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Background: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2009, Issue 3).Tea is one of the most commonly consumed beverages worldwide. Teas from the plant Camellia sinensis can be grouped into green, black and oolong tea, and drinking habits vary cross-culturally. C sinensis contains polyphenols, one subgroup being catechins. Catechins are powerful antioxidants, and laboratory studies have suggested that these compounds may inhibit cancer cell proliferation. Some experimental and nonexperimental epidemiological studies have suggested that green tea may have cancer-preventative effects., Objectives: To assess possible associations between green tea consumption and the risk of cancer incidence and mortality as primary outcomes, and safety data and quality of life as secondary outcomes., Search Methods: We searched eligible studies up to January 2019 in CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and reference lists of previous reviews and included studies., Selection Criteria: We included all epidemiological studies, experimental (i.e. randomised controlled trials (RCTs)) and nonexperimental (non-randomised studies, i.e. observational studies with both cohort and case-control design) that investigated the association of green tea consumption with cancer risk or quality of life, or both., Data Collection and Analysis: Two or more review authors independently applied the study criteria, extracted data and assessed methodological quality of studies. We summarised the results according to diagnosis of cancer type., Main Results: In this review update, we included in total 142 completed studies (11 experimental and 131 nonexperimental) and two ongoing studies. This is an additional 10 experimental and 85 nonexperimental studies from those included in the previous version of the review. Eleven experimental studies allocated a total of 1795 participants to either green tea extract or placebo, all demonstrating an overall high methodological quality based on 'Risk of bias' assessment. For incident prostate cancer, the summary risk ratio (RR) in the green tea-supplemented participants was 0.50 (95% confidence interval (CI) 0.18 to 1.36), based on three studies and involving 201 participants (low-certainty evidence). The summary RR for gynaecological cancer was 1.50 (95% CI 0.41 to 5.48; 2 studies, 1157 participants; low-certainty evidence). No evidence of effect of non-melanoma skin cancer emerged (summary RR 1.00, 95% CI 0.06 to 15.92; 1 study, 1075 participants; low-certainty evidence). In addition, adverse effects of green tea extract intake were reported, including gastrointestinal disorders, elevation of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin/subcutaneous reactions. Consumption of green tea extracts induced a slight improvement in quality of life, compared with placebo, based on three experimental studies. In nonexperimental studies, we included over 1,100,000 participants from 46 cohort studies and 85 case-control studies, which were on average of intermediate to high methodological quality based on Newcastle-Ottawa Scale 'Risk of bias' assessment. When comparing the highest intake of green tea with the lowest, we found a lower overall cancer incidence (summary RR 0.83, 95% CI 0.65 to 1.07), based on three studies, involving 52,479 participants (low-certainty evidence). Conversely, we found no association between green tea consumption and cancer-related mortality (summary RR 0.99, 95% CI 0.91 to 1.07), based on eight studies and 504,366 participants (low-certainty evidence). For most of the site-specific cancers we observed a decreased RR in the highest category of green tea consumption compared with the lowest one. After stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: oesophageal, prostate and urinary tract cancer, and leukaemia showed an increased RR in cohort studies and a decreased RR or no difference in case-control studies., Authors' Conclusions: Overall, findings from experimental and nonexperimental epidemiological studies yielded inconsistent results, thus providing limited evidence for the beneficial effect of green tea consumption on the overall risk of cancer or on specific cancer sites. Some evidence of a beneficial effect of green tea at some cancer sites emerged from the RCTs and from case-control studies, but their methodological limitations, such as the low number and size of the studies, and the inconsistencies with the results of cohort studies, limit the interpretability of the RR estimates. The studies also indicated the occurrence of several side effects associated with high intakes of green tea. In addition, the majority of included studies were carried out in Asian populations characterised by a high intake of green tea, thus limiting the generalisability of the findings to other populations. Well conducted and adequately powered RCTs would be needed to draw conclusions on the possible beneficial effects of green tea consumption on cancer risk., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

The n -butanolic extract, from an Iranian specimen of Nepeta asterotricha Rech. f. (NABE), displayed anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated J774A.1 macrophages, which reduced nitrites and cytokines production. Bioassay guided fractionation of the extract led to the isolation of four iridoid glycosides, including a new one known as nepetamoside ( 1 ), one hexenyl-diglycoside, and some polyphenol and flavonoid components. None of the isolated iridoid components displayed significant effects on nitrites formation in an in vitro LPS-induced model of inflammation, thus suggesting that the plant anti-inflammatory effect is probably due to a synergistic action among its constituents.

