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Item Anticonvulsant Effect Of Ethanolic Leaf Extract Of Ehretia Cymosa Thonn (Boraginaceae) In Murine Models.(University Of Ghana, 2018-07) Nelson, L.R.Purpose: Ehretia cymosa is used locally in Ghana to treat epilepsy. To validate this anecdotal information with scientific data, the anticonvulsant effect of the ethanolic extract of the leaves of Ehretia cymosa was studied in murine models. Materials and Methods: The potential anticonvulsant activity of an ethanol extract of Ehretia cymosa (ECE) (30, 100, and 300 mg kg-1) was tested employing the acute pentylenetetrazole (PTZ)-, PTZ-induced kindling, picrotoxin-induced seizures and maximal electroshock (MES) in mice. The extract‘s effect on motor co-ordination and nociception was also tested using the rota-rod and the hot plate tests respectively. Acute and sub-chronic toxicity tests were also done to ascertain how safe the extract is in rodents. Results: This study showed that, the ethanolic extract of ECE possesses anticonvulsant effects in the various seizure threshold models used, except in the maximal electroshock seizure model. The latencies to the first myoclonic jerks were increased by ECE while both the duration and frequencies of seizures reduced significantly. There was however no effect on motor coordination even when highest dose of 300 mg kg-1 was used. No mortalities were recorded in the animals used during the period of this study. The ECE also did not have any significant effect on any of the serum biochemical parameters after the study. Conclusions: The ethanolic extract of the leaves of the Ehretia cymosa was found to possess anticonvulsant properties, and possibly acts through the GABAergic transmission pathway but has no muscle relaxant properties. The findings from this study, therefore, give scientific credence to the traditional use of Ehretia cymosa to manage epilepsy. The 10-week oral administration of the extract of Ehretia cymosa under the prevailing laboratory conditions was found to be relatively safe in male Sprague–Dawley rats.Item Analgesic Effects Of Annona Muricata Leaf Extract In Paclitaxel And Streptozotocin-Induced Diabetic Neuropathy In Murine Models.(University Of Ghana, 2022-08) Koomson, F.A.Background: Annona muricata have demonstrated antinociceptive and anxiolytic effects in animal models through its leaf extracts. This study evaluates the aqueous leaf extract of the plant for possible analgesic properties in hyperalgesia and allodynia associated with paclitaxel-induced neuropathy in mice and streptozotocin (STZ)- induced diabetic neuropathy in rats. Methods:10kg of the coarse crushed leaves was soaked in 3 liters of distilled water to make a decoction, cooled, filtered and freeze dried for use. Sub-acute toxicity test was carried out for 14- days after which blood samples were taken and examined for haematological analysis. Phytochemistry of the extract was conducted and analgesic property was accessed using hot plate test. Irwin test was also conducted to observe alterations in behavior and physiological activity, neurotoxicity and mortality. Diabetic- induced neuropathy in Sprague-Dawley rats was accomplished by injecting 55mg/kg body weight of STZ followed by 120mg/kg body weight of nicotinamide to achieve type 2 diabetes mellitus. Paclitaxel-induced neuropathy was also achieved by injecting ICR mice with 2mg/kg body weight body weight of paclitaxel continuously for 5 days. Parameters which include cold allodynia mechanical hyperalgesia and thermal hyperalgesia were measured before the administration of paclitaxel and on day 1 – 5 and after the administration of paclitaxel. In STZ-induced diabetic neuropathy experiment parameters were measured before the administration of STZ and after the administration of STZ on day 2, 4, 6, 8, 10, 12 and 14. These animals were then treated with Annona muricata extract (AME) (30, 100 and 300 mg/kg body weight), pregabalin (10, 30 and 100 mg/kg body weight) and distilled water as a vehicle daily for 5 days and 14 days continuously in paclitaxel- and diabetic-induced peripheral neuropathy respectively. Pain thresholds were measured on day 1, 2, 3 and 5 in paclitaxel-induced neuropathy experiment and that of STZ-induced - diabetic