ISSN 2278- 4136

ZDB-Number: 2668735-5

IC Journal No: 8192 Volume 1 Issue 6

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Journal of Pharmacognosy and Phytochemistry

Bioprospecting of (Moringaceae): Microbiological Perspective

Daljit Singh Arora1*, Jemimah Gesare Onsare1 and Harpreet Kaur1

1. Microbial Technology Laboratory, Department of Microbiology, Guru Nanak Dev University, Amritsar 143005, . [E-mail: [email protected]; Tel: 91-183-2258802-09, Ext: 3316; Fax: 91- 183- 2258819]

Plants produce primary and secondary metabolites which encompass a wide array of functions. Some of these have been subsequently exploited by humans for their beneficial role in a diverse array of applications. However, out of 750,000 species available on earth, only 1 to 10 % is being potentially used. Moringa is one such belonging to the family of Moringaceae, a monotypic family of single genera with around 33 species. Most of these species have not been explored fully despite the enormous bioactivity reports concerning various potentials such as: cardiac and circulatory stimulants; anti-tumor; antipyretic; antiepileptic; anti-inflammatory; antiulcer; antispasmodic; diuretic antihypertensive; cholesterol lowering; antioxidant; antidiabetic; hepato protective; antibacterial and antifungal activities. They are claimed to treat different ailments in the indigenous system of medicine. Surprisingly, some of the species have been reported to be extinct from the face of earth before their exploration and exploitation for economic benefits. This review focuses on the bio-prospects of Moringa particularly on relatively little explored area of their microbiological applications Keyword: Applied microbiology, Antimicrobials, Moringa species.

1. Introduction resistant pathogens[3] and for this, have been and will remain vital to phytomedicine is becoming popular in mankind, animals as well as environment. They developing and developed countries owing to produce primary and secondary metabolites its natural origin and lesser[4] side effects. which encompass a wide array of functions[1] Plants are the richest bio-resource of drugs of many of which have been subsequently traditional systems of medicine, modern exploited by humans for their beneficial role in medicines, nutraceuticals, food supplements, a diverse array of applications[2]. The most folk medicines, pharmaceutical intermediates important of these bioactive constituents of and chemical entities for synthetic drugs. It is plants are the secondary metabolites which estimated that today, materials are present include alkaloids, phenolic compounds, tannins, in, or have provided the models for 50% phytosterols, and terpenoids. Infectious diseases Western drugs[5,6]. The list of benefits of plants’ are the leading cause of death worldwide in the bioactive compounds to human health such as current scenario where clinical efficacy of anti- cancer, anti-hypertension, anti- many conventional antibiotics is being hypoglycaemia, anti-oxidants and antimicrobial threatened by the emergence of multidrug activities have been reported[7-14].

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The search for plants as a source of potential extract in the warfront. The Elixir drink was candidate for drug development is still unsound. believed to add them extra energy and relieve Out of 250,000 to 500,000 species available on them of the stress and pain incurred during war. earth only 1-10% percent are being potentially The Moringa species are currently of wide used[15]. Moringa is one such genus whose interest because of their outstanding economic various species have not been explored fully potential. Amongst these species, M. oleifera is despite the enormous reports concerning the the most prevalent for its nutritious and various parts of a few species’ potentials such numerous medicinal uses that have been as: cardiac and circulatory stimulants; anti- appreciated for centuries in many parts of its tumor; antipyretic; antiepileptic; anti- native and introduced ranges[22-24].Recently, a inflammatory; antiulcer; antispasmodic; diuretic few others like M. stenopetala, M. peregrina antihypertensive; cholesterol lowering; and M. concanensis have been discovered to be antioxidant; antidiabetic; hepato- protective; having equal potential such as nutritious antibacterial and antifungal activities. These are , high-quality seed oil, antibiotics and also being used for treatment of different water clarification agents just like the M. ailments in the indigenous system of oleifera. In this review we focus on the bio- medicine[16-21]. The indigenous knowledge and prospects of Moringa species particularly on use of Moringa is referenced in more than 80 relatively little explored area of their countries and it’s known in over 200 local microbiological applications and ascertain the languages. Moringa has been used by various prevailing gaps. societies including the Roman, Greek, , India and many others for thousands of years 2. Moringaceae Family with writings dating as far back as 150 AD. The The family Moringaceae is a monotypic family history of Moringa dates back to 150 B.C. of single genera with around 33 species (Table 1) where ancient kings and queens used Moringa of which 4 are accepted, 4 are synonym and 25 leaves and fruit in their diet to maintain mental are unassessed[25]. Out of these, 13 species, alertness and healthy skin. Ancient Maurian native of old world tropics[26] are documented. warriors of India were fed with Moringa leaf (Table 2, Figure1 a, b, c)

2.1. Taxonomic classification: [27]

Kingdom : Plantae Subkingdom : Tracheobionta Super division : Spermatophyta Division : Magnoliophyta Class : Subclass : Order : Family : Moringaceae Genus : Moringa

