Sub-acute toxicity study on hydromethanolic leaves extract of Combretum hypopilinum (Combretaceae) Diels in Wistar rats.

The plant Combretum hypopilinum Diels (Combretaceae) has been utilized in Nigeria and other African nations to treat many diseases including liver, inflammatory, gastrointestinal, respiratory, infectious diseases, epilepsy and many more. Pharmacological investigations have shown that the plant possesses anti-infective, antidiarrhoeal, hepatoprotective, anti-inflammatory, anticancer, sedative, antioxidant, and antiepileptic potentials. However, information on its toxicity profile is unavailable despite the plant's therapeutic potential. As such, this work aimed to determine the acute and sub-acute oral toxic effects of the hydromethanolic leaves extract of C. hypopilinum. The preliminary phytochemical evaluation was carried out based on standard procedures. The acute toxicity evaluation was conducted by oral administration of the extract at the dose of 5000 mg/kg based on the guideline of the Organization of Economic Co-operation and Development (OECD) 423. To investigate the sub-acute toxicity effects, the extract was administered orally to the animals daily for 28-consecutive days at the doses of 250, 500, and 1000 mg/kg. Mortality, body weight and relative organ weight were observed. The hepatic, renal, haematological, and lipid profile parameters were investigated. The liver, kidney, heart, lung, small intestine, and stomach were checked for any histopathological alterations. The results of the phytochemical investigation showed cardiac glycosides, tannins, steroids, flavonoids, alkaloids, saponins, and triterpenes. Based on the acute toxicity investigation outcome, no death and signs of toxic effects were observed. The result showed that the oral median lethal dose (LD50) of the extract was more than the 5000 mg/kg. The extract remarkably reduced the weekly body weight of the animals at 500 mg/kg in the first and second weeks. It also significantly decreased the relative kidney weight, alkaline phosphatase, glucose, potassium, and low-density lipoprotein. There was a remarkable elevation in the percentage of eosinophils, basophils, monocytes, and granulocyte. There were histopathological abnormalities on the kidney, lung, stomach, and small intestine. The extract is relatively safe on acute exposure but moderately toxic at higher doses on sub-acute administration, particularly to the kidney.

Effect of methanol root extract of Eriosema psoraleoides on biochemical and haematological parameters and cyclooxygenase levels in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Eriosema psoraleoides is a remedial plant utilised traditionally in the African continent. It is said to possess a wide range of pharmacological activity. In a previous study, the analgesic and anti-inflammatory activity of its methanol root extract have been scientifically demonstrated. The growing use of medicinal plants by people from low-income countries and the plethora of adverse effects accompanying this increasing use has demonstrated the need for comprehensive toxicological evaluation of these plants which have shown therapeutic activity. However, in the capsule that is Nigeria, these studies are seldom done even though locals continue to patronize these plants for their health benefits. AIM OF THE STUDY: To establish the repeated dose toxicity profile of the methanol root extract of Eriosema psoraleoides (EPE) in rats and also to investigate a possible mechanism for its analgesic and anti-inflammatory activity. MATERIALS AND METHODS: Male Wistar rats were utilised for the test. All animals used for the test were healthy. The oral repeated dose study was carried out for 28 days with animals being given the following doses daily; 250, 500 and 1000 mg/kg orally. The Wistar rats were euthanized afterwards and blood samples were taken. The samples were subjected to serum biochemistry in tandem with haematological testing. After acute induction of inflammation with 1% carrageenan in normal saline, sera samples were obtained from the animals: serum cyclooxygenase 1 and 2 levels (COX 1 and COX 2) were assayed using Enzyme-Linked Immunosorbent Assay kits. Data were analysed utilising the appropriate software and tests. RESULTS: Oral Repeated dose administration of EPE for 28 days didn't produce any lethality in any animal throughout the duration of the test. Repeated dose administration of EPE showed a significant (p < 0.05) decrease in the serum levels of Alanine Aminotransferase as well as Aspartate Aminotransferase at 250 and 1000 mg/kg dose levels. Total protein and albumin were also significantly (p < 0.01) decreased. A statistically significant (p < 0.05) decrease in serum urea level was also observed compared to the normal saline group (1 ml/kg). Sodium levels also showed a decrease with a statistically significant level only in the group treated with the extract at a dose of 1000 mg/kg (p < 0.05). Haematological parameters were not significantly affected by EPE. The extract demonstrated an ability to down-regulate serum concentration of both COX 1 and 2, though not to a statistically significant level. CONCLUSION: The results of this study suggest that prolonged use of EPE might potentially adversely affect vital organs in the body and EPE may potentially act through its downregulation of COX 1 and 2.

