Evaluation of the antiulcerogenic activity of hydromethanol extracts of Solanum incanum L. (Solanaceae) leaves and roots in mice; single and repeated dose study.

OBJECTIVE: The aim of this study was to evaluate the antiulcer activity of hydromethanol extracts of Solanum incanum L. (Solanaceae) leaves and roots in mice. METHODS: The antiulcerogenic activity of the plant extracts were evaluated using Pylorus ligation and ethanol induced gastric ulcers in fasted mice. Data were analyzed using one way ANOVA, and P-values <0.05 were considered statistically significant. RESULTPYLORUS LIGATION-INDUCED ULCER: Single dose and repeated daily dose administration of the leaf and root extracts for 10 days didn't significantly (P > 0.05) affect pH, total acidity and volume of gastric secretion. Single dose of both extracts significantly reduced ulcer score (P = 0.036) and ulcer index (leaf, P = 0.037; root, P = 0.041) at the dose of 400 mg/kg. Similarly, significant reduction in ulcer score was observed after repeated daily treatment with 200 mg/kg (P = 0.030) and 400 mg/kg (P = 0.005) of the leaf extract and 400 mg/kg (P = 0.005) of the root extract. In addition, repeated administration of 400 mg/kg of the leaf (P = 0.004) and root (P = 0.005) extracts significantly reduced ulcer index. ETHANOL-INDUCED ULCER: Single dose of both extracts significantly reduced ulcer score at the dose of 200 mg/kg (leaf, P = 0.017; root, P = 0.036) and 400 mg/kg (leaf, P = 0.001; root, P = 0.001). Similarly, 200 mg/kg (leaf, P = 0.002; root, P = 0.018) and 400 mg/kg (leaf, P = 0.001; root, P = 0.001) of the extracts significantly reduced ulcer index after single dose treatment. Repeated daily treatment with leaf and root extracts for ten days caused a significant (P = 0.037, 0.001 and 0.001 for 100, 200 and 400 mg/kg leaf extract; P = 0.026, 0.018 and 0.001 for 100, 200 and 400 mg/kg root extract, respectively) reduction in ulcer score. In addition, both extracts significantly (P = 0.041, 0.004 and 0.000 for 100, 200 and 400 mg/kg leaf extract; P = 0.038, 0.008 and 0.000 for 100, 200 and 400 mg/kg root extract, respectively) reduced ulcer index after 10 days of treatment. CONCLUSION: This study has revealed hydromethanol extracts of Solanum incanum leaves and roots have antiulcerogenic activity using in vivo models. The antiulcer activity of the plant is not related to acid anti-secretory action, suggesting the plant may have cytoprotective effect on the gastric mucosa.

Evaluation of the Antimalarial Activity of the Leaf Latex of Aloe weloensis (Aloaceae) against Plasmodium Parasites.

BACKGROUND: The lack of available vaccines and the emerging resistance to antimalarial drugs have provided the necessity to find noble antimalarial plant-based medicines. The leaf latex Aloe weloensis has been used in folk medicine against malarial and other human ailments in Ethiopia. Hence, the present study aimed to investigate the antimalarial activity of the leaf latex of A. weloensis against Plasmodium parasites. MATERIALS AND METHODS: The prophylactic and curative models were employed to determine the in vivo antimalarial activity of the leaf latex A. weloensis against P. berghei infected mice, and the antioxidant activity of the latex was assessed using diphenyl-1-picrylhydrazine (DPPH) assay. Female mice were recruited for toxicity study, and the leaf latex was administered to fasted mice at a dose of 5000 mg/kg. The mice were kept under continuous observation for fourteen days for any signs of overt toxicity. RESULTS: The leaf latex of A. weloensis was safe up to 5000 mg/kg, and the latex endowed free radical inhibition activity (IC50 = 10.25 µg/ml). The latex of A. weloensis leaf demonstrated the inhibitory activity against the 3D7 strain of P. falciparum (IC50 = 9.14 µg/ml). The prophylactic and curative effect of the latex was found to be dose-dependent. The mice's parasitemia level was significantly (p < 0.001) reduced at all tested doses of the leaf latex compared to negative control in the curative test. Parasitemia reduction was significant (200 mg/kg, p < 0.01, and 400 and 600 mg/kg, p < 0.001) in the prophylactic test compared to the control. In addition, the leaf latex significantly (p < 0.01) improved mean survival time, packed cell volume, rectal temperature, and bodyweight of P. berghei infected mice. CONCLUSION: The leaf latex of Aloe weloensis was endowed with the antimalarial activity at various doses, corroborating the plant's claimed traditional use.

