Modulation of Penile Erection in Rabbits by Mondia Whitei: Possible Mechanism of Action

Mondia whitei root was evaluated to validate its anecdotal use and determine its possible mode of action in the management of erectile dysfunction. Rabbits were administered with daily oral doses of 100–400 mg kg⁻¹ crude ethanolic extract of M. whitei and sildenafil (50 mg kg⁻¹) as positive control for 6 weeks. Cavernosal tissue NOS activity and levels of NO and cGMP, and NOS and PDE protein expressions were investigated. The effect of the crude extract, chloroform and petroleum ether fractions in vitro on cavernosal tissue NOS activity and levels of NO and cGMP at 0.01 and 0.10 mg g⁻¹ tissue were also investigated. Results indicate that the crude extract increased NOS activity by 7% at 200 mg kg⁻¹ with corresponding increases in NO (88%) and cGMP (480%) levels. No significant changes in these measurements were observed with the 100 and 400 mg kg⁻¹ doses whilst sildenafil slightly reduced them (15.9–37.5%). NOS and PDE protein expressions in test animals were not different from controls. Pre-incubation of cavernosal tissue in vitro with the crude extract of M. whitei and its chloroform fraction markedly increased NOS activity (26–132%) and levels of NO (25%) and cGMP (50–400%) at 0.01 mg g⁻¹ tissue but these were reduced to near control levels when their concentrations were increased to 0.10 mg g⁻¹ tissue whilst the petroleum ether fraction had no effect. These findings suggest that M. whitei may influence erectile function through activation/stimulation of NOS with corresponding increases in tissue NO and cGMP levels and that certain chemical constituents present in the chloroform fraction may be responsible for biological activity.     

Absence of Organ Specific Toxicity in Rats Treated with Tonica, an Aqueous Herbal Haematinic Preparation

The sub-chronic toxicity of Tonica, an aqueous herbal haematinic prepared from the stem barks of Khaya senegalensis, Mitragyna stipulosa and Kigelia africana, was investigated in male Sprague-Dawley rats at 28, 280 and 560 mg kg⁻¹ day⁻¹, representing the normal human dose, 10x and 20x that dose, respectively for 6 weeks. The growth rate of animals over the period of treatment and certain serum biochemical and haematological indices as well as urinalysis and weight of selected organs at termination, were determined. Results show that the extract did not affect the weight gain of the animals with time or the mean wet weights of selected organs. Although there were slight but insignificant (p>0.05) elevations in WBC (16–27%) and PLT (8–11%) counts in Tonica-treated animals compared to controls at 10x and 20x the normal dose, most serum biochemical, haematological and urinalysis data indicated no significant differences (p>0.05) between tests and control rats. There were also no changes in the morphology of liver, kidney, lung and heart tissues as a result of Tonica treatment. These findings suggest that Tonica is safe at the dosage regimens administered to the animals in this study, and there appears to be no overt organ specific toxicity associated with it.     

Qualitative Phytochemical Screening and In Vitro Antimicrobial Effects of Methanol Stem Bark Extract of Ficus Thonningii (Moraceae)

The methanolic stem bark extract of Ficus thonningii (Moraceae) was subjected to preliminary phytochemical screening and in vitro antimicrobial tests. The phytochemical tests was carried out using standard methods of analysis and these investigations revealed the presence of alkaloids, anthraquinones, carbohydrates, flavonoids, saponins and tannins. The antimicrobial activity of the plant extract was assayed using the agar plate disc diffusion and nutrient broth dilution techniques. Test micro organisms were: Escherichia coli, Klebsiella spp, Pseudomonas aeruginosa, Salmonella typhi (Gram-negative), Staphylococcus aureus and Streptococcus spp. (Gram-positive). The extracts inhibited the growth of all the test organisms at different concentrations especially against Pseudomonas aeruginosa and Streptococcus spp. which had mean inhibition zone of 33.33±7.33 mm and 32.33±2.51 mm respectively. The results showed the MIC of 10 mg ml⁻¹ against pseudomonas and 1.25 against remaining organisms tested. The MBC against Staphylococcus aureus was 2.5 mg ml⁻¹ and that of Streptococcus spp. was found to be 0.625mg ml⁻¹. The extracts showed varied inhibitory activity against the organisms studied.     

