Evaluation of phytochemical and medicinal properties of Moringa (Moringa oleifera) as a potential functional food

SAJB-02233; No of Pages 7 South African Journal of Botany xxx (2018) xxx

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Evaluation of phytochemical and medicinal properties of Moringa (Moringa oleifera) as a potential functional food Z.F. Ma a,b,c,⁎,1, J. Ahmad d,1, H. Zhang e, I. Khan d, S. Muhammad f a

Department of Health and Environmental Sciences, Xi'an Jiaotong-Liverpool University, Suzhou 215123, China School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu 15200, Kelantan, Malaysia Health and Sustainability Innovation (HSI) Lab, Health Technologies University Research Centre (HT-URC), