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1.  The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study 
Background
Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels.
Methods
A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded.
Results
Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the serum alkaline phosphatase (ALP), TB, and lipids levels were not modified. There were no reported severe AEs during this study, or abnormalities observed on blood glucose, total protein, albumin, blood urea nitrogen (BUN), and creatinine levels.
Conclusion
The data of this trial indicate that FTP is effective and safe, generally well-tolerated without severe AEs, in the treatment of subjects with elevated ALT levels over a 12 weeks period.
Trial registration
ClinicalTrials.gov: http://NCT01634256
doi:10.1186/1472-6882-13-58
PMCID: PMC3600681  PMID: 23497020
2.  Guava leaf extracts promote glucose metabolism in SHRSP.Z-Leprfa/Izm rats by improving insulin resistance in skeletal muscle 
Background
Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) have been associated with insulin-resistance; however, the effective therapies in improving insulin sensitivity are limited. This study is aimed at investigating the effect of Guava Leaf (GL) extracts on glucose tolerance and insulin resistance in SHRSP.Z-Leprfa/Izm rats (SHRSP/ZF), a model of spontaneously metabolic syndrome.
Methods
Male rats at 7 weeks of age were administered with vehicle water or treated by gavage with 2 g/kg GL extracts daily for six weeks, and their body weights, water and food consumption, glucose tolerance, and insulin resistance were measured.
Results
Compared with the controls, treatment with GL extracts did not modulate the amounts of water and food consumption, but significantly reduced the body weights at six weeks post treatment. Treatment with GL extracts did not alter the levels of fasting plasma glucose and insulin, but significantly reduced the levels of plasma glucose at 60 and 120 min post glucose challenge, also reduced the values of AUC and quantitative insulin sensitivity check index (QUICKI) at 42 days post treatment. Furthermore, treatment with GL extracts promoted IRS-1, AKT, PI3Kp85 expression, then IRS-1, AMKP, and AKT308, but not AKT473, phosphorylation, accompanied by increasing the ratios of membrane to total Glut 4 expression and adiponectin receptor 1 transcription in the skeletal muscles.
Conclusions
These data indicated that GL extracts improved glucose metabolism and insulin sensitivity in the skeletal muscles of rats by modulating the insulin-related signaling.
doi:10.1186/1472-6882-13-52
PMCID: PMC3599057  PMID: 23452929
3.  Photoprotective and antioxidant effects of Rhubarb: inhibitory action on tyrosinase and tyrosine kinase activities and TNF-α, IL-1α and α-MSH production in human melanocytes 
Background
Exposure to ultraviolet (UV) radiation causes various forms of acute and chronic skin damage, including immunosuppression, inflammation, premature aging and photodamage. Furthermore, it induces the generation of reactive oxygen species, produces proinflammatory cytokines and melanocyte-stimulating hormone (MSH) and increases tyrosinase activity. The aim of this study was to evaluate the potential photoprotective effects of Rheum rhaponticum L. rhizome extract on human UV-stimulated melanocytes.
Methods
The effects of Rheum rhaponticum rhizome extract on tyrosine kinase activity, and on interleukin-1α (IL-1α), tumour necrosis factor α (TNF-α), and α-MSH production in human epidermal melanocytes were evaluated under UV-stimulated and non-stimulated conditions. Antioxidant activity was evaluated by lipid peroxidation and 1,1-dyphenyl-2-picryl-hydrazyl (DPPH) assays, while anti-tyrosinase activity was evaluated by the mushroom tyrosinase method.
Results
Rheum rhaponticum L. rhizome extract showed in vitro antioxidant properties against lipid peroxidation, free radical scavenging and anti-tyrosinase activities, and inhibited the production of IL-1α, TNF-α, α-MSH, and tyrosine kinase activity in melanocytes subjected to UV radiation.
Conclusions
These results support the inclusion of Rheum rhaponticum L. rhizome extract into cosmetic, sunscreen and skin care products for the prevention or reduction of photodamage.
doi:10.1186/1472-6882-13-49
PMCID: PMC3598645  PMID: 23445687
Rheum rhaponticum; Skin-lightening; Photoprotection; α-MSH; UV radiation; Melanocytes
4.  Propolis changes the anticancer activity of temozolomide in U87MG human glioblastoma cell line 
Background
Propolis is a honey bee product which contains many active compounds, such as CAPE or chrysin, and has many beneficial activities. Recently, its anti-tumor properties have been discussed. We have tested whether the ethanolic extract of propolis (EEP) interferes with temozolomide (TMZ) to inhibit U87MG cell line growth.
Methods
The U87MG glioblastoma cell line was exposed to TMZ (10-100 μM), EEP (10-100 μg/ml) or a mixture of TMZ and EEP during 24, 48 or 72 hours. The cell division was examined by the H3-thymidine incorporation, while the western blot method was used for detection of p65 subunit of NF-κB and ELISA test to measure the concentration of its p50 subunit in the nucleus.
Results
We have found that both, TMZ and EEP administrated alone, had a dose- and time-dependent inhibitory effect on the U87MG cell line growth, which was manifested by gradual reduction of cell viability and alterations in proliferation rate. The anti-tumor effect of TMZ (20 μM) was enhanced by EEP, which was especially well observed after a short time of exposition, where simultaneous usage of TMZ and EEP resulted in a higher degree of growth inhibition than each biological factor used separately. In addition, cells treated with TMZ presented no changes in NF-κB activity in prolonged time of treatment and EEP only slightly reduced the nuclear translocation of this transcription factor. In turn, the combined incubation with TMZ and EEP led to an approximately double reduction of NF-κB nuclear localization.
Conclusions
We conclude that EEP presents cytotoxic properties and may cooperate with TMZ synergistically enhancing its growth inhibiting activity against glioblastoma U87MG cell line. This phenomenon may be at least partially mediated by a reduced activity of NF-κB.
doi:10.1186/1472-6882-13-50
PMCID: PMC3598711  PMID: 23445763
Propolis; Glioblastoma; Temozolomide; Cell viability; DNA synthesis; NF-κB
5.  Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells 
Background
Capsaicin, a pungent phytochemical in a variety of red peppers of the genus Capsicum, has shown an anti-proliferative effect on various human cancer cell lines. In contrast, capsaicin has also been considered to promote the growth of cancer cells. Thus, the effects of capsaicin on various cell types need to be explored. The anti-proliferative effects of capsaicin on human KB cancer cells are still unknown. Therefore, we examined the viability, cell cycle progression, and factors associated with apoptosis in KB cells treated with capsaicin.
