In vivo Safety Evaluation of a Nigerian Polyherbal Mixture in Female Wistar Rats.

The present study evaluates the oral safety and oral toxicity reversibility of a Nigerian Polyherbal Mixture (NPM) in female Wistar rats. In this study, acute oral toxicity was conducted on 20 female Wistar rats using the limit dose test of Up-And-Down Procedure of the OECD Acute Oral Toxicity Testing 425 guidelines at 5000 mg/kg of NPM. Additionally, 40 female Wistar rats (120-150 g) were divided into 4 groups (n=10) and orally treated with 10ml/kg of distilled water, 82 mg/kg, 410 mg/kg and 2050 mg/kg of NPM, respectively, for 90 days. Five rats from each group were sacrificed while the remaining rats in each group were kept for another 14 days for oral toxicities reversibility test. Blood samples and vital organs were obtained for biochemical, hematological and histological changes. Results showed that acute oral toxicity testing of NPM caused no death in any of the three sequentially treated rats and its estimated LD50 value was greater than 5000 mg/kg. Chronic oral treatment with 82-2050 mg/kg NPM caused significant elevations in the serum urea and creatinine and full blood count parameters (except differential WBC counts). The elevated renal function parameters were corroborated by dose-related histological changes of renal tubular congestions. also caused profound thrombocytosis and histopathological changes of pulmonary interstitial widening and gastritis. In conclusion, NPM may not be considered safe for consumption on prolonged use and at a high dose due to its profound tendencies to cause pulmonary fibrosis, nephrotoxicity, gastritis and thrombo-embolism. However, all the biochemical and hematological but histopathological alterations induced by NPM were reversed 14 days after the treatment cessation.

Acridocarpus Smeathmannii (DC.) Guill. & Perr. Root enhanced reproductive behavior and sexual function in male wistar rats: Biochemical and pharmacological mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Novel therapeutic opportunities from medicinal agents continue to arouse scientific interest in recent times. Still, there is a dearth of information as regards experimental evidence generated from medicinal plants that would yield pharmacological agents for the treatment of erectile dysfunction. Acridocarpus Smeathmannii (DC.) Guill. & Perr. Root (ASR) has a long history as an aphrodisiac in African traditional medicine. Thus, this study investigated the reproductive potentials and associated biochemical mechanisms of its hydroethanolic extract (HEASR) in male Wistar rats. Also, the bioactive compounds were identified. MATERIALS AND METHODS: Fifty-four male albino rats (180 ±â€¯20 g) were divided into nine groups of six rats/group. Control, group 1 received normal saline (10 mL/kg). Groups 2-6 rats were administered sildenafil (1.43 mg/kg/day), mesterolone (0.36 mg/kg/day), doxazocin (0.03 mg/kg/day), HEASR1 (50 mg/kg/day) and HEASR2 (200 mg/kg/day) respectively. Others received co-administration of HEASR2 with standard drugs. Treatment lasted for 28 days via oral gavage. RESULTS: An acute oral toxicity of HEASR up to 2 g/kg produced no mortality in mice p.o. while the median lethal dose was estimated to be 810 mg/kg i.p. HEASR2 administration or in combination with sildenafil, mesterolone and doxazocin increased mounting frequencies on day 28 by 77.44%, 122.65%, 148.5% and 93.88% and sperm counts by 38.29%, 55.21%, 42.48%, and 48.98% respectively in treated rats. HEASR2 + sildenafil elevated testosterone and follicle stimulating hormone levels by 36.33% and 24.55% while HEASR2 + doxazocin elevated luteinizing hormone levels by 97.44% in rats. HEASR modulated prostate-specific antigen and malondialdehyde levels respectively. Reduced glutathione, superoxide dismutase, and catalase activities were raised in five selected organs. Serum nitric oxide but not cyclooxygenase-2 or tumor necrosis factor-α levels was moderately improved in rats. CONCLUSION: Overall, the results obtained demonstrated the potential of HEASR as a male reproductive enhancer, thus justify its folklore applications. Further, octadecanoic acid ethyl ester was the most abundant bioactive component present.

Toxicological evaluation of therapeutic and supra-therapeutic doses of Cellgevity® on reproductive function and biochemical indices in Wistar rats.

