Plant Medicines in Cancer Treatment

Plant Medicines in Cancer Treatment Review of Literature Plants as therapeutic agents Plant medicines are the most widely used medicines in the world today. The use of herbs and plants as the first medicine is a universal phenomenon. Every culture on earth, through written or oral tradition, has relied on the vast variety of natural chemistry found in healing plants for their therapeutic properties (Serrentino 1991). Plants with therapeutic potential may be defined as any plant that can be put to culinary or medicinal use. Recent researches found that food and their constituents act in a manner similar to modern drugs without the dreaded side effects (Serrentino 1991). Sometimes plant medicine is viewed as complementary medicine, working closely with allopathic drugs. Nearly 5.1 billion people worldwide employ natural plant-based remedies as their primary medicines for both acute and chronic health problems, from treating common cold to controlling blood pressure and cholesterol (Stockwell, 1988). Most of the drugs were substances with a particular therapeutic action extracted from plants. Some medicines, such as the cancer drug Taxol from Taxus brevifolia and the anti-malarial quinine from Cinchona pubescens are manufactured from the plants. Other medicinal agents such as pseudoephedrine originally derived from ephedra species and methylsalicylate, derived from gaultheria procumbens are now synthesized. Plant medicines remain indispensable to modern pharmacology and clinical practice. Much of the current drug discovery and development process are plant-based, and new medicines derived from plants are inevitable. Functional foods A food can be regarded as a functional food if it is demonstrated to affect one or more target functions in the body beyond adequate nutrition and improves health/well-being or reduces the risk of diseases (Tsao and Akhtar, 2005). On this basis, a functional food can be a natural food, a food to which a positive component has been added, or from which a deleterious component has been removed or a food where the nature of one or more components has been modified (Tsao and Akhtar, 2005). While searching for new sources of functional food, attention has been paid to vegetables from the Cruciferae family, which more often used in the human diets. The cruciferous vegetables may thus become a potential source of a nutritious food or food ingredients. Recent research showed that cruciferous vegetables contain an appropriate amount of bioactive compounds such as GLs, ITCs, tocopherols, L-ascorbic acid, vitamin B, reduced glutathione, inositol phosphates and polyphenolic compounds [Nakamura e t al, 2001; Zielinski and Kozlowska, 2003; Zielinski et al, 2005; Takaya et al, 2003]. Cruciferous plants The family Cruciferae (Brassicaceae) is an economically important family with about 350 genera and 3000 species that includes several edible plants. Despite the great diversity among the crucifers, members of only a few genera are eaten. The most commonly eaten cruciferous vegetables belong to the genus Brassica that includes broccoli, cabbage, cauliflower, kale and Brussels sprouts. Other cruciferous vegetables used in the human diet such as radish, water cress, wasabi, horseradish, garden cress, Italian cress, Swiss chard and crambe belong to another genera of the family such as Raphanus, Nasturtium, Wasabia, Armoracia, Lepidium, Eruca, Beta and Crambe respectively. Cruciferous vegetables are important dietary constituents in many parts of the world and appear to account for about 10 15% of total vegetable intake, reaching almost 25% in countries with a high consumption (Bosetti et al, 2002; Chiu et al, 2003). However, regional pattern of crucifer consumption varies substantially in different parts of the world. The highest intake of cruciferous vegetable was reported to that of people in China, who consumed more than 100 g per day, representing about one-fourth of their total vegetable intake (Chiu et al, 2003). Other Asians and some Middle Eastern populations in Japan, Singapore, Thailand and Kuwait also have a relatively high intake of cruciferous vegetables, ranging from 40 80 g per day (Bosetti et al, 2002; Seow et al, 2002; Shannon et al, 2002; Memon et al, 2002). However, the only study carried out in India (Rajkumar et al, 2003) showed a lower daily intake of cruciferous plants, of about 17 g per day. In North