Purpose: Erectile dysfunction (ED) is a common condition that significantly affects quality of life and interpersonal relationships., Objective: Our objective was to perform a systematic review and meta-analysis to evaluate the efficacy of herbal dietary supplements in the treatment of ED., Materials and Methods: We searched five databases to identify randomized controlled trials (RCTs) that evaluated the clinical efficacy of herbal medicines in ED. Quality was assessed and risk of bias was estimated using the Jadad score and the Cochrane risk-of-bias tool., Results: In total, 24 RCTs, including 2080 patients with ED, were identified. Among these, 12 evaluated monopreparations (five ginseng [n = 399], three saffron [n = 397], two Tribulus terrestris [n = 202], and one each Pinus pinaster [n = 21] and Lepidium meyenii [n = 50]), seven evaluated formulations (n = 544), and five investigated dietary supplements in combination with pure compounds (n = 410). Ginseng significantly improved erectile function (International Index of Erectile Function [IIEF]-5 score: 140 ginseng, 96 placebo; standardized mean difference [SMD] 0.43; 95% confidence interval [CI] 0.15-0.70; P < 0.01; I 2  = 0), P. pinaster and L. meyenii showed very preliminary positive results, and saffron and T. terrestris treatment produced mixed results. Several herbal formulations were associated with a decrease of IIEF-5 or IIEF-15, although the results were preliminary. The quality of the included studies varied, with only seven having a prevalent low risk of bias. The median methodological quality Jadad score was three out of a maximum of five. Adverse events were recorded in 19 of 24 trials, with no significant differences between placebo and verum in placebo-controlled studies., Conclusions: Encouraging evidence suggests that ginseng may be an effective herbal treatment for ED. However, further, larger, and high-quality studies are required before firm conclusions can be drawn. Promising (although very preliminary) results have also been generated for some herbal formulations. Overall, more research in the field, adhering to the CONSORT statement extension for reporting trials, is justified before the use of herbal products in ED can be recommended.

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.)

Recognition of the adverse effects of medicinal herbs is not routine and the reports on such effects are even less frequent in clinical practice. Potential herb-drug interactions are of a major safety concern, especially for drugs with narrow therapeutic indices like warfarin, which can lead to severe adverse reactions that are sometimes life-threatening. The interactions between warfarin and medicinal herbs described in the literature have been summarized in this paper relying on Medline database (via PubMed) using the key words: warfarin, herbal supplements and interactions. The references on the analyzed literature have been investigated in order to collect the existing data. The case reports with severe adverse effects such as spontaneous postoperative bleeding, formation of hematomas, hematemesis, melena, thrombosis, subarachnoid hemorrhage and/or subdural hematomas after concomitant use of warfarin and the medicinal herbs: Panax ginseng, Hypericum perforatum, Salvia milthiorizza, Gingko biloba, Serenoa repens, Angelica sinensis, Vaccinium species, Allium sativum, Zingiber officinale, Tanacetum parthenium, Lucium barbarum, Matricaria chamomilla, Boswellia serrata and Camellia sinensis have been estimated. Some of the interactions between warfarin and medicinal herbs have been well assessed proving that they are closely-dependent. The interactions between warfarin and medicinal herbs, not generally reported in previous reviews, are presented in our review. The health professionals who are involved in treating the patients are expected to be fully informed about the interactions between warfarin and medicinal herbs in order to minimize the health risks of the patients.

