Assessment of toxicity and anti-plasmodial activities of chloroform fractions of Carapa procera and Alchornea cordifolia in murine models.

Background: Plant as a source of medicine has gained international popularity in recent times because of its natural origin, availability in local communities, cheaper to purchase, ease of administration, and its usefulness as an alternative treatment in case of numerous side effects and drug resistance. However, the use of herbal formulations can also result in short-term and long-term organ damage or dysfunction to the host. In this study, chloroform fractions of the leaves of two medicinal plants, Alchornea cordifolia (ACL) and Carapa procera (CPL), were investigated for their toxicological and anti-malarial effects in murine models. Method: Acute (14-day) and sub-acute (28-day) studies were conducted based on the Organization for Economic Cooperation and Development (OECD) Guidelines in Institute for Cancer Research (ICR) mice and Sprague Dawley (SD) rats respectively. A dosage of 2000 mg/kg body weight was administered orally to each ICR mouse during the acute study and 100, 300, and 1000 mg/kg body weight to each SD rat during the sub-acute study. A 5-day curative anti-plasmodial activity was assessed in ICR mouse model. Results: The assessment of toxicity revealed that all three fractions did not influence mortality, clinical appearance, body weight gain, or necropsy at the various doses. Hematological and serum biochemical analysis indicated no significant elevations in liver and renal function parameters. Histopathological examinations of the liver indicated reversible liver degeneration with the chloroform fraction of the 100% ethanol extract of Carapa procera leaves (CPL100%) at 1000 mg/kg. Anti-plasmodial assessments showed CPL100% exhibiting dose-dependent anti-plasmodial activity from 16% to 26.67%. On the other hand, chloroform fraction of the 100% ethanol extract of Alchornea cordifolia leaves (ACL100%) showed declining anti-plasmodial activity from 21.1% to 15.1%. Conclusion: These preliminary findings demonstrate that chloroform fractions of the leaves of Carapa procera and Alchornea cordifolia may be safe agents for treating malaria hence further development for drug discovery must be pursued.

Antimicrobial Activity of Selected Medicinal Plants from a Sub-Saharan African Country against Bacterial Pathogens from Post-Operative Wound Infections.

BACKGROUND: Globally, the application of medicinal plants in the management of acute and chronic wounds can be considered a common occurrence in most traditional medicine practices. In view of this, many plants in the tropical and subtropical regions have been screened for their wound-healing activities. Consequently, plants having antimicrobial activity against multidrug-resistant (MD-R) pathogens can be considered great assets. Therefore, this study evaluated ethanolic and aqueous extracts of five medicinal plants (Psidium guajava, Myrianthus arboreus, Alchornea cordifolia, Momordica charantia, and Justicia flava) for their antimicrobial activities against MD-R bacterial pathogens isolated from post-operative wounds; Methods: This involved the aqueous and ethanolic extraction of the selected medicinal plants. Preliminary phytochemical constituents of the plants were examined. The agar well diffusion method was then used to determine the antibacterial activity of the leaves against reference strains (Escherichia coli ATCC 25922, Salmonella typhi ATCC 19430, Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 25923, and a Methicillin-Resistant Staphylococcus aureus strain) as well as the MDR clinical isolates (E. coli, P. aeruginosa, S. aureus and CoNS) from the wounds; Results: The preliminary phytochemical analysis of the leaves showed the presence of saponins, phenolics, and reducing sugars in almost all the plants tested. All plant extracts were observed to have some antimicrobial activity against at least one reference strain. For the clinical MDR isolates, A. cordifolia from this study showed highest inhibition to growth of all bacteria used. Activity of J. flava against S. aureus was highest as compared to that of E.coli and P. aeruginosa. Similar observation was made for M. arboreus, P. guajava and M. charantia where the highest activity was observed against S. aureus; Conclusion: This study has mainly shown that P. guajava, M. arboreus, A. cordifolia, M. charantia, and J. flava exhibits antimicrobial activities against MD-R bacterial pathogens isolated from post-operative wounds. Also, these plants has bioactive phytochemical compounds with potential medicinal values for the treatment of numerous infections. Therefore, these plants may be helpful in the management of acute and chronic wounds, especially in traditional medicine practices.