Protective Effects of Annona Muricata Linn. (Annonaceae) Leaf Aqueous Extract on Serum Lipid Profiles and Oxidative Stress in Hepatocytes of Streptozotocin-Treated Diabetic Rats

Extracts from various morphological parts of Annona muricata Linn. (Annonaceae) are widely used medicinally in many parts of the world for the management, control and/or treatment of a plethora of human ailments, including diabetes mellitus (DM). The present study was undertaken to investigate the possible protective effects of A. muricata leaf aqueous extract (AME) in rat experimental paradigms of DM. The animals used were broadly divided into four (A, B, C and D) experimental groups. Group A rats served as ‘control’ animals and received distilled water in quantities equivalent to the administered volumes of AME and reference drugs'' solutions intraperitoneally. Diabetes mellitus was induced in Groups B and C rats by intraperitoneal injections of streptozotocin (STZ, 70 mg kg⁻¹). Group C rats were additionally treated with AME (100 mg kg⁻¹ day⁻¹, p.o.) as from day 3 post STZ injection, for four consecutive weeks. Group D rats received AME (100 mg kg⁻¹ day⁻¹ p.o.) only for four weeks. Post-euthanization, hepatic tissues were excised and processed biochemically for antioxidant enzymes and lipid profiles, such as catalase (CAT), reactive oxygen species (ROS), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), thiobarbituric acid reactive substances (TBARS), triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL), respectively. Treatment of Groups B and C rats with STZ (70 mg kg⁻¹ i. p.) resulted in hyperglycaemia, hypoinsulinaemia, and increased TBARS, ROS, TC, TG and LDL levels. STZ treatment also significantly decreased (p<0.05) CAT, GSH, SOD, GSH-Px activities, and HDL levels. AME-treated Groups C and D rats showed significant decrease (p<0.05) in elevated blood glucose, ROS, TBARS, TC, TG and LDL. Furthermore, AME treatment significantly increased (p<0.05) antioxidant enzymes'' activities, as well as serum insulin levels. The findings of this laboratory animal study suggest that A. muricata extract has a protective, beneficial effect on hepatic tissues subjected to STZ-induced oxidative stress, possibly by decreasing lipid peroxidation and indirectly enhancing production of insulin and endogenous antioxidants.     

Enhanced antimalarial effects of chloroquine by aqueous Vernonia amygdalina leaf extract in mice infected with chloroquine resistant and sensitive Plasmodium berghei strains

Background

The emergence and spread of Plasmodium falciparum with resistance to chloroquine (CQ), the safest and cheapest antimalarial drug coupled with the increasing cost of alternative drugs especially in developing countries have necessitated the need to optimize antimalarial actions of plant extracts and restore chloroquine efficacy.

Objective

The present study determines the ability of Vernonia amygdalina leaf extract to enhance the prophylactic and therapeutic efficacy of chloroquine against Plasmodium berghei malaria in mice.

Methods

Chloroquine sensitive (P. berghei^S) and resistant (P.berghei^R) ANKA clones of Plasmodium berghei maintained by serial passage in mice were used to develop respective experimental rodent malaria models based on intraperitoneal injection of 10⁶ parasitize erythrocyte suspension in PBS (pH 7.2) and subsequent development of parasitaemia. These models were then used to investigate the prophylactic enhancement of chloroquine (CQ) at 5 mg/kg via combination with selected doses (31.25, 62.5, 125mg/kbw) of Vernonia amygdalina leaf extracts using a 4-day suppression test. Effect of these combinations on the therapeutic efficacy of CQ at 30mg/kg over 3 days were evaluated. Treatment outcomes including parasite clearance (PCT) and rescrudescent time (RT) were compared with CQ-chlorpheniramine combination. The acute toxicity of the extract-CQ combinations was also determined enzymatically.

