Lkshmipriy GoplkrishnnKruthi DoriyDevri Snthosh Kumr

a Department of Chemical Engineering,Ordnance Factory Estate,Yeddumailaram,Indian Institute of Technology Hyderabad,Telangana,India

b Department of Biotechnology,PES University,Bangalore,India

Abstract Moringa oleifera, native to India, grows in the tropical and subtropical regions of the world. It is commonly known as ‘drumstick tree’ or‘horseradish tree’.Moringa can withstand both severe drought and mild frost conditions and hence widely cultivated across the world.With its high nutritive values,every part of the tree is suitable for either nutritional or commercial purposes.The leaves are rich in minerals,vitamins and other essential phytochemicals.Extracts from the leaves are used to treat malnutrition,augment breast milk in lactating mothers.It is used as potential antioxidant,anticancer,anti-inflammator ,antidiabetic and antimicrobial agent.M.oleifera seed,a natural coagulant is extensively used in water treatment.The scientifi effort of this research provides insights on the use of moringa as a cure for diabetes and cancer and fortificatio of moringa in commercial products.This review explores the use of moringa across disciplines for its medicinal value and deals with cultivation,nutrition,commercial and prominent pharmacological properties of this“Miracle Tree”.

Keywords: Moringa oleifera;Miracle Tree;Antidiabetic;Anticancer;Coagulant

1. Introduction

Moringa oleiferabelonging to the family of Moringaceae is an effective remedy for malnutrition.Moringa is rich in nutrition owing to the presence of a variety of essential phytochemicals present in its leaves, pods and seeds. In fact, moringa is said to provide 7 times more vitamin C than oranges,10 times more vitamin A than carrots,17 times more calcium than milk,9 times more protein than yoghurt, 15 times more potassium than bananas and 25 times more iron than spinach[1].The fact that moringa is easily cultivable makes it a sustainable remedy for malnutrition. Countries like Senegal and Benin treat children with moringa [2]. Children deprived of breast milk tend to show symptoms of malnutrition. Lactogogues are generally prescribed to lactating mothers to augment milk production.The lactogogue, made of phytosterols, acts as a precursor for hormones required for reproductive growth.Moringa is rich in phytosterols like stigmasterol,sitosterol and kampesterol which are precursors for hormones. These compounds increase the estrogen production, which in turn stimulates the proliferation of the mammary gland ducts to produce milk. It is used to treat malnutrition in children younger than 3 years [3]. About 6 spoonfuls of leaf powder can meet a woman’s daily iron and calcium requirements,during pregnancy.This study provides an overview on the cultivation,nutritional values,medicinal properties for commercial use and pharmacological properties of moringa. There are no elaborate reports on treatment of diabetes and cancer using moringa.This study aims to bridge the gap.

2. Plantation and soil conditions

M. oleiferacan be grown in any tropical and subtropical regions of the world with a temperature around 25–35◦C. It requires sandy or loamy soil with a slightly acidic to slightly alkaline pH and a net rainfall of 250–3000 mm [4]. The direct seeding method is followed as it has high germination rates.Since moringa seeds are expected to germinate within 5–12 days after seeding and can be implanted at a depth of 2 cm in the soil.Moringa can also be propagated using containers.The saplings are placed in plastic bags containing sandy or loamy soil.After it grows to about 30 cm,it can be transplanted.However,utmost care has to be taken while transplanting as the tap roots are tender and tend to get affected.The tree can also be cultivated from cuttings with 1 m length and 4–5 cm in diameter,but these plants may not have a good deep root system.Such plants tend to be sensitive to drought and winds.For commercial purposes large scale intensive and semi-intensive plantation of moringa may be followed.In commercial cultivation,spacing is important as it helps in plant management and harvest.M. oleiferadiffers in nutrient composition at different locations [5]. The tree grown in India has slightly different nutritional components than a tree grown in Nigeria.Asante et al.[6]studied the nutritional differences in the leaves from two ecological locations semi-deciduous and Savannah regions.It showed that the latter was less nutritious than the former and attributed this to high temperatures at the Savannah regions. At higher temperature,proteins and enzymes get denatured and this could be the cause for the difference in nutrient content.

Soil is an important factor that define nutrient content and strength of the plant.Dania et al.[7]showed that fertilizers when applied solely or in combination with others resulted in different nutrient compositions on plant parts.NPK fertilizer,poultry manure and organic base fertilizer was provided to study the effect on the nutrient content and found that poultry manure gave the best results than phosphorous,potassium,sodium and manganese. Likewise the stem girth and vegetative growth of moringa increased on application of poultry manure.The overall nutrient attributes of the plant remains same albeit nutrient variability. This makes moringa viable as a potential nutraceutical anywhere in the world.

