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Diarrhea continues to be one of the top causes of death in children under the age of five, particularly in developing nations. In Ethiopian traditional medicine, a variety of medicinal plants are used to treat diarrhea. One of these plants is Maytenus addat (Loes.) Sebsebe (fam. Celastraceae), which is endemic to the Afromontane forests, especially along forest margins, of Ethiopia. The air‐dried powdered leaves of M. addat were macerated with 80% methanol to yield a crude extract. Additionally, the powdered plant material underwent sequential solvent extraction using chloroform, methanol, and water to obtain solvent fractions. The 80% methanol leaf extract, solvent fractions, and an isolated compound from M. addat were evaluated for their antidiarrheal activity using castor oil‐induced diarrheal model, anti‐enteropooling test, and charcoal meal test in mice. The results showed that the 80% methanolic leaf extract significantly reduced the onset of diarrhea, the weight of feces, and the frequency of defecation in all the tested doses. The methanol and water fractions of the hydroalcoholic extract also exhibited dose‐dependent antidiarrheal activity, with the methanol fraction showing the highest activity at 400 mg/kg dose. Subsequently, the most active methanol fraction was subjected to C‐18 solid phase extraction, resulting in the isolation of a 3‐hydroxyflavone, identified as quercetin by ESI‐qToF‐MS, 1H, and 13C‐NMR spectroscopic techniques. Quercetin demonstrated a strong antidiarrheal activity in a dose‐dependent manner. Thus, the present study provided evidence that the leaves of M. addat possess genuine antidiarrheal activity upholding the traditional medicinal use of the plant for the treatment of diarrhea. The findings also suggest that quercetin is responsible, in full or in part, for the activity of the plant. [ABSTRACT FROM AUTHOR]

For centuries, various species from the genus Cirsium have been utilized in traditional medicine worldwide. A number of ethnopharmacological reports have pointed out that Cirsium plants can be applied to diminish digestive problems. Among them, Cirsium palustre (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 C. palustre affect colon contractility under ex vivo conditions. An alternative model with porcine-isolated colon specimens was used to identify the effects of C. palustre 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 n-butanol (CP6) fractions. Additionally, the impacts of four flavonoids, apigenin (API), luteolin (LUT), apigenin 7-O-glucuronide (A7GLC), and chrysoeriol (CHRY), on spontaneous and acetylcholine-induced motility were assessed under isometric conditions. The results showed that C. palustre 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, C. palustre could potentially provide benefits in the treatment of functional gastrointestinal disorders characterized by hypomotility and hypermotility. [ABSTRACT FROM AUTHOR]

In recent years, the scientific world has become more interested in genistein. It has been the subject of extensive research for its potential in treating various diseases and as a functional food. The medical benefits of genistein are well documented in the literature. Several studies have been performed to better understand the mechanisms of its beneficiary effects on health and to improve its pharmacokinetic and pharmacodynamic parameters. It has been approved for relieving menopausal symptoms and has received attention for its use in the treatment of inflammatory and age-related disorders, cancer, metabolic illnesses, genetic disorders, and skin care. Genistein shows considerable similarity to endogenous estradiol. It is classified in the group known as phytoestrogens exhibit properties corresponding to estrogen in the human body. The estrogenic activity resulting from the aforementioned similarity in the appearance of genistein and estradiol molecules makes it possible for genistein to act as both an estrogen agonist and antagonist, depending on the number of endogenous hormones present in the environment in which it is found and the type of tissue. The similarity of the chemical structure of genistein and estradiol and interactions occurring between estradiol and genistein and the amino acid binding site of the estrogen receptors were analyzed. Further controlled trials are needed to determine the efficacy and safety of genistein. Future research will focus on enhancing its bioavailability through structural modification and innovative delivery methods and conducting human trials to confirm its biological and pharmacological effects. [ABSTRACT FROM AUTHOR]

