Evaluation of anti-gastric ulcer activity of aqueous and 80% methanol leaf extracts of Urtica simensis in rats.

Background: Gastric ulcer is a major public health problem globally and associated with severe complications including hemorrhages, perforations, gastrointestinal obstruction, and malignancy. Urtica simensis is widely used for traditional management of gastric ulcer in different parts of Ethiopia. The present study was undertaken to evaluate the anti-gastric ulcer activity of aqueous and 80% methanol extracts of U.simensis in rats. Methods: The leaf extracts were prepared using decoction (aqueous) and maceration (80% methanol) techniques and in vivo anti-gastric ulcer effects of various doses of U. simensis extracts and the effect were determined using the pylorus ligation, indomethacin and ethanol induced gastric ulcer models. Results: In pylorus ligation induced gastric ulcer model, both aqueous and 80% methanol extracts at doses of 200 and 400 mg/kg were exhibited significant reduction in total acidity, volume of gastric secretion (p < 0.001) and substansial rise in pH (p˂0.05) of the gastric secretion. In indomethacin induced ulcer model, both aqueous and methanol extracts were exhibited dose dependent increment in gastric wall mucus compared to control (p < 0.001). In ethanol induced ulcer model, all doses of extract produced significant increment in gastric wall mucus from 46.66 ± 0.96 (AQ100) to 75.87 ± 1.52 (ME 400) µg alcian blue/g wet stomach. Five days pre-treatment with 200 mg/kg of both and aqueous and methanolic extracts exhibited significant (P < 0.001) ulcer inhibition in both indomethacin and ethanol-induced ulcer models. Conclusion: Both extracts of U.simensis exhibited a promising anti-gastric ulcer activity in all of the three models and this findings supports for traditional claimed use of the leaf of U. simensis.

In Vivo Diuretic Activity of Hydromethanolic Extract and Solvent Fractions of the Root Bark of Clerodendrum myricoides Hochst. (Lamiaceae).

INTRODUCTION: Clerodendrum myricoides (Lamiaceae) has been traditionally used for the treatment of various ailments, including body swelling and urine retention. The present study aimed to evaluate the diuretic activity of a crude extract and solvent fractions of the root bark of C. myricoides. Methodology. The coarsely powdered root bark of C. myricoides was extracted by a cold maceration method using 80% methanol. A portion of the extract was fractionated based on the polarity index of solvents to obtain chloroform, ethyl acetate, and aqueous fractions. To investigate the diuretic activity of the plant, rats were divided into fifteen groups. The normal control groups received either water or 2% tween 80, the standard group received furosemide (10 mg/kg), and the test groups were administered the hydromethanolic extract and solvent fractions at the doses of 100, 200, and 400 mg/kg by the oral route. The urine volume, urine pH, urine, and serum electrolytes were determined and compared with the standard and normal control groups. RESULTS: The crude hydromethanolic extract, ethyl acetate, and chloroform fractions induced significant diuresis at a dose of 400 mg/kg (P < 0.001) compared to the aqueous fraction. The hydromethanolic extract at 200 mg/kg and 400 mg/kg also caused noticeable diuresis (P < 0.001) compared to the standard, furosemide. Rats treated with hydromethanolic extract, ethyl acetate, and chloroform fractions showed delayed onset and prolonged diuresis in a dose-dependent fashion compared to the aqueous fraction (P < 0.05). The hydromethanolic extract and solvent fractions produced the highest saliuretic and natriuretic index compared to the standard, furosemide. The crude hydromethanolic extract also failed to produce any sign of toxicity up to 2000 mg/kg. CONCLUSION: From this study, the hydromethanolic extract and ethyl acetate fraction of the root bark of C. myricoides produced a prominent diuretic effect in rats.

Glycopeptides as Potential Interventions for COVID-19.

