Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item The Effect of Cassia auriculata and Cardiospermum halicacabum teas on the steady state blood level and toxicity of carbamazepine(Elsevier, 2004) Thabrew, M.I.; Munasinghe, C.; Chackrewarthy, S.; Senarath, S.A study was conducted using male Wistar rats as the experimental model, to compare the effects of concurrent administration of herbal tea prepared from dried flowers of Cassia auriculata or aerial parts of Cardiospermum halicacabum and carbamazepine, on (a). steady state serum levels of the prescription drug, and (b). changes in toxicity (as assessed by changes in general behaviour, haematological parameters, and liver and kidney function) that may occur due to drug interaction. Results demonstrate that in rats receiving the Cassia auriculata tea and carbamazepine, the blood levels of the prescription drug were significantly enhanced by 47.1% (P<0.04), when compared with the levels in animals receiving only carbamazepine for the same time period, with no apparent changes in toxicity. In animals receiving the Cardiospermum halicacabum tea, there were no significant changes in the blood levels of carbamazepine or drug-related toxicity. Cassia auriculata tea has therefore the potential to influence the bioavailability of carbamazepine, and hence its therapeutic actions. Concurrent ingestion of carbamazepine with herbal teas containing Cassia auriculata is therefore best avoided by patients under treatment for epilepsy.Item Possible interaction of herbal tea and carbamazepine(De Gruyter, 2003) Thabrew, M.I.; Munasinghe, T.M.J.; Chackrewarthy, S.; Senarath, S.A study was conducted using Wistar rats to determine the effect of concurrent administration of a herbal tea prepared from dried flowers of Cassia auriculata and carbamazepine on (a) blood levels of the prescription drug and (b) changes in toxicity (as assessed by changes in hematological parameters, liver and kidney function, and histology of major body organs) that may occur due to drug interaction. Results demonstrate that in rats receiving the herbal tea and carbamazepine, the blood levels of the prescription drug were significantly enhanced by 47.1% (p <0.04) when compared with the levels in animals receiving only carbamazepine, with no apparent changes in toxicity. Concurrent ingestion of the herbal tea prepared from Cassia auriculata flowers with carbamazepine may therefore influence the bioavailability of the prescribed drug and hence its therapeutic potential.Item Oral hypoglygaemic activity of Ipomea aquatica in streptozotocin induced diabetic wistar rats and type II diabetics(Wiley, 2003) Malalavidhane, T.S.; Wickremasinghe, S.M.D.N.; Perera, M.S.A.; Jansz, E.R.Ipomoea aquatica Forsk is a common green leafy vegetable consumed in many parts of the world. The present study was designed to investigate theoral hypoglycaemic activity of Ipomea aquatica in streptozotocin induced diabetic Wistar rats, and Type II diabetic patients. Experimental diabetes was induced with streptozotocin in Wistar rats. The rats were then divided into test and control groups. In addition to the standard feed given to both groups the test was fed with the shredded leaves of Ipomoea aquatica (3.4 g/kg) for one week. Type II diabetic patients were subjected to a glucose challenge before and after a single dose of blended I. aquatica. Patients acted as their own controls. The results revealed that consumption of the shredded, fresh, edible portion of I. aquatica for one week, effectively reduced the fasting blood sugar level of streptozotocin-induced diabetic rats (p = 0.01). When subjected to a glucose challenge, the Type II diabetic subjects showed a significant reduction (p = 0.001) in the serum glucose concentration 2 h after the glucose load. However, it was not significantly reduced at 1 h (p < 0.09) post glucose load. There was a 29.4% decrease in the serum glucose concentration of the diabetic patients when treated with the plant extract.Item In-vitro studies on the immunomodulatory effects of extracts of Osbeckia aspera(Elsevier, 2001) Nicholl, D.S.; Daniels, H.M.; Thabrew, M.I.; Grayer, R.J.; Simmonds, M.S.J.; Hughes, R.S.Ayruvedic medical practitioners in Sri Lanka use aqueous extracts of the mature leaves of Osbeckia aspera to treat liver disease. The extract has been shown to have hepatoprotective effects in vitro and in vivo, and to have inhibitory effects on