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Background and Aim: Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM) with significant effects on outcome. We aim to compare the left atrial (LA) diameter measurement with HCM-AF Score in predicting atrial fibrillation (AF) development in HCM., Methods: From the regional cohort of the Campania Region, Italy, 519 HCM patients (38% women, age45 ± 17 years) without history of AF, were enrolled in the study. The primary clinical endpoint was the development of AF, defined as at least 1 episode documented by ECG., Results: During the follow-up (mean 8 ± 6, IQ range 2.5-11.2 years), 99 patients (19%) developed AF. Patients who developed AF were more symptomatic, had higher prevalence of ICD implantation, had larger LA diameter, greater left ventricular (LV) maximal wall thickness and LV outflow tract obstruction (p < 0.01). Both LA diameter and HCM-AF score were higher in patients who developed AF versus those who did not (LA diameter 49 ± 7 versus 43 ± 6 mm; HCM-AF score 22 ± 4 versus 19 ± 4; p < 0.0001); however, ROC curve analysis demonstrated that LA diameter had a significant greater area under the curve than HCM-AF Score (p < 0.0001). At 5 years follow-up, a LA diameter > 46 mm, showed a similar accuracy in predicting AF development of HCM-AF score ≥ 22, which identifies patients at high risk to develop AF., Conclusion: Our analysis shows that LA diameter, a worldwide and simple echocardiographic measure, is capable alone to predict AF development in HCM patients., (Copyright © 2023 Elsevier Ireland Ltd. All rights reserved.)

