Analgesic, anti-inflammatory and anti-platelet activities of Buddleja crispa.

BACKGROUND: Buddleja crispa Benth (Buddlejaceae) is a dense shrub; several species of genus Buddleja have been used in the management of various health conditions including pain and inflammation. The present study was aimed to investigate the analgesic, anti-inflammatory and anti-platelet properties of B. crispa. METHODS: Male rats (220-270 gm,) and mice (25-30 gm) were randomly divided into different groups (n = 6). Various doses of plant extract of B. crispa, its fractions and pure compounds isolated from the plant were administered intraperitoneally (i.p). The analgesic, anti-inflammatory and anti-platelet activities were assessed using acetic acid and formalin-induced nociception in mice, carrageenan-induced rat paw edema and arachidonic acid-induced platelets aggregation tests. RESULTS: The intraperitoneal administration of the methanolic extract (50 and 100 mg/kg), hexane fraction (10 and 25 mg/kg i.p) exhibited significant inhibition (P < 0.01) of the acetic acid-induced writhing in mice and attenuated formalin-induced reaction time of animals in second phase of the test. Pure compounds BdI-2, BdI-H3 and BH-3 isolated from B. crispa produced significant (P < 0.01) analgesic activity in acetic acid-induced and formalin tests. The crude extract of B. crispa (50-200 mg/kg i.p.) and its hexane fraction inhibited carrageenan-induced rat paw edema with maximum inhibition of 65 and 71% respectively (P < 0.01). The analgesic and anti-inflammatory effect of the plant extract and isolated pure compounds were comparable to diclofenac sodium. B. crispa plant extract (0.5-2.5 mg/mL) produced significant anti-platelet effect (P < 0.01) with maximum inhibition of 78% at 2.5 mg/ml. CONCLUSION: The findings from our present study suggest that B. crispa possesses analgesic, anti-inflammatory and anti-platelet properties. B. crispa could serve a potential novel source of compounds effective in pain and inflammatory conditions.

Almonds inhibit dyslipidemia and vascular dysfunction in rats through multiple pathways.

BACKGROUND: Almonds are reported to be protective against cardiovascular diseases (CVDs); however, the possible mode of action has only infrequently been explored. OBJECTIVE: This study aimed at investigating the mechanistic basis for the benefits of almonds in atherosclerotic CVDs. METHODS: Three studies in 3 groups of rats were designed with the use of tyloxapol (study 1), a high-fat diet (HFD; study 2), and white-flour fructose (WFF; study 3). In each of the studies, the first group acted as the control [administered saline in study 1 and fed a normal diet (ND) in studies 2 and 3]; the second and third groups were treated with tyloxapol in study 1, an HFD in study 2, and WFF in study 3. The third group in each study was also fed almonds (3 g/kg) for 4 wk, after which blood was collected for biochemical evaluation. Livers and aortas were isolated from the rats in studies 1 and 2 for enzyme assays and vascular analysis, respectively. RESULTS: Almond supplementation significantly (P < 0.05) prevented hyperlipidemia in all of the rat models. Supplementation suppressed cholesterol synthesis, leading to a 65% inhibition of tyloxapol-induced activation of hepatic ß-hydroxy-ß-methylglutaryl coenzyme A reductase. The almond intervention inhibited by 56% the HFD-induced increase in serum concentrations of hepatic aminotransferases. Almonds also protected against an HFD-induced increase in uric acid (0.9-fold), phosphorus (1.1-fold), alkaline phosphatase (4.6-fold), and γ-glutamyltransferase (1-fold), with resultant concentrations that were not different from those in ND-fed rats (P > 0.05). Almonds partially restored the vascular reactivity of isolated aortas and prevented HFD-induced endothelial dysfunction by reducing inhibition of endothelial nitric oxide (NO) synthase and promoting NO release. The 70% decrease in HDL cholesterol that was observed in the WFF group was prevented by almond supplementation; serum and LDL cholesterol were also normalized. CONCLUSIONS: The inhibition of de novo cholesterol synthesis, prevention of hepatic damage, and restoration of vascular function via the protection of endothelium and influence on the NO pathway are some of the mechanisms underlying the medicinal value of almonds in CVDs.

Studies on antidiarrhoeal, antispasmodic and bronchodilator activities of Operculina turpethum Linn.

