Medicinal Plants Used for the Treatment of Erectile Dysfunction in Ethiopia: A Systematic Review.

BACKGROUND: Erectile dysfunction has remained as one of the major global health issues. Since the discovery of phosphodiesterase type 5 inhibitors, a significant portion of the patients has solved the issue of erectile dysfunction. However, the wide distribution of phosphodiesterase type 5 enzymes at various sites of the body led phosphodiesterase type 5 inhibitors to cause various unnecessary outcomes. Hence, it is vital to look for and find optional agents that could solve these limitations. The people of Ethiopia depend heavily on medicinal plants to ease their ailments, including erectile dysfunction. Aim of the study. The current study was carried out to systematically review the traditional medicinal plants used for the management of erectile dysfunction in Ethiopia. METHOD: A systematic and manual search was conducted to retrieve relevant articles published from 2000 to August 2020. Electronic databases of PubMed (Medline), Google Scholar, and grey literature were employed to access the studies. Accordingly, fifty-four published articles and thesis papers were finally included in this study. RESULT: Seventy plant species have been reported for the management of erectile dysfunction in Ethiopia. The commonly recorded family was Fabaceae, followed by Asteraceae, Malvaceae, Convolvulaceae, and Solanaceae. The plant species that represented the highest number of citations were Asparagus africanus, succeeded by Ricinus communis and Carissa spinarum. The commonest plant part used was roots. Majority of the medicinal plants were administered orally. The growth forms of the reported species were primarily herbs followed by shrubs. CONCLUSION: The present review compiled medicinal plants utilized by the Ethiopian community to manage erectile dysfunction. The findings will serve as a reference for the selection of plants for further pharmacological, toxicological, and phytochemical investigations in developing new plant-based drugs used for the treatment of erectile dysfunction.

Cardioprotective Effect of Crude Extract and Solvent Fractions of Urtica simensis Leaves on Cyclophosphamide-Induced Myocardial Injury in Rats.

BACKGROUND: Globally, cardiovascular diseases (CVDs) are becoming the major cause of death. Urtica simensis is one of endogenous plant which treats a wide range of disease conditions including heart diseases. However, there is limited information on safety and efficacy of the plant. OBJECTIVE: To evaluate the in vitro antioxidant, the in vivo cardioprotective activity of crude extract and solvent fractions of Urtica simensis leaves on cyclophosphamide-induced myocardial injury. METHODS: The cardioprotective activity of the crude extract, aqueous and hexane fraction of Urtica simensis leaves was evaluated based on anatomical, biochemical and histopathological methods. The in vitro antioxidant activity of the plant was also assayed in terms of free radical scavenging activity (RSA). RESULTS: Crude extract and solvent fractions of Urtica simensis significantly prevented the deleterious effect of cyclophosphamide on body weight (P<0.001), heart weight to body ratio (P<0.01), cardiac biomarkers including troponin I (P<0.01), alanine transaminase (ALT) (P<0.001), aspartate aminotransferase (AST) (P<0.01) and lipid profiles including triglycerides (P<0.001) and total cholesterol (P<0.01). The histopathological study confirmed presence of necrosis, oedema and haemorrhage on cyclophosphamide alone-treated groups while the 200mg/kg and 400mg/kg of the crude extract and aqueous fraction showed normal cardiocytes. The antioxidant assay of Urtica simensis plant exhibited free radical scavenging activity of inhibitory concentration of 50% (IC50) for the crude extract with the values of 63.27µg/mL, aqueous fraction with the values of 136.38µg/mL and hexane fraction with the values of 258.70µg/mL. CONCLUSION: Crude extract and solvent fractions of Urtica simensis leaves have cardioprotective activities. The cardioprotective effect could be attributed to the antioxidant activity of the plant extracts. However, this requires further in-depth understanding.

Repurposing of N-Acetylcysteine for the Treatment of Dengue Virus-Induced Acute Liver Failure.