Results

Prophylatically, chloroquine (5mg/kg) in combination with vernonia extracts achieved a dose-dependent (57.2–72.7%) suppression of parasitaemia due to CQ sensitive and resistant P berghei strains in the experimental animals. Therapeutically, chloroquine (30mg/kg for 3 days) combined with vernonia to dose-dependently shorten the parasite clearance times (2.6–4.4 vs. 4.8 days; P < 0.05 for CQ-V62.5/125 combination), prolong the recrudescent times (8.9–18.9 vs. 7.2 days; P < 0.05) and improve day 14 cure rate (66.7–100 vs. 58.3%) in the treated P. berghei^S infected mice compared to CQ monotherapy. Whereas CQ monotherapy failed, resolution of parasitaemia due to the CQ resistant parasite with day 14 cure rates of 25 – 100% were also observed with these combinations. In therapeutic terms, the potencies of CQ-V125 combination were comparable to those of CQ-chlorpheniramine (0.25mg/kg, 12hourly, 7 days) in the infected animals. Toxicity testing indicates that these combinations elicited mild to - moderate increases in the liver enzymes measured when administered orally to mice for 7 days.

Conclusion

This study indicates that Vernonia amygdalina leaf extract dose - dependently restore the efficacy of CQ against CQ resistance P. berghei malaria in mice.     

Association of FGFR2 gene polymorphisms with the risk of breast cancer in population of West Siberia

Polymorphisms within intron 2 of the FGFR2 gene have been associated with increased risk of breast cancer (BC) in European and Asian populations. The study by Easton et al reported two FGFR2 SNPs, rs2981582 and rs7895676, to be among those most strongly associated with BC risk. Statistical modeling suggested that rs7895676 was the variant responsible for the association observed in the region. In this work, we studied the association between seven FGFR2 SNPs, including rs2981582 and rs7895676, and BC risk in the Russian population of 766 case and 665 control women from Siberia, Russian Federation. In our population, allelic frequencies and the magnitude of linkage disequilibrium (LD) were different from those observed in European and Asian populations. The following three SNPs were significantly associated with BC in our study: rs7895676[C] (odds ratio (OR)=1.28 (1.12–1.43), P=1.7 × 10⁻³), rs2981582[T] (OR=1.46 (1.30–1.62), P=2 × 10⁻⁶) and rs3135718[G] (OR=1.43 (1.27–1.58), P=6 × 10⁻⁶). The latter two SNPs were in strong (r²=0.95) LD in our sample. Maximum likelihood analysis showed that the model, including rs7895676, only explains that the association is significantly (P<0.001) worse than any of the models, including either rs2981582 or rs3135718. Thus, in addition to the confirmation of association of FGFR2 with the BC risk in this new population, our study has suggested that rs7895676 is not likely to represent the causative variant.     

Specific association of a CLEC16A/KIAA0350 polymorphism with NOD2/CARD15? Crohn's disease patients

Independent genome-wide association studies highlighted the function of CLEC16A/KIAA0350 polymorphisms modifying the risk to either multiple sclerosis (rs6498169) or type 1 diabetes (rs2903692). This C-type lectin gene maps to a linkage disequilibrium block at 16p13 and a functional role of this gene could be envisaged for other immune-related conditions, such as inflammatory bowel disease (IBD). The present study, aimed at investigating the association of those two polymorphisms with IBD, included 720 IBD patients and 550 ethnically matched healthy controls. The effect of rs2903692 previously described in diabetes was observed specifically for Crohn''s disease (CD) patients lacking the main susceptibility factor described to date, that is, three polymorphisms within another pattern recognition gene, NOD2/CARD15 (NOD2⁻ vs NOD2⁺ CD patients, G vs A: P=0.008; OR (95% CI)=1.54 (1.10–2.15); NOD2⁻ CD patients vs controls: P=0.008; OR (95% CI)=1.37 (1.08–1.73)). Replication of these findings was performed in independent Spanish cohorts of 544 IBD patients and 340 controls and the combined data yielded significant differences (405 NOD2⁻ vs 204 NOD2⁺ CD patients, G vs A: P=0.0012; OR_M-H (95% CI)=1.49 (1.17–1.90); NOD2⁻ CD patients vs controls: P=0.0007; OR_M-H (95% CI)=1.35 (1.13–1.60)). The pooled analysis of the ulcerative colitis patients vs controls also yielded a significant risk (P=0.0005; OR (95% CI)=1.52 (1.19–1.93)). These data would suggest that microbial recognition through different pathways seems to converge in the development of these polygenic bowel diseases.     