Functional gastrointestinal diseases (FGID) are worldwide prevalent conditions. Pharmacological treatments can be ineffective, leading the population to turn to herbal or traditional remedies. Helichrysum stoechas (L.) Moench is a medicinal plant traditionally used in the Iberian Peninsula to treat digestive disorders, but its effects on gastrointestinal motility have not been scientifically demonstrated. The aim of this work was to evaluate the antispasmodic effect of a polyphenolic extract of H. stoechas (HSM), its mechanism of action and its antioxidant activity. Isometric myography studies were performed in rat ileum, and malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) levels were measured in rat jejunum. HSM reduced the integrated mechanical activity of spontaneous contractions. In Ca2+-free medium, HSM reduced the concentration–response curve of CaCl2 similarly to verapamil. Pre-incubation with the extract blocked the contraction induced by Bay K8644, KCl and carbachol. L-NAME, ODQ, Rp-8-Br-PET-cGMPS, KT-5823, apamin, TRAM-34 and charybdotoxin reduced the relaxant effect of the extract on spontaneous contractions. MDA+4-HDA levels in LPS-treated tissue were reduced by the extract, showing antioxidant activity. In conclusion, HSM showed antispasmodic activity through inhibition of Ca2+ influx, activation of the NO/PKG/cGMP pathway and opening of Ca2+-activated K+ channels. The results suggest that H. stoechas could help in the prevention or treatment of FGIDs. [ABSTRACT FROM AUTHOR]

Background: Quercetin has recently become a remarkably popular subject of research due to its broad beneficial pharmacological properties. The goal of our study was to observe its effects on contractility of human gastric smooth muscles in reference to the NO pathway and direct influence of potassium channels. Methods: Tissues were obtained from patients undergoing sleeve gastrectomy due to morbid obesity (n = 10 aged 24–56; BMI 47.16 ± 1.84). The following parameters were evaluated in the recordings: area under the curve (AUC), average baseline muscle tone, and relative change in muscle contraction. Key Results: Quercetin induced noticeable, dose‐dependent relaxation of the carbachol treated gastric strips. The substantial effect was noted at concentrations higher than 10−7 mol/L and maximal at 10−4 mol/L (81.82 ± 3.32%; n = 10; p < 0.0001) of the control. Neither NOS blockers nor guanylyl cyclase blockers had inhibitory effects on the relaxation of strips induced by examined polyphenol. Glibenclamide inhibited the relaxing effect of quercetin, significant at concentrations higher than 5⋅10−5 mol/L. Preincubation with charybdotoxin or apamin extended the relaxing effect of quercetin (from 10−6 mol/L). Tamoxifen, in turn, significantly increased muscle relaxation at all quercetin concentrations. Conclusions & Inferences: In conclusion, the current study was the first to show that quercetin‐induced relaxation of human gastric smooth muscle occurs directly through K+ATP channels and independently to NO pathways. The present results suggest that quercetin is a potential nutraceutical in the treatment of functional gastrointestinal dyspepsia and other minor gastric muscle motility disturbance. [ABSTRACT FROM AUTHOR]

G's Formula is a novel equine feed additive formulated to promote optimal GI function. The objective of this study was to determine whether the addition of a simulated digest of the composite feed additive G's Formula (FA) would alter the contractile response of gastric smooth muscle to acetylcholine (Ach). Smooth muscle strips from porcine stomachs were excised and attached to an isometric force transducer. An experiment was run to compare tissue contraction between tissue exposed to FA (FA; n = 8, simulated digest of FA was added to the bath) and control tissue (CO; n = 8, no additions made). Increasing concentrations of Ach were added into the bath such that the concentration increased from 10–8–10−3 M. Based on the analysis of these data, a difference between FA and CO was observed. Therefore, another trial was run which included a blank group (BL n = 6) in which the tissue was exposed to the simulated digest without FA. More CO (n = 5) and FA (n = 4) tissue was also run. Force was compared to baseline and between groups. In FA group, mean force for 1‐min following all Ach additions was higher than baseline (p <.05) and by 2‐min the integral‐under‐force/time curve (AUC) was higher than baseline from 10–7–10−3 M compared to lower concentrations of Ach in both CO (10−6 M for both) and BL (10−5 M and 10−6 M, respectively). By 8‐min AUC of all Ach concentrations were higher than baseline in FA compared to an Ach of 10−6 M in both CO and BL. A simulated digest of FA appears to sensitize gastric smooth muscle to Ach in vitro. FA may increase GI contractility, and the functional effect of this should be studied further in vivo. [ABSTRACT FROM AUTHOR]

