Citrus limon (L.) Osbeck Fruit Peel Extract Attenuates Carbon Tetrachloride-Induced Hepatocarcinogenesis in Sprague-Dawley Rats.

Background: Traditional herbal medicine practitioners in the Ashanti region of Ghana use the fruit peels of Citrus limon (L.) Osbeck (C. limon) in preventive and curative treatment of many cancers including liver cancer. This ethnobotanical claim remains to be verified scientifically. Aim of the Study. This study investigated prophylactic hepatoprotective and anti-HCC effects of C. limon peel extract (LPE) in CCl4/olive oil-induced HCC-like rats. Materials and Methods: After preparation of LPE, it was subjected to phytochemical screening using standard phytochemical methods. A total of 30 healthy adult male Sprague-Dawley rats (weighing 150-200 g) were randomly assigned into six groups of 5 rats each. Rats in the control group received olive oil (5 mL/kg ip) twice weekly for 16 weeks. Rats in the model group received CCl4/olive oil (2 mL/kg, ip) twice weekly for 16 weeks. Rats in capecitabine (10 mg/kg po) and LPE (50, 100, and 200 mg/kg po) groups received CCl4/olive oil (2 mL/kg, i.p) in the morning and their respective treatments in the afternoon twice a week for 16 weeks. Rats in all groups had free access to food and water ad libitum. Body weight and survival rates were monitored. Rats were sacrificed under deep anesthesia, blood was collected, and liver and other organs were isolated. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), prothrombin time, bilirubin, C-reactive protein (CRP), alpha- (α-) fetoprotein (AFP), and liver histology were assessed. Results: Alkaloids, tannins, flavonoids, terpenoids, and saponins were detected in LPE. Model rats demonstrated increased serum levels of AFP, CRP, ALP, GGT, ALT, and AST, prothrombin time, total bilirubin, direct bilirubin, blood lymphocyte, and monocyte counts, but decreased serum albumin and total protein compared to control rats. Unlike the control, model rats demonstrated fat accumulation in periportal and centrilobular hepatocytes and neoplastic transformation. Semiquantitation of periodic acid Schiff- (PAS-) stained liver sections showed decreased glycogen storage in hepatocytes of model rats compared to control rats. Compared to the model, LPE treatment protected against CCl4-induced hepatocarcinogenesis, which was evidenced by decreased AFP, CRP, liver enzymes, total and direct bilirubin, prothrombin time, and blood lymphocyte and monocyte counts; attenuation of fat accumulation; and increased glycogen storage, albumin, and total protein. Conclusion: LPE abates CCl4-induced hepatocarcinogenesis by attenuating liver inflammation and improving metabolic, biosynthetic, and detoxification functions of the liver. The prophylactic hepatoprotective and anti-hepatocarcinogenic effects of LPE are attributable to its phytochemical composition raising hopes of finding potential anticancer bioactive compounds from C. limon fruit peels.

Adverse drug effects among students following mass de-worming exercise involving administration of Praziquantel and Albendazole in KEEA Municipality, Ghana.

BACKGROUND: To manage the deleterious effects of parasitic infections such as lymphatic filariasis (LF) and schistosomiasis among school children, most countries including Ghana make use of mass drug administration (MDA). Although MDA has proven effective in reducing worm burden, unfortunately adverse drug effects (ADEs) post-MDA are derailing the gains and also remain poorly monitored. The study assessed incidence and factors associated with ADEs among students following a school-based mass de-worming exercise involving administration of Praziquantel (PZQT) and Albendazole (ADZ) against LF and SCH at Komenda-Edina-Eguafo-Abirem (KEEA) Municipal. METHODOLOGY: After fulfilling all ethical obligations, a total of 598 students aged 5-20 years who received PZQT or ADZ monotherapy or a combination of the two (PZQT + ADZ) as part of the mass de-worming exercise were recruited through quota and random sampling. Bodyweight and height of students were measured and body mass index (BMI) calculated. Students were orally interviewed to obtain information such as age, sex, intake of diet before taking drugs. Subsequently, students were monitored over 24 hours post-MDA for cases of ADEs. Descriptive statistics and logistic regression analysis using SPSS version 26 was used to describe data collected and to determine associations between incidence of ADEs and predictor variables. PRINCIPAL FINDINGS: Out of the 598 students, 243 (40.64%) represented by 124 males (51.03%) and 119 females (48.97%) with mean (SD) age of 13.43 (2.74) years experienced one or more forms of ADE. In decreasing order, the detected ADEs included headache (64.6%), Abdominal pain (48.6%), fever (30.0%), diarrhea (21.4%) and itching (12.8%). Multivariable statistical analysis showed that age 5-9 years (OR: 2.01, p = 0.041) and underweight (OR: 2.02, p = 0.038) were associated with incidence of ADEs. Compared with students who received combination therapy, students who received ADZ only (OR: 0.05, p < 0.001) and PZQT only (OR: 0.26, p < 0.001) had low cases of ADEs. Gender and diet intake before MDA were not associated with ADE incidence. CONCLUSION: ADE incidence was common among students in the KEEA municipality. Age, underweight, and double dosing were associated with increase in ADE incidence, while gender and food intake were not associated with increase in ADE incidence. The Disease Control Unit of the Ghana Health Service should incorporate stringent ADE monitoring in post-MDA surveillance in the National MDA program in order to be able to detect, manage and report ADEs to inform planning for future MDA programs. Such initiatives will help not only in improving effectiveness of MDA programs but also identify high risk groups and exact strategies to reduce negative influence of ADE on MDA coverage and anthelminthic drug compliance.