Ethnopharmacological Relevance: In the Mediterranean Area, the flowers of Helichrysum italicum ssp. italicum are a traditional remedy for the treatment of intestinal complaints and are used as herbal tea for curing digestive, stomachic and intestinal diseases. In order to find scientific evidence for the traditional utilization of this plant, the effect of an ethanolic extract of Helichrysum italicum was investigated by using in vivo and in vitro experimental models. Then, through bioassay-guided fractionation procedures, active component(s) were identified., Material and Methods: Contractility in vitro was evaluated by stimulating the isolated ileum, in an organ bath, with acetylcholine and barium chloride; motility in vivo was evaluated by measuring upper gastrointestinal transit, both in control mice and in mice with experimental intestinal inflammation induced by croton oil. Chromatographic separation techniques such as HPLC and silica gel columns have yielded the active principles of Helichrysum italicum., Results: We found that the ethanolic extract of Helichrysum italicum ssp. italicum flowers elicited antispasmodic actions in the isolated mouse ileum and inhibited transit preferentially in the inflamed gut. A bioassay guided fractionation of the extract yielded the known compounds 12-acetoxytremetone (1) and 2,3-dihydro-2-[1-(hydroxymethyl)ethenyl]-5-benzofuranyl]-ethanone (2)., Conclusion: Present study supported the traditional use of Helichrysum italicum ssp. italicum flowers for intestinal complaints and through bioassay-guided fractionation procedures from the crude extract we showed that 12-acetoxytremetone (1) and 2,3-dihydro-2-[1-(hydroxymethyl)ethenyl]-5-benzofuranyl]-ethanone (2) acted in a synergistic way to produce an intestinal antispasmodic effect., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Functional dyspepsia (FD) is a highly prevalent gastrointestinal disorder characterized by alterations in gastric motility. Yarrow (Achillea millefolium L., Fam Asteraceae) preparations are traditional remedies used to treat dyspeptic complaints. Herein, we investigated the effect of a standardized dry water extract obtained from A. millefolium flowering tops (AME) on gastric motility., Methods: The effect of AME on motility was evaluated on the resting tone of the isolated gastric antrum and on gastric emptying in vivo (phenol red meal method) both in control mice and in the model of cancer chemotherapy (cisplatin)-induced gastric abnormalities., Key Results: The AME contracted mouse and human gastric strips and this action was unaffected by hexamethonium and tetrodotoxin, but strongly reduced by atropine. Among various chemical ingredients in yarrow, choline, but not the flavonoids rutin and apigenin, mimicked the action of AME. Furthermore, AME deprived of choline did not exert a contractile effect. In vivo, AME stimulated gastric emptying both in control and in cisplatin-treated mice, being more active in pathological states., Conclusions & Inferences: It is concluded that (i) AME exerts a direct spasmogenic effect on gastric antrum; (ii) choline is the chemical ingredient responsible of such effect; (iii) the prokinetic effect of AME observed in vivo could provide the pharmacological basis underlying its traditional use in the treatment of dyspepsia., (© 2011 Blackwell Publishing Ltd.)

Objectives: To evaluate the effect of a Cannabis sativa extract enriched in cannabidiol (CBD) botanic drug substance (BDS) and pure CBD, on bladder contractility in vitro. Cannabis based-medicines, including CBD-enriched extracts, have been shown to reduce urinary urgency, incontinence episodes, frequency, and nocturia in patients with multiple sclerosis., Methods: Strips were cut from male Wistar rats and the human bladder body and placed in organ baths containing Krebs solution. Contractions were induced by electrical field stimulation, acetylcholine, KCl, and α,β-methylene adenosine triphosphate., Results: CBD BDS significantly reduced the contractions induced by acetylcholine, but not those induced with electrical field stimulation, KCl, or α,β-methylene adenosine triphosphate in the isolated rat bladder. The inhibitory effect of CBD BDS was not significantly modified by the cannabinoid or opioid receptor antagonists or by modulators of calcium levels, but it was increased by ruthenium red and capsazepine, 2 transient receptor potential vanilloid type-1 blockers. In humans, CBD BDS and pure CBD significantly reduced acetylcholine-induced contractions, an effect that was not changed by the transient receptor potential vanilloid type-1 blockers., Conclusions: Our data have suggested that CBD BDS reduces cholinergic-mediated contractility and that this effect is modulated by transient receptor potential vanilloid type-1 in rats but not in humans. CBD is the chemical ingredient of CBD BDS responsible for such activity. If confirmed in vivo, such results could provide a pharmacologic basis to explain, at least in part, the efficacy of Cannabis medicines in reducing incontinence episodes in patients with multiple sclerosis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background and Aims: Free radicals are implicated in the aetiology of some gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. In the present study we investigated the antioxidant and genoprotective activity of some rotenoids (i.e. boeravinones) isolated from the roots of Boerhaavia diffusa, a plant used in the Ayurvedic medicine for the treatment of diseases affecting the gastrointestinal tract., Methods/principal Findings: Antioxidant activity has been evaluated using both chemical (Electron Spin Resonance spectroscopy, ESR) and Caco-2 cells-based (TBARS and ROS) assays. DNA damage was evaluated by Comet assay, while pERK(1/2) and phospho-NF-kB p65 levels were estimated by western blot. Boeravinones G, D and H significantly reduced the signal intensity of ESR induced by hydroxyl radicals, suggesting a scavenging activity. Among rotenoids tested, boeravinone G exerted the most potent effect. Boeravinone G inhibited both TBARS and ROS formation induced by Fenton's reagent, increased SOD activity and reduced H(2)O(2)-induced DNA damage. Finally, boeravinone G reduced the levels of pERK(1) and phospho-NF-kB p65 (but not of pERK(2)) increased by Fenton's reagent., Conclusions: It is concluded that boeravinone G exhibits an extraordinary potent antioxidant activity (significant effect in the nanomolar range). The MAP kinase and NF-kB pathways seem to be involved in the antioxidant effect of boeravinone G. Boeravinone G might be considered as lead compound for the development of drugs potentially useful against those pathologies whose aetiology is related to ROS-mediated injuries.