Methods
The cell proliferation/viability and cytotoxicity of KB cells exposed to capsaicin were determined by a sulforhodamine B colorimetric assay and trypan blue exclusion. Apoptosis was detected by Hoechst staining and confirmed by western blot analysis of poly-(ADP-ribose) polymerase cleavage. Cell cycle distribution and changes of the mitochondrial membrane potential were analyzed by flow cytometry. Furthermore, the expression of caspase 3, 8 and 9 was evaluated by immunoblotting.
Results
We found that treatment of KB cells with capsaicin significantly reduced cell proliferation/viability and induced cell death in a dose-dependent manner compared with that in the untreated control. Cell cycle analysis indicated that exposure of KB cells to capsaicin resulted in cell cycle arrest at G2/M phase. Capsaicin-induced growth inhibition of KB cells appeared to be associated with induction of apoptosis. Moreover, capsaicin induced disruption of the mitochondrial membrane potential as well as activation of caspase 9, 3 and poly-(ADP-ribose) polymerase in KB cells.
Conclusions
Our data demonstrate that capsaicin modulates cell cycle progression and induces apoptosis in human KB cancer cells through mitochondrial membrane permeabilization and caspase activation. These observations suggest an anti-cancer activity of capsaicin.
doi:10.1186/1472-6882-13-46
PMCID: PMC3599796  PMID: 23433093
Capsaicin; KB cells; Cell cycle; Apoptosis; Mitochondria
6.  Physicochemical and antioxidant properties of Malaysian honeys produced by Apis cerana, Apis dorsata and Apis mellifera 
Background
The aim of the present study was to evaluate the physicochemical and antioxidant properties of Malaysian monofloral honey samples—acacia, pineapple and borneo honey—and compare them with tualang honey. Acacia and pineapple honey are produced by Apis mellifera bees while borneo and tualang honey are produced by Apis cerana and Apis dorsata bees, respectively.
Methods
The physical parameters of honey, such as pH, moisture content, electrical conductivity (EC), total dissolved solids (TDS), color intensity, total sugar and apparent sucrose content, were measured. Hydroxymethylfurfural (HMF) was measured using high performance liquid chromatography, and a number of biochemical and antioxidant tests were performed to determine the antioxidant properties of the honey samples.
Results
Acacia honey was the most acidic (pH 3.53), whereas pineapple honey had the lowest moisture content (14.86%), indicating that both types of honey can resist microbial spoilage more effectively when compared to tualang honey (pH 3.80 and 17.53% moisture content). Acacia honey contained the highest EC (0.76 mS/cm), whereas borneo honey had the highest (377 ppm) TDS. The mean HMF content in Malaysian honey was 35.98 mg/kg. Tualang honey, which is amber color, had the highest color intensity (544.33 mAU). Acacia honey is the sweetest, and contained the highest concentration of total sugar, reducing sugar and apparent sucrose. Tualang honey had the highest concentration of phenolic compounds (352.73 ± 0.81 mg galic acid/kg), flavonoids (65.65 ± 0.74 mg catechin/kg), DPPH (59.89%), FRAP values (576.91 ± 0.64 μM Fe (II)/100 g) and protein content (4.83 ± 0.02 g/kg) as well as the lowest AEAC values (244.10 ± 5.24 mg/kg), indicating its strong antioxidant properties. Proline, an important amino acid that is present in honey was also measured in the present study and it was found at the highest concentration in pineapple honey. Several strong correlations were found among the biochemical and antioxidant parameters of all the Malaysian honeys.
Conclusion
Although Malaysian honeys are of good quality, tualang honey contains the strongest antioxidant properties by far.
doi:10.1186/1472-6882-13-43
PMCID: PMC3598513  PMID: 23433009
Acacia honey; Pineapple honey; Tualang honey; Antioxidants; Apis cerana; Apis dorsata; Apis mellifera
7.  Citrus aurantium L. essential oil exhibits anxiolytic-like activity mediated by 5-HT1A-receptors and reduces cholesterol after repeated oral treatment 
Background
The current treatments for anxiety disorders and depression have multiple adverse effects in addition to a delayed onset of action, which has prompted efforts to find new substances with potential activity in these disorders. Citrus aurantium was chosen based on ethnopharmacological data because traditional medicine refers to the Citrus genus as useful in diminishing the symptoms of anxiety or insomnia, and C. aurantium has more recently been proposed as an adjuvant for antidepressants. In the present work, we investigated the biological activity underlying the anxiolytic and antidepressant effects of C. aurantium essential oil (EO), the putative mechanism of the anxiolytic-like effect, and the neurochemical changes in specific brain structures of mice after acute treatment. We also monitored the mice for possible signs of toxicity after a 14-day treatment.
Methods
The anxiolytic-like activity of the EO was investigated in a light/dark box, and the antidepressant activity was investigated in a forced swim test. Flumazenil, a competitive antagonist of benzodiazepine binding, and the selective 5-HT1A receptor antagonist WAY100635 were used in the experimental procedures to determine the mechanism of action of the EO. To exclude false positive results due to motor impairment, the mice were submitted to the rotarod test.
Results
The data suggest that the anxiolytic-like activity observed in the light/dark box procedure after acute (5 mg/kg) or 14-day repeated (1 mg/kg/day) dosing was mediated by the serotonergic system (5-HT1A receptors). Acute treatment with the EO showed no activity in the forced swim test, which is sensitive to antidepressants. A neurochemical evaluation showed no alterations in neurotransmitter levels in the cortex, the striatum, the pons, and the hypothalamus. Furthermore, no locomotor impairment or signs of toxicity or biochemical changes, except a reduction in cholesterol levels, were observed after treatment with the EO.
Conclusion
This work contributes to a better understanding of the biological activity of C. aurantium EO by characterizing the mechanism of action underlying its anxiolytic-like activity.
doi:10.1186/1472-6882-13-42
PMCID: PMC3598547  PMID: 23432968
Anxiolytic; Citrus aurantium; Essential oil; Mice; Neurochemistry; Serotonin
8.  Induction of selective cytotoxicity and apoptosis in human T4-lymphoblastoid cell line (CEMss) by boesenbergin a isolated from boesenbergia rotunda rhizomes involves mitochondrial pathway, activation of caspase 3 and G2/M phase cell cycle arrest 
Background
Boesenbergia rotunda (Roxb.) Schlecht (family zingiberaceae) is a rhizomatous herb that is distributed from north-eastern India to south-east Asia, especially in Indonesia, Thailand and Malaysia. Previous research has shown that the crude extract of this plant has cytotoxic properties. The current study examines the cytotoxic properties of boesenbergin A isolated from Boesenbergia rotunda.
Methods
MTT assay was used to check the cytotoxicity of boesenbergin A. The morphological assessment of apoptosis was monitored using normal and fluorescence microscopy. The early and late phase of apoptosis was investigated using annexin V and DNA laddering assays, respectively. The mitochondrial membrane potential (MMP) was assessed by fluorescence microscopy. Human apoptosis proteome profiler assays were performed to investigate the mechanism of cell death. In addition, the protein levels of Bax, Bcl2 and HSP 70 were also analyzed using western blot. Assays of caspase =-3/7, -8 and =-9 were carried out in order to test for induction during treatment. Lastly, cell cycle progression was analyzed using flow cytometry.
Results
Boesenbergin A was found to have the highest toxicity towards CEMss cancer cells (IC50 = 8 μg/ml). The morphology of CEMss cells after treatment showed evidence of apoptosis that included blebbing and chromatin condensation. The annexin V assay revealed that early apoptosis is induced after treatment. The DNA laddering assay confirmed that DNA fragmentation had occurred during late apoptosis. The cell cycle analysis indicated that boesenbergin A was able to induce G2/M phase arrest in CEMss cells. The activity of caspases -3/7, -8 and -9 was increased after treatment which indicates both intrinsic and extrinsic pathways are induced during apoptosis. The involvement of mitochondria was established by increased mitochondrial membrane potential and up and down regulation of Bcl2 and Bax proteins as well as HSP70.
Conclusion
In conclusion, the results demonstrated that boesenbergin A induced apoptosis of CEMss cells through Bcl2/Bax signaling pathways with the involvement of caspases and G2/M phase cell cycle arrest. The current findings warrant further research on boesenbergin A as a novel chemotherapeutic agent for leukemia intervention including studies in animal models.
doi:10.1186/1472-6882-13-41
PMCID: PMC3600682  PMID: 23432947
Boesenbergia rotunda; Boesenbergin A; CEMss; Anticancer; Cytotoxicity
9.  Antidiabetic and antihyperlipidemic activity of Piper longum root aqueous extract in STZ induced diabetic rats 
Background
The available drugs for diabetes, Insulin or Oral hypoglycemic agents have one or more side effects. Search for new antidiabetic drugs with minimal or no side effects from medicinal plants is a challenge according to WHO recommendations. In this aspect, the present study was undertaken to evaluate the antihyperglycemic and antihyperlipidemic effects of Piper longum root aqueous extract (PlrAqe) in streptozotocin (STZ) induced diabetic rats.
Methods
Diabetes was induced in male Wister albino rats by intraperitoneal administration of STZ (50 mg/kg.b.w). Fasting blood glucose (FBG) levels were measured by glucose-oxidase & peroxidase reactive strips. Serum biochemical parameters such as glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol were estimated. The activities of liver and kidney functional markers were measured. The statistical analysis of results was carried out using Student t-test and one-way analysis (ANOVA) followed by DMRT.
Results
During the short term study the aqueous extract at a dosage of 200 mg/kg.b.w was found to possess significant antidiabetic activity after 6 h of the treatment. The administration of aqueous extract at the same dose for 30 days in STZ induced diabetic rats resulted in a significant decrease in FBG levels with the corrections of diabetic dyslipidemia compared to untreated diabetic rats. There was a significant decrease in the activities of liver and renal functional markers in diabetic treated rats compared to untreated diabetic rats indicating the protective role of the aqueous extract against liver and kidney damage and its non-toxic property.
Conclusions
From the above results it is concluded that the plant extract is capable of managing hyperglycemia and complications of diabetes in STZ induced diabetic rats. Hence this plant may be considered as one of the potential sources for the isolation of new oral anti hypoglycemic agent(s).
doi:10.1186/1472-6882-13-37
PMCID: PMC3583796  PMID: 23414307
Antihypeglycemic; Antihyperlipidemic; Diabetes mellitus; Piper longum; Streptozotocin
10.  In vitro antitumor actions of extracts from endemic plant Helichrysum zivojinii 
Background
The aim of this research was to determine the intensity and mechanisms of the cytotoxic actions of five extracts isolated from the endemic plant species Helichrysum zivojinii Černjavski & Soška (family Asteraceae) against specific cancer cell lines. In order to evaluate the sensitivity of normal immunocompetent cells implicated in the antitumor immune response, the cytotoxicity of extracts was also tested against healthy peripheral blood mononuclear cells (PBMC).
Methods
The aerial parts of the plants were air-dried, powdered, and successively extracted with solvents of increasing polarity to obtain hexane, dichloromethane, ethyl-acetate, n-butanol and methanol extracts. The cytotoxic activities of the extracts against human cervix adenocarcinoma HeLa, human melanoma Fem-x, human myelogenous leukemia K562, human breast adenocarcinoma MDA-MB-361 cells and PBMC were evaluated by the MTT test. The mode of HeLa cell death was investigated by morphological analysis. Changes in the cell cycle of HeLa cells treated with the extracts were analyzed by flow cytometry. The apoptotic mechanisms induced by the tested extracts were determined using specific caspase inhibitors.
Results
The investigated Helichrysum zivojinii extracts exerted selective dose-dependent cytotoxic actions against selected cancer cell lines and healthy immunocompetent PBMC stimulated to proliferate, while the cytotoxic actions exerted on unstimulated PBMC were less pronounced. The tested extracts exhibited considerably stronger cytotoxic activities towards HeLa, Fem-x and K562 cells in comparison to resting and stimulated PBMC. It is worth noting that the cytotoxicity of the extracts was weaker against unstimulated PBMC in comparison to stimulated PBMC. Furthermore, each of the five extracts induced apoptosis in HeLa cells, through the activation of both intrinsic and extrinsic signaling pathways.
Conclusion
Extracts obtained from the endemic plant Helichrysum zivojinii may represent an important source of novel potential antitumor agents due to their pronounced and selective cytotoxic actions towards malignant cells.
doi:10.1186/1472-6882-13-36
PMCID: PMC3585823  PMID: 23414290
Helichrysum zivojinii; Cytotoxicity; Cancer cells; Peripheral blood mononuclear cells; Apoptosis
11.  The prevalence of traditional herbal medicine use among hypertensives living in South African communities 
Background
In South Africa, over 6 million people are hypertensive and the burden of disease shows that cardiovascular diseases (CVDs) are the leading cause of death among adults. Although treatments exist, few people comply or adhere to recommended treatment due to side effects or costs of the drugs, hence the reliance on alternative forms of treatment. Traditional herbal medicines (THM) are used for the management of hypertension but the prevalence of its use among hypertensive patients living in South African communities is not sufficiently known.
Methods
This was a cross-sectional descriptive study to determine the prevalence of THM use for hypertension, among 135 purposefully selected South African participants of the Prospective Urban and Rural Epidemiological (PURE) study, who are THM users. Data on THM use were collected by way of face to face interviews using structured questionnaires administered by trained field workers. Standard descriptive measures were used to characterize the study sample and responses to the questionnaire. Chi-square test was used when making comparisons between groups.
Results
There were 135 THM users, 21% of whom used THM to treat hypertension. Majority (82.1%) of the hypertensive THM users were females, only 29% were married or co-habitating, virtually all (96%) were unemployed and 86% were Christians. More than half (56%) of the respondents were aged between 55 and 64 years. THM was occasionally used (51.9%) as a combination of tea and other mixtures (63%) and prescribed by family/ friends/self-administered. There was a significant difference in the age, marital and employment status, as well as the form and frequency of THM use of hypertensive THM users compared to other THM users.
Conclusions
The study gives an insight into the prevalence of THM use by hypertensive patients in selected South African communities. The practice of self-medication was also observed which raises concern regarding the safety of medications taken by the participants. Health care providers should however be more aware of THM use and counsel patients regarding the combination of prescribed treatment regimen and herbal medicines and the potential of herb-drug interactions.
doi:10.1186/1472-6882-13-38
PMCID: PMC3598715  PMID: 23414344
12.  The eCALM Trial-eTherapy for cancer appLying mindfulness: online mindfulness-based cancer recovery program for underserved individuals living with cancer in Alberta: protocol development for a randomized wait-list controlled clinical trial 
Background
Elevated stress can exacerbate cancer symptom severity, and after completion of primary cancer treatments, many individuals continue to have significant distress. Mindfulness-Based Cancer Recovery (MBCR) is an 8-week group psychosocial intervention consisting of training in mindfulness meditation and yoga designed to mitigate stress, pain, and chronic illness. Efficacy research shows face-to-face (F2F) MBCR programs have positive benefits for cancer patients; however barriers exist that impede participation in F2F groups. While online MBCR groups are available to the public, none have been evaluated. Primary objective: determine whether underserved patients are willing to participate in and complete an online MBCR program. Secondary objectives: determine whether online MBCR will mirror previous efficacy findings from F2F MBCR groups on patient-reported outcomes.
Method/design
The study includes cancer patients in Alberta, exhibiting moderate distress, who do not have access to F2F MBCR. Participants will be randomized to either online MBCR, or waiting for the next available group. An anticipated sample size of 64 participants will complete measures online pre and post treatment or waiting period. Feasibility will be tracked through monitoring numbers eligible and participating through each stage of the protocol.
Discussion
47 have completed/completing the intervention. Data suggest it is possible to conduct a randomized waitlist controlled trial of online MBCR to reach underserved cancer survivors.
Trial registration
Clinical Trials.gov Identifier: NCT01476891
doi:10.1186/1472-6882-13-34
PMCID: PMC3576301  PMID: 23414206
Mindfulness; Cancer; Oncology; Randomized waitlist controlled trial; Online; Stress reduction; Meditation; Yoga
13.  Complementary and alternative medicine utilization by a sample of infertile couples in Jordan for infertility treatment: clinics-based survey 
Background
Although there is little information available to quantify the use of complementary and alternative medicine (CAM), growing evidence suggests that CAM prevalence among patients seeking infertility treatment is increasing worldwide. There are many products available on the market and many infertile patients demand information about CAM from their health care providers. This paper investigates the prevalence of CAM use among infertile couples in Jordan. Additionally, trends and factors contributing to CAM use for infertility treatment among these couples have been evaluated.
Methods
A face-to-face questionnaire inquiring demographic information, use of CAM for medical conditions, in general, and types of CAM used for infertility treatment, in specific, was completed by one thousand twenty one infertile patients attending at two types of facilities; in vitro Fertilization (IVF) centers at both public and private hospitals and infertility private clinics. Both types of facilities were distributed in different areas of Amman, the capital city of Jordan. The study was conducted between May and August 2012.
Results
Our results show that CAM therapies for infertility treatment were encountered in 44.7% of the study sample. The vast majority of CAM users were females. The most commonly used CAM therapies were herbs and spiritual healing. A clear correlation between the use of CAM for infertility versus the use of CAM for other chronic medical conditions has been found.
Conclusions
The prevalence of CAM use for infertility treatment in Jordan is relatively high, particularly among young females, well educated and with a low income, in consistence with the studies reported elsewhere. Herbs and spiritual healing are widely used among patients in adjunct to conventional medical interventions. As CAM use is prevalent among patients, there is a clear need for health providers to become more aware of this phenomenon and for further research in this field.
doi:10.1186/1472-6882-13-35
PMCID: PMC3599001  PMID: 23414246
Complementary and alternative medicine; Infertility treatment
14.  A potential anti-tumor herbal medicine, Corilagin, inhibits ovarian cancer cell growth through blocking the TGF-β signaling pathways 
Background
Phyllanthus niruri L. is a well-known hepatoprotective and antiviral medicinal herb. Recently, we identified Corilagin as a major active component with anti-tumor activity in this herbal medicine. Corilagin is a member of the tannin family that has been discovered in many medicinal plants and has been used as an anti-inflammatory agent. However, there have been few reports of the anti-tumor effects of Corilagin, and its anti-tumor mechanism has not been investigated clearly. The aim of the present study is to investigate the anticancer properties of Corilagin in ovarian cancer cells.