A drug repositioning success: The repositioned therapeutic applications and mechanisms of action of thalidomide.

BACKGROUND: Thalidomide is the most teratogenic human medicine ever marketed and was associated with birth defects in approximately 10,000 children in the 1960s. The pharmacological effects of thalidomide are attributed to its anti-angiogenic, anti-inflammatory and modulatory effect on cytokines principally tumor necrosis factor-α, while the teratogenic effects are linked to two molecular targets, namely cereblon and tubulin. Teratogenicity is the gravest adverse effect of thalidomide depending on the dose and time of exposure. Nonetheless, with System for Thalidomide Education and Prescribing Safety program, the possibility of teratogenicity can be completely avoided. The sensitive period during pregnancy for thalidomide teratogenicity in humans is approximately 20-34 days after fertilization. METHODS: Relevant articles were identified from Google scholar and PubMed (MEDLINE) using different search strategies. CONCLUSION: Clinical trials showed that thalidomide has been found effective in the treatment of advanced renal cancer, esophageal cancer, chemotherapy refractory endometrial cancer and pancreatic cancer, which can suggest its future therapeutic potential in cancer treatment. Thalidomide is also used in the treatment of inflammatory skin disorders and has shown promising effect in the treatment of autoimmune disorders and inflammatory bowel disease. Despite thalidomide being a renowned teratogen and neurotoxin, it has been successfully repositioned and FDA approved for the treatment of erythema nodosum leprosum and multiple myeloma under strict control.

Evaluation of Antidiabetic Activity of the Leaf Latex of Aloe pulcherrima Gilbert and Sebsebe (Aloaceae).

The leaf latex of Aloe pulcherrima has been used as remedy for diabetes mellitus. This was carried out to determine in vitro and in vivo antidiabetic activities of the leaf latex of Aloe pulcherrima. Methods. Sucrase and maltase inhibitory activity of the leaf latex of A. pulcherrima was determined in glucose oxidase assay, and α-amylase inhibitory activity was determined in dinitrosalicylic acid assay. Normoglycemic, glucose-loaded, and streptozotocin-induced diabetic mice were treated orally to determine blood glucose lowering activity of the latex. Effect of the latex on serum lipid level and body weight was measured in streptozotocin-induced diabetic mice. Additionally, DPPH assay was used to determine free radical scavenging capacity of the latex. Results. Antioxidant activity of the latex was concentration dependent; the strongest inhibition was measured at 800 µg/ml (80.57%). The leaf latex of A. pulcherrima inhibited sucrase (IC50 = 2.92 µg/ml), maltase (IC50 = 11.81 µg/ml) and α-amylase (IC50 = 14.92 µg/ml) enzymes. All doses of the leaf latex induced hypoglycemic effect after 4 h in normal mice, and low dose of the latex did not show significant effect after 6 h. Glucose reduction of the leaf latex of A. pulcherrima was significant (p < 0.05) in oral glucose-loaded mice compared to the vehicle control. Blood glucose level of diabetic mice was significantly (p < 0.05) reduced on week one and weak two in a streptozotocin-induced diabetic mouse model. Glucose reduction increased with increasing the doses of the leaf latex of A. pulcherrima on week one (p < 0.05 (200 mg/kg), p < 0.01 (400 mg/kg), and p < 0.001 (600 mg/kg)). Administration of the leaf latex of A. pulcherrima for two weeks significantly (p < 0.05) improved diabetic dyslipidemia and body weight of diabetic mice. Conclusion. The study confirmed that the leaf latex of the plant showed a significant antidiabetic activity justifying the traditional uses of the plant.