Radiation-induced gastrointestinal injury or radiation enteropathy is an imminent risk during radiation therapy of abdominal or pelvic tumors. Despite remarkable technological advancements in image-guided radiation delivery techniques, the risk of intestinal injury after radiotherapy for abdominal or pelvic cancers has not been completely eliminated. The irradiated intestine undergoes varying degrees of adverse structural and functional changes, which can result in transient or long-term complications. The risk of development of enteropathy depends on dose, fractionation, and quality of radiation. Moreover, the patients' medical condition, age, inter-individual sensitivity to radiation and size of the treatment area are also risk factors of radiation enteropathy. Therefore, strategies are needed to prevent radiotherapy-induced undesirable alteration in the gastrointestinal tract. Many natural plant products, by virtue of their plethora of biological activities, alleviate the adverse effects of radiation-induced injury. The current review discusses potential roles and possible mechanisms of natural plant products in suppressing radiation enteropathy. Natural plant products have the potential to suppress intestinal radiation toxicity. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study? Does the inhibition of the protein kinase casein kinase 2 (CK2) alter the uterine contractility? What is the main finding and its importance? Inhibition of CK2 impaired the spontaneous and oxytocin‐induced contractility in late pregnant mouse uterus. This finding suggests that CK2 is a novel pathway mediating oxytocin‐induced contractility in the uterus and thus opens up the possibility for this class of drugs to be developed as a new class of tocolytics. Abstract: The protein kinase casein kinase 2 (CK2) is a ubiquitously expressed serine or threonine kinase known to phosphorylate a number of substrates. The aim of this study was to assess the effect of CK2 inhibition on spontaneous and oxytocin‐induced uterine contractions in 19 day pregnant mice. The CK2 inhibitor CX‐4945 elicited a concentration‐dependent relaxation in late pregnant mouse uterus. CX‐4945 and another selective CK2 inhibitor, apigenin, also inhibited the oxytocin‐induced contractile response in late pregnant uterine tissue. Apigenin also blunted the prostaglandin F2α response, but CX‐4945 did not. Casein kinase 2 was located in the lipid raft fractions of the cell membrane, and disruption of lipid rafts was found to reverse its effect. The results of the present study suggest that CK2, located in lipid rafts of the cell membrane, is an active regulator of spontaneous and oxytocin‐induced uterine contractions in the late pregnant mouse. [ABSTRACT FROM AUTHOR]

Eight compounds were isolated from the seeds of Holarrhena antidysenterica Wall.ex A.DC. On the basis of physico-chemical properties and spectroscopic data, holarrhenanan (1) was identified as a new compound, compounds 2–3 were isolated from H. antidysenterica for the first time, and five known compounds were also obtained. Inhibitory effects of some compounds and extracts to the intestinal peristalsis were evaluated. Results showed that the extracts and compounds 4, 6 exhibited remarkable inhibitory effects with tension inhibition rate of 32.77, 32.77% and amplitude inhibition rate of 59.51, 55.98%, respectively on the vitro rabbit intestinal peristalsis. [ABSTRACT FROM AUTHOR]