America, the daily estima ted consumption was in the range of 16 40 g per day (Lin et al, 1998) and in South America, it was about 3 15 g per day (Atalah et al, 2001). The daily intake of cruciferous vegetables was reported to be about 5 30 g per day in Europe (Bosetti et al, 2002), 50 g per day in Australia (Nagle et al, 2003) and 15 g per day in South Africa (Steyn et al, 2003) respectively. Raphanus sativus R. sativus is believed to have originated in southern Asia and was cultivated in Egypt. The first cultivated R. sativus was black variety and later on white and red R. sativus were developed. It was highly esteemed in ancient Greece, and the Greek physician Androcydes ordered his patients to eat R. sativus as a preservative against intoxication. The Japanese white R. sativus, also named daikon, is the vegetable for which the literature reports the highest per capita consumption, quoted at 55 g per day in Japan (Talalay and Fahey, 2001). In addition to this, Japanese also consumes R. sativus sprouts under the name of Kaiware Daikon. Varieties of R. sativus There are six main varieties of R. sativus such as Daikons, Red Globe, White Globe, Black, White Icicles and California Mammoth White Daikons (R. sativus L) This variety is native to Asia. They are large and carrot-shaped, have a white flesh that is juicy and a bit hotter than a red radish, but milder than black. Red Globe (R. sativus var. red) This variety is the most popular in the United States. It is small, round or oval shaped, referred to as button red radishes and have a solid crisp flesh. White Globe (R. sativus var.white) This variety is small and oval shaped, referred to as hailstone or white button. They have white flesh and milder than the red variety. Black (R. sativus var. niger) This variety is thought to be native to Egypt and Asia. They are turnip-like in size and shape. They are quite pungent and drier than other varieties of radishes. White Icicles (R. sativus L var. thin) This variety is long and tapered. They have a white flesh that is milder than the red variety. California Mammoth White (R. sativus L var. large) A larger variety than the white icicle, these varieties have oblong- shaped roots and their flesh is slightly pungent. Nutritive value of R. sativus R. sativus root and its leafy part are ideal vegetables as they provide an excellent source of vitamin C. Leafy part contains almost six times the vitamin C content of its root and also a good source of calcium and iron. R. sativus is also a good source of potassium and folic acid. It is very low in fats. Approximately, 100 g of raw vegetable provides roughly 20 Kcal, coming largely from carbohydrates (Table 2.1). Thus R. sativus is a dietary food that is relatively filling for its caloric value. Some sources list R. sativus as being rich in dietary fiber, whereas other sources differ in respect of its roughage content (USDA Nutrient Database, 1999; Duke and Ayensu, 1985). Health benefits of R. sativus (Traditional usage of R. sativus) According to Hakeem Hashmi, an eminent Unani physician from India, R. sativus is unparallel in curing any kind of ailments. All the parts of R. sativus including its seed, stem, root and leaves are used in food and medicine. R. sativus is a unique vegetable having a hot and cold effect on the body simultaneously. R. sativus, like other members of the cruciferous family (cabbage, kale, broccoli, Brussels sprouts) contains cancer-protective properties. Liver and gall bladder disorders Throughout the history, R. sativus root and seeds have been effective when used as medicinal food for liver disorders. They contain sulfur-based compounds such as GLs and ITCs that increase the flow of bile and help to maintain healthy gallbladder and liver (Chevallier, 1996). They are useful in treating jaundice and also an excellent remedy for gall bladder stone. Kidney disorders R. sativus root, seeds and leaves are diuretic in nature and increase the urine output. Their diuretic properties help to flush out the toxins accumulated in the kidneys and protect them from infections and inflammatory conditions. It is an old belief that R. sativus can aid in the treatment as well as prevention of kidney stones (Chopra et al, 1986). Respiratory disorders R. sativus is an anti-congestive and relieves congestion of the respiratory system. It has found to be beneficial in problems associated with bronchitis (Bown, 1995) and asthma (Duke and Ayensu, 1985). Skin disorders R. sativus helps to cure skin disorders such as leucoderma, rashes, cracks, etc and also refreshes the skin by maintaining the moisture content of the skin (Duke and Ayensu, 1985). Digestive disorders R. sativus root, seeds and leaves are rich in roughage (indigestible carbohydrates) which facilitates digestion, retain water and relieve constipation (Chopra et al, 1986). They also soothe the digestive system and stimulate appetite (Chevallier, 1996) Nervous and vascular disorders R. sativus decreases nervous tensions and is also useful in enhancing blood circulation. It is a remedy for insomnia, hypochondria and irritative conditions of the central nervous system (Panda, 1999). Other benefits R. sativus is germicidal and suppresses phlegm. It is a good appetizer, mouth fresher, laxative, regulates metabolism, remedy for headache, acidity, piles, nausea, obesity, sore throat, whooping cough, dyspepsia, etc (Nadkarni, 1976; Kapoor, 1990). Chemical constituents of R. sativus GLs are an important and unique class of secondary plant metabolites found in the seeds, roots and leaves of R. sativus (Daxenbichler et al, 1991; Blazevic and Mastelic, 2009). GLSs include several naturally occurring thioglucosides with a common structure (Figure 2.2) characterized by side chains (R) with varying aliphatic, aromatic and heteroaromatic carbon skeletons, all presumably derived from amino acids by a chain-lengthening process and hydroxylation or oxidation (Larsen, 1981). In the intact cell, GLs are separated from thioglucosidase (EC 3.2.3.11), an enzyme generally known as myrosinase. When the plant cell structure is damaged, myrosinase catalyzes the hydrolysis of GLs to yield D-glucose, sulfate and a series of compounds including isothiocyanates, thiocyanates and nitriles, depending on both the substrate and the reaction conditions, especially the pH (Figure 2.2). GLs are also hydrolyzed by thioglucosidase activity of the intestinal microflora (Jeffery and Jarrell, 2001). 4-(methylthio)-3-butenyl glucosinolate (glucoraphasatin), 4-(methylsulfinyl) butyl glucosinolate (glucoraphanin) and 4- (methylsulfinyl)-3-butenyl glucosinolate (glucoraphenin) are the most predominant GLs in the root and seeds of R. sativus (Daxenbichler et al, 1991; Carlson et al, 1985). These GLs on hydrolysis by myrosinase yield MTBITC, sulforaphane and sulforaphene respectively. GLs are not uniformly distributed and are highest in the distal end of the root, decreasing in upper root sections with the lowest level in vegetative tops (Esaki and Onozaki, 1980). Apart from GLs and their breakdown products, R. sativus also contains polyphenolics such as phenolic acid, flavonoids and anthocyanins. Several polyphenolic compounds including sinapic acid esters and kaempferol were isolated from R. sativus sprouts (Takaya et al, 2003). Twelve acylated anthocyanins (pelargonidin) were isolated from R. sativus red variety (Otsuki et al, 2002). Phytochemical screening showed the presence of other phytochemicals such as triterpenes, alkaloids, saponins and coumarins in R. sativus seeds (Mohamed et al, 2008). The myrosinase catalyzed hydrolysis of glucosinolates. (Adapted from Rusk et al, 2000) Novel classes of plant defensins (small basic cysteine rich peptides) such as Raphanus sativus antifungal peptide 1 and 2 (RsAFP1 and RsAFP2) were isolated from the seeds of R. sativus (Terras et al, 1992a). RsAFP1 and RsAFP2 are highly basic oligomeric proteins composed of small (5 KDa) polypeptides that are rich in cysteine. Both RsAFP1 and RsAFP2 have a broad spectrum antifungal activity and show a high degree of specificity to filamentous fungi (Terras et al, 1992b). They are active against both phytopathogenic fungi such as Fusarium culmorum and Botrytis cinerea (Terras et al, 1992b), human pathogenic fungi such as Candida albicans (Aerts et al, 2007) and occasionally possess antibacterial activity. However, they are non-toxic to humans and plant cells. R. sativus 2S storage albumins were identified as second novel class of antifungal protein (Terras et al, 1992a). They also inhibit the growth of different plant pathogenic fungi and certain bacteria (Terras et al, 1992a). At least eight distinguishable isoperoxidases were isolated and purified to apparent homogeneity from Korean R sativus roots. Among them are two cationic isoperoxidases such as C1 and C3 and four anionic isoperoxidases such as