Alexander Nyarko | University Of Ghana, Accra,Legon (original) (raw)

Papers by Alexander Nyarko

The American journal of Chinese medicine, Jan 28, 2015

Alnus japonica Steud is a tree that grows in damp areas of mountain valleys and has been used as ... more Alnus japonica Steud is a tree that grows in damp areas of mountain valleys and has been used as a traditional medicine in Asia. We investigated the antiproliferative activity of hirsutanone (Hir) and oregonin (Ore) in human cancer cell lines and elucidated their mechanisms of action. A cytotoxicity study using a panel of 12 human cancer and 4 normal cell lines indicated that Hir exhibited potent antiproliferative activity against 4 leukemia (Jurkat, U937, THP-1, and HL-60) and 2 colon cancer cell lines (HCT-15 and Colo205). Although Ore suppressed the cell growth of Jurkat and THP-1, its inhibitory potency was weaker than that of Hir. The IC50 values of Hir and Ore in Jurkat were 11.37 μM and 22.16 μM, respectively. Further analysis on Jurkat cells demonstrated that Hir caused a sequence of events involved in apoptosis, including nuclear morphological changes and accumulation of cells with sub-G1 DNA content. Hir led to the cleavage of poly(ADP-ribose) polymerase (PARP) and activat...

Malaria continues to be a major parasitic disease in the world. Moreover, sub-Saharan African cou... more Malaria continues to be a major parasitic disease in the world. Moreover, sub-Saharan African countries including Ghana still suffer from a great burden of the disease. A great challenge to malaria chemotherapy is resistance of malaria parasites to antimalarial drugs. Thus, there is the need to search for new antimalarial agents. Plant medicines including antimalarial remedies have been important source of therapies. Studies have shown that a decoction AM-1 formulated from Jatropha curcas, Gossypium hirsutum, Physalis angulata and Delonix regia and used in treating malaria, was administered to patients attending a herbal clinic. The hospitalized patients were treated with AM-1 and parasite clearance, biochemical and haematological parameters were monitored. The decoction eliminated malaria parasites from peripheral blood of patients. Additionally, AM-1 did not show any toxic effects on patients and rats. In vitro antimalarial investigations on Phyllanthus amarus, Tridax procumbens, ...

Bioorganic & Medicinal Chemistry Letters, 2015

Human African trypanosomiasis (HAT), commonly known as sleeping sickness has remained a serious h... more Human African trypanosomiasis (HAT), commonly known as sleeping sickness has remained a serious health problem in many African countries with thousands of new infected cases annually. Chemotherapy, which is the main form of control against HAT has been characterized lately by the viewpoints of toxicity and drug resistance issues. Recently, there have been a lot of emphases on the use of medicinal plants world-wide. Morinda lucida Benth. is one of the most popular medicinal plants widely distributed in Africa and several groups have reported on its anti-protozoa activities. In this study, we have isolated one novel tetracyclic iridoid, named as molucidin, from the CHCl3 fraction of the M. lucida leaves by bioassay-guided fractionation and purification. Molucidin was structurally elucidated by (1)H and (13)C NMR including HMQC, HMBC, H-H COSY and NOESY resulting in tetracyclic iridoid skeleton, and its absolute configuration was determined. We have further demonstrated that molucidin presented a strong anti-trypanosomal activity, indicating an IC50 value of 1.27μM. The cytotoxicity study using human normal and cancer cell lines indicated that molucidin exhibited selectivity index (SI) against two normal fibroblasts greater than 4.73. Furthermore, structure-activity relationship (SAR) study was undertaken with molucidin and oregonin, which is identical to anti-trypanosomal active components of Alnus japonica. Overlapping analysis of the lowest energy conformation of molucidin with oregonin suggested a certain similarities of aromatic rings of both oregonin and molucidin. These results contribute to the future drug design studies for HAT.