Safety and Efficacy of Novasil Clay (Calcium Montmorillonite) in Children Exposed to Aflatoxin in Ejura-Sekyedumase District in Ghana.

Background. Aflatoxin levels are very high in animals and humans in places where cereals are poorly stored. In this study, Novasil was evaluated for safety and efficacy in children. Methods. Children (200) aged between 2 and 9 years were put into Novasil and placebo group. Participants received either 1.5 g of Novasil or calcium carbonate in their food. Urine samples were analyzed for AFM1 by HPLC, blood samples were assayed for complete blood count and chemistries. Results. Aflatoxin M1 levels in the Novasil treated group, significantly reduced to 60% compared to an increase of urine AFM1 in the placebo group. Hematological parameters did not change except for an increase in hemoglobin level in the Novasil group. Biochemical parameters remained unchanged except calcium ions. Glutathione levels in the Novasil increased, compared group to the placebo group. Conclusion. Novasil is safe, reduce aflatoxin bioavailability in humans while improving GSH antioxidant capacity as well. The trial has been registered with Pan African Clinical Trial Registry (www.pactr.org). A WHO registry for clinical trials with a unique identification number PACTR202202797930675.

Wound Healing Properties and Antimicrobial Effects of Parkia clappertoniana Keay Fruit Husk Extract in a Rat Excisional Wound Model.

Background: Parkia clappertoniana Keay (Family: Fabaceae) (P. clappertoniana) fruit husk is commonly used in northern Ghana for wound treatment. However, this folk claim remains to be confirmed scientifically. Objective: This study investigated wound healing and antimicrobial effects of P. clappertoniana fruit husk extract (PCFHE) by using excision wound model in rats. Materials and Methods: After preparation and phytochemical analysis of PCFHE, it was reconstituted in purified water and emulsifying ointment yielding a wound healing formula (0.3, 1, and 3%). Excision wounds were established in healthy male Sprague-Dawley rats (aged 8-10 weeks; weighing 150-200 g). Rats were randomly assigned into six groups (model, 1% silver sulfadiazine [SSD], vehicle, and PCFHE [0.3, 1, and 3%, respectively]) and topically treated daily until complete wound healing. The endpoints (period of epithelialization, wound contraction, collagen content, erythema index, oedema index, inflammatory cell infiltration, and antimicrobial activity) were assessed for all groups. Minimum fungicidal concentration (MFC), minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill were assessed. Results: Quercetin and catechin were detected in PCFHE. Compared to model and vehicle groups, PCFHE-treatment groups improved wound healing and antimicrobial (MBC, MFC, and MIC) endpoints. PCFHE demonstrated bacteriostatic and fungicidal effects against identified wound contaminants (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Candida albicans). Conclusion: P. clappertoniana fruit husk possesses wound healing and antimicrobial effects in excisional wounds in rats that confirms its folk use, and the reported pharmacological properties of PCFHE are attributable to its quercetin and catechin phyto-constituents.

Thiamine Demonstrates Bio-Preservative and Anti-Microbial Effects in Minced Beef Meat Storage and Lipopolysaccharide (LPS)-Stimulated RAW 264.7 Macrophages.

This study assessed the anti-inflammatory effect of thiamine (TA) in lipopolysaccharide-stimulated RAW264.7 cells and also assessed the preservative properties of TA in minced beef. TA demonstrated a concentration-dependent antimicrobial effect on microbial contaminants. Inhibition zones and MIC from the effect of TA on the tested bacterial strains were respectively within the ranges 15−20 mm and 62.5−700 µg/mL. TA significantly (p < 0.05) decreased all the pro-inflammatory factors [(nitric oxide (NO), prostaglandin E2 (PGE2), TNF-α, IL-6, IL-1ß, and nuclear factor-κB (NF-κB)] monitored relative to LPS-stimulated RAW264.7 cells. TA inhibited the expression of both iNOS and COX-2. In minced beef flesh, the growth of Listeria monocytogenes was inhibited by TA. TA improved physicochemical and microbiological parameters of stored minced beef meat compared to control. Principal component analyses and heat maps elucidate the quality of the tested meats.

Oxidative stress and associated clinical manifestations in malaria and sickle cell (HbSS) comorbidity.