Response to the Novel Corona Virus (COVID-19) Pandemic Across Africa: Successes, Challenges, and Implications for the Future.

BACKGROUND: The COVID-19 pandemic has already claimed considerable lives. There are major concerns in Africa due to existing high prevalence rates for both infectious and non-infectious diseases and limited resources in terms of personnel, beds and equipment. Alongside this, concerns that lockdown and other measures will have on prevention and management of other infectious diseases and non-communicable diseases (NCDs). NCDs are an increasing issue with rising morbidity and mortality rates. The World Health Organization (WHO) warns that a lack of nets and treatment could result in up to 18 million additional cases of malaria and up to 30,000 additional deaths in sub-Saharan Africa. OBJECTIVE: Document current prevalence and mortality rates from COVID-19 alongside economic and other measures to reduce its spread and impact across Africa. In addition, suggested ways forward among all key stakeholder groups. OUR APPROACH: Contextualise the findings from a wide range of publications including internet-based publications coupled with input from senior-level personnel. ONGOING ACTIVITIES: Prevalence and mortality rates are currently lower in Africa than among several Western countries and the USA. This could be due to a number of factors including early instigation of lockdown and border closures, the younger age of the population, lack of robust reporting systems and as yet unidentified genetic and other factors. Innovation is accelerating to address concerns with available equipment. There are ongoing steps to address the level of misinformation and its consequences including fines. There are also ongoing initiatives across Africa to start addressing the unintended consequences of COVID-19 activities including lockdown measures and their impact on NCDs including the likely rise in mental health disorders, exacerbated by increasing stigma associated with COVID-19. Strategies include extending prescription lengths, telemedicine and encouraging vaccination. However, these need to be accelerated to prevent increased morbidity and mortality. CONCLUSION: There are multiple activities across Africa to reduce the spread of COVID-19 and address misinformation, which can have catastrophic consequences, assisted by the WHO and others, which appear to be working in a number of countries. Research is ongoing to clarify the unintended consequences given ongoing concerns to guide future activities. Countries are learning from each other.

COVID-19 pandemic in resource-poor countries: challenges, experiences and opportunities in Ghana.

The novel coronavirus, SARS-CoV-2, which causes COVID-19, is seen world-wide. In developing countries, adequate health facilities and staff numbers are a concern. Ghana recorded its first 2 cases of COVID-19 on 12 March 2020. On 30 March 2020, a partial lockdown for 14 days was imposed and later extended along with other measures. By the end of the initial lockdown, 19 April 2020, an estimated 86,000 people had been traced and 68,591 tests performed. Of the 68,591 tests, there were 1,042 (1.5%) positive cases, 9 deaths, and 99 recoveries, with Ghana ranked number one among African countries in administering tests per million people. Ghana's effective track and trace system, as well as lockdown and other measures, have helped limit mortality with only 85 recorded deaths by 23 June 2020. Scientists from three facilities of the University of Ghana have also successfully sequenced the genomes of COVID-19 from 15 confirmed cases, and the Food and Drugs Authority in Ghana have also helped address shortages by fast-tracking certification of hand sanitizers and local production of 3.6 million standardized personal protective equipment. There has also been the development of prototypes of locally-manufactured mechanical ventilators to meet local need at intensive care units. Most people have also resorted to changing diets and the use of supplements to boost their immune system. Although initial results are encouraging, further research is needed to understand the dynamics of COVID-19 in Ghana and provide additional guidance.