Objective: Several studies have shown the antispasmodic activity of Matricaria recutita without detailing the underlying mechanism(s). The present study was designed to determine whether the antispasmodic mechanisms of M. recutita extract mediated via histaminergic/cholinergic receptors, Ca2+channels, activation of PKA2 and NO release in isolated rabbit jejunum. Materials and Methods: The concentration-dependent (3 × 10-3-1.3 × 10-2 mg/ml) antispasmodic effect of the hydro-alcoholic extract of M. recutita flowers was studied in isolated rabbit jejunum. The isolated jejunum preparations were divided into seven groups, including the pharmacological probes that modulate cholinergic, histaminergic, and nitrergic receptors, as well as PKA2. Results: M. recutita inhibited spontaneous smooth muscle contractility of the jejunum in a concentration-dependent manner (3 × 10-3-1.3 × 10-2 mg/ml) and reduced both K+- and Ca2+-induced contractions, which is similar to the effect of verapamil. The antispasmodic effect of M. recutita was inhibited by H89 (a PKA2 inhibitor). The myorelaxant effect of M. recutita increased in the presence of ACh/His and H89. Conclusion: M. recutita evoked antispasmodic and spasmolytic effects mediated through different signaling pathways. Our results have shown this dual inhibitory effect is mediated by blocking Ca2+ channels, activating His and ACh receptors, releasing NO, and activating PKA2. [ABSTRACT FROM AUTHOR]

Background: Quercetin regulates gastrointestinal (GI) motor activity but the molecular mechanism involved has not been determined. The authors investigated the effects of quercetin, a flavonoid present in various foods, on the pacemaker activities of interstitial cells of Cajal (ICCs) in murine small intestine in vitro and on GI motility in vivo. Materials and Methods: Enzymatic digestion was used to dissociate ICCs from mouse small intestines. The whole-cell patch-clamp configuration was used to record pacemaker potentials in cultured ICCs in the absence or presence of quercetin and to record membrane currents of transient receptor potential melastatin (TRPM) 7 or transmembrane protein 16A (Tmem16A, anoctamin1 (ANO1)) overexpressed in human embryonic kidney (HEK) 293 cells. The in vivo effects of quercetin on GI motility were investigated by measuring the intestinal transit rates (ITRs) of Evans blue in normal mice. Results: Quercetin (100-200 μM) decreased the amplitudes and frequencies of pacemaker activity in a concentration-dependent manner in current clamp mode, but this action was blocked by naloxone (a pan-opioid receptor antagonist) and by GDPβS (a GTP-binding protein inhibitor). However, potassium channels were not involved in these inhibitory effects of quercetin. To study the quercetin signaling pathway, we examined the effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of guanylate cyclase, and of RP-8-CPT-cGMPS, an inhibitor of protein kinase G (PKG). These inhibitors blocked the inhibitory effects of quercetin on pacemaker activities. Also, L-NAME (100 μM), a non-selective NO synthase (NOS) inhibitor, blocked the effects of quercetin on pacemaker activity and quercetin stimulated cGMP production. Furthermore, quercetin inhibited both Ca2+-activated Cl- channels (TMEM16A, ANO1) and TRPM7 channels. In vivo, quercetin (10-100 mg/kg, p.o.) decreased ITRs in normal mice in a dose-dependent manner. Conclusions: Quercetin inhibited ICC pacemaker activities by inhibiting TRPM7 and ANO1 via opioid receptor signaling pathways in cultured murine ICCs. The study shows quercetin attenuates GI tract motility, and suggests quercetin be considered the basis for the development of novel spasmolytic agents for the prevention or alleviation of GI motility dysfunctions. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Resveratrol (3,5,4l-trihydroxystilbene) is a polyphenolic compound (stilbene) and a phytoalexin. The purpose of this study was to determine the mechanism which mediated the resveratrol-induced relaxation of cholecystokinin octapeptide- or KCl-induced tension in male guinea pig gallbladder strips. Methods: Gallbladder strips were prepared and suspended in in vitro chambers filled with Krebs-Henseleit solution. The strips were attached to force displacement transducers, and the changes in tension were recorded on a polygraph. All reagents were added directly into the chambers. Results: To determine if intracellular Ca2+ release mediated the resveratrol-induced relaxation of cholecystokinin octapeptide-induced tension, 2-aminoethoxydiphenylborane (2-APB) was used. 2-APB significantly (P < 0.01) decreased the amount of RSVL-induced relaxation. To determine if protein kinase A (PKA) mediated the resveratrol-induced relaxation, PKA inhibitor 14-22 amide myristolated (PKA-IM) was used. PKA-IM had no effect on resveratrol-induced relaxation. Neither KT5823, NG-methyl-L-arginine acetate salt, a nitric oxide synthase inhibitor, nor fulvestrant had a significant effect on the amount of resveratrol-induced relaxation. Genistein, a protein tyrosine kinase inhibitor, significantly (P < 0.01) increased the RSVL-induced relaxation. To determine if protein kinase C mediated the RSVL-induced relaxation, the protein kinase C inhibitors bisindolymaleimide IV and chelerythrine Cl- were used together, and a significant (P < 0.05) increase in resveratrol-induced relaxation was observed. The pretreatment of the strips with resveratrol significantly (P < 0.001) decreased the amount of KCl- and cholecystokinin octapeptide- induced tension. Conclusions: Resveratrol-induced relaxation is mediated by its effects on L-type Ca2+ channels and intracellular Ca2+ release. [ABSTRACT FROM AUTHOR]