European Journal of Medicinal Plants, 2015

International Journal of Toxicology, 2014

Polyhexamethylene guanidine hydrochloride (PHMGH) is used worldwide as an antimicrobial agent wit... more Polyhexamethylene guanidine hydrochloride (PHMGH) is used worldwide as an antimicrobial agent with broad spectra of activity and also for treating pool water. This non-GLP preliminary study aims at investigating in a subchronic toxicity study possible effects at supra-optimal doses of this biocide. Both acute and subchronic toxicity studies were conducted. LD(50) for PHMGH was estimated to be 600 mg/kg (ie LC(50) 2 ml of 7.5% solution) when administered as a single dose by gavage via a stomach tube in accordance with the expected route of administration. The acute studies showed that the median lethal dose (LD(50)) of 600 mg/kg was accompanied by signs of neurotoxicity. Haematological and biochemical parameters of subchronic toxicity studies were non-significant. Subchronic doses of 0.006 mg/kg, 0.012 mg/kg and 0.036 mg/kg were administered. 20% of the animals at a dose of 0.006 mg/kg and 0.036 mg/kg showed mild degrees of hydropic changes in proximal tubules while 10% of animals at all the doses had their liver tissues showing local areas of mild pericentral hepatocytes degeneration. PHMGH did not produce any major organ defect with regard to the kidney, heart, and liver. The LD(50) was much higher than the recommended dosage by a factor of about 50,000. The recommended residual concentration is far less than the median lethal dose using rats as test subjects. These results could serve as a basis for investigating the full toxicological profile if it is to be used for the treatment of raw water to make it potable.

Biochemical and Biophysical Research Communications, 2015

Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency ... more Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replicationcompetent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-kB and MAPK signaling pathways because either overexpression of a superrepressor form of IkBa or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by C1. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the C1-induced HIV-1 reactivation. Although C1-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-kB-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainment of HIV-1 expression. These results suggest that procyanidin C1 trimer is a potential compound for reactivation of latent HIV-1 reservoirs.

Tropical Medicine and Health, 2014

We performed drug susceptibility testing on first-and second-line drugs in Mycobacterium tubercul... more We performed drug susceptibility testing on first-and second-line drugs in Mycobacterium tuberculosis (M. tuberculosis) for the first time in Ghana to obtain preliminary data on drug-resistant tuberculosis. Of 21 isolates (4 new cases and 17 treated cases), 5 (23.8%) were multi-drug resistant tuberculosis (MDR-TB) and 19 (90.5%) were resistant to at least one drug, but no extensively drug-resistant TB (XDR-TB) was identified. Since the target patients were Category II, IV or smear positive at follow-up microscopy, it is understandable that there were many drug-resistant TB cases. Six isolates were resistant to one or two second-line drugs, but the secondline drugs were not approved in Ghana. It is considered that the bacilli were imported from abroad. Preventing the import of drug-resistant TB bacilli is probably one of best ways to control TB in Ghana.

Interdisciplinary Toxicology, 2011

Phyllanthus niruri is a plant with medicinal properties. It is often used to treat mild malaria a... more 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 2 000 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 5 000 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 > 5 000 mg/kg. b.w.

Pharmaceutical Biology, 2013

Context: Phyllanthus niruri L. (Euphorbiaceae), a medicinal plant traditionally known for dissolv... more 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 ¼ 6] received water. Group 2 [low-dose test group (LD), n ¼ 6] received 50 mg/ kg body weight (b.wt.) aqueous leaf extract orally. Group 3 [high-dose test group (HD), n ¼ 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 AE 25, 385 AE 122 and 962 AE 357 pg/ml, respectively. In the same order, progesterone values were 96 AE 24, 155 AE 45 and 320 AE 80 pg/ ml, respectively. Testosterone levels were 5210 AE 1090, 4710 AE 220 and 4500 AE 580 pg/ml, respectively. Significant differences were observed in the estrogen and progesterone levels (p ¼ 0.001). Degenerative changes were observed histologically. Cytotoxicity at 50% (CC 50 ) was 10.0 mg/ml. Discussion and conclusion: This antimalarial plant is mildly cytotoxic with male antifertility properties.