Oxidised low-density lipoprotein, a possible distinguishing lipid profile biomolecule between prostate cancer and benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) share common conditions such as lower urinary tract symptoms (LUTS) and dyslipidaemia. Whether an extensive lipid profile analysis could discriminate between BPH and PCa was the objective. Thirty-six (36) BPH and twenty (20) PCa outpatients of a urology clinic plus forty (40) controls without LUTS, but normal PSA, were recruited. Body mass index (BMI), lipid profile (total cholesterol [CHOL], triglycerides [TG], high-density lipoprotein [HDL], very-low-density lipoprotein [VLDL], low-density lipoprotein [LDL] and Castelli's risk index I [CR I] [TC/HDL]), oxidised LDL, apolipoprotein E, ceramide and PSA were determined. Mean ages for BPH, PCa and control were 69 ± 13, 67 ± 10 and 53 ± 7 years respectively. Most parameters apart from BMI and HDL were significantly different compared to the control group. oxLDL for BPH versus control, PCa versus control and BPH versus PCa was significant (p < 0.001, p = 0.02 and p < 0.001 respectively). Ceramide showed significant group differences. Between BPH and PCa, total cholesterol, LDL and Apo E were significantly different (p = 0.00, p = 0.01 and p = 0.03 respectively). Apo E could potentially be a discriminating biomarker. Receiver operating characteristic curves for TPSA, Apo E and oxLDL demonstrated sensitivity of 69.44 and specificity of 88.24 for oxLDL, hence more discriminatory.

Lipid associated antioxidants: arylesterase and paraoxonase-1 in benign prostatic hyperplasia treatment-naïve patients.

BACKGROUND: Oxidative stress and antioxidants have been implicated in many diseases including prostate cancer and benign prostatic hyperplasia (BPH). Lipid peroxidation contributes to oxidative stress. However, new and emerging antioxidants such as paraoxonase 1 (PON1) and arylesterase (ARE) associated with lipoprotein peroxidation have not been examined in BPH patients. PON1 and ARE, a high-density lipoprotein (HDL) cholesterol-bound enzyme system of antioxidants, protect low-density lipoprotein (LDL) cholesterol and HDL from oxidation by hydrolysis. The study primarily determined paraoxonase (PON1) and ARE activities in BPH treatment-naïve patients. MATERIALS AND METHODS: Sixty newly diagnosed patients (treatment-naïve) alongside 30 apparently healthy controls were recruited. Blood examinations included lipid profile (total cholesterol, triglycerides, LDL, HDL), glutathione peroxidase, PON1, ARE, and prostate specific antigen (PSA).Prostate volume and International Prostate Symptoms Score (IPSS) were determined. RESULTS: PSA was significantly different between patient and control groups (P < 0.0001). Total cholesterol, triglycerides, and LDL were significantly higher in the patient group (P = 0.002, P < 0.001, P = 0.003, respectively). Glutathione peroxidase was very low in the patient group compared to the control group (5.65 ± 2.30 ng/mL and 17.43 ± 10.98 ng/mL, respectively). Although PON1 was higher in the patient group (50.22 ± 19.68/61.30 ± 29.55 ng/mL; P > 0.05), ARE was significantly lower in the patient group (61.31 ± 21.76/49.30 ± 19.82 ng/mL; P = 0.0098). No correlation was established between antioxidants and the lipid profile except for the LDL and PON1 patient group (r = 0.1486, P = 0.0374). Similarly, a weak correlation was also established between PSA and LDL in the patient group (r = -0.275, P = 0.033). PON1/HDL ratio was not significantly different. However, the ARE/HDL ratio was significantly lower in the patient group (P < 0.0001). CONCLUSION: These results signify the presence of a higher lipoprotein peroxidation activity and lower lipid-associated antioxidant activity in the patient group. The ARE/HDL ratio is a better indicator of the HDL associated antioxidant than the PON1/HDL ratio or the individual antioxidants (PON1 and ARE) as reported by others.

Endogenous Sphingolipid Signaling Pathway Implicated in the Action of Croton membranaceus on the Prostate Gland in BPH Patients.