3. Nutritive properties

Every part ofM.oleiferais a storehouse of important nutrients and antinutrients. The leaves ofM. oleiferaare rich in minerals like calcium, potassium, zinc, magnesium, iron and copper [2]. Vitamins like beta-carotene of vitamin A, vitamin B such as folic acid, pyridoxine and nicotinic acid, vitamin C, D and E also present inM. oleifera[8]. Phytochemicals such as tannins, sterols, terpenoids, fl vonoids, saponins,anthraquinones,alkaloids and reducing sugar present along with anti-cancerous agents like glucosinolates,isothiocyanates,glycoside compounds and glycerol-1-9-octadecanoate[9].Moringa leavesalsohavealowcalorifi valueandcanbeusedinthedietof the obese.The pods are fibrou and are valuable to treat digestive problems and thwart colon cancer[10,62].A research shows that immature pods contain around 46.78%fibe and around 20.66%protein content.Pods have 30%of amino acid content,the leaves have 44%and fl wers have 31%.The immature pods and fl wers showed similar amounts of palmitic,linolenic,linoleic and oleic acids[11].

Moringa has lot of minerals that are essential for growth and development among which,calcium is considered as one of the important minerals for human growth.While 8 ounces of milk can provide 300–400 mg,moringa leaves can provide 1000 mg and moringa powder can provide more than 4000 mg.Moringa powder can be used as a substitute for iron tablets, hence as a treatment for anemia.Beef has only 2 mg of iron while moringa leaf powder has 28 mg of iron.It has been reported that moringa contains more iron than spinach [12]. A good dietary intake of zinc is essential for proper growth of sperm cells and is also necessary for the synthesis of DNA and RNA.M.oleiferaleaves show around 25.5–31.03 mg of zinc/kg,which is the daily requirement of zinc in the diet[13].

PUFAs are linoleic acid,linolenic acid and oleic acid;these PUFAs have the ability to control cholesterol. Research show that moringa seed oil contains around 76% PUFA, making it ideal for use as a substitute for olive oil[14].A point to note is that the nutrient composition varies depending on the location.Fuglie[12]revealed that seasons influenc the nutrient content.It was shown that vitamin A was found abundantly in the hotwet season,while vitamin C and iron were more in the cool-dry season[15].The difference in results can be attributed to the fact that the location,climate and the environmental factors significantly influenc nutrient content of the tree [16]. A complete list of nutrients available in leaves,pods and seeds are shown in Table 1.

4. Processing of moringa

Most plants lose their nutritive properties when processed.When compared, the nutritive content of raw, germinated and fermented moringa seed flou,it was found that phytochemicals were higher in raw seed flou and amino acid content was at its peak in fermented and germinated seed flou [17,59]. This can be a result of the biochemical activities during germination and microbial activity during fermentation. However, a study reviewed the effect of boiling,simmering and blanching to see the retention of nutrient content of moringa leaves.Interestingly,boiling was the most effective of all the techniques as it reduced the cyanide, oxalate and phytate contents, more significantl than the other two methods.The presence of phytate and other anti-nutrients can reduce the bioavailability of certain nutrients and processing can hence be done for maximum utilization of required nutrients from the seeds and leaves[18,63].Yang et al.[15]reported that boiling increased the availability of iron and antioxidantcontent.Hence,theprocessedmoringaseedflou can be used to treat malnutrition problems.However,some studies have shown that children refuse to take in moringa due to its slight bitter taste[70].Kiranawati et al.[19]designed moringa noodles by three methods of cooking noodles,sautéing,steaming and boiling.These noodles were tested on rats and the effects on mammary glands were studied. Interestingly, the sautéednoodles had a better effect on the mammary glands of rats and improved milk production.The effect of sautéing on the noodles improved lactogogum values, because the oil used was rich in sterols.M.oleiferahave also been incorporated into chocolates.A recent report tested different percentages of moringa in the chocolate fortificatio and found that,20%moringa incorporationincocoapowderwasideal.Similarly,moringaincorporation inhalawatahiniaalsoincreasedthenutrientvalueofthedelicacy.Such studies have shown the potential for developing protein and minerals-rich chocolate and halawa tahinia [20]. Several such moringa fortification are possible to ensure intake of adequate amounts of nutrients in children.

Table 1 The nutrient compositionsa of leaves,leaf powder,seeds and pods.

