INTRODUCTION

Medicinal powers in plants are an old idea. A small percentage of plants are used by human as food, even more are used for medicinal purposes. Medicinal plants are an important parts of the medicine background. Most of the populations in the world depend on herbal medicine for their health care needs (Manandhar, 1994). Phytochemicals in fruits, vegetables, spices and traditional herbal have been found to play protecting roles against human diseases (Schippmann et al., 2002). Crude or fractionated extracts and sometimes individual plant compounds are used for antibacterial, anti-inflammatory, antioxidant activities (Lev and Amar, 2002, Adam and Abdull Rasad, 2015).

Historically, man depends on the plants for medicine. The plant kingdom represents a rich store of traditional medicines and organic compounds that may lead to development of new agents that are considered as important drugs in one or more countries in the world. Unlike current drugs which are single active components that effect a specific pathway, medicinal plants may work in a way that depends on an synergetic effects. A plant contains a multiple different molecules may act synergistically on targeted elements of the complex cellular pathway (Durmowicz and Stenmark. 1999). In addition, the use of medicinal plants in medical synthesis becomes well-liked due to toxicity and side effects of synthetic drugs. Thus, medicinal plants play an important role in the enlargement of new healing agents (Verma and Singh 2008).

Jordan has a huge variation in wild plants due to the geographical and climatic diversity. It is known to have more than 2000 plant species belonging to about 700 genera. Among these plants, there are many of 485 species from around 99 plant families were categorized as medicinal plants (Oran and Al-Eisawi, 1998).  Ethnopharmacological  examination of traditional drugs sold in Jordan showed that there are 236 local and imported plants used in Jordan traditionally for treatment of different disease (Lev and Amar, 2002).

Moringa has a direct impact on health, nutrition, agriculture, biodiversity and environment. Moringa peregrina is considered as miracle tree, because all of its parts are used. Thus, this review is prepared to highlighted  the  Antimicrobial and Immunomodulatory activities of Moringa peregrine extracts. Moringa is a perennial soft wood tree with wood of low value, but for many centuries it has been used for traditional medicine and industrial uses. In the Philippines, where the leaves of the Moringa were cooked and fed to babies, its called “mother’s best friend” (Fuglie, 1999). Moringa trees have been used to combat starvation, especially among infants and tending mothers. Three non-governmental organizations, Trees for Life, Church World Service and Educational Concerns for Hunger Organization, have considered Moringa as natural nutrition for the tropics. Leaves can be eaten fresh, cooked, or stored as dried powder for many months without loss of nutritional value (Fahey, 2005; Mughal et al., 1999). The Moringa could become one of the world’s most important plants, at least in humanitarian area.

The uses for Moringa include: crop (biomass production), animal feed (leaves and treated seed- cake), biogas (from leaves), home cleaning agent (crushed leaves), blue dye (wood), fence (living trees), fertilizer (seed-cake), foliar nutrient (juice expressed from the leaves), green fertilizer (from leaves), gum (from tree trunks), honey- and sugar cane juice-clarifier (powdered seeds), honey (flower nectar), medicine (all plant parts), ornamental plantings, biopesticide (soil incorporation of leaves to prevent seedling damping off), pulp (wood), cord (bark), tannin for tanning hides (bark and gum),  water purification (powdered seeds) (Fuglie, 1999). Thus, Moringa promotes economic development (Kebreab et al, 2005).

Phytochemicals are those chemicals produced by plants. Chemicals which may have direct  contact with health, taste, odor, and color of the plants, but are not required by humans as essential main nutrients. Test of the phytochemicals of Moringaceae species were afford to examine a range of exclusive compounds that it contains. Moringaceae family is rich in compounds containing the simple sugar, rhamnose, and it is rich in a compounds called glucosinolates and isothiocyanates (Bennett et. al., 2003; Fahey et. al., 2001).