Acute Toxicity and Vascular Properties of Seed of Parkia Biglobosa (JACQ) R. Br Gift (Mimosaceae) on Rat Aorta

The authors report here the results of study on Parkia biglobosa seeds used in Burkina Faso for arterial hypertension treatment. Investigations were done on acute toxicity and vascular properties of fermented and roasted seeds. Acute toxicity test using mice, revealed by the intraperitoneal route a lethal dose 50 (LD₅₀) of 1800 mg/kg and 1600 mg/kg of body weight for aqueous extract from roasted and fermented seeds respectively. According to the scale of Hodge and Sterner and that of the World Health Organization, such drugs would be classified lightly toxic. Oral administration (up to 3000 mg/kg) did not induce any death of animal. For the vascular properties, the effects of these products were tested on the aorta isolated from rats. The cumulative administration of extract from roasted and fermented seeds (0.1–10 mg/mL) in an organ bath induced a concentration-dependent relaxation of the aorta pre contracted by phenylephrine, with or without functional endothelium. The extracts (10 mg/mL) inhibited for 100% the contraction induced by phenylephrine. The EC₅₀ values in presence and absence of endothelium were respectively of 5.37 ± 0.12 and 4.19 ± 1.02 mg/mL for fermented seeds; for roasted seeds these values were respectively, 5.39 ± 1.12 and 5.93 ± 0.95 mg/mL. Nevertheless, low concentration of roasted seeds (1–4 mg/mL) induced endothelium-dependent relaxation and this effect was inhibited by indomethacin (10⁻⁵M), and not by L-NAME (310⁻⁴M). These experimental results revealed a vasorelaxant effect of P. biglobosa seeds. P. biglobosa seems to act directly on the smooth muscle and via endothelium involving the generation of vasodilatating prostaglandins. This vasodilator effect would be in favor of an anti hypertensive property of P. biglobosa seeds.     

Gynura procumbens Merr. decreases blood pressure in rats by vasodilatation via inhibition of calcium channels

INTRODUCTION:

Gynura procumbens has been shown to decrease blood pressure via inhibition of the angiotensin‐converting enzyme. However, other mechanisms that may contribute to the hypotensive effect have not been studied.

OBJECTIVES:

To investigate the cardiovascular effects of a butanolic fraction of Gynura procumbens in rats.

METHODS:

Anaesthetized rats were given intravenous bolus injections of butanolic fraction at doses of 2.5–20 mg/kg in vivo. The effect of butanolic fraction on vascular reactivity was recorded in isolated rat aortic rings in vitro.

RESULTS:

Intravenous administrations of butanolic fraction elicited significant (p<0.001) and dose‐dependent decreases in the mean arterial pressure. However, a significant (p<0.05) decrease in the heart rate was observed only at the higher doses (10 and 20 mg/kg). In isolated preparations of rat aortic rings, phenylephrine (1×10^‐6 M)‐ or potassium chloride (8×10^‐2 M)‐precontracted endothelium‐intact and ‐denuded tissue; butanolic fraction (1×10^‐6–1×10^‐1 g/ml) induced similar concentration‐dependent relaxation of the vessels. In the presence of 2.5×10^‐3 and 5.0×10^‐3 g/ml butanolic fraction, the contractions induced by phenylephrine (1×10^‐9–3×10^‐5 M) and potassium chloride (1×10^‐2–8×10^‐2 M) were significantly antagonized. The calcium‐induced vasocontractions (1×10^‐4–1×10^‐2 M) were antagonized by butanolic fraction concentration‐dependently in calcium‐free and high potassium (6×10^‐2 M) medium, as well as in calcium‐ and potassium‐free medium containing 1×10^‐6 M phenylephrine. However, the contractions induced by noradrenaline (1×10^‐6 M) and caffeine (4.5×10^‐2 M) were not affected by butanolic fraction.