In Ghana, uncomplicated malaria and sickle cell disease (SCD) is common, hence comorbidity is not farfetched. However, the extent of oxidative stress and the array of clinical manifestations in this comorbidity (presence of both malaria and SCD) has not been fully explored. This study highlights the impact of uncomplicated malaria on SCD. The level of isoprostane, 8-iso-prostaglandin F2α (8-iso-PGF2α) was used to assess oxidative stress while plasma biochemistry and urinalysis was used to assess renal function. Hematological profiling was also done to assess the impact of comorbidity on the hematological cell lines. Of the 411 study participants with malaria, 45 (11%) had SCD. Mean body temperature was significantly higher in comorbidity compared to malaria and SCD cohorts, while a lower parasite density range was obtained in comorbidity compared to malaria cohorts. Furthermore, in comorbidity, the 8-iso-PGF2α oxidative stress biomarker was significantly elevated in all ages, parasite density ranges and gender groups. Comorbidity affected both leukocytic and erythrocytic cell lines with significant eosinophilia and monocytosis coexisting with erythrocytic parameters consistent with severe anemia. Biochemically, while plasma creatinine and bilirubin were significantly elevated in comorbidity, spot urinary creatinine was significantly reduced. Additionally, urine samples in the comorbid state were slightly acidic and hypersthenuric with significant hematuria, proteinuria, and bilirubinemia. Finally, 80% or more malaria-SCD presented with chills, fever, anorexia, headache, joint pains, lethargy, and vomiting. In conclusion, malaria could induce vaso-occlusive crisis in sickle cell disease, therefore, prompt management will alleviate the severity of this comorbidity.

Antimicrobial Activity against Oral Pathogens Confirms the Use of Musa paradisiaca Fruit Stalk in Ethnodentistry.

BACKGROUND: Ethnodentistry is the use of indigenous oral cleansing agents such as plant parts by local folks not only to maintain oral hygiene but also to treat oral infections. Mostly, ethnodentistry is inspired by traditions and belief systems of local communities. Musa paradisiaca is extensively cultivated and used in many cultures for its nutritional and medicinal values. In Ghana, the fruit stalk of Musa paradisiaca is used as an oral cleansing agent to maintain oral hygiene; yet this folk claim remains to be ascertained scientifically. OBJECTIVE: The study assessed the antibacterial and antifungal effects of three extract fractions (aqueous, ethanol, and ethyl acetate fractions) of Musa paradisiaca fruit stalk against Lactobacillus acidophilus, Aggregatibacter actinomycetemcomitans, and Candida albicans, common oral pathogens implicated in dental caries and periodontitis. MATERIALS AND METHODS: Aqueous, ethanol, and ethyl acetate fractions of Musa paradisiaca fruit stalk were prepared by cold maceration and qualitatively screened for their phytochemical composition. Antimicrobial effects of the three extract fractions were assessed by using serial broth dilutions at increasing concentrations (62.5, 125, 250, 500, and 1000 µg/ml) and compared to standard antimicrobial agents (erythromycin, doxycycline, and fluconazole). Subsequently, the absorbances of the microbial suspensions treated with increasing concentrations of the extract fractions were measured at 450 nm, and the cell densities were determined. RESULTS: Except for the aqueous extract, which was less effective in decreasing microbial growth, the ethyl acetate and the ethanol extract fractions demonstrated antimicrobial efficacies comparable to those of the standard drugs. All three extract fractions demonstrated concentration-dependent growth inhibitory effects on the tested oral pathogens although not as effective as the standard drugs used. CONCLUSION: Musa paradisiaca fruit stalk has demonstrated antimicrobial effects against Lactobacillus acidophilus, Aggregatibacter actinomycetemcomitans, and Candida albicans, common oral pathogens implicated in dental caries and periodontitis, and this finding confirms in part folk use of Musa paradisiaca fruit stalk as a traditional dental care agent. Thus, the fruit stalk of Musa paradisiaca could be explored for use as a cheap and readily available dental care agent for people entrapped in the poverty line.

Zanthoxylum zanthoxyloides Alkaloidal Extract Improves CCl4-Induced Hepatocellular Carcinoma-Like Phenotypes in Rats.

BACKGROUND: Despite the enrollment of new small molecules such as Sorafenib for the treatment of hepatocellular carcinoma (HCC), HCC still remains a significant contributor to cancer-related mortality and morbidity globally. Zanthoxylum zanthoxyloides is long suspected of possessing anticancer bioactive compounds that may hold the prospect of adjunctive therapy against inflammation-related cancers such as HCC. OBJECTIVE: This study assessed the effects of an alkaloidal extract of the leaves of Zanthoxylum zanthoxyloides on CCl4/olive oil (1 : 1 v/v)-induced HCC-like phenotypes in rats. MATERIALS AND METHODS: Zanthoxylum zanthoxyloides alkaloidal extract (ZZAE) was prepared using Soxhlet and liquid-liquid extraction methods. Subsequently, ZZAE was characterized phytochemically. In the curative method, experimental HCC was established in adult (8-10 weeks old) male Sprague-Dawley rats weighing 150-300 g by twice-daily administration of CCl4/olive oil (1 : 1 v/v) (2 mL/kg ip). After confirmation of experimental HCC in rats, the rats were randomly reassigned into seven (7) groups of seven (7) rats each and treated daily for 12 weeks as follows: control (normal saline, 5 ml/kg po), model (CCl4, 5 ml/kg, ip), ZZAE (50, 100, and 200 mg/kg po), carvedilol (6.25 mg/kg po), and 20% Tween20 (1 mL/rat, po). To assess whether ZZAE has a prophylactic (preventive) effect, rats were first treated with ZZAE and later exposed to CCl4 reconstituted in olive oil. RESULTS: ZZAE (100 and 200 mg/kg) and carvedilol decreased tumor incidence compared to that of control. Compared to control, ZZAE (100 and 200 mg/kg) significantly (P < 0.05) improved serum GGT. Compared to control, ZZAE improved hepatohistological distortions induced by CCl4/olive oil and also improved liver/body weight ratio. Compared to water, ZZAE arrested mitosis in the Allium cepa assay. CONCLUSION: ZZAE ameliorated CCl4/olive oil-induced HCC-like phenotype in rats and demonstrated general hepatoprotective effects by improving liver and kidney function markers. This finding rationalizes the need for further studies on ZZAE as a potential source of bioactive anti-HCC compounds.

