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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.)

Purpose: Colon cancer is a major public health problem. Cannabis-based medicines are useful adjunctive treatments in cancer patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS, i.e. CBD botanical drug substance, on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo., Methods: Proliferation was evaluated in colorectal carcinoma (DLD-1 and HCT116) as well as in healthy colonic cells using the MTT assay. CBD BDS binding was evaluated by its ability to displace [(3)H]CP55940 from human cannabinoid CB1 and CB2 receptors. In vivo, the effect of CBD BDS was examined on the preneoplastic lesions (aberrant crypt foci), polyps and tumours induced by the carcinogenic agent azoxymethane (AOM) as well as in a xenograft model of colon cancer in mice., Results: CBD BDS and CBD reduced cell proliferation in tumoral, but not in healthy, cells. The effect of CBD BDS was counteracted by selective CB1 and CB2 receptor antagonists. Pure CBD reduced cell proliferation in a CB1-sensitive antagonist manner only. In binding assays, CBD BDS showed greater affinity than pure CBD for both CB1 and CB2 receptors, with pure CBD having very little affinity. In vivo, CBD BDS reduced AOM-induced preneoplastic lesions and polyps as well as tumour growth in the xenograft model of colon cancer., Conclusions: CBD BDS attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabis-based medicines in cancer patients., (Copyright © 2013 Elsevier GmbH. 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.

Garlic (Allium sativum L. fam. Alliaceae) is one of the best-researched, best-selling herbal remedies and is also commonly used as a food and a spice. Garlic constituents include enzymes (for example, alliinase) and sulfur-containing compounds, including alliin, and compounds produced enzymatically from alliin (for example, allicin). Traditionally, it has been employed to treat infections, wounds, diarrhea, rheumatism, heart disease, diabetes, and many other disorders. Experimentally, it has been shown to exert antilipidemic, antihypertensive, antineoplastic, antibacterial, immunostimulant and hypoglycemic actions. Clinically, garlic has been evaluated for a number of conditions, including hypertension, hypercholesterolemia, intermittent claudication, diabetes, rheumatoid arthritis, common cold, as an insect repellent, and for the prevention of arteriosclerosis and cancer. Systematic reviews are available for the possible antilipidemic, antihypertensive, antithrombotic and chemopreventive effects. However, the clinical evidence is far from compelling. Garlic appears to be generally safe although allergic reactions may occur.

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.

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.

Chronic use of anthraquinone laxatives has been blamed for the induction of habituation and the development of colonic cancer, but there are no definitive studies which have demonstrated this. To evaluate the carcinogenic potential of anthraquinones, the effect of long-term senna pod extract (SE) treatment on either healthy rats or rats treated with an initiating tumor agent (azoxymethane--AOM) has been studied. SE (30 and 60mg/kg), administered for 110 weeks, did not induce the development of aberrant crypt foci (ACF) and tumors in healthy rats. The development of ACF and tumors in rats treated with AOM were significantly reduced by SE (30 and 60 mg/kg). These results suggest that a chronic SE use does not predispose to colon cancer. By contrast, SE might exert an anti-tumoral activity on rat colon carcinogenesis.

Objective: Conventional antiemetics are burdened with the potential of teratogenic effects during the critical embryogenic period of pregnancy. Thus, a safe and effective medication would be a welcome addition to the therapeutic repertoire. This systematic review was aimed at assessing the evidence for or against the efficacy and safety of ginger (Zingiber officinale) therapy for nausea and vomiting during pregnancy., Data Sources: Systematic literature searches were conducted in 3 computerized databases (MEDLINE, EMBASE, and Cochrane Library), and the reference lists of all papers located were checked for further relevant publications., Methods of Study Selection: For the evaluation of efficacy, only double-blind, randomized controlled trials (RCTs) were included. All retrieved clinical data, including uncontrolled trials, case reports, observational studies, and RCTs, were included in the review of safety., Tabulation, Integration, and Results: Six double-blind RCTs with a total of 675 participants and a prospective observational cohort study (n = 187) met all inclusion criteria. The methodological quality of 4 of 5 RCTs was high. Four of the 6 RCTs (n = 246) showed superiority of ginger over placebo; the other 2 RCTs (n = 429) indicated that ginger was as effective as the reference drug (vitamin B6) in relieving the severity of nausea and vomiting episodes. The observational study retrieved and RCTs (including follow-up periods) showed the absence of significant side effects or adverse effects on pregnancy outcomes. There were no spontaneous or case reports of adverse events during ginger treatment in pregnancy., Conclusion: Ginger may be an effective treatment for nausea and vomiting in pregnancy. However, more observational studies, with a larger sample size, are needed to confirm the encouraging preliminary data on ginger safety., Level of Evidence: I.