CONCLUSION:

Butanolic fraction contains putative hypotensive compounds that appear to inhibit calcium influx via receptor‐operated and/or voltage‐dependent calcium channels to cause vasodilation and a consequent fall in blood pressure.     

Hypoglycemic Effect of Treculia Africana Decne Root Bark in Normal and Alloxan-Induced Diabetic Rats

The solvent partitioned purified fractions of the hydro-acetone root bark extract of the African breadfruit (Treculia africana Decne) were evaluated for hypoglycemic activities in normal and diabetic albino rats. Fasting blood glucose levels were estimated by the use of a glucometer at pre-determined intervals after oral administration of the test extracts/fractions. Results revealed that the test fractions have only a slight effect on blood sugar level of normal rats. On short term and chronic administration in diabetic rats however, diethyl ether-soluble (DEF) and the water-soluble (WSF) fractions significantly reduced the fasting blood sugar levels (p<0.05) at differing rates when compared with the control group of animals. The diethyl ether soluble fraction (10 mg kg⁻¹ dose level) was found to exhibit the highest activity giving 69.4% reduction in blood sugar level (at 240 hours) which was in comparable range with the reference standard glibenclamide (0.5 mg kg⁻¹) which reduced blood sugar levels by 65.8% below the initial baseline values.     

Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia

Genome-wide association studies followed by replication provide a powerful approach to map genetic risk factors for asthma. We sought to search for new variants associated with asthma and attempt to replicate the association with four loci reported previously (ORMDL3, PDE4D, DENND1B and IL1RL1). Genome-wide association analyses of individual single nucleotide polymorphisms (SNPs), rare copy number variants (CNVs) and overall CNV burden were carried out in 986 asthma cases and 1846 asthma-free controls from Australia. The most-associated locus in the SNP analysis was ORMDL3 (rs6503525, P=4.8 × 10⁻⁷). Five other loci were associated with P<10⁻⁵, most notably the chemokine CXC motif ligand 14 (CXCL14) gene (rs31263, P=7.8 × 10⁻⁶). We found no evidence for association with the specific risk variants reported recently for PDE4D, DENND1B and ILR1L1. However, a variant in IL1RL1 that is in low linkage disequilibrium with that reported previously was associated with asthma risk after accounting for all variants tested (rs10197862, gene wide P=0.01). This association replicated convincingly in an independent cohort (P=2.4 × 10⁻⁴). A 300-kb deletion on chromosome 17q21 was associated with asthma risk, but this did not reach experiment-wide significance. Asthma cases and controls had comparable CNV rates, length and number of genes affected by deletions or duplications. In conclusion, we confirm the association between asthma risk and variants in ORMDL3 and identify a novel risk variant in IL1RL1. Follow-up of the 17q21 deletion in larger cohorts is warranted.     

No association of PTGDR -441C/T polymorphism with asthma in a North Indian population

Background: Asthma is the most prevalent disease in India according to the national survey conducted by NFHS 2 in 1998–399. Prostaglandin D2 (PGD2) is a bronchoconstriction inducing metabolite of arachidonic acid in the mast cells, which is produced on exposure to allergens and acts as a ligand for the Prostaglandin D2 Receptor (PTGDR). Polymorphisms in the PTGDR gene have been suggested to be involved in the mechanism of asthma. Objective: This is the first study conducted in India, investigating the role of PTGDR −441C/T promoter polymorphism in asthma pathogenesis. Methods: A case-control study was performed with a total of 992 subjects, including 410 adult asthmatics and 582 healthy controls from regions of North India. The PTGDR−441C/T polymorphism was genotyped by Tetra-Primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-Primer ARMS PCR). Results: Statistical analysis of the results between asthma cases and controls for the PTGDR −441C/T polymorphism showed Chi² (χ²) = 0.29, OR = 0.95, 95% CI (0.70–1.15) and p = 0.599. Neither the genotypic nor the allelic frequencies observed for the PTGDR −441C/T polymorphism, were significantly associated with asthma or asthma phenotypes. Conclusions: The PTGDR −441C/T polymorphism is not associated with asthma or its phenotypes in the studied North Indian population.     