neuropathic experiment, it was measured from day 1-7. Results: Annona muricata Extract (AME) showed no toxicity as no death were observed during the 14-day study period in sub-acute toxicity studies. Preliminary phytochemical screening of the extract indicated the presence of secondary metabolites which includes alkaloids, saponins, flavonoids, tannins, glycosides, triterpenoids and sterols. The extract showed analgesic property during the hot plate test. CNS safety pharmacology using Irwin test indicated no mortality when experimental animals were observed for 24 hours after various treatment doses were employed. Observable physiological/ pharmacological effects were noted which include straub tail, defecation, sniffing among others. Relative organ weight of the experimental animals also indicated no obvious abnormally when compared to the control during Irwin’s test. AME and pregabalin produced analgesic properties which was exhibited in paclitaxel and STZ-induced - neuropathy as increased paw withdrawal latencies to mechanical, cold-water stimuli and thermal hyperalgesic tests. Conclusions: The findings from this study suggest that aqueous extract of Annona muricata is sub acutely safe with observable CNS physiological effect and no observable CNS toxicity. Again, the extract possesses an analgesic property as seen in both paclitaxel- and STZ-induced diabetic neuropathy in animal models which may contribute to its traditional use in managing neuropathic pain.Item Analgesic Effects Of Annona Muricata Leaf Extract In Paclitaxel And Streptozotocin-Induced Diabetic Neuropathy In Murine Models(University Of Ghana, 2022-08) Koomson, F.A.Background: Annona muricata have demonstrated antinociceptive and anxiolytic effects in animal models through its leaf extracts. This study evaluates the aqueous leaf extract of the plant for possible analgesic properties in hyperalgesia and allodynia associated with paclitaxel-induced neuropathy in mice and streptozotocin (STZ)- induced diabetic neuropathy in rats. Methods:10kg of the coarse crushed leaves was soaked in 3 liters of distilled water to make a decoction, cooled, filtered and freeze dried for use. Sub-acute toxicity test was carried out for 14- days after which blood samples were taken and examined for haematological analysis. Phytochemistry of the extract was conducted and analgesic property was accessed using hot plate test. Irwin test was also conducted to observe alterations in behavior and physiological activity, neurotoxicity and mortality. Diabetic- induced neuropathy in Sprague-Dawley rats was accomplished by injecting 55mg/kg body weight of STZ followed by 120mg/kg body weight of nicotinamide to achieve type 2 diabetes mellitus. Paclitaxel-induced neuropathy was also achieved by injecting ICR mice with 2mg/kg body weight body weight of paclitaxel continuously for 5 days. Parameters which include cold allodynia mechanical hyperalgesia and thermal hyperalgesia were measured before the administration of paclitaxel and on day 1 – 5 and after the administration of paclitaxel. In STZ-induced diabetic neuropathy experiment parameters were measured before the administration of STZ and after the administration of STZ on day 2, 4, 6, 8, 10, 12 and 14. These animals were then treated with Annona muricata extract (AME) (30, 100 and 300 mg/kg body weight), pregabalin (10, 30 and 100 mg/kg body weight) and distilled water as a vehicle daily for 5 days and 14 days continuously in paclitaxel- and diabetic-induced peripheral neuropathy respectively. Pain thresholds were measured on day 1, 2, 3 and 5 in paclitaxel-induced neuropathy experiment and that of STZ-induced - diabetic neuropathic experiment, it was measured from day Results: Annona muricata Extract (AME) showed no toxicity as no death were observed during the 14-day study period in sub-acute toxicity studies. Preliminary phytochemical screening of the extract indicated the presence of secondary metabolites which includes alkaloids, saponins, flavonoids, tannins, glycosides, triterpenoids and sterols. The extract showed analgesic property during the hot plate test. CNS safety pharmacology using Irwin test indicated no mortality when experimental animals were observed for 24 hours after various treatment doses