Moringa peregrina, is known in Arabic as “Habb El Yasar, Habb El Pan”, the seeds are known as “Habba Ghalia”. It is occur in nature in dry or semiarid countries neighboring the Red Sea, from Somalia and Yemen to Palestine and to Syria (Somali et al.,  1984). Flowers appear before leaves in May. The pod is pendulous and contains slanting, nut-like white seeds which are of bitter sweet taste and rich in oil. Flowering and fruiting: February-April (Morton, 1991). When Moringa peregrina seedlings start out, they have broad leaflets and a large tuber. As the plant gets older, the leaves get longer and longer, but the leaflets get smaller and smaller and more widely spaced. Adult trees produce leaves with a full complement of tiny leaflets, only to drop them as the leaf matures. However, the naked leaf axis remains, giving the tree a translucent look similar to Tamarix (Al-Kahtani, 1993).

Even though there is worry about the decline of Moringa peregrina especially where it collected for fuel, it is not listed in the IUCN Red List 2006. It is endangered in the Sinai in Egypt. Hard work to restore the local flora by restoring the stand of the dominant species, were resulted in an increase in the numbers of it. Moringa peregrina is included in a field gene bank of fodder plants in Oman (Olson., 2002).

Antimicrobial activity

Since, there are increasing incidences of fresh and unwanted infectious diseases, appearance of unwanted side effects of certain antibiotics, as well as the increasing development of conflict to the antibiotics in clinical use, the nonstop search for a new antimicrobial compounds is highly needed. This search may yield to various chemical structures and new mechanisms of action for antimicrobial agents (Cowan, 1999).

Many previous studies were reported that various parts of Moringa roots, flowers, bark, and stem including seeds possess antimicrobial properties (Lockett et al., 2000; Anwar and Rashid, 2007). Powdered of Moringa oleifera seeds were traditionally used for water purification because of their ability to clot of suspended mud and other materials causing turbidity (Lalas and Tsaknis, 2002). During this process a decrease of the total microorganisms accounts of the purified water were observed, indicative of that the seeds contain substances with antimicrobial activity (Bhoomika et al., 2007).

Broin et al. (2002) reported that a recombinant protein in the seed of Moringa is able to flocculate gram-positive and gram-negative bacteria. In this case, microorganisms can be removed by settling in the same manner as the removal of colloids in properly coagulated water. On the other hand, the seeds may act directly upon microorganisms and result in growth inhibition. Antimicrobial peptides are acts by disrupting the cell membrane or by inhibiting essential enzymes (Suarez et al., 2003).

Moringa oleifera seed extracts were assayed for antimicrobial activity against bacterial strains: Pasturella multocida, Escherichia coli, Bacillus subtilis and Staphlocuccus aureus and fungal:

Fusarium solani and Rhizopus solani strains. The crude, supernatant, residue and dialyzed samples inhibited the growth of all microbes at different variety. The zones of inhibition showed greater sensitivity against the bacterial strains as compared to the fungal strains. The Moringa oleifera extracts worked in dose dependent manner and resulted in distorted hyphae and apical branching in fungi. Minimum inhibitory concentrations (MIC) of Moringa oleifera extracts revealed that Pasturella multocida and Bacillus subtilis were the most sensitive strains to the extracts. However, the activity of the extracts was antagonized by cations (Na+, K+, Mg2+ and Ca2+). Maximum activity were found between temperature 4 -37 °C and pH 7 (Jabeen et al., 2008).

Sutherland et al. (1990) reported that Moringa seeds could inhibit the replication of bacteriophages. The antimicrobial effects of the seeds are attributed to the compound benzyl isothiocynate. Jahn et al. (1986) identified the bactericidal substances in Moringa seeds as pterygospermin, moringine and the glycosides benzylisothiocyanate and 4-(α-L- rhamnosyloxy)-phenylacetonitrile. These substances inhibited mainly Bacillus subtilis, Mycobacterium phei, Serratia marcescens, E. coli, Pseudomonas aeruginosa, Shigella and Streptococcus. In addition, Harvey (2005) reported that Pterygospermin, a bactericidal and fungicidal compound contained in an aqueous extract made from seed of Moringa oleifera was effective against Staphylococcus aureus as the antibiotic neomycin.

