Pharmacological properties of
About 80% of the worldwide population use herbal products for their basic health care (primary care), such as extracts, teas and their active principles . Despite the interest in molecular modeling, combinatorial chemistry and other chemical synthesis techniques by institutions and pharmaceutical industries, the natural products, particularly medicinal plants, persist as an important source of new therapeutic agents against infectious (fungal or bacterial) and cardiovascular diseases, insects, cancer, immunomodulation and on nervous system diseases [2-7].
According to the World Health Organization, medicinal plant is any plant that contains, in one or more of its organs, substances that can be employed for therapeutic purposes or used as precursors of substances utilized for such purposes . The phytotherapic, in turn, is a drug obtained exclusively based on active vegetables raw material and is characterized by knowledge of its effectiveness and risks of their consumption as well as the reproducibility and consistency of its quality . Therefore, the production of vegetal drugs obeys specific laws in a way to maintain attributes and properties from manufacturing to importation and marketing, whatever use (oral and topical) or manner of preparation (infusions, decoctions and macerations) .
The most hazardous concept is that which declares that medicinal plants are nontoxic and without risks to human health since they are natural and have been tested worldwide through centuries. Adverse events, including 101 deaths associated with dietary supplements were reported to the FDA (Food and Drug Administration), but these adverse effects were not well reported whereas there is no an efficient monitoring system in the United States like that for allopathic medicines . Researches conducted in the United Kingdom suggest an incidence around 7% attributed to plants and phytotherapics. Studies conducted in Taiwan and Hong Kong hospitals showed an admission rate caused by plants ranging from 0.2 to 0.5% [11,12]. In Brazil, there were 1037 reports of human poisoning with plants in 2009 (1.29% of total), with 61.9% of poisonings occurred in patients with 1-9 years old. About 0.31% deaths were directly linked to herbal poisoning . The quality of the commercialized medicinal plants, the population inexperience, the origin of the plant, period and methods of collection, storage, drying, packaging, contamination by fungi and other microorganisms and the quantity ingested are factors that obscure the diagnosis and complicate the treatment in cases of poisoning by toxic plants [14,15].
The folk usage of the different parts of
2. Taxonomy, distribution and general use and consumption
With several popular names such as “morunga”, “árbol de rábano”, “árbol de los espárragos”, horseradish tree, drumstick tree, never die tree, “sajna”, Ben oil tree, “lírio-branco” and “quiabo de quina” [16-19].
Its seeds are anemochoric, bitegumetend, exalbuminous and winged (Figure 1C), making seed dispersal more effective . They can be introduced directly in a definitive way or in seedbeds, though their dissemination can also be made by poles, without previous exceptional requirements, growing quickly up to 4m in the first year and 15 m in height in development later stages. Under favorable conditions, a plant might produce 50-70 kg of fruits/year [18,20,21].
Historically, ancient Romans, Greeks and Egyptians utilized all parts of the plant for human consumption as well as Asian communities have been made now [3, 16]. This primeval use in the East World has been attributed to its Asian origin and a massive popular use of the flora in the Asiatic continent . The flowers (Figure 1D) are rich in Ca2+and K+and leaves are widely used as food complement, with appreciable amounts of vitamins [(A, 7-fold higher than in oranges), B and C], Fe2+and proteins [23-25]. Leaves put in soups are used by Philippines’ women to improve the breast milk production and possess 4-fold the calcium in milk [16,26]. The roots, presenting alkaloids (0.2% of total), are scarcely consumed [16, 27]. However, when powdered, are appreciated as a spicy flavor similar to that showed by horseradish, explaining why the plant is commonly called "Horseradish Tree".
The seed oil is used in industry to manufacture cosmetics, lubricate machines and clocks, such as cooking oil, fuel for lamps and it is highly appreciated in perfume industries due to its ability in retaining fragrances  and high stability to oxidative rancidity . Cooked fresh pods are very consumed in Haiti due to its taste comparable to asparagus or green beans; when dried and crushed, they show suitable characteristics to substitute traditional beds of laboratory animals (pine, for example), exhibiting a high absorptive capacity, low concentration of antinutritional compounds and endurance to autoclaving . Stems are extensively used in paper factories and construction of furniture and fences .