were employed. Observable physiological/ pharmacological effects were noted which include straub tail, defecation, sniffing among others. Relative organ weight of the experimental animals also indicated no obvious abnormally when compared to the control during Irwin’s test. AME and pregabalin produced analgesic properties which was exhibited in paclitaxel and STZ-induced - neuropathy as increased paw withdrawal latencies to mechanical, cold-water stimuli and thermal hyperalgesic tests. Conclusions: The findings from this study suggest that aqueous extract of Annona muricata is sub acutely safe with observable CNS physiological effect and no observable CNS toxicity. Again, the extract possesses an analgesic property as seen in both paclitaxel- and STZ-induced diabetic neuropathy in animal models which may contribute to its traditional use in managing neuropathic pain.Item In Vitro And In Vivo Kinetic Characteristics Of Chitosan-Pectin-Based Matrix Of Levodopa And Carbidopa(University Of Ghana, 2021-12) Imbeah, E.P.Background: Parkinson's disease is a progressive neurodegenerative disorder that causes disability usually among the elderly. Levodopa remains the drug of choice in the management of Parkinson's disease. Levodopa is extensively metabolized in the periphery by aromatic amino acid decarboxylases; thus, it is routinely co-administered with carbidopa, a peripheral decarboxylase inhibitor. Although the aforementioned combination therapy is effective, there is variable absorption and fluctuating plasma levels of levodopa after oral administration. New oral levodopa plus carbidopa (levodopa/carbidopa) formulations are needed to overcome this irregular absorption and maintain near constant plasma concentrations. Aim: The aim of this study was to evaluate the kinetic characteristics of chitosan-pectin-based multiparticulate matrix of levodopa/carbidopa, using in vitro and in vivo models. Methodology: Pectin was extracted from cocoa pod husk with hot aqueous solution. Preparation of the chitosan-pectin-based matrix was done by the wet granulation. The formulations were evaluated for drug-excipient compatibility, drug content, flowability and precompression properties and in vitro release. In evaluating in vivo pharmacokinetic and biodistribution characteristics, male Sprague Dawley rats were administered either chitosan-pectin based matrix of levodopa/carbidopa, Sinemet CR (a controlled release formulation of levodopa/carbidopa) or levodopa/carbidopa immediate release powder (20/5 mg/kg) via the oral route every 12 hours. After the third dose, tail vein samples and brain tissues were taken at predetermined times. Pharmacokinetic parameters (Cmax, Tmax, AUC and t1/2) of levodopa were estimated for the various treatment, levels of levodopa in rat brains were estimated and compared. Results: The yield of cocoa pod husk pectin extracted with hot aqueous solution was 7.91%. The excipients for drug formulation were compatible with levodopa/carbidopa. The content of levodopa and carbidopa in the various formulations were within the acceptance criteria (not less than 90% and not more than 110% of the stated amount) with the exception of F5. There was controlled and sustained release of levodopa and carbidopa in vitro. In vivo pharmacokinetic studies showed kinetic profiles of levodopa/carbidopa multiparticulate matrix as compared to the conventional control release formulation. The AUC0-24 for optimized levodopa/carbidopa multiparticulate matrix (F3: 484.98 ± 18.70; F4: 535.60 ± 33.04), and Cmax (F3: 36.28 ± 1.52; F4: 34.80 ± 2.19 μg/mL) were relatively higher than Sinemet CR (AUC0-24 262.84 ± 16.73 and Cmax 30.62 ± 3.37 μg/mL). Conclusion: Findings from the study suggest that chitosan-pectin based matrix of levodopa/carbidopa may have the potential to control and maintain therapeutic concentrations of levodopa in circulation over a period of time.Item Acute Toxicity Studies On Aphrodisiacs Of Herbal Origin In Pharmacies Within Greater Accra Metropolis(University Of Ghana, 2022-08) Amankwah, D.Background: Erectile dysfunction (ED) is the inability of a man to attain and sustain adequate erection for satisfactory coitus. Herbal medicines are widely promoted as remedies for ED. The safety profile of these products are