in isometric conditions. Doses of PPF in the range of 0.032–100 μM were used in the experiments. The obtained results indicate that PPF affected significantly the spontaneous activity of duodenum and jejunum strips, PPF caused the muscle relaxation when used in the concentration of 0.8 μM and higher. The reaction to acetylcholine (ACh) when PPF preceded or followed ACh application was also reduced. It is demonstrated that the reduction of the contraction caused by ACh was stronger when duodenum strips were preincubated in the presence of PPF solution than in case of ACh-precontracted strips. The first significant reaction of duodenal strips appeared in the presence of PPF in a dose of 0.16 μM and 0.8 μM when the insecticide application preceded and followed ACh treatment, respectively. Besides, the duodenum turned out to be much more susceptible to the tested insecticide than jejunum. Taking into account PPF kinetic data obtained in animals, the observed disturbances were caused by the insecticide used in relatively high concentrations. However, the full risk estimation requires the kinetic data obtained in human, especially from monitoring studies on general population after long-term exposure to PPF.
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•Pyriproxyfen affects the activity of rats intestine under in vitro conditions.•Duodenum seems to be much more susceptible to this insecticide than jejunum.•Pyriproxyfen interacts probably with the intestine cholinergic pathway.•The disturbances are caused by relatively high concentrations of pyriproxyfen.
The article describes the effect of pyriproxyfen, an insecticide added to drinking-water, on the gut motility. The study was performed under in vitro conditions on rat isolated duodenum and jejunum segments.
Citrus flavonoids are acknowledged for numerous pharmacological activities, including the myorelaxant effect on various smooth muscles. However, there is no data on their effect on jejunum ...contractility. Therefore, the aim of the study at hand was to evaluate the impact of hesperetin and diosmetin along with their glycosides on the motoric activity of intestine and to verify the possible mechanism of hesperetin-induced effect. The experiments were performed on rat isolated jejunum strips and were conducted under isometric conditions.
Hesperetin and diosmetin, but not hesperidin and diosmin, dose-dependently (10–100µM) and reversibly inhibited acetylcholine (1µM) and KCl (80mM) induced contractile activity. The antispasmodic effect of hesperetin was partially blocked by 4-aminopyridine (100µM), glibenclamide (100µM) and NG-nitro-L-arginine methyl ester (L-NAME, 100µM). By contrast, apamin (0.1µM), tetraethylammonium (500µM) and methylene blue (10µM) did not affect the magnitude of hesperetin-induced myorelaxant effect. Indomethacin (10µM) increased the force of hesperetin-evoked reaction.
In conclusion, hesperetin and diosmetin are potent myorelaxant agents. The antispasmodic effect of hesperetin is partially mediated by fast current low-voltage activated K+ channels, voltage-independent K+ channels and involves the nitric oxide pathway. Finally, hesperetin shows a synergistic effect with indomethacin towards jejunal KCl-precontracted smooth muscle.
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