ABSTRACT

There is growing attention on medicinal plants use as food for cancer inhibiting potential, so that

chemo preventive dietary inclusion can be identified for human use. One of such plant is Curcurbita

maxima commonly known as Giant pumpkin. The preventive effect of dietary inclusion at 2.5%, 5%

and 10% with the leaf of Cucurbita maxima on colon carcinogenesis induced by N-methyl N-

nitrosourea(MNU) for 12 weeks was assessed in male albino Wistar rats. The colon and liver of rats

administered the Cucurbita maxima leaf included diet, showed significant(P˂0.05) increase in the

activity of the endogenous    antioxidant enzymes (CAT and SOD) in the treated groups when

compared with the MNU control group. A dose-dependent decrease in oxidative stress was observed

in the colon of treatment group with the highest percentage inclusion(10%) showing the lowest MDA

value. A significant (P˂0.05) increase in some hematological parameters like PCV, Red blood cell

(RBC), heamglobin count (HB) were observed in the treated group when compared with the MNU

control group. While an increase in white blood cell count (WBC) and neutrophils was observed in

the MNU control group when compared with the normal control group. A significant (P˂0.05)

decrease in the level of Carcinoembrayonic antigen (CEA) was observed in the Cucurbita maxima

leaf diet fed group when compared with the MNU control group. Immunohistochemical observation

of the colon tissue showed mild to moderate expression of the DNA mismatch repair (MLH1) gene in

the treated groups when compared with the MNU control group showing mild to no expression of the

MLH1 gene. Histological observation of colon tissue showed a severe damage to the mucosa cell,

with mucosa ulceration and sclerosis being observed in the MNU control group when compared with

the treated groups and normal control that both showed a better architecture of the cells. The results

therefore,shows the ability of Cucurbita maxima leaf dietary inclusion to improve endogenous

antioxidant system maintain or improve heamatological parameter ,prevent oxidative stress, protect

organ damage induced by MNU carcinogen, thus indicating the potential of Cucurbita maxima leaf to

prevent          the          process          of          chemically          induced         colon          carcinogenesis.

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CHAPTER ONE INTRODUCTION

1.1 Background Information

Medicinal plants have been used throughout human history for treatment and management of

different ailments (Aliyu et al., 2008). The reason is because these plants have the ability to

synthesize a wide variety of chemical compounds that have been found useful to man. these

compounds perform important biological functions for the plant like defense against attack from

predators such as insects, and fungi e.t.c with at least 12,000 of such compounds isolated so far; a

number estimated to be less than 10% of the total available compounds (Tapsell et al., 2006; Lai

and Roy, 2004). This then justifies the chemopreventive and therapeutic effects of these plants on

cancer and other diseases related to oxidative damage (Atawodi et al.,2010).These plants which

are also referred to asherbs have been used to prevent and treat disease/disorderscommonly

throughout non-industrialized societies because they are more affordable than purchasing

expensive modern pharmaceutical drugs (Edgar et al., 2002). A report made by World Health

Organization (2000) puts it that, about 80% of the population of some Asian and African countries

presently use herbal medicine for some aspect of primary healthcare, also according to a survey

report released in May 2004 by the National Centre for Complementary and Alternative Medicine,

herbal therapy, or use of natural products other than vitamins and minerals, was the most

commonly used complementary alternative medicine therapy amounting to 18.9% in the United

States (Barnes et al., 2004). Furthermore, it is stated that these compounds found in these herbs

are often responsible for mediating their therapeutic effects on the human body through processes

that are identical to those already well understood mechanisms in conventional drugs (Tapsell et

al., 2006). The medicinal or therapeutic properties of these plants could be based on the

antioxidant, antimicrobial , antipyretic and other physiological effects of the phytochemicals in

1

them (Ayo, 2014; Adesokan et al., 2008). It is interesting to note that one of the major challenge of

modern medicine is in the treatment and management of colon cancer and also absence of a

reliable colon cancer preventive drugs.Thereforeedible medicinal plants becomes key in the

prevention, treatment and management of colon cancer (Bufalo et al.,2009). Many edible plants

have been favored in the prevention and treatment of diverse ailment, One of such plant is

Cucurbita maxima (Munteanet al., 2013), Despite the wide investigation of plants for preventive

and curative potency in different form of cancer.The menace of cancer is far from being over.

Hence, there is a need to investigate more naturally abundant edible plants of medicinal potency in

the fight against colon cancer until total and absolute protection from     colorectal cancer is

guaranteed. The focus of this investigation therefore, is to consider the possible preventive effect

of the leaf of Cucurbita maxima formulated diet on colon carcinogenesis,      using a

carcinogen(MNU) in male albino wistar rats and thereafter enlisting it as one potent preventive

plant against colon cancer if found/proved so.