largely unknown. In this study, five products of herbal origin, sold as aphrodisiacs in pharmacies within the Greater Accra region, are screened for activity across three functional domains: autonomic, neuromuscular/motor, and CNS using the modified Irwin test. Method: Groups of male Sprague-Dawley rats (150 - 200 g, n = 5) were used. Each candidate herbal product was administered p.o. at three dose levels to different groups of rats. Chlorpromazine (30 mg/Kg, p. o) and caffeine (25 mg/Kg, p. o.) were used as positive controls. The vehicle-treated controls were given normal saline (1 ml/kg, p.o.). Following drug administration, animals were monitored for changes in behaviours indicating alterations in autonomic, neuromuscular/motor, and CNS activity at 0-15 mins, 30 mins, 1 hr., 2 hr., 4 hr., 8 hr., 24 hr. and 48 hr. Hematological, biochemical, and histopathological analyses were performed on blood and isolated organs of the experimental animals 14 days’ post drug administration. Results: No mortality was recorded after 48 h in all groups. Except for sedation, there were no clinical signs of interference with any system such as autonomic, CNS and motor activity for all the five herbal aphrodisiac products. Products 1, 2 and 4 caused significant (p<0.05) increases in the weights of the liver, heart, and spleen at 1200, 150 and 400 mg/kg, p.o. respectively. Products 1 and 2 caused elevated levels of only ALP at low doses while higher doses produced no change in enzyme levels. From the biochemical indices, there was therefore no definite evidence of toxicity from the Products to the liver. Haematological parameters of animals were not adversely affected after 14 days of administration of the Products. Histopathological studies did not also provide any equivocal evidence of toxicity to any organ. Conclusion: The extracts produced no evidence of significant toxicity to major organs of the rats. Transient behavioural alterations, lasting less than 48 hours, suggesting involvement of peripheral and central nervous systems were observed. Caution should be exercised in the use of these Products while further tests are carried out to elucidate the safety profile of the commercial herbal aphrodisiacs.Item Parasitaemia Clearance And Pharmacokinetics Of Artemether/ Lumefantrine Co-Administered With Unsweetened Natural Cocoa Powder(University Of Ghana, 2020-11) Appiah, A.P.Background: One major setback of the use of Artemether/Lumefantrine (A/L) is its high dependence on fatty diets for maximum gastrointestinal (GI) absorption. This is further compounded by nausea and lack of appetite by malaria-infected patients posing a risk of treatment failure and poor therapeutic outcomes. The antimalarial activity and fat content in Unsweetened Natural Cocoa Powder (UNCP) may produce synergism when taken as a dietary supplement with A/L in the efficient treatment of uncomplicated malaria. Aim: To evaluate the effect of UNCP on plasma concentration and malaria parasite clearance of A/L co-administration in murine models. Methodology: An antimalarial experimental study was carried out in A/L-sensitive Plasmodium berghei-infected male Sprague-Dawley (SD) rats to examine the effect of UNCP (300, 600, 900, 1,200 and 1,500 mg/kg), n = 5, when administered alone and in combination with A/L. Also, a pharmacokinetic study was performed on healthy non-malarious male SD rats co-administered A/L with varying doses of UNCP (300, 600, 900, 1,200 and 1,500 mg/kg), n = 3, to assess the effect of UNCP on the plasma drug concentration, bioavailability and other pharmacokinetic parameters using HPLC/UV-Vis method. This was followed by a Liver Function Test (LFT) on the serum samples of the various groups. Phytochemical screening was performed on UNCP to determine the various phytochemicals present. A total fat assay was also performed using the Soxhlet solvent extraction method to ascertain the percentage fat content of UNCP. Results Results indicate a significant difference in parasite clearance for A/L+UNCP (1,200 and 1,500 mg/kg) groups at 36 and 48 hours of administration. A/L + UNCP (1,500 mg/kg) group recorded the most significant parasite decrease (F₆,28=1333, P < 0.0001) in comparison with Coartem® only group (positive control) with a percentage