Chemo Suppressive and Curative Potential of Hypoestes forskalei Against Plasmodium berghei: Evidence for in vivo Antimalarial Activity.

BACKGROUND: The emergence of drug resistance together with the global burden of malaria triggers the necessity for the searching of new antimalarial agents. This study, therefore, was initiated to investigate the in vivo antimalarial activity of Hypoestes forskalei in mice based on the strong supported evidence from the ethnobotanical claims and the in vitro anti-plasmodial activity of the plant. METHODS: The 4-day suppressive (crude extract and fractions) and the Rane's (n-butanol fraction) tests were used to evaluate the antimalarial activity of the plant. A cold maceration technique with 80% methanol was used for the crude extraction of the plant. The crude extract was then fractionated using solvents of different polarity (chloroform, n-butanol, and water). RESULTS: All the test doses of the crude extract as well as the fractions reduced parasitemia and prolonged mean survival time significantly (P<0.001) as compared to their negative control groups. Maximum parasitemia suppression effect (56%) was observed at the highest dose (600 mg/kg) of the crude extract during the 4-day suppressive test. Likewise, the n-butanol, chloroform, and aqueous fractions showed a percentage suppression of about 50, 38, and 19, respectively, at the dose of 600 mg/kg. Therefore, the n-butanol fraction showed the highest parasitemia suppression followed by the chloroform fraction and then the aqueous fraction. Moreover, the n-butanol fraction showed a significant curative effect (P<0.001) in Rane's test with a percentage suppression of about 49 at a dose of 600 mg/kg. CONCLUSION: The study has revealed that the plant has a promising antimalarial activity, the activity being more in the crude extract than the fractions. The highest antimalarial activity of the n-butanol fraction suggests that non-polar and medium polar principles could be responsible for the observed activity.

Evaluation of Hepatoprotective Activity of the Crude Extract and Solvent Fractions of Clutia abyssinica (Euphorbiaceae) Leaf Against CCl4-Induced Hepatotoxicity in Mice.

BACKGROUND: Liver is a vital organ that plays a major role in the elimination of xenobiotics from the body. Diseases that affect the liver become major health problems and challenge health-care professionals as well as the pharmaceutical industry. Since the conventional treatment of liver diseases is associated with a wide range of adverse effects, botanical agents are commonly used. Among these agents, Clutia abyssinica is the most widely used herb in Ethiopian traditional medicine. OBJECTIVE: To evaluate the hepatoprotective activity of the crude 80% methanol extract and solvent fractions of Clutia abyssinica leaves in mice. METHODS: The leaves of Clutia abyssinica were extracted by cold maceration using 80% methanol as a solvent, and the solvent fractions were obtained in liquid-liquid extraction with chloroform, n-butanol and distilled water. Male mice were treated with the vehicles (distilled water or 2% Tween 80), three different doses (100, 200 and 400 mg/kg) of the crude 80% methanol extract and three solvent fractions, the standard drug (silymarin 100 mg/kg), and the hepatotoxicant carbon tetrachloride (CCl4). Then, the levels of biomarkers of liver injury - such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) - and liver function such as total protein, albumin, and bilirubin were measured. Evaluation of the change in body weight and liver weight, histopathologic examination and in vitro antioxidant assay against CCl4-induced hepatotoxicity were also carried out. RESULTS: The 80% methanol extract decreased the absolute and relative weight of the liver of mice at the doses of 200 and 400 mg/kg (p<0.01 and p<0.001, respectively). It also suppressed the plasma levels of AST, ALT and ALP (p<0.001) in the aforementioned doses. Among fractions, the n-butanol fraction showed maximum hepatoprotective activity in its dose of 200 and 400 mg/kg (p<0.001, in all cases). Likewise, the chloroform fraction (400 mg/kg) reduced to a similar extent (p<0.001 in all cases). In stark contrast, the aqueous fraction failed to affect the levels of all biomarkers of hepatocyte injury. The crude methanol extract and n-butanol fraction were able to return the normal hepatic architecture of hepatocytes and scavenge free radicals in the 1,1-diphenylpicrylhydrazyl (DPPH) assay. CONCLUSION: Clutia abyssinica is endowed with hepatoprotective activity, probably mediated via its antioxidant activity. Thus, Clutia abyssinica can be taken as one candidate for the development of hepatoprotective agents because of its good safety profile.