Methods
The ovarian cancer cell lines SKOv3ip, Hey and HO-8910PM were treated with Corilagin and analyzed by Sulforhodamine B (SRB) cell proliferation assay, flow cytometry, and reverse phase protein array (RPPA). Corilagin was delivered intraperitoneally to mice bearing SKOv3ip xenografts.
Results
Corilagin inhibited the growth of the ovarian cancer cell lines SKOv3ip and Hey, with IC50 values of less than 30 μM, while displaying low toxicity against normal ovarian surface epithelium cells, with IC50 values of approximately 160 μM. Corilagin induced cell cycle arrest at the G2/M stage and enhanced apoptosis in ovarian cancer cells. Immunoblotting assays demonstrated that Cyclin B1, Myt1, Phospho-cdc2 and Phospho-Weel were down-regulated after Corilagin treatment. Xenograft tumor growth was significantly lower in the Corilagin-treated group compared with the untreated control group (P <0.05). More interestingly, Corilagin inhibited TGF-β secretion into the culture supernatant of all tested ovarian cancer cell lines and blocked the TGF-β-induced stabilization of Snail. In contrast, a reduction of TGF-β secretion was not observed in cancer cells treated with the cytotoxic drug Paclitaxel, suggesting that Corilagin specifically targets TGF-β secretion. Corilagin blocked the activation of both the canonical Smad and non-canonical ERK/AKT pathways.
Conclusions
Corilagin extracted from Phyllanthus niruri L. acts as a natural, effective therapeutic agent against the growth of ovarian cancer cells via targeted action against the TGF-β/AKT/ERK/Smad signaling pathways.
doi:10.1186/1472-6882-13-33
PMCID: PMC3598193  PMID: 23410205
Corilagin; Herbal medicine; TGF-β; Ovarian cancer; Epithelial-mesenchymal transition; Cell cycle G2/M arrest; Apoptosis
15.  Chemical constituents and antihistamine activity of Bixa orellana leaf extract 
Background
Bixa orellana L. has been traditionally used in Central and South America to treat a number of ailments, including internal inflammation, and in other tropical countries like Malaysia as treatment for gastric ulcers and stomach discomfort. The current study aimed to determine the major chemical constituents of the aqueous extract of B. orellana (AEBO) and to evaluate the antihistamine activity of AEBO during acute inflammation induced in rats.
Methods
Acute inflammation was produced by subplantar injection of 0.1 mL of 0.1% histamine into the right hind paw of each rat in the control and treatment groups. The degree of edema was measured before injection and at the time points of 30, 60, 120, 180, 240 and 300 min after injection. Changes of peritoneal vascular permeability were studied using Evans blue dye as a detector. Vascular permeability was evaluated by the amount of dye leakage into the peritoneal cavity in rats. To evaluate the inhibitory effect of AEBO on biochemical mediators of vascular permeability, the levels of nitric oxide (NO) and vascular endothelial growth factor (VEGF) were determined in histamine-treated paw tissues. The major constituents of AEBO were determined by gas chromatography–mass spectrometry (GC-MS) analysis.
Results
AEBO produced a significant inhibition of histamine-induced paw edema starting at 60 min time point, with maximal percentage of inhibition (60.25%) achieved with a dose of 150 mg/kg of AEBO at 60 min time point. Up to 99% of increased peritoneal vascular permeability produced by histamine was successfully suppressed by AEBO. The expression of biochemical mediators of vascular permeability, NO and VEGF, was also found to be downregulated in the AEBO treated group. Gas chromatography–mass spectrometry (GC-MS) analysis revealed that the major constituent in AEBO was acetic acid.
Conclusions
The experimental findings demonstrated that the anti-inflammatory activity of AEBO was due to its inhibitory effect on vascular permeability, which was suppressed as a result of the reduced expression of biochemical mediators (NO and VEGF) in tissues. Our results contribute towards the validation of the traditional use of Bixa orellana in the treatment of inflammatory disorders.
doi:10.1186/1472-6882-13-32
PMCID: PMC3582463  PMID: 23410184
Bixa orellana; Histamine; Anti-inflammatory; Vascular permeability
16.  Vasorelaxant effect of Prunus yedoensis bark 
Background
Prunus yedoensis Matsum. is used as traditional medicine—‘Yaeng-Pi’ or ‘Hua-Pi’—in Japan and Korea. However, no studies have examined the pharmacological activities of the P. yedoensis bark. Only the antioxidant and antiviral activities of P. yedoensis fruit and the anti-hyperglycaemic effect of P. yedoensis leaf have been investigated. While studying the antihypertensive effects of several medicinal plants, we found that a methanol extract of P. yedoensis bark (MEPY) had distinct vasorelaxant effects on rat aortic rings.
Methods
The aortic rings were removed from Sprague–Dawley rats and suspended in organ chambers containing 10 ml Krebs-Henseleit solution. The aortic rings were placed between 2 tungsten stirrups and connected to an isometric force transducer. Changes in tension were recorded via isometric transducers connected to a data acquisition system.
Results
MEPY relaxed the contraction induced by phenylephrine (PE) both in endothelium-intact and endothelium-denuded aortic rings concentration dependently. However, the vasorelaxant effects of MEPY on endothelium-denuded aortic rings were lower than endothelium-intact aortic rings. The vasorelaxant effects of MEPY on endothelium-intact aortic rings were reduced by pre-treatment with l-NAME, methylene blue, or ODQ. However, pre-treatment with indomethacin, atropine, glibenclamide, tetraethylammonium, or 4-aminopyridine had no affection. In addition, MEPY inhibited the contraction induced by extracellular Ca2+ in endothelium-denuded rat thoracic aorta rings pre-contracted by PE (1 μM) or KCl (60 mM) in Ca2+-free solution.
Conclusions
Our results suggest that MEPY exerts its vasorelaxant effects via the activation of NO formation by means of l-Arg and NO-cGMP pathways and via the blockage of extracellular Ca2+ channels.
doi:10.1186/1472-6882-13-31
PMCID: PMC3585796  PMID: 23410148
17.  Pharmacological, antioxidant, genotoxic studies and modulation of rat splenocyte functions by Cyperus rotundus extracts 
Background
Cyperus rotundus Linn. (Cyperaceae) is a Tunisian medicinal plant used in folkloric (traditional) medicine to treat stomach disorders and inflammatory diseases. The present study explored the analgesic, anti-inflammatory and genotoxic activities of extracts from the aerial parts of C. rotundus. The antioxidant capacity and the modulation of splenocyte functions by these extracts were also investigated in mice. The phytochemical analysis was carried out using standard methods.
