Supplementation of conventional anti-diabetic therapy with alpha-lipoic acid prevents early development and progression of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Current pharmacological interventions only retard DN progression. Alpha-lipoic acid (ALA) is a potent antioxidant with beneficial effect in other diabetic complications. This study investigates whether ALA supplementation prevents early development and progression of DN. METHOD: Fifty-eight male Sprague-Dawley rats were randomly assigned to healthy control and diabetic groups and subjected to overnight fasting. Type 2 diabetes mellitus (T2DM) was induced in diabetic group by intraperitoneal administration of nicotinamide (110 mg/kg) and streptozotocin (55 mg/kg). On day 3 after T2DM induction, diabetic rats received oral daily administration of ALA (60 mg/kg), gliclazide (15 mg/kg), ramipril (10 mg/kg) or drug combinations for 6 weeks. Untreated diabetic rats served as diabetic control. Blood, kidneys and pancreas were harvested for biochemical and histological analyses. RESULT: Induction of T2DM resulted in hypoinsulinemia, hyperglycemia and renal pathology. ALA supplementation maintained ß-cell function, normoinsulinemia and normoglycemia in diabetic rats, and prevented renal pathology (PAS, KIM-1, plasma creatinine, total protein, blood urea nitrogen, uric acid and urine albumin/creatinine ratio) and triglycerides level compared to diabetic control (p < 0.001). Additionally, ALA supplementation significantly prevented elevated serum and tissue malondialdehyde, collagen deposition, α-SMA expression, apoptosis and serum IL-1ß and IL-6 levels while it markedly increased renal glutathione content and plasma HDL-C compared to diabetic control group (p < 0.001). CONCLUSION: ALA supplementation prevents early development and progression of DN by exerting anti-hyperglycemic, antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic effects. Our findings provide additional option for clinical treatment of DN in T2DM patients.

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.

Immunogenicity and safety of the RTS,S/AS01 malaria vaccine co-administered with measles, rubella and yellow fever vaccines in Ghanaian children: A phase IIIb, multi-center, non-inferiority, randomized, open, controlled trial.

BACKGROUND: To optimize vaccine implementation visits for young children, it could be efficient to administer the first RTS,S/AS01 malaria vaccine dose during the Expanded Programme on Immunization (EPI) visit at 6 months of age together with Vitamin A supplementation and the third RTS,S/AS01 dose on the same day as yellow fever (YF), measles and rubella vaccines at 9 months of age. We evaluated the safety and immunogenicity of RTS,S/AS01 when co-administered with YF and combined measles-rubella (MR) vaccines. METHODS: In this phase 3b, open-label, controlled study (NCT02699099), 709 Ghanaian children were randomized (1:1:1) to receive RTS,S/AS01 at 6, 7.5 and 9 months of age, and YF and MR vaccines at 9 or 10.5 months of age (RTS,S coad and RTS,S alone groups, respectively). The third group received YF and MR vaccines at 9 months of age and will receive RTS,S/AS01 at 10.5, 11.5 and 12.5 months of age (Control group). All children received Vitamin A at 6 months of age. Non-inferiority of immune responses to the vaccine antigens was evaluated 1 month following co-administration versus RTS,S/AS01 or EPI vaccines (YF and MR vaccines) alone using pre-defined non-inferiority criteria. Safety was assessed until Study month 4.5. RESULTS: Non-inferiority of antibody responses to the anti-circumsporozoite and anti-hepatitis B virus surface antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus RTS,S/AS01 alone was demonstrated. Non-inferiority of antibody responses to the measles, rubella, and YF antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus YF and MR vaccines alone was demonstrated. The safety profile of all vaccines was clinically acceptable in all groups. CONCLUSIONS: RTS,S/AS01 can be co-administered with Vitamin A at 6 months and with YF and MR vaccines at 9 months of age during EPI visits, without immune response impairment to any vaccine antigen or negative safety effect.

In Vivo Modulation of Rat Liver Microsomal Cytochrome P450 Activity by Antimalarial, Anti-HIV, and Antituberculosis Plant Medicines.