A1, A2, A3n and A3 (Lee and Kim, 1994). Plant peroxidases play an important role in several physiological functions such as removal of peroxide, oxidation of indole-3-acetic acid and toxic reductants, wound healing and cell wall biosynthesis (Hammerschmidt et al, 1982). Further, peroxidase represents an important component of an early response in plants to pathogen attack and plays a key role in the biosynthesis of lignin, which limits the extent of pathogen spread (Bruce and West, 1989). The products of this enzyme in the presence of a hydrogen donor and hydrogen peroxide have antimicrobial activity and even antiviral activity (Van Loon and Callow, 1983). Recently, a novel heme peroxidase intrinsically resistant to H2O2 was isolated from R. sativus (Japanese d aikon), which showed relatively stronger oxidative stability than that of reference horse radish peroxidase (HRPA2) (Rodrà ­guez et al, 2008). Biological activities of R. sativus Evidence from numerous investigations reveals that the biological and pharmacological functions of R. sativus are mainly due to its GLs and its breakdown products ITCs (Esaki and Onozaki, 1982; Nakamura et al 2001; Barillari et al, 2006; Papi et al, 2008). These compounds provide to R. sativus its characteristic odor and flavor as well as most of their biological properties. GLs and/or ITCs have long been known for their fungicidal, bacteriocidal, nematocidal and allelopathic properties (Brown et al, 1991) and have attracted intense research interest because of their cancer chemoprotective attributes (Fahey et al, 2001; Verhoeven et al, 1997). Polyphenolics, alkaloids, saponins, isoperoxidases and antifungal peptides are also accountable for significant part of the health benefits of R. sativus. These constituents are reported to exhibit several biological effects, including radical scavenging activity (Takaya et al, 2003), gut stimulatory, uterotonic and spasmogenic effects (Gilani and Ghayur, 2004; Ghayur and Gilani, 2005), anti-hyperlipidemic activity (Wang et al, 2002) and anti-atherogenic effects (Suh et al, 2006) and would perhaps work synergistically with GLSs and ITCs of R. sativus. Antioxidant activity Damage to proteins, lipids and DNA by reactive oxygen species (ROS) and reactive nitrogen species (RNS) can lead to a variety of chronic diseases such as cancer, cardiovascular, inflammatory and age-related neurodegenerative diseases (Borek, 1997; Richardson, 1993). ROS/RNS can damage cell membranes, disrupt enzymes, reduce immunity (Ahsan et al, 2003) and induce mutations (Loft and Poulsen, 1996). ROS/RNS are by-products of normal aerobic metabolism and could occur during mitochondrial/microsomal electron transport chain, phagocytic activity or generated from oxidase enzymes and transition metal ions (Nohl et al, 2003; Aruoma et al, 1989). Other sources of ROS/RNS are environmental factors such as pollution, sun damage, cigarette smoke or even some kinds of the foods (Schroder and Krutmann, 2004). These reactive species and the resulting oxidative damages are usually counteracted by the antioxidant defense mechanisms (Bagchi and Puri, 1998). Recent studies evidence that plant-based diets, particularly those rich in vegetables and fruits, provide a considerable amount of antioxidant phytochemicals such as vitamins C and E, glutathione, polyphenolics, sulfur containing compounds and pigments, which offer protection against cellular damage (Dimitrios, 2006). Vitamins Ascorbic acid is found to be the most effective antioxidant in inhibiting lipid peroxidation initiated by a peroxyl radical initiator among several types of antioxidants including a-tocopherol (Fei et al, 1989). Ascorbic acid is also capable of scavenging hydrogen peroxide, singlet oxygen, superoxide and hydroxyl radicals efficiently (Fei et al, 1989). It is also involved in the regeneration and recycling of tocopherols and ß-carotene (Niki et al, 1995). Numerous studies have shown that ascorbic acid is effective in lowering the risk of developing cancers (Block, 1991) and cardiovascular diseases (Trout, 1991). In spite of the overwhelming evidence on the health benefits, however, there are reports that demonstrated the pro-oxidant activity of ascorbic acid (Podmore, 1998). Tocopherols are essential vitamins with their major role as antioxidants in protecting polyunsaturated fatty acids (PUFAs) and other components of cell membranes and low-density lipoprotein (LDL) from oxidation , thereby preventing the onset of heart diseases (Rimm et al, 1993). Polyphenolics Polyphenolics is an extremely comprehensive phrase that covers many different subgroups of phenols and phenolic acids. These compounds are most commonly present in fruits and vegetables. They are essential to the physiology of plants, being involved in diverse functions such as lignification, pigmentation, pollination, allelopathy, pathogen/predator resistance and growth (Haslam, 1996). Polyphenolics include single-ring structure such as hydroxybenzoic acids and hydroxycinnamic acids and multi-ring structure such as flavonoids, which can be further classified into anthocyanins, flavan-3-ols, flavones, flavanones and flavonols. Some of the flavonoids such as flavan-3-ols can be found in their dimeric, trimeric and polymeric forms. Most of the polyphenolics are often associated or conjugated with sugar moieties that further complicate the polyphenolic profile of vegetables. Polyphenolics are especially important as antioxidants, because they have high redox potentials, which permit the m to act as reducing agents, hydrogen donors, singlet oxygen quenchers and metal chelator (Kahkonen et al, 1999) and alleviate free radical mediated cellular injury (Shahidi and Wanasundara, 1992). The antioxidant ability of individual polyphenolics may differ, but, as a group, they are one of the strongest groups of antioxidants. The antioxidant activity of a polyphenolic compound is chiefly determined by its structure, in particular the electron delocalization over an aromatic nucleus (Tsao and Akhtar, 2005). When these compounds react with a free radical, delocalization of the gained electron over the phenolic antioxidant and the stabilization of the aromatic nucleus by the resonance effect take place that prevent the continuation of the free radical-mediated chain reaction (Tsao and Akhtar, 2005). Sulfur-containing compounds GLs are a group of sulfur-containing compounds found in the cruciferous plants such as R. sativus, broccoli, cabbage, mustard, wasabi etc. These compounds are found to be strong antioxidants, which are indeed through activation of detoxification enzyme mechanisms for the efficient removal of xenobiotics, rather than through direct radical scavenging capability (Zhang and Talalay, 1998). This property of GLs and its hydrolysis products ITCs is considered as one of the major contributors to its anti-cancer activity (Zhang and Talalay, 1998). Antioxidant activity of R. sativus R. sativus is one of the major sources of dietary phenolic acids and flavonoids, which are mostly present as sugar conjugates (Takaya et al, 2003). The major phenolic acids found in R. sativus sprout are sinapic acid and ferulic acid, which are present in conjugated form as 1-sinapoyl-1-ß-D-glucopyranoside, ß-D-(3-sinapoyl) frucofuranosyl -a-D-(6-sinapoyl) glucopyranoside and 1-feruloyl-ß-D-glucopyranoside (Takaya et al, 2003). The major flavonoids present in R. sativus sprouts is kaempferol that occurs in a conjugated form as kaempferol-3,7-O- a-L-dirhamnopyranoside and kaempferol-3-O- a-L-rhamnopyranosyl-(1-4)- ß-D-glucopyranoside (Takaya et al, 2003). Lugasi et al (1998) demonstrated the strong antioxidant property of squeezed juice extracted from a black R. sativus root through its ability to donate electrons, chelate metal ions and scavenge free radicals in a H2O2/ ·OH-luminol system. Since HPLC analysis revealed the presence of a considerable amount of GLs degradation products and polyphenols in the squeezed juice of black R. sativus, antioxidant activity of black R. sativus root could be attributed to these compounds. Takaya et al (2003) tested methanolic extracts from 11 different plants including Daikon R. sativus sprouts for their ability to scavenge free radicals. Daikon R. sativus sprouts proved to be the most potent, almost 1.8 times more effective than Vitamin C. Souri et al (2004) studied the antioxidant activity of 26 commonly used vegetables in Iranian diet and found that methanolic extract of R. sativus leaf significantly inhibited the peroxidation of linoleic acid as compared to standard antioxidant such as a-tocopherol and quercetin. Katsuzaki et al (2004) found that hot water extract of Daikon R. sativus extract showed more significant antioxidant activity than the extract obtained at an ambient temperature. L-tryptophan was isolated and identified as the compound responsible