Background: Croton membranaceus extract has apoptotic effects on BPH-1 cells. This study determined if the apoptotic effects were created through the ceramide pathway. Methods: The study was a follow-up to a previous observational study of 30 histologically confirmed patients with benign prostatic hyperplasia (BPH) who were on C. membranaceus ethanolic extract at 20 mg t.i.d orally for 3 mo. Thereafter, total and free prostate-specific antigen (PSA), lipid profile plus Apo lipoprotein A and B, ceramide/Sphingophospho-kinase 1 (SphK1) and 2 (SphK2), sphingosine lyase (SPL), the cytotoxic adducts of oxidative stress 4-hydroxy-2-nonenal (4HNE) and malondialdehyde (MDA), were determined. Results: Total and free PSA were significantly (p < 0.05) different after treatment. Apo lipoprotein A was significantly different (p = 0.024). The SphK1/SphK2 ratio reduced significantly (p = 0.049). Furthermore, SPL, ceramide, and MDA increased significantly after treatment (p = 0.05, p = 0.004, and p = 0.007, respectively). A weak positive correlation was found between high-density lipoprotein (HDL) cholesterol and SphK1, and HDL and ceramide before treatment (p = 0.036, r = 0.3826; p = 0.018, r = 0.4286, respectively. Conclusions:C. membranaceus uses the ceramide pathway by modulating the SphK1/SphK2 ratio and increasing SPL to generate oxidative stress and consequently apoptosis.

Calcium - Magnesium imbalance implicated in benign prostatic hyperplasia and restoration by a phytotherapeutic drug - Croton membranaceus Müll.Arg.

BACKGROUND: Calcium (Ca)- magnesium (Mg) imbalance is implicated in prostate cancer. Ca/Mg ratio increases or decreases with proliferation or apoptosis, respectively. The study examined whether this Ca/Mg imbalance exists in BPH patients and the effect of a phytotherapeutic drug on the Ca/Mg ratio. METHODS: Thirty (30) BPH patients who used the ethanolic root extract of Croton membranaceus (60 mg/day) for 3 months were examined for serum Ca, Mg, phosphate, parathyroid hormone (PTH), vitamin D, prostate specific antigen (PSA) levels and renal function tests (RFT) before (BT) and after treatment (AT) alongside thirty (30) controls. Twenty (20) trace element including Mg and Ca were determined in the drug by neutron activation analysis (NAA). RESULTS: RFT, PTH and vitamin D for BT, AT and controls (C) were normal. Mean PSA was 1.0 ± 0.64 (C), 27.9 ± 19.0 (BT) and 16.2 ± 11.8 ng/mL (AT) (p = 0.002). Mg, Ca/Mg ratio BT, AT and control were significantly different (p = 0.0001, respectively). After treatment, Mg and Ca/Mg ratio were not different from controls. The prevalence of Ca/Mg imbalance was 80% (BT), 13.3% (AT) and 3.3% (control group). CONCLUSION: Ca/Mg ratio imbalance is associated with BPH. This has previously not been demonstrated. The imbalance was significantly corrected after treatment with the phytotherapeutic drug.

Anaemia in pregnant adolescent girls with malaria and practicing pica.

INTRODUCTION: Pregnancy during the adolescent period is challenging mainly because of the nutritional demands of both the adolescent and pregnancy period. The risk for anaemia increases especially in developing countries such as Ghana where malaria is endemic and the practice of pica is common. In this study, we sought to determine the prevalence of anaemia, pica practice and malaria infection among pregnant adolescent girls and assess the extent to which these factors are associated. METHODS: Two hundred and sixty five (265) pregnant adolescent girls were recruited from three hospitals in Accra. Haemoglobin levels, malaria infection and the practice of pica were assessed. Pearson's Chi squared tests were used to determine associations and logistic regression analysis was used to determine the odds of being anaemic. Significance was set at p≤0.05. RESULTS: Anaemia prevalence was 76% with severity ranging from mild (47.8%) to severe (0.8%). About 27.5% were moderately anaemic. Pica was practiced in only 9.1% of the girls. Malaria infection was prevalent in 17.7% of the girls. The logistic regression analysis indicated that pregnant girls with malaria infection were 3.56 times more likely to be anaemic when compared to those without malaria. Also, those who practiced pica were 1.23 times more likely to be anaemic when compared to those who did not practice pica. CONCLUSION: Anaemia is very prevalent in pregnant adolescent girls and is a public health problem. Drastic measures should be taken to reduce the high prevalence.

