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.

Phytolacca dodecandra (Phytolaccaceae) Root Extract Exhibits Antioxidant and Hepatoprotective Activities in Mice with CCl4-Induced Acute Liver Damage.

BACKGROUND: The liver is a hub of metabolism and detoxification of substances. Since many redox reactions take place in the liver, it is prone to oxidative damage. Unlike conventional agents, botanicals act through several mechanisms in preventing oxidative damage. Among these Phytolacca dodecandra is the most commonly used agent in Ethiopian folk medicine. OBJECTIVE: To evaluate antioxidant and hepatoprotective activities of the 80% methanol extract of P. dodecandra root. METHODS: Male mice were divided into six groups and treated accordingly. Negative control was given 2% Tween 80, toxicant control administered with carbon tetrachloride (CCl4), positive control treated with silymarin 100 mg/kg, and test groups were treated with 100, 200, and 400 mg/kg of the extract. Then, serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, albumin, total protein, and bilirubin were determined. Determination of the change in body weight and liver weight, histopathologic examination of the liver, and in vitro and in vivo antioxidant assays were also carried out. RESULTS: The levels of ALP, ALT, AST, GGT, LDH, and bilirubin were significantly reduced, while albumin and total protein were significantly increased after treatment with P. dodecandra root extract at the doses of 200 and 400 mg/kg in CCl4 intoxicated mice. Cholesterol metabolism and lipoprotein synthesis capabilities of the liver of mice were also returned to normal in the two doses. Besides, the 200 and 400 mg/kg doses were able to return the normal architecture and morphology of hepatocytes. Furthermore, the plant extract was found to scavenge free radicals in vitro and inhibit lipid peroxidation in vivo. CONCLUSION: The results suggest that the 80% methanol extract of P. dodecandra root can be used for the management of liver disease.

Updates on the molecular mechanisms of aspirin in the prevention of colorectal cancer: Review.

Colorectal cancer is one of the commonest malignancies worldwide. The estimated lifetime risk of the disease is about 5% with an incidence of one million new cases and 600,000 deaths worldwide every year. It is estimated that in 2019, approximately 134,490 new cases of colorectal cancer will be diagnosed with 49,190 mortalities. Though the disease is regarded as a disorder of the more developed world, the occurrence is steadily increasing in many developing countries. Since chronic inflammation is a known aggravating risk factor for colorectal cancer, anti-inflammatory agents such as aspirin have been used to prevent the development of colorectal cancer and related mortality. The potential mechanisms for the effect of aspirin in the prevention of colorectal cancer have been proposed and broadly classified as cyclooxygenase (COX) dependent and COX-independent. Some of the primary effectors of COX-dependent mechanisms in carcinogenesis are likely to be prostaglandins. In contrast to the reversible action of other nonsteroidal anti-inflammatory drugs, aspirin is known to irreversibly inactivate COX enzymes to suppress production of prostaglandins. COX-independent mechanisms of anticancer effects of aspirin include down-regulation of nuclear factor kappa B activity and Akt activation, modulation of Bcl-2 and Bax family proteins, suppression of vascular endothelial growth factor, induction of apoptosis, disruption of DNA repair mechanisms, and induction of spermidine/spermine N1-acetyltransferase that modulates polyamine catabolism.

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 Diuretic Activity and Phytochemical Contents of Aqueous Extract of the Shoot Apex of Podocarpus falcactus.

BACKGROUND: In Ethiopian folk medicine Podocarpus falcactus is used to treat stomachache, cancer, diabetes, and difficulty of urination. However, its diuretic activity has not been proven scientifically. OBJECTIVE: To determine the diuretic activity and phytochemical contents of the aqueous extract of the shoot apexes of Podocarpus falcactus. METHODS: The coarse powder of Podocarpus falcactus shoot apex was extracted by cold maceration using distilled water. Male rats were treated with distilled water, the standard drug (furosemide 10 mg/kg), and three different doses (100, 200, and 400 mg/kg) of the aqueous extract. The diuretic activity was determined by measuring parameters such as time to the first urination, volume, electrolyte concentration, and pH of urine. Electrolyte indices were calculated to elucidate the possible mechanism of diuresis. Additionally, qualitative and quantitative determination of phytochemicals in the plant extract was carried out. RESULTS: The aqueous extract induced diuresis, natriuresis, and kaliuresis in a dose- and time-dependent manner as compared to the negative control. The extract at 200 and 400 mg/kg doses produced significant diuresis (p<0.001) by the end of the fifth hour compared to the negative control. Excretion of sodium, potassium, and chloride also significantly (p<0.001) increased following extract administration. In addition, there was a significant change in the pH of urine samples of the extract-treated group compared with the negative control. Qualitative and quantitative determination of phytochemicals revealed the presence of alkaloids, flavonoids, phenolics, and tannins with the value of 128.4 mg atropine equivalents (AE)/g, 142.23 mg quercetin equivalents (QE)/g, 196.84 mg gallic acid equivalents (GAE)/g, and 25.5 mg tannic acid equivalents (TAE)/g, respectively. The aqueous extract exhibited significant diuretic activity due to its phytochemical content, which could be used as a starting point for further studies. CONCLUSION: The aqueous extract showed significant diuretic activity and confirmed the folkloric use of Podocarpus falcactus.

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.

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.