BACKGROUND: Traditionally, Operculina turpethum has been used in a wide range of ailments such as, gastrointestinal disturbances and asthma. It is found in China, South Asia, Pacific Islands, and Australia. This study was aimed to provide a possible pharmacological basis for the medicinal use of O. turpethum in gut and airways disorders. METHODS: Castor oil-induced diarrhoeal mice model and isolated tissue preparations such as, rabbit jejunum and guinea-pig tracheal preparations were used to test the antidiarrhoeal, antispasmodic and bronchodilator effects and the possible mode of action(s) of the 70% aqueous-ethanolic extract of O. turpethum black variety (OTB). RESULTS: In the castor oil-induced diarrhoea in mice, the crude extract of OTB caused a dose-dependent (300-1000 mg/kg) protection from diarrhoea, similar to that of loperamide. In isolated rabbit jejunum preparations, OTB produced a dose-dependent inhibition of spontaneous and high K+(80 mM)-induced contractions with resultant median effective concentrations (EC50 with 95% confidence interval) of 1.04 mg/ml (0.59-1.54) and 0.12 mg/ml (0.10-0.15; n = 4) respectively, thus showing more potency against K+. Pretreatment of the tissue with OTB (0.01 and 0.03 mg/ml) caused a rightward shift in the concentration response curves of Ca++, similar to that of verapamil. In isolated guinea-pig tracheal preparations, OTB caused inhibition of carbachol and high K+-induced constriction at similar concentrations with respective EC50 value of 0.66 mg/ml (0.53-0.82) and 0.59 mg/ml (0.45-0.62). Activity-directed fractionation revealed that the ethyl acetate fraction was more potent than the parent crude extract and hexane fraction. CONCLUSION: These results suggest that the crude extract of O. turpethum possesses antidiarrhoeal, antispasmodic and bronchodilator activities, mediated possibly through the presence of Ca++ antagonist like constituent(s), though additional mechanism(s) cannot be ruled out. Thus, this study provides the evidence for the medicinal use of plant in diarrhoea and asthma.

Fiber-free white flour with fructose offers a better model of metabolic syndrome.

BACKGROUND: The metabolic syndrome (MS) is a combination of metabolic abnormalities that lead to an increased risk of cardiovascular diseases. Due to its rising incidence and demanding life-long use of multiple drugs, there is a growing interest in testing and developing new allopathic, complementary and alternative therapies for controlling or curing disorders of MS. The discovery of new therapeutic modalities requires animal models of disease and currently available models have limitations. Developing an appropriate animal model for MS to achieve various therapeutic targets remains a challenge and this study aims to develop a rat model which closely depicts MS in humans. METHODOLOGY: Rat model of MS was developed by replacing 60% of diet with fructose. Four groups of Sprague-Dawley rats were either given whole wheat or refined flour with and without fructose for 8 weeks. Data were analyzed on SPSS and Graphpad Prism using ANOVA with Tukey's and Bonferonni tests for multiple group comparison. A p-value of less than 0.05 was considered significant for differences between groups. RESULTS: Replacing whole wheat with refined wheat flour in rat chow in 60% fructose-fed Sprague-Dawley rats resulted in hypertension (p 0.01), hyper-insulinemia (p < 0.001), hyperglycemia (p 0.03) and a reduction in HDL levels (p 0.002) at 4 weeks while hyper-triglyceridemia (p 0.001) with endothelial dysfunction was observed at 8 weeks. CONCLUSION: It is concluded that the refined wheat flour with 60% fructose in diet hastens the development of metabolic syndrome in 4 weeks and replacing whole wheat flour with refined flour in diet induces a more effective abnormality including a low HDL. Further studies may be directed to assess the associated pathological changes, which can be used to study the effect of different therapeutic modalities on an animal model of MS with low HDL.

An insight investigation to the antiurolithic activity of Trachyspermum ammi using the in vitro and in vivo experiments.

