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- Larvicidal effect of aqueous and ethanolic extracts of Senna alata on Anopheles gambiae, Culex quinquefasciatus and Aedes aegypti. [Journal Article]
- Pak J Pharm Sci 2013 May; 26(3):561-6.
Senna alata is locally used in South Eastern Nigeria in the treatment of several infections which include ringworm and other parasitic skin diseases.The larvicidal activities of aqueous and ethanolic leaf and stem extracts of S. alata were evaluated in static bioassays, on fourth instar larvae of Anopheles gambiae, Culex quinquefasciatus and Aedes aegypti, at extract concentrations of 0.15, 0.30, 0.45, 0.60 and 0.75% w/v, for 72 hours. Mortality of larvae exposed to the different extracts increased with increase in extract concentration and time of exposure. This study revealed a differential potency of the extracts used and a difference in susceptibility of larvae to the extracts as evident by the 72hLC50 values obtained. The leaf extract proved to be more lethal to the larvae than the stem extract as judged by the 72hLC50 values obtained both for the aqueous as well as the ethanolic extracts assayed. Phytochemical screening of the plant parts investigated revealed the presence of some plant metabolites, which have been reported in separate studies to be lethal to mosquito larvae. Results obtained from this study suggest that the leaf and stem extracts of S. alata possess a promising larvicidal potential which can be exploited in mosquito vector control.
- The Role of Benzodiazepines in Breathlessness: A Single Site, Open Label Pilot of Sustained Release Morphine Together with Clonazepam. [JOURNAL ARTICLE]
- J Palliat Med 2013 Apr 18.
Background:Breathlessness at rest or on minimal exertion despite optimal treatment of underlying cause(s) is distressing and prevalent. Opioids can reduce the intensity of chronic refractory breathlessness and an anxiolytic may be of benefit. This pilot aimed to determine the safety and feasibility of conducting a phase III study on the intensity of breathlessness by adding regular benzodiazepine to low-dose opioid.
Methods:This is a single site, open label phase II study of the addition of regular clonazepam 0.5 mg nocte orally to Kapanol(R) 10 mg (sustained release morphine sulphate) orally mane together with docusate/sennosides in people with modified Medical Research Council Scale ≥2. Breathlessness intensity on day four was the efficacy outcome. Participants could extend for another 10 days if they achieved >15% reduction over their own baseline breathlessness intensity.
Results:Eleven people had trial medication (eight males, median age 78 years (68 to 89); all had COPD; median Karnofsky 70 (50 to 80); six were on long-term home oxygen. Ten people completed day four. One person withdrew because of unsteadiness on day four. Five participants reached the 15% reduction, but only three went on to the extension study, all completing without toxicity.
Conclusion:This study was safe, feasible and there appears to be a group who derive benefits comparable to titrated opioids. Given the widespread use of benzodiazepines for the symptomatic treatment of chronic refractory breathlessness and its poor evidence base, there is justification for a definitive phase III study.
- High-Volume PEG Versus Low-Volume PEG Plus Laxative Versus Sennosides for Colonoscopy Preparation in Children: A Randomized Study. [JOURNAL ARTICLE]
- J Pediatr Gastroenterol Nutr 2013 Apr 4.
BACKGROUND::Many protocols of bowel preparation are available for use in children, however none of them is commonly accepted.
AIM:: To evaluate the efficacy and accepatability of high-volume polyethylene glycol (PEG) versus low-volume PEG combined with bisacodyl (BPEG) versus sennosides for colonoscopy preparation in children.
METHODS::Participants aged 10-18 years were randomly assigned to receive either PEG 60 ml/kg/day or PEG 30 ml/kg/day plus oral bisacodyl 10-15 mg/day or sennosides 2 mg/kg/day for 2 days. A blinded assessment of bowel cleansing was made by the endoscopist according to the Aronchick and Ottawa scale. The patient acceptability was evaluated with the visual analog scale. Analysis was done on an available case analysis basis.
RESULTS::Of 240 patients enrolled into the study 234 patients were available for analysis of the efficacy of colon cleansing. There were no significant differences found among the three groups for the proportions of participants with excellent/good (PEG: 35/79, BPEG: 26/79, sennosides 25/76) and poor/inadequate (PEG: 20/79, BPEG: 28/79, sennosides 28/76) bowel preparation evaluated with the Aronchick scale and for the mean Ottawa total score (PEG: 5.47 ± 3.63, BPEG: 6.22 ± 3.3, sennosides: 6.18 ± 3.53) Acceptability of bowel cleansing protocol was similar in all the groups (p = 0.8).
CONCLUSION:: All three cleansing methods showed similar efficacy and tolerability, however none of them were satisfactory.
