Evaluation of Grewia ferruginea Hochst ex A. Rich Mucilage as Suspending Agent in Metronidazole Benzoate Suspension.

Various species of the genus Grewia have been investigated for different pharmaceutical applications as excipients, yet a study on the potential use of Grewia ferruginea mucilage (GFM) as a suspending agent is lacking. Thus, this study is aimed at evaluating the efficacy of Grewia ferruginea mucilage (GFM) as a suspending agent in metronidazole benzoate suspension. The suspensions were prepared using 0.5%, 1%, 1.5%, and 2% w/v of GFM and compared with suspensions prepared from xanthan gum (XGM) and sodium carboxyl methyl cellulose (SCMC) in similar concentrations. The prepared suspensions were evaluated for visual appearance, pH, rheology, sedimentation volume, redispersibility, degree of flocculation, and in vitro drug release profile. Stability study was done at different storage conditions for three months. The results indicated that all the prepared suspension formulations exhibited pseudoplastic flow characteristics with viscosity imparting ability of the suspending agents in the order of XGM > GFM > SCMC (p < 0.05). The flow rate and redispersibility of the formulations prepared with GFM were significantly lower than those with SCMC and higher than those prepared with XGM. At 0.5% w/v suspending agent concentrations, the sedimentation volume of the formulations was in the order of XGM > GFM > SCMC (p < 0.05). However, at all other concentrations, the sedimentation volume of the formulations prepared with GFM had similar results with XGM but exhibited significantly higher sedimentation volume than SCMC. The formulations with GFM showed a higher degree of flocculation at 0.5% w/v concentration but were comparable at 1.5% w/v with XGM containing formulations. The pH, assay, and in vitro release profile of all assessed formulations were within the pharmacopial limit. Thus, based on the finding of this study, it can be concluded that Grewia ferruginea bark mucilage has the potential to be utilized as a suspending agent in suspension formulations.

Multiple Pathway-Mediated Gut-Modulatory Effects of Maerua subcordata (Gilg) DeWolf.

BACKGROUND: Gastrointestinal disorders are often poorly managed, especially in developing countries, where there are limited resources and therapeutic options. Despite the rich diversity of medicinal plants that offer effective treatment options with fewer side effects, studies that provide scientific verification are lacking. Maerua subcordata (Gilg) DeWolf is among the plants claimed to have wide traditional medicine, use, including as a remedy against gastrointestinal problems. Therefore, this work aimed to evaluate the gut-modulatory effects of a crude leaf extract of M. subcordata (MSL.Cr), as well as its possible mechanism of action. METHODS: A castor oil (10 mL/kg)-induced diarrheal mouse model was used to evaluate the antidiarrheal effect of MSL.Cr, and the spasmodic/antispasmodic effect of the extract was assessed using isolated rabbit jejunum with and without addition of standard cholinergic agonists/antagonists to predict the possible mechanism of action. RESULTS: MSL.Cr exhibited 40% and 80% protection against castor oil-induced diarrhea in mice at doses of 500 and 1,000 mg/kg, respectively. In isolated rabbit jejunum, the extract increased spontaneous contractions at low doses (0.01-0.1 mg/mL), and was sensitive to atropine, whereas it showed complete inhibition at higher doses (0.3-1 mg/mL). It was shown that the relaxant effect was possibly mediated by the involvement of phosphodiesterase-enzyme inhibition and K+-channel activation. The extract potentiated the control concentration-response curve of carbachol, shifting it to the left, similarly to the control drug papaverine. The potassium-channel opening-like activity of MSL.Cr was possibly mediated by the involvement of aspecific K+-channels inhibition, since tetraethylammonium, anunselective antagonist of K+ channels, significantly reversed its inhibitory effect. CONCLUSION: This study showed that the M. subcordata leaf extract demonstrated gut-modulatory effects, possibly mediated by a combination of muscarinic-receptor stimulation, phosphodiesterase inhibition, and aspecific K+-channel activation.

In Vivo Antimalarial Evaluation of Crude Extract, Solvent Fractions, and TLC-Isolated Compounds from Olea europaea Linn subsp. cuspidata (Oleaceae).