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Table 1: Different species of Moringa Species Authorship Taxonomic status Moringa amara Durin Unresolved M. aptera Gaertn. Unresolved M. arabica Pers. Unresolved M. arborea Verdc. Unresolved M. borziana Mattei Unresolved M. concanensis Nimmo ex Dalzell & A.Gibson Unresolved M. concanensis Nimmo Unresolved M. domestica Buch.-Ham. Unresolved M. drouhardii Jum. Unresolved M. edulis Medik. Unresolved M. erecta Salisb. Unresolved M. hildebrandtii Engl. Unresolved M. longituba Engl. Unresolved M. Moringa (L.) Millsp. Synonym M. myrepsica Thell. Unresolved M. nux-eben Desf. Unresolved M. octogona Stokes Unresolved M. oleifera Lam. Accepted M. ovalifolia Dinter & A.Berger Accepted M. ovalifolia Dinter & Berger Unresolved M. ovalifoliolata Dinter & A. Berger Synonym M. parvifolia Noronha Unresolved M. peregrine (Forssk.) Fiori Accepted M. polygona DC. Unresolved M. pterygosperma Gaertn. Synonym M. pygmaea Verdc. Unresolved M. rivae Chiov. Unresolved M. robusta Bojer Unresolved M. ruspoliana Engl. Unresolved M. stenopetala (Baker f.) Cufod. Accepted M. streptocarpa Chiov. Unresolved M. sylvestris Buch.-Ham. Unresolved M. zeylanica Burmann Synonym Source data[25]

Table 2: Geographic distribution of documented 13 Moringa species and their morphotypes Species Geographical location Bottle trees M. drouhardii Jum M. hildebrandtii Engl. -do- M. ovalifolia Dinter & A. Berger and S.W. M. stenopetala (Baker f.) Cufod and Slender trees M. concanensis Nimmo. India M. oleifera Lam. -do- M. peregrina (Forssk) Fiori Red Sea, Arabia, Horn of Tuberous and herbs of North Eastern Africa M. arborea Verdc. North Eastern Kenya M. borziana Mattei Kenya and M. longituba Engl. Kenya, Ethiopia, Somalia M. pygmaea Verdc. North Somalia M. rivae Chiov. Kenya and Ethiopia M. ruspoliana Engl Kenya, Ethiopia, Somalia Source data[28]

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(a)

(b)

(c)

Figure 1: Morphological pictorials of three Moringa species; a): Bottle Trees; b): Slender Trees; c): Tuberous shrubs. Reprinted with permission from[28]

Figure 3. Distribution of Moringa in the old world tropics. Reprinted with permission from[28]

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3. Bioactivity feasibility of Moringa Though the information is not of scientific 3.1. Indigenous claims of unexplored background, the claims by various Moringa species indigenous people on their medicinal uses Out of the 33 species listed in Table 1, only are an indication of the untapped potential documentation of 13 species is available. (Table 3).

Table 3: Unexplored species of Moringa

Geographic Species Morphological characteristics Indigenous claims location M. drouhardii Scented bark used for Bloated bright white trunk Madagascar Jum. Colds and coughs M. ovalifolia Dinter & A. Bloated white trunk Not documented Namibia Berger M. Pygmaea* Tuberous with tiny leaflets and yellow flowers Not documented Somalia M. rivae Kenya, Large spray of pale pink & wine Red flowers Not documented Chiovenda* Ethiopia A small tree with thick, tough & large Leaves, large Somalia, M. ruspoliana flowers, thick taproot which becomes more globose as Not documented Ethiopia, Engler the plant ages Kenya Root extracts used for Kenya, M. longituba treating intestinal Bright red flowers, large tuber Ethiopia, Engler infections of Somalia domestic animals M. arborea Unspecified Kenya, Large sprays of pale pink & wine red flowers Verdcour medicinal uses Ethiopia Bears one or two stems which die back to the tuber every few years, sometimes due to variation of M. borziana Used for treatment of Kenya and environmental parameters the plant grows into a small Mattei different ailments Somalia tree, Greenish cream to yellow flowers with brown Used for treatment of smudges on the tips M. A massive water storing bloated trunk, deep red stem Unspecified hilderbrandtii tip of young plants, large spray of small whitish Madagascar medicinal uses Engler flowers[29,30] Erect trunk and white bark, small long and remote Used as an analgesic M. Peregrine leaflets, pendulous pods with angled nut like white in the ancient Egypt (Forssk) Fiori seeds world[31] *: Extinct species; Source data[28]

3.2. Documented Moringa species and has a spreading, open crown of drooping, their known bioactivities fragile branches, feathery foliage of Lamarck (Lam.) also tripinnate leaves and thick corky, whitish known by different common names as per the bark [21,22,32]. The uses of its roots, root bark, different countries’ vernacular names and can stem bark, exudates, leaves, flowers and be found in the following link: seeds in the treatment of a wide variety of http:/www.treesforlife.org/our-work/our- ailments have been discussed in the Sanskrit initiatives/Moringa. It is a small, fast texts on medicinal plants[24] and the tree growing or tree that continues to have an important role usually grows up to 10 or 12m in height. It particularly as counter-irritant in the