Coronavirus disease 2019 (COVID-19), an infectious disease that primarily attacks the human pulmonary system, is caused by a viral strain called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak emerged from Wuhan, China, and later spread throughout the world. Until the first week of May 2020, over 3.7 million cases had been reported worldwide and more than 258,000 had died due to the disease. So far, off label use of various drugs has been tried in many clinical settings, however, at present, there is no vaccine or antiviral treatment for human and animal coronaviruses. Therefore, repurposing of the available drugs may be promising to control emerging infections of SARS-COV2; however, new interventions are likely to require months to years to develop. Glycopeptides, which are active against gram-positive bacteria, have demonstrated significant activity against viral infections including SARS-COV and MERS-COV and have a high resemblance of sequence homology with SARS-COV2. Recent in vitro studies have also shown promising activities of aglycon derivative of glycopeptides and teicoplanin against SARS-COV2. Hydrophobic aglycon derivatives and teicoplanin, with minimal toxicity to human cell lines, inhibit entry and replication of SARS-COV2. These drugs block proteolysis of polyprotein a/b with replicase and transcription domains. Teicoplanin use was associated with complete viral clearance in a cohort of patients with severe COVID-19 symptoms. This review attempts to describe the activity, elucidate the possible mechanisms and potential clinical applications of existing glycopeptides against corona viruses, specifically SARS-COV2.

Targeting Netrin-1 and -4 as a Novel Diagnostic Parameter and Treatment Option for Diabetic Retinopathy.

Diabetic retinopathy (DR) is a retinal vascular disorder associated with both type 1 and type 2 diabetes mellitus (DM). It is characterized by specific loss of pericytes, which leads to an augmented blood vessel permeability, and development of new blood vessels (retinal neovascularization). Moreover, stiffening of eye membrane, inflammation, and apoptosis of endothelial cells also lead to damage of the blood-retinal barrier and blindness in most cases unless it's detected and managed early. Hence, this review was intended to assess the potential roles of Netrin-1 and -4 as new/alternative biomarkers and therapeutic options for DR. Netrin-1 and -4 have been the most known ligands and are well known for their role in neural guidance. DR has both neural and vascular components; therefore, biomarkers used for both neural and vascular retinal tissues are potentially important. According to different experimental and clinical studies, as compared to the normal groups, there was a significant increment in both retinal Netrin-1 and -4 mRNA and protein levels in the retinopathy groups. In addition, exogenous supplementation of these proteins is also used as a therapeutic agent for DR.

Antimicrobial Evaluation of Latex and TLC Fractions from the Leaves of Aloe adigratana Reynolds.

BACKGROUND: The highest prevalence and emergence of microbial infections coupled with the threat of antimicrobial resistance constitute a global concern, which entails searching for novel antimicrobial agents. Medicinal plants are among the major sources of medicines for novel drug discovery. Aloe adigratana is one of the endemic Aloe species in Ethiopia where the leaf latex of the plant is traditionally used for the treatment of various pathogenic conditions such as wound, dandruff, malaria, and diabetes. In spite of such claims, there was no scientific study done so far. The aim of the current study was, therefore, to evaluate the antimicrobial effect of leaf latex of A. adigratana and its thin layer chromatography (TLC) fractions. METHODS: Thin layer chromatography (TLC) separation was employed for isolation of bioactive compounds. Agar well diffusion and microdilution assay method were used to evaluate the antimicrobial actions of the leaf latex and TLC fractions against six bacterial strains and four Candida species of reference and clinical isolate microbial strains. RESULTS: Three major fractions, AA01, AA02, and AA03, were identified by TLC. Among the tested microbial strains, the reference strain of Staphylococcus aureus ATCC 29213 (MIC = 0.06 mg/mL) and clinical Candida krusei 242/18 (MIC = 0.14 mg/mL) exhibited higher susceptibility towards AA02, while reference strains of Klebsiella pneumoniae ATCC 700603 (MIC = 0.19 mg/mL) revealed the highest susceptibility towards AA01. The leaf latex displayed the highest activity against Staphylococcus aureus ATCC 29213 and clinical Candida krusei 242/18 with a MIC value of 0.19 mg/mL. CONCLUSION: The leaf latex and TLC fractions were found to be active against the tested bacterial and Candida species. Therefore, this finding supports the traditional claim of Aloe adigratana and the need for characterization of the TLC fractions to provide as lead compounds for further comprehensive antibacterial and antifungal activities.

Potential Effect of Hydroxychloroquine in Diabetes Mellitus: A Systematic Review on Preclinical and Clinical Trial Studies.