Objective: to assess the inter-rater reliability (IRR) of the revised Cochrane risk-of-bias tool for randomised trials (RoB2)., Methods: Four raters independently applied RoB2 on critical and important outcomes of individually randomized parallel-group trials (RCTs) included in the Cochrane Review "Cannabis and cannabinoids for people with multiple sclerosis." We calculated Fleiss' Kappa for multiple raters and time to complete the tool; we performed a calibration exercise on five studies, then we developed an implementation document (ID) specific for the condition, and the intervention addressed by the review with instructions on how to answer the signalling questions of RoB2 tool. We measured IRR before and after the ID adoption RESULTS: Eighty results related to seven outcomes from 16 RCTs were assessed. During calibration exercise we reached no agreement for overall judgment (IRR -0.15); IRR for individual domains ranged from no agreement to fair. Mean time to apply the tool was 168.5 minutes per study. Time to complete the calibration exercise and develop the ID was about 40 hours. After the ID adoption ID, overall agreement increased to slightly (IRR 0.11) for the first five studies and moderate (IRR 0.42) for the remaining 11. IRR for individual domains ranged from no agreement to almost perfect. Mean time to apply the tool decreased to 41 minutes., Conclusion: RoB2 tool is comprehensive but complex even for high experienced raters. The development of an ID specific for the review may improve reliability substantially., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Patients with ulcerative colitis (UC) using marijuana have been reported to experience symptomatic benefit. Cannabidivarin (CBDV) is a safe non-psychoactive phytocannabinoid able to activate and desensitize TRPA1, a member of the TRP channels superfamily, which plays a pivotal role in intestinal inflammation. Here, we have investigated the potential intestinal anti-inflammatory effect of CBDV in mice and in biopsies from pediatric patients with active UC. Colonic inflammation was induced in mice by dinitrobenzenesulfonic acid (DNBS). The effect of orally administered CBDV on macroscopic and microscopic damage, inflammatory parameters (i.e. myeloperoxidase activity, intestinal permeability and cytokine production) and faecal microbiota composition, was evaluated 3 days after DNBS administration. TRPA1 expression was studied by RT-PCR in inflamed colons of mice as well as in mucosal colonic biopsies of children with active UC, whose response to incubation with CBDV was also investigated. CBDV attenuates, in a TRPA1-antagonist sensitive manner, DNBS-induced signs of inflammation including neutrophil infiltration, intestinal permeability, and cytokine (i.e. IL-1β, IL-6 and the chemokine MCP-1) production. CBDV also alters the dysregulation of gut microbiota associated to colitis. Finally, CBDV lessens cytokine expression in colonic biopsies from pediatric patients with ulcerative colitis, a condition in which TRPA1 was up-regulated. Our preclinical study shows that CBDV exerts intestinal anti-inflammatory effects in mice via TRPA1, and in children with active UC. Since CBDV has a favorable safety profile in humans, it may be considered for possible clinical trials in patients with UC., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The clinical efficacy of curcumin-containing nutraceuticals (e.g. turmeric preparations, curcumin, curcuminoids) for a range of conditions has been assessed by several systematic reviews, in some instances with contradictory conclusions. Our aim was to provide an up-to-date and rigorous synthesis of these data and to evaluate the quality of the available systematic reviews., Methods: Electronic searches were conducted (up to December 2017) to locate all systematic reviews (SRs) related to the use of curcumin-containing nutraceuticals for any condition. The quality of the retrieved SRs was assessed by using AMSTAR an OQAQ tolls., Results: Twenty-two SRs met our inclusion criteria. Overall, four SRs were of high quality using the AMSTAR scale, whereas twelve SRs achieved an high quality classification according to the OQAQ score. There is some evidence that curcumin-containing nutraceuticals can exert systemic antioxidant actions (1 SR) and may be effective i) in inflammatory conditions such as arthritis-related diseases and inflammatory bowel disease (12 SRs), ii) in reducing lipid levels and cardiovascular risk factors (5 SRs) as well as iii) in skin diseases (1 SR). Cautious preliminary positive results were reported for depressive disorders (3 SRs), while no efficacy was observed in Alzheimer's disease patients (1 SR). Curcumin-containing nutraceuticals appear to be safe, as assessed by the adverse events reported in twelve SRs., Conclusions: Based on the currently available SRs, the efficacy of curcumin-containing nutraceuticals has been demonstrated for several conditions; however, due to the poor quality of the primary trials and the low-to-moderate level of some SRs, there is still some uncertainty., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Colorectal cancer (CRC) is a major health problem in Western countries. The endocannabinoid 2-arachidonoyl-glycerol (2-AG) exerts antiproliferative actions in a number of tumoral cell lines, including CRC cells. Monoacylglycerol lipase (MAGL), a serine hydrolase that inactivates 2-AG, is highly expressed in aggressive human cancer cells. Here, we investigated the role of MAGL in experimental colon carcinogenesis. The role of MAGL was assessed in vivo by using the xenograft and the azoxymethane models of colon carcinogenesis; MAGL expression was evaluated by RT-PCR and immunohistochemistry; 2-AG levels were measured by liquid chromatography mass spectrometry; angiogenesis was evaluated in tumor tissues [by microvessel counting and by investigating the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) proteins] as well as in human umbilical vein endothelial cells (HUVEC); cyclin D1 was evaluated by RT-PCR. MAGL and 2-AG were strongly expressed in tumor tissues. The MAGL inhibitor URB602 reduced xenograft tumor volume, this effect being associated to down-regulation of VEGF and FGF-2, reduction in the number of vessels and down-regulation of cyclin D1. In HUVEC, URB602 exerted a direct antiangiogenic effect by inhibiting FGF-2 induced proliferation and migration, and by modulating pro/anti-angiogenic agents. In experiments aiming at investigating the role of MAGL in chemoprevention, URB602 attenuated azoxymethane-induced preneoplastic lesions, polyps and tumors. MAGL, possibly through modulation of angiogenesis, plays a pivotal role in experimental colon carcinogenesis. Pharmacological inhibition of MAGL could represent an innovative therapeutic approach to reduce colorectal tumor progression., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Historical and scientific evidence suggests that Cannabis use has immunomodulatory and anti-inflammatory effects. We have here investigated the effect of the non-psychotropic phytocannabinoid Δ 9 -tetrahydrocannabivarin (THCV) and of a Cannabis sativa extract with high (64.8%) content in THCV (THCV-BDS) on nitric oxide (NO) production, and on cannabinoid and transient receptor potential (TRP) channel expression in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. THCV-BDS and THCV exhibited similar affinity in radioligand binding assays for CB 1 and CB 2 receptors, and inhibited, via CB 2 but not CB 1 cannabinoid receptors, nitrite production evoked by LPS in peritoneal macrophages. THCV down-regulated the over-expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin 1β (IL-1β) proteins induced by LPS. Furthermore, THCV counteracted LPS-induced up-regulation of CB 1 receptors, without affecting the changes in CB 2 , TRPV2 or TRPV4 mRNA expression caused by LPS. Other TRP channels, namely, TRPA1, TRPV1, TRPV3 and TRPM8 were poorly expressed or undetectable in both unstimulated and LPS-challenged macrophages. It is concluded that THCV - via CB 2 receptor activation - inhibits nitrite production in macrophages. The effect of this phytocannabinoid was associated with a down-regulation of CB 1 , but not CB 2 or TRP channel mRNA expression., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A new acetophenone derivative named gnaphaliol 9-O-propanoate (1) was isolated from the chloroform fraction of EtOH extract of Helichrysum italicum ssp. italicum flowers along with the five known acetophenones 12-acetoxytremetone (2), 13-(2-methylpropanoyloxy)toxol (3), [2,3-dihydro-2-[1-(hydroxymethyl)ethenyl]-5-benzofuranyl]-ethanone (4), 1-[2-[1-[(acetyloxy)methyl]ethenyl]-2,3-dihydro-3-hydroxy-5-benzofuranyl]-ethanone (5) and gnaphaliol (6). The structures of compounds 1-6 were elucidated by extensive spectroscopic methods including 1D- ((1)H and (13)C) and 2D-NMR (DQF-COSY, HSQC, HMBC, TOCSY and ROESY) experiments as well as ESIMS analysis. The isolated compounds were investigated for their cytotoxicity, anti-inflammatory and antioxidant properties. Biological assays on human colonic epithelial cells showed that compound 2 possessed antioxidant effects reducing reactive oxygen species (ROS) production., (Copyright © 2014 Elsevier B.V. All rights reserved.)