drop of 55.89% and 39.63% respectively and this was followed by A/L + UNCP (1,200 mg/kg) (F₆,28=1333, P < 0.0210) with a percentage drop of 51.98% at 36 hours. A similar trend was observed at 48 hours for A/L + UNCP (1,500 mg/kg) (F₆,28=1333, P < 0.0017) and A/L + UNCP (1,200 mg/kg) groups (F₆,28=1333, P < 0.0391) with percentage drop of 71.97% and 71.3% respectively in comparison with Coartem® only group, (percentage drop of 57.68%) at 48 hours. The UNCP only groups however did not show significant antimalarial activity, but results showed that 1,200 mg/kg and 1,500 mg/kg UNCP only groups survived 24 hours longer than the other UNCP only groups with their survival rate expressed as Mean Survival Time (MST); 2 ± 0.4 days/animals and 2 ± 0.8 days/animals respectively. On the other hand, there was no significant difference in MST for the A/L+UNCP groups (28 ± 0.6 days/animals). Pharmacokinetic studies indicated a significant difference in the area under the curve (AUC0→24) over the 24 hours post drug administration of Lumefantrine for A/L+UNCP (1,200 mg/kg) and A/L+UNCP (1,500 mg/kg) groups (**P < 0.0091) and (***P < 0.0003) in comparison with the Coartem® only group respectively. Similarly, there was a significant difference in peak serum concentration (Cmax) for A/L+UNCP (1,200 mg/kg) (**P < 0.0051) and A/L+UNCP (1,500 mg/kg) (***P < 0.0003) groups in comparison with the Coartem® only group. However, there was no significant difference for (half-life) t1/2, (elimination rate constant) Ke and (peak time) Tmax amongst the various groups. Phytochemical analysis showed the presence of alkaloids, saponins, tannins, glycosides, flavonoids, phenols and the absence of reducing sugars and terpenoids with a percentage fat content of 28.11%. Also, LFT results did not show any significant difference amongst the various groups. Conclusion Higher doses of UNCP (1,200 and 1,500 mg/kg) co-administered with A/L showed significant antimalarial activity and a higher plasma concentration of A/L with a safe hepatic profile.Item Genotoxic And Cardio-Protective Effects Of Kalanchoe Integra In Doxorubicin-Induced Cardiotoxicity In A Rat Model(University Of Ghana, 2022-06) Arhin, E.Background: Advancement in cancer therapy has improved survival among patients. However, the use of anticancer drugs like the anthracyclines (e.g., doxorubicin) are not without untoward or side effects. Notable among these is its cardiotoxic effect which ranges from mild transient blood pressure changes to potentially serious heart failure. Kalanchoe integra (KI) is used in folklore medicine in the management of several clinical conditions. The components of KI predict its cardioprotective potential which could be beneficial among its numerous uses. The aim of the study was to determine the cardio-protective effect of KI against doxorubicin-induced cardiotoxicity using a rat model. Methods: The leaves of Kalanchoe integra (KI) were collected, air-dried, pulverized and extracted using 70% ethanol. HPLC fingerprinting analyses of KI was carried out using an Agilent 1100 system (Santa Clara, CA, USA), composed of quaternary pump, autosampler, diode array detector (DAD), and HP ChemStation Software. Chromatographic separation was carried out on a Tskgel ODS C18 (250 x 4.6 mm i.d., 5 μm particle size) analytical column maintained at 40 oC. The single cell gel electrophoresis assay (SCGE, also known as comet assay) was also employed to ascertain the genotoxic effects of the KI extract. The comet assay was used to study the potential genotoxic effect of KI on the liver, kidney, epithelium of the rectum and bone marrow. A total number of 42 Sprague-Dawley rats (150-200g) were put into 7 groups (n=6). Group I: Vehicle control, received normal saline (1 ml/kg p.o) for 30 days. Group II: Toxic control, received doxorubicin (DOX) (20 mg/kg i.p.) once on the 29th day. Group III: KI control, received KI (300 mg/kg p.o) for 30 days. Group IV: Vitamin E control, received Vitamin E (100 mg/kg p.o) for 30 days. Group V: KI treated-1, received KI (300 mg/kg p.o) for 30 days and DOX (20 mg/kg i.p) on the 29th day. Group VI: KI treated-2, received KI (600 mg/kg p.o) for 30 days and DOX (20mg/kg i.p) on the 29th day. Group VII: Vitamin E treated, received Vitamin E (100 mg/kg