Methods
Aqueous, ethyl acetate, methanol and TOF-enriched extracts (300, 150, and 50 μg/ml) were evaluated for their analgesic and anti-inflammatory activities. 4, 2, and 1 mg/ml of each extract were tested to investigate their effect on lipid peroxidation. The genotoxic study was monitored by measuring the structural chromosome aberrations of mice treated with 300 mg/kg of extract. The proliferation of lymphocytes in the absence and presence of mitogens was assessed at a concentration range 1–1000 μg/ml.
Results
The tested extracts were able to decrease the mouse ear oedema induced by xylene. Furthermore, it was shown that the same extracts reduced the number of abdominal contractions caused by acetic acid in mice, revealing the peripheral analgesic activity of these extracts. It is worth noting that mice treated with doses up to 300 mg/kg b.w. of Cyperus rotundus extracts did not exhibit any toxicity. The tested extracts significantly enhance lymphocyte proliferation at 1 mg/ml.
Conclusions
It appears that C. rotundus extracts contain potent components such as flavonoids that may potentially be useful for modulating the immune cell functions, provoking analgesic, anti-inflammatory and antioxidant effects.
doi:10.1186/1472-6882-13-28
PMCID: PMC3570401  PMID: 23388107
Cyperus rotundus; Analgesic activity; Anti-inflammatory activity; Lipid peroxidation effect; Chromosome aberrations; Immunomodulatory effect
18.  Cytotoxic and apoptotic evaluations of marine bacteria isolated from brine-seawater interface of the Red Sea 
Background
High salinity and temperature combined with presence of heavy metals and low oxygen renders deep-sea anoxic brines of the Red Sea as one of the most extreme environments on Earth. The ability to adapt and survive in these extreme environments makes inhabiting bacteria interesting candidates for the search of novel bioactive molecules.
Methods
Total 20 i.e. lipophilic (chloroform) and hydrophilic (70% ethanol) extracts of marine bacteria isolated from brine-seawater interface of the Red Sea were tested for cytotoxic and apoptotic activity against three human cancer cell lines, i.e. HeLa (cervical carcinoma), MCF-7 (Breast Adenocarcinoma) and DU145 (Prostate carcinoma).
Results
Among these, twelve extracts were found to be very active after 24 hours of treatment, which were further evaluated for their cytotoxic and apoptotic effects at 48 hr. The extracts from the isolates P1-37B and P3-37A (Halomonas) and P1-17B (Sulfitobacter) have been found to be the most potent against tested cancer cell lines.
Conclusion
Overall, bacterial isolates from the Red Sea displayed promising results and can be explored further to find novel drug-like molecules. The cell line specific activity of the extracts may be attributed to the presence of different polarity compounds or the cancer type i.e. biological differences in cell lines and different mechanisms of action of programmed cell death prevalent in different cancer cell lines.
doi:10.1186/1472-6882-13-29
PMCID: PMC3598566  PMID: 23388148
Marine bacteria; Deep sea brine pools; Extracts; Cytotoxicity; Apoptosis
19.  Acute and chronic antihypertensive effects of Cinnamomum zeylanicum stem bark methanol extract in L-NAME-induced hypertensive rats 
Background
Previous study showed that the aqueous extract of the stem bark of Cinnamomum zeylanicum possesses antihypertensive and vasodilatory properties. The present work investigates the acute and chronic antihypertensive effects of the methanol extract of Cinnamomum zeylanicum stem bark (MECZ) in L-NAME-induced hypertensive rats.
Methods
The acute antihypertensive effects of MECZ (5, 10 and 20 mg/kg) administered intravenously were evaluated in rats in which acute arterial hypertension has been induced by intravenous administration of L-NAME (20 mg/kg). For chronic antihypertensive effects, animals were treated with L-NAME (40 mg/kg/day) plus the vehicle or L-NAME (40 mg/kg/day) in combination with captopril (20 mg/kg/day) or MECZ (300 mg/kg/day) and compared with control group receiving only distilled water. All drugs were administered per os and at the end of the experiment that lasted for four consecutive weeks, blood pressure was measured by invasive method and blood samples were collected for the determination of the lipid profile. The heart and aorta were collected, weighed and used for both histological analysis and determination of NO tissue content.
Results
Acute intravenous administration of C. zeylanicum extract (5, 10 and 20 mg/kg) to L-NAME-induced hypertensive rats provoked a long-lasting decrease in blood pressure. Mean arterial blood pressure decreased by 12.5%, 26.6% and 30.6% at the doses of 5, 10 and 20 mg/kg, respectively. In chronic administration, MECZ and captopril significantly prevented the increase in blood pressure and organs’ weights, as well as tissue histological damages and were able to reverse the depletion in NO tissue’s concentration. The MECZ also significantly lower the plasma level of triglycerides (38.1%), total cholesterol (32.1%) and LDL-cholesterol (75.3%) while increasing that of HDL-cholesterol (58.4%) with a significant low atherogenic index (1.4 versus 5.3 for L-NAME group).
Conclusion
MECZ possesses antihypertensive and organ protective effects that may result from its ability to increase the production of the endogenous NO and/or to regulate dyslipidemia.
doi:10.1186/1472-6882-13-27
PMCID: PMC3572416  PMID: 23368533
Antihypertensive; Antihyperlipidemic; Cinnamomum zeylanicum; L-NAME-hypertensive rat; NO
20.  Antibacterial activities of the methanol extracts of ten Cameroonian vegetables against Gram-negative multidrug-resistant bacteria 
Background
Many edible plants are used in Cameroon since ancient time to control microbial infections. This study was designed at evaluating the antibacterial activities of the methanol extracts of ten Cameroonian vegetables against a panel of twenty nine Gram negative bacteria including multi-drug resistant (MDR) strains.