The crude extract of Trachyspermum ammi seeds (Ta.Cr) was studied for its antiurolithic activity using the in vivo and in vitro experiments. In the in vivo experiments, Ta.Cr treatment showed a diuretic activity at the dose of 30 and 100 mg/kg and exhibited curative effect in male hyperoxaluric Wistar rats, which received 0.75% ethylene glycol (EG) in drinking water given for 3 weeks, with 1% ammonium chloride (AC) for initial three days. In the in vitro experiments, Ta.Cr delayed the slopes of nucleation and inhibited the calcium oxalate (CaOx) crystal aggregation in a concentration-dependent manner like that of potassium citrate. Ta.Cr also inhibited DPPH free radicals like standard antioxidant drug butylated hydroxytoluene (BHT), and significantly reduced cell toxicity and LDH release in Madin-Darby canine kidney (MDCK) cells, exposed to oxalate (0.5 mM) and COM (66 µg/cm2) crystals. In isolated rabbit urinary bladder strips, Ta.Cr relaxed high K+ (80 mM) and CCh (1 µM)-induced contractions, showing antispasmodic activity. The findings of this study suggest that the antiurolithic activity of crude extract of Trachyspermum ammi seeds may be mediated by a number of mechanisms, including a diuretic, an inhibitor of CaOx crystal aggregation, an antioxidant, renal epithelial cell protection, and an antispasmodic, thus, showing the therapeutic potential in urolithiasis, for which there is no viable non-invasive option in modern medicine.

Studies on the in vitro and in vivo antiurolithic activity of Holarrhena antidysenterica.

Holarrhena antidysenterica has a traditional use in the treatment of urolithiasis, therefore, its crude extract has been investigated for possible antiurolithic effect. The crude aqueous-methanolic extract of Holarrhena antidysenterica (Ha.Cr) was studied using the in vitro and in vivo methods. In the in vitro experiments, Ha.Cr demonstrated a concentration-dependent (0.25-4 mg/ml) inhibitory effect on the slope of aggregation. It decreased the size of crystals and transformed the calcium oxalate monohydrate (COM) to calcium oxalate dehydrate (COD) crystals, in calcium oxalate metastable solutions. It also showed concentration-dependent antioxidant effect against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and lipid peroxidation induced in rat kidney tissue homogenate. Ha.Cr (0.3 mg/ml) reduced (p < 0.05) the cell toxicity and LDH release in renal epithelial cells (MDCK) exposed to oxalate (0.5 mM) and COM (66 µg/cm(2)) crystals. In male Wistar rats, receiving 0.75 % ethylene glycol (EG) for 21 days along with 1 % ammonium chloride (AC) in drinking water, Ha.Cr treatment (30-100 mg/kg) prevented the toxic changes caused by lithogenic agents; EG and AC, like loss of body weight, polyurea, oxaluria, raised serum urea and creatinine levels and crystal deposition in kidneys compared to their respective controls. These data indicate that Holarrhena antidysenterica possesses antiurolithic activity, possibly mediated through the inhibition of CaOx crystal aggregation, antioxidant and renal epithelial cell protective activities and may provide base for designing future studies to establish its efficacy and safety for clinical use.

Studies on the antihypertensive and antidyslipidemic activities of Viola odorata leaves extract.

BACKGROUND: This study was undertaken to provide pharmacological basis for the medicinal use of Viola odorata Linn. in hypertension and dyslipidemia using the in vivo and in vitro assays. RESULTS: Viola odorata leaves extract (Vo.Cr), which tested positive for alkaloids, saponins, tannins, phenolics, coumarins and flavonoids, caused a dose-dependent (0.1-1.0 mg/kg) decrease in mean arterial blood pressure in anaesthetized rats. In isolated guinea-pig atria, Vo.Cr equally inhibited force and rate of spontaneous atrial contractions. On the baseline of rat thoracic aortae (endothelium-intact and denuded), the plant extract caused phentolamine-sensitive vasoconstriction. When tested on phenylephrine (PE, 1 µM) and K(+) (80 mM)-induced vasoconstriction, Vo.Cr caused a concentration-dependent relaxation and also caused a rightward shift of Ca(++) concentration-response curves as well as suppression of PE (1 µM) control peaks in Ca(++)-free medium, similar to that caused by verapamil. In the presence of L-NAME, the relaxation curve of Vo.Cr was partially inhibited showing involvement of Nitric oxide (NO) mediated pathway. In Tyloxapol-induced dyslipidemia, Vo.Cr caused reduction in total cholesterol and triglyceride levels. In high-fat diet-induced dyslipidemia model, the plant extract caused a significant decrease in total cholesterol, LDL-C, atherogenic index and prevented the increase in average body weights, while it increased HDL-C. CONCLUSIONS: These data indicate that the vasodilator effect of the plant extract is mediated through multiple pathways like inhibition of Ca(++) influx via membranous Ca(++) channels, its release from intracellular stores and NO-mediated pathways, which possibly explain the fall in BP. The plant also showed reduction in body weight and antidyslipidemic effect which may be due to the inhibition of synthesis and absorption of lipids and antioxidant activities. Thus, this study provides a pharmacologic rationale to the medicinal use of Viola odorata in hypertension and dyslipidemia.