Breastfeeding is widely acknowledged to have important health benefits for infants and mothers. Milk thistle (Silybum marianum fruits) has been recently proposed to be used by nursing mothers for stimulating milk production; however, the mode of action of this herbal drug is still unknown. In this paper, we have evaluated the effect of a micronized standardized extract of S. marianum (Silymarin BIO-C=Piùlatte) on the serum levels of prolactin in female rats. A 14-day treatment with Silymarin BIO-C (25-200mg/kg, given orally) increased, in a dose dependent manner, the serum prolactin levels. Moreover, after a 66-day discontinuation of Silymarin BIO-C treatment, prolactin levels were still significantly elevated although we observed a trend to decrease that was counteracted by a further 7-day treatment with Silymarin BIO-C. Bromocriptine, a dopamine D(2) receptor agonist, (1-10mg/kg, os) significantly and in a dose dependent manner, reduced the serum prolactin levels; bromocriptine, at the dose of 1mg/kg, significantly reduced the high serum prolactin levels induced by Silymarin BIO-C. In conclusion, we have shown that an extract from S. marianum fruits significantly increases circulating prolactin levels in female rats; this effect seems to involve, at least in part, dopamine D(2) receptors.

Marrubium globosum ssp. libanoticum is a medicinal plant used in Lebanon to reduce pain and smooth muscle spasms. A chloroform extract obtained from M. globosum aerial parts reduced acetylcholine-induced contractions in the isolated mouse ileum. The purification of this extract identified, among 12 isolated labdane diterpenoids, four new compounds, named 13-epicyllenin A (4), 13,15-diepicyllenin A (5), marrulibacetal (9), and marrulactone (11). Their structures were determined by spectroscopic methods. Compound 9, which exerted antispasmodic activity, is likely the active ingredient of the extract. Preliminary structure-activity relationships for this class of compounds are suggested.

Ethnopharmacological Importance: Celastrus paniculatus Willd. (Celastraceae) is an Ayurvedic remedy used for the treatment of a number of diseases, including bowel spasms., Aim of the Study: To investigate the mode of the relaxing action of a methanolic extract prepared from the seeds of Celastrus paniculatus (CPE, 0.0001-10 microg/mL) in the rat ileum and to try to confirm on human tissues the intestinal pharmacological activity of the extract., Materials and Methods: The relaxant effect of CPE was studied in vitro by evaluating its effect on the spontaneous contractions of the isolated ileum., Results: CPE exerted a tetrodotoxin- and omega-conotoxin-resistant inhibitory effect on rat ileum motility (IC(50): 0.24+/-0.02 microg/mL; E(max): 99.0+/-0.60%). The inhibitory effect was reduced by nifedipine but not by cyclopiazonic acid. Experiments with specific antagonists enabled us to exclude the involvement of the main endogenous spasmogenic (i.e. acetylcholine and tachykinins) and relaxing (noradrenaline, nitric oxide, ATP) compounds. CPE also relaxed the isolated human ileum (IC(50): 0.26+/-0.02 microg/mL; E(max): 99.1+/-0.46%)., Conclusion: It is concluded that (i) CPE exerted a powerful myogenic and L-type Ca(2+)-dependent relaxing effect in the isolated rat ileum and that (ii) the human ileum is sensitive to the inhibitory effect of CPE. If confirmed in vivo, our data could explain the traditional use of this herb in the treatment of intestinal spasms.