α-Hexylcinnamaldehyde (HCA) and p-tert-butyl-alpha-methylhydrocinnamic aldehyde (BMHCA) are synthetic aldehydes, characterized by a typical floral scent, which makes them suitable to be used as fragrances in personal care (perfumes, creams, shampoos, etc.) and household products, and as flavouring additives in food and pharmaceutical industry. The aldehydic structure suggests the need for a safety assessment for these compounds. Here, HCA and BMHCA were evaluated for their potential genotoxic risk, both at gene level (frameshift or base-substitution mutations) by the bacterial reverse mutation assay (Ames test), and at chromosomal level (clastogenicity and aneuploidy) by the micronucleus test. In order to evaluate a primary and repairable DNA damage, the comet assay has been also included. In spite of their potential hazardous chemical structure, a lack of mutagenicity was observed for both compounds in all bacterial strains tested, also in presence of the exogenous metabolic activator, showing that no genotoxic derivatives were produced by CYP450-mediated biotransformations. Neither genotoxicity at chromosomal level (i.e. clastogenicity or aneuploidy) nor single-strand breaks were observed. These findings will be useful in further assessing the safety of HCA and BMHCA as either flavour or fragrance chemicals., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Acylethanolamides (AEs) are a group of lipids occurring in both plants and animals. The best-studied AEs are the endocannabinoid anandamide (AEA), the anti-inflammatory compound palmitoylethanolamide (PEA), and the potent anorexigenic molecule oleoylethanolamide (OEA). AEs are biosynthesized in the gastrointestinal tract, and their levels may change in response to noxious stimuli, food deprivation or diet-induced obesity. The biological actions of AEs within the gut are not limited to the modulation of food intake and energy balance. For example, AEs exert potential beneficial effects in the regulation of intestinal motility, secretion, inflammation and cellular proliferation. Molecular targets of AEs, which have been identified in the gastrointestinal tract, include cannabinoid CB(1) and CB(2) receptors (activated by AEA), transient receptor potential vanilloid type 1 (TRPV1, activated by AEA and OEA), the nuclear receptor peroxisome proliferators-activated receptor-alpha (PPAR-alpha, activated by OEA and, to a less extent, by PEA), and the orphan G-coupled receptors GPR119 (activated by OEA) and GPR55 (activated by PEA and, with lower potency, by AEA and OEA). Modulation of AE levels in the gut may provide new pharmacological strategies not only for the treatment of feeding disorders but also for the prevention or cure of widespread intestinal diseases such as inflammatory bowel disease and colon cancer.