Anti-Acanthamoebic properties of resveratrol and demethoxycurcumin.

Acanthamoeba is an opportunist protist pathogen that is known to infect the cornea to produce eye keratitis and the central nervous system to produce fatal granulomatous encephalitis. Early diagnosis, followed by aggressive treatment using a combination of drugs is a prerequisite in successful treatment but even then, prognosis remains poor due to lack of effective drugs. The overall aim of the present study was to determine the anti-Acanthamoebic potential of natural compounds, resveratrol and curcuminoids. Adhesion and cytotoxicity assays were performed using primary human brain microvascular endothelial cells, which constitute the blood-brain barrier. Pre-exposure of organisms to 100 µg resveratrol and demethoxy curcumin prevented amoeba binding by 57% and 73%, respectively, while cytotoxicity of host cells was inhibited by 86%. In an assay for viability of amoebae in the absence of host cells, resveratrol and de-methoxy curcumin exhibited significant amoebicidal effects (23% and 25%, respectively) at 100 µg concentrations (P<0.01). Neither resveratrol nor demethoxycurcumin had any effect on the proteolytic activities of Acanthamoeba castellanii. Of both compounds, resveratrol is of most interest for further investigation, because of the selective toxicity of resveratrol on A. castellanii but not the human brain microvascular endothelial cells.

Over prescription of antibiotics for adult pharyngitis is prevalent in developing countries but can be reduced using McIsaac modification of Centor scores: a cross-sectional study.

BACKGROUND: Although Group A beta hemolytic streptococcus (GABHS) can cause bacterial pharyngitis, the most common etiology is viral; despite this viral etiology, antibiotics are commonly prescribed for this infection in industrialized countries. We investigated the prevalence of GABHS in adult pharyngitis patients from lower socioeconomic settings in Karachi, Pakistan, how often antibiotics are prescribed for pharyngitis and if appropriate agents were used in a developing world setting. Finally, we wanted to see the usefulness of modified McIsaac scores in predicting positive cultures. METHODS: Adult patients were recruited from three local hospital outpatient dispensaries (OPDs). All patients aged 14-65 years who were suspected of having bacterial pharyngitis had throat swabs taken. Laboratory results for GABHS pharyngitis were then compared with their prescriptions. Appropriateness (using the World Health Organization's definition) and type of antibiotic prescribed were assessed. RESULTS: Of 137 patients, 30 patients each were studied for scores of 0, 1, 2 and 3; 17 patients were studied for score 4. Although 6 (4.4%) patients were GABHS+, for a prevalence of 43.8 per 1000 population, antibiotics were prescribed to 135 patients (98.5%). Of these, only 11.1% received appropriate antibiotics while 88.9% received inappropriate antibiotics. Penicillins were prescribed most (34.1%), especially amoxicillin/clavulanate; followed by macrolides (31.1%), especially the second-generation agents, and fluoroquinolones (14.8%). McIsaac scores were found to be 100% sensitive and 68.7% specific, giving a positive predictive value (PPV) of 12.7% and a negative predictive value (NPV) of 100%. CONCLUSIONS: Antibiotics were prescribed irrationally to adult pharyngitis patients, as most cultures were negative for bacterial infection. McIsaac modification of Centor scores related directly to culture results. We would therefore highly recommend its use to help family physicians make treatment decisions for adult pharyngitis patients.

Species and tissue-specificity of prokinetic, laxative and spasmodic effects of Fumaria parviflora.