the complement system and on in vitro phagocytosis by polymorphonuclear cells. The aim of this study was to investigate the effect of an aqueous extract of Osbeckia on lymphocyte proliferation stimulated by mitogens and antigen. In control peripheral blood mononuclear cells (PBMC), high concentrations of the Osbeckia extract were inhibitory to proliferation stimulated by phytohaemagglutinin (PHA) and tuberculin purified protein derivative (PPD). On stimulation by phorbol myristate acetate and ionomycin (PMA+I) the extract showed stimulation of proliferation at low concentrations (<10 microg/ml) with inhibition at higher concentrations. A similar inhibitory pattern on mitogen/antigen stimulation was seen with PBMC from patients with chronic hepatitis C virus (HCV) infection. These results suggest that the inhibitory agent(s) in the aqueous extract of Osbeckia may have an effect on antigen-presenting cell function. The combined hepatoprotective and immunosuppressive effects of the extract are more likely to be beneficial in acute hepatitis rather than chronic hepatitis viral infection.Item The Oral hypoglacaemic activity of Ipomea aquatica(Elsevier, 2000) Malalavidhane, T.S.; Wickremasinghe, S.M.D.N.; Jansz, E.R.Ipomoea aquatica is a commonly consumed green leafy vegetable in Sri Lanka which is supposed to possess an insulin-like activity [Jayaweera, D.M.A., 1982. Medicinal Plants (Indigenous and Exotic) Used in Ceylon. Part 11. National Science Council, Colombo, Sri Lanka, pp. 99]. Only a little attention has been paid to the therapeutic use of this plant. We studied the oral hypoglycaemic activity of single and multiple doses of I. aquatica in healthy, male Wistar rats after a glucose challenge. There was a significant reduction in the serum glucose concentrations with both single (33%, P<0.0027) and multiple (25%, P<0.02) doses. The optimum dose was 3.4 g/kg while the optimum activity was given 2 h after the administration of the extract. The present study indicates that a boiled, whole extract of I. aquatica exerts an oral hypoglycaemic effect in healthy, male, Wistar rats after a glucose challenge.Item Protection by Osbeckia aspera against carbon tetrachloride-mediated alterations in microsomal drug metabolizing enzyme activity(Wiley, 2000) Jayathilake, K.A.P.W.; Thabrew, M.I.Previous investigations have confirmed the protective effect of Osbeckia aspera leaf extract on carbon tetrachloride-mediated liver injury in rat models. It is well known that the earliest alterations in liver cell structure and function following carbon tetrachloride poisoning involve the endoplasmic reticulum and its drug metabolizing enzymes. Therefore, we investigated whether an aqueous leaf extract of O. aspera could offer protection againstcarbon tetrachloride-induced changes in the microsomal drug metabolizing enzymes aniline hydroxylase and p-aminopyrine N-demethylase. Thisenzyme activity was compared with phenobarbital-induced righting reflex and lipid peroxidation. Treatment of rats with the aqueous leaf extract of O.aspera (before or after the administration of carbon tetrachloride) resulted in a marked decrease in carbon tetrachloride-mediated alterations in aniline hydroxylase and p-aminopyrine N-demethylase activity, phenobarbital-induced loss of righting reflex and malondialdehyde formation due to lipid peroxidation. The Km value of these enzymes in control and Osbeckia-treated rats were the same. These results show that the plant extract can markedly decrease the carbon tetrachloride-mediated reduction in aniline hydroxylase and p-aminopyrine N-demethylase activity and inhibit peroxidative damage to the cell membrane. Phenobarbital-induced sleeping time in rats and kinetic enzyme studies suggested that the effects of the plant extract was neither due to an induction of the drug-metabolizing enzymes under investigation, nor due to an alteration in the Km values of these enzymes.Item Protective effects of Osbeckia octandra against galactosamine and tert-butyl hydroperoxide induced hepatocyte damage(Elsevier, 1995) Thabrew, M.I.; Gove, C.D.; Hughes, R.D.; McFarlane, I.G.; Williams, R.Ayurvedic and other 'traditional' medical practitioners in Sri Lanka use the mature leaves of the plant Osbeckia octandra for its hepatoprotective properties. In this study the effects of an aqueous extract of Osbeckia octandra against injury induced by D-galactosamine and tert-butyl hydroperoxide (TBH) were investigated in freshly isolated rat hepatocytes. The plant extract (500 micrograms/ml) significantly reduced the inhibition of protein synthesis (as assessed by the incorporation of 14C-leucine into protein) in hepatocytes incubated for 1 h with 10 mM galactosamine by a mean of 25.6 +/- 3.6% and decreased the release of cellular lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) enzyme activities into the medium by 55.3% and 32.8%, respectively. With TBH, the plant extract decreased lipid peroxidation (estimated from malondialdehyde formation) by a mean of 29.9 +/- 1.1% together with a 46.8% and 54.7% decrease in the release of LDH and AST, respectively into the incubation medium. Significant protection was also obtained when the Osbeckia extract was added to the incubation medium up to 30 min after pre-exposure of the hepatocytes to either galactosamine or, to a lesser extent, TBH. The results support the use of Osbeckia as a hepatoprotective agent.Item Protective effects of Osbeckia octandra against paracetamol-induced liver injury(Informa Healthcare, 1995) Thabrew, M.I.; Hughes, R.D.; Gove, C.D.; Portmann, B.; Williams, R.; McFarlane, I.G.Osbeckia octandra is a plant used in traditional medicine to treat jaundice and other liver disorders. In this study, the effects of Osbeckia leaf extract on paracetamol-induced liver injury were investigated both in vivo in mice and in rat hepatocytes in vitro. 2. Oral administration of Osbeckiaextract (330 mg/kg) at the same time as paracetamol (450 mg/kg) to mice, resulted in a significant protection (p < 0.05) against liver damage, as assessed by improvements in the blood Normotest (39.1 +/- 1.9 versus 46.3 +/- 2.0 s), total liver glutathione (730 +/- 39 versus 574 +/- 27 micrograms/250 mg liver), plasma aspartate aminotransferase level (916 +/- 225 versus 1965 +/- 291 iu/l), and liver histopathology at 24 h after paracetamol administration. 3. In experiments to assess the direct effects of Osbeckia extract, significant protection was also found in freshly isolated rat hepatocytes against damage induced by 185 microM 2,6-dimethyl N-acetyl p-quinoneimine (2,6-diMeNAPQI, an analogue of NAPQI, the toxic metabolite of paracetamol) in vitro. When Osbeckia extract (500 micrograms/ml) was added to the incubation medium at the same time as 2,6-diMeNAPQI significant changes in cell viability (78.4 +/- 3.3 versus 47.2 +/- 5.8% of control, p < 0.001), cell reduced glutathione (GSH) level (35.0 +/- 3.1 versus 23.8 +/- 1.5%, p = 0.009), and reduced release of lactate dehydrogenase (129.9 +/- 6.6 versus 224.6 +/- 12.1%, p < 0.001) were demonstrated after 1 h incubation as compared with 2,6-diMeNAPQI alone. 4. Significant protection was still obtained against 2,6-diMeNAPQI in vitro when addition of Osbeckia extract was delayed by 20 min. These results indicate that Osbeckia extract can protect against paracetamol-induced liver injuryItem Effect of Artocarpus heterophyllus and Asteracanthus longifolia on glucose tolerance in normal human subjects and in maturity-onset diabetic patients(Elsevier, 1991) Fernando, M.R.; Wickramasinghe, N.; Thabrew, M.I.; Ariyananda, P.L.; Karunanayake, E.H.Investigations were carried out to evaluate the effects of hot-water extracts of Artocarpus heterophyllus leaves and Asteracanthus longifolia whole plant material on the glucose tolerance of normal human subjects and maturity-onset diabetic patients. The extracts of both Artocarpus heterophyllus and Asteracanthus longifolia significantly improved glucose tolerance in the normal subjects and the diabetic patients when investigated at oral doses equivalent to 20 g/kg of starting material.Item Immunomodulatory activity of three Sri-Lankan medicinal plants used in hepatic disorders(Elsevier, 1991) Thabrew, M.I.; de Silva, K.T.; Labadie, R.P.; de Bie, P.A.; van der Berg, B.The effects of aqueous extracts of Osbeckia octandra whole plant, Melothria maderaspatana whole plant and Phyllanthus debelis leaves on the human immune system were investigated. The extracts showed strong anticomplement effects on both the classical and alternate pathways of the human complement system in vitro. The effects were dose-dependent and most pronounced in the classical complement pathway assay. The extracts also exhibited a direct dose-dependent inhibition of luminol-induced chemiluminescence of human polymorphonuclear leukocytes upon stimulation with zymosan.