Black cohosh (Cimicifuga racemosa) is used most often to treat symptoms that can occur during menopause. However, in the last years, several concerns regarding its safety have been voiced. The aim of this systematic review was to evaluate the clinical evidence for or against the safety of black cohosh. Systematic literature searches were conducted in 5 computerized databases (Medline, Embase, Amed, Phytobase, and Cochrane Library). The references of all located articles were scanned for further relevant publications. Any type of clinical data that included case reports and observational studies was considered. No language restrictions were imposed. Thirteen clinical trials (all of which indicated relative safety), 3 postmarketing surveillance studies, 4 case series, and 8 single case reports were identified. Clinical studies suggest black cohosh to be safe. In most case reports, causal attribution is problematic. In conclusion, black cohosh has been associated with serious safety concerns that urgently require further investigation.

Since conventional hormone replacement therapy has fallen out of favour, alternatives are being sought by many women. These therapies include herbal preparations such as black cohosh (Cimicifuga racemosa). The purpose of this update of a previous systematic review is to evaluate the clinical evidence for or against the efficacy of black cohosh in alleviating menopausal symptoms. Five computerized databases (Medline, Embase, Amed, Phytobase and Cochrane Library) were searched to identify all clinical data that provided evidence on the efficacy of C. racemosa. Bibliographies of the articles thus located were scanned for further relevant publications. Only double blind, randomized, clinical trials (RCTs) were included in the evaluation of efficacy. No language restrictions were imposed. Trials were excluded if they did not focus on menopausal problems, they included women suffering medically induced menopause, they did not use black cohosh monopreparations, or they did not use placebo or a standard drug treatment for the control group. Six studies with a total of 1112 peri- and post-menopausal women met our inclusion criteria. The evidence from these RCTs does not consistently demonstrate an effect of black cohosh on menopausal symptoms; a beneficial effect of black cohosh on peri-menopausal women cannot be excluded. The efficacy of black cohosh as a treatment for menopausal symptoms is uncertain and further rigorous trials seem warranted.

Use of herbal medicines among patients under cardiovascular pharmacotherapy is widespread. In this paper, we have reviewed the literature to determine the possible interactions between herbal medicines and cardiovascular drugs. The Medline database was searched for clinical articles published between January 1996 and February 2003. Forty-three case reports and eight clinical trials were identified. Warfarin was the most common cardiovascular drug involved. It was found to interact with boldo, curbicin, fenugreek, garlic, danshen, devil's claw, don quai, ginkgo, papaya, lycium, mango, PC-SPES (resulting in over-anticoagulation) and with ginseng, green tea, soy and St. John's wort (causing decreased anticoagulant effect). Gum guar, St. John's wort, Siberian ginseng and wheat bran were found to decrease plasma digoxin concentration; aspirin interactions include spontaneous hyphema when associated with ginkgo and increased bioavailability if combined with tamarind. Decreased plasma concentration of simvastatin or lovastatin was observed after co-administration with St. John's wort and wheat bran, respectively. Other adverse events include hypertension after co-administration of ginkgo and a diuretic thiazide, hypokalemia after liquorice and antihypertensives and anticoagulation after phenprocoumon and St. John's wort. Interaction between herbal medicine and cardiovascular drugs is a potentially important safety issue. Patients taking anticoagulants are at the highest risk.