Drug interactions are key reasons for adverse drug reactions and attrition from market. Major infectious diseases causing morbidity/mortality in Ghana are malaria, tuberculosis, and HIV/AIDS. In this study, plant medicines commonly used to treat/manage these diseases in Ghana were investigated for their potential to modulate rat cytochrome P450 enzyme activities. Fluorescence and high-performance liquid chromatography-based assays were used to assess effects of antimalarial plant medicines, Fever (FEV), Mal-TF (MAL), and Kantinka terric (KT); anti-TB medicines, Chestico (CHES), CA + ST Pains + HWNT (TF), and Kantinka herbatic (KHB); and anti-HIV/AIDS medicines, Wabco (WAB), AD + T/AD (LIV) and Kantinka BA (KBA) on rat liver microsomal cytochrome P450 enzyme activities. Effects of medicines on rat biochemical and hematological parameters were also assessed. Generally, the medicines altered microsomal CYP1A1/1A2, CYP2B1/2B2, CYP2C9, and CYP2D6 activities. Only KBA elicited an increase (80%) in CYP1A1/1A2 activity. FEV, MAL, CHES, WAB, and LIV strongly inhibited the enzyme activity. All the medicines significantly inhibited CYP2C9 (24%-80%) activity. CYP2D6 activity increased after treatment with MAL, KBA, LIV, and TF. Also, MAL, WAB, LIV, KHB, and CHES increased CYP2B1/2B2 activity, while KT decrease the activity. Generally, the medicines altered liver function in the rats. Cholesterol levels declined after KBA treatment only. White and red blood cell counts, hemoglobin and hematocrit levels were significantly reduced in KT- and KBA-treated rats. Our results suggest that use of the medicines could have implications for drug interactions and safety, particularly if the medicines are administered over prolonged periods. Further investigations are imperative to establish clinical relevance of these results.

An extract of Synedrella nodiflora (L) Gaertn exhibits antidepressant properties through monoaminergic mechanisms.

Synedrella nodiflora (SNE) has been used traditionally for many neurological conditions and some of these neuroactive effects have been scientifically substantiated. The usefulness of SNE in depression has however not been investigated despite the availability of data in other disease models indicating it may be useful. The present study therefore examined the effect of SNE in acute murine models of depression and the possible mechanisms mediating its activities in these models. Preliminary qualitative phytochemical and high performance liquid chromatography (HPLC) screening were conducted on SNE. The behavioural effects of SNE (100, 300 and 1000 mg/kg) pre-treated mice were examined in the forced swimming (FST) and tail suspension (TST) tests. Behavioural events such as mobility (swimming, climbing, curling and climbing), and immobility, were scored. The possible involvement of monoamines in the effects of SNE was assessed in the TST by pre-treating mice with α-methyldopa, reserpine and para-chlorophenylalanine (pCPA) in separate experiments. Flavonoids, tannins, saponins, alkaloids, cardiac glycosides, coumarins, triterpenes, sterols, anthraquinones and phenolic compounds were present in SNE. HPLC analysis revealed the presence of two major constituents observed at retention times 42.56 and 46.51 min, with percentage composition of 45.72% and 36.88% respectively. SNE significantly reduced immobility scores in both FST and TST, suggesting antidepressant effects. The antidepressant properties of SNE were reversed by the pre-treatment of α-methyldopa, reserpine and pCPA, suggesting a possible involvement of monoamines (noradrenaline and serotonin) in its mechanism(s) of actions. SNE exhibits antidepressant effects, possibly mediated through an interplay of enhancement of noradrenergic and serotoninergic mechanisms.

Psychotropic Effects of an Alcoholic Extract from the Leaves of Albizia zygia (Leguminosae-Mimosoideae).

BACKGROUND: Albizia zygia is used in Ghanaian traditional medicine for the management of mental disorders. The present study tested the hypothesis that an extract of the leaves of Albizia zygia (AZE) may possess antipsychotic and antidepressant properties. METHOD: The novelty- and apomorphine-induced locomotor and rearing behaviours of AZE in mice were explored in an open-field observational test system. The effects of AZE in apomorphine-induced cage climbing test, extract-induced catalepsy, and haloperidol-induced catalepsy on mice were also investigated. Lastly, the forced swimming and tail suspension tests in mice were employed to screen the possible antidepressant effects of AZE. RESULTS: AZE (100-3000 mg/kg) showed signs of central nervous system (CNS) depression under observation, with no lethality, 24 h after treatment in mice. AZE (100-1000 mg/kg) produced a significant decrease in the frequency of novelty- and apomorphine-induced locomotor activities in mice. The extract also significantly decreased the frequency and duration of apomorphine-induced climbing activities in mice. AZE, while failing to produce any cataleptic event in naïve mice, significantly enhanced haloperidol-induced catalepsy at a dose of 1000 mg/kg. However, AZE did not produce any significant antidepressant effects in the test models employed. CONCLUSION: The extract of Albizia zygia exhibited an antipsychotic-like activity in mice.