BACKGROUND: Fumaria parviflora Linn. (Fumariaceae), is a small branched annual herb found in many parts of the world including Saudi Arabia and Pakistan. This study was designed to provide pharmacological basis for the medicinal use of Fumaria parviflora in gut motility disorders. METHODS: The in-vivo prokinetic and laxative assays were conducted in mice. Isolated intestinal preparations (ileum and jejunum) from different animal species (mouse, guinea-pig and rabbit) were separately suspended in tissue baths containing Tyrode's solution bubbled with carbogen and maintained at 37°C. The spasmogenic responses were recorded using isotonic transducers coupled with PowerLab data acquisition system. RESULTS: The aqueous-methanol extract of Fumaria parviflora (Fp.Cr), which tested positive for the presence of alkaloids, saponins, tannins and anthraquinones showed partially atropine-sensitive prokinetic and laxative activities in the in-vivo in mice at 30 and 100 mg/kg. In the in-vitro studies, Fp.Cr (0.01-1 mg/ml) caused a concentration-dependent atropine-sensitive stimulatory effect both in mouse tissues (jejunum and ileum), and rabbit jejunum but had no effect in rabbit ileum. In guinea-pig tissues (ileum and jejunum), the crude extract showed a concentration-dependent stimulatory effect with higher efficacy in ileum and the effect was partially blocked by atropine, indicating the involvement of more than one types of gut-stimulant components (atropine-sensitive and insensitive). This could be a plausible reason for the greater efficacy of Fp.Cr in gut preparations of guinea-pig than in rabbit or mouse. CONCLUSIONS: This study shows the prokinetic, laxative and spasmodic effects of the plant extract partially mediated through cholinergic pathways with species and tissue-selectivity, and provides a sound rationale for the medicinal use of Fumaria parviflora in gut motility disorders such as, indigestion and constipation. This study also suggests using different species to know better picture of pharmacological profile of the test material.

Antispasmodic and Antidiarrheal Activities of Valeriana hardwickii Wall. Rhizome Are Putatively Mediated through Calcium Channel Blockade.

Valeriana hardwickii is indigenous to Pakistan, Burma and Ceylon, where it is traditionally being used as an antispasmodic and antidiarrheal, besides its culinary use as spice. The aim of this paper was to provide pharmacological validation to these medicinal uses. The crude aqueous-methanolic extract of Valeriana hardwickii rhizome (Vh.Cr) was studied on isolated rabbit jejunum and castor oil-induced diarrhea in mice for spasmolytic and antidiarrheal properties, respectively. Vh.Cr caused concentration-dependent (0.01-1 mg/mL) relaxation of spontaneous contractions in isolated rabbit jejunum and inhibited K(+)-induced contractions (0.01-0.3 mg/mL), similar to verapamil, suggestive of calcium channel blockade (CCB). The CCB effect was confirmed when pretreatment of the jejunum preparations with Vh.Cr produced a concentration-dependent (0.03-0.1 mg/mL) rightward shift in the Ca(++) concentration-response curves, as caused by verapamil. Vh.Cr exhibited dose-dependent (100-300 mg/kg) protection against castor oil-induced diarrhea in mice. Loperamide, a standard antidiarrheal drug, similarly prevented the diarrhea. These data indicate the presence of CCB effect in the extract of Valeriana hardwickii rhizome, possibly mediating its antispasmodic and antidiarrheal activities and provide a scientific base for its traditional use in hyperactive gut disorders.

Antiurolithic activity of Origanum vulgare is mediated through multiple pathways.

BACKGROUND: Origanum vulgare Linn has traditionally been used in the treatment of urolithiasis. Therefore, we investigated the crude extract of Origanum vulgare for possible antiurolithic effect, to rationalize its medicinal use. METHODS: The crude aqueous-methanolic extract of Origanum vulgare (Ov.Cr) was studied using the in vitro and in vivo methods. In the in vitro experiments, supersaturated solution of calcium and oxalate, kidney epithelial cell lines (MDCK) and urinary bladder of rabbits were used, whereas, in the in vivo studies, rat model of urolithiasis was used for the study of preventive and curative effect. RESULTS: In the in vitro experiments, Ov.Cr exhibited a concentration-dependent (0.25-4 mg/ml) inhibitory effect on the slope of nucleation and aggregation and also decreased the number of calcium oxalate monohydrate crystals (COM) produced in calcium oxalate metastable solutions. It also showed concentration-dependent antioxidant effect against DPPH free radical and lipid peroxidation induced in rat kidney tissue homogenate. Ov.Cr reduced the cell toxicity using MTT assay and LDH release in renal epithelial cells (MDCK) exposed to oxalate (0.5 mM) and COM (66 µg/cm(2)) crystals. Ov.Cr relaxed high K(+) (80 mM) induced contraction in rabbit urinary bladder strips, and shifted the calcium concentration-response curves (CRCs) towards right with suppression of the maximum response similar to that of verapamil, a standard calcium channel blocker. In male Wistar rats receiving lithogenic treatment comprising of 0.75% ethylene glycol in drinking water given for 3 weeks along with ammonium chloride (NH(4)Cl) for the first 5 days, Ov.Cr treatment (10-30 mg/kg) prevented as well as reversed toxic changes including loss of body weight, polyurea, crystalluria, oxaluria, raised serum urea and creatinine levels and crystal deposition in kidneys compared to their respective controls. CONCLUSION: These data indicating the antiurolithic activity in Ov.Cr, possibly mediated through inhibition of CaOx crystallization, antioxidant, renal epithelial cell protective and antispasmodic activities, rationalizes its medicinal use in urolithiasis.