Abrus precatorius Leaf Extract Reverses Alloxan/Nicotinamide-Induced Diabetes Mellitus in Rats through Hormonal (Insulin, GLP-1, and Glucagon) and Enzymatic (α-Amylase/α-Glucosidase) Modulation.

BACKGROUND: Abrus precatorius is used in folk medicine across Afro-Asian regions of the world. Earlier, glucose lowering and pancreato-protective effects of Abrus precatorius leaf extract (APLE) was confirmed experimentally in STZ/nicotinamide-induced diabetic rats; however, the underlying mechanism of antidiabetic effect and pancreato-protection remained unknown. OBJECTIVE: This study elucidated antidiabetic mechanisms and pancreato-protective effects of APLE in diabetic rats. MATERIALS AND METHODS: APLE was prepared by ethanol/Soxhlet extraction method. Total phenols and flavonoids were quantified calorimetrically after initial phytochemical screening. Diabetes mellitus (DM) was established in adult Sprague-Dawley rats (weighing 120-180 g) of both sexes by daily sequential injection of nicotinamide (48 mg/kg; ip) and Alloxan (120 mg/kg; ip) over a period of 7 days. Except control rats which had fasting blood glucose (FBG) of 4.60 mmol/L, rats having stable FBG (16-21 mmol/L) 7 days post-nicotinamide/Alloxan injection were considered diabetic and were randomly reassigned to one of the following groups (model, APLE (100, 200, and 400 mg/kg, respectively; po) and metformin (300 mg/kg; po)) and treated daily for 18 days. Bodyweight and FBG were measured every 72 hours for 18 days. On day 18, rats were sacrificed under deep anesthesia; organs (kidney, liver, pancreas, and spleen) were isolated and weighed. Blood was collected for estimation of serum insulin, glucagon, and GLP-1 using a rat-specific ELISA kit. The pancreas was processed, sectioned, and H&E-stained for histological examination. Effect of APLE on enzymatic activity of alpha (α)-amylase and α-glucosidase was assessed. Antioxidant and free radical scavenging properties of APLE were assessed using standard methods. RESULTS: APLE dose-dependently decreased the initial FBG by 68.67%, 31.07%, and 4.39% compared to model (4.34%) and metformin (43.63%). APLE (100 mg/kg) treatment restored weight loss relative to model. APLE increased serum insulin and GLP-1 but decreased serum glucagon relative to model. APLE increased both the number and median crosssectional area (×106 µm2) of pancreatic islets compared to that of model. APLE produced concentration-dependent inhibition of α-amylase and α-glucosidase relative to acarbose. APLE concentration dependently scavenged DPPH and nitric oxide (NO) radicals and demonstrated increased ferric reducing antioxidant capacity (FRAC) relative to standards. CONCLUSION: Antidiabetic effect of APLE is mediated through modulation of insulin and GLP-1 inversely with glucagon, noncompetitive inhibition of α-amylase and α-glucosidase, free radical scavenging, and recovery of damaged/necro-apoptosized pancreatic ß-cells.

A cytokine in turmoil: Transforming growth factor beta in cancer.