Extract of Synedrella nodiflora (L) Gaertn exhibits antipsychotic properties in murine models of psychosis.

BACKGROUND: The hydro-ethanolic whole plant extract of Synedrella nodiflora (SNE) has demonstrated anticonvulsant, sedative and analgesic effects. Preliminary studies conducted in animals, SNE significantly decreased stereotypic behaviours suggesting antipsychotic potential. Coupled with the central nervous system depressant effects of SNE, we hypothesized that it may have utility in the management of psychosis. The present study therefore investigated the antipsychotic potential of the SNE in several murine models of psychosis. METHOD: The primary central nervous system activities of SNE (30-3000 mg/kg, p.o) were investigated using the Irwin's test. The novelty-induced rearing, locomotion and stereotypy counts provoked by SNE (100-1000 mg/kg, p.o) were conducted using the open-field paradigm. The antipsychotic test models used in the screening of SNE (100-1000 mg/kg, p.o) included apomorphine-induced stereotypy, rearing, locomotion and cage climbing activities. The combined effects of a low dose of SNE (100 mg/kg) with various doses of haloperidol and chlorpromazine were analysed using the apomorphine-induced cage climbing and stereotypy, respectively. The ability of SNE to cause catalepsy in naïve mice as well as its effect on haloperidol-induced catalepsy was assessed. RESULTS: SNE showed acetylcholine-like and serotonin-like activities in the Irwin test, with sedation occurring at high doses. SNE significantly reduced the frequencies of novelty- and apomorphine-induced rearing and locomotion; stereotypy behaviour and the frequency and duration of apomorphine-induced cage climbing in mice. In all the tests performed, SNE was less potent than the reference drugs used (chlorpromazine and haloperidol). In addition, SNE potentiated the effects of haloperidol and chlorpromazine on apomorphine-induced cage climbing and stereotypy activities in mice. CONCLUSION: SNE, while exhibiting antipsychotic properties itself, can also potentiate the antipsychotic effects of chlorpromazine and haloperidol.

An ethanolic extract of Desmodium adscendens exhibits antipsychotic-like activity in mice.

BACKGROUND: Desmodium adscendens extract (DAE) is used traditionally in Ghana for the management of psychosis. The present study aimed at providing pharmacological evidence for its ethnomedical use by testing the hypothesis that an ethanolic extract of Desmodium adscendens may possess antipsychotic properties. METHODS: The primary behavioral effects of DAE on the central nervous system of mice were investigated using Irwin's test paradigm. Novelty-induced and apomorphine-induced locomotor and rearing behaviors in mice were explored in an open-field observational test system. Apomorphine-induced cage climbing test in mice was used as the antipsychotic animal model. The ability of DAE to induce catalepsy and enhance haloperidol-induced catalepsy was also investigated in mice. RESULTS: The DAE produced sedation, cholinergic-, and serotonergic-like effects in mice when evaluated using the Irwin's test. No lethality was observed after 24 h post-treatment. The LD50 in mice was estimated to be greater than 3000 mg/kg. The DAE significantly decreased the frequency of novelty- and apomorphine-induced rearing and locomotor activities in mice. It also significantly lowered the frequency and duration of apomorphine-induced climbing activities in mice. It did not induce any cataleptic event in naïve mice but only significantly enhanced haloperidol-induced catalepsy at a dose of 1000 mg/kg. CONCLUSIONS: The ethanolic extract of Desmodium adscendens exhibited antipsychotic-like activities in mice. Motor side effects are only likely to develop at higher doses of the extract.

Analgesic effects of a hydro-ethanolic whole plant extract of Synedrella nodiflora (L.) Gaertn in paclitaxel-induced neuropathic pain in rats.