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indigenous medicine in Asia and West doubts about the advisability of introducing Africa[33,21,34]. Based on the indigenous aluminium into the environment by the claims, Moringa oleifera (the drumstick tree) continuous use of aluminium sulphate as a has been prevalently the subject of much coagulant in water treatment[39,40,41]. This has research and development. M. stenopetala aggravated the search for safer organic (Baker f.) Cufodontis is another species in alternatives. Moringa seeds have been focus due to its equal potential as M. oleifera. commonly known and used in many rural It is an important food plant in southwestern areas for clarification of drinking water to Ethiopia, where it is cultivated as a crop reduce the health risks associated with plant. Moringa concanensis, Nimmo. Tree excessive turbidity. Turbidity has also been commonly known as Horseradish tree, found to have a significant effect on the Drumstick tree, Never die tree, West Indian microbiological quality of drinking water and ben tree, and Radish tree which is native can interfere with the detection of bacteria through the sub- Himalayan tracts of and viruses[42].Though not a direct indicator India[35,36]. It has a very strong central trunk of health risk, a strong relationship between that is covered with an extremely distinctive turbidity removal and protozoa removal has layer of very furrowed bark. The flowers also been established[43]. have distinctive green patches at the tips of A simplified, low cost, point of use, the and . It is commonly known low risk drinking water treatment protocol as Kattumurungai by tribal peoples of using M. oleifera seeds has been invented for Nilgiris hill region in Tamil Nadu, India, and use by the rural and pre – urban people living widely used since the Ayurveda and Unani in extreme poverty who are presently using medicinal systems for the treatment of highly turbid and microbiologically several ailments[37,24]. In Microbiological contaminated water. Systematic research has perspective, the various parts of these plants shown that M. oleifera seeds acts as an have been explored and reported for their effective water clarifying agent across a wide potential in medical, food industry, range of various colloidal suspensions[44]. agriculture and the environment as explained They yield water soluble organic polymer further; also known as natural cationic (net positive charge) poly-electrolyte[45]. It was confirmed 3.2.1. Moringa in Water Treatment later to be a low molecular weight water Water is vital to life; however, due to soluble protein with a positive charge acting indiscriminate human activities its quality has as a coagulant responsible for binding with deteriorated causing about 80% of diseases predominantly negative charged particulate which plague the human race especially in matter that make raw water turbid[46]. In an many developing countries. Promising water investigation on Moringa oleifera treatment techniques are far much costly for (Drumstick) seed as natural absorbent and the ‘have nots’ and many disinfectants antimicrobial agent for river water treatment, currently used can be harmful. For instance, it a reduction of microbial colonies on plate has been indicated that the chemicals used for with increase in concentration of sample was can cause serious health observed[47]. This endorsed the previous hazards if mishandled in the course of study[34,48] as 4 alpha rhamnosyl oxybenzyl treatment process[38,39]. These reports isothiocyanate and presently known as suggested that a high level of aluminium in glucosidal mustard oil which coagulates the the brain may be a risk factor for Alzheimer’s solid matter in water and removes a good disease. Several researchers have raised portion of suspended bacteria. Similar studies

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show that Moringa flocculants are basic active in low doses[55]. This could be due to polypeptides with molecular weight between less oil in low concentrations and it goes well 6 and 16kDa with an isoelectric pH of 10 with observations made[46] regarding the to11[49].The natural poly-elecrolytes released effect of oil on the bioactive agent which from the crushed seed kernels function as forms an emulsion of film coating that natural flocculating agents, binding inhibits the reaction. Moringa seeds contain suspended particles in a colloidal suspension, an antibiotic principle known as forming larger sedimenting particles (flocs) pterygospermin which is responsible for in which microorganisms are generally destruction of micro-organisms in water[56]. attached. Hence, treatment employing M. In though not proven scientifically, the oleifera seed (press cake) can remove 90% to seeds of M. peregrina have been used as 99% of fecal coliforms bacterial load[50]. coagulant to purify water[57]. However, it has to be noted that after several hours of storage, temperature-induced 3.2.2. Moringa a Source of bacteria might regrow within the storage Pharmacological Products container and there’s no guarantee for 100% virus and /or bacteria-free water immediately 3.2.2.1. Alternative Medicine for Human after treatment or storage hence additional Pathogens disinfection process may be required. An escalating antibiotic resistance by the Similarly, a group of researchers in their pathogenic bacteria has been observed since study on traditional water purification using last decade and the adverse effects of Moringa oleifera seeds discovered a steroidal conventional antibiotics calls for a friendly glycoside – strophantidin as a bioactive agent alternative. Out of the 250,000 to 500,000 which was more efficient in the clarification species of plants on earth[15], Moringa is one and sedimentation of inorganic and organic of the 10% which have a profound potential matter in raw water and reduced 55% and in pharmaceutical industry as a source of 65% microbial and coliform load respectively bioactive constituents for drug development. after 24 hours whereas alum achieved 65% Chen[58] in her studies on the synergistic and 83% reduction under similar effect of M. oleifera seeds and chitosan (an conditions[51]. The difference in efficacy as essential and abundant component of shown in both cases above may be attributed exoskeletons – the mucoadhesive polymer to the effect of oil on the bioactive agent. It which is derived from chitin) on antibacterial forms an emulsion of film coating which may activity against Bacillus subtilis and inhibit its contact with the surface of reaction Pseudomonas putida found the individual and thus reduce floc formation[46]. Similarly, samples to be more effective than the two the difference in location of cultivation as combined. However, in another study to reported[52,53] may cause the variation. determine antimicrobial potential of different The seeds of have been plant seed extracts against Multidrug found to have flocculating and anti-microbial Resistant Methicillin Resistant properties. The active substances are found Staphylococcus aureus (MDR – MRSA), it only in the cotyledons of the seeds[54]. In a was established that Moringa oleifera seeds recent study on the antibacterial activity of had a synergistic potential to restore the Moringa oleifera and Moringa stenopetala effectiveness of B – lactam antibiotics methanol and n-hexane seeds extracts against MRSA[59]. The synergistic properties exhibited highest inhibition of E. coli, S. could be attributed to β – lactamase inhibition typhi and V. cholera and the samples were by the Flo peptide (a specific polypeptide