The antimicrobial activity of the oil extracted with n- hexane from the seeds of Moringa peregrina was tested against Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae. The oil proved effective against all of the tested bacterial strains (Lalas et al., 2012). Furthermore, Spiliotis et al. 1997 tested the antimicrobial activity of seed water extracts and seed oil of three Moringa oleifera varieties on various microorganisms (including S. aureus, S. epidermidis, P. aeruginosa, E. coli and C. albicans).

Roots of Moringa oleifera have antimicrobial and anti-inflammatory compounds. The antimicrobial activity of isolated compounds from  Moringa oleifera root extracts were against Staphylococcus aureus and gram negative Shigella dysenteriae, Shigella boydii, Salmonella typhimurium and Pseudomonas aeruginosa. All produced zone of inhibitions between 9 to 13mm in diameter (Nikkon et al., 2003).

Antibacterial activity of aqueous and ethanolic extracts of Moringa oleifera seeds were tested against Staphylococcus aureus, Vibrio cholerae, Escherichia coli and Salmonella enteritidis. Antibacterial activity were as inhibition zones >13mm in diameter against Staphylococcus aureus, Vibrio cholerae and Escherichia coli (Vieira et al. 2010).

Balanites aegyptiaca and Moringa oleifera aqueous and organic leaves extracts traditionally used for the treatment of infectious disease, they tested for their activity against Salmonella typhimurium by Doughari et al., (2007). Extracts of Moringa oleifera resulted  in 8mm zone of inhibition at 100 mg/ml. Three solvents were used and ethanol extracts of both plants demonstrated the highest activity, whereas the aqueous extracts showed the least activity at 100 mg/ml. The activities of these plant extracts were comparable to those of antibiotics, ciprofloxacin, cotrimoxazole. The antibacterial activity appears to increase when extracts of the two plants were used in combination at 100 mg/ml each (18 mm zone of inhibition). The antibacterial activities of the extracts on Salmonella typhimurium was reasonably stable when treated at 4, 30, 60 and 100 °C for 1 hour, however it is reduced significantly when the pH was changed to more than 8 (Doughari et al., 2007).

Moringa oleifera isolated compounds have wide  band of antimicrobial activity which recorded by Eilert et al. (1981). These compounds were screened for antimicrobial activity against six gram positive and seven gram negative bacteria and were found that water extract, ethanol and petroleum, ether extracts possess high antimicrobial activity. The water extract of M. oleifera leaves inhibited the growth of Escherichia coli and Enterobacter aerogenes. The zone of inhibition of Escherichia coli were 7 mm for 200 mg/ml and 10 mm for 1000 mg/ml of the extract compared to 12 mm produced by the standard drug, tetracycline (250 mg/ml) (Thilza et al., 2010).

Nikkon et al. (2003) reported that the antimicrobial activity of aglycone of Deoxy-Niazimicine which is characterized as N-benzyl, S-ethyl thio-formate from the chloroform extract of Moringa oleifera roots barks. The compound was showed antibacterial activities against Shigella boydii, Shigella  dysenteriae and Staphylococcus aureus.

Moringa oleifera roots have antibacterial activity and are rich in antimicrobial agents. The latter is mainly because they contain an active antibiotic principle, pterygospermin. Pterygospermin considered as the active compound in Moringacaea that causes its antibacterial action, once consumed, it break down into two separate benzyl isothiocyanate, a substance with known antimicrobial properties (Ruckmani et al., 1998). Cáceres et al. (1991) reported the antimicrobial activities of Moringa oleifera leaves, roots, barks and seeds in vitro against bacteria, yeast, by a disk-diffusion method. The fresh leaf juice and aqueous extracts from the seeds inhibit the growth of Pseudomonas aeruginosa and Staphylococcus aureus.

Ethanol extract of fresh leaves were showed a wide antibacterial effect against all the tested gram- negative bacteria (S. shinga, P. aeruginosa, S. sonnei, Pseudomonas spp.) and some gram-positive bacteria (B. cereus, B. subtilis, S. lutea, B. megaterium) and their respective diameter zones of inhibition were 17.5, 21.21, 21.5, 21.25 and 16.25, 20.23, 19.50, 20.50 mm in diameter, respectively. The activity of the plant against both gram-positive and gram negative bacteria may be indicative of the presence of broad-spectrum antimicrobial compounds in the Moringa oleifera (Siddhuraju and Becker, 2003; Vaghasiya and Chanda, 2007).