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.

The seed oil obtained from Celastrus paniculatus has been used in Ayurvedic medicine for the treatment of several complaints including intestinal disorders. The muscle relaxing activity of C. paniculatus has been studied in vitro on isolated preparations of rat intestine. C. paniculatus seeds extract (0.001 - 100 microg/mL) produced a concentration-related relaxation of the rat ileum [IC (50) (95 % c. l.) 0.24 (0.13 - 0.45) microg/mL]. Among the four fractions ( n-hexane, CCl (4), CHCl (3), n-BuOH) obtained from the methanolic extract of C. paniculatus, only the carbon tetrachloride fraction (0.01 - 10 000 ng/mL) induced a significant relaxation of the intestinal muscle [IC (50) (95 % c. l.): 1.9 (1.38 - 2.87) ng/mL]. Three new sesquiterpene polyol esters have been isolated from the carbon tetrachloride fraction. These new metabolites, characterised as 1alpha,8beta,14-triacetoxy-9beta-furoyloxydihydro-beta-agarofuran ( 1), 1alpha, 6beta,8beta,14-tetraacetoxy-9beta-benzoyloxydihydro-beta-agarofuran ( 2) and 1alpha,8beta-diacetoxy-9beta-benzoyloxydihydro-beta-agarofuran ( 3), at the concentration of 1 microg/mL produced a relaxant effect of 30.6 +/- 12.2 %, 26.9 +/- 4.7 % and 7.27 +/- 1.7 %, respectively.

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.)

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.

Background: Cimicifuga racemosa has long been advocated as an alternative to hormone-replacement therapy. However, recent experimental studies and a clinical trial have raised some questions on its utility. The aim of this systematic review is principally to summarise the trial evidence regarding the efficacy of C. racemosa in the treatment of menopausal symptoms. In addition, we also explore the evidence relating to the mechanism of action of this herbal medicine., Methods: Searches of seven computerised databases were performed to identify all randomised clinical trials (RCTs) on C. racemosa as well as animal and in vitro experiments. No language restrictions were imposed. Data were extracted by both authors according to predefined criteria and are summarised in narrative form., Results: Four RCTs of C. racemosa as a treatment of menopausal symptoms were included. They yielded no compelling evidence for the efficacy of C. racemosa on menopausal symptoms. The small beneficial effects observed in some studies could be explained by a central activity, and an oestrogenic activity cannot be completely excluded., Conclusions: In spite of plausible mechanisms of action of C. racemosa, its clinical efficacy for the treatment of menopausal symptoms has not been convincingly demonstrated through rigorous clinical trials. Additional rigorous RCTs and biochemical and chemical investigations are warranted.

Conventional antidepressants are associated with a range of adverse drug reactions. The herb Hypericum perforatum (St John's wort) might offer another approach to the treatment of depression. Biochemical and animal studies suggest that the phloroglucinol derivative hyperforin is the main active ingredient of St John's wort, and inhibits the synaptosomal uptake of 5-HT, noradrenaline, dopamine, glutamate and GABA. St John's wort has been shown to alleviate symptoms of mild to moderate depression, and seems to offer significant advantages over conventional antidepressants because it is associated with fewer adverse reactions. However, important herb--drug interactions have been described. In view of its efficacy and safety records, St John's wort should be considered for the first-line treatment of mild to moderate depression.

Phytogenic agents have traditionally been used by herbalists and indigenous healers for the prevention and treatment of peptic ulcer. This article reviews the anti-acid/anti-peptic, gastro-protective and/or anti-ulcer properties of the most commonly employed herbal medicines and their identified active constituents. Botanical compounds with anti-ulcer activity include flavonoids (i.e. quercetin, naringin, silymarin, anthocyanosides, sophoradin derivatives) saponins (i.e. from Panax japonicus and Kochia scoparia), tannins (i.e. from Linderae umbellatae), gums and mucilages (i.e. gum guar and myrrh). Among herbal drugs, liquorice, aloe gel and capsicum (chilli) have been used extensively and their clinical efficacy documented. Also, ethnomedical systems employ several plant extracts for the treatment of peptic ulcer. Despite progress in conventional chemistry and pharmacology in producing effective drugs, the plant kingdom might provide a useful source of new anti-ulcer compounds for development as pharmaceutical entities or, alternatively, as simple dietary adjuncts to existing therapies.