The prevalence of dengue infection-induced acute liver damage is increasing from time to time. Since it has no specific antiviral treatment in the world, people in endemic areas suffer more from dengue disorders. Thus, there is a need for searching options for the treatment of dengue-induced acute liver failure. N-acetylcysteine, which is used for the treatment of nasal congestion disorder and paracetamol overdose toxicity, could be used as a definitive therapy for dengue virus-induced acute liver disease. Therefore, this review discusses the therapeutic use of N-acetylcysteine for dengue-induced acute liver disease. Various case reports and case series showed that patients received NAC recovered from their clinical status. Additionally, a preclinical study showed that N-acetylcysteine has anti-dengue virus activity. Thus, N-acetylcysteine could be used as a definitive therapy in dengue virus-induced hepatitis. This might encourage researchers to further investigate the importance of N-acetylcysteine for dengue virus-induced hepatitis.

Protective Effect of Croton macrostachyus (Euphorbiaceae) Stem Bark on Cyclophosphamide-Induced Nephrotoxicity in Rats.

BACKGROUND: Cyclophosphamide is an alkylating antineoplastic agent and its major limitation is injury to normal tissue, leading to multiple organ toxicity, including kidney, heart, liver and reproductive toxicity. Croton macrostachyus (Euphorbiaceae) has been used in Ethiopian traditional medicine to manage renal diseases. OBJECTIVE: The present study aims to assess the protective effect of the stem bark extract and solvent fractions of Croton macrostachyus on cyclophosphamide-induced nephrotoxicity in rats. METHODS: Nephrotoxicity was induced using cyclophosphamide 200 mg/kg i.p injection on the first day of the experiment. The negative control groups were administered with cyclophosphamide alone (200 mg/kg, i.p.). The crude extracts were administered at three dose levels (100, 200, and 400 mg/kg), while aqueous and ethyl acetate fractions were given at two dose levels (100 and 200 mg/kg). Excepting the normal control, all groups were subjected to cyclophosphamide toxicity on the first day. RESULTS: Treatment with crude extract 100 mg/kg and ethyl acetate fraction significantly decreased kidney-to-body weight ratio (P < 0.001). In addition, treatment with Croton macrostachyus crude extract and solvent fractions significantly decreased serum blood urea nitrogen (BUN) level (P < 0.001). Treatment with 100 and 200 mg/kg of ethyl acetate fraction significantly decreased serum creatinine level. Histopathological results confirmed the protective effect of the crude extract and solvent fractions of Croton macrostachyus. CONCLUSION: Croton macrostachyus possesses nephroprotective activities and it could be a possible source of treatment for cyclophosphamide-induced nephrotoxicity.

Prevalence of Hypertensive Emergency and Associated Factors Among Hospitalized Patients with Hypertensive Crisis: A Retrospective Cross-Sectional Study.

BACKGROUND: Hypertensive emergency (HE) is an acute stage of uncontrolled blood pressure which poses a substantial cardiovascular morbidity and mortality in developing countries. In our setting, the prevalence of HE and the characteristics of patients with a hypertensive crisis are not certainly known yet. OBJECTIVE: The study assessed the prevalence of hypertensive emergency and associated factors among hospitalized patients with hypertensive crisis. METHODS: A retrospective cross-sectional study was conducted by reviewing records of patients having a diagnosis of hypertensive crisis with systolic/diastolic blood pressure raised to more than 180/120 mmHg admitted to Ayder Comprehensive Specialized Hospital (ACSH) from September 2018 to August 2019. Patients' medical records with complete information were enrolled consecutively. Socio-demographic, clinical characteristics, and other related variables were collected using a structured data collection tool from patient medical records. Data were entered and analyzed using SPSS version 20. Logistic regression was employed to determine factors associated with HE. RESULTS: A total of 141 patients' records with a diagnosis of a hypertensive crisis were enrolled in the study; the majority were females 77 (54.6%) and residing in the urban setting 104 (73.8%). The mean age of the participants was 58.8 years. HE was found in 42 (29.8%) of patients. Intravenous Hydralazine 39 (27.7%) and oral calcium channel blocker 102 (72.3%) were the prescribed drugs for acute blood pressure reduction in the emergency setting. Surprisingly, patients who had no history of hypertension (adjusted odds ratio (AOR)=2.469; 95% confidence interval (CI): 0.176‒0.933) and female sex (AOR=2.494; 95% CI: 1.111‒5.596) were found to be independently associated factors with HE. CONCLUSION: The prevalence of HE was found to account a significant proportion of patients. Hence, hypertensive patients should be strictly managed accordingly, and promoting screening programs could reduce the risk of target organ damage.