4.1. Preservation methods

Moringa can also be preserved for a long time without loss of nutrients.Drying or freezing can be done to store the leaves.A report by Yang et al.[15]shows that a low temperature oven used to dehydrate the leaves retained more nutrients except vitamin C than freeze-dried leaves. Hence, drying can be done using economicalhouseholdappliancelikestovetoretainacontinuous supply of nutrients in the leaves. Preservation by dehydration improves the shelf life of Moringa without change in nutritional value

An overdose of moringa may cause high accumulation of iron.High iron can cause gastrointestinal distress and hemochromatosis.Hence,a daily dose of 70 g of moringa is suggested to be good and prevents over accumulation of nutrients[21].

5. Medicinal properties

M. oleiferais often referred as a panacea and can be used to cure more than 300 diseases. Moringa has long been used in herbal medicine by Indians and Africans. The presence of phytochemicals makes it a good medicinal agent.In this section,the effect of moringa on diseases like diabetes and cancer are reviewed.

5.1. Anti-diabetic properties

Moringa has been shown to cure both Type 1 and Type 2 diabetes.Type 1 diabetes is one where the patients suffer from non-production of insulin,which is a hormone that maintains the blood glucose level at the required normal value.Type 2 diabetes is one associated with insulin resistance.Type 2 diabetes might also be due to Beta cell dysfunction, which fails to sense glucose levels,hence reduces the signaling to insulin,resulting in high blood glucose levels[22].Several studies have shown that,moringa can act as an anti-diabetic agent. A study has shown that the aqueous extracts ofM.oleiferacan cure streptozotocininducedType1diabetesandalsoinsulinresistantType2diabetes in rats [23]. In another study, the researchers fed the STZinduced diabetes rats with Moringa seed powder and noticed that the fasting blood glucose dropped[50].Also,when the rats were treated with about 500 mg of moringa seed powder/kg body weight, the antioxidant enzymes increased in the serum. This shows that the antioxidants present in moringa can bring down the ROS caused in the Beta-cells due to the STZ induction[8].STZcausesATPdephosphorylationreactionsandhelpsxanthine oxidase in the formation of superoxides and reactive oxygen species(ROS)in Beta cells[24].In hyperglycemic patients,the beta cells get destructed(Fig.1).Therefore,high glucose enters the mitochondria and releases reactive oxygen species. Since beta cells have low number of antioxidants,this in turn causes apoptosis of the beta cells[25,26].This reduces insulin secretion leading to hyperglycemia and in turn diabetes mellitus Type-2.The fl vonoids like quercitin and phenolics have been attributed as antioxidants that bring about a scavenging effect on ROS.It can be hypothesized that the fl vonoids in Moringa scavenge the ROS released from mitochondria,thereby protecting the beta cells and in turn keeping hyperglycemia under control[27,50].

Fig. 1. Mechanism of high glucose leading to diabetes and the effect of moringa on progression of diabetes. The high glucose in blood enters glycolysis in the mitochondria of beta cells and forms reactive oxygen species.This then causes apoptosis of beta cells which in turn leads to decreased insulin secretion,hyperglycemia and finall Type-2 diabetes.However,the cell apoptosis of beta cells can be averted by the use of moringa.Moringa has antioxidants which combine with the reactive oxygen species and prevent cell damage and further consequences[8,22,25,50].

Diabetes leads to several complications such as retinopathy,nephropathy and atherosclerosis etc.Moringa can be used to prevent such ailments. When there is hyperglycemia, the blood glucose reacts with proteins and causes advanced glycated end products (AGEs). These AGEs bind to RAGE which gets expressed on the surface of immune cells.This interaction leads to increased transcription of cytokines like interleukin-6 and interferons. At the same time, the cell adhesion molecules are expressed on the surface endothelium of arteries[28].This facilitates transendothelial migration which causes inflammatio in the arteries and leads to atherosclerosis(Fig.2).Moringa is used as an anti-atherosclerotic agent[29].The anti-atherogenic nature can be accounted for by the antioxidant properties of moringa.