Flavonoids are widely distributed secondary metabolites and currently consumed in large amounts in the daily diet. In this article, some of the most recent developments in flavonoid - and related polyphenolic compounds - pharmacology are discussed, with particular emphasis on very recent data, most of which are published in Phytotherapy Research, which highlight new aspects in flavonoid anti-inflammatory, antilipidemic, antihyperglycemic, antiviral, hepatoprotective, gastric antiulcer, cardioprotective, neuroprotective, antioxidant and anticancer actions. These updated data confirm the well-established diverse beneficial pharmacological actions and might support the perspective for a therapeutic use. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Artemisia copaPhil. (Compositae) is used in popular medicine as a digestive and for gastric pains. The effects ofA. copaaqueous extract and its isolated compounds were evaluated on isolated rat jejunum. The extract inhibited non-competitively the cumulative concentration–response curves induced by acetylcholine and CaCl2. The tonic jejunum contractions induced by 80 mM KCl were inhibited byA. copa. Relaxant effects ofA. copaon the tonic contraction induced by 25 mM KCl, [EC50: 0.94 mg mL−1(0.64–1.39)], was not inhibited by glibenclamide, TEA, l-NAME or methylene blue. Chrysoeriol, spinacetin and luteolin (30 µg mL−1), produced an antagonism on the CaCl2concentration–response curve, showing an inhibition of the maximum contractions (70.0% ± 5.0%, 49.1% ± 4.5% and 77.0% ± 3.5% ofEmax, respectively), whereas tricin did not inhibit when the same concentration was used.A. copaexerts spasmolytic activity by blocking calcium channels and three isolated compounds could be, at least partly, responsible for the effect. [ABSTRACT FROM PUBLISHER]

The aim of this study was to investigate the effect of aerial parts of Stachys lavandulifolia Vahl. extract on the rat ileum contractions. The crude extract was prepared by maceration method (90% methanol) followed by fractionating into chloroform, ethyl acetate, petroleum ether and water. In adult male Wistar rats, ileum was sectioned and mounted in tissue bath and their contractility was recorded isotonically. KCl (60 mM)-induced ileum contractions were attenuated by crude extract and its fractions. The most potent fraction was chloroformic fraction (CF) with IC50 = 0.126 + 0.018 mg/mL. In calcium-free Tyrode solution with high K+, the CF (0.01 - 0.04 mg/mL) attenuated CaCl2-induced contractions (p < 0.001). The CF (0.05- 0.8 mg/mL) attenuated the carbachol-induced contraction (p<0.001). The CF antispasdomic effect was reduced by naloxone (as a non-selective opioid antagonist), not by propranolol and L-NAME as β-adrenoceptors antagonist and nitric oxide synthase inhibitor respectively. It was concluded that S. lavandulifolia can inhibit ileum contractility mainly via disturbing the calcium mobilization and partly by opioid receptors’ activation. Our results may support the traditional usage of this herb for treating diarrhea. [ABSTRACT FROM AUTHOR]

The article presents abstracts on pharmacology which include virus-transformed tumor cells as experimental models for the screening of new agents with antineoplastic properties, effect of selenium supplementation on lipid peroxidation in spontaneously hypertensive rats, and biological activity of newly synthesized aminopiperidinones with aminoacid and/or phosphonate radicals.