Malaria is a major global public health problem caused by Plasmodium parasites. Drug resistance is becoming a great challenge. New drugs with novel mechanism of action are urgently required. In malarious countries, medicinal plants are commonly used for malaria treatment. Olea europaea is traditionally used against malaria in Ethiopia. The aim of this study was to isolate and evaluate antimalarial activity of chemical constituents extracted from Olea europaea against chloroquine-sensitive Plasmodium berghei-infected mice. Stem bark of Olea europaea was extracted with 80% methanol and fractionated with three solvents. The butanol fraction was subjected to isolation with preparative thin-layer chromatography (PTLC). Acute oral toxicity studies were conducted in mice as per the Organization for Economic Co-operation and Development (OECD) guideline 425. Antimalarial activities of the test substances were evaluated using Peter's 4-day suppressive test. The crude extract showed significant (p < 0.01) antiplasmodial activity at all doses with a chemosuppression value of 52.40% at a dose of 600 mg/kg. All fractions also suppressed parasitaemia significantly (p < 0.05), the highest suppression (45.42%) being with butanol fraction. In the phytochemical analysis, two compounds were isolated. Both compounds showed significant (p < 0.05) antimalarial activities. Compound C inhibited parasitaemia up to 38.19% at a dose of 200 mg/kg. The crude extract, butanol fraction, and isolated compounds also prolonged survival time of mice. No sign of toxicity and mortality was seen in the test substances at up to a single dose of 2 g/kg. Findings of the current study may confirm the traditional antimalarial claim of Olea europaea and its relative safety as well as the potentiality of compound C for further investigations.

Physicochemical Characterization of Grewia ferruginea Hochst. ex A. Rich Mucilage for Potential Use as a Pharmaceutical Excipient.

Gum and mucilages from natural sources are in recent times increasingly investigated for pharmaceutical applications. Different studies have shown that the gum and mucilage fraction of various species of the genus Grewia were found to be effective viscosity enhancers, stabilizers, disintegrants, suspending agents, gelling agents, bioadhesives, film coating agents, and binders. However, no study has been conducted on the potential use of Grewia ferruginea mucilage (GFM) as a pharmaceutical excipient. Therefore, this study was aimed at characterizing the Grewia ferruginea bark mucilage for its potential use as a pharmaceutical excipient. The mucilage was extracted from the Grewia ferruginea inner stem bark through aqueous extraction, precipitated with 96% ethanol, dried, and powdered. The powdered mucilage was characterized for different physicochemical properties such as powder property, loss on drying, solubility and swelling index, ash value, pH, viscosity, moisture sorption property, microbial load, and acute oral toxicity. According to the results, the percentage yield of the final dried and powdered GFM was found to be 11.96% (w/w). The density and density-related properties of the mucilage showed good powder flow property. The GFM exhibited pseudoplastic flow behavior. Moisture sorption property of GFM revealed its hygroscopic nature, and its solubility and swelling property was increased with temperature. The pH of GFM was near neutral. Microbial load of the mucilage was within the pharmacopoeial limit, and the oral acute toxicity test revealed that the mucilage is safe up to 2000 mg/kg. From the investigations of this study, it can be concluded that Grewia ferruginea bark mucilage has the potential to be utilized as an excipient in pharmaceutical formulations.

Antidiabetic Activity of Extracts of Terminalia brownii Fresen. Stem Bark in Mice.

BACKGROUND: Diabetes mellitus is a chronic metabolic disorder that imposes a huge health and economic burden on societies. Because the currently available medications have many drawbacks, it is important to search for alternative therapies. Medicinal plants used in traditional medicines are ideal candidates. Hence, this study was undertaken to investigate the antidiabetic activity of crude extract and solvent fractions from the stem bark of Terminalia brownii Fresen. (Combretaceae) in mice. MATERIALS AND METHODS: The in vitro α-amylase inhibition assay was performed using the chromogenic 3, 5-dinitrosalicylic acid (DNSA) method while the antihyperglycemic activity was assessed using three mouse models: streptozotocin-induced diabetic mice, normoglycemic mice, and oral glucose challenged mice. Experimental diabetes was induced by a single intraperitoneal injection of streptozotocin at a dose of 150 mg/kg and animals with fasting blood glucose level (BGL) >200 mg/dL were considered diabetic. Glibenclamide (5 mg/kg) was used as a standard drug. Fasting BGL and body weight were used to assess the antidiabetic activity. The result was analyzed using GraphPad Prism software version 8 and one-way ANOVA followed by Tukey's post hoc test with p<0.05 considered as statistically significant. RESULTS: The crude extract of T. brownii at all tested dose levels (250, 500 and 750 mg/kg) showed a significant BGL reduction in all the three animal models. Moreover, the ethyl acetate and aqueous fractions (at 500 mg/kg) significantly (p<0.01) reduced the BGL in the streptozotocin induced diabetic model. The crude extract and different solvent fractions also showed a dose-dependent in vitro α-amylase inhibitory activity and improvement of body weight. CONCLUSION: T. brownii crude extract and its solvent fractions showed a significant antihyperglycemic activity in STZ induced diabetic mice, hypoglycemic activity and improvement of oral glucose tolerance in normal mice.