Exit-Knowledge About Dispensed Medications and Associated Factors Among Ambulatory Patients Attending Ayder Comprehensive Specialized Hospital, Mekelle, Ethiopia.

BACKGROUND: Optimizing exit-knowledge of ambulatory patients is a major professional responsibility of pharmacists to reassure safe and cost-effective medicines use. The study assessed the exit-knowledge of ambulatory patients on their dispensed medications and associated factors. PATIENTS AND METHODS: Institutional-based cross-sectional study was conducted among ambulatory patients who visited the outpatient pharmacy of Ayder Comprehensive Specialized Hospital (ACSH) from December 2019 to February 2020. Data were entered, cleaned, and analyzed using SPSS version 20. Binary logistic regression was employed to determine factors associated with exit-knowledge on their dispensed medications. At a 95% confidence interval (CI), p≤0.05 was considered statistically significant. RESULTS: The study analyzed 400 patients; more than half of the participants were males (55.5%). The mean age of the participants was 41.3 years (mean ± standard deviation (SD), ±13). Less than half of the patients did not recall the name (44.5%) and major side effects (31.2%) of each medication. Furthermore, the overall sufficient knowledge was found to be 81%. Patients with single marital status were 4.454 times to have sufficient exit-knowledge of their dispensed medications than widowed (p=0.050) participants. Besides, patients who responded neutral clarity of pharmacist instruction had 4.745 times sufficient exit-knowledge than those who responded not clear (p=0.049). On the other hand, participants who got "enough" (p<0.0001) and "not enough" (p=0.006) information from the pharmacist were found to have a positive association with sufficient exit-knowledge than those who responded "I do not know". CONCLUSION: The majority of patients had sufficient exit-knowledge of their dispensed medications. Martially single, neutral clarity of pharmacist's instructions and adequacy of the information delivered by the pharmacist were positively associated with participants' exit-knowledge of their dispensed medications. Hence, conducting a multicenter study, we recommend pharmacists to counsel their patients to underpin patients' knowledge of their dispensed medications.

A Systematic Review on Rho-Kinase as a Potential Therapeutic Target for the Treatment of Erectile Dysfunction.

BACKGROUND: Erectile dysfunction (ED) is a common clinical condition with limited treatment options. The main aim of the present systematic review was to synthesize information on Rho-kinase as a novel therapeutic approach for the treatment of ED. METHODS: We performed a systematic literature study in PubMed, Google Scholar and Scopus. Included studies were original articles studied the role of Rho-kinase in the pathogenesis and/or new treatment approach for ED in animal models and clinical studies, published between 2014 and 2019. Data derived from each study were study design used, interventions applied and main treatment outcomes. The quality of the selected articles was assessed by CAMARADES criteria and data were analyzed using descriptive statistics. RESULTS: A total of 1067 original articles were retrieved in the given period and eighteen papers met our inclusion criteria. Five articles explain the role of Rho-kinase in ED pathogenesis using different models such as cavernous nerve crush injury, heart failure-induced ED, vasculogenic and post-radical prostatectomy ED, diabetes-induced ED and age-related ED. Other ten papers explain the role of novel drugs evaluated for ED treatment by targeting Rho-kinase as a new approach for ED therapy. The rest three papers discuss the role of plant extracts used by traditional society for the treatment of ED and assess their potential function in targeting Rho-kinase in animal models. The penile erectile functional index has shown that the ratio of intracavernosal pressure to mean arterial pressure (ICP/MAP) was decreased due to age and various chronic diseases. Whilst, ROCK I and ROCK II expression were increased. Western blot findings have also shown that ROCK II and MYPT-1 phosphorylation rates increased in cavernous tissue after ED induction. Besides, compounds which can inhibit the action of Rho-kinase activity showed relaxation of the corpus cavernosum, decrease in corporal fibrosis, and alleviate increased apoptosis and caspase-3 activity in an NO-independent manner. Moreover, histological and molecular dysregulation have been improved by inhibition of Rho-kinase. CONCLUSION: Targeting Rho-kinase may be a possible target for the treatment of ED secondary to specific causes, and Rho-kinase inhibitors may be a new drug family for the treatment of ED. However, this requires further studies for in-depth understanding.