Dysmenorrhea is directly related to elevated PGF2α levels. It is treated with nonsteroid antiinflammatory drugs (NSAIDs) in Western medicine. Since NSAIDs produce many side effects, Chinese medicinal therapy is considered as a feasible alternative medicine. Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) has been used as a traditional Chinese medicine for treating dysmenorrhea. However, the relationship between smooth muscle contraction and adlay extracts remains veiled. Therefore, we investigated this relationship in the rat uterus by measuring uterine contraction activity and recording the intrauterine pressure. We studied the in vivo and in vitro effects of the methanolic extracts of adlay hull (AHM) on uterine smooth muscle contraction. The extracts were fractionated using four different solvents: water, 1-butanol, ethyl acetate, and n-hexane; the four respective fractions were AHM-Wa, AHM-Bu, AHM-EA, and AHM-Hex. AHM-EA and its subfractions (175 μg/ml) inhibited uterine contractions induced by PGF2α, the Ca2+ channel activator Bay K 8644, and high K+ in a concentration-dependent manner in vitro. AHM-EA also inhibited PGF2α-induced uterine contractions in vivo; furthermore, 375 μg/ml of AHM-EA inhibited the Ca2+-dependent uterine contractions. Thus 375 μg/ml of AHM-EA consistently suppressed the increases in intracellular Ca2+ concentrations induced by PGF2α and high K+. We also demonstrated that naringenin and quercetin are the major pure chemical components of AHM-EA that inhibit PGF2α,-induced uterine contractions. Thus AHM-EA probably inhibited uterine contraction by blocking external Ca2+ influx, leading to a decrease in intracellular Ca2+ concentration. Thus adlay hull may be considered as a feasible alternative therapeutic agent for dysmenorrhea. [ABSTRACT FROM AUTHOR]

Functional gastrointestinal disorders (FGIDs) are characterized by abdominal pain, bloating and bowel disturbances. FGID therapy is primarily symptomatic, including treatment with herbal remedies. Flower extract of Tilia tomentosa Moench (TtM) is occasionally used as an anti-spasmodic in popular medicine. Since its effect on intestinal response is unknown, we evaluated the influence of TtM extract on small intestine contractility. Ileal preparations from C57BL/6J mice were mounted in organ baths to assess changes in muscle tension, following addition of TtM extract (0.5–36 μg/mL) or a vehicle (ethanol). Changes in contractile response to receptor- and non-receptor-mediated stimuli were assessed in ileal preparations pretreated with 12 μg/mL TtM. Alterations in the enteric nervous system neuroglial network were analyzed by confocal immunofluorescence. Increasing addition of TtM induced a marked relaxation in ileal specimens compared to the vehicle. Pretreatment with TtM affected cholinergic and tachykininergic neuromuscular contractions as well as K+-induced smooth muscle depolarization. Following incubation with TtM, a significant reduction in non-adrenergic non-cholinergic-mediated relaxation sensitive to Nω-Nitro-L-arginine methyl ester hydrochloride (pan-nitric oxide synthase inhibitor) was found. In vitro incubation of intestinal specimens with TtM did not affect the myenteric plexus neuroglial network. Our findings show that TtM-induced intestinal relaxation is mediated by nitric oxide pathways, providing a pharmacological basis for the use of TtM in FGIDs. [ABSTRACT FROM AUTHOR]