The hallucinogenic plant Salvia divinorum has been used for medical treatments of gastrointestinal disorders. Here, we evaluated the effect of a standardized extract from the leaves of Salvia divinorum (SDE) and of its active ingredient salvinorin A on motility in vivo, both in physiological states and during croton oil-induced intestinal inflammation. SDE (1-100 mg kg(-1)) significantly inhibited motility only in inflamed, but not in control, mice. In control mice, salvinorin A (0.01-10 mg kg(-1)) significantly inhibited motility only at the highest doses tested (3 and 10 mg kg(-1)) and this effect was not counteracted by naloxone or by the kappa-opioid receptor (KOR) antagonist nor-binaltorphimine. Inflammation significantly increased the potency of salvinorin A (but not of the KOR agonist U-50488) in reducing motility. The inhibitory effects of both salvinorin A and U-50488 in inflamed mice were counteracted by naloxone or by nor-binaltorphimine. We conclude that salvinorin A may reduce motility through activation of different targets. In physiological states, salvinorin A, at high doses, inhibited motility through a non-KOR mediated mechanism. Gut inflammation increased the potency of salvinorin A; this effect was mediated by KOR, but it was not shared by U-50488, thus suggesting that salvinorin A may have target(s) other than KOR in the inflamed gut.

A new sesquiterpene polyol ester characterized as 1alpha,6beta,8beta-triacetoxy-9beta-benzoyloxydihydro-beta-agarofuran (1), along with the three known compounds: 1alpha,6beta,8alpha-triacetoxy-9alpha-benzoyloxydihydro-beta-agarofuran (2), angulatueoid C (3), and 1alpha,6beta,8beta,14-tetraacetoxy-9alpha-benzoyloxydihydro-beta-agarofuran (4), was isolated from the CCl (4)-soluble fraction of Celastrus paniculatus methanolic seed extract. All four compounds produce at a concentration of 1 microg/mL a relaxant effect on the isolated rat ileum of 31.4 +/- 7.5, 24.3 +/- 9.6, 24.4 +/- 4.9, and 16.2 +/- 7.2 %, respectively.

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.

A new natural labdane diterpene, marrulibanoside, was isolated from the acetonic extract of aerial parts of M. globosum Montbr. et Auch. ex Benth. ssp. libanoticum Boiss. (Lamiaceae). Its structure was determined by spectroscopic methods such as 1D and 2D NMR and mass spectrometry. Pharmacological studies have shown that the extract of M. globosum exerts anti-inflammatory effects in the rat paw oedema induced by carrageenin resulting in reduced paw swelling. This activity, which seems due to marrulibanoside, is a consequence of iNOS and COX-2 activities inhibition.

A bioassay-guided separation of a methanolic extract obtained from the roots of Boerhaavia diffusa L. (Nyctaginaceae) allowed us to isolate five compounds belonging to the class of rotenoids: the known boeravinone D ( 1), boeravinone E ( 2), compound 5 and two novel compounds that we have named boeravinone G ( 3) and boeravinone H ( 4). The structures of the new molecules have been determined on the basis of their HR-EI-MS, (1)H- and (13)C-NMR and 2D-NMR (HMQC, HMBC) data. All the isolated rotenoids have been evaluated for their effect on intestinal motility in vitro. Three of them (boeravinone G, boeravinone E and compound 5) exhibited spasmolytic activity. Preliminary structure-activity relationships have been established highlighting the effect of substitutions on rings B and D.

Bacopa monniera (BM), a traditional Ayurvedic medicine, used for centuries as a memory enhancing, anti-inflammatory, analgesic, antipyretic, sedative and antiepileptic agent. The plant, plant extract and isolated bacosides (the major active principles) have been extensively investigated in several laboratories for their neuropharmacological effects and a number of reports are available confirming their nootropic action. In addition, researchers have evaluated the anti-inflammatory, cardiotonic and other pharmacological effects of BM preparations/extracts. Therefore, in view of the important activities performed by this plant, investigation must be continued in the recently observed actions described in this paper. Moreover, other clinical studies have to be encouraged, also to evidence any side effects and possible interactions between this herbal medicine and synthetic drugs.

Objectives: To evaluate the effect of St. John's wort (SJW), an effective and safe herbal antidepressant, on rat bladder contractility. Recent data have suggested a strong association between depression and urinary incontinence., Methods: Strips were cut from the bladder body and placed in organ baths containing Krebs solution. Contractions were induced by electrical field stimulation (EFS) and, in some experiments, by exogenous alpha,beta (alpha,beta)-methylene adenosine triphosphate., Results: St. John's wort was significantly more active in inhibiting the EFS-induced contractions than the alpha,beta-methylene adenosine triphosphate-induced contractions, suggesting both a presynaptic site of action and a direct inhibition of bladder smooth muscle. The inhibitory effect of SJW on EFS-induced contractions was unaffected by methysergide, haloperidol, phentolamine plus propranolol (antagonists that block the action of the neurotransmitters 5-hydroxytriptamine, dopamine, and noradrenaline on their own receptors), the L-type calcium channel antagonist verapamil, capsazepine (which blocks the vanilloid receptor), or cannabinoid CB1 receptor antagonist SR141716A. However, the opioid receptor antagonist naloxone significantly reduced the inhibitory effect of SJW on EFS-induced contractions. Among the chemical constituents of SJW tested, hyperforin and, to a lesser extent, the flavonoid kaempferol showed inhibitory effects., Conclusions: The results of our study demonstrated that SJW inhibits excitatory transmission of the rat urinary bladder and also directly inhibits smooth muscle contractility. The inhibitory effect on excitatory transmission could involve, at least in part, opioid receptors. SJW may be evaluated for its possible use in treating urinary incontinence in depressed patients.