Diabetic ketoacidosis in children and adolescents with newly diagnosed type 1 diabetes in Tigray, Ethiopia: retrospective observational study.

Background: Diabetic ketoacidosis (DKA) is the most severe acute complication of type 1 diabetes mellitus which results in increased risk of morbidity and mortality especially in developing countries. Objective: To assess prevalence and associated factors of diabetic ketoacidosis in children and adolescents with newly diagnosed type 1 diabetes in hospitals of the Tigray region, Ethiopia. Methods: A facility based retrospective observational study design was conducted in newly diagnosed type 1 diabetic children and adolescents up to the age of 18 years who were registered in 13 general and two referral hospitals from January 1, 2013 to December 30, 2017. The diagnosis of diabetic ketoacidosis was made with the criteria below, Children presenting with polysymptoms, weight loss, vomiting, dehydration, and also the indirect signs or effects of acidosis on respiratory and central nervous systems like Kussmaul breathing, lethargy or coma and biochemically random blood sugar level >11 ml/L, glucosuria and urine ketone >+1 and diagnosed with type 1 diabetes for the first time. Descriptive, Mann-Whitney U and logistic regression analysis were carried out to describe and identify the associated factors with diabetic ketoacidosis. Results: More than three-quarters, 258/328 (78.7%) of the newly diagnosed type 1 diabetes patients, presented with diabetic ketoacidosis at initial diagnosis. Median age of diabetic ketoacidosis patients was 11 years. The patients with diabetic ketoacidosis were younger than nondiabetic ketoacidosis patients (11 vs 13 years, P=0.002). The mortality rate of diabetic ketoacidosis was 4.3%. Young age, presence of precipitating factors and symptoms of DKA/diabetes were found to be highly associated with diabetic ketoacidosis at initial diagnosis. Conclusions: The prevalence of diabetic ketoacidosis was alarmingly high. Young age group patients, precipitating factors and the presence of symptoms of diabetes/DKA like excessive drinking, vomiting and fatigue were highly associated with diabetic ketoacidosis.

Evaluation of Senna singueana leaf extract as an alternative or adjuvant therapy for malaria.

The emergence of malarial resistance to most antimalarial drugs is the main factor driving the continued effort to identify/discover new agents for combating the disease. Moreover, the unacceptably high mortality rate in severe malaria has led to the consideration of adjuvant therapies. Senna singueana leaves are traditionally used against malaria and fever. Extracts from the leaves of this plant demonstrated in vitro and in vivo antioxidant activities, which in turn could reduce the severity of malaria. Extracts from the root bark of this plant exhibited antiplasmodial activity; however, the leaves are the more sustainable resource. Thus, S. singueana leaf was selected for in vivo evaluation as a potential alternative or adjuvant therapy for malaria. Using malaria [Plasmodium berghei ANKA, chloroquine (CQ) sensitive]-infected Swiss albino mice of both sexes, 70% ethanol extract of S. singueana leaves (alone and in combination with CQ) was tested for antimalarial activity and adjuvancy potential. The 4-day suppressive test was used to evaluate antimalarial activity. The dose of S. singueana extract administered was safe to mice and exhibited some parasite suppression effect: extract doses of 200 mg/kg/d, 400 mg/kg/d, and 800 mg/kg/d caused 34.54%, 44.52%, and 47.32% parasite suppression, respectively. Concurrent administration of the extract with CQ phosphate at varied dose levels indicated that the percentage of parasite suppression of this combination was higher than administering CQ alone, but less than the sum of the effects of the extract and CQ acting separately. In conclusion, the study indicated that 70% ethanol extract of S. singueana leaf was safe to mice and possessed some parasite suppression effect. Coadministration of the extract with CQ appeared to boost the overall antimalarial effect, indicating that the combination may have a net health benefit if used as an adjuvant therapy.