Research by | Sidney J. Stohs* and Michael J. Hartman
Plano, TX 75074, USA
Moringa oleifera leaves, seeds, bark, roots, sap, and flowers are widely used in traditional medicine, and the leaves and immature seed pods are used as food products in human nutrition. Leaf extracts exhibit the greatest antioxidant activity, and various safety studies in animals involving aqueous leaf extracts indicate a high degree of safety. No adverse effects were reported in association with human studies. Five human studies using powdered whole leaf preparations of M. oleifera have been published, which have demonstrated anti-hyperglycemic (antidiabetic) and anti-dyslipidemic activities. These activities have been confirmed using extracts as well as leaf powders in animal studies. A rapidly growing number of published studies have shown that aqueous, hydroalcohol, or alcohol extracts of M. oleifera leaves possess a wide range of additional biological activities including antioxidant, tissue protective (liver, kidneys, heart, testes, and lungs), analgesic, antiulcer, antihyper-tensive, radioprotective, and immunomodulatory actions. A wide variety of polyphenols and phenolic acids as well as flavonoids, glucosinolates, and possibly alkaloids is believed to be responsible for the observed effects. Standardization of products is an issue. However, the results of published studies to date involving M. oleifera are very promising. Additional human studies using standardized extracts are highly desirable. © 2015 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.
Moringa oleifera Lam. is a tree that grows widely in many tropical and subtropical countries. It is grown commercially in India, Africa, South and Central America, Mexico, Hawaii, and throughout Asia and Southeast Asia. It is known as the drumstick tree based on the appearance of its immature seed pods, the horse-radish tree based on the taste of ground root prepara-tions, and the ben oil tree from seed-derived oils. In some areas, immature seed pods are eaten, while the leaves are widely used as a basic food because of their high nutrition content (Thurber and Fahey, 2009; Mbikay, 2012; Razis et al., 2014). No human clinical trials have been conducted looking at the efficacy of M. oleifera for treating undernutrition.
Seeds, leaves, oil, sap, bark, roots, and flowers are widely used in traditional medicine. Moringa leaves have been characterized to contain a desirable nutritional balance, containing vitamins, minerals, amino acids, and fatty acids (Moyo et al., 2011; Teixeira et al., 2014; Razis et al., 2014). Additionally, the leaves are reported to contain various types of antioxidant compounds such as ascorbic acid, flavonoids, phenolics, and carotenoids (Alhakmani et al., 2013; Vongsak et al., 2014).
antihyperlipidemic, antineoplastic, antipyretic, antiulcer, cardioprotectant, and hepatoprotectant activities. The therapeutic potential of M. oleifera leaves in treating hyperglycemia and dyslipidemia was reviewed by Mbikay (2012). Razis et al. (2014) summarized po-tential health benefits of M. oleifera, focusing on their nutritional content as well as antioxidant and antimicrobial characteristics.
No adverse effects were reported in any of the hu-man studies that have been conducted to date, and these studies will be described in more detail later in the text. Furthermore, various preparations have been and continued to be used around the world as foods and as medicinals without the report of ill effects. Several animal studies have specifically assessed the potential toxicity of various preparations on M. oleifera.
The safety of an aqueous leaf extract given orally to rats at doses of 400, 800, 1600, and 2000 mg/kg body weight was examined (Adedapo et al., 2009). The treatment was either an acute single dose or given daily for 21 days except the highest dose. Various pa-rameters were assessed including blood cell counts and serum enzyme levels. The authors concluded that consumption of M. oleifera leaves at doses of up to 2000 mg/kg were safe. A dose-dependent decrease in body weights of the rats occurred over the 21 days of the study.
Received 08 October 2014
Revised 20 December 2014
© 2015 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd. Accepted 14 February 2015 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Asare et al. (2012) examined the potential toxicity of an aqueous leaf extract of M. oleifera in several different experimental systems. In one set of experiments, rats were given 1000 and 3000 mg/kg of the extract, and the animals were assessed for up to 14 days. The M. oleifera leaf extract was shown to be genotoxic based on blood cell analysis at the 3000 mg/kg dose, a dose that greatly exceeds commonly used doses. A dose of 1000 mg/kg was deemed safe and did not produce genotoxicity when given to rats, a dose still in excess of commonly used doses.
Ambi et al. (2011) divided 24 rats into four groups and fed varying amounts of M. oleifera powdered leaves mixed with standard livestock feed (25%, 50%, 75%, and control) for 93 days. Total amount of M. oleifera leaves consumed was not quantified. Following the experimental period, some organs of the treated animals had observable microscopic lesions with the 75% group developed necrosis of hepatic cells, splenic blood ves-sels, and neuronal glial cells. The control animals had no observable microscopic lesions in all organs exam-ined. No photomicrographs of any tissues were pro-vided. The amounts of leaves consumed, although not quantified by the authors, greatly exceeded doses that would be typically used in either rats or humans. For example, if the rats consumed an average of 15–20 g of chow per day, even at the low dose of 25% of the chow, the daily dose would be approximately 15–20 g of leaves per kilogram for an adult rat, which would equate to 195–260 g for an 80-kg human.