Evaluation of Antidiabetic and Antioxidant Potential of Hydromethanolic Seed Extract of Datura stramonium Linn (Solanaceae).

BACKGROUND: Nature has gifted a variety of phytochemicals having a potential effect against diabetes mellitus. Datura stramonium has been used as a remedy for the treatment of diabetes mellitus. The study aimed to determine the in vivo antidiabetic potential of hydromethanolic seed extract of the plant. METHODS: Dried seeds of Datura stramonium were macerated in hydromethanol. Three doses (100, 200, and 400 mg/kg) of the seed extract were given orally to normoglycemic, glucose-loaded, and Streptozocin-induced diabetic mice. Diphenyl-1-picrylhydrazine (DPPH) assay was employed to determine antioxidant activity of the seed extract. RESULTS: All doses of hydromethanolic seed extract of D. stramonium were devoid of any significant hypoglycemic effect in normoglycemic mice compared to the negative control group. Acute glucose reduction was significant (P<0.05 at 100, P<0.01 at 200 and 400 mg/kg) with respect to negative control in oral glucose-loaded mice. All doses of seed extract significantly (P<0.0l) reduced blood glucose level on weeks 1 and 2 in STZ-induced daily-treated diabetic mice. The seed extract at the doses of 200 and 400 mg/kg significantly (P<0.05) improved the body weight of diabetic mice on weeks 1 and 2. A low (100 mg/kg) dose of the seed extract delayed and significantly (P<0.05) increased body weight of mice on week 2 compared to negative control. The finding showed that the antioxidant activity of the hydromethanolic seed extract was concentration dependent and comparable with ascorbic acid. IC50 of the seed extract and ascorbic acid was found to be 11.95 and 5.07 mg/mL, respectively. CONCLUSION: The findings of the study showed that hydromethanolic seed extract of Datura stramonium endowed significant antihyperglycemic and antioxidant activity.

Antibacterial Potential of Aloe weloensis (Aloeacea) Leaf Latex against Gram-Positive and Gram-Negative Bacteria Strains.

OBJECTIVE: To evaluate the antibacterial effects of the leaf latex of Aloe weloensis against infectious bacterial strains. METHODS: The leaf latex of A. weloensis at different concentrations (400, 500, and 600 mg/ml) was evaluated for antibacterial activities using the disc diffusion method against some Gram-negative species such as Escherichia coli (ATCC 14700) and Pseudomonas aeruginosa (ATCC 35619) and Gram-positive such as Staphylococcus aureus (ATCC 50080) and Enterococcus fecalis (ATCC 4623). RESULTS: The tested concentrations of the latex ranging between 400 and 600 mg·mL-1 showed significant antibacterial activity against bacterial strain. The highest dose (600 mg/ml) of A. weloensis leaf latex revealed the maximum activity (25.93 ± 0.066 inhibition zone) followed by the dose 500 mg/ml against S. aureus. The lowest antibacterial activity was observed by the concentration 400 mg/ml (5.03 ± 0.03) against E. coli. CONCLUSION: The results of the present investigation suggest that the leaf latex of A. weloensis can be used as potential leads to discover new drugs to control some bacterial infections.