BACKGROUND: Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia. It affects millions of people globally. In spite of many antidiabetic drugs that are available, an adequate level of control remains challenging. Hydroxychloroquine is an immunomodulatory drug that has been used for the treatment of malaria and autoimmune diseases. There is an emerging evidence that suggests its beneficial effect against diabetes mellitus. Therefore, this systematic review is aimed at discoursing the role of hydroxychloroquine against diabetes mellitus and its potential mechanisms of actions. METHODS: A systematic and manual searching was carried out to retrieve relevant articles (preclinical and clinical studies) published from January 2014 to July 2019. Electronic databases including PubMed and Scopus as well as clinicaltrials.gov have been searched using different searching terms: "hydroxychloroquine," "diabetes mellitus," "hyperglycemia," and "insulin resistance." The MeSH terms (PubMed) and text words were combined with "AND" or "OR." In addition, manual searching of Google Engine and Google Scholar was conducted. Quality assessment of all the included studies was performed using CAMARADES (preclinical studies) and the Newcastle-Ottawa Scale and Cochrane Collaboration's tools (clinical studies). RESULTS: A total of eighteen studies (three experimental and fifteen clinical studies) were found to be eligible for the present systematic review. Among the included clinical studies (six randomized control trials, five observational studies, and four cohort studies), about 55,776 study participants were involved. Most of these studies showed significant improvement of lipid profile and insulin levels and substantial diminution of hemoglobin A1c, fasting plasma glucose, and postprandial blood glucose levels. Reduction in lysosomal degradation of the internal insulin-insulin receptor complex and enhancement in insulin sensitivity and adiponectin levels are some of the hypothesized mechanisms for the antidiabetic effect of hydroxychloroquine. CONCLUSION: The current review provides preliminary evidence for potential antidiabetic properties of hydroxychloroquine. Though the provided available data were promising, further clinical trials and mechanistic studies are needed to determine its long-term effects.

Antidiabetic Effect of Germinated Lens culinaris Medik Seed Extract in Streptozotocin-Induced Diabetic Mice.

BACKGROUND: Lens culinari s Medik seed has been used in traditional practices to treat various ailments, including diabetes mellitus, in Ethiopia. Previous phytochemical screening studies indicated that germination of the seed of L. culinaris contains more bioactive constituents compared to raw seeds. The aim of this study was to investigate the antidiabetic activity of an aqueous methanol extract of germinated L. culinaris seed extract in streptozotocin (Stz)-induced diabetic mice. METHODS: The antidiabetic effect of germinated L. culinaris seed extract was determined using Stz-induced diabetic mice. An 80% aqueous methanol extract of germinated L. culinaris seed at doses of 100, 200, and 400 mg/kg was used in the treatment group. Glibenclamid (5 mg/kg) and dimethyl sulfoxide 2% were used as positive and negative controls, respectively. The test extract and controls were given daily for 3 weeks. Blood-glucose levels and body-weight changes were measured weekly. Lipid-profile levels were measured at the end of each experiment. Oral glucose-tolerance tests were performed to evaluate the postprandial effect of the extract. RESULTS: The aqueous methanol extract of germinated L. culinaris significantly reduced blood-glucose levels and increased body weight (p<0.05). The extract also improved serum-lipid profiles in diabetic mice after 21 days (p<0.05). The seed extract also resulted in significant reductions in blood-glucose levels after an oral glucose load in normal mice (p<0.05). CONCLUSION: An aqueous methanol extract of germinated L. culinaris seed has both antidiabetic and antihyperlipidemic effects.

Nigella sativa L. (Black Cumin): A Promising Natural Remedy for Wide Range of Illnesses.

The seed of Nigella sativa (N. sativa) has been used in different civilization around the world for centuries to treat various animal and human ailments. So far, numerous studies demonstrated the seed of Nigella sativa and its main active constituent, thymoquinone, to be medicinally very effective against various illnesses including different chronic illness: neurological and mental illness, cardiovascular disorders, cancer, diabetes, inflammatory conditions, and infertility as well as various infectious diseases due to bacterial, fungal, parasitic, and viral infections. In spite of limited studies conducted so far, the promising efficacy of N. sativa against HIV/AIDS can be explored as an alternative option for the treatment of this pandemic disease after substantiating its full therapeutic efficacy. Moreover, the strong antioxidant property of this valued seed has recently gained increasing attention with regard to its potential role as dietary supplement with minimal side effects. Besides, when combined with different conventional chemotherapeutic agents, it synergizes their effects resulting in reducing the dosage of concomitantly used drugs with optimized efficacy and least and/or no toxicity. A number of pharmaceutical and biological properties have been ascribed to seeds of N. sativa. The present review focuses on the profile of high-value components along with traditional medicinal and biological principles of N. sativa seed and its oil so as to explore functional food and nutraceutical potential of this valued herb.