BACKGROUND: Synedrella nodiflora is used by traditional healers in Ghana for the management of epilepsy and pain. The hydro-ethanolic extract of the whole plant has demonstrated antinociceptive effect in various animal models of pain. This study investigated the potential benefit of the hydro-ethanolic extract in a rat model of paclitaxel-induced neuropathic pain. METHODS: Neuropathy was induced in rats by a continuous intraperitoneal administration of paclitaxel (2 mg/kg) for 5 days. Baseline latencies to thermal pain were recorded before the first injection of paclitaxel and during the 5 day induction period. Following the induction, the rats in designated treatment group were treated with the hydro-ethanolic extract (100, 300 and 1000 mg/kg, p.o) or pregabalin (10, 30 and 100 mg/kg) or vehicle (distilled water) and their responses to thermal hyperalgesia measured every 30 for a total period of 3 h. RESULTS: There was a significant difference between the baseline reaction latency and what was observed on the 5th day of the induction of neuropathy. Two days after the induction of neuropathy, the extract and pregabalin significantly and dose-dependently produced antinociceptive effect during the 3-h test period. CONCLUSION: The hydro-ethanolic extract of the whole plant of Synedrella nodiflora possess analgesic effect in paclitaxel-induced neuropathy in rats.

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.

Long-term continuous administration of a hydro-ethanolic extract of Synedrella nodiflora (L) Gaertn in male Sprague-Dawley rats: biochemical, haematological and histopathological changes.

BACKGROUND: Conflicting reports about the toxicity of Synedrella nodiflora (L) Gaertn (family Asteraceae), a plant traditionally used in Ghana for the management of epilepsy, abound in literature. The present study evaluates the effect of a 90-day continuous oral administration of a hydro-ethanolic whole plant extract of Synedrella nodiflora (SNE) in male Sprague-Dawley rats. METHODS: The toxicological evaluation of the extract (100, 300 and 1000 mgkg-1) was focused on haematological, serum biochemical parameters and histopathological changes of some isolated organs. RESULTS: The extract produced no mortality in the rats treated during the study period. Only SNE 100 mgkg-1 produced significant decrease in white blood cell and neutrophil counts and an increase in albumin, globulin, total bilirubin, total protein and potassium levels. The higher doses (SNE 300 and 1000 mgkg-1) had no significant effect on all the haematological and biochemical parameters measured. Histopathological assessment of the liver, kidney and heart revealed no abnormalities in rats treated with the extracts. Only the SNE 1000 mgkg-1 produced distortions of the branching arrangements of the myocardial fibres and a congested vessel which indicates a healed infarction. CONCLUSIONS: The findings suggest hydro-ethanolic extract of Synedrella nodiflora (L) Gaertn generally has a low toxicity profile following a 90-day continuous oral administration in male Sprague-Dawley rats under the present laboratory conditions. However patients with renal or cardiac problems should use the plant with caution. FUNDING: Jointly supported by the International Foundation for Science, Stockholm, Sweden, through a grant (# F/5191-1) to Dr. Patrick Amoateng and the Office of Research, Innovation and Development (ORID), University of Ghana, Accra, Ghana, grant awarded to Dr. Patrick Amoateng (reference number: URF/6/ILG-002/2012-2013).

A dietary strategy for the management of artemether-lumefantrine-induced cardiovascular and renal toxicity.

BACKGROUND: Unsweetened natural cocoa has antimalarial properties. Unsweetened natural cocoa powder (UNCP), obtained as a result of the removal of cocoa butter from a cocoa bean protects against malaria episodes. Cocoa powder, which is prepared after removal of the cocoa butter, contains about 1.9 % theobromine and 0.21 % caffeine. Concomitant consumption of cocoa and artemether/lumefantrine (A/L) is a common practice in Ghana, West Africa. This study seeks to determine the elemental composition of UNCP and its protective effect on the heart and kidney against (A/L) administration. METHODS: Energy dispersive x-ray fluorescence spectroscopy was used to detect the quality and quantity of the elemental composition in UNCP. Thereafter, 30 nonmalarious male guinea pigs were divided into five groups of six animals each. One group was administered with 75 mg/kg body weight A/L only and another group distilled water (control group). The rest received 300 mg/kg, 900 mg/kg and 1500 mg/kg body weight UNCP for 14 days orally and A/L for the last 3 days (ie day 11 to day 14). Biochemical and histopathological examinations were carried out after euthanisation of the animals. RESULTS: A total of thirty-eight (38) micro and macro elements were detected with the ED-XRF. Macro elements like sodium (Na), magnesium (Mg), aluminium (Al), phosphorus (P), chlorine (Cl), potassium (K), calcium (Ca), manganese (Mn) and iron (Fe) and micro elements like chromium (Cr), copper (Cu), zinc (Zn), arsenic (As), and lead (Pb) were identified and evaluated. Biochemical analysis revealed increases in HDL levels (p>0.05) while there were decreases in LDL levels (p>0.05), creatine kinase and AST levels (P<0.05) in animals that received UNCP compared to A/L only administered group. Urea levels reduced significantly by 53 % (p<0.05) in group that received 1500 mg/kg UNCP. Histopathological examinations of the heart and kidney buttressed the protective effects of cocoa administration. CONCLUSION: The percentage of recommended daily allowance of UNCP for chromium is 3750 % for men and 5250 % for women while % RDA for copper corresponds to 103.6 % in both sexes. UNCP proved to possess cardioprotective and renoprotective potential during artemether-lumefantrine administration.