Berberis vulgaris root bark extract prevents hyperoxaluria induced urolithiasis in rats.

Berberis vulgaris is a widely used plant for the treatment of urolithiasis. To evaluate its antiurolithic potential, the crude aqueous-methanol extract of Berberis vulgaris root bark (Bv.Cr) was tested in an animal model of urolithiasis, developed in male Wistar rats by adding 0.75% ethylene glycol in drinking water. Bv.Cr (50 mg/kg) inhibited CaOx crystal deposition in renal tubules and protected against associated changes including polyuria, weight loss, impaired renal function and the development of oxidative stress in kidneys. Activity-guided fractionation revealed the concentration of antiurolithic constituent(s) mainly in the aqueous fraction. These data, indicating the presence of antiurolithic activity in Berberis vulgaris root bark, rationalize its medicinal use for the treatment of urolithiasis.

Analgesic, anti-inflammatory and anti-platelet activities of the methanolic extract of Acacia modesta leaves.

The current study was aimed to evaluate Acacia modesta for analgesic, anti-inflammatory, and anti-platelet activities. The analgesic and anti-inflammatory effects were assessed in rodents using acetic acid and formalin-induced nociception, hot plate and carrageenan-induced rat paw oedema tests. The intraperitoneal (i.p.) administration of the methanolic extract (50 and 100 mg/kg) produced significant inhibition (P\0.01) of the acetic acid-induced writhing in mice and suppressed formalin-induced licking response of animals in both phases of the test. In the hot plate assay the plant extract (100 mg/kg) increased pain threshold of mice. Naloxone (5 mg/kg i.p.) partially reversed the analgesic effect of the extract in formalin and hot plate tests.A. modesta (100 and 200 mg/kg i.p.) exhibited sedative effect in barbiturate-induced hypnosis test similar to that produced by diazepam (10 mg/kg i.p.). The plant extract(50-200 mg/kg i.p.) produced marked anti-inflammatory effect in carrageenan-induced rat paw oedema assay comparable to diclofenac and produced a dose-dependent(0.5-2.5 mg/mL) inhibitory effect against arachidonic acid induced platelet aggregation. These data suggest that A. modesta possesses peripheral analgesic and antiinflammatory properties, with analgesic effects partially associated with the opioid system.

Studies on the antioxidant and analgesic activities of Aztec marigold (Tagetes erecta) flowers.

Commercially available Aztec marigold (Tagetes erecta) flower extract (Af.Cr) was evaluated for the in vitro antioxidant activity and in vivo analgesic effect on acetic-acid-induced abdominal writhing. The results revealed the presence of pronounced antioxidant potential in Aztec marigold flowers and a dose-dependent (100 and 300 mg/kg) analgesic effect. The antioxidant and analgesic activities obtained seem to be in good accordance with the medicinal uses of Aztec marigold as an anti-inflammatory and analgesic.

Children's environmental health in Central Asia and the Middle east.

Children in Central Asia and the Middle East bear disproportionate environmental threats to health, of which the most widespread and serious result from poverty, malnutrition, lack of access to safe drinking water and food, and exposures to toxic chemicals. Their psychological health is threatened in several parts of this region by internal wars and strife. Many, or even most, children are regularly exposed to environmental tobacco smoke. In many of these countries, children constitute very high percentages of the population. Because children constitute the future, it is critical that these threats to their health be addressed and reduced to the greatest extent possible through both provision of safe and adequate drinking water and nutrition and reduction of exposures to environmental contaminants.

Preparation, structure and spasmolytic activities of some derivatives of harmine series of alkaloids.

Keeping in view the interesting chemistry and pharmacological importance of harmine series of bases -- the beta-carboline alkaloids, a number of new derivatives of tetrahydroharmine and harmalol have been prepared and characterized through spectral studies. Some of these derivatives showed spasmolytic activity. It was observed that all the N-acyl tetrahydroharmine derivatives are stable, not labile and no ring opening occurs in these compounds, as reported recently.