p.o) for 30 days and DOX (20mg/kg i.p) on the 29th day. Aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), lactate dehydrogenase (LDH), enzymatic antioxidants such as glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) were assayed from blood taken via cardiac puncture 36 hours after last treatment administration. Excised hearts from rats from each group were taken through histopathological examination. Results: In the HPLC fingerprint analysis, 13 peaks were identified. The first peak with retention time of 3.4min had a peak area of 1.1754 x10 4 mAU and overall percentage peak area of 19.2%. Also peak with retention time of 24.0 min had the highest peak area of 3.223 x104 mAU and overall percentage peak area of 52.63% which is directly proportional to high concentration of that compound in the plant extract. The criterion for toxicity was a statistically significant increase in the number of deoxyribonucleic acid (DNA) comets in the organs and tissues studied compared with controls. Results showed that the KI extract was non-genotoxic. Pre-treatment with KI protected rats against doxorubicin- induced cardiotoxicity as evidenced by the low levels of AST, ALT, ALP, CK and LDH compared with the controls (p < 0.05). SOD, CAT and GPX levels were also high for KI extracts; further showing that KI protected rats against doxorubicin induced cardiotoxicity. Histological examinations revealed that in the KI pretreated groups there were no signs of abnormal myocardial fibers. The myocardia were of normal shape, size and configuration. It was also observed that there was no evidence of vacuolation, neither was there any sign of necrosis or inflammation. The observations contrasted with what was observed in the doxorubicin only group (without treatment). Rats in the doxorubicin only group showed signs of abnormal hypertrophic myocardial fibers, and the myocardia also had small and large vacuoles. Conclusion: The current study showed that the ethanolic (70%) leaf extract of KI offered cardio protection in rats administered with doxorubicin. This is evident in AST, ALT, ALP, CK, LDH, GPX, SOD and CAT levels of assayed blood samples. KI also protected the heart of the rats against histopathological changes such as necrosis, abnormal myocardial fibers, and edema. The study also showed that KI is non-genotoxic.Item Parasitaemia Clearance And Pharmacokinetics Of Artemether/ Lumefantrine Co-Administered With Unsweetened Natural Cocoa Powder(University Of Ghana, 2020-11) Appiah, A.PBackground: One major setback of the use of Artemether/Lumefantrine (A/L) is its high dependence on fatty diets for maximum gastrointestinal (GI) absorption. This is further compounded by nausea and lack of appetite by malaria-infected patients posing a risk of treatment failure and poor therapeutic outcomes. The antimalarial activity and fat content in Unsweetened Natural Cocoa Powder (UNCP) may produce synergism when taken as a dietary supplement with A/L in the efficient treatment of uncomplicated malaria. Aim: To evaluate the effect of UNCP on plasma concentration and malaria parasite clearance of A/L co-administration in murine models. Methodology: An antimalarial experimental study was carried out in A/L-sensitive Plasmodium berghei-infected male Sprague-Dawley (SD) rats to examine the effect of UNCP (300, 600, 900, 1,200 and 1,500 mg/kg), n = 5, when administered alone and in combination with A/L. Also, a pharmacokinetic study was performed on healthy non-malarious male SD rats co-administered A/L with varying doses of UNCP (300, 600, 900, 1,200 and 1,500 mg/kg), n = 3, to assess the effect of UNCP on the plasma drug concentration, bioavailability and other pharmacokinetic parameters using HPLC/UV-Vis method. This was followed by a Liver Function Test (LFT) on the serum samples of the various groups. Phytochemical screening was performed on UNCP to determine the various phytochemicals present. A total fat assay was also performed using the Soxhlet solvent extraction method to ascertain the percentage fat content of UNCP. Results : Results indicate a significant difference in parasite clearance for A/L+UNCP (1,200 and 1,500 mg/kg) groups at 36 and 48 hours of administration. A/L + UNCP (1,500 mg/kg) group recorded the most significant