Quinones which are a group of naturally occurring phenol compounds are found in M. oleifera leaves and tend to have laxative effects. Terpenoids and steroids present in M. oleifera leaves were described as being active against bacteria such as Staphylococcus aureus. M. oleifera leaves contains alkaloids which are nitrogen-containing naturally occurring compounds, commonly found to have antimicrobial properties due to their ability to intercalate with DNA of the  microorganisms (Bennett et al., 2003).

 Moringa flavonoids, which are many in numbers, were found to be strong antimicrobial substances in vitro against a wide collection of microorganisms by inhibiting the membrane bound enzymes. They reported to possess substantial anti carcinogenic and anti mutagenic activities due to their antioxidant and inflammatory properties (Li-Weber, 2009).

Immunomodulatory

Immunomodulator is a substance which stimulates or regulates the immune system including both innate and adaptive immune responses. The modulation of immune system by various medicinal plant products has become a subject for scientific investigation. The immune system is the basic defense system of the body against pathogens and other foreign substances. Its function is to prevent foreign substances fm invading the body and causing disease (Sherwood and Kinsky, 2004).

Immunomodulatory effect of ethanolic extract of M. oleifera leaves were studied in normal and immunosuppressed mice models. Pre-treatment of Moringa                ethanolic       extract inhibited cyclophosphamide bone marrow suppressive effect and phagocytic activity in mice (Anamika et al., 2010). Furthermore, different doses of Moringa oleifera caused significant increase in the level of white blood cell counts and immunoglobulin levels (Adedapo et al., 2005).

Since Moringa is rich in ginseng and ginseng saponins were reported to have antioxidant, anti- inflammatory, anti-apoptotic and immune-stimulant properties, this raised theory that Moringa plant and its extracts could be play part in immunomodulation (Rausch et al. 2006). Furthermore, Sashidhara et al., (2009) isolated aurantiamide acetate and 1, 3- dibenzyl urea, from roots of Moringa oleifera . Aurantiamide acetate showed significant inhibition on tumor necrosis factor (TNF-α) and interleukin two (IL-2) but not on interleukin (IL-6), while 1,3- dibenzyl urea showed to significantly induce analgesic activity in dose dependant manner and significant inhibition on IL 2. These results indicates that these compounds may be responsible for the anti-inflammatory, anti-arthritic and analgesic activity of Moringa oleifera root.

Moringa peregrina extracts exhibited antioxidant activity and the extracts could be considered as a source of natural antioxidants. Moringa  peregrina has potential as an anti-inflammatory and antioxidant agent against inflammation and free radicals. Anti- inflammatory and antioxidant activities of Moringa peregrina seeds ethanolic and aqueous extracts were tested by Koheil et al (2011). The results indicated that Moringa peregrina ethanolic and aqueous extracts (100-300 mg/kg) inhibited significantly fresh egg albumin-induced acute inflammation. In addition, ethanolic and aqueous extracts of Moringa peregrina exhibited a strong reducing power, Fe2+ chelating effect, free radical scavenging activity, hydrogen peroxide scavenging ability, and hydroxyl radical scavenging activity. These latter effects were shown to be dose dependent.

The antioxidant properties of Moringa leaves allow the immune system to scrap infections and cancers more effectively, providing the body with a secondary line of defense against pathogens and offering hope to those pain from reduced immunity due to illness. The flavonoids such as quercetin and kaempferol were identified as the most potent antioxidants in Moringa leaves. Their antioxidant activity was higher than the conventional antioxidants such as ascorbic acid, which is also present in large amounts in Moringa leaves (Siddhuraju and Becker, 2003). Moringa is found to be rich in quercetin and glucosinolates. These phytochemicals are precursors of a wide range of bioactive compounds among established antibiotic, anticancer and antioxidant properties. Significant variations in antioxidant activity were reported in four Moringa species, with M. peregrina showing the maximum antioxidant activity (Ray et al., 2006).

Source : Antimicrobial Immunomodulatory activities of Moringa peregrine