Cancer remains one of the debilitating health threats to mankind in view of its incurable nature. Many factors are complicit in the initiation, progression and establishment of cancers. Early detection of cancer is the only window of hope that allows for appreciable management and possible limited survival. However, understanding of cancer biology and knowledge of the key factors that interplay at multi-level in the initiation and progression of cancer may hold possible avenues for cancer treatment and management. In particular, dysregulation of growth factor signaling such as that of transforming growth factor beta (TGF-ß) and its downstream mediators play key roles in various cancer subtypes. Expanded understanding of the context/cell type-dependent roles of TGF-ß and its downstream signaling mediators in cancer may provide leads for cancer pharmacotherapy. Reliable information contained in original articles, reviews, mini-reviews and expert opinions on TGF-ß, cancer and the specific roles of TGF-ß signaling in various cancer subtypes were retrieved from major scientific data bases including PubMed, Scopus, Medline, Web of Science core collections just to mention but a sample by using the following search terms: TGF-ß in cancer, TGF-ß and colorectal cancer, TGF-ß and brain cancer, TGF-ß in cancer initiation, TGF-ß and cell proliferation, TGF-ß and cell invasion, and TGF-ß-based cancer therapy. Retrieved information and reports were carefully examined, contextualized and synchronized into a coherent scientific content to highlight the multiple roles of TGF-ß signaling in normal and cancerous cells. From a conceptual standpoint, development of pharmacologically active agents that exert non-specific inhibitory effects on TGF-ß signaling on various cell types will undoubtedly lead to a plethora of serious side effects in view of the multi-functionality and pleiotropic nature of TGF-ß. Such non-specific targeting of TGF-ß could derail any beneficial therapeutic intention associated with TGF-ß-based therapy. However, development of pharmacologically active agents designed specifically to target TGF-ß signaling in cancer cells may improve cancer pharmacotherapy. Similarly, specific targeting of downstream mediators of TGF-ß such as TGF-ß type 1 and II receptors (TßRI and TßRII), receptor-mediated Smads, mitogen activated protein kinase (MAPK) and importing proteins in cancer cells may be crucial for cancer pharmacotherapy.

Efficacy of Artemether-Lumefantrine on various Plasmodium falciparum Kelch 13 and Pfmdr1 genes isolated in Ghana.

INTRODUCTION: Artemether-Lumefantrine (A-L) remains the drug of choice for the treatment of uncomplicated malaria in Ghana. However, the pharmaco-activity of A-L has not been assessed on various Plasmodium falciparum Kelch 13 and Pfmdr1 genes. Therefore, this study sought to determine the therapeutic efficacy of A-L on P. falciparum parasites isolated from Ghana. METHODS: The clinical study was done in Ga West Municipality, Ghana, where 78 uncomplicated malaria patients were recruited with prior consent. The patients were treated orally with A-L according to national treatment guidelines. Baseline parasitaemia was determined before treatment and 8-hourly parasitaemia posttreatment were determined till initial clearance of parasitaemia and at days 7, 14, 21, and 28. Kelch 13 and Pfmdr1 genes were genotyped by sequencing using baseline samples. Parasite clearance characteristics were determined using Parasite Clearance Estimator beta 0.9 application. RESULTS: Five Kelch 13 (F446I, S466N, R539I, A578S, and A676S) and three Pfmdr1 mutations (N86Y, Y184F and D1246Y) were identified in 78 infected samples. About 8% of the samples contained two Pfmdr1 double mutations (N86Y & D1246Y and Y184F & N86Y). Additionally, three samples (3.8%) were found to contain both Kelch 13 mutations and Pfmdr1 wild type genes. In all patients, parasitaemia persisted within the first 24 h of A-L therapy. However, at hour 40, only two patients were parasitaemic while all patients were aparasitaemic at hour 48. The genotypic profiles of the two persistent parasites at hour 40 were F446I and D1246Y, and R539I, Y184F, and N86Y. The slope half-life of the former was 6.4 h while the latter was 6.9 h and their respective PCT99 were 47.9 h and 49.2 h as well as a clearance rate constants of 0.109 and 0.092 respectively. CONCLUSION: This study reports the effectiveness of A-L on various P. falciparum mutant alleles. However, continuous surveillance of Kelch 13 mutations and Pfmdr1 gene in Ghana and regular assessment of the therapeutic efficacy of A-L and other artemisinin derivatives is recommended.

Male predisposition to severe COVID-19: Review of evidence and potential therapeutic prospects.

The severe form of COVID-19 has significant sex disparities, with high fatalities commonly reported among males than females. The incidence of COVID-19 has also been higher in males compared with their female counterparts. This trend could be attributed to a better responsive and robust immune system in females. Cytokine storm is one of the pathophysiological features of severe COVID-19, and it occurs as a result of over-activation of immune cells leading to severe inflammation and tissue damage. Nevertheless, it is well modulated in females compared to their male counterparts. Severe inflammation in males is reported to facilitate progression of mild to severe COVID-19. The sex hormones, estrogens and androgens which exist in varying functional levels respectively in females and males are cited as the underlying cause for the differential immune response to COVID-19. Evidence abounds that estrogen modulate the immune system to protect females from severe inflammation and for that matter severe COVID-19. On the contrary, androgen has been implicated in over-activation of immune cells, cytokine storm and the attendant severe inflammation, which perhaps predispose males to severe COVID-19. In this review efforts are made to expand understanding and explain the possible roles of the immune system, the sex hormones and the angiotensin-converting enzyme (ACE) systems in male bias to severe COVID-19. Also, this review explores possible therapeutic avenues including androgen deprivation therapy (ADT), estrogen-based therapy, and ACE inhibitors for consideration in the fight against COVID-19.

What works and what does not work in response to COVID-19 prevention and control in Africa.