Evaluation of in-vivo antidiarrhoeal and in-vitro antibacterial activities of the root extract of Brucea antidysenterica J. F. Mill (Simaroubaceae).

BACKGROUND: Diarrhoea has been the major cause of death especially in children of developing countries. Brucea antidysenterica is one of the several medicinal plants used traditionally for the treatment of diarrhoea in Ethiopia. Hence, the present study was undertaken to investigate the antidiarrhoeal and antibacterial activities of the root extract of B. antidysenterica. METHODS: Plant material was extracted by maceration technique using 80% methanol. The antidiarrhoeal activity was tested using castor oil-induced diarrhoea, castor oil-induced charcoal meal test, and castor oil-induced enteropooling models in mice. Whilst, the antibacterial activity of the crude extract was evaluated using agar well diffusion and broth microdilution methods. RESULTS: The 80% methanolic crude extract significantly delayed the diarrhoeal onset at the two higher doses (p < 0.001) and it has also inhibited the number and weight of faecal output at all tested doses as compared with the negative control. Moreover, it showed a significant anti-motility effect (p < 0.001) at all tested doses. Whereas it displayed a significant reduction in the weight and volume of intestinal contents at the doses of 200 and 400 mg/kg (p < 0.01). The highest concentration (800 mg/mL) of test extract showed maximum zone of inhibition in all tested standard strains of bacteria (18.3 mm-22 mm). While MIC and MBC values (0.39 mg/mL and 1.56 mg/mL) showed that S. flexneri was the most susceptible pathogen for test extract. CONCLUSION: The study revealed that the root extract of B. antidysenterica has antidiarrhoeal and antibacterial activities.

Plasma Adipsin as a Biomarker and Its Implication in Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) is a worldwide health threat affecting millions of people, which is associated with different micro- and macro-vascular complications. Type 2 diabetes mellitus (T2DM) is one of the different types of DM caused by insulin resistance and/or reduced secretion of insulin from the pancreas. A validated novel biomarker is required to enhance the accuracy of disease prediction, provide novel insights into pathophysiology and contribute to future prevention of T2DM. Various newer diagnostic methods have been developed by targeting endogenous proteins among which Adipsin is one of the promising target. Therefore, this review discusses Adipsin as a potential biomarker and its implication in T2DM. Adipsin is one of the adipokines secreted by adipose tissues which is involved in maintaining adipose tissue homeostasis and increasing insulin secretion in response to glucose. According to different experimental and clinical studies, plasma Adipsin concentrations are low in animals and patients with DM which support its use as a biomarker in combination to the other diagnostic modalities for DM. Additionally, the existence of Adipsin could be important in improving hyperglycemia by preserving ß-cell mass through improving ß-cell survival and maintaining their transcriptional identity.

The Role of Antioxidants in Ameliorating Cyclophosphamide-Induced Cardiotoxicity.

The chemotherapeutic and immunosuppressive agent cyclophosphamide has previously been shown to induce complications within the setting of bone marrow transplantation. More recently, cardiotoxicity has been shown to be a dose-limiting factor during cyclophosphamide therapy, and cardiooncology is getting wider attention. Though mechanism of cyclophosphamide-induced cardiotoxicity is not completely understood, it is thought to encompass oxidative and nitrative stress. As such, this review focuses on antioxidants and their role in preventing or ameliorating cyclophosphamide-induced cardiotoxicity. It will give special emphasis to the cardioprotective effects of natural, plant-derived antioxidants that have garnered significant interest in recent times.