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).

Three new diterpenoids belonging to the clerodane (2-3) and halimane (4) structural types have been isolated from the bark of Croton eluteria Bennet, commonly known as cascarilla. Their structures have been fully characterized by spectroscopic means. Cascarilla extract and its major component, cascarillin, were found to significantly increase histamine-induced gastric acid secretion in the mouse stomach. These preliminary results provide the first rationale for the use of cascarilla in bitter preparations aimed at improving digestion.

Bacopa monniera L. (family Scrophulariaceae) (BM) is an Ayurvedic medicine, clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative. In this work, the free radical scavenging capacity of a methanol extract of BM and the effect on DNA cleavage induced by H2O2 UV-photolysis was investigated. In addition, we examined whether this plant extract is capable of reducing the hydrogen peroxide-induced cytotoxicity and DNA damage in human non-immortalized fibroblasts. It showed a dose-dependent free radical scavenging capacity and a protective effect on DNA cleavage. These results were confirmed by a significant protective effect on H2O2-induced cytoxicity and DNA damage in human non-immortalized fibroblasts. The antioxidant capacity of BM may explain, at least in part, the reported antistress, immunomodulatory, cognition-facilitating, antiinflammatory and antiaging effects produced by it in experimental animals and in clinical situations and may justify further investigation of its other beneficial properties. Moreover, this experimental evidence suggests that because of its antioxidant activity, this Ayurvedic drug may be useful in the treatment of human pathologies in which free radical production plays a key role., (Copyright 2003 John Wiley & Sons, Ltd.)

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.

Celastrus paniculatus L. (Celastraceae) (CP), Picrorhiza kurroa L. (Scrophulariaceae) (PK) and Withania somnifera L. (Solanaceae) (WS) are Indian medicinal plants having a remarkable reputation, as a factor of health care, among the indigenous medical practitioners. The plants exhibit varying degrees of therapeutic value some of which useful in the treatment of cognitive dysfunction, epilepsy, insomnia, rheumatism, gout, dyspepsia. In this work, we have investigated the free radical scavenging capacity of methanolic extracts from CP, PK, WS and the effect on DNA cleavage induced by H2O2 UV-photholysis. In addition, we investigated whether these plant extracts are capable of reducing the hydrogen peroxide-induced cytotoxicity and DNA damage in human non-immortalized fibroblasts. These extracts showed a dose-dependent free radical scavenging capacity and a protective effect on DNA cleavage; methanolic extracts from PK was more active than extracts from CP and WS. These results were confirmed by a significant protective effect on H2O2-induced cytoxicity and DNA damage in human non-immortalized fibroblasts. These antioxidant effects of active principle of CP, PK and WS may explain, at least in part, the reported anti-stress, immunomodulatory, cognition-facilitating, anti-inflammatory and antiaging effects produced by them in experimental animal and in clinical situations and may justify the further investigation of their other beneficial biological properties.

Current evidence suggests that aberrant crypt foci (ACF) can be used to evaluate agents for their potential colon carcinogenic activity. The aim of the present study was to determine whether senna pod extract (SE) itself induces ACF and tumors in the rat colon or increases the development of ACF and tumors induced by azoxymethane (AOM). A daily administration of SE 10 mg/kg by mouth for 13-28 weeks produced a weak laxative effect but did not itself cause the appearance of ACF or tumors. The numbers of ACF and tumors induced by AOM were, however, increased by a dose of SE (100 mg/kg) able to induce chronic diarrhea over three months. These results suggest that SE does not cause the appearance of ACF or tumors in the rat colon nor does it have a promoting effect when given to rats at a dose that produces laxation (10 mg/kg), whereas a diarrhogenic dose (100 mg/kg) increases the appearance of tumors induced by AOM. [ABSTRACT FROM AUTHOR]