DSpace Collection: Thesis - Medicinal Chemistry

The role of incretin hormone in type 2 diabetes

Title: The role of incretin hormone in type 2 diabetes

Authors: Dereje, Getachew

Abstract: Background: Type 2 diabetes mellitus is a metabolic disease associated with low quality of life and early death. It is now well established that beta-cell dysfunction and insulin resistance are two central defects in the pathophysiology of T2DM. Recently, improved understanding of the incretin effect on the pathophysiology of type 2 diabetes has led to development of new hypoglycemic agents. The incretin effect refers to the amplification of insulin secretion that occurs when glucose is ingested orally as opposed to infused intravenously in amounts that result in identical glucose excursions. Objective: To review the role of incretin hormone in type 2 diabetes. Methode: The review was conducted as a systemic review. Articles were searched from MEDLINE, HINARI and PUBMED in English language with the key words incretin or gut hormone, type 2 diabetes, and the role of incretin in type 2 diabetes. Result: A total of 65 studies were retrieved. Of these, 12 were considered to be relevant up on initial screening. Abstract of these 12 articles were reviewed and while 5 studies excluded. 7 studies were agreed upon to meet the inclusion criteria. Conclusion: The incretin effect was significantly reduced in patients with type 2 diabetes.GLP-1 concentrations and response is also reduced. But the GIP concentration is increased, reduced or normal. Incretin secretion is increased after oral glucose compared with intravenous infusion.

A SYSTEMIC REVIEW ON ANTIOXIDANT AND HEPATOPROTECTIVE EFFECT OF PSIDIUM GUAJAVA LEAF AND FRUIT EXTRACT

Title: A SYSTEMIC REVIEW ON ANTIOXIDANT AND HEPATOPROTECTIVE EFFECT OF PSIDIUM GUAJAVA LEAF AND FRUIT EXTRACT

Authors: TESFAHUN, MOLLA

Abstract: 11 ABSTRACT Background: Plant derived natural products such as flavonoids, terpenoids, carbohydrates, tannins, saponins, steroids, proteins, amino acids and Vitamin C have received considerable attention in recent years due to their diverse pharmacological properties including antioxidant and hepatoprotective activity. Psidium guajava (Myrtaceae) is one of such plants in folk medicine that has been used for the management of various disease conditions. Various parts of the plant has been used in traditional medicine .Antioxidants from medicinal plants play an important role in inhibiting and scavenging radicals, thus providing protection to human against infection and degeneration diseases. Objective: To review the antioxidant and hepatoprotective activity of psidium guajava. Methods: Computerised literature search was conducted using PubMed, Medline and Google search engine using different key words for studies investigating the antioxidant and hepatoprotective activities of Psidium guajava using the following as heading terms, psidium guajava, antioxidant, hepatoprotectie, Liver injury, oxidative stress. In addition, the reference lists of the retrieved articles helped me to find further articles, relevant to the present review that was not revealed through the searching procedure. Result: Out of a total of 152 articles on guava resulted 19 studies which were related to antioxidant and hepatoprotective activity of leaf and fruit extract were included in this review. These were then categorized into six groups; 1) Six studies on in vitro antioxidant studies with leaf extracts, 2) four studies on in vitro antioxidant studies with fruit extract, 3) one in vivo study on antioxidant with leaf extract in rat, 4) one in vivo study on antioxidant with fruit extract in rat, 5) one study antioxidant fruit extract in human and 6) six in vivo studies on hepatoprotective with leaf extract in rat. Conclusion: The antioxidant activity of Psidium guajava may be due to inhibition of the formation of radicals, scavenging of the formed free radicals, reducing of oxidized intermediates and the presence of the phenolic compounds. It also acts as promising hepato protective which is correlated directly with its ability to reduce activity of serum enzymes and enhance 12 antioxidant defense status. The phenolic content in Psidium guajava extract played a significant role on the antioxidant and hepatoprotective activity.

Antidiabetic activity and phytochemical screening of crude extracts of Stevia rebaudiana Bertoni and Ajuga remota Benth grown in Ethiopia on alloxan-induced diabetic mice

Title: Antidiabetic activity and phytochemical screening of crude extracts of Stevia rebaudiana Bertoni and Ajuga remota Benth grown in Ethiopia on alloxan-induced diabetic mice

Authors: Tadesse, Bekele

Abstract: Diabetes mellitus is a major public health problem in the world. The prevalence of diabetes mellitus is increasing with ageing of the population and lifestyle changes associated with rapid urbanization and westernization. According to the World Health Organization estimate 3% of the world’s populations (194 million) have diabetes and is expected to double (6.3%) by the year 2025 and that of Ethiopia was about 800,000 cases in 2000, and the number is expected to increase to 1.8 million by 2030. Stevia rebaudiana Bertoni (Asteraceae) and Ajuga remota Benth (Lamiaceae) has been used for the treatment of diabetes mellitus and various other ailments in the traditional medical system world wide. This study reports the antidiabetic activity of crude extracts of Stevia rebaudiana Bertoni & Ajuga remota Benth grown in Ethiopia on alloxan-induced diabetic mice A preliminary toxicity study of S. rebaudiana and A. remota crude extracts was done using Swiss albino mice in oral doses of 1000, 2000 and 5000 mg/kg body weight. The result showed that the medium lethal dose (LD50) of the extracts is higher than 5000 mg/kg body weight and hence, in a single dose administration, the plant extracts had no adverse effect. The result obtained is in agreement with that of Geuns (2003) for S. rebaudiana and Worku (2005) for A. remota. The preliminary phytochemical screening indicated the presence of flavonoids, saponins, tannins and steroids in both plants and alkaloids in the leaves of S. rebaudiana. Extracts of both plants did not contain anthraquinones. The result obtained here is in agreement with that of Anonymous-a (1999) for S. rebaudiana and Worku (2005) for A. remota. A concentration of 2.27 % stevioside was obtained in the leaves of S. rebaudiana. The antihyperglycemic activity of the crude aqueous and ethanol extracts of S. rebaudiana and A. remota were studied in alloxan-induced (200 mg/kg body weight, ip.) diabetic mice, after oral administration at a dose of 300 and 500 mg/kg body weight for two weeks. Administration of crude aqueous extract of S. rebaudiana for 14 days lowered elevated blood glucose levels by 30.27% (300 mg/kg) and 42.65% (500 mg/kg) that shows S. rebaudiana has retained its antidiabetic activity when grown out of its natural habitat, i.e. in Ethiopia. In the case of A. remota, blood glucose reduction was 27.96% and 38.98% respectively for the dose levels tested. Crude ethanol extract of S. rebaudiana and A. remota (300 and 500 mg/kg body weight for 14 days) lowered blood glucose level by 28.71% & 33.04% and 28.09% & 28.25% respectively as compared with diabetic untreated mice. Treatment with the known antidiabetic drug, glibenclamide (10 mg/kg body weight) lowered blood glucose level by 51.06%. The effect was more pronounced in the case of the crude aqueous extract as compared with the crude ethanol extract on the respective dose limits for both plant cases.

Description: A Thesis Submitted to the School of Graduate Studies, Addis Ababa University in Partial Fulfilment of the Requirement for the Degree of Masters of Science in Medicinal Chemistry