Since the emergence of the COVID-19 pandemic in December 2019 in Wuhan, China, there have been nearly 6,663,304 confirmed cases of COVID-19, including 392,802 deaths, worldwide as of 10:00 CEST 06 June 2020. In Africa, 152,442 COVID-19 cases and 4334 deaths have been reported as of 02 June 2020. The five countries with the highest commutative number of cases in Africa are South Africa, Egypt, Nigeria, Algeria, and Ghana. Africa, and the rest of world, has had to swiftly undertake the necessary measures to protect the continent from irreversible effects of the COVID-19 pandemic that is claiming lives and destroying livelihoods. The lower number of COVID-19 cases in most African countries is attributed to inadequate health systems, low-to-absent testing capacity, poor reporting systems, and insufficient numbers of medical staff. The COVID-19 pandemic poses a great threat to most African countries, from cities to rural areas, and has created a strong demand on already scarce resources. Intense mobilization of additional resources is required to implement established emergency contingency measures. Measures to prevent the spread of COVID-19 include closure of borders and restricting movement of people within a country; this has resulted in the tourism sector being adversely affected by the loss of income. Cooperative prevention and control measures are one of the promising solutions to deplete the spread of COVID-19 on the continent.

Glucose lowering and pancreato-protective effects of Abrus Precatorius (L.) leaf extract in normoglycemic and STZ/Nicotinamide - Induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Abrus precatorius (L.) leaves are used as folk medicine by the local communities in the western region of Ghana to treat diabetes mellitus; however, this health claim remains unverified scientifically. OBJECTIVE: The study investigated glucose lowering and pancreato-protective effects of Abrus precatorius leaf extract (APLE) in normoglycemic and STZ/nicotinamide (NIC)-induced diabetic rats. METHOD: after preparation of APLE, it was subjected to phytochemical screening, proximate composition and elemental assessments by using standard methods. Oral glucose tolerance test (OGTT) and maltose, lactose and sucrose oral challenge were assessed in normoglycemic rats post-APLE. Morphological characteristics of glucose response curve (time of glucose peak and shape of glucose response curve) were determined. Subsequently, diabetes mellitus was experimentally established in normoglycaemic adult Sprague-Dawley rats (weighing 150-250 g) of both sexes by sequential injection of Streptozotocin (STZ, 60 mg/kg ip)-reconstituted in sodium citrate buffer and NIC (110 mg/kg ip)-reconstituted in normal saline (1:1 v/v) for 16 weeks. Except control rats (normal saline 5 ml/kg ip; baseline fasting blood glucose [FBG] of 6.48 mmol/L), rats having FBG (stable at 11.1 mmol/L or ≥ 250 mg/dL) 3 days post-STZ/NIC injection were randomly re-assigned to one of the following groups: model (STZ/NIC-induced diabetic rats), APLE (100, 200 and 400 mg/kg respectively po) and metformin (300 mg/kg po) and treated daily for 28 days. Bodyweight and FBG were measured on weekly basis. FBG was measured by using standard glucometers. On day 28, rats were sacrificed under chloroform anesthesia, blood collected via cardiac puncture; kidney, liver and pancreas surgically harvested. While the pancreas was processed, sectioned and H&E-stained for histological examination, fresh kidney and liver were homogenized for assessment of total anti-oxidant capacity. Median cross-sectional area of pancreatic islets of Langerhans was determined for each group by using Amscope. RESULTS: Cumulatively, APLE (100, 200 and 400 mg/kg respectively) dose-dependently decreased the initial FBG by 55.22, 76.15 and 77.77% respectively compared to model (-1.04%) and metformin (72.29%) groups. APLE treatment recovered damaged pancreatic ß-cells and also increased median cross-sectional area (x106 µm2) of pancreatic islets compared to that of model group. APLE significantly (P < 0.05) increased total anti-oxidant capacity (5.21 ± 0.02 AscAE µg/mL) of plasma, kidney and liver compared to model (4.06 ± 0.04 AscAE µg/mL) and metformin (4.87 ± 0.03 AscAE µg/mL) groups. CONCLUSION: APLE has demonstrated glucose lowering and pancreato-protective effects in rats and arrested the characteristic loss in bodyweight associated with diabetes mellitus. This finding preliminarily confirms folk use of APLE as an anti-diabetic herbal medicine, whiles providing a rationale for further translational studies on APLE.

The hydroxyl moiety on carbon one (C1) in the monoterpene nucleus of thymol is indispensable for anti-bacterial effect of thymol.