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found in Moringa oleifera that is both a Urinary tract infections are the second most flocculent and a biocide). The cationic Flo common of infection in the world. It is peptide supposedly serves as a highly mainly a bacterial infection that affects efficacious immunity response, interacting peoples throughout their lifespan[67]. These with the anionic cell membranes of are more common in women than men, bacterium[60]. This interaction destabilizes the leading to approximately 8.3 million doctor bacterial membrane, causing leakage of visits per year. Proteus mirabilis is a small cytoplasmic content and killing the bacterial Gram negative bacillus, facultative anaerobe cell. Antimicrobial peptides, such as the Flo belonging to the family of peptide, have been reported to act directly Enterobacteriaceae that commonly cause and non-specifically upon bacterial urinary tract infections and formation of membranes, thus hindering their ability to stones[68]. develop resistance. However, antimicrobial peptides rarely affect the membranes of cells In a study on the antibacterial effect of in multicellular species[61] an indication that Moringa oeifera leaves extracts prepared in they are ineffective against eukaryotes different solvents, petroleum ether extracts especially fungal pathogens. Recently, an in demonstrated the highest activity against vitro antimicrobial activity of Moringa clinical samples and environmental samples oleifera L. seed extracts prepared in aqueous of Proteus mirabilis[69]. However, in a and organic solvents against Staphylococcus separate study chloroform extracts[70] showed aureus, Bacillus subtilis, Escheriachia coli, broad spectrum potential than that of Pseudomonas aeruginosa, Aspergillus niger petroleum ether an indication of the presence and Candida albicans exhibited of different active principles. In vitro studies antimicrobial properties[62]. However, this is on different extracts of the root bark of partly contradicted by the findings in our Moringa oleifera against Staphylococcus laboratory using up to 20% aqueous extracts aureus, Echerichia coli, Salmonella of the same plant (unpublished data) where gallinarum, Pseudomonas aeruginosa one of the seeds sample collected from a among others showed that ethyl acetate and different locality exhibited less active and to acetone extracts exhibited maximum activity a few test organisms among Gram positive, as compared to other solvents[71,72] which Gram negative and yeast pathogens used shows that active compounds are polar in which may be due to differences in source of nature. Antimicrobial activity studies of stem the samples as depicted earlier[52,53]. The bark of Moringa oleifera against some variation may also be brought about by human pathogens demonstrated methanolic environmental changes such as effect of extracts to be the most effective among other pathogens[63], allelopathy and herbivory[64] solvents used[73,74]. In most recent study on in which may trigger production of high levels vitro antibacterial and antifungal potential of of secondary metabolites. On the other hand, Moringa oleifera stem bark against ten water availability, exposure to soil pathogens bacterial strains and six fungal strains, and variations of soil pH and nutrients affect petroleum ether extract was reported the accumulation of secondary inactive[75]. To this point, it emanates that the metabolites[65]. Similarly, environmental different plant parts of Moringa contain a factors such as temperature, rainfall, day vast array of bioactive constituents of varying length and edaphic factors affect the efficacy polarity which can be potential candidates as of the medicinal properties of different drug leads/ development. plants[66].

