ANTI-PLASMODIAL, ANTI-INFLAMMATORY AND ANALGESIC ACTIVITIES OF ALKALOID FRACTION OF MAYTENUS SENEGALENSIS LEAF IN MICE

ABSTRACT

The treatment inadequacy and toxicity associated with conventional anti-malarial, anti- inflammatory and analgesic drugs calls for the search for alternatives from medicinal plants, particularly.  In  the present  study,  alkaloid  fraction  of  Maytenus  senegalensis  leaf was evaluated for anti-malarial, anti-inflammatory and analgesic properties. Phytochemical screening and acute toxicity test were conducted using standard procedures. Antimalarial studies was conducted using Plasmodium berghei-infected mice and four days suppressive test was used at fraction concentrations of 75, 150 and 300 mg/kg bw. Analgesic and anti- inflammatory study were conducted using egg albumin induced paw-oedema and hot plate induced thermal stimuli respectively at fraction concentrations of 75 and 150 mg/kg bw. Sub- acute toxicity study was conducted by administering the extract to rats (5 each group) at dose of 0, 75 and 150 mg/kg bw for 28 days. Results obtained indicated that Maytenus senegalensis crude methanol extract contains alkaloids (198.46±2.56 mg/g) as the most abundant phytochemical  while tannins were the least (12.45±0.95 mg/g). The alkaloid fraction had LD50 of> 5000 mg/kg bw and showed dose dependent anti-plasmodial activity with suppressive effects of 38.22±0.53%, 69.80±0.28% and 79.43±0.42% at 75, 150 and 300 mg/kg bw respectively. Alkaloid fraction also exhibited 53.16±4.09% and 60.76±7.54% anti- inflammatory effects, 43.35±4.98%% and 44.83±3.86% analgesic effects at 75 and 150 mg/kg bw respectively. GC-MS analysis confirmed the presence of 3 alkaloids; 20α)-3- hydroxy-2-oxo-24-nor-friedela-1(10),3,5,7-tetraen-carboxylic acid-(29)-methylester, 2(4H)- Benzofuranone, 5,6,7,7a-tetrahydro- and 3-hydroxy-20(29)-lupen-28-ol and a terpenes (phytol) as the major constituents of the alkaloid fraction. Alkaloid fraction increases the serum total proteins and transaminases concentrations but had no effect on sodium, potassium, chloride, alkaline phosphatase, triglyceride and glucose concentrations in the mice. Based on the result obtained, it can be concluded that the alkaloid fraction of M. senegalensis leaf exhibited promising antimalarial, analgesic and anti-inflammatory activities.

CHAPTER ONE

1.0       INTRODUCTION

1.1       Background to the Study

Malaria is a protozoan and parasitic infectious disease caused by five Plasmodium parasites: vivax, falciparum, malariae, Knowlesi and ovale. More than half of the world’s population are at risk of malaria, which results in a global count of 212 million new infections and 429,000 deaths per year (Odeghe et al., 2012; WHO, 2018). More than 90 percent of malaria infections and deaths in Sub-Saharan Africa mainly in children below five years and pregnant women (El Tahir et al., 2014). Poor rural dwellers in tropical and subtropical areas are highly vulnerable to this attack due to the favorable and ideal climate conditions for vector and parasite reproduction and growth. Additionally, drug resistance is one of the major challenges faced by the wide-ranging malarial eradication program (Da Silva et al., 2011).

Pain is an uncomfortable sensory and emotional experience associated with, or defined in terms of, real or possible tissue harm (IASP, 2015). Like Inflammation, pain may be acute or chronic depending on the lasting impact (Rajagopal, 2006).  Acute pain has a sudden onset, occurs shortly after injury, is extreme in severity and generally short lived (under 30 days). This occurs as a result of stimulating nociceptors from tissue damage and usually disappears when the damage heals (WHO, 2012). Chronic pain is characterized as a pain that persists for one month in addition to the normal course of an acute illness or a fair duration of healing injury, or associated with a persistent pathological mechanism that causes constant pain or recurrent pain for months or years at intervals (Rajagopal, 2006).

Inflammation is part of a multifaceted biological process in vascular tissues attributable to bacteria, wounded cells or irritants causing injurious stimuli. It is an organism’s defensive attempt to remove these injurious stimuli and begin the healing process (Medzhitov, 2008). However, prolonged response to injurious stimuli can result in progressive tissue damage resulting in various chronic conditions such as rheumatoid arthritis, asthma, Alzheimer’s disease, cardiovascular disease, or inflammatory intestinal disease (Conforti et al., 2009; Beg et al., 2011). Symptoms such as swelling, tightness, irritation and pain are usually associated with inflammation and may cause discomfort to the patient (Beg et al., 2011).

Inflammation and pains are gaining research popularity owing to the etiologic role they play in various human diseases. Dexamethasone opioids, morphine and aspirin and other drugs have been established for the management of pain and inflammation, however, these drugs have recorded limited success due to unintended effects such as gastric lesions caused by non-steroidal anti-inflammatory drugs (Odeghe et al., 2012). Thus, the search for drugs alternative from natural product is recommended.