Journal of Ethnopharmacology, 2012

Moringa oleifera Lam. (order -Moringales, family -Moringaceae and genus -Moringa) is a well known... more 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 (1000 and 3000 mg/kg b.wt, respectively) per o.s. alongside negative and positive control rats (0.9% saline and 10 mg/mL N-ethyl-Nnitrosourea -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 20 mg/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 3000 mg/kg b.wt. However, intake is safe at levels ≤ 1000 mg/kg b.wt.

Journal of Ethnopharmacology, 2014

Kalanchoe intergra (Ki) leaf extract is an orally administered multipurpose plant medicine in Gha... more Kalanchoe intergra (Ki) leaf extract is an orally administered multipurpose plant medicine in Ghana and other parts of the world for the treatment of ulcers, pain and adenoma of the prostate gland. There is paucity of information concerning its short-term usage. The present study is aimed at conducting histopathological and biochemical studies in a 14-day sub-acute toxicity studies using female Sprague-Dawley rats. Crude extract of Ki leaves was prepared and freeze-dried. A 14-day sub-acute toxicity studies was conducted using 2 week old nulliparous and non-pregnant female Sprague-Dawley rats (120-150g). Reconstituted Ki was administered at a dosage of 900mgkg(-1) (high dose), 300mgkg(-1) with a control group receiving an equivalent volume of distilled water (as vehicle) by gastric lavage. Histopathological studies of major organs and blood chemistry analysis were performed on blood obtained via cardiac puncture into EDTA tubes after euthanisation. There was a significant decrease in urea (p&amp;amp;amp;amp;amp;amp;amp;lt;0.016) and creatinine levels (p&amp;amp;amp;amp;amp;amp;amp;lt;0.001) in both the high and low dose groups. There was an increase in ALP levels (P=0.01) in both the high and low dose groups. ALT and AST rather decreased significantly in both the high and low dose groups (p&amp;amp;amp;amp;amp;amp;amp;lt;0.0001). Histopathological results did not show any abnormalities in all the H&amp;amp;amp;amp;amp;amp;amp;amp;E stained paraffin sections. Thus the photomicrographs of the liver, kidney and heart were within histopathological limits. Ki leaf extract is non-toxic when administered by the oral route over a time period of 14 days at the above doses.

Bioorganic & Medicinal Chemistry Letters, 2007

Sixteen different taxoid conjugates were prepared by linking various anticancer compounds, includ... more Sixteen different taxoid conjugates were prepared by linking various anticancer compounds, including camptothecin (CPT), epipodophyllotoxin (EP), colchicine (COL), and glycyrrhetinic acid (GA), at the 2 0 -or 7-position on paclitaxel (TXL, 1) through an ester, imine, amine, or amide bond. Newly synthesized conjugates were evaluated for cytotoxic activity against replication of several human tumor cell lines. Among them, TXL-CPT conjugates, 8-10, were more potent than TXL itself against the human prostate carcinoma cell line PC-3 (ED 50 = 14.8, 3.1, 19.4 nM compared with 55.5 nM), and conjugate 10 was also 8-fold more active than TXL against the LN-CAP prostate cancer cell line. These compounds also possessed anti-angiogenesis ability as well as lower inhibitory effects against a normal cell line (MRC-5). Thus, conjugates 8-10 are possible antitumor drug candidates, particularly for prostate cancer.

KAP and parasitological surveys were conducted (in 2002, 2005 and 2007) among primary school chil... more KAP and parasitological surveys were conducted (in 2002, 2005 and 2007) among primary school children in the model site of West African Centre for International Parasite Control (WACIPAC) in Ghana. School-based health intervention was used as a means of ...