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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 Natural products: A rich source of antiviral drug lead candidates for the management of COVID-19(Bentham Science Publishers, 2021) Wijayasinghe, Y.S.; Bhansali, P.; Viola, R.E.; Kamal, M.A.; Poddar, N.K.ABSTRACT: Today, the world is suffering from the pandemic of a novel coronavirus disease (COVID-19), a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the third fatal coronavirus outbreak that has already occurred in the 21st century. Even six months after its emergence, hundreds of thousands of people are still being infected with SARS-CoV-2, and thousands of lives are lost every day across the world. No effective therapy has been approved to date for the prevention or treatment of this disease, suggesting the need to broaden the scope in the search for effective treatments. Throughout history, folk medicine has been successfully used to treat various ailments in humans and Traditional Chinese Medicine has been instrumental in the containment of a number of viral diseases. Owing to their high chemical diversity and safety profiles, natural products offer great promises as potentially effective antiviral drugs. In recent years, a large number of anti-coronaviral phytochemicals with different mechanisms of action have been identified. Among them, tetra-O-galloyl-β-D-glucose, caffeic acid, and saikosaponin B2 block viral entry. A number of flavonoids inhibit viral proteases. Silvestrol inhibits protein synthesis. Myricetin and scutellarein inhibit viral replication. Emodin, luteolin, and quercetin demonstrate anti-coronaviral activity by inhibiting multiple processes in the virus life cycle. In this review, we critically evaluate the findings of the natural product-based anti-coronaviral research that has been published during last two decades, and attempt to provide a comprehensive description about their utility as potential broad-spectrum anti-coronaviral drugs, examining leads that may guide/facilitate anti-SARS-CoV-2 drug development studies. KEYWORDS: COVID-19; Coronavirus; Natural products; Phytochemicals; SARS-CoV-2; Traditional Medicine.Item Extra - pancreatic actions of Trichosanthes cucumerina(Sri Lanka Association for the Advancement of Science, 2008) Arawwawala, L.D.A.M.; Thabrew, M.I.; Arambewela, L.S.R.Trichosanthes cucumerina Linn (Family: Cucurbitaceae), locally known as Dummella is commonly found in Asian countries including Sri Lanka. The aerial parts of T. cucumerina (T.C) are widely used in combination with other plants in the traditional medicinal systems as a remedy for fever, dropsy, acute bronchitis, boils, inflammation, skin diseases, jaundice, gastric lesions and diabetes. In Sri Lanka, the aerial parts of T.C are used as a remedy for diabetes. In a previous study we demonstrated that hot water extract (HWE) of T.C aerial parts can exert significant hypoglycemic activity in both normaglycemic and streptozotocine (STZ) induced diabetic rats. It was also shown that HWE had no effect on intestinal glucose absorption. A study was therefore, carried out to determine if extra - pancreatic effects were the main mechanisms by which the HWE exerts its hypoglycemic effect in rats. Extra - pancreatic effects were investigated by comparison of (a) Liver glycogen levels and (b)Triglyceride level in adipose tissue in normaglycemic and STZ - induced (by i.v. 50 mg/kg) diabetic rats that were orally treated with the HWE with those that did not receive the extract in the corresponding groups. Wistar rats (175 - 200 g body weight) were randomly divided in to 4 groups. Rats in Group 1 (n = 12; normal controls) were orally administered distilled water (1.0 ml/Kg), Group 2 (n = 12; normal test) received HWE (750 mg/kg of body weight), Group 3 (n = 7; diabetic control) received distilled water (1.0 ml/Kg) while group 4 (diabetic test) received HWE consecutively for 28 days. The dose of 750 mg/kg T.C was used because it exerted the maximum hypoglycemic effect in the previous study. Rats were kept fasting and, blood samples were collected from their tails at 14 days and 28 days post treatment and serum glucose levels determined. Subsequently, rats were sacrificed, livers and adipose tissues were harvested and subjected for estimation of glycogen levels and triglyceride levels respectively. In the diabetic rats, compared to the control group HWE significantly reduce the blood glucose levels at the end of 14 days and 28 days. The reduction in blood glucose was comparable to that produced by the antidiabetic drug, glibenclamide (0.6 mg/Kg). In normaglycemic rats HWE reduced the blood glucose levels at the end of 14 and 28 days. At the end of 28 days, it was found that in both normaglycemic and STZ - induced diabetic rats, there was a significant (P= 0.05) increase in the levels of liver glycogen (normaglycemic rats by 55.8 %; diabetic rats by 93.6 %) and adipose tissue triglyceride (normaglycemic rats by 14.3 %; diabetic rats by 16.7 %) in comparison with the respective controls that were not treated with HWE. It may be concluded that hypoglycemic effects demonstrated by T.C are mediated mainly via enhanced up take of blood glucose in to extra - pancreatic tissues. Financial assistance by National Science Foundation (Research Grant NSF/SCH/2005/13) is acknowleged.Item Sri Lankan sanni masks: an ancient classification of disease(British Medical Association, 2006) Bailey, M.S.; de Silva, H.J.No Abstract AvailableItem 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.