for the antioxidant activity. They also found that L-tryptophan changed to 5-hydroxy tryptophan (5-HTP), a precursor to serotonin in the rat liver microsome model system. A plant-based 5-HTP supplement is popular for its anti-depressant, appetite suppressant and sleep aiding properties. Lugasi et al (2005) further demonstrated that squeezed juice from black R. sativus significantly alleviated the free radical reaction in rats with hyperlipidaemia by decreasing the lipid peroxidation reactions and by improving the antioxidant status. Recent study also showed that R. sativus extract reduced the extent of lipid peroxidation in a dose dependent manner in rat liver homogenate treated with cumene hydroperoxide by increasing the levels of reduced glutathione and thereby protecting the liver from the toxin induced oxidative damages (Chaturvedi, 2008). Salah-Abbes et al (2008a) showed the protective effect of Tunisian R. sativus root extract against toxicity induced by zearalenone in mice by virtue of its ability to alleviate oxidative stress through stimulation and improvement of the antioxidant status. Polyphenolics in R. sativus may act in a synergistic or additive manner with GLs and/or ITCs and exert their antioxidant activity through inhibition of lipid peroxidation, enhancing the cellular antioxidant enzymes and increasing the glutathione in the cells. Apart from these phytochemicals, R. sativus also contain several classes of peroxidases that could play a significant role in the elimination of toxic peroxides and thus reduce the impact of free radical mediated cellular injury (Wang et al, 2002). Antimicrobial activity Infectious diseases are the worlds leading cause of untimely death, killing approximately 50,000 people every year. Bacteria have a remarkable ability to develop resistance to most pharmaceutical antibiotics. An increase in such antibiotic-resistant bacteria are menacing the human population with a recurrence of infectious diseases that were once thought to be under control, at least in developed countries (Pinner et al, 1996). These antibiotic-resistant bacteria have also caused unique problems in treating infections in patients with cancer and AIDS (Dennesen et al, 1998). Since tenacious and virulent bacteria develop immunity to solitary antibiotics at an alarming speed, there is an imperative need for a holistic targeted approach to search for novel antimicrobials from natural sources, especially from plant kingdom. Long before mankind ascertained the existence of microbes, the fact that certain plants had therapeutic potential was very well accepted. Since ancient times, man has used plants as the widespread remedial tool to treat common infectious diseases. Some of these traditional medicines are still included as part of the habitual treatment of various maladies. Bearberry (Arctostaphylos uva-ursi) and cranberry juice (Vaccinium macrocarpon) are employed to treat urinary tract infections, while species such as lemon balm (Melissa officinalis), garlic (Allium sativum) and tee tree (Melaleuca alternifolia) are described as broad-spectrum antimicrobial agents (Heinrich et al, 2004). Plant based antimicrobials represent a vast unexploited source for medicines, which need to be explored further. They have an immense therapeutic potential as they are effectual in the treatment of infectious diseases while concomitantly alleviating many of the side effects that are frequently connected with synthetic antimicrobials (Cowan, 1999). Plant based anti-infective agents generally have manifold effects on the body and often act beyond the symptomatic treatment of the infectious diseases. Plants have a virtually unlimited capacity to produce secondary metabolites, especially for their defense against predation by microorganisms, insects and herbivores. Many of these secondary metabolites give plants their characteristic odors and also responsible for plant pigments. Antimicrobial phytochemicals are divided into several categories based on their structural similarity as follows: Phenolic acids These are the simplest bioactive phytochemicals consisting of a single substituted phenolic ring. Cinnamic acid and caffeic acids are the common representatives of this group. Phenolic acids are reported to be effective against viruses (Wild, 1994), bacteria (Brantner et al, 1996) and fungi (Duke, 1985). The number and site of the hydroxyl group on the phenol structure are