parasite decrease (F₆,28=1333, P < 0.0001) in comparison with Coartem® only group (positive control) with a percentage drop of 55.89% and 39.63% respectively and this was followed by A/L + UNCP (1,200 mg/kg) (F₆,28=1333, P < 0.0210) with a percentage drop of 51.98% at 36 hours. A similar trend was observed at 48 hours for A/L + UNCP (1,500 mg/kg) (F₆,28=1333, P < 0.0017) and A/L + UNCP (1,200 mg/kg) groups (F₆,28=1333, P < 0.0391) with percentage drop of 71.97% and 71.3% respectively in comparison with Coartem® only group, (percentage drop of 57.68%) at 48 hours. The UNCP only groups however did not show significant antimalarial activity, but results showed that 1,200 mg/kg and 1,500 mg/kg UNCP only groups survived 24 hours longer than the other UNCP only groups with their survival rate expressed as Mean Survival Time (MST); 2 ± 0.4 days/animals and 2 ± 0.8 days/animals respectively. On the other hand, there was no significant difference in MST for the A/L+UNCP groups (28 ± 0.6 days/animals). Pharmacokinetic studies indicated a significant difference in the area under the curve (AUC0→24) over the 24 hours post drug administration of Lumefantrine for A/L+UNCP (1,200 mg/kg) and A/L+UNCP (1,500 mg/kg) groups (**P < 0.0091) and (***P < 0.0003) in comparison with the Coartem® only group respectively. Similarly, there was a significant difference in peak serum concentration (Cmax) for A/L+UNCP (1,200 mg/kg) (**P < 0.0051) and A/L+UNCP (1,500 mg/kg) (***P < 0.0003) groups in comparison with the Coartem® only group. However, there was no significant difference for (half-life) t1/2, (elimination rate constant) Ke and (peak time) Tmax amongst the various groups. Phytochemical analysis showed the presence of alkaloids, saponins, tannins, glycosides, flavonoids, phenols and the absence of reducing sugars and terpenoids with a percentage fat content of 28.11%. Also, LFT results did not show any significant difference amongst the various groups. Conclusion Higher doses of UNCP (1,200 and 1,500 mg/kg) co-administered with A/L showed significant antimalarial activity and a higher plasma concentration of A/L with a safe hepatic profile.Item Chemoprotective Activity of D-Ribose-L-Cysteine (Riboceine) against the Cytotoxic effects of Methotrexate and Docetaxel on Normal and Cancer Cell Lines(University of Ghana, 2020-03) Janice, P.T.ABSTRACT Background: Methotrexate (MET) and docetaxel (DOC) are chemotherapeutic agents used for the treatment of breast and prostate cancers, respectively. Their action results in the generation of reactive oxygen species (ROS). Excessive ROS consume cellular antioxidants such as glutathione (GSH) that leads to oxidative stress in both normal and cancer cells. Riboceine (RIB), a GSH-enhancer diet supplement, has been shown to protect against oxidative stress. However, there is a dearth of information on the protective effects of RIB on normal and cancer cells during chemotherapy. Aim: This study sought to determine the chemoprotective effects of RIB against the cytotoxic effects of DOC and MET on normal and cancer cells Methodology: The effects of increasing concentrations of MET and DOC and their combination with RIB or N-acetylcysteine (NAC, positive control) on the cell viability of normal human prostate cell (PNT-2), human prostate cancer cell (PC3) and human breast cancer cell (MCF-7) lines were determined using the resazurin assay. Also, the effects of these agents and their combinations on the GSH content and ROS level of the normal and cancer cell lines were measured using O-phthalaldehyde (OPA) and dichlorofluorescein diacetate (DCFDA) assays, respectively. RESULTS MET and DOC dose-dependently decreased (p<0.05) the viability of PNT-2 cell (IC50 = 0.552 and 0.524 μM, respectively) and PC3 cell (IC50 = 0.338 and 0.320 μM, respectively) lines. RIB and NAC significantly reduced (p<0.05) the cytotoxic effect of MET and DOC on PNT-2 cell line (IC50 > 10 μM). On the other hand, RIB and NAC had no significant effect on the cytotoxicity of MET and DOC on PC3 cell line. MET and DOC significantly decreased (p<0.05) GSH content and significantly increased (p<0.05) ROS level of both normal and cancer cell lines when compared to untreated cells. Similarly, RIB and NAC significantly increased (p<0.05) GSH