BACKGROUND: Thymol, a natural monoterpene phenol is not only relevant clinically as an anti-microbial, anti-oxidant and anti-inflammatory agent but also holds the prospect as a natural template for pharmaceutical semi-synthesis of therapeutic agents. It is a major component of essential oils from many plants. Evidence abound linking overall bioactivity of thymol to its monoterpene nucleus, specifically, the hydroxyl (-OH) substituent on carbon number one (C1) on the monoterpene nucleus. Other studies have posited that the overall bioactivity of thymol is not substantially altered by chemical modification of - OH on the C1 of the monoterpene nucleus. In view of this, it is still unclear as to whether removal or modification of the -OH on C1 of the monoterpene nucleus relates generally or context-dependently to bioactivity of thymol. OBJECTIVE: The present study investigated anti-bacterial effects of ester-and-ether substituted derivatives of thymol on S. aureus, P. aeruginosa and E. coli. MATERIALS AND METHODS: twelve ester-and-ether substituted derivatives of thymol (6TM1s and 6TM2s) were synthesized and characterized by using HPLC, Mass spectrometry, and IR techniques. Anti-bacterial activity of the 12 thymol derivatives was evaluated using broth macrodilution and turbidimetric methods against pure clinical isolates (S. aureus, P. aeruginosa and E. coli). Standard anti-biotics used were Thymol Streptomycin and flucloxacillin, while DMSO was used as vehicle for thymol derivatives. MIC and MBC were determined. RESULTS: Thymol produced broad-spectrum growth inhibition on all isolates. At equimolar concentrations, thymol and reference drugs produced concentration-dependent growth inhibition against the isolates (Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli) compared to DMSO. Although the growth inhibitory effects of the ester-and-ether derivatives of thymol was significant (P ≤ 0.05) compared to DMSO, it was however insignificant (P ≥ 0.05) compared to thymol and reference antibiotics. Comparatively, at equimolar concentrations, ester-substituted derivatives of thymol, particularly the branched chain derivative (TM1C) produced more effective growth inhibition on the isolates than the ether-substituted derivatives of thymol. Thymol was twice as potent (MIC and MBC, 500 µg/ml) than both ester-and-ether substituted derivatives of thymol (MIC and MBC, > 1000 µg/ml) on all the three clinical isolates. Increase in side chain bulkiness of -OH moiety on the monoterpene nucleus of thymol decreased growth inhibition on isolates. CONCLUSION: Thymol has demonstrated broad-spectrum anti-bacterial effects attributable to the hydroxyl moiety on C1 of the monoterpene nucleus. Structural modification of the hydroxyl moiety on C1 of the monoterpene nucleus of thymol with either ether-or-ester substitutions yielded no significant anti-bacterial effects.

Histoprotective Effect of Essential Oil from Citrus aurantifolia in Testosterone-Induced Benign Prostatic Hyperplasia Rat.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common urological disorder reported among ageing men. OBJECTIVE: The study assessed histoprotective effect of lime essential oil (LEO) in a rat model of testosterone-induced benign prostatic hyperplasia (BPH) and evaluated its ability to reverse testosterone-mediated changes in the testis, kidney, and liver. MATERIALS AND METHODS: Adult Sprague Dawley (aged 12 weeks, 240-390 g) male rats were intramuscularly injected with testosterone enanthate (TE) (10 mg/kg) reconstituted in olive oil for ten days to establish benign prostatic hyperplasia (serum PSA level ≥ 1.24 ng/ml) in. After confirmation of BPH (sustained serum PSA level ≥ 1.24 ng/ml), rats in all groups (LEO: 30, 100, and 300 mg/kg, po, n = 6; finasteride: 15 mg/kg, po, n = 6) except model (BPH without treatment) and sham (no BPH and no treatment) groups were treated for 21 days. At the end of treatment, rats were anesthetised and blood was collected via cardiac puncture to determine serum PSA and total antioxidant capacity (TAC) levels. The prostate gland, testis, kidney, and liver were harvested, weighed, histologically processed and stained with H&E. RESULTS: LEO- and finasteride-treated groups recorded lesser mean prostatic weights relative to their model group. Baseline mean serum PSA level of LEO- and finasteride-treated groups reduced significantly (p < 0.05) relative to model group. Serum TAC levels were also higher in LEO- and finasteride-treated groups relative to model group. LEO-treated groups had less thickened glandular epithelium, smaller acini, fewer prostatic secretions and more fibromuscular stroma relative to model group. LEO and finasteride treatment produced improved histomorphological characteristics of testis, kidney, and liver compared to model group. CONCLUSION: By the current results, Citrus aurantifolia LEO may possess active agents that can be explored for translational medicine against BPH.

Evaluating 18s-rRNA LAMP and selective whole genome amplification (sWGA) assay in detecting asymptomatic Plasmodium falciparum infections in blood donors.