BACKGROUND: The misconception about dietary supplements being safe has led many into the in-patient wards. Cellgevity® (CGV) is a Max International premiere antioxidant supplement formula used by a large population. This study evaluated the effects of therapeutic and supra-therapeutic doses of CGV on reproductive function and biochemical indices in Wistar rats. METHODS: Seventy-two Wistar rats weighing 130 ± 15.8 g were grouped into two categories (male or female) of six rats per group. Control group received distilled water (10 ml/kg). Others received therapeutic (14.3 mg/kg or 28.6 mg/kg) and supra-therapeutic CGV doses (1000, 2000 or 3000 mg/kg) body weight per oral respectively. RESULTS: After 60 days, supra-therapeutic doses of CGV reduced sperm motility (p < 0.05) by 31.8%, 31.3% and 34.5% respectively and increased (p < 0.05) abnormality in sperms by 200%, 241% and 141.3% respectively. CGV altered male (luteinizing, follicle stimulating hormones and testosterone) and female reproductive hormones (luteinizing, follicle stimulating hormones estrogen and progesterone) respectively. Therapeutic doses of CGV elevated reduced glutathione, superoxide dismutase, catalase and glutathione S-transferase, although, this was exceeded by supra-therapeutic doses and more in females than male rats. Supra-therapeutic dose (3000 mg/kg CGV) decreased body weight in both male and female rats by 50% (F(1.5, 30) = 1.2, p = 0.041) and 62.7% (F(2.1, 30) = 0.38, p = 0.038) respectively in treated rats. Supratherapeutic (3000 mg/kg) dose of CGV increased (p < 0.05) creatinine level by 99.1% while serum total protein was reduced (p < 0.05) by 60.1% (2000 mg/kg) and 57.2% (3000 mg/kg) respectively in male animals. In Female rats, supra-therapeutic doses of CGV elevated creatinine levels by 72.2% (1000 mg/kg), 60.2% (2000 mg/kg) and 124.8% (3000 mg/kg) respectively and 3000 mg/kg produces elevated serum low density lipoprotein by 34.6% in treated rats. Serum cholesterol, triglycerides, albumin, alkaline phosphatase were unaltered by CGV dosing. Histology shows seminiferous tubules with reduced spermatogenic cells. Also, female rat kidney revealed acute tubular necrosis at highest dose used in this study. CONCLUSION: Overall, these data suggest that pro-oxidant potential of the supra-therapeutic CGV doses is evident. Hence, it is necessary that its administration be done with caution using appropriate doses.

Safety evaluation of Bon-santé cleanser® polyherbal in male Wistar rats: Further investigations on androgenic and toxicological profile.

BACKGROUND: The global increase in acceptance and use of herbal remedies in recent times is still accompanied with poor knowledge of their potential adverse effects and the toxicological implications of their use are underestimated. METHODS: Bon-santé Cleanser® (BSC), a polyherbal containing Anogeissus leiocarpus, Terminalia ivorensis, Massularia acuminate and Macuna pruriens, is an "energizer and hormone booster". We assessed the effect of BSC on reproductive function after administration for 60 days in male Wistar rats. Rats (150-300 g) were assigned into four groups of 8/group. Control received distilled water (10 ml/kg) while other groups received BSC 250, 500 and 1000 mg/kg/day p.o. respectively. Animals were euthanized by cervical dislocation and samples collected for analysis. RESULTS: BSC (250 mg/kg) elevated (p < 0.05) follicle stimulating hormone and luteinizing hormone levels respectively. BSC decreased sperm motility and the live-dead ratio at 1000 mg/kg and reduced reproductive hormone at 500 mg/kg and 1000 mg/kg respectively. BSC at 500 mg/kg increased (p < 0.05, F = 3.18-13.21) testicular reduced glutathione level (50.3%) and catalase (43.7%) but not activities of superoxide dismutase, glutathione S-transferase, and malondialdehyde level. Further, BSC influenced Mg, Zn, Cu, P, Mn, Ni and Fe levels (p < 0.05). BSC (1000 mg/kg) decreased testis weight (p < 0.05) and induced mild inflammation characterized by atrophic tubules. CONCLUSION: Overall, our data suggest BSC at low doses may increase reproductive hormones regulated by FSH and LH as observed in this study. However, BSC administration should be done with caution as it may induce reproductive toxicity in large doses.