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.

The Bewildering Effect of AMPK Activators in Alzheimer's Disease: Review of the Current Evidence.

Alzheimer's disease is a multifactorial neurodegenerative disease characterized by progressive cognitive dysfunction. It is the most common form of dementia. The pathologic hallmarks of the disease include extracellular amyloid plaque, intracellular neurofibrillary tangles, and oxidative stress, to mention some of them. Despite remarkable progress in the understanding of the pathogenesis of the disease, drugs for cure or disease-modifying therapy remain somewhere in the distance. From recent time, the signaling molecule AMPK is gaining enormous attention in the AD drug research. AMPK is a master regulator of cellular energy metabolism, and recent pieces of evidence show that perturbation of its function is highly ascribed in the pathology of AD. Several drugs are known to activate AMPK, but their effect in AD remains to be controversial. In this review, the current shreds of evidence on the effect of AMPK activators in Aß accumulation, tau aggregation, and oxidative stress are addressed. Positive and negative effects are reported with regard to Aß and tauopathy but only positive in oxidative stress. We also tried to dissect the molecular interplays where the bewildering effects arise from.

Thioredoxin-Interacting Protein as a Novel Potential Therapeutic Target in Diabetes Mellitus and Its Underlying Complications.

Diabetes mellitus (DM) is a common metabolic disorder which is characterized by a persistent increment of blood glucose. Globally, DM affects millions of people and the prevalence is increasing alarmingly. The critical step in the pathophysiology of DM is the loss of ß-cells of the pancreas, which are responsible for the secretion of insulin. Thioredoxin-interacting protein (TXNIP) is among the factors that control the production and loss of the pancreatic ß-cells. TXNIP is an α-arrestin that can bind and inhibit thioredoxin (the antioxidant protein) which is produced in the pancreatic islet after glucose intake. Numerous studies illustrated that elevated TXNIP levels were found to induce ß-cell apoptosis; whereas TXNIP deficiency protects against type I and type II diabetes by promoting ß-cell survival. Nowadays, TXNIP depletion is becoming a key factor in pancreatic ß-cell survival enhancement. In the present review, targeting TXNIP is found to be relevant as a unique therapeutic opportunity, not only to improve insulin secretion and sensitivity, but also ameliorating the long term microvascular and macrovascular complications of the disease. Thus, TXNIP inhibitors that could reduce the expression and/or activity of TXNIP to non-diabetic levels are promising agents to halt the alarming rate of diabetes and its related complications.

Antimalarial Activity of Cordia africana (Lam.) (Boraginaceae) Leaf Extracts and Solvent Fractions in Plasmodium berghei-Infected Mice.

BACKGROUND: Malaria remains a major worldwide public health problem leading to death of millions of people. Spread and emergence of antimalarial drug resistance are the major challenge in malaria control. Medicinal plants are the key source of new effective antimalarial agents. Cordia africana (Lam.) is widely used for traditional management of malaria by local people in different parts of Ethiopia. The present study aimed to evaluate in vivo antimalarial effects of leaf extracts and solvent fractions of Cordia africana on Plasmodium berghei-infected mice. METHODS: The leaf extracts were prepared and tested for oral acute toxicity according to the OECD guideline. In vivo antimalarial effects of various doses of C. africana extracts and solvent fractions were determined using the four-day suppression test (both crude and fractions), as well as curative and chemoprophylactic tests (crude extracts). RESULTS: The acute toxicity test of the plant extract revealed that the medium lethal dose is higher than 2000 mg/kg. The crude extract of the plant exhibited significant parasitemia suppression in the four-day suppression (51.19%), curative (57.14%), and prophylactic (46.48%) tests at 600 mg/kg. The n-butanol fraction exhibited the highest chemosuppression (55.62%) at 400 mg/kg, followed by the chloroform fraction (45.04%) at the same dose. CONCLUSION: Our findings indicated that both the crude leaf extracts and fractions of C. africana possess antimalarial effects, supporting the traditional claim of the plant.

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.