- Antidiarrheal properties of different extracts of Chinese herbal medicine formula Bao-Xie-Ning. [Journal Article]
- J Integr Med 2013 Mar; 11(2):125-34.
Bao-Xie-Ning (BXN), a traditional Chinese herbal medicine (CHM) formula composed of Fructus Evodiae, Flos Caryophylli and Cortex Cinnamomi, and used for the treatment of infant diarrheal illness, was subject to systematic assessment for its putative multiple pharmacodynamic effects and pharmacological antidiarrheal mechanisms.High-performance liquid chromatography-diode array detector-electrospray ionization-mass spectrometric/mass spectrometry was developed and validated for identification and quantification of the main constituents in different extracts of BXN. Male Kunming mice weighing 20 to 25 g were used for detecting the antidiarrheal activity of the extracts. Ethanolic extract (EE), volatile oil extract (VOE), and aqueous extract (AE) of BXN were respectively subjected to pharmacodynamic and pharmacological comparison in assessing antidiarrheal effects with senna-induced diarrhea, castor oil-induced diarrhea, acetic acid-induced writhing assay, and isolated duodenum test.The highest yields of three detected components of BXN, rutaecarpine, eugenol and cinnamaldehyde were observed in EE. EE showed the most remarkable antidiarrheal activity in dose-dependent and time-dependent manners in both senna- and castor oil-induced diarrhea models, and presented dose-dependent analgesic activity in acetic acid-induced algesthesia model. In addition, EE extract of BXN also exhibited strong antimobility action on the intestine and strongest depression on spontaneous contraction of isolated duodenum.Ethanol extraction is an efficient method to extract the active constituents of BXN. BXN extract demonstrated multiple pharmacological activities affecting the main mechanisms of diarrhea, which validated BXN's usage in the comprehensive clinical treatment of diarrhea.
- α-Glucosidase and α-amylase inhibitory activity of Senna surattensis. [Journal Article, Research Support, Non-U.S. Gov't]
- J Acupunct Meridian Stud 2013 Feb; 6(1):24-30.
In this study, we investigated the inhibitory effects of ethanolic extract of the leaves of Senna surattensis (EESS) on α-glucosidase and α-amylase. We also studied the in vitro antidiabetic activity of S. surattensis using the glucose uptake by isolated rat hemidiaphragm model. In vitro studies using mammalian α-glucosidase extracted from the small intestine homogenate of mouse showed that the extract was found to be more effective in inhibiting the activities of maltase [half maximal inhibitory concentration (IC(50)): 209.15 μg/mL] and sucrase (IC(50): 366.44 μg/mL) when compared with the control group (acarbose). The extract of S. surattensis were further quantified with respect to porcine pancreatic α-amylase inhibition using the chromogenic 3,5-dinitrosalicylic acid method. Interestingly, S. surattensis was also found to exhibit α-amylase (IC(50): 123.95 μg/mL) inhibitory activity. The glucose uptake in the rat hemidiaphragm was significantly (p < 0.01) increased by EESS (220.95 ± 5.4 mg/g/30 minute) when compared with the control group. The total polyphenolic content of EESS was found to be 98 μg pyrocatechol/mg of the extract. These results suggest that EESS inhibited carbohydrate digestive enzymes and increased the peripheral uptake of glucose. This study endorses the use of this plant for further studies to determine their potential for managing type II diabetes.
- Effects of organic extracts of six Bangladeshi plants on in vitro thrombolysis and cytotoxicity. [Journal Article, Research Support, Non-U.S. Gov't]
- BMC Complement Altern Med 2013.:25.
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.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.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).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.
- In vitro antioxidant and antiproliferative activities of plants of the ethnopharmacopeia from northwest of Mexico. [Journal Article, Research Support, Non-U.S. Gov't]
- BMC Complement Altern Med 2013.:12.
The aim of this study, is to investigate the in vitro antioxidant activity, the total phenols content, the flavonoids content and the antiproliferative activity of methanolic extracts of the plants: Krameria erecta, Struthanthus palmeri, Phoradendron californicum, Senna covesii and Stegnosperma halimifolium, used by different ethnic groups from northwestern Mexico in the treatment and cure of various diseases.The in vitro antioxidant activity was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reducing/Antioxidant Power assay (FRAP), the total phenols content was measured by Folin-Ciocalteau assay, the flavonoids content by the AlCl(3) colorimetric method and the antiproliferative activity (line cells HeLa, RAW 264.7, M12A(k).C3.F6 and L929) using MTT method.The K. erecta extract showed the higher radical scavenging activity (67.88%), antioxidant activity by FRAP (1.41 mg Trolox Eq), the highest total phenols content (598.51 mg Galic Acid Eq/g extract), the highest flavonoids content (3.80 mg Quercetin Eq/g extract) and the greatest antiproliferative activity in a dose dependent manner against most Cell line evaluated. A positive correlation was found between the antioxidant activity and the flavonoids content.This study is the first report on the antioxidant and antiproliferative activities of the five species evaluated. The results demostrate that there is a positive correlation between antioxidant activity and the flavonoids content, indicating that these type of polyphenols could be the major contributors to the observed antioxidant activity in the evaluated plant extracts. Of the extracts evaluated, that of Krameria erecta showed the greatest antioxidant and antiproliferative activities, a discovery that makes this species a promising candidate for future research.