The toxicity of an aqueous extract of M. oleifera leaves has also been evaluated in mice (Awodele et al., 2012). In an acute study, mice were administered the extract at up to 6400 mg/kg orally and 1500 mg/kg intra-peritoneally. In a subchronic study, mice received 250, 500, and 1500 mg/kg orally for 60 days. The lethal dose of 50% LD50 was estimated to be 1585 mg/kg. No signif-icant effects were observed with respect to hematologi-cal or biochemical parameters or sperm quality. A high degree of safety was observed on oral administration.
The toxicological effects associated with consump-tion of 50, 100, 200, or 400 mg/kg of methanol extract of M. oleifera for 8 weeks was performed in 30 rats (Oyagbemi et al., 2013). The extract was a 30:1 con-centration. All experimental animals that received M. oleifera had a significant increase in body weight in a dose-dependent manner, contrary to what is observed with an aqueous extract (Adedapo et al., 2009). Rats that received M. oleifera at 200 and 400 mg/kg showed a sig-nificant increase in serum alanine aminotransferase, as-partate aminotransferase, blood urea nitrogen, and creatinine. It should be noted that the extract was pre-pared with methanol and not water. The 30:1 concentra-tion of the methanol extract at a dose of 400 mg/kg would be equivalent to 12 g of leaves per kilogram, a very unre-alistic dose. The composition of the extract was not re-ported, and it is not clear how the composition of the methanol extract relates to the composition of aqueous extracts, which are commonly used.
Bakre et al. (2013) determined that the lethal dose of 50% of an orally administered ethanol extract of M. oleifera leaves in mice was greater than 6.4 g/kg.
The dietary effects of M. oleifera leaves as a dietary sup-plement for liver function were performed by Zvinorova et al. (2014). Thirty-two weanling rats were randomly assigned to diets of normal rat feed fed at 20% and 14% of body mass, or Moringa-supplemented feeds fed at 20% and 14% of body mass for 5 weeks. Moringa sup-plementation did not affect blood metabolite concentra-tions, liver glycogen, or lipid storage.
The potential toxicological effects of a single oral dose of 5000 mg/kg of an aqueous M. oleifera extract as well as oral doses of up to 1000 mg/kg of the same ex-tract for 14 days on rats were examined (Asiedu-Gyekye et al., 2014). The authors noted that no overt adverse reactions were observed at these doses, and no histo-pathological findings were found. Small but statistically significant dose-dependent increases in several liver en-zymes were observed. A dose of 1000 mg/kg in a rat is equivalent to over 30 times a typical 400 mg dose of an aqueous extract in an 80-kg human.
The genotoxicity of an aqueous M. oleifera seed extract was assessed using three separate assay systems including the Ames assay (Rolim et al., 2011). The seed extract was not genotoxic without metabolic activation, and did not pose a risk to human health. The effect of a hexane extract of M. oleifera leaves on reproductive organs of male rats was examined (Cajuday and Pocsidio, 2010). The extract was given orally at doses of 17, 170, and 1700 mg/kg body weight for 21 days. A dose-dependent increase in testis and epididymis weights, in seminiferous tubule diameter, and epididy-mal epithelium thickness without change in plasma gonadotropin levels was observed. The authors con-cluded that the changes were associated with an in-crease in spermatogenesis.
For the sake of completeness, several studies involv-ing M. oleifera seeds and roots will be described, although the results cannot be directly compared or equated with studies involving leaves. Cytotoxicity of an aqueous extract of M. oleifera seeds was evaluated by Araújo et al. (2013). Following 14 days of the extract administration (500 and 2000 mg/kg) in mice, no signs of systemic toxicity were observed, and all the animals sur-vived. There were no changes in organ indices between treatment and control groups. Small but insignificant changes were observed in erythrocytes, platelets, hemo-globin, and hematocrit. All values remained within the normal range.
A methanol extract of seeds of M. oleifera were screened phytochemically for chemical components and used for acute and subacute toxicity studies in rats (Ajibade et al., 2013). The phytochemical screening revealed the presence of saponins, tannins, terpenes, alkaloids, flavonoids, carbohydrates, and cardiac glyco-sides but the absence of anthraquinones. Although signs of acute toxicity were observed at an extract dose of 4000 mg/kg, mortality was recorded at 5000 mg/kg. No adverse effects were observed at concentrations lower than 3000 mg/kg. The authors concluded that methanol extracts of seeds of M. oleifera are safe for nutritional use.
Paul and Didia (2012) investigated the effect(s) of methanol extract of M. oleifera root on the histo-architecture of the liver and kidney of 24 guinea-pigs. Experimental conditions included daily intraperitoneal injections of the root extract at doses of 3.6, 4.6, and 7.0 mg/kg, and control for 3 weeks. Histological sections
© 2015 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd. Phytother. Res. 29: 796–804 (2015)
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of all treated groups had ballooning degeneration of the liver, suggesting time-dependent hepatotoxicity rather than a dose-dependent response. Examination of the kidneys, demonstrated mild tubular damage and inter-stitial inflammation in the 4.6 mg/kg group, while the 7.0 mg/kg group had infiltration of the interstitium by inflammatory cells and amorphous eosinophilic mate-rials. No information was provided regarding extract composition or degree of concentration. The results of this study cannot be compared or equated with studies involving aqueous extracts of leaves. This study involved a methanol extract of roots, which was given intraperitoneally and not orally.
In summary, based on human, animal, and in vitro studies, and the extrapolation of results from animal studies to humans, various preparations of M. oleifera leaves including aqueous extracts appear to be exceed-ingly safe at the doses and in the amounts commonly utilized.