Spasmogenic effect of the Aqueous Extract of Tamarindus Indica L. (Caesalpiniaceae) on the Contractile Activity of Guinea-Pig Taenia Coli

The effect of aqueous extract of Tamarindus indica (AETI) was studied on the guinea pig taenia coli, due to its use for treatment of constipation in traditional medicines. AETI, at concentrations ranging from 10⁻⁸ mg/ml to 10⁻² mg/ml, increased the spontaneous contractile activity of guinea pig taenia coli in a dose-dependent manner (EC50= 4×10⁻⁶ mg/ml). This activity was unaffected by atropine. In high K⁺, Ca²⁺-free solution containing EDTA, AETI as well as acetylcholine, used as a control, induced tonic contraction. These results suggest that the plant extract exert a spasmogenic effect that would not involve cholinergic mechanism of action. However, these active principles could mobilize both extra cellular calcium and intracellular calcium from internal stores.     

Role of Wormwood (Artemisia Absinthium) Extract on Oxidative Stress in Ameliorating Lead Induced Haematotoxicity

Effects of ROS generation have been postulated to be major contributors to lead-exposure related disease. The aim of the study was to investigate the effect of aqueous extract of wormwood (Artemisia absinthium) on oxidative stress in rats protractedly exposed to lead. Aqueous extract of wormwood plant was administered orally (200 mg.kg⁻¹ body weight). Plasma vitamin C, E and non-protein thiol concentrations, red blood cells (RBC) thiobarbituric acid reactive substances, reduced glutathione levels and haemolysis test were evaluated. In addition, RBC antioxidant enzymes activities such as superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase were also estimated. After 11-weeks, significant decreases of plasma vitamin C, E, non protein-thiol (NP-SH) and RBC-reduced glutathione levels were observed in Pb compared to control group (−32.9%, −57.1%, −53.1%, −33.9%, respectively); superoxide dismutase, glutathione peroxidase, uric aminolevulinic acid and haemolysis test significantly increased in Pb compared to control group (+64.3%, +40.3%, +145%, +44.3%, respectively). In our investigation, after 4-weeks of treatment all treated groups did not show any difference compared to the control group, except for glutathione peroxidase and RBC-superoxide dismutase activity (−15.7% and +16.4%, respectively). The findings of this study suggest that wormwood (Artemisia absinthium) extract restored the enzymes activities perturbed by exposure to lead, and had a protective role against lipid peroxidation     

Antibacterial and Anti-Biofilm Activity of Flavonoids and Triterpenes Isolated from the Extracts of Ficus Sansibarica Warb. Subsp. Sansibarica (Moraceae) Extracts

Background

Ficus species are used in African traditional medicine in the treatment of a wide variety of ailments and diseases such as convulsive disorder, wound healing, gonorrhea, tuberculosis, diabetes, diarrhoeal infections, dysentery, malaria and HIV. The aim of this study was to isolate the phytochemical constituents in the plant and test them for their antibacterial activity.

Materials and methods

The fruits, leaves and stem bark were extracted with organic solvents and the compounds in the extracts separated and purified by column chromatography before being identified by NMR spectroscopy and by comparison of the NMR data against values reported in the literature. The antibacterial activity of the pure compounds and extracts were tested using the disk diffusion method.

Results

Three triterpenes and three flavonoids: lupeol acetate (1); cycloart-23-ene-3,25-diol (2); β-sitosterol (3); 5,7,4′-trihydroxyflavan-3-ol (4); epicatechin (5); and isovitexin (6) were isolated in this study. Antimicrobial activity was observed at 8 mg mL⁻¹ for Staphylococcus aureus ATCC 29213 with four of the six isolated compounds, with no activity being observed at 1 – 4 mg mL⁻¹ against Escherichia coli ATCC 25922, E. coli ATCC 35218 and S. aureus ATCC 43300. Epicatechin (5) was found to decrease adhesion of E. coli ATCC 25922 and S. aureus ATCC 29213. Decreased adhesion of S. aureus ATCC 29213 was also observed with 5,7,4′-trihydroxyflavan-3-ol (4) and isovitexin (6).