- Revising the absolute configurations of coatlines via density functional theory calculations of electronic circular dichroism spectra. [Journal Article, Research Support, Non-U.S. Gov't]
- Chirality 2013 Mar; 25(3):180-4.
Coatline A (1) and α-epi-coatline A (4) co-occur in the trunk extract of Andira coriacea. Inspection of their chiroptical properties led to intriguing results. After a careful examination of the experimental data used for the previously reported absolute configuration of these compounds, some uncertainties were identified. A combined theoretical approach including conformational analyses and calculation of electronic circular dichroism (ECD) spectra, in addition with experimental data obtained for schoepfin A (5) and the new schoepfin D (6) isolated from Senna quinquangulata, allowed the revision of the absolute configuration of coatlines A (1) and B (2).
- Antidiabetic components of Cassia alata leaves: identification through α-glucosidase inhibition studies. [Journal Article, Research Support, Non-U.S. Gov't]
- Pharm Biol 2013 Mar; 51(3):345-9.
Cassia alata Linn. [syn. Senna alata (L.) Roxb.] (Caesalpiniaceae) is used for treating various disease conditions including diabetes but its mechanism(s) of action and active principles remain to be elucidated.The antidiabetic principles were identified using an in vitro α-glucosidase inhibition study.The methanol extract of leaves of C. alata, which showed potent α-glucosidase inhibitory activity (IC(50), 63.75 ± 12.81 µg/ml), was fractionated. Active fractions were taken for further analysis by a variety of techniques including HPLC and Combiflash chromatography. The identity of the isolated compounds was established by spectroscopic analysis while their potential antidiabetic activity was assessed by in vitro enzyme inhibition studies.The α-glucosidase inhibitory effect of the crude extract was far better than the standard clinically used drug, acarbose (IC(50), 107.31 ± 12.31 µg/ml). A subsequent fractionation of the crude extract was made using solvents of ascending polarity (petroleum ether, chloroform, ethyl acetate, n-butanol and water). The ethyl acetate (IC(50), 2.95 ± 0.47 µg/ml) and n-butanol (IC(50), 25.80 ± 2.01 µg/ml) fractions which contained predominantly kaempferol (56.7 ± 7.7 µM) and kaempferol 3-O-gentiobioside (50.0 ± 8.5 µM), respectively, displayed the highest carbohydrate enzyme inhibitory effect.One of the possible antidiabetic mechanisms of action of C. alata is by inhibiting carbohydrate digestion. This is the first report on α-glucosidase activity of kaempferol 3-O-gentiobioside.Considering the activity profile of the crude extract and isolated bioactive compounds, further in vivo and clinical studies on C. alata extracts and compounds are well merited.
- Toxicology and Carcinogenesis Study of Senna in C3B6.129F1-Trp53tm1Brd N12 Haploinsufficient Mice. [JOURNAL ARTICLE]
- Toxicol Pathol 2012 Nov 2.
Senna is a pod or leaf of Senna alexandrina P. Mill and is used as a stimulant laxative. In the large intestine, bacterial enzymes reduce sennosides to rhein-9-anthrone, the active form for the laxative effect. To determine the potential toxic effects of senna, a 5-week dose range finding study in the C57BL/6N mouse and a 40-week toxicology and carcinogenesis study in the C3B6.129F1-Trp53 (tm1Brd) N12 haploinsufficient (p53(+/-)) mouse were conducted. In the 5-week study, C57BL/6N mice were exposed to up to 10,000 ppm senna in feed. Increased incidences of epithelial hyperplasia of the cecum and colon were observed in males and females exposed to 5,000 or 10,000 ppm senna. These intestinal lesions were not considered to be of sufficient severity to cause mortality and, thus, in the p53(+/-) mouse 40-week study, the high dose of 10,000 ppm was selected. Significant increases in the incidences of epithelial hyperplasia of the colon and cecum were observed at 10,000 ppm in p53(+/-) males and females, and the incidence of hyperplasia of the colon was significantly increased at 3,000 ppm in females. In conclusion, the large intestine was the major target of senna-induced toxicity in both wild-type and the p53(+/-) mouse model. There was no neoplastic change when senna was administered to p53(+/-) mouse.