Methods
The broth microdilution method was used to determine the Minimal Inhibitory Concentrations (MIC) and the Minimal Bactericidal Concentrations (MBC) of the studied extracts. When chloramphenicol was used as a reference antibiotic, the MICs were also determined in the presence of Phenylalanine-Arginine β-Naphtylamide (PAβN), an efflux pumps inhibitor (EPI). The phytochemical screening of the extracts was performed using standard methods.
Results
All tested extracts exhibited antibacterial activities, with the MIC values varying from 128 to 1024 mg/L. The studied extracts showed large spectra of action, those from L. sativa, S. edule, C. pepo and S. nigrum being active on all the 29 bacterial strains tested meanwhile those from Amaranthus hybridus, Vernonia hymenolepsis, Lactuca.carpensis and Manihot esculenta were active on 96.55% of the strains used. The plant extracts were assessed for the presence of large classes of secondary metabolites: alkaloids, anthocyanins, anthraquinones, flavonoids, phenols, saponins, steroids, tannins and triterpenes. Each studied plant extract was found to contain compounds belonging to at least two of the above mentioned classes.
Conclusion
These results confirm the traditional claims and provide promising baseline information for the potential use of the tested vegetables in the fight against bacterial infections involving MDR phenotypes.
doi:10.1186/1472-6882-13-26
PMCID: PMC3598735  PMID: 23368430
Antibacterial; Gram-negative bacteria; Multi-drug resistant; Extract; Vegetable
21.  Effects of organic extracts of six Bangladeshi plants on in vitro thrombolysis and cytotoxicity 
Background
Thrombus formed in blood vessels lead to atherothrombotic diseases such as myocardial or cerebral infarction. Thrombolytic agents are used to dissolve the already formed clots in the blood vessels; however, these drugs sometimes cause serious and fatal consequences. Herbal preparations have been used since ancient times for the treatment of several diseases although they show little toxicity in some cases. Aqueous extracts of herbs used in thrombolysis have been reported before with cytotoxic data, however, the organic extracts of herbs have not been documented. This study aims to investigate whether organic extracts possess thrombolytic properties with minimal or no toxicity.
Methods
An in vitro thrombolytic model was used to check the clot lysis effect of six Bangladeshi herbal extracts viz., Ageratum conyzoides L., Clausena suffruticosa, Leea indica (Burm.f.) Merr., Leucas aspera Willd., Senna sophera L. Roxb., and Solanum torvum Swartz. using streptokinase as a positive control and water as a negative control. Briefly, venous blood drawn from twenty healthy volunteers was allowed to form clots which were weighed and treated with the test plant materials to disrupt the clots. Weight of clot after and before treatment provided a percentage of clot lysis. Cytotoxicity was screened by brine shrimp lethality bioassay using vincristine sulfate as positive control.
Results
Using an in vitro thrombolytic model, Ageratum conyzoides, Clausena suffruticosa, Leea indica, Leucas aspera, Senna sophera and Solanum torvum showed 18.12 ± 2.34%, 48.9 ± 2.44%, 39.30 ± 0.96%, 37.32 ± 2.00%, 31.61 ± 2.97% and 31.51 ± 0.57% and clot lysis respectively. Among the herbs studied Clausena suffruticosa, Leea indica and Leucas aspera showed very significant (p < 0.0001) percentage (%) of clot lysis compared to reference drug streptokinase (75.00 ± 3.04%). In brine shrimp cytotoxic assay, the extracts Ageratum conyzoides, Clausena suffruticosa, Leea indica, Leucas aspera, Senna sophera and Solanum torvum showed LC50 values 508.86 ± 6.62,41.16 ± 1.26, 2.65 ± 0.16, 181.67 ± 1.65, 233.37 ± 7.74 and 478.40 ± 3.23 μg/ml, respectively, with reference to vincristine sulfate (LC50 0.76 ± 0.04).
Conclusion
Through our study it was found that Clausena suffruticosa, Leea indica and Leucas aspera possessed effective thrombolytic properties whereas Senna sophera and Solanum torvum showed moderate to mild thrombolytic effects while Ageratum conyzoides showed no significant effect. No extract was found cytoxic compared to positive control. Clausena suffruticosa, Leea indica and Leucas aspera could be incorporated as a thrombolytic agent with in vivo effects to improve the atherothrombotic patients. However, Clausena suffruticosa could be the best one to use in this purpose.
doi:10.1186/1472-6882-13-25
PMCID: PMC3567938  PMID: 23363538
Thrombolysis; Clausena suffruticosa; Leea indica; Leucas aspera; Streptokinase
22.  Electroacupuncture preconditioning reduces cerebral ischemic injury via BDNF and SDF-1α in mice 
Background
This study was designed to determine if electroacupuncture (EA) preconditioning improves tissue outcome and functional outcome following experimentally induced cerebral ischemia in mice. In addition, we investigated whether the expression of brain-derived neurotrophic factor (BDNF) and stromal cell derived factor-1α (SDF-1α) and infarct volume were related with improvement in neurological and motor function by interventions in this study.
Methods
After treatment with EA at the acupoints ‘Baihui (GV20)’ and ‘Dazhui (GV14)’ for 20 min, BDNF was assessed in the cortical tissues based on Western blot and the SDF-1α and vascular endothelial growth factor (VEGF) levels in the plasma determined by ELISA. To assess the protective effects of EA against ischemic injury, the mice received once a day 20 min EA preconditioning for three days prior to the ischemic event. Focal cerebral ischemia was then induced by photothrombotic cortical ischemia. Infarct volumes, neurobehavioral deficit and motor deficit were evaluated 24 h after focal cerebral ischemia.
Results
The expression of BDNF protein increased significantly from 6 h, reaching a plateau at 12 h after the end of EA treatment in the cerebral cortex. Furthermore, SDF-1α, not VEGF, increased singnificantly from 12 h to 48 h after EA stimulation in the plasma. Moreover, EA preconditioning reduced the infarct volume by 43.5% when compared to control mice at 24 h after photothrombotic cortical ischemia. Consistent with a smaller infarct size, EA preconditioning showed prominent improvement of neurological function and motor function such as vestibule-motor function, sensori-motor function and asymmetric forelimb use. The expression of BDNF colocalized within neurons and SDF-1α colocalized within the cerebral vascular endothelium was observed throughout the ischemic cortex by EA.