Anti-nociceptive and anti-inflammatory activities of crude root extract and solvent fractions of Cucumis ficifolius in mice model.

Background: Societies in developing countries use traditional medicine as alternatives for management of pain and inflammation. The plant Cucumis ficifolius has been used in Ethiopia to treat many ailments including inflammation and pain. The objective of this study was to evaluate the antinociceptive and anti-inflammatory activities of the crude root extract and solvent fractions of C. ficifolius. Methods: The analgesic activity of crude extract and solvent fractions of C. ficifolius was evaluated with acetic acid-induced writhing, hot plate, and formalin-induced paw licking tests. The anti-inflammatory effect of crude methanolic root extract and solvent fractions of C. ficifolius was evaluated using carrageenan-induced paw edema. The crude extract was given at 200, 400 and 800 mg/kg. Butanol and aqueous fractions were given at 100 and 200 mg/kg doses. The negative control groups were treated with distilled water (10 mL/kg). Standard drugs used were acetylsalicylic acid (ASA) in acetic acid, formalin tests and carrageenan-induced paw edema and morphine (20 mg/kg) in hot plate test. Results: The crude extract, at its maximum dose, produced comparable analgesic activity (72.5%) to ASA in acetic acid writhing test. In the hot plate test, both the crude extract and solvent fractions exhibited a significant prolongation of nociception reaction time. Formalin test result indicated a significant reduction of mean lick time with maximal protection of 64% (early phase) and 83% (late phase). Aqueous and butanol fractions showed good analgesic activity in the three models. Inflammation was decreased by 69% with butanol (200 mg/kg); 71% (800 mg/kg) of crude extract and by 41% and 56% with the use of aqueous fraction at 100 and 200 mg/kg, respectively (p<0.001). Conclusion: The present study indicates that the crude methanolic root extract, as well as butanol and aqueous solvent fractions, showed anti-nociceptive and anti-inflammatory activities.

Repurposing of the ß-Lactam Antibiotic, Ceftriaxone for Neurological Disorders: A Review.

To date, there is no cure or disease-modifying agents available for most well-known neurological disorders. Current therapy is typically focused on relieving symptoms and supportive care in improving the quality of life of affected patients. Furthermore, the traditional de novo drug discovery technique is more challenging, particularly for neurological disorders. Therefore, the repurposing of existing drugs for these conditions is believed to be an efficient and dynamic approach that can substantially reduce the investments spent on drug development. Currently, there is emerging evidence that suggests the potential effect of a beta-lactam antibiotic, ceftriaxone (CEF), to alleviate the symptoms of different experimentally-induced neurological disorders: Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, epileptic-seizure, brain ischemia, traumatic brain injuries, and neuropathic pain. CEF also affects the markers of oxidative status and neuroinflammation, glutamatergic systems as well as various aggregated toxic proteins involved in the pathogenesis of different neurological disorders. Moreover, it was found that CEF administration to drug dependent animal models improved the withdrawal symptoms upon drug discontinuation. Thus, this review aimed to describe the effects of CEF against multiple models of neurological illnesses, drug dependency, and withdrawal. It also emphasizes the possible mechanisms of neuroprotective actions of CEF with respective neurological maladies.

The Effect of Metformin in Experimentally Induced Animal Models of Epileptic Seizure.