The approximate composition of
Additionally, studies demonstrate that the high content of proteins has ideal levels of essential amino acids and good availability for intestinal absorption and rumen degradability of nitrogen comparable to soybean meal [30,39,40], indicating a great potential of the leaves as a food supplement for ruminants, though little is known about changes that these proteins may cause in the final composition of the milk or how they may affect the animal growth. Recently, leaves and twigs’ flour prepared by drying and grinding was given in substitution to the standard feedstuff of grass (
In a study of 45 days exposure, sheep were fed with 4-6 g/day of MO delipidated seeds. It was found a significant increase in body weight gain with 4g/day of supplementation, corroborated by a higher nitrogen retention and efficiency in the microbial nitrogen production. These animals also showed elevated levels of plasmatic glucose , suggesting a relationship between sugar absorption rate and metabolizable energy intake. This result indicates that intake of 4g/day improved diet energy value due to, at least in part, the alterations in gastrointestinal tract microbial population which led to upper fermentative efficiency than those cows fed only with soybean meal. In another report, rats that consumed the aqueous extract of seeds during 30 days showed increased serum albumin and retention of body nitrogen (67.53 ± 2.49 g/100 g) compared to the control group that consumed only tap water (59.55 ± 3.02 g/100g) . The albumin capacity in acting as a reservoir of amino acids may explain the improvement in body nitrogen, since those amino acids not incorporated into a high molecular weight protein are rapidly eliminated by the urinary system .
It is known that the seed meal has high levels of essential amino acids, except to lysine, threonine and valine amino acids which are present at low amounts and are important for children nutrition between 2-5 years-old. Elevated contents of methionine and cysteine residues are close to that realized in human and cow's milk and hen eggs. This abundance in essential amino acids stimulates its use as an excellent food supplement for vegetables that are normally poor in sulfur amino acids. Concerning mice requirements in growth phase, the lysine is the first limiting amino acid in the seeds, followed by isoleucine and leucine [30,43]. When added as a supplement to a child’s diet, just 25 g of the leaf powder supplies all the calcium and vitamin A daily needs, about half the protein and potassium, and about three-quarters of the iron daily needs . With advances in molecular techniques to manipulate genes, the seeds serve as ideal model for improving the protein quality of foods.
3. Coagulating properties
There are troubles of water distribution for human consumption in many parts over the world. To treat this water before distribution, inorganic and synthetic compounds have been used for sedimentation, filtration and disinfection. Aluminum [aluminum sulphate, Al2(SO4)3] and iron [ferric sulfate, Fe2(SO4)3] salts, positively charged, lead to the flocculation of negative particles in water via neutralization . Notwithstanding this extensive usage, these salts and synthetic polymers have high costs and low distribution, making their use in developing countries and impecunious sites an interfering economic factor that affects the quality of drinking water [45,46]. Although alum and iron salts are the most widely used chemical coagulants for community drinking water treatment, other coagulants have been and are being used to coagulate household water at point of use, including alum potash, crushed almonds or beans and seeds of
Advantages in exploiting the seeds include coagulation efficiency comparable to aluminum salts, complete degradation, pH maintenance, water conductivity, concentration of anions and cations [46,54], and its ability to dramatically decrease bacteria content in 99.9% [55,56]. Stored seeds up to 18 months kept the turbidity reduction in similar percentages. On the other hand, seeds with 24 months displayed a significant reduction in flocculation efficiency. Flocculating effects are greater at pH 6.5 while low temperature (< 15 °C) drops the efficiency of this process . Cationic peptides of low molecular mass (6-16 kDa) are considered the main responsible for sedimentation of the suspended material in water, juices and drinks [56,58,59]. On the other hand, a non-protein active component with 3kDa isolated from seeds was able to flocculate a kaolin suspension .