Unsweetened Natural Cocoa Powder Has the Potential to Attenuate High Dose Artemether-Lumefantrine-Induced Hepatotoxicity in Non-Malarious Guinea Pigs.

Objective. This study investigated the elemental composition of unsweetened natural cocoa powder (UNCP), its effect on nitric oxide, and its hepatoprotective potential during simultaneous administration with high-dose artemether/lumefantrine (A/L). Method. Macro- and microelements in UNCP were analyzed with EDXRF spectroscopy. Thirty (30) male guinea-pigs were then divided into five groups. For groups 3 (low-dose), 4 (medium-dose), and 5 (high-dose), the animals received oral UNCP prophylactically for 14 days. Group 1 received distilled water (14 days) and group 2 A/L for the last 3 days (days 12 to 14). After euthanisation, biochemical and histopathological examinations were carried out in all groups. Results. Phytochemical analysis of UNCP showed the presence of saponins, flavonoids, tannins, and cardiac glycosides. Thirty-eight (38) macro- and microelements were found. UNCP produced significant decreases in ALT, ALP, GGT, and AST levels. A significant increase in total protein levels was observed during A/L+UNCP administration in comparison to 75 mg/kg A/L group. Histopathological examinations buttressed the protective effects of cocoa administration. UNCP administration increased nitric oxide levels 149.71% (P < 0.05) compared to controls. Conclusion. UNCP increases nitric oxide levels and has hepatoprotective potential during A/L administration. A high level of copper was observed which may be detrimental during high daily consumptions of UNCP.

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.

A hydro-ethanolic extract of Synedrella nodiflora (L.) Gaertn ameliorates hyperalgesia and allodynia in vincristine-induced neuropathic pain in rats.

BACKGROUND: The hydro-ethanolic extract of Synedrella nodiflora (L.) Gaertn whole plant has demonstrated analgesic effects in acute pain models. The extract has also demonstrated anticonvulsant effects in murine models of experimental epilepsy. The present study illustrates an evaluation of the hydro-ethanolic extract of the plant for possible analgesic properties in hyperalgesia and allodynia associated with vincristine-induced neuropathy in rats. METHODS: Neuropathic pain was induced in Sprague-Dawley rats by injecting 100 µg/kg of vincristine sulphate on alternative days for 6 days (days 0, 2, 4, 8, 10 and 12). Vincristine-induced cold allodynia, mechanical hyperalgesia and thermal hyperalgesia were measured pre-vincristine administration and on days 15, 17 and 19 post-vincristine administration. The rats were then treated with S. nodiflora extract (SNE) (100, 300 and 1000 mg/kg), pregabalin (10, 30 and 100 mg/kg) and distilled water as vehicle daily for 5 days and pain thresholds were measured on alternate days for 3 days. RESULTS: SNE and pregabalin produced analgesic properties observed as increased paw withdrawal latencies to mechanical, tactile, cold water stimuli and thermal hyperalgesic tests during the 5 days of treatment. CONCLUSIONS: The findings suggest that hydro-ethanolic extract of S. nodiflora possesses anti-hyperalgesic and anti-allodynic effects in vincristine-induced neuropathic pain in rats.

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.

Treatment of benign prostatic hyperplasia with Croton membranaceus in an experimental animal model.