Ginger (Zingiber officinale rhizome) is a widespread herbal medicine mainly used for the treatment of gastrointestinal diseases, including dyspepsia, nausea and diarrhoea. In the present study we evaluated the effect of this herbal remedy on the contractions induced by electrical stimulation (EFS) or acetylcholine in the isolated rat ileum. Ginger (0.01-1000 microg/ml) inhibited both EFS- and acetylcholine-evoked contractions, being more potent in inhibiting the contractions induced by EFS. The depressant effect of ginger on EFS-induced contractions was reduced by the vanilloid receptor antagonist capsazepine (10(-5) M), but unaffected by the alpha(2)-adrenergic antagonist yohimbine (10(-7) M), the CB(1) receptor antagonist SR141716A (10(-6) M), the opioid antagonist naloxone (10(-6) M) or by the NO synthase inhibitor L-NAME (3 x 10(-4) M). Zingerone (up to 3 x 10(-4) M), one of the active ingredients of ginger, did not possess inhibitory effects. It is concluded that ginger possesses both prejunctional and postjunctional inhibitory effects on ileal contractility; the prejunctional inhibitory effect of ginger on enteric excitatory transmission could involve a capsazepine-sensible site (possibly vanilloid receptors).

There is growing evidence that high concentrations of nitric oxide (NO), generated by activated astrocytes, might be involved in a variety of neurodegenerative diseases, such as Alzheimer's disease, ischemia and epilepsy. It has recently been suggested that glial cells may produce NO under superoxide radical stimulation by enzyme-independent mechanism. This suggests that also natural antioxidants may have therapeutical relevance in neurodegenerative diseases. Studies of Bhattacharya et al. have evidenced that Bacopa monniera (BM) (family Scrophulariaceae), an Ayurvedic medicinal plant clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative, is able to reduce the memory-dysfunction in rat models of Alzheimer's disease, but the molecular mechanisms of this action are yet to be determined. In the present study, we examined the effect of a methanolic extract of BM on toxicity induced by the nitric oxide donor, S-nitroso-N-acetyl-penicillamine (SNAP), in culture of purified rat astrocytes. Our results indicate that, after 18 h of treatment, SNAP induced an increase in the production of reactive species, but did not induce the rupture of cellular membrane. Conversely, this NO donor induced a fragmentation of genomic DNA compared to control astrocytes. The extract of BM inhibited the formation of reactive species and DNA damage in a dose dependent manner. This data supports the traditional use of BM and indicates that this medicinal plant has a therapeutic potential in treatment or prevention of neurological diseases.

Cimicifuga racemosa is widely employed to relieve menopause symptoms for its hormonal-like action. However, recent experimental studies have not found an estrogenic action by this plant. The purpose of this systematic review is to analyse all experimental studies (in vivo and in vitro) performed on C. racemosa to elucidate its mechanism of action. Animal and in vitro experiments on C. racemosa were identified through a computerised literature searches performed on Medline (PubMed), Embase, Amed, CISCOM and Cochrane Library databases. In addition, bibliographies of the articles thus located were scanned for further relevant publications and manufactures of commercial C. racemosa preparations were asked to contribute published and unpublished material. No language restrictions were imposed. A total of 15 animal and 15 in vitro studies on C. racemosa have been found. Their results suggest that C. racemosa possesses a central activity instead of a hormonal effect. Further biological and chemical investigations are required to define its mechanism of action and to identify the compounds responsible of its actions.

Propolis, a natural product derived from plant resins collected by the honeybees, has been used for thousands of years in folk medicine for several purposes. The extract that contains amino acids, phenolic acids, phenolic acid esters, flavonoids, cinnamic acid, terpenes and caffeic acid, possesses several biological activities such as anti-inflammatory, immunostimulatory, anti-viral and anti-bacterial. In this study, we assay the effects of propolis extract on the production of key molecules released during chronic inflammatory events as nitric oxide (NO) and glycosaminoglycans (GAGs) in cultures of human cartilaginous tissues and chondrocytes, stimulated with interleukin-1beta (IL-1beta). We observed that this natural compound and its active principle, caffeic acid phenethyl ester (CAPE), were able to contrast the harmful effects of IL-1beta. Our data clearly demonstrated the protective action of propolis in cartilage alteration, that appears greater than that elicited by indomethacin, commonly employed in joint diseases.