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Still within this genus, a project on chemical changes, satisfy the conditions of development of pharmaceutical products biodegradability, bio-compatibility and from medicinal plants was carried out in delivery speed of the drug[81,82]. The drug is Ethiopia by the institute of Pathobiology, dissolved, entrapped, encapsulated or Addis Ababa University in 1996, Moringa attached to a nanoparticle matrix and Stenopetala was one of the plants assessed. It depending upon the method of preparation, was reported that the biological active nanoparticles, nanospheres or nanocapsules compounds isolated from both leaves and can be obtained[83,84]. Generally metal seeds of the plant by a bioassay guided nanoparticles are synthesized and stabilized fractionation exhibited antimicrobial activity by using chemical methods such as chemical against Staphylococcus aureus, Salmonella reduction[85,86] which are too costly and typhi, Shigella and Candida albicans. A hazardous. For this reason, cheaper and number of Laehiums prepared by herbal environmental friendly biological methods venders in South India was tested for are sought for. Synthesis of nanoparticles antimicrobial activity. It was reported that within the biological means using bacteria ethanol, petroleum ether, hexane (prepared in and fungi[87,88], has been proved efficient and 1000 ppm) and aqueous extracts (20%) resins safer. However, it has been established that of Moringa concanensis (which were use of plant leaves extract is cheaper[89] as it traditionally used for treatment of fire burns) reduces the costs and does not require any exhibited antimicrobial activity against special culture preparation and isolation Bacillus subtilis, Staphylococcus aureus, techniques. Use of plants in synthesis of Escherichia coli, Pseudomonas aeruginosa nanoparticles is quite novel leading to truly and Candida albicans[76]. green chemistry which provides advancement over chemical and physical method as it is 3.2.2.2. Synthesis of Nanoparticles cost effective and eco-friendly. It can be In addition to above searches, the possibility easily scaled up for large scale synthesis and of using Moringa in nanotechnology is being there is no need to use high pressure, energy, explored for useful products. Nanoparticles temperature and toxic chemicals. In this are defined as particulate dispersions or solid regard, investigations in the biofabrication of particles with a size in the range of 10- Ag nanoparticles using M. oleifera leaves 1000nm. Metal nanoparticles which have a extract revealed the leaves to have the high specific surface area and a high fraction potential of producing Ag nanoparticles of surface atoms have been studied extracellularly by rapid reduction of silver extensively because of their unique ions (Ag+ to Ag0) which were quite stable in physicochemical characteristics including solution[90]. In subsequent testing for catalytic activity, optical properties, antimicrobial activity against a number of electronic properties, antibacterial properties pathogens, this Ag nanoparticles suspended and magnetic properties[77]. Nanoparticles hydrosol showed considerable antimicrobial have a long list of applicability in improving activity in comparison to chloramphenicol human life as well the environment and and ketoconazole antibiotics. among this drug delivery technology. The technology has come into spotlight due to its 3.2.2.3. Bio- Enhancing Properties benefits such as shorter development periods Some parts of this multipurpose genus have and lower costs compared to the development also been associated with bio-enhancing of a new drug[78-80]. The ideal nanoparticle properties. Bio-enhancers are molecules materials are those which do not undergo which do not possess drug activity of their

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own but promote and augment the biological microbial spoilage and oxidative activity or bioavailability or the uptake of deterioration of food[106]. However, in recent drugs in combination therapy, resulting in years; consumers are demanding partial or reduced drug associated toxicity, reduced complete substitution of chemically cost and duration of chemotherapy. Isolated synthesised preservatives due to their plant biomolecules or their semisynthetic possible adverse health effects. This fact has derivatives have provided useful clues in the led to an increasing interest in developing production of medicines[91]. Recently, in a more “natural” alternatives in order to pre-clinical study on the influence of enhance shelf-life and safety of the food[107]. Moringa oleifera pods on Pharmacokinetic Though not so extensive work in this field in disposition of rifampicin using HPLC- PDA regard to the plant under review, a recent method established that the active fraction study indicated that seeds exhibited the isolated from air dried pods of the plant when potential as sanitizers/preservatives by mixed with rifampicin and administered to inhibiting the growth of organisms such as E. the experimental animals enhanced systemic coli, S. aureus, P. aeruginosa, S. typhi, S. availability of the drug and suppression of the typhimurium and E. aerogenes which range drug metabolizing cytochrome P-450[92]. In from pathogenic to toxigenic organisms another study, a bioenhancing property of M. liable to cause food – borne illnesses to oleifera pods extract was reported. It was spoilage-causing organisms liable to spoil found that niaziridin rich fraction of M. food products[108]. oleifera pods enhances the bioactivity of commonly used antibiotics such as 3.2.4. Moringa in Agriculture rifampicin, tetracycline and ampicillin The practice of using plant derivatives or against Gram positive and Gram negative botanical insecticides in agriculture dates bacteria. It also facilitated the absorption of back to at least two millennia in ancient drugs, vitamins and nutrients through the China, Egypt, Greece, and India 109,110. What gastro-intestinal membrane thus increasing is clear from recent history is that synthetic their bio-availability[91]. This lowering of the insecticides effectively relegated botanicals dosage level and shortened treatment course from an important role in agriculture to an of rifampicin as an anti-tuberculosis drug essentially trivial position in the marketplace minimize its associated side effects to the among crop protectants. However, history advantage of the patients. also shows that overzealous use of synthetic insecticides led to numerous problems 3.2.2.4. Other Pharmacological Potentials unforeseen at the time of their introduction: Though the review focuses on the economic acute and chronic poisoning of applicators, potentials of Moringa from the farm workers, and even consumers; Microbiological perspective, it will be worth destruction of fish, birds, and other wildlife; listing the prospects of this genus in other disruption of natural biological control and pharmacological fields (Table4) ; extensive groundwater contamination, potentially threatening human 3.2.3. Moringa in Food Preservation and environmental health; and the evolution Protection of food from microbial or of resistance to pesticides in pest chemical deterioration has traditionally been populations[111-114]. Trials on the potential of an important concern in the food industry. Moringa oleifera for agricultural and Chemically synthesized preservatives have been classically used to decrease both