Safety evaluation of Bon-santé cleanser® polyherbal in male Wistar rats.

BACKGROUND: The potential harm of medicinal herbs has been recently observed following herbal toxicity studies after ingestion of polyherbal remedies. This was the rationale for the food and drug regulatory agency decision for thorough safety evaluation of herbal medicines. Androgenic, antipyretic, analgesic and anti-inflammatory potentials as well as chemical compositions of extracts of massularia acuminata, terminalia ivorensis, anogeissus leiocarpus and macuna pruriens respectively have been documented. Thus, Bon-santé cleanser® (BSC) is formulated from these medicinal plants with the intention to boost body hormones and energizes the body. Considering the wide usage of BSC, we investigated on its safety in male Wistar rats. METHODS: Thirty-two male Wistar rats weighing 201.9 ± 7.5 g were grouped into four treatment groups of eight per group. Group I, (control) received distilled water (10 ml/kg). Groups II-IV received 250 mg/kg, 500 mg/kg and 1000 mg/kg of BSC per oral respectively. Each group was treated for sixty days. RESULTS: Acute toxicity test, in male Wistar albino mice, showed that LD50 was 600 mg/kg via i.p. while 4 g/kg was nonlethal after oral administration in mice. Hepatic and renal biomarker enzymes were unaltered in all rats. Increased in PCV (p <0.05) was observed at 500 mg/kg. BSC modulates antioxidants biomarkers following sub-chronic administration and increased serum Na(+) (p >0.05). BSC at 1000 mg/kg caused mild inflammation of the liver and heart but not kidneys histologically. CONCLUSIONS: BSC has been found to be relatively safe in Wistar rats. Although, our findings indicate that herbal therapy with BSC should be done with caution as a mild alteration in the liver and heart architectures were observed.

A study on pharmacovigilance of herbal medicines in Lagos West Senatorial District, Nigeria.

BACKGROUND: There is an increasing use of herbal products and herbal medicines globally with the belief that herbal medicines are always 'safe' and carry no risk because they are from natural sources. However, there are concerns regarding medicinal plants and their ability to produce adverse effects. The growing herbal medicine usage has increased the need to monitor the safety of herbal medicines. Thus, the recommended approach by the World Health Organization (WHO) is to include herbal medicines in existing national pharmacovigilance systems. OBJECTIVE: This study aimed to determine the knowledge of pharmacovigilance of herbal medicines amongst herbal medicine practitioners. METHODS: The study was carried out in Lagos West Senatorial District of Lagos State, Nigeria. Three categories of practitioners (378 respondents) were engaged and they include Traditional Herbal Sellers, Natural Health Practitioners and Pharmacists. RESULTS: The results showed that herbal medicines are commonly recommended for malaria, typhoid, diabetes and fever. 281 (74.3%) of the respondents claimed that herbal medicines have no adverse effects and only 91 (24.1%) of the respondents said there were some adverse effects reported by the users. Adverse effects reported include nausea, diarrhoea and weight loss. Amongst those that received reports of adverse effects, only 19 (20.9%) documented these reported adverse effects; none of these documentations were forwarded to the regulatory bodies or national pharmacovigilance centre in Nigeria. CONCLUSIONS: These results showed inadequate adverse effects monitoring (Pharmacovigilance) amongst the practitioners and underscore the necessity to educate and enlighten herbal medicine practitioners on the need for pharmacovigilance activity of herbal products.

Traditional medicinal plants in Nigeria--remedies or risks.