content and decreased (p<0.05) ROS level in both normal and cancer cell line, in the presence of MET and DOC. CONCLUSION: The current study suggests that RIB protected the normal cells PNT-2 against the cytotoxic effects of MET and DOC. RIB and NAC also protected MCF-7 but not PC3 cell lines against the cytotoxic effects of MET and DOC. The protective effect of RIB was associated with an increase in GSH content and a decrease in ROS level in both normal and cancer cell lines. The effect of RIB was similar but less pronounced than the effect of NAC, the standard drug. Further studies should be conducted to confirm these findings at the molecular and in vivo levels. Also, other antioxidant defences such as catalase, superoxide dismutase and peroxidase should be investigated.Item Anticonvulsant and Sedative Effects of the Hydro-Ethanolic Whole Plant Extract of Cleome Rutidosperma (Dc.) (Cleomeceae) in Mice.(University of Ghana, 2019-07) Tabariyeng, N.J.BACKGROUND: Cleome rutidosperma (DC.) (Family: Cleomeceae) is a low-growing herb used for the treatment of epilepsy in African traditional medicine. This study presents the anticonvulsant, sedative effects and safety profile of the hydro-ethanolic extract of the whole plant of Cleome rutidosperma (CRE) in murine experimental models. METHODS: Preliminary phytochemical screening of the extract was conducted using standard colorimetric assays. The general effect of the extract, CRE (10, 30, 100, 300, 1000 and 3000 mg kg-1 p.o.) on the central nervous system of mice was assessed using the Irwin test. The anticonvulsant screening of CRE (100, 300 and 1000 mg kg-1 p.o.) utilized four murine models of experimental epilepsy; pentylenetetrazole (PTZ)-, picrotoxin (PIC)-, maximal electroshock (MES)- induced seizures and pentylenetetrazole-induced kindling. Phenobarbitone and carbamazepine were used as reference anticonvulsant agents in the anticonvulsant screening experiments. The duration, frequency and latency to seizures were measured for each treated animal. The extract’s ability to induce sedation was also investigated using the thiopental sleeping time test. Acute and subacute toxicity studies were conducted to determine the safety of the extract in mice. RESULTS: Preliminary phytochemical screening indicated the presence of flavonoids, alkaloids, glycosides, phytosterols and saponins. In the Irwin test, the extract produced sedation as its major effect. In the acute seizure models, the extract caused significant increase in the latency to seizure (P< 0.0001) and a significant reduction in the duration of tonic-clonic convulsions (P< 0.0001) in PTZ- induced seizure model. Also, the extract significantly decreased duration of seizures (P< 0.0001) and increased the latency to seizure in the PIC- induced seizure model (P< 0.0001). In the MES test, the extract did not significantly reduce the duration of hind limb tonic extension (P= 0.6446) and it did not increase the latency to hind limb tonic extension (P= 0.3257). In PTZ-induced kindling test, the extract significantly (P=0.0002) reduced the percentage severity of seizures in the mice and prevented the animals from being fully kindled. The extract (30, 100, 300 and 1000 mg kg-1 p.o.) dose-dependently and significantly decreased the latency to sleep (P< 0.0001) and increased significantly the duration of sleep (P< 0.0001) induced by thiopental sodium. There were no deaths recorded in the acute toxicity studies even at a dose of 3000 mg kg-1 thus the LD50 was estimated to be more than 3000 mg kg-1. The relative organ to body weight ratio for both control and treatment groups were not significantly different in both acute (P= 0.9987) and subacute (P= 0.9887) toxicity studies. Histopathological examination of the brain, and heart showed no prominent abnormalities in the extract-treated group. However, the histopathological examination of the kidney and liver showed tubular dilatation with erythrocyte infiltration and hepatocellular oedema respectively. CONCLUSIONS: The hydro-ethanolic extract of the whole plant of Cleome rutidosperma produces anticonvulsant and sedative effects in mice. The extract was relatively safe in the acute and sub-acute toxicity investigations in mice, with an LD50 greater than 3000 mg kg-1.