This study was aimed to investigate the vascular activity of caffeic acid phenethylester (CAPE), one of the major components of honeybee propolis. Experiments were performed on rat thoracic aortic rings, mounted in an isolated organ bath and connected to an isometric force transducer. The effect of CAPE (0.1-300 microM) was evaluated on tissue pre-contracted with phenylephrine (PE, 1 microM) or with KCl (100 mM). In another set of experiments, tissue was incubated with CAPE (1-100 microM) and responses to PE (0.01-3 microM) or KCl (60 mM) were evaluated. The effect of CAPE on cytosolic Ca(2+) concentration in aortic smooth muscle cells stimulated with PE or KCl was also evaluated. CAPE (0.1-300 microM) caused a concentration-dependent relaxation (pEC(50) 4.99 +/- 0.19; Emax 100.75 +/- 1.65%; n = 4) of tissue pre-contracted with PE that was reduced by endothelium removal or by incubation with N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM). CAPE also relaxed KCl-precontracted tissue (pEC(50) 4.40 +/- 0.08; n = 4). CAPE inhibited contractile responses to PE or to KCl, and also inhibited the contractile response to PE obtained in a Ca(2+)-free medium. In addition, CAPE inhibited the increase in cytosolic Ca(2+) concentration triggered by stimulation of aortic smooth muscle cells with PE or KCl. Our results demonstrate a vascular activity for CAPE, that is only partially dependent on nitric oxide. Indeed, at high concentrations, CAPE vasorelaxant effect occurs also in absence of endothelium and it is likely due to an inhibitory effect on calcium movements through cell membranes.

Nimesulide, a selective inhibitor of cyclooxygenase-2, has been reported to cause less gastric damage, compared to other NSAIDs. We investigated the effect of nimesulide on basal gastric acid secretion, a contributing factor in NSAID-induced gastric damage, and histamine, pentagastrin, 5-methylfurmethide, isobutyl methylxanthine or high K(+) stimulated acid secretion in the isolated mouse stomach. The stomachs, removed from mice, were transferred into an organ bath and continuously perfused. Changes in pH following the addition of secretagogues were measured by a pH electrode system. The effects of nimesulide on basal and secretagogues-stimulated acid secretion were compared to those of indomethacin. Nimesulide (1 microM to 100 microM) produced a rightward concentration-dependent shift and reduction of maximum acid secretion of all the agonist-stimulated acid secretion curves. Indomethacin was only effective at the higher concentration of 100 microM. Compared to their effects singly, nimesulide (20 microM) and famotidine (0.15 microM) together caused a further shift without further reduction in maximum acid output of the histamine-stimulated curve, suggesting that nimesulide was not acting at the histamine H(2)-receptor. Nimesulide concentration-dependent reduction of stimulated acid secretion in the isolated mouse stomach was not by antagonism of the histamine H(2) receptor and is probably beyond the level of adenylate cyclase stimulation. A direct effect on the calcium channel is demonstrated.

Two ethanolic propolis extracts (EPE) with and without the caffeic acid phenethyl ester (CAPE), CAPE and galangin (major components of propolis) were investigated for anti-inflammatory activity in rats using carrageenin foot oedema, carrageenin pleurisy and adjuvant arthritis. In our experiments, EPE with CAPE and CAPE alone significantly inhibited carrageenin oedema, carrageenin pleurisy and adjuvant arthritis. In contrast EPE without CAPE and galangin did not exhibit anti-inflammatory effects in acute and chronic inflammation. These results suggest that the anti-inflammatory activity of propolis is due to CAPE.