Presence of cholinergic and calcium channel blocking activities explains the traditional use of Hibiscus rosasinensis in constipation and diarrhoea.

The aqueous-ethanolic extract of the aerial parts of Hibiscus rosasinensis Linn. (Malvaceae) was studied for the possible presence of spasmogenic and spasmolytic constituents to rationalize its traditional use in gastrointestinal disorders. The crude extract (Hr.Cr) caused a concentration-dependent (1-10mg/mL) spasmogenic effect in isolated guinea-pig ileum, which was blocked in the presence of atropine (0.1 microM). In spontaneously contracting rabbit jejunum, the plant extract exhibited a weak stimulatory effect at lower doses (0.03-0.30 mg/mL) followed by an inhibitory effect at higher doses (1.0-3.0mg/mL). Pretreatment of the tissues with atropine blocked the stimulatory effect resulting in the potentiation of the spasmolytic effect. Hr.Cr (0.03-1.0mg/mL) also showed an inhibitory effect on K(+) (80 mM)-induced contractions. The calcium channel blocking activity was confirmed when Hr.Cr shifted the Ca(2+) concentration-response curves to the right, similar to verapamil. Activity-directed fractionation revealed that the spasmolytic component(s) was separated in the ethyl acetate, while the spasmogenic in the petroleum ether fraction. The aqueous fraction exhibited a combination of weak spasmogenic and spasmolytic effects. These data indicate that the crude extract contains spasmogenic and spasmolytic constituents mediating their effect through cholinergic receptors activation and blockade of Ca(2+) influx, respectively, which may explain its traditional use in constipation and diarrhoea.

Pharmacological basis for the use of Fumaria indica in constipation and diarrhea.

The crude extract of Fumaria indica whole plant (Fi.Cr) and its fractions were studied in vitro for spasmogenic and spasmolytic effects to rationalize some of the traditional uses. Fi.Cr (1.0-5.0 mg/mL) caused a moderate degree of atropine-sensitive spasmogenic effect in guinea-pig ileum. In spontaneously contracting rabbit jejunum, Fi.Cr (0.03-0.3 mg/mL) caused a mild spasmogenicity followed by relaxation at the higher doses. In the atropinized preparations, Fi.Cr inhibited spontaneous and K(+)-induced contractions at the similar doses (0.1-1.0 mg/mL), which suggests calcium channel blockade (CCB). CCB effect was confirmed when pretreatment of the tissue with the Fi.Cr produced a dose-dependent shift in the Ca(2+) dose-response curves to the right, similar to that produced by verapamil. Activity-directed fractionation revealed that the spasmolytic effect is concentrated in the petroleum ether fraction, while dichloromethane fraction contains both spasmogenic and spasmolytic constituents. These data indicate that the presence of cholinergic and CCB constituents in Fi.Cr may explain the respective traditional use of Fumaria indica in constipation and diarrhoea.

Antispasmodic and blood pressure lowering effects of Valeriana wallichii are mediated through K+ channel activation.

Crude extract of Valeriana wallichii rhizome (Vw.Cr) and its fractions were studied for possible antispasmodic and blood pressure lowering activities to rationalize some of the folkloric uses. In rabbit jejunum preparations, Vw.Cr (0.1-3.0 mg/mL) caused relaxation of spontaneous contractions. When tested against high K(+) (80 mM)-induced contractions it produced weak inhibitory effect, while caused complete relaxation of the contractions induced by low K(+) (20 mM). In the presence of glibenclamide (3 microM), the inhibitory effect of low K(+) was shifted to the right, similar to that produced by cromakalim while, verapamil caused no differentiation in its inhibitory effect against low and high K(+)-induced contractions. In guinea pig ileum, the plant extract produced similar results as in rabbit jejunum. Intravenous administration of Vw.Cr, produced fall in arterial blood pressure in normotensive anaesthetized rats and this effect was partially blocked by glibenclamide. In rabbit aortic preparations, plant extract also caused a selective and glibenclamide-sensitive relaxation of low K(+) (20 mM)-induced contractions. Activity-directed fractionation studies revealed that the observed activity was distributed both in the chloroform and aqueous fractions. These results indicate that the antispasmodic and hypotensive effects of Valeriana wallichii are mediated possibly through K(ATP) channel activation, which justify its use in gastrointestinal and cardiovascular disorders.