Conclusions
Pretreatment with EA increased the production of BDNF and SDF-1α, which elicited protective effects against focal cerebral ischemia. These results suggest a novel mechanism of EA pretreatment-induced tolerance against cerebral ischemic injury.
doi:10.1186/1472-6882-13-22
PMCID: PMC3562247  PMID: 23356671
Focal cerebral ischemia; Electroacupuncture; BDNF; SDF-1α; Preconditioning
23.  Antidiarrhoeal and antimicrobial activity of Calpurnia aurea leaf extract 
Background
In Ethiopia, Calpurnia aurea is used for the treatment of syphilis, malaria, rabies, diabetes, hypertension, diarrhoea, leishmaniasis, trachoma, elephantiasis, fungal diseases and different swellings. However, despite its traditional usage as an antidiarrhoeal and antimicrobial agent, there is limited or no information regarding its effectiveness and mode of action in diarrhoea which may be caused by Shigella flexneri, Staphylococcus aureus, Escherichia coli and Salmonella typhi. Hence, we evaluated the 80% methanol (MeOH) extract of dried and powdered leaves of C. aurea for its antidiarrhoeal and antimicrobial activities.
Methods
Swiss albino mice of either sex were divided into five groups (five/group): Group I served as control and received vehicle (1% Tween 80) at a dose of 10 ml/kg orally; Group II served as standard and received loperamide at the dose of 3 mg/kg orally; Groups III, IV and V served as test groups and received the 80% MeOH leaf extract of C. aurea at doses of 100, 200 and 400 mg/kg orally, respectively. Diarrhoea was induced by oral administration of 0.5 ml castor oil to each mouse, 1 h after the above treatments. During an observation period of 4 h, time of onset of diarrhea, total number of faecal output (frequency of defecation) and weight of faeces excreted by the animals were recorded. Data were analyzed using one way analysis of variance followed by Tukey post test. Antimicrobial activity test was conducted using agar well diffusion assay. Clinical isolates tested were Salmonella typhi, Salmonella paratyphi, Salmonella typhimurium, Shigella species, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli.
Results
In castor oil induced diarrhea model, the 80% methanol leaf extract of C. aurea at 100, 200 and 400 mg/kg and the standard drug loperamide (3 mg/kg) significantly reduced the time of onset of diarrhea, the frequency of defecation (total number of faecal output) and weight of faeces. C. aurea leaf extract also showed good antimicrobial activity against all tested organisms.
Conclusions
C. aurea possesses good antidiarrhoeal and antimicrobial activity which support the traditional use of the plant in the treatment of diarrhea in Ethiopia.
doi:10.1186/1472-6882-13-21
PMCID: PMC3565866  PMID: 23351272
Calpurnia aurea leaf extract; Antidiarrhoeal; Antimicrobial; Ethiopia
24.  Antimicrobial and antiproliferative activities of stingless bee Melipona scutellaris geopropolis 
Background
Geopropolis is a type of propolis containing resin, wax, and soil, collected by threatened stingless bee species native to tropical countries and used in folk medicine. However, studies concerning the biological activity and chemical composition of geopropolis are scarce. In this study, we evaluated the antimicrobial and antiproliferative activity of the ethanolic extract of geopropolis (EEGP) collected by Melipona scutellaris and its bioactive fraction against important clinical microorganisms as well as their in vitro cytotoxicity and chemical profile.
Methods
The antimicrobial activity of EEGP and fractions was examined by determining their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against six bacteria strains as well as their ability to inhibit Streptococcus mutans biofilm adherence. Total growth inhibition (TGI) was chosen to assay the antiproliferative activity of EEGP and its bioactive fraction against normal and cancer cell lines. The chemical composition of M. scutellaris geopropolis was identified by reversed-phase high-performance liquid chromatography and gas chromatography–mass spectrometry.
Results
EEGP significantly inhibited the growth of Staphylococcus aureus strains and S. mutans at low concentrations, and its hexane fraction (HF) presented the highest antibacterial activity. Also, both EEGP and HF inhibited S. mutans biofilm adherence (p < 0.05) and showed selectivity against human cancer cell lines, although only HF demonstrated selectivity at low concentrations. The chemical analyses performed suggest the absence of flavonoids and the presence of benzophenones as geopropolis major compounds.
Conclusions
The empirical use of this unique type of geopropolis by folk medicine practitioners was confirmed in the present study, since it showed antimicrobial and antiproliferative potential against the cancer cell lines studied. It is possible that the major compounds found in this type of geopropolis are responsible for its properties.
doi:10.1186/1472-6882-13-23
PMCID: PMC3568042  PMID: 23356696
Melipona scutellaris; Geopropolis; Antimicrobial activity; Antiproliferative activity; Chemical profile
25.  Efficacy and safety of Suanzaoren decoction for primary insomnia: a systematic review of randomized controlled trials 
Background
Insomnia is a widespread human health problem, but there currently are the limitations of conventional therapies available. Suanzaoren decoction (SZRD) is a well known classic Chinese herbal prescription for insomnia and has been treating people’s insomnia for more than thousand years. The objective of this study was to evaluate the efficacy and safety of SZRD for insomnia.
Methods
A systematic literature search was performed for 6 databases up to July of 2012 to identify randomized control trials (RCTs) involving SZRD for insomniac patients. The methodological quality of RCTs was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions.
Results
Twelve RCTs with total of 1376 adult participants were identified. The methodological quality of all included trials are no more than 3/8 score. Majority of the RCTs concluded that SZRD was more significantly effective than benzodiazepines for treating insomnia. Despite these positive outcomes, there were many methodological shortcomings in the studies reviewed, including insufficient information about randomization generation and absence of allocation concealment, lack of blinding and no placebo control, absence of intention-to-treat analysis and lack of follow-ups, selective publishing and reporting, and small number of sample sizes. A number of clinical heterogeneity such as diagnosis, intervention, control, and outcome measures were also reviewed. Only 3 trials reported adverse events, whereas the other 9 trials did not provide the safety information.
Conclusions
Despite the apparent reported positive findings, there is insufficient evidence to support efficacy of SZRD for insomnia due to the poor methodological quality and the small number of trials of the included studies. SZRD seems generally safe, but is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further large sample-size and well-designed RCTs are needed.
doi:10.1186/1472-6882-13-18
PMCID: PMC3554563  PMID: 23336848
Insomnia; Suanzaoren decoction; Systematic review

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