In reference  have shown that a seed recombinant protein (isoelectric point of 12.6) expressed in
4. Pharmacological properties
Many medicinal properties of
|Abortifacient||Leaves, roots||, |
|Against ||Seeds||, |
|Anticlastogenic||Leaves, pods||, |
|Anticonvulsant||Leaves, roots||, , |
|Anti-inflammatory||Seeds, leaves, roots||, , , |
|Antioxidant||Leaves, seeds||, , , , , , |
|Antitumor||Seeds, stem, leaves||, , , |
|Antiulcerogenic||Leaves, seeds||, |
|Bactericidal||Leaves, stem, pods||, , , , , |
|Bradycardic/Hipotensive||Seeds||, , |
|Fungicide||Leaves, seeds||, , |
|Hepatoprotective||Seeds, leaves||, |
|Hypocholesterolemic||Leaves, seeds, stem||, , , |
|Immunomodulatory||Seeds||, , , |
4.1. Antioxidant, antiulcer, hypocholesterolemic and hypotensive
Medicinal plants are good sources of cytoprotective compounds . A single dose (150 mg/kg body weight) of methanolic extract of
The leaf methanolic extract (100 and 150mg/kg) inhibits significantly the formation of gastric lesions caused by acetylsalicylic acid (55 and 78.3%), serotonin (86.5 and 92.4%), indomethacin (86 and 88 8%) and acetic acid (66.2 and 73.4%), respectively, and improves the healing rate of gastric ulcers induced by acetic acid . In a similar way, water extract of
Antioxidant compounds from
The authors of the reference  demonstrated that treated rabbits with ground cooked seeds (200 mg/kg/day) showed reduction in plasma levels of total cholesterol (TC), phospholipids, triglycerides (TG), LDL-C and VLDL-C (very low density lipoprotein cholesterol) as well as decreasing in lipid content in kidney, liver, heart and aorta. In this way,  and  working with similar doses (400 and 300-600 mg/kg, respectively) showed substantial increase in HDL-C (high density lipoprotein cholesterol), the latter also demonstrating dropping in blood levels of TC, TG, LDL-C and VLDL-C. This HDL-C increasing is a desirable event in an ideal hypocholesterolemic agent, since it indicates a possible role in reducing the atherosclerosis incidence. Related findings were seen in  and , who also divulged the great therapeutic potential and prevention of cardiovascular diseases showed by the water extract of leaves, reducing serum TC and TG and declining formation of atheroma plaques with efficacy equivalent to simvastatin.
The research  suggest a direct relationship between phenolic compounds present in leaves and hypolipidemic action, demonstrating that the water extract inhibited oxidative modifications in LDL-C molecule and probably suppressed initiation and propagation of lipid peroxidation and cellular damage induced by free radicals at levels similar to vitamin E [42, 68]. Since vitamin C might scavenge free radicals and regenerate, indirectly, vitamin E , this synergism between vitamins A and C have attracted interest as agents to delay and/or blockade atherosclerosis by LDL-C oxidation reducing as a way to keep the intracellular redox state and avoid damage to endothelial cells. Then, it is possible that the atherogenic index decreasing could represent an anti-inflammatory action of antioxidants present in
Correlated with cardioprotective effects, extracts from leaves, stem bark and pods and nitrile compounds, mustard glycosides and thiocarbamates isolated [4-(α-L-rhamnosyloxy)-benzyl isothiocyanate (Figure 2A), niazirinin, niazinins (A and B) and niaziminin] has negative inotropic and chronotropic effects on heart musculature causing bradycardia and hypotension (1-20mg/kg), suggesting that amide or-N=C-moieties and/or sulfur atoms could be critical for the cardiodepressant action [77-79]. Smooth muscle relaxation studied in isolated ileum and uterus certainly corroborates the popular use of the plant in gastrointestinal disorders and explains its antispasmodic activity . Since pre-treatment with atropine did not abolish the hypotensive effects of
4.2. Anti-inflammatory and antitumor
The aqueous (1000 mg/kg), ethanolic, hexane and butanolic (3000 mg/kg) extracts of
Inflammation, polycyclic aromatic hydrocarbons such as benzo[a]pyrene and 7,12-dimethylbenzanthracene (DMBA), alcohol, bacteria (
In carcinogenesis studies, niazimicin-treated animals showed delay in skin carcinoma formation induced by DMBA (initiator) and TPA (12-O-tetradecanoylphorbol-13-acetate, promoter) and they also revealed reducing in the number of papillomas, displaying greater activity than β-carotene and glycyrrhetic acid against cancer promoters . The antimutagenic activity evidenced by micronucleus formation attenuation [63,64] may be a factor involved in deferring carcinoma progression. Hence, antioxidants like β-carotene and glycyrrhetic acid might be very effective in combating cancer. Moreover, since the methanolic extract of leaves caused emerging of apoptotic bodies, chromatin condensation, cell shrinking, DNA fragmentation and induce the generation of reactive oxygen species (ROS) in epidermoid carcinoma KB cells, it is believed that
Seeds and leaves (and extracts) show activity against different species of fungi (
Initially, it was difficult to accurately identify the responsible component(s) for the antimicrobial properties, since majority of studies was performed with seed and leaf crude extracts. Tannins and polyphenols found in
Outcomes have demonstrated that these extracts are more effective in low and moderate temperatures (4-37°C), whereas temperatures greater than 70°C lead to loss of antibacterial and antifungal activities, suggesting that specific bioactive compounds would be proteins capable of binding to negatively charged surfaces [32,93]. This finding partially explains the seed water purification efficiency to drop bacteria suspension after 1-2 h of treatment, whose ability has been accredited to basic flocculent proteins [55,61]. Besides, positive monovalent and divalent ions (Na+, K+, Ca2+, Mg2+) diminished the antifungal and bactericidal activities of plant proteins due to plasma membrane structure stabilization .