Natural products represent ample sources of natural bioactive metabolite with therapeutic values against several diseases (Mostafa et al., 2010). The therapeutic properties of these plants are however, attributed to the quality and quantity of the secondary metabolites particularly alkaloids, and flavonoids, which are known to play defensive role in plants but exert different pharmacological effects such as anti-inflammatory, analgesic, antidiabetics, antimicrobial, anti-parasitic and antioxidants effects in human and animals (Mohiuddin et al., 2018).

Maytenus senegalensis (family; celastraccae) is an African medicinal plant traditionally used in the folk medicine for the treatment of a number of ailments, including rheumatism, snake bites, diarrhoea, eye infection, and dyspepsia (Greenwood, 2008). Maytenus senegalensis (Lam.) is one of the most frequently used specie of the Maytenus Molina genus in the African traditional medicine (along with M. Obsc) Maytenus senegalensis is traditionally used as anti- microbial and anti-inflammatory agents, it is also used to treat respiratory ailments and inflammation. The use of this anti-inflammatory herbal drug is common in many African countries like Nigeria, Benin, Kenya, Zambia, Tanzania, Senegal and Zimbabwe. Maytenus senegalensis leaves are also used to treat toothaches in India (Gurib-Fakim, 2006). Previous study has demonstrated that the leaf, root and stem bark extracts of M. senegalensis possess in vitro anti-plasmodial, anti-leishmanial, and antibacterial activities (Odeghe et al., 2012). However, literature survey revealed dearth of scientific information on the pharmacological activities of alkaloids and flavonoid fraction.

1.2       Statement of the Research Problem

Anti-malarial drug resistance has emerged as one of the greatest challenges facing malaria control today and has also been implicated in the spread of malaria to new areas and re- emergence of malaria in areas where the disease had been eradicated. This resistance is common to numerous drugs used to treat malaria (Olasehinde et al., 2014). Thus, there is an urgent need for increased efforts in anti-malarial drug discovery especially in Africa. Fake medications are coming onto the scene as a result of deliberate criminal activity, while substandard drugs are becoming more common because of poor manufacturing practices. Not only are scores of patients being inadequately treated, but the presence of these undesirable and illegal medications significantly raises the risk of drug resistance by the malaria parasites.

Approximately 438,000 people are thought to have died from malaria in 2015 (World Health Organisation, 2015).

According to the 2006 National Center for Health Statistics Report, one in 10 Africans overall and three in five of those 60 years or older said that they experienced pain that lasted a year or more. More than one-quarter of adults said they had experienced low back pain, and 15 % of adults experienced migraine or severe headache in the past three months. Between the periods 1988-1994 and 1999-2002, the percentage of adults who took a narcotic drug to alleviate pain in the past month rose from 3.2 to 4.2 %.  For the millions of people who experience persistent pain, the impact on function and quality of life can be profound (Kim et al., 2004).

Due to extensive use of analgesic and anti-inflammatory agents, the toxicity and untoward effects do occur especially when pain and inflammation therapy involves the use of higher doses for longer periods. This result in a reduction of living quality and functional situation of the patients, increase in the fatigue levels and impairments in daily life activities in working capacity and social interactions (Allard et al., 2001). Considering the probable adverse effects of these synthetic drugs, as well as their limited ability to provide long-term remission, there is a need of a new, effective and safe anti-inflammatory agent which can reduce pain and other associated symptoms. To overcome these problems the preparations from plant origin become a hope for mankind.

1.3       Justification for the Study

Medicinal plants, since time immemorial, have been used in virtually all cultures as a source of medicine (Hoareau and Dasilva, 1999). Traditional plants play an important role in medical system in Nigeria and plant materials remain an important resource to combat serious diseases in the world. Pharmacognostic investigations of plants are carried out to find novel drugs or templates for the development of new therapeutic agents. Since many drugs, e.g. quinine and artemisinin were isolated from plants and because of the increased resistance of many pathogens, e.g. malaria parasites, towards established drugs, investigation of the chemical compounds within traditional plants is necessary (Phillipson and Wright, 1991). In recent times, natural products of plant sources have been the center of focus as the main source of new, safer and more effective bioactive compounds with medicinal properties (Ogbuehi et al., 2014).

1.4       Aim and Objectives of the study

Aim

To evaluate the anti-plasmodial, analgesic and anti-inflammatory activities of alkaloidal extract of Maytenus senegalensis leaf.

Objectives of the study

The objectives of the study are to:

i.      to determine the phytochemical compositions of M. senegalensis leaf extract

ii.      to determine the LD50 of the alkaloid extract of M. Senegalensis

iii.     to evaluate the antiplasmodial activity of the alkaloid extract of M. Senegslensis

iv.      to determine the anti-inflammatory and analgesic activities of the alkaloid extract of M. Senegalensis

v.      to  deterrmine  the  effect  of  sub-acute  administration  of  alkaloid  extract  of  M. senegalensis on biochemical parameters in mice

vi.      to characterize the alkaloid extract of M. Senegalensis leaf using Gas Chromatography Mass Spectrometry (GC-MS).

₦8,000.00 – DOWNLOAD FULL PROJECT DOWNLOAD FULL PROJECT Added to cart

---

---

---

---

Related Project Topics :