In this study we investigated the effect of an ethanolic extract of propolis, with and without CAPE, and some of its components on cyclooxygenase (COX) activity. Propolis (0.00003-0.03%) significantly and concentration-dependently inhibited COX activity from lung homogenate of saline- or LPS-treated rats. Same results were obtained with CAPE (0.1-100 microM). COX activity from lung homogenate of saline- or LPS-treated rats was also inhibited by galangin (0.1-100 microM), although the inhibition induced by the lowest concentration was not significant. Caffeic, ferulic, cinnamic and chlorogenic acids and pinocembrin, (0.1-100 microM) did not affect COX activity. The inhibition curves showed that CAPE and propolis were equipotent inhibitors, whereas galangin was significantly (P<0.001) less potent than propolis and CAPE. In order to better investigate the role of CAPE, we tested the action of an ethanolic extract of propolis (0.00003-0.03%) without CAPE. This extract significantly and concentration-dependently inhibited COX activity from lung homogenate of saline- or LPS-treated rats, however, it resulted to be approximately 10 times less potent than the extract containing CAPE. The analysis of the inhibition curves of the extract with and without CAPE showed a significant (P<0.001) difference. These results suggest that both CAPE and galangin contribute to the overall activity of propolis, CAPE being more effective.

We have studied the effect of propolis and its main active ingredient caffeic acid phenetyl ester (CAPE) on formation of aberrant crypt foci (ACF) and tumors in the rat colon in vivo. CAPE (50 mg/kg i.p.) reduced the formation of ACF and tumor induced by azoxymethane, while propolis ethanolic extract was without effect. These results suggest a potential anti-carcinogenesis of CAPE but not propolis.

We have investigated the effect piperine on castor oil-stimulated fluid accumulation in the mouse small intestine. Piperine (2.5-20 mg/kg, i.p.) dose-dependently reduced castor oil-induced intestinal fluid accumulation. The inhibitory effect of piperine (10 mg/kg i.p.) was strongly attenuated in capsaicin (75 mg/kg in total, s.c.)-treated mice but it was not modified by the vanilloid receptor antagonist capsazepine (30 mg/kg i.p.). Pretreatment of mice with hexamethonium (1 mg/kg i.p.), naloxone (2 mg/kg i.p.), yohimbine (1 mg/kg i.p.) or the cannabinoid CB(1) receptor antagonist SR141716A (0.3 mg/kg i.p.) did not modify the inhibitory effect of piperine (10 mg/kg i.p.). These results suggest that piperine reduces castor oil-induced fluid secretion with a mechanism involving capsaicin-sensitive neurons, but not capsazepine-sensitive vanilloid receptors.

Laxatives abuse has been associated with an increased risk for colon cancer. However, little is known about laxatives long-term carcinogenic potential in experimental studies. The present study was designed to investigate the effects of bisacodyl (4.3 and 43 mg/kg) and cascara (140 and 420 mg/kg) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) and tumors. Animals, divided in 10 groups were treated with AOM and laxatives (alone or in combination) for 13 weeks. At the end of treatment animals were killed and the colon removed and analysed for the determination of ACF and tumors. Bisacodyl (4.3 and 43 mg/kg), given alone, did not induce the development of colonic ACF and tumors. Bisacodyl (4.3 mg/kg) coupled with AOM increased the number of crypt per focus, but not the number of tumors. Bisacodyl (43 mg/kg) significantly increased the number of crypt per focus and tumors. Cascara (140 and 420 mg/kg) did not induce the development of colonic ACF and tumors and did not modify the number of AOM-induced ACF and tumors. The results of the present study indicate a possible promoting effect of bisacodyl on rat colon carcinogenesis (especially at higher doses) and absence of any promoting or initiating activity of a laxative and diarrhoeal dose of cascara.

The intravenous LD50 of the hypothalamic tetradecapeptide somatostatin was determined in mice and rats of both sexes. It was found that somatostatin has a sex-related toxicity both in mice and rats. The interaction of low and high doses of peptide with the LD50s of two central nervous system (CNS) drugs, namely pentobarbital and strychnine, was also studied in male and female mice. Differential effects were observed as follows: a very low dose (0.1 mg/kg) of somatostatin does not affect the toxicity of these compounds, whereas the injection of 1 mg/kg of peptide increased pentobarbital toxicity and decreased the toxicity of strychnine. However, an increase in the toxicity of both substances was obtained with very high non-lethal doses of peptide (20 and 30 mg/kg, in female and male mice, respectively).