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Table 4: Scientific / Traditional claims of pharmacological potentials of Moringa species

a: M. oleifera; b: Comprehensively covered; c: L- leaves, LT- tender leaves, F-flowers, B-bark, Bs- stem bark, R- roots, P-pods, S-seeds, O-oil (from seeds), G-gum, W-wood; d: M. stenopetala; e:M. concanensis; f:M. peregrina; ;GNS: General not specific٭٭٭ ;NS: Not specified٭٭ ;Combination therapy :٭;g: M. hildebrandtii; h: M. drouhardii Other species not documented :٭٭٭٭

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industrial use have shown that the leaves of In light of the above, there is scanty this plant contains a bioactive substance literature on Moringa genus in regard to which when sprayed on crops indicates toxicological studies. However, the few accelerated growth of young plants, which reports on M. oleifera and M. stenopetala become more resistant to pests and available are not exhaustive. Adedapo et diseases[115]. Though no further literature is al.[124] established in their study that aqueous available in this regard, the potential of extract of Moringa oleifera leaves was Moringa in agriculture is obvious in this nontoxic in rats both oral and sub-acute on study and needs extensive exploration. haematological biochemical and histological parameters. In a similar study, Ashong and 4. Toxicological reports on some Moringa Brown[125] observed no impact and short species term toxicity of aqueous leaf extracts of Toxicological evaluation of medicinal plants various concentration on feed intake of has often been neglected by many traditional poultry. The ethanolic and aqueous extracts healers with the notion that plants are of M. oleifera bark were found to have no harmless and therefore historical usage of adverse effect on growth related and such products cannot always be a reliable biochemical parameters in rats, an guarantee of safety. It is difficult for these indication that neither steroids, triterpenoids, practitioners to detect or monitor delayed saponins, alkaloids nor effects (e.g. mutagenicity), rare adverse phytoconstituents identified were toxic 126. effects arising from long-term use[116] as in Kasolo et al.[127] in their in vivo study food supplements and nutraceuticals e.g. established that acute toxicity tests with Glycyrrhiza glabra, which is used for aqueous and ethanol extracts of M. oleifera conditions like bronchitis and peptic ulcers roots exhibited a safe range where the LD50 causes not only hypertension, weight gain for aqueous extracts was 15.9mg/kg and for and hypokalaemia but also low levels of ethanolic extract was 17.8mg/kg. However, aldosterone and anti-diuretic hormone on in the most recent studies on the effect of excessive or prolonged usage[117]. Many methanolic extracts of M. oleifera roots on widely used medicinal plants have been histology of kidney and liver on Guinea Pigs implicated as possible causes of long-term was found to distort the histo-architecture of disease manifestations such as liver and both the organs and the effects were time as kidney diseases for instance widespread use well as dose dependent[128]. Several in vivo of Scenecio, Crotalaria and Cynoglossum studies indicate aqueous extracts of M. has been implicated in the occurrence of oleifera seeds to be safe[129,130]. However, liver lesions and tumours, lung and kidney Oluduro and Aderiye[131] contradicted these diseases in certain areas of Ethiopia 118. findings in their study on the effect of M. Similarly, reports are available on accidents oleifera aqueous seed extracts on vital due to mistakes of botanical identification, organs and tissue enzyme activities of male plants that interfere with pharmacological albino rats where their findings suggested therapy (such as those containing that prolonged consumption of water treated coumarinic derivatives, high tyramine with ≥ 2mg/ml of M. oleifera seeds may content, those containing oestrogenic lead liver infarction. Similar observations compounds, those that cause irritation and though with methanolic extracts were made allergy, those containing photosensitive in a different study which confirmed that compounds)[119-123]. administration of these seeds extracts appears relatively nontoxic to animals at low

