Abstract

Background

Medicinal plants have been recognized as important source of therapeutically active compounds.  Calliandra surinamensis (Mimosaceae family) have been shown to have antimicrobial, anti-inflammatory, antiparasitic, antidiabetic and antineoplastic properties but there is little or no data on the acute toxicity and neurotoxicity profile of this plant.

Objective

This study was carried out to investigate the acute toxicity and neurotoxicity effects of the aqueous extract of Calliandra surinamensis on mice.

Methods

Acute toxicity was evaluated at a single dose of 2000mg/kg and acute toxicity signs such as (locomotory activity, body weight, stool state, and animal death) were evaluated as per OECD guidelines. For neurotoxic activity, open field test was carried out at the extract doses of 100mg/kg, 200mg/kg and 400mg/kg. the negative control group received distilled water (10ml/kg) orally and the positive control group was administered diazepam(1mg/kg) intraperitonially. Data was analyzed and calculated using ANOVA, Graph pad prism version 5.03 and expressed as a mean value ±Standard error of mean (SEM).

Results

This study found out that the oral administration of the aqueous extract of Calliandra surinamensis at the dose of 2000 mg/kg observed during the limit test as per OECD 425   interestingly, showed no sign of mortality and/or adversity in mice. The doses 200mg/kg and 400mg/kg at the 120th minute of the open field test showed a significant decrease (p<0.01) and (p<0.05) respectively on the locomotory activity in mice for neurotoxicity testing.

Conclusion

Based on these findings, it was concluded that the aqueous extract of Calliandra surinamensis does not exhibit acute toxicity effects in mice and may be neurotoxic at the doses of 200mg/kg and 400mg/kg.

CHAPTER ONE

INTRODUCTION

1. 1 Background of the Study

Medicinal plants and their herbal preparations have been used for therapeutics for over thousands of years. Across civilizations and cultures, they have had an impact in healthcare practice[1] and therefore assumed safe. However, it is important to evaluate the toxic effects of medicinal plants especially when developing therapeutic leads from plant sources.

According to the World Health Organisation (WHO) toxicity is the degree to which a substance can cause damage or harm to a living organism and according to the Globally Harmonised System of Classification and Labelling of Chemicals (G.H.S), acute toxicity refers to those adverse effects occurring following oral or dermal administration of a single dose of a substance, or multiple doses given within 24 hours, or an inhalation exposure of 4 hours. While neurotoxicity is the capacity of chemical, biologic, or physical agents to cause adverse functional or structural change in the nervous system. Acute toxicity studies or evaluation of an aqueous extract of a plant involves the harmful effect and toxic dose resulting from a single or short-term exposure of the test model to the extract. In acute toxicity studies using animals the  LD50 dose is assigned if the extract is found to be toxic,( the dose at which 50% or half of the test animals die after exposure)[2].

Neurotoxicity of medicinal plant extracts are evaluated through their mechanism on the central nervous and/or peripheral nervous system, these mechanisms include excitotoxicity, oxidative stress, disruption of neurotransmitter systems and interference with receptors in the nervous system, which can lead to the disruption of coordination and balance in the test animal[3]. Neurotoxicity can be acute, subacute, or chronic.

Toxicity screening is carried out in-vivo or in-vitro with animal and non-animal models before clinical trials, The use of laboratory animals such as rats, mice, zebrafish, guinea pigs, and rabbits are considered a gold standard for toxicity findings or evaluation of medicinal plants [4].

In Cameroon majority of the population prefer herbal medicine for their primary health care to conventional medical treatment because they believe its save and cheap giving more reason to screen these plants for toxicity. In screening medicinal plants for toxicity their herbal preparations  are made through processes such as decoction,  maceration fumigation, or purification [5].

The Organisation for Economic Cooperation and Development has elaborated guidelines for the testing of chemical compounds and phytochemicals. Several plants have been documented for their neurotoxic and acute toxic effects on animal models, like , Hyoscyamus niger[6], , Aconitum columbianum[7], Digitalis purpurea[8], Podophyllum pelatum[9], and Catharanthus roseus[10]

The plant Calliandra surinamensis (C. surinamensis) has been extensively studied in other parts of the world and proven to have many bioactivities such as antimicrobial, anti-inflammatory, antiparasitic, antidiabetic, and antineoplastic, activities. C. surinamensis has a long history of ethnomedicinal use in the management of various diseases in Africa [11].

Due to the frequent use of its stem bark and roots in traditional phytotherapy, this species is getting threatened in its distributional ranges[12]. Despite documented evidence on the ethnopharmacological potential of C. surinamensis and its potential for new drug development, little or no information exists on the neurotoxicity and acute toxicity profile of this plant. This information gap does not guarantee the safe use of this plant hence limiting new drug development.

1.2 Problem Statement

Long-term clinical usage is the main rational for the toxicity profiling and usage of medicinal plants.  Recent studies on the aqueous extract of Calliandra surinamensis is lacking on the aspect of its toxicity profile thereby posing a threat to people using this plant for therapeutics as it may show some sign of acute toxicity and neurotoxicity. There is a need of filling this knowledge gab by conducting a study on this aspect.

1.3 Research Questions

1. Does the administration of the aqueous extract of Calliandra surinamensis induce acute toxicity or neurotoxicity in mice?
2. Is there a dose-response relationship between the administration of aqueous extract of Calliandra surinamesis and its neurotoxic and acute toxicity effects in mice?
3. How does the administration of the aqueous extract of Calliandra surinamesis affect the motor coordination and behavioural activities of mice?

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