ETHNO-PHARMACOLOGICAL RELEVANCE: Soil pollution due to increasing industrialization is a reality that is taking its toll on mankind today. Considering the population of people that use herbal remedies especially in developing countries and the discharge of industrial waste on surrounding herbal vegetation, it is imperative to determine the heavy metals contamination in some commonly used medicinal plants. MATERIALS AND METHODS: Representative samples of five medicinal plants Ageratum conyzoides, Aspilia africana, Alchornea cordifolia, Amaranthus brasiliensis and Chromolaena odorata were collected from Ikpoba-Okha L.G.A, Edo State Nigeria, around a paint company and another set of same plants were collected from a non-polluted source. Dried leaves and roots of collected plants were digested and analyzed using Atomic Absorption Spectrophotometer (AAS) for the presence of Lead (Pb), Cadmium (Cd), Chromium (Cr), Nickel (Ni) and Zinc (Zn). Soil samples from polluted and non-polluted areas were also analyzed to ascertain the levels of these heavy metals in the environment. RESULTS: Results show that the concentrations of these heavy metals in the leaves and roots of plants collected from polluted soil were significantly higher than those obtained from unpolluted soil. Correspondingly heavy metal concentrations were significantly higher in polluted than in unpolluted soil samples. CONCLUSION: As part of continuing effort in the standardization of traditional remedies, environmental contamination control and abatement is evident. The source of medicinal plants/herbs should also be a cause for concern since the toxicity of medicinal plants is sometimes associated with environmental sources of the plants.

Antidiarrhoeal activity of DAS-77 (a herbal preparation).

BACKGROUND: DAS-77 is a traditional herbal preparation composed of the young callous bark of mango (Mangifera indica Linn., Anacardiaceae) and the dried root of pawpaw (Carica papaya Linn., Caricaceae). This phytomedicine is claimed to have beneficial effects in the treatment of gastrointestinal disorders, including diarrhoea. OBJECTIVE: To investigate the antidiarrhoeal effect of DAS-77 using standard pharmacological models. METHODS: Normal and castor oil-induced intestinal transit, and castor oil-induced diarrhoea tests wore carried out in mice while intestinal fluid accumulation and gastric emptying tests were carried out in rats. Acute toxicity test and preliminary phytochemical analysis were also conducted. RESULTS: The results obtained in this study revealed that DAS-77 had no significant inhibitory effect on normal intestinal transit, castor oil-induced diarrhoea, intestinal fluid accumulation and gastric emptying. However, the inhibitory effect of DAS-77 was significant (p<0.001) relative to control in the castor oil-induced intestinal transit test. Peak effect was produced at the dose of 100 mg/kg (p.o.). The effect of DAS-77 in this respect was reversed by pilocarpine and propranolol, but not by phenoxybenzamine. DAS-77 did not produce any mortality given p.o. up to 10 g/kg, indicating the relative safety of the preparation. The i.p. LD50 was estimated to be 1122 mg/kg. The remedy was found to contain saponins, tannins, phenols and alkaloids. CONCLUSION: Findings in this study suggest that DAS-77 possesses antidiarrhoeal activity due to the inhibition of intestinal motility possibly mediated by muscarinic and alpha adrenergic receptors.

The use of artemisinin-based combination therapies (ACTs) in public secondary health facilities in Lagos, Nigeria.

OBJECTIVES: The objectives of the study were to assess the prescription pattern of Artemisinin Combination Therapies (ACTs) in uncomplicated malaria and the knowledge, attitude and practice of physicians as regards use of ACTs in the outpatient clinics of public secondary health facilities in Lagos State. PATIENTS AND METHODS: All the ten General Hospitals under the Lagos State Health Management Board were studied and classified as either rural or urban. 1878 retrospective antimalarial prescriptions of outpatients between March, 2005--March, 2006 were systematically sampled and questionnaires were distributed to prescribers in April--May, 2006. Prescription assessment was based on the recent Nigerian National Antimalarial Treatment Policy and WHO/INRUD drug use indicators. RESULTS: The percentage of prescriptions containing ACTs was found to be rather small (5.9%) inspite of the high proportion (59.2%) of prescribers who were favourably disposed to the National antimalarial policy change from Chloroquine to ACTs as first line. There was no statistically significant difference in frequency of ACTs prescription between the rural and urban health facilities. The prescription of Artemisinin derivatives as monotherapy was 18.2%. The prescription of Chloroquine was found to be more predominant, (48.8%) in all the health facilities. CONCLUSION: Despite the national policy change from Chloroquine to (ACTs) as the first line antimalarial, their use in the public secondary health facilities in Lagos State does not reflect this policy change and it appears that Chloroquine still remains the choice antimalarial drug.