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doses. However, at high dosages, the intervention of more rapid and less alterations observed in various parameters expensive approaches to work at the in vitro tested suggested a dose sensitive toxicity as well as in vivo toxicity. when repeatedly consumed on a daily basis for a prolonged time[132]. 5. Phytoconstituents of Moringa The cytotoxicity of extracts from a widely Out of the 13 species of Moringa, Moringa used species of plant, Moringa stenopetala, oleifera has been given much publicity was assessed in HEPG2 cells, by measuring including its phytoconstituents. A few others the leakage of lactate dehydrogenase (LDH) such as M. stenopetala, M. peregrina, M. and cell viability. The functional integrity of concanensis have been reported. extract-exposed cells was determined by Nevertheless, the various studies reported measuring intracellular levels of ATP and (Table 5) are not exhaustive and much work glutathione (GSH). The ethanol extracts of is needed to establish the comprehensive leaves and seeds significantly increased (p < phytoconstituents of these and other 0.01) LDH leakage in a dose- and time- Moringa species, and further explore and dependent manner. However, aqueous exploit their antimicrobial properties not extract of leaves and ethanol extract of the forgetting to ascertain the safety of the root did not increase LDH leakage. A highly active principles. significant (p < 0.001) decrease in HEPG2 viability was found after incubating the cells with the highest concentration (500µg/ml) of In light of the limitations in the various the ethanol leaf and seed extracts. The water studies reported herein, looking at different extract of the leaves did not alter GSH or parameters in a systematic way in this LDH levels or affect cell viability, context and not just a single assay for suggesting that it may be non-toxic. This determining the biological efficacy of plants was an indication that not all compounds of is of essence based on the following facts: these morphological parts tested were toxic but only those extractable by ethanol[98]. In  Some compounds which show good activity another study to establish the effects of M. in vitro may be metabolized in vivo into inactive metabolites. Alternatively, extracts stenopetala on Blood parameters and may only show in vivo activity due to the histopathology of liver and kidney in mice, metabolism of inactive compounds into it was reported that the extract did not show active forms 140. any morphological changes in the liver cells  Similarly, the pharmacological investigation as well as no histopathological changes in of drug interactions in multi-compound preparations is difficult due to the presence the kidneys of the treated mice with all 101 of several constituents where some may doses used (600,750,900mg/kg) . From show less specific activity and some may these studies we cannot make a haste camouflage the toxicity and activity of the conclusion of safety or toxicity of the more therapeutically effective compounds. sample under study since different solvents  There is no one solvent which can extract all the phyto-constituents and thus several of are responsible for extracting different them should be used for better comparison. compounds. Therefore, a compound of  Some of the most common side effects are interest should be tested on its own or a difficult to recognize in animal models e.g. systematic extraction (using all possible nausea, nervousness, lethargy, heartburn, solvents) and subsequent toxicity testing of headache, depression, stiffness, etc. the compound of interest is of paramount  In vitro findings may not extrapolate into in vivo models such as animals and humans. importance. However, it calls for Therefore a thorough investigation and trials

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to authenticate such findings is the need of  Efforts are required for wholesome research tomorrow. including elucidation of structure of  Toxicological studies are mandatory at the responsible compound/s and establishing the initial stages of pharmacological studies to mechanism of action. avoid waste of resources on unsuitable compounds.

Table 5: Phytoconstituents of various Moringa species

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Anti-inflammatory :٭a: M. oleifera; b: M. stenopetala; c: M. peregrine; d: M. Concanesnsis; e: Other species; NS Not yet: ٭٭٭٭Not reported; NT:٭٭٭Antibacterial reported but not specified; NR :٭٭reported but not specified; NS .Literature not available :٭٭٭٭٭ ;tested

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6.0. Strength, Opportunities and Threats whose toxicity has not been Out of the 33 species of Moringa, 13 have established. been documented where M. oleifera, M. concanensis, M. peregrina and M. stenopetala and the unexplored ones have 7. Acknowledgements been proven scientifically as well as The scholarship offered to Jemimah G. untapped indigenous claims to have prospects Onsare by the Government of India through as potential candidates for development of ICCR and the support by Government of useful products. Hence, the establishment of Kenya through MOHEST to pursue this the location as well as continual study is duly appreciated. documentation of information of the various species of this family is a breakthrough 8. Conflict of Interest towards exploration and exploitation of their The authors declare no conflict of interest in potentials. However, amid the much work on the contents of this paper. the Indian Moringa oleifera, gaps in comprehensive microbiological studies in 9. References this as well as the other unexplored species of 1. Croteau R, Kutchan TM, Lewis NG. Natural the genus still exist. A systematic research of products (secondary metabolites). In: B. this prospective Moringaceae family will lead Buchanan, W. Gruissem, R. Jones, (Eds.), Biochemistry and molecular to potential bio-products of vast array biology of plants. Rockville, MD: applications in fields such as; water, American Society of Plant Physiology, pharmaceutical, food and agricultural 2000, 1250-1318. industries thus, 2. Balandrin MF, Klocke JA, Wurtele ES, 1. A great hope to the two million Bollinger WH. Natural plant chemicals: people who die from diseases caught Sources of industrial and medicinal materials. Science 1985; 228, 1154-1160. from contaminated water every year, 3. Bandow JE, Botz H, Leitchert LIO, with the majority of these deaths Labischinski H, Hecker M. Proteomic occurring among children under five approach to understanding antibiotic years of age. action. Antimicrob. Agents Chemother. 2. Safer and eco-friendly products. 2003; 47, 948-955. 4. Brahmachari UN. The role of science in 3. Empowerment to the ‘have nots’ and recent progress of medicine. Curr. Sci. hope to unemployed. 2001; 81: 15- 16. 4. It should be noted with concern that 5. Robbers J, Speedie M Tyler V. some of the species are reported to be Pharmacognosy and extinct from the face of the earth. pharmacobiotechnology. Williams Human activities and the aggravating and Wilkins, Baltimore, 1996, 1–14. 6. Hammer KA, Carson CF Riley TV. effects of climate change may lead to Antimicrobial activity of essential oils and loss of the remaining species unless other plant extracts. J. Appl. Microbiol. appropriate measures are taken into 1999; 86, 985-990. consideration. Similarly from the 7. Arora DS, Kaur J Antimicrobial activity of technical point of view, due to lack of spices. Int. J. Antimicrob. Ag. 1999; 12, 257-262. systematic research in addition to 8. Bandyopadhyay U, Biswas K, Sengupta A, limitations already heighted, the lives Moitra P, Dutta, P, Sarkar D, Debnath P, of many may be at stake especially Ganguly CK, Banerjee RK. Clinical studies those who rely on herbal products on the effect of Neem (Azadirachta indica) bark extract on gastric secretion cancer. Life Sci. 2004; 75, 2867-2878.

