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.

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.

Prevalence of obesity and overweight, its clinical markers and associated factors in a high risk South-Asian population.

BACKGROUND: Obesity is a global epidemic, which is a risk factor for cardiovascular diseases and metabolic abnormalities. It is measured by body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), body fat (BF) distribution and abdominal fat mass, each having its own merits and limitations. Variability in body composition between ethnic groups in South-Asians is significant and may not be truly reflected by BMI alone, which may result in misclassification. This study therefore, aims to determine the frequency of obesity, body fat composition and distribution, in a high risk population of an urban slum of Karachi, Pakistan. This survey included 451 participants selected by systematic sampling who were administered pre-tested questionnaires on socio-demographics, diet and physical activity. Chi-square was used to determine the association between categorical variables and multiple linear regression was used for quantitative variables. A P value of less than 0.05 was considered significant. RESULTS: Classified by BMI, 29% study subjects were overweight and 21% obese (58.7% with central obesity). Body fat percent (BF%) classified 81% as overweight. Females were more obese (P 0.03) with higher prevalence of central obesity (P <0.001) and WHR (P 0.003) but with a lower muscle mass (P 0.001). Activity score and muscle mass showed inverse linear association with BF% whereas, WC, weight, BMI and WHR had a positive linear association with BF%. The relationship between BMI and BF% was quadratic with a weaker association at lower BMI. Adjusting for socio-demographic variables, BF%, weight, diastolic blood pressure (DBP), BMI and score on the diet questionnaire had a positive linear association with WC, while WC, WHR and BP had a positive linear association with BF%. BF%, muscle content and WC had a positive linear association with BMI. CONCLUSION: Considering lower cut-offs for South-Asians BMI and WC, this study showed a high prevalence of obesity among a sub-urban population of Karachi, which was even higher when BF% was measured. Considering the rising prevalence of non-communicable diseases, BF%, WC, WHR and BMI measurements are convenient and feasible means of identifying population at risk and hence addressing it through public awareness and early detection.

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.

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.

Citrullus colocynthis (L.) Schrad (bitter apple fruit): a review of its phytochemistry, pharmacology, traditional uses and nutritional potential.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrullus colocynthis (L.) Schrad is a valuable cucurbit plant, widely distributed in the desert areas of the world. Citrullus colocynthis fruits are usually recognized for its wide range of medicinal uses as well as pharmaceutical and nutraceutical potential. This review aims to appraise the published information on the ethnobotanical knowledge, phytochemistry, ethnopharmacology, nutraceutical potential and safety studies of Citrullus colocynthis (bitter apple) fruit, with critical analysis on the gaps and potential for future studies. MATERIAL AND METHODS: A literature survey was performed by searching the scientific databases including PubMed, Scopus, SciFinder, Google Scholar, Web of Science, ACS as well as published books. RESULTS: The plant has been reported to possess a wide range of traditional medicinal uses including in diabetes, leprosy, common cold, cough, asthma, bronchitis, jaundice, joint pain, cancer, toothache, wound, mastitis, and in gastrointestinal disorders such as indigestion, constipation, dysentery, gastroenteritis, colic pain and different microbial infections. Several bioactive chemical constituents from fruits were recorded, such as, glycosides, flavonoids, alkaloids, fatty acids and essential oils. The isolation and identification of curcurbitacins A, B, C, D, E, I, J, K, and L and Colocynthosides A, and B were also reported. The fruit of Citrullus colocynthis has been studied extensively for its wide range of biological activities, which include antioxidant, cytotoxic, antidiabetic, antilipidemic, insecticide, antimicrobial and anti-inflammatory. The plant was also shown to be rich in nutritional value with high protein contents and important minerals as well as edible quality of seed oil. CONCLUSION: It is evident from the literature that Citrullus colocynthis possesses a wide range of medicinal uses and has been well studied for its antidiabetic, anticancer, antioxidant, antimicrobial and anti-inflammatory activities, while its therapeutic potential for gut, airways and cardiovascular disorders remains to be explored. Critical analysis revealed that the plant has the huge potential for pharmaceutical and nutraceutical application, with some indications for the presence of synergistic and /or side effects neutralizing combinations of activities.

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.

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.

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.

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.

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.

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.

Gastrointestial and respiratory activities of Acacia leucophloea.

ETHNOPHARMACOLOGICAL RELEVANCE: The barks of Acacia leucophloea (Fabaceae) are used in Pakistan traditional medicine as an astringent, a bitter, a thermogenic, a styptic, a preventive of infections, an anthelmintic, a vulnery, a demulcent, an expectorant, an antipyretic, an antidote for snake bites and in the treatment of bronchitis, cough, vomiting, wounds, ulcers, diarrhea, dysentery, internal and external hemorrhages, dental caries, stomatitis, and intermittent fevers and skin diseases. MATERIALS AND METHODS: A study was carried out for the possible elucidation of mechanisms justifying the traditional medicinal uses of A. leucophloea (Fabaceae) in gastrointestinal and respiratory diseases. In vitro experiments were carried out over isolated rabbit jejunum and guinea-pig ileum in order to determine spasmolytic and bronchorelaxant activities, while in vivo studies were conducted in mice for antidiarrheal properties. RESULTS: A methanol crude extract of barks of the plant caused a concentration-dependent relaxation (0.1-3 mg/ml) of isolated rabbit jejunum preparations in a pattern similar to that of nifedipine and dicyclomine, suggesting a Ca(2+) channel-blocking mechanism in addition to an anticholinergic effect. In guinea-pig ileum the extract caused a parallel shift in the Ach-curves without suppression of maximum contractile response, followed by a non-parallel shift with the suppression of maximum contractile response at higher concentration similar to that caused by dicyclomine. Moreover, in rabbit trachea, it also caused the relaxation of carbachol (1 µM) and high K(+)-induced contractions at a dose ranging between 0.1578 and 0.734 mg/ml and 0.46-0.94 mg/ml, respectively. These findings indicate that the extract possesses spasmolytic and bronchodilator activities, mediated possibly through blockade of Ca(2+) channels, thus justifying its medicinal use in diarrhea and asthma. Acacia leucophloea methanol extract exhibited dose-dependent (100-500 mg/ml) protective effect against castor oil induced diarrhea. CONCLUSIONS: The data obtained contribute to the validation of the traditional use of Acacia leucophloea bark in treating gastrointestinal and respiratory disorders, providing an hypothesis on the possible mechanisms of action.