Conclusions

The results of this study provide baseline information on F. sansibarica''s potential validity in the treatment of infections associated with Gram-positive microorganisms.     

Analgesic and Antipyretic Activities of Drymaria Cordata (Linn.) Willd (Caryophyllaceae) Extract

Drymaria cordata (Linn.) Willd (Caryophyllaceae) is an herbaceous plant widely used in traditional African medicine (TAM) for the treatment of diverse ailments including painful and febrile conditions. This study was conducted to investigate the analgesic and antipyretic properties of the whole plant extract of D. cordata. The acetic acid-induced writhing, formalin, and tail clip tests were used to evaluate analgesic activity while the 2,4-dinitrophenol (DNP)-, d-amphetamine-, and yeast-induced hyperthermia tests were used to investigate antipyretic activity in rodents. D. cordata (100, 200, and 400 mg kg⁻¹, p.o) produced significant (p<0.05) analgesic activity in the mouse writhing, formalin (second phase), and tail clip tests. The effects of D. cordata were generally comparable to those of acetylsalicylic acid (ASA, 100 mg kg⁻¹, p.o) and morphine (2 mg kg⁻¹, s.c). Also, D. cordata produced significant (p<0.05) dose-dependent inhibition of temperature elevation in the 2,4-DNP and yeast-induced hyperthermia models with peak effects produced at the dose of 400 mg kg⁻¹. The effect at this dose was comparable to that of ASA in the two models. In the d-amphetamine method, D. cordata produced significant (p<0.05) dose- and time-dependent reduction of temperature elevation with peak effect produced at the dose of 200 mg kg⁻¹. The effect of the extract at this dose was greater than that of ASA. The results obtained in this study demonstrate that the aqueous whole plant extract of Drymaria cordata possesses analgesic and antipyretic properties mediated through peripheral and central mechanisms.     

Anti-Inflammatory and Antioxidant Effects of an Ethanolic Extract of the Aerial Parts of Hilleria Latifolia (Lam.) H. Walt. (Phytolaccaceae)

Various parts of the perennial herb Hilleria latifolia (Lam.) H. Walt. (Family: Phytolaccaceae) are used in Ghanaian traditional medicine for the treatment of several inflammatory-related disorders. The present study examined the anti-inflammatory effect of an ethanolic extract of the aerial parts of Hilleria latifolia (HLE) in acute and chronic inflammation models. Since free radicals and reactive oxygen species are implicated in inflammatory diseases, the antioxidant potential of HLE was also investigated in in vitro experimental models. HLE (10–300 mg kg⁻¹, p.o.), either preemptively or curatively, significantly inhibited carrageenan-induced foot oedema in 7-day old chicks. Similarly, the NSAID diclofenac (10–100 mg kg⁻¹, i.p.) and the steroidal anti-inflammatory agent dexamethasone (0.3–3 mg kg⁻¹, i.p.) dose-dependently reduced the oedema in both pre-emptive and curative treatments. In the Freund''s adjuvant induced-arthritis model in rats, HLE as well as the positive controls, dexamethasone and methotrexate, showed significant anti-arthritic properties when applied to established adjuvant arthritis. HLE (10–300 mg kg⁻¹, p.o.) significantly reduced oedema in the ipsilateral paw of rats but failed to prevent systemic arthritic spread. The DMARD methotrexate (0.1–1 mg kg⁻¹, i.p.) and dexamethasone (0.3–3 mg kg⁻¹, i.p.) reduced significantly the total polyarthritic oedema as well as the spread of the arthritis from the ipsilateral to the contralateral paws of the treated animals. The extract (0.03–1.00 mg ml⁻¹) exhibited Fe³⁺ reducing activity, scavenged DPPH and prevented lipid peroxidation. These findings suggest that the extract exerts in vivo anti-inflammatory activity after oral administration and also has antioxidant properties which may contribute to its activity.     