Data on the mechanisms of antidiarrhoeal activity of methanol leaf extract of Combretum hypopilinum Diels (Combretaceae): Involvement of opioidergic and (α1 and ß)-adrenergic pathways.

This article describes the dataset for the elucidation of the possible mechanisms of antidiarrhoeal actions of methanol leaves extract of Combretum hypopilinum (Diels) Combretaceae in mice. The plant has been used in traditional medicine to treat diarrhoea in Nigeria and other African countries. We introduce the data for the antidiarrhoeal activity of the methanol leaf extract of Combretum hypopilinum at 1,000 mg/kg investigated using charcoal meal test in mice with loperamide (5 mg/kg) as the standard antidiarrhoeal agent. To elucidate the possible mechanisms of its antidiarrhoeal action, naloxone (2 mg/kg), prazosin (1 mg/kg), yohimbine (2 mg/kg), propranolol (1 mg/kg), pilocarpine (1 mg/kg) and isosorbide dinitrate (150 mg/kg) were separately administered to different groups of mice 30 minutes before administration of the extract. Each mouse was dissected using dissecting set, and the small intestine was immediately removed from pylorus to caecum, placed lengthwise on moist filter paper and measured the distance travelled by charcoal relative to the length of the intestine using a calibrated ruler in centimetre. Besides, the peristaltic index and inhibition of charcoal movement of each animal were calculated and recorded. The methods for the data collection is similar to the one used to investigate the possible pathways involved in the antidiarrhoeal action of Combretum hypopilinum in mice in the research article by Ahmad et al. (2020) "Mechanisms of Antidiarrhoeal Activity of Methanol Leaf Extract of Combretum hypopilinum Diels (Combretaceae): Involvement of Opioidergic and (α1 and ß)-Adrenergic Pathways" (https://doi.org/10.1016/j.jep.2020.113750) [1]. Therefore, this datasets could form a basis for in-depth research to elucidate further the pharmacological properties of the plant Combretum hypopilinum and its bioactive compounds to develop standardized herbal product and novel compound for management of diarrhoea. It could also be instrumental for evaluating the plant's pharmacological potentials using other computational-based and artificial intelligence approaches, including predictive modelling and simulation.

