Evaluation of the toxicity potential of acute and sub-acute exposure to the aqueous root extract of Aristolochia ringens Vahl. (Aristolochiaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Aristolochia ringens Vahl. (Aristolochiaceae) is used traditionally in Nigeria for managing a number of ailments including gastrointestinal disturbances, rheumatoid arthritis, pile, insomnia, oedema, and snake bite venom. Some studies in our laboratory have demonstrated a scientific justification for some of such uses. This study aims at investigating the toxicological actions of the aqueous root extract of Aristolochia ringens (AR). MATERIALS AND METHODS: Brine shrimp lethality assay was carried out using 10, 100 and 1000 µg/ml of the extract. Oral and intraperitoneal acute toxicity tests were carried out using mice. The effect of sub-acute (30 days) repeated oral exposure to the extract at 10, 50 and 250 mg/kg in rats was also evaluated via weekly assessments of body weights and general observations as well as end of exposure haematological, biochemical and histological examinations of blood and tissue samples of treated rats. Phytochemical analyses to determine the presence of aristolochic acid I in the extract was also carried out using high performance liquid chromatography (HPLC). RESULTS: The aqueous root extract of A. ringens showed potential for biological activity and cytotoxicity with an LC50 of 175 µg/ml in brine shrimps. AR was found to be relatively safe on acute oral exposure with LD50 estimated to be greater than 10 g/kg, while its LD50 on intraperitoneal administration was 407.38 mg/kg. Upon 30 days sub-chronic exposure, AR induced significant weight loss in female rats, enlargement of male rats' stomach, oxidative stress in male and female rats' kidney and liver tissues and disruption of leukocytes level in female rats. It also showed evidence of kidney and liver injuries inducible by oxidative damage and the potential to cause male sterility. HPLC revealed the presence of 0.003 mg/1 g of aristolochic acid in AR. CONCLUSION: These results show that AR contains detectible aristolochic acid I and has potential to induce toxic responses. Caution must therefore be exercised in its medicinal application especially when required for a prolonged use.

Isorhamnetin enhanced cortico-hippocampal learning and memory capability in mice with scopolamine-induced amnesia: Role of antioxidant defense, cholinergic and BDNF signaling.

Isorhamnetin (IRN), a 3'-O-methylated metabolite of quercetin has antioxidant, anti-inflammatory and neuroprotective properties. In this study, we investigated the learning and memory enhancing effects of IRN on spatial and non-spatial learning and memory deficits induced by scopolamine (3 mg/kg, i.p; muscarinic antagonist) using the novel object recognition test (NORT) and Morris water maze (MWM) task. IRN (1, 5 or 50 mg/kg, p.o.) or vehicle was administered to male albino for 3 consecutive days, scopolamine was given 1 h after last administration on day 3. Five minutes post scopolamine administration the behavioural test of cognitive function was carried out. One hour after probe test (MWM task) on day 7, the brains were isolated to assay for oxidative stress, cholinesterase activity and brain derived neurotrophic factor (BDNF) levels in the prefrontal cortex (PFC) and hippocampus (HIPPO). IRN treatment significantly improved scopolamine-induced learning and memory impairment in behavioural tests. IRN reduced malondialdehyde and nitrite generation induced by scopolamine through increase in glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities in the prefrontal cortex and hippocampus. In addition, IRN attenuates scopolamine induced cholinesterase activity and BDNF level in the prefrontal cortex and hippocampus of mice. Findings from this study showed that IRN possesses cognition and memory enhancing properties possibly through enhancement of antioxidant defense system, cholinergic signaling and synaptic plasticity.