BACKGROUND: Epilepsy is one of the common neurological illnesses which affects millions of individuals globally. Although the majority of epileptic patients have a good response for the currently available antiepileptic drugs (AEDs), about 30-40% of epileptic patients are developing resistance. In addition to low safety profiles of most of existing AEDs, there is no AED available for curative or disease-modifying actions for epilepsy so far. OBJECTIVES: This systematic review is intended to evaluate the effect of metformin in acute and chronic animal models of an epileptic seizure. METHODS: We searched PubMed, SCOPUS, Sciences Direct, and grey literature in order to explore articles published in English from January 2010 to November 2018, using key terms "epilepsy," "seizure," "metformin," "oral hypoglycemic agents," and "oral antidiabetic drugs". The qualities of all the included articles were assessed according to the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES). RESULTS: Out of six hundred fifty original articles retrieved, eleven of them fulfilled the inclusion criteria and were included for final qualitative analysis. In these studies, metformin showed to control seizure attacks by attenuating seizure generation, delaying the onset of epilepsy, reducing hippocampal neuronal loss, and averting cognitive impairments in both acute and chronic models of an epileptic seizure. The possible mechanisms for its antiseizure or antiepileptic action might be due to activation of AMPK, antiapoptotic, antineuroinflammatory, and antioxidant properties, which possibly modify disease progression through affecting epileptogenesis. CONCLUSION: This review revealed the benefits of metformin in alleviating symptoms of epileptic seizure and modifying different cellular and molecular changes that affect the natural history of the disease in addition to its good safety profile.

Netrin as a Novel Biomarker and Its Therapeutic Implications in Diabetes Mellitus and Diabetes-Associated Complications.

Diabetes is a multifactorial metabolic syndrome and is one of the shared long-lasting illnesses globally. It is linked to long-term microvascular and macrovascular complications that contribute to disability, compromised quality of life, and reduction in lifespan, which eventually leads to death. This disease is not only incurring significant economic burden but also adversely affects the patients, caregivers, communities, and the society at large. The interruption of diabetes progress and its complications is a primary focus of scientific communities. In spite of various diagnostic modalities for diabetes, there is a limited marker to investigate the risk and progress of its complications. Netrin has recently received more attention as a biomarker of diabetes and a broader range of long-term complication. Therefore, the impetus of this review is to exhaustively discuss the role of Netrin as a potential biomarker and its therapeutic implication in diabetes and diverse sets of microvascular and macrovascular complications of diabetes. It also discourses the possible mechanisms of Netrin for the said pharmacological effect for a better understanding of the development and progression of diabetes and its complications in relation to this protein. It enables protective measures to be applied at the subclinical stage and the responses to preventive or therapeutic measures to be scrutinized. Besides, it might also facilitate the appraisal of novel therapeutic options for diabetes and various complications through modifying the endogenous Netrin and provide surrogate endpoints for intervention.

Drug Resistance Patterns of Escherichia coli in Ethiopia: A Meta-Analysis.

BACKGROUND: Antimicrobial drug resistance is a global threat for treatment of infectious diseases and costs life and money and threatens health delivery system's effectiveness. The resistance of E. coli to frequently utilized antimicrobial drugs is becoming a major challenge in Ethiopia. However, there is no inclusive countrywide study. Therefore, this study intended to assess the prevalence of E. coli resistance and antimicrobial-specific resistance pattern among E. coli clinical isolates in Ethiopia. METHODS: Articles were retrieved from PubMed, Embase, and grey literature from 2007 to 2017. The main outcome measures were overall E. coli and drug-specific resistance patterns. A random-effects model was used to determine pooled prevalence with 95% confidence interval (CI), using DerSimonian and Laird method. In addition, subgroup analysis was conducted to improve the outcome. The study bias was assessed by Begg's funnel plot. This study was registered in PROSPERO as follows: PROSPERO 2017: CRD42017070106. RESULTS: Of 164 articles retrieved, 35 articles were included. A total of 19,235 study samples participated in the studies and 2,635 E. coli strains were isolated. Overall, E. coli antibacterial resistance was 45.38% (95% confidence interval (CI): 33.50 to 57.27). The resistance pattern ranges from 62.55% in Addis Ababa to 27.51% in Tigray region. The highest resistance of E. coli reported was to ampicillin (83.81%) and amoxicillin (75.79%), whereas only 13.55% of E. coli isolates showed resistance to nitrofurantoin. CONCLUSION: E. coli antimicrobial resistance remains high with disparities observed among regions. The bacterium was found to be highly resistant to aminopenicillins. The finding implies the need for effective prevention strategies for the E. coli drug resistance and calls for multifaceted approaches with full involvement of all stakeholders.