Mechanisms of antidiarrhoeal activity of methanol leaf extract of Combretum hypopilinum diels (combretaceae): Involvement of opioidergic and (α1 and ß)-adrenergic pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Combretum hypopilinum Diels (Combretaceae) is used in traditional medicine for the treatment of diarrhoea and other diseases in Africa. Previously, the antidiarrhoeal activity of its methanol leaf extract was reported. However, the mechanism(s) responsible for this activity is yet to be evaluated. AIM OF THE STUDY: This study aimed to elucidate the possible mechanism(s) of antidiarrhoeal activity of methanol leaf extract of Combretum hypopilinum (MECH) in mice. MATERIALS AND METHODS: Phytochemical screening and acute toxicity study were conducted according to standard methods. Adult mice were orally (p.o) administered distilled water (10 ml/kg), MECH (1000 mg/kg) and loperamide (5 mg/kg). The probable mechanisms of antidiarrhoeal activity of MECH were investigated following pretreatment with naloxone (2 mg/kg, subcutaneously), prazosin (1 mg/kg, s.c), yohimbine (2 mg/kg, intraperitoneally), propranolol (1 mg/kg, i.p), pilocarpine (1 mg/kg, s.c) and isosorbide dinitrate (150 mg/kg, p.o) 30 min before administration of MECH (1000 mg/kg). The mice were then subjected to castor oil-induced intestinal motility test. RESULTS: The oral median lethal dose (LD50) of MECH was found to be higher than 5000 mg/kg. There were significant (p < 0.05) decrease in the charcoal movement in the mice treated with the MECH (1000 mg/kg) and loperamide (5 mg/kg). The pretreatment of the mice with naloxone, prazosin and propranolol each significantly (p<0.05) reversed the antidiarrhoeal activity produced by MECH. CONCLUSION: The results obtained in this study suggest the probable involvement of opioidergic and (α1 and ß)-adrenergic systems in the antidiarrhoeal activity of the methanol leaf extract of Combretum hypopilinum.

Khaya senegalensis inhibits piroxicam mediated gastro-toxicity in wistar rats.

OBJECTIVE: The purpose of this study was to investigate the effects of piroxicam co-administration with ethanolic stem-bark extract of Khaya senegalensis on biomarkers of oxidative stress and gastro-toxicity in Wistar rats. MATERIALS AND METHODS: Thirty healthy male and female Albino Wistar rats (190-220 g) were grouped into six (n = 5) with designated treatments including: Normal saline, piroxicam (20 mg/kg), extract (200 and 400 mg/kg) alone and both doses of the extract co-administered with piroxicam. The drugs were administered orally to all the rats for fourteen consecutive days and on the fifteenth day, they were euthanized with chloroform inhalation. Blood samples and the stomachs were isolated for evaluation of the oxidative stress biomarkers and gastro integrity, respectively. RESULTS: The results of the study revealed that the levels of oxidative stress markers didn't differ significantly between the groups receiving the extract alone, the extract in combination or piroxicam alone. Gross and histological observations of the stomach showed gastric mucosal changes and mild atrophic lesions in the piroxicam group only. CONCLUSION: This study illustrates the interaction of Khaya senegalensis and piroxicam results in the gastro-protective beneficial effects. The extract's outcome on various prostaglandin levels and synthesis is being considered towards possible elucidation regarding the exact mechanism of cytoprotection.

Evaluation of five medicinal plants used in diarrhoea treatment in Nigeria.

Five medicinal plants [Acacia nilotica, Acanthospermun hispidum, Gmelina arborea, Parkia biglobosa and Vitex doniana] used in diarrhoeal treatment in Kaduna State, Nigeria, were investigated. This study was carried out on perfused isolated rabbit jejunum and castor oil-induced diarrhoea in mice. The aqueous methanol extracts (0.5, 1.0, 2.0 and 3.0 mg/ml) were generally found to cause a dose-dependent response in the isolated rabbit jejunum, though this was not uniform in all the plants. Gmelina arborea and Vitex doniana showed concentration dependent relaxation at low doses (0.5, 1.0 mg/ml), but showed no significant relaxation at higher doses (2.0, 3.0 mg/ml). Other extracts showed biphasic effects. For example, Acacia nilotica at 3.0 mg/ml caused initial relaxation quickly followed by contraction. In the castor oil-induced diarrhoeal, 100% protections were shown by extracts of Acacia nilotica and Parkia biglobosa (100, 200 mg/kg) while Vitex doniana showed a dose-dependent effect. The least protection was shown by Acanthospermun hispidum, at the same dose, when compared with the other four plants. The results obtained revealed that the aqueous methanol extracts of all the five medicinal plants investigated have pharmacological activity against diarrhoea. This may explain their use in traditional medicine for the treatment of diarrhoea.