Journal/Magazine Articles
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This collection contains original research articles, review articles and case reports published in local and international peer reviewed journals by the staff members of the Faculty of Medicine
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Item A Comparative study of the beneficial effects of Osbeckia octandra and Osbeckia aspera in liver dysfunction in rats(University of Colombo, 1999) Thabrew, M.I.; Jayathilake, K.A.P.W.A study was conducted to compare the protective effects of aqueous extracts of Osbeckia octandra and Osbeckia aspera against carbon tetrachloride (CCl4)-mediated liver damage in Sprague Dawley rats by assessing their ability to protect livers against the toxin-mediated alterations in the liver histopathology and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase. Within 24 h of administering a sub-lethal dose (0.2 ml/l00 g, i.p.) of CCI4 to rats, the ALT, AST and alkaline phosphatase activities were found to be 380.8 percent, 101.4 percent and 222.2 percent higher respectively, than the corresponding base values in control animals untreated with the toxin. By pre-treatment of rats for 7 days with an aqueous extract of either the O.octandra or O.aspera, the CCI4-mediated changes in the serum enzyme activities could be considerably reduced. Thus, in rats pre-treated with an extract of O.octandra or O.aspera, the CCI4 was able to cause only a 33.7 percent or 27.6 percent increase in ALT activity, a 9.2 percent or 4.2 percent increase in AST activity and a 16.6 percent or 17.6 percent increase in alkaline phosphatase activity respectively, above the corresponding values in control animals. In post-treatment experiments also when serum enzyme levels in rats treated only with CCI4 and left to recover for 4 days were compared with those in rats treated orally for 3 days with either plant extract starting 24 h after the toxin administration, it was found that both plant extracts were able to protect the livers against the toxin mediated changes, to a similar extent. Thus, on the 4th day after CCI4 treatment, the serum ALT, AST and alkaline phosphatase activities were still 162 percent,76.5 percent and 90.1 percent respectively, higher than the corresponding values in control animals. In the O.octandra and O.aspera post-treated groups, the corresponding increases in the activities of ALT, AST and alkaline phosphatase respectively, were only 53.8 percent and 35.5 percent for ALT, 39.2 percent and 41.6 percent for AST and 29 percent and 18.6 percent for alkaline phosphatase. In both the pre-treatment and the post-treatment experiments it was also observed that, the CCl4 -mediated alterations in liver histopathology could be prevented to a similar extent by both plant extracts. The overall results indicate that aqueous extracts of the leaves of both O.octandra and O.aspera possess very similar hepatoprotective abilities, thus rationalizing the use of both these plants in traditional medicine for the treatment of liver disease.Item Cytoprotective effect of Osbeckia aspera against oxidative damage to HepG2 cells(Lippincott Williams and Wilkins, 1998) Thabrew, M.I.Aqueous extracts of the leaves of plants of the Osbeckia family are used in Sri Lanka for treatment of liver disease. The extract contains antioxidant compounds and in vitro experiments were performed to determine the antioxidant effects of an extract of Osbeckia aspera. The plant extract significantly protected HepG2 cells against the peroxidating effects of cumene hydroperoxide and tert-butyl hydroperoxide. The protection against cell damage from both hepatotoxic compounds was similar to that of silymarin, but not asgreat as that shown by (+)-catechin. Antioxidant compounds in Osbeckia aspera may be an important mechanism responsible for the in vivo hepatoprotective activity of this plant.Item Screening of hepatoprotective plant components using a HepG2 cell cytotoxicity assay(Wiley, 1997) Thabrew, M.I.; Hughes, R.D.; Mcfarlane, I.G.Identification of the active components of plants with hepatoprotective properties requires screening of large numbers of samples during fractionation and purification. A screening assay has been developed based on protection of human liver-derived HepG2 cells against toxic damage. Various hepatotoxins were incubated with HepG2 cells in 96-well microtitre plates (30,000 cells well-1) for 1 h and viability was determined by metabolism of the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS). Bromobenzene (10 mM) and 2,6-dimethyl-N-acetyl-p-quinoneimine (2,6-diMeNAPQI, 200 mM) had greater toxic effects than tert-butyl hydroperoxide (1.8 mM) or galactosamine (10 mM), reducing mean viability to 44.6 +/- 1.2% (s.e.m.) and 56.1 +/- 2.1% of control, respectively. Protection against toxic damage by these agents was tested using a crude extract of a known hepatoprotective Sri Lankan plant, Osbeckia aspera, and two pure established hepatoprotective plant compounds, (+)-catechin and silymarin (1 mg mL-1). Viability was significantly improved by Osbeckia (by 37.7 +/- 2.4%, P < 0.05, and 36.5 +/- 2.1%, P < 0.05, for bromobenzene and 2,6-diMeNAPQI toxicity, respectively). Comparable values for (+)-catechin were 68.6 +/- 2.9% and 63.5 +/- 1.1%, and for silymarin 24.9 +/- 1.4% and 25.0 +/- 1.6%. This rapid and reproducible assay should prove useful for the isolation and identification of active hepatoprotective compounds in crude plant extracts.Item Phytogenic agents in the therapy of the Liver disease(1996) Thabrew, M.I.; Hughes, R.D.Plant extracts have been used by traditional medical practitioners for the treatment of liver disorders for centuries. This article reviews the clinical trials carried out with thirteen plants and their constituents in patients with liver disease, including acute viral hepatitis, chronic viral hepatitis, chronic cholecystitis, alcoholic liver disease and mushroom poisoning. There is considerable scientific evidence that phytogenic agents can have significant beneficial effects on liver dysfunction and the course of liver disease. At present, silymarin has the most proven overall clinical hepatoprotective effects, although glycyrrhizin appears to be more beneficial in chronic viral hepatitis. With the high worldwide incidence of viral hepatitis, further study of isolated phytochemicals is important in relation to their potential antiviral activity against the different hepatitis viruses.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 Protection against galactosamine and test-butyl hydroperoxide induced hepatocyte damage by Melothria maderaspatana extract(Wiley, 1995) Thabrew, M.I.; Gove, C.D.; Hughes, R.D.; McFarlane, I.G.; Williams, R.The aqueous extract of Melothria maderaspatana is used by traditional medical practitioners to treat jaundice in man. The effect of Melothria maderaspatana extract on damage induced in freshly isolated rat hepatocytes by D-galactosamine and tert-butyl hydroperoxide (TBH) has been investigated. On incubation of hepatocytes with galactosamine or TBH in the presence of the plant extract, a significant dose-dependent protection against hepatocyte damage was observed, with maximum protection at a concentration of 500 g/mL. At this concentration the galactosamine-induced release of lactate dehydrogenase (LDH) and aspartate amino-transferase (AST) were reduced by 40.7 percent + or - 4.2 percent and 37.7 percent + or - 6.1 percent respectively, compared with control incubations. The TBH-induced lipid peroxidation (estimated from malondialdehyde production) was decreased by 26.0 + or - 3.7 percent together with a 38.4 percent + or - 4.4 percent and 40.8 + or - 7.6 percent reduction in the release of cellular LDH and AST respectively into the incubation medium. On post-treatment with the plant extract the protective activity was found to decrease with increase in time of exposure of the cells to either of the toxins. The direct protective effects of Melothria extract on hepatocytes support the use of this plant as a herbal remedy.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.Item Hypoglycaemic activity of some medicinal plants in Sri-Lanka(Elsevier, 1990) Fernando, M.R.; Thabrew, M.I.; Karunanayake, E.H.Investigations were carried out to determine whether aqueous extracts of Osbeckia octandra, Artocarpus heterophyllus and Bambusa vulgaris truly possess oral hypoglycaemic activity. 2. All three plant extracts significantly lowered the fasting blood glucose level and markedly improved glucose tolerance in Sprague-Dawley rats. 3. A maximum hypoglycaemic activity was observed at +3 hr with O. octandra and B. vulgaris; with A. heterophyllus a maximum effect was not observed even at +5 hr. 4. The hypoglycaemic activity of O. octandra was comparable with that of tolbutamide while that of A. heterophyllus or B. vulgaris was better than that of tolbutamide. 5. The magnitude of the hypoglycaemic effects varied with the dosage used and the time of storage (except with A. heterophyllus, whose activity did not change with storage even up to 3 days).