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121. Catalun˜a P, Rates SMK. The organs and tissue enzymes activities traditional use of the latex from of male albino rats. Afr. J. Microbiol. Res. tirucalli Linnaeus 2009; 3:537-540. () in the treatment of 131. Ajibade TO, Olayemi FO, Arowolo cancer in south Brazil, Acta Hortic.1999; ROA. The haematological and biochemical 501: 289–295. effects of methanol extract of the seeds of 122. Schenkel EP, Zannin M, Mentz LA, Moringa oleifera in rats. J. Med. Plants Sal B Irgang B. Poisonous plants. Res. 2012; 6: 615-621. In: C.M.O. Simões, E.P. 132. Maria K, Mohammed A. Schenkel, G. Gosmann, J.C.P. Mello, L.A. Phytochemical investigation of the stem Mentz and P.R. Petrovick. bark of Moringa oleifera Lam. Int. J. Res. Pharmacognosy: the medicinal Ayurv. Pharm. 2011; 2: 1577-1579. plant, Porto Alergre, University/ UFRGS 133. Usman MRM, Barhate DS. Barhate. and Florianopolis, Editor of UFSC, Phytochemical investigation and study of 2000, 755 -788. anti- inflammatory activity of M. 123. Adedapo AA, Mogbojuri OM, oleifera Lam. Int. J. Pharmac. Res. Dev. Emikpe BO. Safety evaluations of 2012; 3: 114- 119. the aqueous extract of the 134. Manivasagaperumal R, Vonoth B, leaves of Moringa oleifera in rats. J. Med. Balamurugan S. Phytochemical analysis Plants Res. 2009; 3: 586-591. and antibacterial activity of Moringa 124. Ashong JO, Brown DL. Acute oleifera Lam. Int. J. Res. Biol. Sci. 2012; 2: toxicity of aqueous extracts of Moringa 98 – 102. oleifera leaf in growing poultry. 135. Mekoya M. Hypotensive effects of J. Anim. Sci. 2011; 89: 577-580. aqueous extract of Moringa stenopetala in 125. Lambole V, Kumar U. both in vivo and in vitro animal models. M. Phytochemicals and acute toxicity of M. Sc. Thesis. Addis Ababa University, School oleifera barks in rats. Int. J. of Graduate Studies, 2007. Biochem. Res. 2011; 2: 548-553. 136. Kjaer A, Malver O, El-Menshawi B, 126. Kasolo JN, Bimenya GS, Ojok L, Reisch J. Isothiocyanates in myrosinase- Ogwal-okeng JW. Phytochemicals and treated seed extracts of Moringa acute toxicity of M. oleifera peregrine. Phytochem. 1979; 18: 1485- roots in mice. J. Pharmacog. Phytother. 1487. 2011; 3: 38- 42. 137. Dayrit FM, Alcantar AD Villasenor 127. Paul CW, Didia BC. The Effect of IM . Studies on Moringa oleifera seeds, Methanolic Extract of Moringa oleifera Part I: The antibiotic compound and Lam. Roots on the histology of kidney its deactivation in aqueous solution. and Liver of guinea pigs. Asian J. Med. Sci. Philippine J. Sci. 1992; 119: 23. 2012; 4: 55-60. 138. Ravichandran V, Arunachalam G, 128. Ferreira PMP, Carvalho AFU, Subramanian N, Suresh B. Farias DF, Cariolano NG, Melo VMM, Pharmacognostical and phytochemical Queiroz MGR, et al. Larvicidal Activity of investigations of Moringa concanensis the Water Extract of Moringa oleifera (Moringaceae) an ethno medicine Seeds Against Aedes Aegypti and its of Nilgiris. J. Pharmacog. Toxicity upon Laboratory Animals. Ann. Phytother. 2009; 1: 76-81. Braz. Acad. Sci. 2009; 81:207- 216. 139. Farnsworth NR. Biological 129. Ayotunde EO, Fagbenro OA, approaches to the screening and Adebayo OT. Toxicity of aqueous extract evaluation of natural products. In: of Moringa oleifera seed powder to Rasoanaivo P, Ratsimamanga-Urverg S, Nile tilapia Oreochromis niloticus (LINNE (eds.) Biological Evaluation of Plants I779), fingerlings. Int. Res. J. Agric. Sci. Soil with Reference to the Malagasy Sci. 2011; 1:142-150. Flora,Monograph from the IFS- NAPRECA 130. Oluduro AO, Aderiye BI. Effect of Workshop on Bioassays. Moringa oleifera seed extract on vital Madagascar, 1993, 35– 43.

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