ETHNOPHARMACOLOGICAL RELEVANCE: Croton membranaceus leaf extracts are used in the Bahamas to aromatize tobacco. In Nigeria it is used to improve digestion and in Ghana, the root extract is used for the treatment of benign prostatic hyperplasia (BPH). Despite claims of efficacy no data exists to support this. The aim of this study was to determine if Croton membranaceus aqueous root extract (CMARE) could attenuate the development of BPH in an animal model. MATERIALS AND METHODS: Fifty (50) adult male Sprague-Dawley rats weighing 200-250g were randomly divided into 5 groups. Group 1 served as the control and received normal saline p.o. Groups 2-5 were castrated and injected with 5mg/kg b.wt. testosterone propionate subcutaneously for 28 days. Group 2 (model group) had no further treatment. Group 3 was simultaneously given 0.5mg/kg b.wt. finasteride p.o. throughout. Groups 4 and 5 received 30mg/kg b.wt. [low dose (LD)] and 300mg/kg b.wt. [high dose (HD)] CMARE, respectively, for 28 days. Rats were sacrificed at the end of the study and all prostate organs harvested. Wet weights, volumes and prostatic index (PI) were determined. Tissues were histologically examined. Serum prostate specific antigen (PSA) and dihydrotestosterone (DHT) levels were determined. RESULTS: Prostate volume of the control group was 0.67±0.23cm(3). The model, finasteride, CMARE LD and HD groups had the following volumes: 0.92±0.12, 0.84±0.16, 0.79±0.16 and 0.80±0.19cm(3), respectively. Only the model group showed significant statistical differences with the control (p=0.007). PI for control, model, finasteride, LD and HD groups was as follows: 0.19±0.04, 0.30±0.04, 0.25±0.04, 0.21±0.05 and 0.22±0.05. No statistical differences between the control PI and the CMARE treated groups were observed. Histologically, the model group had massive growth of columnar stromal and epithelial cells. CMARE and finasteride attenuated this growth with a resultant thin layer of stromal and epithelial cells similar to the control. PSA levels were significantly lower in the treatment groups. CONCLUSION: CMARE reduces stromal and epithelial cell growth, and subsequently shrinks enlarged prostate. This is the first scientific proof validating the anecdotal evidence of CMARE efficacy in the management of BPH.

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 Croton membranaceus root extract.

AIM OF THE STUDY: Croton membranaceus root and leaf extracts are used in the Bahamas to aromatize tobacco, in Nigeria to improve digestion, and in Ghana, for benign prostate hyperplasia. Despite claims of success there is paucity of information on its toxicity. The aim of this study was to determine if Croton membranaceus has acute toxicity properties. MATERIALS AND METHODS: Roots were air-dried in a solar dryer for one week before milling. The powder was extracted with 96% ethanol, freeze-dried and re-extracted with distilled water and freeze-dried. 15 male Sprague-Dawley rats (180-200 g) were divided equally into 2 treatment groups [low dose (LD) and high dose (HD)], plus a control group (C). LD and HD received 1500 and 3000 mg/kg b.wt. Croton membranaceus aqueous extract, respectively, one time and observed for 14 days. Haematological [Full Blood Count and haemoglobin (Hb)], biochemical [bilirubin, alanine aminotransferase (ALA), aspartate aminotransferase (AST), total protein, albumin, globulin, alkaline phosphatise (ALP), γ-glutamyltranspetidase (GGT), urea, creatinine, creatinine kinase - Muscle and Brain (CK-MB), creatinine kinase - Total (CK-R)] examinations were performed. RESULTS: Control group's CK-MB (5444±534 U/L) and LD group CK-MB (4014±1016 U/L) were significantly different (p<0.05). Control and the HD group CK-MB (3955±1135 U/L) were significantly different (p<0.05). Both LD and HD CK-R levels (697±197U/L and 732±203 U/L, respectively), were lower than the control (1139±220 U/L) at 48 h and 14 days (p<0.05, p<0.05, respectively). γ-GT levels of the HD group was 4.8±0.4 U/L compared to the Control group value of 0.9±0.2 U/L (p<0.05). CONCLUSIONS: Taking all factors into consideration, Croton membranaceus ingestion does not produce general acute toxicity. However, its creatinine kinase lowering ability could be explored.