Dynamics of urinary oxidative stress biomarkers: 8-hydroxy-2'-deoxyguanosine and 8-isoprostane in uterine leiomyomas.

BACKGROUND: Perturbations of antioxidant levels and lipid peroxidation, but not oxidative DNA damage as a biomarker of oxidative stress have been reported in uterine myoma patients. AIMS: The study aimed at examining the patterns and influence of oxidative stress/damage biomarkers, 8-isoprostane (8-IP) and 8-hydroxy-2'-deoxyguanosine (8OHdG), on the ovulatory and luteal phases of normal and fibroid women. SETTINGS AND DESIGN: Twenty women diagnosed of fibroids (1-5 years) and 20 nonfibroid women were age-matched. Selection was randomly done at the National Obstetrics and Gynaecology Department. SUBJECTS AND METHODS: Three successive samples of urine were taken at 8:00 am on the 14(th), 18(th), and 21(st) days of the menstrual cycle. Mid-stream urine was collected from subjects, after they had cleaned genitals. The samples were kept in an ice chest, transported to the laboratory, and stored at - 70°C until the time of analysis. Samples were analyzed by ELISA technique using commercial kits for 8OHdG and 8-IP. Results were calculated using a computer program. STATISTICAL ANALYSIS USED: Statistical Package for Social Sciences, version 20.0, was used for data management and statistical analysis. The results were expressed as mean ± standard deviation. Differences in continuous data were compared using Student's t-test (two groups) and one-way ANOVA (three or more groups) followed by Bonferroni post hoc test. Relationship between variables was ascertained by Spearman's correlation coefficient. All results were considered significant at 5% level of probability. RESULTS: Significant differences were observed between day 14 and day 21 in control and test groups' estrogen levels (P = 0.0047 and P = 0.004, respectively). Significant progesterone differences were observed between control and test groups on the same days (P = 0.002 and P = 0.001, respectively). A positive correlation was observed between day 21 estrogen and progesterone levels (P = 0.0003) of the control group. Test group had higher levels of 8-IP and 8OHdG than control groups on day 21, with 8OHdG at maximum in the test group but minimum in the control group. The influence of 8OHdG was seen by a negative correlation with estrogen and progesterone on day 21 (P = 0.0002) and a positive correlation between 8OHdG and 8-IP on the same day in the test group. Finally, there was a positive correlation between 8-IP and 8OHdG on day 14, but a negative correlation on day 21 (P = 0.0016). CONCLUSIONS: Oxidative damage was absent in the control group but was very much present in the test group on day 14 and day 21 with progesterone and estrogen acting in concert with oxidative damage biomarkers. An inverse pattern of biomarkers was observed between control and fibroid groups. Oxidative stress biomarkers influenced hormonal levels and pattern of the fibroid group.

Proteomic analysis of microparticles isolated from malaria positive blood samples.

BACKGROUND: Malaria continues to be a great public health concern due to the significant mortality and morbidity associated with the disease especially in developing countries. Microparticles (MPs), also called plasma membrane derived extracellular vesicles (PMEVs) are subcellular structures that are generated when they bud off the plasma membrane. They can be found in healthy individuals but the numbers tend to increase in pathological conditions including malaria. Although, various studies have been carried out on the protein content of specific cellular derived MPs, there seems to be paucity of information on the protein content of circulating MPs in malaria and their association with the various signs and symptoms of the disease. The aim of this study was therefore to carry out proteomic analyses of MPs isolated from malaria positive samples and compare them with proteins of MPs from malaria parasite culture supernatant and healthy controls in order to ascertain the role of MPs in malaria infection. METHODS: Plasma samples were obtained from forty-three (43) malaria diagnosed patients (cases) and ten (10) healthy individuals (controls). Malaria parasite culture supernatant was obtained from our laboratory and MPs were isolated from them and confirmed using flow cytometry. 2D LC-MS was done to obtain their protein content. Resultant data were analyzed using SPSS Ver. 21.0 statistical software, Kruskal Wallis test and Spearman's correlation coefficient r. RESULTS: In all, 1806 proteins were isolated from the samples. The MPs from malaria positive samples recorded 1729 proteins, those from culture supernatant were 333 while the control samples recorded 234 proteins. The mean number of proteins in MPs of malaria positive samples was significantly higher than that in the control samples. Significantly, higher quantities of haemoglobin subunits were seen in MPs from malaria samples and culture supernatant compared to control samples. CONCLUSION: A great number of proteins were observed to be carried in the microparticles (MPs) from malaria samples and culture supernatant compared to controls. The greater loss of haemoglobin from erythrocytes via MPs from malaria patients could serve as the initiation and progression of anaemia in P.falciparum infection. Also while some proteins were upregulated in circulating MPs in malaria samples, others were down regulated.

Shrinkage of Prostate and Improved Quality of Life: Management of BPH Patients with Croton membranaceus Ethanolic Root Extract.

Benign prostatic hyperplasia (BPH) is an enlargement of the prostate. The study aimed at validating the use of freeze-dried Croton membranaceus ethanolic root extract for BPH management. Thirty-three patients were observed before and after 3-month administration of 20 mg t.i.d orally. The International Prostate Symptom Score (IPSS), and the International Index of Erectile Function (IIEF) questionnaires were used. Total/free PSA (tPSA, fPSA), renal, liver function, lipid tests, and ultrasonographic imaging were performed. Thirty (30) patients (66 ± 11 years) completed the study. IPSS results showed 37% had severe, 40% moderate, and 23% mild symptoms before; 57% and 43% had moderate and mild symptoms, respectively, after treatment. IIED of patients' results showed 30% with severe, 40% moderate, 24% mild-moderate, 3% mild, and 3% no erectile dysfunction before treatment and 20% severe, 43% moderate, and 37% mild-moderate dysfunction, after treatment. Quality of life (QoL) improved (P = 0.001). Significant but non-pathological increases in total and indirect bilirubin as well as apolipoprotein A occurred. Mean tPSA reduced from 27.9 ± 19.0 to 16.2 ± 11.8 ng/mL (P = 0.002); fPSA from 6.1 ± 4.8 to 3.9 ± 2.9 ng/mL (P = 0.045); and prostate volume from 101.8 ± 41.3 to 54.5 ± 24.8 cm(3) (P = 0.023). C. membranaceus shrinks the prostate and improves QoL.

Croton membranaceus Improves Some Biomarkers of Cardiovascular Disease and Diabetes in Genetic Animal Models.

INTRODUCTION: Cardiovascular disease (CVD) accounts for 17.3 million deaths per year globally. In Ghana, CVD accounts for 22.2% of deaths. Croton membranaceus (CM) Mull. Arg. (Euphorbiaceae), a medicinal plant in Ghana is mainly used traditionally for the treatment of benign prostatic hyperplasia and measles. However, some hypoglycaemic and hypotensive effects have recently been reported but not scientifically examined. AIM: The study aimed at establishing whether Croton membranaceus (CM) used for prostatitis had any effect on CVD markers. MATERIALS AND METHODS: In experiment 1, lipid profile changes were determined. Twenty four male Spontaneously Hypertensive Rats (SHR) were divided into 4 groups. Low (LD), intermediate (ID) and high dose (HD) groups received 25, 50 and 100 mg/kg b.wt. CM aqueous root extracts (CMARE) for 60 days, respectively, the controls received distilled water. In experiment 2, blood glucose levels (BGL) were determined. 21 db/db mice were divided into 3 groups of 7 mice each alongside db/+ mice (7) (negative control). Groups 1 and 2 received 250 mg/kg b.wt CMARE and metformin, respectively. Group 3 (positive control) and db/+ mice (negative control) received distilled water. Mice were monitored for 15 hours. Data collected were analysed using SPSS version 20. RESULTS: Hypotriglyceridaemic effect was observed (p=0.005). High Density Lipoprotein cholesterol (HDL) and Low Density Lipoprotein cholesterol (LDL) showed significant increases (p=0.013) and decreases (p=0.003), respectively. A significant CRP reduction was observed for ID and HD groups (p = 0.010, p = 0.011, respectively). BGL was reduced in Metformin and Croton groups (p=0.000; p= 0.006, respectively) after 3 hours. CONCLUSION: In conclusion, CMARE has positive effects on some CVD biomarkers and a hypoglycaemic effect.