BACKGROUND: Undesirable consequences of donor Plasmodium falciparum parasitaemia on stored donor blood have been reported. Therefore, it is imperative that all prospective blood donors are screened for P. falciparum infections using sensitive techniques. In this study, the sensitivities of microscopy, rapid diagnostic test (RDT), loop-mediated isothermal amplification (LAMP) assay and selective whole genome amplification (sWGA) technique in detecting P. falciparum infections in blood donors was assessed. METHODS: Randomly selected blood donors from 5 districts in Greater Accra Region of Ghana were screened for asymptomatic P. falciparum infections. Each donor sample was screened with SD Bioline RDT kit for P. falciparum histidine rich protein 2 and Plasmodium lactate dehydrogenase antigens, sWGA and 18s-rRNA LAMP. Crude DNA LAMP (crDNA-LAMP) was compared to purified DNA LAMP (pDNA-LAMP). RESULTS: A total of 771 blood donors were screened. The respective overall prevalence of P. falciparum in Ghana by microscopy, RDT, crDNA-LAMP, pDNA-LAMP and sWGA was 7.4%, 11.8%, 16.9%, 17.5% and 18.0%. Using sWGA as the reference test, the sensitivities of microscopy, RDT, crDNA-LAMP and pDNA-LAMP were 41.0% (95% CI 32.7-49.7), 65.5% (95% CI 56.9-73.3), 82.6% (95% CI 75.8-88.3) and 95.7% (95% CI 90.1-98.4), respectively. There was near perfect agreement between LAMP and sWGA (sWGA vs. crDNA-LAMP, κ = 0.87; sWGA vs. pDNA-LAMP, κ = 0.96), while crDNA-LAMP and pDNA-LAMP agreed perfectly (κ = 0.91). Goodness of fit test indicated non-significant difference between the performance of LAMP and sWGA (crDNA-LAMP vs. sWGA: x2 = 0.71, p = 0.399 and pDNA-LAMP vs. sWGA: x2 = 0.14, p = 0.707). Finally, compared to sWGA, the performance of LAMP did not differ in detecting sub-microscopic parasitaemia (sWGA vs. crDNA-LAMP: x2 = 1.12, p = 0.290 and sWGA vs. pDNA-LAMP: x2 = 0.22, p = 0.638). CONCLUSIONS: LAMP assay agreed near perfectly with sWGA with non-significant differences in their ability to detect asymptomatic P. falciparum parasitaemia in blood donors. Therefore, it is recommended that LAMP based assays are employed to detect P. falciparum infections in blood donors due to its high sensitivity, simplicity, cost-effectiveness and user-friendliness.

Compound Astragalus and Salvia miltiorrhiza extract inhibits hepatocellular carcinoma progression via miR-145/miR-21 mediated Smad3 phosphorylation.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Astragalus and Salvia miltiorrhiza extract (CASE), containing astragalosides, astragalus polysaccharide extracted from Astragalus membranaceus (Fisch.) Bge. and salvianolic acids from Salvia miltiorhiza Bge., has been found to inhibit hepatocarcinogenesis via mediating transforming growth factor-ß (TGF-ß)/Smad signaling, especially Smad3 phosphorylation. The crucial interaction between microRNA-145/microRNA-21 (miR-145/miR-21) and Smad3 phosphorylation is implicated in the pathogenesis and progression of hepatocellular carcinoma (HCC). However, effects of CASE on HCC progression involved in the expression of miR-145/miR-21 and their interaction with Smad3 phosphorylation downstream of TGF-ß/MAPK/Smad pathway remain unclear. This study addressed above questions using in vitro (HepG2 cells) and in vivo (Xenografts of nude mice) models of HCC. MATERIALS AND METHODS: In vivo [Diethylnitrosamine (DEN)-induced HCC in rats] and in vitro [TGF-ß1-stimulated HepG2 cells] models of HCC were established and co-administrated using graded doses/concentrations CASE (60, 120, 240 mg/kg used in rats; 20, 40, 80 µg/ml used in HepG2 cells), miR-145 and miR-21 were measured. HepG2 cells were transfected with miR-145 antagomir, miR-21 agomir and Smad3C/L plasmids (Smad3 EPSM, Smad3 3S-A and Smad3 WT related to up-regulated expression of pSmad3C, pSmad3L and pSmad3C/3L respectively) and then treated by CASE (80 µg/ml). Similarly, HepG2 cell xenografted nude mice were administered with miR-145 antagomir, miR-21 agomir and CASE (310 mg/kg); Smad3 WT, Smad3 EPSM and Smad3 3S-A plasmids stably transfected HepG2 cell lines were constructed respectively and their xenografted nude mice were established, and then treated by CASE (310 mg/kg). Cell proliferation, migration, apoptosis, tumor growth and histopathologic characteristics of xenografts were assessed; also, domain-specific Smad3 phosphorylation isoforms (pSmad3C/pSmad3L), activated MAPKs (pERK1/2, pJNK1/2, pp38) and miR-145, miR-21 were measured. RESULTS: CASE up-regulated miR-145 while down-regulated miR-21 expression in both rats with DEN-induced HCC and TGF-ß1-stimulated HepG2 cells; CASE inhibited cell migration, proliferation and tumor growth while facilitated cell apoptosis in TGF-ß1-stimulated HepG2 cells and xenografts of nude mice with miR-145 antagomir/miR-21 agomir treatment via increasing miR-145 and facilitating miR-145 modulated pSmad3L→pSmad3C signaling switch while decreasing miR-21 and inhibiting miR-21 modulated MAPK-dependent Smad3L phosphorylation. Also, up-regulated pSmad3C enhanced inhibited effect of CASE on tumor growth and facilitated effect of CASE on cell apoptosis involved in increased miR-145 while decreased miR-21 expression, however, inverse phenomena were observed when up-regulated pSmad3L. CONCLUSION: Our results suggest that CASE inhibits HCC progression via mediating the interaction of miR-145/miR-21 and Smad3 phosphorylation, especially miR-145/miR-21 mediated Smad3 phosphorylation, which maybe provides an important theoretical foundation for CASE's anti-HCC therapy used for patients in a near future.