5.2. Anticancer properties

Cancer is a common disease and one in seven deaths is attributed due to improper medication.Around 2.4 million cases are prevalent in India, while there are no specifi reasons for cancer to develop.Several factors like smoking,lack of exercise and radiation exposure can lead to the disease[69].Cancer treatments like surgery, chemotherapy and radiation are expensive and have side effects.M.oleiferacan be used as an anticancer agent as it is natural, reliable and safe, at established concentrations. Studies have shown that moringa can be used as an anti-neoproliferative agent,thereby inhibiting the growth of cancer cells. Soluble and solvent extracts of leaves have been proven effective as anticancer agents. Furthermore, research papers suggest that the anti-proliferative effect of cancer may be due to its ability to induce reactive oxygen species in the cancer cells. Researchs show that the reactive oxygen species induced in the cells leads to apoptosis. This is further proved by the up regulation of caspase 3 and caspase 9,which are part of the apoptotic pathway [30,31,64]. Moreover, the ROS production by moringa is specifi and targets only cancer cells,making it an ideal anticancer agent. Tiloke et al. [30] also showed that the extracts increased the expression of glutathione-S-transferase, which inhibits the express of antioxidants.Anticancer agents targeting cancer using ROS induction are common, but these substances should also be able to attack the antioxidant enzymes [32]. However, Moringa leaf extracts have been shown to be antioxidants and anticancer agents which induce ROS.The exact behavior of the two contrary attributes of the leaves is yet to be explored. The compounds of the leaves that are held responsible for the anticancer activities are glucosinolates,niazimicin and benzyl isothiocyanate[33].Benzyl isothiocyanate has been shown to be linked with cancer.ResearchshowsthatBITCcausesintracellularROS,whichleads to cell death.This could be one of the reasons for moringa to be a good anticancer agent[34,35,65].

Fig.2. Mechanism of diabetes leading to atherosclerosis and effect of moringa on the progression of atherosclerosis.High blood glucose due to glycolysis releases ROS,which then forms AGEs and LDLs.The LDLs can directly lead to inflammation while the AGE when combined to RAGE expressed on cell surface,can cause expression of NFk-B.This can further lead to transcription of other cytokines and in turn inflammation Inflammatio causes transendothelial migration of immune cells and LDLs,leading to atherosclerosis.Moringa can prevent atherosclerosis by scavenging ROS and preventing the formation of AGE and LDL,thereby acting as an anti-atherosclerotic agent[8,24,28,29].

Table 2 Nutritional compositions and medicinal uses of different parts of Moringa.

5.3. Other diseases

Moringa can be used as a potent neuroprotectant. Cerebral ischemia is caused due to obstruction of blood fl w to the brain.This leads to reperfusion and lipid peroxidation,which in turn results in reactive oxygen species.Moringa with its antioxidants can reduce the reactive oxygen species, thereby protecting the brain[36,37].M.oleiferais used to treat dementia,as it has been shown to be a promoter of spatial memory.The leaf extracts have shown to decrease the acetylcholine esterase activity, thereby improving cholinergic function and memory [38]. Adeyemi et al. [39] showed that moringa in diet of rats, can increase protein content and decrease levels of urea and creatinine in blood,preventing renal dysfunction.Moringa decreased acidity in gastric ulcers by a percentage of 86.15% and 85.13% at doses of 500 mg and 350 mg,respectively and therefore can be used as an antiulcer agent[40].Moringa is prescribed by herbal practitioners for patients with AIDS. Moringa is suggested to be included in the diet, with the view of boosting the immune system of HIV positive individuals. However, more research is essential to validate the effect of moringa on anti-retroviral drugs [41]. The hydro-alcoholic extract of moringa f owers reduced the levels of rheumatoid factor,TNF-alpha and IL-1 in arthritic rats.This proves that moringa can be a potent therapy for arthritis [42]. Microbial diseases are widespread and there is a need for antimicrobial agents,M.oleiferahas been proven as a good antimicrobial agent [66]. A study by Viera et al.[43] has shown that the extracts ofM. oleiferacan act against bacteria likeBacillus subtilis,Staphylococcus aureusandVibrio cholera. The antibacterial effects of the seeds were accounted for by the presence of pterygospermin, moringine and benzyl isothiocyanate [67]. Table 2 presents nutritional composition and medicinal uses of different parts of Moringa.