Antiproliferative activity of aqueous leaf extract of Annona muricata L. on the prostate, BPH-1 cells, and some target genes.

BACKGROUND: Annona muricata L. has been reported to possess antitumor and antiproliferative properties. Not much work has been done on its effect on BPH-1 cell lines, and no in vivo studies targeting the prostate organ exist. The study determined the effect of A muricata on human BPH-1 cells and prostate organ. METHODS: The MTT assay was performed on BPH-1 cells using the aqueous leaf extract of A muricata. Cells (1 × 10(5) per well) were challenged with 0.5, 1.0, and 1.5 mg/mL extract for 24, 48, and 72 hours. Cell proliferation and morphology were examined microscopically. BPH-1 cells (1 × 10(4) per well) were seeded into 6-well plates and incubated for 48 hours with 0.5, 1.0, and 1.5 mg/mL A muricata extract. Reverse transcriptase polymerase chain reaction was performed using mRNA extracted from the cells. Possible target genes, Bax and Bcl-2, were examined. Twenty F344 male rats (≈200 g) were gavaged 30 mg/mL (10 rats) and 300 mg/mL (10 rats) and fed ad libitum alongside 10 control rats. Rats were sacrificed after 60 days. The prostate, seminal vesicles, and testes were harvested for histological examination. RESULTS: Annona muricata demonstrated antiproliferative effects with an IC50 of 1.36 mg/mL. Best results were obtained after 48 hours, with near cell extinction at 72 hours. Bax gene was upregulated, while Bcl-2 was downregulated. Normal histological architecture was observed for all testes. Seminal vesicle was significantly reduced in test groups (P < .05) and demonstrated marked atrophy with increased cellularity and the acinii, empty of secretion. Prostate of test groups were reduced with epithelial lining showing pyknotic nucleus, condensation, and marginalization of the nuclear material, characteristic of apoptosis of the glandular epithelium. Furthermore, scanty prostatic secretion with flattening of acinar epithelial lining occurred. CONCLUSION: Annona muricata has antiproliferative effects on BPH-1 cells and reduces prostate size, possibly through apoptosis.

Male rat hormone imbalance, testicular changes and toxicity associated with aqueous leaf extract of an antimalarial plant: Phyllanthus niruri.

CONTEXT: Phyllanthus niruri L. (Euphorbiaceae), a medicinal plant traditionally known for dissolving kidney stones, is used prophylactically as an antimalarial agent. OBJECTIVE: The study was undertaken to determine its effect on some male hormones and other toxicological properties due to paucity of its data despite its wide use. MATERIAL AND METHODS: Male Sprague-Dawley rats (100-140 g) were used. Group 1 [control group (C), n = 6] received water. Group 2 [low-dose test group (LD), n = 6] received 50 mg/kg body weight (b.wt.) aqueous leaf extract orally. Group 3 [high-dose test group (HD), n = 6] received 500 mg/kg b.wt. extract for 90 days. Upon sacrifice, among other organs the testes were harvested. Blood samples drawn were used for biochemical (including progesterone, estrogen and testosterone), cytotoxicity and hematological assays. RESULTS: C, LD and HD estrogen values were 192 ± 25, 385 ± 122 and 962 ± 357 pg/ml, respectively. In the same order, progesterone values were 96 ± 24, 155 ± 45 and 320 ± 80 pg/ml, respectively. Testosterone levels were 5210 ± 1090, 4710 ± 220 and 4500 ± 580 pg/ml, respectively. Significant differences were observed in the estrogen and progesterone levels (p = 0.001). Degenerative changes were observed histologically. Cytotoxicity at 50% (CC50) was 10.0 µg/ml. DISCUSSION AND CONCLUSION: This antimalarial plant is mildly cytotoxic with male antifertility properties.