considered to be related to their relative toxicity to microorganisms. Phenolic acids which are in the higher oxidized state are often more inhibitory towards microorganisms than the one with the lower oxidation state (Scalbert, 1991). Thus the mechanisms thought to be responsible for the antimicrobial activity of phenolic acid could include enzyme inhibition by the oxidized compound through interaction with SH groups or through nonspecific interaction with the microbial proteins (Mason and Wasserman, 1987). Quinones They are aromatic compounds with two ketone substitutions in the phenolic ring. They are ubiquitous in nature and show general antimicrobial properties (Duke, 1997). They are extremely active as they can switch between hydroquinone and quinone through oxidation/reduction reactions. Quinones bind with proteins irreversibly, leading to inactivation of proteins and loss of function (Stern et al, 1996). They may also make substrates unavailable to the microbes. Flavonoids They are phenolic structures containing hydroxyl groups. They are ubiquitous and are commonly found in fruits, vegetables, nuts, tea, wine, honey, etc. They are known to be effective antimicrobial compounds against a wide variety of microorganisms (Cushnie and Lamb, 2005). Catechins are the most extensively researched flavonoids for their possible antimicrobial activity due to their occurrence in green tea (Toda et al, 1989). Flavonoids have the ability to complex with extracellular proteins as well as with bacterial cell walls, rendering them inactive (Cushnie and Lamb, 2005). More lipophilic flavonoids may also have the ability to disrupt microbial membrane (Tsuchiya et al, 1996). Terpenoids and essential oils Essential oils are secondary metabolites that are highly supplemented in compounds based on an isoprene structure (Cowan, 1999). They are called as terpenes and usually occur as di, tri, tetra, hemi and sesquiterpenes. When the compounds contain extra elements such as oxygen, they are called as terpenoids. Camphor, farnesol, artemisin and capsaicin are the common examples of terpenoids. Terpenes and terpenoids are active against an array of bacteria (Habtemariam et al, 1993) and fungi (Rana et al, 1997). Previous research showed that terpenoids present in the essential oils of plants could be useful in the control of Listeria monocytogenes (Aureli et al, 1992). The mechanism action of terpenes is not yet established precisely, but is speculated to be due to the disruption of bacterial cell membrane by the lipophilic terpenoids (Mendoza et al, 1997). Alkaloids Alkaloids constitute large groups of compounds containing a nitrogen atom in a heterocyclic ring, with a broad range of biological activities. The first medically functional alkaloid was morphine isolated from Papaver somniferum (Fessenden and Fessenden, 1982). Alkaloids are generally found to have potent antimicrobial activity (Ghoshal et al, 1996). Solamargine, a glycoalkaloid from the berries of Solanum khasianum reported to be useful against HIV infection and intestinal infections associated with AIDS (McMahon et al, 1995). Berberine is an important and frequently studied member of the alkaloid group. It is potentially efficient against trypanosomes (Freiburghaus et al, 1996) and plasmodial infections (Wright et al, 1992). The mode of action responsible for the antimicrobial activity of alkaloids may be attributed to their ability to intercalate with DNA and arresting the metabolic activity of the bacterial cells (Phillipson and ONeill, 1987). Sulfur-containing compounds Sulfur-containing compounds encompass a wide array of compounds and usually found in the plants as glucosides (glucosinolates, alliin, etc). These glucosides, during the rupturing of the plant cell wall, are hydrolyzed into volatile sulfur compounds such as ITCs, allicin, allyl sulfide, diallyl disulfate, etc. Biological activity of sulfur-containing compounds is considered to be chiefly due to glucoside degradation products, as intact glucosides usually display much fewer biological activities than their subsequent hydrolysis products (Donkin et al, 1995). The mechanism of action responsible for the antimicrobial activity of sulfur-containing compounds varies. Antimicrobial activity of ITCs, degradation products of GLs, is thought to be related to its NCS group, in which the central carbon atom is highly electrophilic, which could interact irreversibly with