Acute Effects of Aqueous Leaf Extract of Aspilia Africana C.D. Adams on Some Haematological Parameters in Rats

Several medicinal plants have been documented for their haematological effects either at low or high concentration but very little is known about Aspilia africana. The aim of the study was to investigate the acute effects of aqueous leaf extract of Aspilia africana at different concentrations on some haematological parameters in rats. Following 14 days of oral administration of aqueous extract of A. africana, Haematocrit (HCT), Haemoglobin concentration (HB), Mean Cell Haemoglobin Concentration (MCHC), Red Blood Cell Count (RBC Count), Total White Blood Cell Count (Total WBC Count), Absolute Neutrophils count (NEUT#), Absolute Lymphocytes count (LYM#), Absolute Eosinophils Count (EOSIN#) and Absolute Monocytes (MONO#) were evaluated in twenty (20) male Wistar albino rats. The rats weighed 174±20g, and were randomly assigned into 4 groups viz: Group 1, Control; Group 2, 250mg/Kg/d aqueous extract; Group 3, 500mg/Kg/d aqueous extract; and Group 4, 750mg/Kg/d aqueous extract. HCT, HB, MCHC, RBC Count, Total WBC Count, NEUT#, LYM#, EOSIN# and MONO# were significantly increased (P<0.001) in 500mg/Kg/d of A. africana extract (61.13±1.65%, 13.5±1.29g/dl, 23.33±0.0.02g/dl, 3.68±0.02 X 10¹²Cells/l, 2.33±0.02 X 10⁹Cells/l, 1.32±0.04 X 10⁹Cells/l, 1.43±0.05 X 10⁹Cells/l, 0.47±0.02 X 10⁹Cells/l and 0.47±0.04 X 10⁹Cells/l, respectively) when compared to the Control (51.13±0.85%, 9.56±0.43g/dl, 19.22±0.19g/dl, 2.69±0.01 X 10¹²Cells/l, 1.79±0.01 X 10⁹Cells/l, 0.80±0.00 X 10⁹Cells/l, 0.83±0.00 X 10⁹Cells/l, 0.18±0.00 X 10⁹Cells/l and 0.24±0.00 X 10⁹Cells/l, respectively) which received no extract at all. The 500mg/Kg of A. africana extract proved to be the most effective, while the 750mg/Kg proved to be the least effective in comparison with the control. The results of this study further strengthened the earlier works on the medicinal benefits of Aspilia africana and its virtue as a good pharmacological source of haematopoiesis.     

Methionine synthase A2756G polymorphism and cancer risk: a meta-analysis

Polymorphisms in methionine synthase (MTR) gene may be involved in carcinogenesis by affecting DNA methylation. However, association studies on MTR A2756G polymorphism in cancers have reported conflicting results. Therefore we performed a meta-analysis to better assess the associations. A total of 24 896 cancer patients and 33 862 controls from 52 articles for MTR A2756G were investigated. Overall, individuals carrying MTR 2756GG genotype had a subtly reduced cancer risk under a recessive genetic model (odds ratio (OR), 0.92; P=0.053; 95% confidence interval (95% CI), 0.84–1.00; I²=0.0% P_{heterogeneity}=0.61). In the subgroup analyses by ethnicity, 2756GG was associated with a significantly reduced cancer risk in European populations (OR, 0.83; P=0.001; 95% CI, 0.74–0.93; I²=0.0% P_{heterogeneity}=0.99). However, in Asian populations, a significantly elevated association between 2756GG genotype and cancer risk was observed (OR, 1.33; P=0.012; 95% CI, 1.06–1.65; I²=0.0% P_{heterogeneity}=0.50). In studies stratified by tumor site, there was a significantly reduced risk of acute lymphoblastic leukemia (ALL) (OR, 0.54; P=0.049; 95% CI, 0.29–1.00; I²=10.7% P_{heterogeneity}=0.33) and colorectal cancer (OR, 0.63; P=0.004; 95% CI, 0.47–0.87; I²=0.0% P_{heterogeneity}=0.73) in European populations. Our study indicates that MTR A2756G polymorphism is a candidate gene polymorphism for cancer susceptibility regardless of environmental factors. Large-scale, well-designed, and population-based studies are required to further investigate gene–gene and gene–environment interactions on MTR A2756G polymorphism and tissue-specific cancer risk in an ethnicity-specific population.