The search for novel products that improve the epidemiological control of vector-borne diseases is relevant, whereas the selective pressure of conventional and synthetic insecticides has amplified mosquitoes resistance for different classes of insecticides (e.g. DDT and other chlorinated hydrocarbons) and present undesirable effects on non-targets organisms, requesting innovative substances that are specific, biodegradable and safer environmentally as mosquito control agents [32,98]. In this event, products derived from plants have promising outcomes since they have been traditionally used by communities against insects .
Aqueous extract of moringa seeds exhibited larvicidal action against
At work  has associated this larvicidal potential with flocculating proteins such as lectins found in the seeds, which delay and/or impede the larvae development of the
Thus, low toxicity of “morunga” extracts, competence of dispersion and plant maintenance, resistance to inhospitable environments, low cost and simple technology are some factors that convert
4.5. Action on Central Nervous System (CNS)
Aqueous (100-450 mg/k, oral) and methanolic (350-700 mg/kg, intraperitoneal) root extracts reduced locomotor activity of rats and the number of seizures induced by penicillin and strychnine [27, 103]. Aqueous extract also amplified rates of 5-HT and reduced levels of dopamine in the brain cortex, cerebellum and caudate nucleus and noradrenaline measure in the cerebral cortex . Methanol extract produced CNS depression, decreases the mortality of strychnine-and leptazol-treated animals, increased the sleeping time, caused analgesia and potentiated morphine analgesic effects . This sleepiness extension and anticonvulsant and analgesic activities can be justified by the 5-HT brain rising.
More recently, discoveries also showed that ethanol extract from
Other pharmacological activities of
5. Toxicological aspects
Plants have a variety of indispensable macro and micronutrients to feed heterotrophic organisms, including ruminants and monogastric animals such as sheeps, rats, mice and humans. However, side effects and aversions to vegetal substances as alkaloids, tannins, cyanogenic glycosides, terpenes, lectins and glucosinolates are habitual . Thus, animals can identify tastes from sweet (carbohydrate, for example, an indication of calories) to the unpleasant taste of toxins. Among these, some present bitter flavor (alkaloids, saponins and cyanogenic glycosides), astringent (tannins) or offensive odors (terpenes). Dislikes can be wild (temporary) or strong (permanent) depending on the toxin dosages and how they affect the gut and central nervous system. These aversions hardly develop if toxins act gradually (days to weeks). Furthermore, toxins can activate the emetic center, causing nausea and vomiting . Tropical seeds usually have high content of antinutritional factors, specially tannins and lectins .
5.1. Leaves, flowers and roots
Water extract of roots inhibit development of uterus and blastocyst implantation , indicating an abortifacient effect that interferes in estrogen and progesterone levels, modifying the normal physiology of the genital tract during the fertile period. Relatedly, Indian women frequently use leaf extracts as natural oral contraceptives .
Extracts from roots and flowers (200 mg/kg/day) were able to maintain transaminase (aspartate aminotransferase, AST; alanine aminotransferase, ALT) and bilirubin levels, protect against hepatotoxicity induced by acetaminophen toxic metabolites produced by P450 monooxygenase enzymes and presented slight acute toxicity, since it was found LD50 values of 1023 and 1078 mg/kg for root and 1047 and 1092 mg/kg for flowers extracts (ethanolic and aqueous extracts, respectively)  (Table 2).