Toxicological evaluation of the aqueous whole plant extract of Aerva lanata (l.) Juss. ex Schult (Amaranthaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Aerva lanata (L.) of the family Amaranthaceae is a Nigerian medicinal plant used traditionally for the management of lithiasis, headache, renal disorder, haematemesis, bronchitis, nasal bleeding, cough, scorpion stings, fractures and spermatorrhoea. Studies that show the pharmacological basis for some of such uses have been reported. There is, however, no scientific report on its toxicity profile to the best of our knowledge. AIM OF THE STUDY: This study was therefore aimed at investigating the toxicity profile of the aqueous extract of Aerva lanata. MATERIALS AND METHODS: Acute toxicity tests for the extract administered orally at 1-30g/kg and intraperitoneally at 0.1-2g/kg were carried out in albino mice; while a sub-chronic toxicity test was done by daily oral administration of the extract at 40-1000mg/kg to albino rats for 90 days. Anthropometric, biochemical and haematological parameters' assessments as well as vital organs histological examinations were performed in the sub-chronic toxicity study. RESULTS: The LD50 of the extract for oral and intraperitoneal acute toxicity tests were 22.62g/kg and 0.432g/kg respectively. The extract produced apparent changes in body weights of both male and female rats and significantly (p < 0.05) increased the weights of lungs, brain and pancreas of female rats while reducing the weight of testes in male rats. Haematological parameters were also altered with total leukocytes significantly (p < 0.05) increased and platelets significantly (p < 0.05) reduced in female rats; while neutrophils significantly (p < 0.05) increased in male rats. The extract (40-1000mg/kg) produced significant (p < 0.05) reduction of serum alanine transaminase concentration in both male and female rats. Aspartate transaminases and albumin were also significantly (p < 0.05) reduced in both male (at 1000mg/kg) and female (at 200mg/kg) rats. Alkaline phosphatase was also significantly (p < 0.05) reduced in female rats at 200mg/kg of the extract. Substantial alterations of creatinine, urea and uric acid were also observed. Triglyceride and cholesterol concentrations were significantly increased in male rats but decreased in female rats. At 1000mg/kg, the extract significantly elevated catalase and superoxide dismutase levels with no effect on malondialdehyde levels. It also reduced sperm count and motility of male rats. Mild to moderate cellular changes in the brain, kidney, liver, lungs, spleen and testes of treated rats were observed on histological examinations. Significant changes in biochemical and haematological parameters were also noted in treated animals when compared to control animals 30 days after cessation of treatment. CONCLUSION: The overall findings of this study suggest that the aqueous extract of A. lanata is relatively safe on acute oral exposure, moderately toxic on acute intraperitoneal administration and is relatively safe with antioxidant actions on prolonged exposure. It however shows potentials for toxic effects such as cellular damage to organs, dyslipidaemia and reduction in male reproductive capacity. Caution must therefore be applied in its use on a long term basis.

Antinociceptive, anti-inflammatory and antiulcerogenic activities of ethanol root extract of Strophanthus hispidus DC (Apocynaceae).

BACKGROUND: Strophanthus hispidus DC (Apocynaceae) is a medicinal plant widely used in traditional African medicine in the treatment of rheumatic afflictions, ulcer, conjunctivitis, leprosy and skin diseases. This study sought to investigate the antinociceptive, anti-inflammatory and antiulcer properties of the ethanol root extract of S. hispidus. METHODS: Antinociceptive activity was evaluated using acetic acid-induced writhing and formalin tests in mice. The carrageenan- and egg albumin-induced rat paw edema tests were used to investigate the anti-inflammatory actions, whereas the antiulcer activity was investigated using ethanol-, HCl- and pyloric ligation-induced gastric ulcer models in rats. RESULTS: S. hispidus [100-800 mg/kg orally (po)] produced significant (p<0.05) inhibition of writhing reflex with peak effect of 74.13% inhibition observed at 800 mg/kg. Similarly, S. hispidus significantly (p<0.05) attenuated formalin-induced early and late phase of nociception with peak effect of 61.84% and 89.43%, respectively, at 200 mg/kg. S. hispidus (25-800 mg/kg po) caused significant (p<0.05) inhibition of edema development in the carrageenan and egg albumin models with peak effect (93.40% and 90.10% inhibition of edema formation) observed at 50 mg/kg. With respect to antiulcer activity, S. hispidus (100-800 mg/kg) showed potent antiulcer activity with respective peak effects of 96% (ethanol-induced), 99% (HCl-induced) and 70.60% inhibition of ulcer. CONCLUSIONS: The findings in this study suggest that the ethanol root extract of S. hispidus possesses antinociceptive, anti-inflammatory and antiulcerogenic activities. This justifies the use of the extract in folklore medicine for the treatment of ulcer and inflammatory disorders.