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.

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 effect of berberine is mediated through multiple pathways.

Berberine is an isoquinoline alkaloid, occurring in nature as the main constituent of several plants with medicinal use in kidney stone disease. This work was undertaken to evaluate its antiurolithic potential and explore the possible underlying mechanism(s). Berberine was tested in vitro for the antioxidant effect and in vivo for diuretic and antiurolithic effects on an animal model of calcium oxalate urolithiasis. Berberine exhibited concentration-dependent (50-150µg/ml) antioxidant effect against ferrous-ascorbate induced lipid peroxidation in rat kidney homogenate with potency slightly higher than the reference antioxidant, butylated hydroxytoluene. In Wistar rats, berberine (5-20mg/kg) increased urine output accompanied by increased pH and Na(+) and K(+) excretion and decreased Ca(2+) excretion, similar to hydrochlorothiazide. In an animal model of calcium oxalate urolithiasis developed in male Wistar rats by adding 0.75% ethylene glycol in drinking water, berberine (10mg/kg) prevented as well as eliminated calcium oxalate crystal deposition in renal tubules and protected against deleterious effects of lithogenic treatment including weight loss, impaired renal function and oxidative stress, manifested as increased malondialdehyde and protein carbonyl contents, depleted GSH and decreased antioxidant enzyme activities of the kidneys. In naïve rats, berberine (10mg/kg) increased urine volume and pH and decreased Ca(2+) excretion. Results of this study suggest the presence of antiurolithic effects in berberine against calcium oxalate stones mediated through a combination of antioxidant, diuretic, urinary alkalinizing and hypocalciuric effects. These data invite future studies on berberine to establish its efficacy for clinical use.

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.

Antiurolithic effect of Bergenia ligulata rhizome: an explanation of the underlying mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Bergenia ligulata is widely used plant in South Asia, mainly India and Pakistan, as a traditional medicine for treatment of urolithiasis. AIM OF THE STUDY: To rationalize the Bergenia ligulata use in kidney stones and to explain the underlying mechanisms. MATERIALS AND METHODS: The crude aqueous-methanolic extract of Bergenia ligulata rhizome (BLR) was studied using in vitro and in vivo methods. RESULTS: BLR inhibited calcium oxalate (CaC(2)O(4)) crystal aggregation as well as crystal formation in the metastable solutions and exhibited antioxidant effect against 1,1-diphenyl-2-picrylhydrazyl free radical and lipid peroxidation in the in vitro. BLR caused diuresis in rats accompanied by a saluretic effect. In an animal model of urolithiasis, developed in male Wistar rats by adding 0.75% ethylene glycol (EG) in drinking water, BLR (5-10 mg/kg) prevented CaC(2)O(4) crystal deposition in the renal tubules. The lithogenic treatment caused polyuria, weight loss, impairment of renal function and oxidative stress, manifested as increased malondialdehyde and protein carbonyl contents, depleted reduced glutathione and decreased antioxidant enzyme activities of the kidneys, which were prevented by BLR. Unlike the untreated animals, EG intake did not cause excessive hyperoxaluria and hypocalciuria in BLR treated groups and there was a significant increase in the urinary Mg(2+), instead of a slight decrease. CONCLUSIONS: These data indicate the antiurolithic activity in Bergenia ligulata mediated possibly through CaC(2)O(4) crystal inhibition, diuretic, hypermagneseuric and antioxidant effects and this study rationalizes its medicinal use in urolithiasis.

Coriander fruit exhibits gut modulatory, blood pressure lowering and diuretic activities.

AIM OF THE STUDY: Coriander (Coriandrum sativum) is traditionally used for various gastrointestinal and cardiovascular disorders and this study was designed to rationalize its use in dyspepsia, abdominal colic, diarrhea, hypertension and as diuretic. MATERIALS AND METHODS: Coriander crude extract (Cs.Cr) was evaluated through in vitro and in vivo techniques. RESULTS: Cs.Cr caused atropine sensitive stimulatory effect in isolated guinea-pig ileum (0.1-10 mg/ml). In rabbit jejunum preparations, Cs.Cr evoked a similar contractile response but in the presence of atropine, it exhibited relaxation against both spontaneous and high K(+) (80 mM)-induced contractions as well as shifted the Ca(2+) concentration-response curves to right, similar to that caused by verapamil. Cs.Cr (1-30 mg/ml) caused fall in arterial blood pressure of anesthetized animals, partially blocked by atropine. Cs.Cr produced vasodilatation against phenylephrine and K(+) (80 mM)-induced contractions in rabbit aorta and cardio-depressant effect in guinea-pig atria. Cs.Cr produced diuresis in rats at 1-10mg/kg. Bio-assay-directed fractionation revealed the separation of spasmogenic and spasmolytic components in the aqueous and organic fractions respectively. CONCLUSIONS: These results indicate that coriander fruit exhibits gut stimulatory, inhibitory and hypotensive effects mediating possibly through cholinergic, Ca(2+) antagonist and the combination of these mechanisms respectively. Diuretic activity adds value to its use in hypertension.