6. Commercial applications

Moringa seeds are used to extract oil called the Ben oil.This oil is rich in oleic acid, tocopherols and sterols. It can also withstand oxidative rancidity. The oil can be used in cooking as a substitute for olive oil, as perfumes and also for lubrication [14,44]. The pods can absorb organic pollutants and pesticides.Moringa seeds also have great coagulant properties and can precipitate organics and mineral particulates out of a solution [1,53]. Chemical coagulants such as aluminum sulfate (Alum) and ferric sulfate or polymers removes suspended particles in waste water by neutralizing the electrical charges of particles in the water to form floc making particles fil terable.M. oleiferaseed is a natural coagulant, containing a cationic protein that can clarify turbid water. This property ofM. oleiferaseeds is attracting much research as other coagulants such as alum, activated carbon and ferric chloride are expensive and rare[58].Suhartini et al.[45]developed a twostage clarifie for the treatment of tapioca starch waste water by placing coconut fibe followed by a layer of sand media mixed with powderedM.oleifera,this lead to improvement on physical and chemical characteristics,stabilizing pH value.Moringa seed extract has the ability to eliminate heavy metals (such as lead,copper,cadmium,chromium and arsenic)from water[46].M.oleiferafunctionalized with magnetic nanoparticles such as iron oxide were found beneficia in surface water treatment by lowering settling time [55]. Seed extracts have antimicrobial properties that inhibit bacterial growth,which implies preventing waterborne diseases.These properties ofM.oleiferaseeds have wide applicability in averting diseases and can enhance the quality of life in rural communities as it is highly abundant.

Moringa seeds can be used in cosmetics and are sources of biodiesel while the seedcakes, can be used as a green manure or a fertilizer. The fl wers of moringa are used to make tea with hypocholesterolemic properties.Moringa f owers are said to taste like mushrooms when fried[68].The moringa f owers are great sources of nectar and are used by beekeepers.The root bark has medicinal values and is used for dyspepsia, eye diseases and heart complaints[51].The tap root of Moringa is used as a spice. The gum from the tree can be used in calicoprinting. The gum and roots also have antibacterial, antifungal and anti-inflammator properties [54]. The growth hormone from the leaves,called Zeatin is an excellent foliar and can increase the crop yield by 25%–30%[12].Incorporation and fortificatio of moringa can be significan to tackle nutrient deficiencie and malnutrition. Studies have tried fortifying moringa in snacks.Aluko et al.[47]did a sensory evaluation on cookies made from a mix of maize flou and moringa seed flou. The flou was mixed with different percentages of the two flour and the best acceptance was for 92.5%maize and 7.5%moringa seed flou combination.This was well accepted due to its crispness,aroma,taste and color.Cereal gruels have also been fortifie by moringa leaves in order to improve the protein content and energy.The cereal gruel with 65% popcorn and 35% moringa leaves was blanched and fermented. The fermented ones showed higher protein and energy while the blanched cereal had higher mineral content[48].Owusu et al.[49]also used moringa as a fortifican and produced cream and butter crackers with moringa andIpomoea batatasas fortificants with the hope of adding additional nutrients to snacks. The sensory evaluation proved the cream crackers to be widely accepted.M.oleiferaleaves can be incorporated in the diet of hens and layers thereby providing excellent protein source,substituting other expensive ingredients such as soybean meal and ground nut cake[56,57].

Considering the views of several such fortifications it is suggested that such addition can be done to other snacks as well.Addition of moringa to the snacks can add nutritive value to the snacks.Most snacks are made up of corn meal and several studies demonstrated that a little addition of moringa to maize flou can add nutritive value to the snack in terms of protein,energy and minerals. However, further studies on moringa as a fortifie Indian snack is required before bringing commercialized moringa to the market.

7. Conclusion and future prospects

The research onM.oleiferais yet to gain importance in India.It is essential that the nutrients of this wonder tree are exploited for a variety of purposes.M.oleiferahas great anti-diabetic and anti-cancerproperties.However,doubleblindresearchesareless prevalent to further substantiate these properties of moringa.More studies are needed to corroborate the primary mechanisms of moringa as antidiabetic and anticancer agents.Several puzzling questions are unanswered. Research on the antioxidant nature of aqueous extracts on cancer cells needs further inquiry.Studies have proven that moringa causes ROS in cancer cells that leads to apoptosis or necrosis. However, the aqueous extracts also have antioxidants present in them. The exact mechanism of this irony is yet to be explored. The effect of environmental factors affecting the nutrient levels of leaves and other parts ofM.oleiferagrown across the globe require further analysis.

Further research to isolate endophytic fungi and identify the enzymes or proteins fromM. oleiferathat are accountable for the anticancer and antidiabetic activity may lead to development of novel therapeutic compounds. Yet another focal area is to evaluate the commercial use ofM.oleiferaas a bio-coagulant.It might be a viable alternative for water purification The demand for snacks in the market is huge.Hence Moringa fortificatio in snacks to eradicate malnutrition has a twin advantage.The tree as a native to India can become a great source of income for the nation if this potential for highly nutritional food is exploited by the industries and researchers by undertaking further research to corroborate earlier studies.

Acknowledgements

The authors sincerely thank Director Indian Institute of Technology Hyderabad for their continued encouragement and support.LG thanks DSK for constant support and valuable suggestions in completing this manuscript.