However, root methanolic extracts (intraperitoneally and weekly doses greater than 46 mg/kg/day) produced hepatotoxicity and nephrotoxicity associated with hematological and plasma changes, particularly, AST, ALT, cholesterol, bilirubin, urea, proteins and causing leukocytosis and clotting time increasing . Histological examinations in guinea pigs also propose toxicity of root methanolic extract (3.5, 4.6 and 7.0 mg/kg), whereas balloon degeneration and micro and macrovesicular steatosis (in liver) and interstitial inflammation, tubular damage and amorphous eosinophilic materials (in kidneys) were seen, demonstrating reversible signals of histo-architectural distortions .
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Reference  reported that acute and sub-cronic exposure to higher doses of aqueous leaf extracts (400 to 6400 mg/kg) revealed to be relatively safe for human and rodents, since any mortality was detected when administered orally. These results are in according to , who documented that moringa leaf extracts are non-lethal at 2000 mg/kg and , whose publication demonstrated that ethanol extract from moringa leaves were not toxic to mice and revealed a LD50 higher than 6.4 g/kg in oral acute toxicity studies. Nevertheless, i.p. injection presented 20% and 80% mortality in Wistar albino mice at doses of 1000 and 2000 mg/kg, with LD50 of 1585 mg/kg and acute administration at 3000mg/kg reduces urea and albumin levels, indicating liver and renal dysfunction  probably initiated by toxicants such as isothiocinates and glycosides during biotransformation and corroborating those outcomes described by  and , whose mice presented biochemical alterations suggestive of renal damage. An opposing discovery to all previous researches divulged, for the first time, showed that
The best advantage of using
In  verified that seeds orally administered for 5 days at 500 mg/kg/day protected against toxic arsenic effects and recovery physiological measures to normal values (hemoglobin, erythrocytes and levels of δ-aminolevulinic acid dehydratase and glutathione S-transferase), probably due to the arsenic tissue removal. Previously,  showed that oral administration of hydroalcoholic extract of
Despite investigations have indicated absence of toxicity following oral consumption of the seed aqueous extract, reproducing the intake of treated water with clarifying agent [32,74,123], nutritional assessments reported that those growing rats fed during 10 days with a diet whose total protein content (10%) was replaced by seed flour and whose doses were 24-fold higher than the highest dose tested by , suffered from severe growth disorders, loss of appetite and weight, hyperplasia of the small and large intestine, liver, pancreas, kidneys, heart, stomach and atrophy of key organs like spleen and thymus, though protein digestibility is similar to the foodstuff presenting egg white . The antinutritional compounds prevailing in mature seeds, mainly glucosinolates (65.5 mmol/g), phytic acid (41 g/kg) and lectins [30,39,124,125] should be responsible for these effects. Phytates, when found in percentages between 1-6% and ingested for extended periods, they may reduce the bioavailability of minerals (Ca2+and Zn2+), starch and proteins in monogastric animals. Glucosinolates disturb growth and reproduction.
Lectins, in turn, are proteins or glycoproteins with reversible binding sites to carbohydrates . They interact with the intestinal mucosa and interfere with digestion and absorption of nutrients, reduce activity of amylase, establish stable complexes with trypsin/chymotrypsin , cause pancreatic hypertrophy  and decrease growth rate . In fact, studies have emphasized the
Additionally, weight gain reduction in sheep supplemented with 6 g/dia of
The bitter taste in the seeds, important to provide its typical aroma, is alleviated by treatment , suggesting that its taste would not be a limiting factor for using them, since even cow’s milk whose dairy cattle was treated with moringa meal did not reveal changes in quality . Furthermore, it is known that most adverse effects are eliminated by suitable methods as washing, storage, drying and/or heating. For example, lectin biological properties are lost after protein denaturation by temperature and pH. Nevertheless, these techniques are expensive and prolonged cooking of seeds result in nutritional value reduction and loss of micronutrients, specifically vitamins and minerals. The text  showed that roasted seeds promote formation of mutagenic compounds [4-(alpha-L-rhamnosyloxy)phenylacetonitrile, 4 hydroxyphenylacetontrile and 4-hydroxyphenyl-acetamide). On the other hand, it was observed that moringa seed flour has post-treated proteins with good digestibility and absorption [39,41].
Environmental assessments with seed water extract using the microcrustaceans
In summary, results obtained by [30,32,74,104,116,117,119,123,133,] confirm that toxicity of
Relatively safe for human,
We wish to thank the Brazilian Agencies Fundação de Amparo à Pesquisa do Estado do Piauí (FAPEPI), FUNCAP (Fundação Cearense de Apoio ao Desenvolvimento Científico de Tecnológico) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brasil) for the financial support.