Apigenin (4′, 5, 7-trihydroxyflavone) is a plant flavone that has been found to have various actions against cancer cells. We evaluated available evidence to determine whether it is feasible for apigenin to have such effects in human patients. Apigenin taken orally is systemically absorbed and recirculated by enterohepatic and local intestinal pathways. Its bioavailability is in the region of 30%. Once absorbed from the oral route it reaches maximal circulating concentration (Cmax) after a time (Tmax) of 0.5–2.5h, with an elimination half-life (T1/2) averaging 2.52 ± 0.56h. Using a circulating concentration for efficacy of 1–5μmol/L as the target, we evaluated data from both human and rodent pharmacokinetic studies to determine if a therapeutic concentration would be feasible. We find that oral intake of dietary materials would require heroic ingestion amounts and is not feasible. However, use of supplements of semi-purified apigenin in capsule form could reach target blood levels using amounts that are within the range currently acceptable for other supplements and medications. Modified formulations or parenteral injection are suitable but may not be necessary. Further work with direct studies of pharmacokinetics and clinical outcomes are necessary to fully evaluate whether apigenin will contribute to a useful clinical strategy, but given emerging evidence that it may interact beneficially with chemotherapeutic drugs, this is worthy of emphasis. In addition, more effective access to intestinal tissues from the oral route raises the possibility that apigenin may be of particular relevance to gastrointestinal disorders including colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Animal studies show that Catha edulis inhibits gastrointestinal tract motility. However, there is little or no information on its effect on colon motility and the mechanism of action and active constituents responsible for this effect. This study therefore attempted to discern the effect, suggest the mechanism, and identify the active compounds from the crude extract. Methods: A crude extract of Catha edulis was fractionated and subfractionated using column chromatography and HPLC. The activity of all fractions and subfractions was evaluated on rat colon longitudinal muscle. Nuclear magnetic resonance (NMR) spectroscopic data elucidations were used to identify the active compounds. An ileal segment preparation was used to investigate the possible mechanism of action. Results: The crude extract of Catha edulis (0.05‐0.5 mg/mL) inhibited spontaneous contraction of rat colon and ileum (P < 0.05), and tetrodotoxin (TTX, 10 µmol/L) failed to block this effect. Similar to verapamil (0.01‐0.1 μmol/L), the Catha edulis extract (0.05‐0.5 mg/mL) inhibited high K+ (80 mmol/L)‐induced sustained ileal contraction and decreased the response to Ca2+. Analysis of the NMR data showed that quercetin, kaempferol, and myricetin were the active phytochemicals. All the identified compounds were flavonoids and significantly inhibited (P < 0.05) spontaneous contraction of the rat colon longitudinal muscle compared to controls. Conclusions: The crude extract of Catha edulis has a spasmolytic effect on the rat ileum, which is mediated through blocking Ca2+ channels, and quercetin, kaempferol, and myricetin were found to be the causative compounds. [ABSTRACT FROM AUTHOR]

The present study investigated the anti-asthmatic activity of quercetin glycosides in neonatal asthmatic rats. Rats were divided into four groups: sham (non-asthmatic), asthmatic control, quercetin (25 mg/kg), and quercetin (50 mg/kg). Inflammatory cells in bronchoalveolar lavage fluid (BALF), inflammatory markers, apoptosis, fibrinogen level, prothrombin time, thrombin time, activated partial thromboplastin time, coagulation factor activity, and histopathology were monitored. Quercetin significantly reduced total leukocytes, eosinophils, tumor necrosis factor-α (TNF-α), interleukin (IL-6), nitric oxide (NO), and apoptosis. It also considerably reduced blood coagulation time and coagulation factor activity compared to the controls. The mRNA expression levels of TNF-α, IL-6, and inducible nitric oxide synthase (iNOS) were elevated in asthmatic rats by 1.3-, 1.04-, and 1.1-fold, respectively. However, treatment with 50 mg/kg quercetin glycosides significantly reduced the mRNA expression of TNF-α, IL-6, and iNOS by more than 40%. Quercetin considerably reduced the protein expression of iNOS. Airway and blood vessel narrowing, as well as the accumulation of eosinophils in the lungs were observed in neonatal asthmatic rats. However, treatment with quercetin glycosides significantly reduced inflammation and eosinophil infiltration. In summary, quercetin glycosides significantly attenuated levels of inflammatory markers, demonstrating its protective effects against neonatal asthma in rats. [ABSTRACT FROM AUTHOR]