Toxicity potentials of the nutraceutical Moringa oleifera at supra-supplementation levels.

Moringa oleifera Lam. (order -Moringales, family -Moringaceae and genus -Moringa) is a well known nutraceutical used in the treatment of hypercholesterolemia and hyperglycemia, and also, as a nutritional supplementation. Its popularity use raises the question of possible toxicity at supra-supplementation levels. The objective of the study was to ascertain possible acute toxicity with supra-supplementation using Sprague-Dawley (S-D) rats. In experiment 1, human peripheral blood mononuclear cells were given graded doses of Moringa oleifera aqueous leaf extract to induce cytotoxicity. In experiment 2, two groups of rats received low and high dose (LD and HD, respectively) levels (1,000 and 3,000 mg/kgb.wt, respectively) per o.s. alongside negative and positive control rats (0.9% saline and 10mg/mL N-ethyl-N-nitrosourea - administered i.m., respectively). Each group consisted of five rats. Rats were killed after 48 h and the femur bone marrow aspirate examined for polychromatic micronucleated erythrocytes (PCEMN)/normochromatic micronucleated erythrocytes (NCEMN) ratios after Giemsa/Leishman staining. In experiment 3, control, LD and HD groups were established. The LD and HD extracts were administered per o.s. to the respective groups and observed for 14 days. Each group consisted of five rats. Blood was sampled after 48 h and 14 days and examined biochemically and haematologically for acute toxicity. Experiment 1 showed that Moringa oleifera was cytotoxic at 20mg/mL. In experiment 2, PCEMN/NCEMN ratios were: negative control=2.087; LD=1.849; HD=1.397; positive control=1.257. Statistically, LD and HD ratios were significant (p=0.020). Experiment 3 showed that hepatonephro-toxicity was nil with no abnormal haematology results. Genotoxicity results have hitherto not been shown. Moringa oleifera is genotoxic at supra-supplementation levels of 3,000 mg/kg b.wt. However, intake is safe at levels ≤ 1,000 mg/kg b.wt.

Acute toxicity studies of aqueous leaf extract of Phyllanthus niruri.

Phyllanthus niruri is a plant with medicinal properties. It is often used to treat mild malaria and the elimination of renal stones. However, studies on its toxicity are scarce. The study was carried out to determine if the aqueous leaf extract of P. niruri administered to female Sprague-Dawley rats would illicit evidence of toxicity. Fifteen female rats weighing 150-200 g were divided into 3 groups. Rats in Group 1 were given a single low dose (LD) of 2000 mg/kg b.w. of the extract by oral gavage within 24 hrs. Rats in Group 2 were given a single high dose (HD) of 5000 mg/kg b.w. of the extract by oral gavage within 24 hrs. Rats in Group 3 were not given any extract but drinking water and served as the control group (C). All the rats were observed for signs of toxidromes for 14 days. On the 15(th) day, all the rats were sacrificed. Body organs were harvested for macroscopic examination. Urine and blood samples were drawn and analyzed. Hematological tests performed included full blood count and hemoglobin. Biochemical examinations included bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin, alkaline phosphatse (ALP), γ-glutamyltranspeptidase (GGT), urea, and creatinine. The results of the three groups were not significantly different. Examination of the various body organs did not show any abnormality. Thus no toxicity was observed at the levels administered. The LD(50) of the aqueous extract is>5000 mg/kg. b.w.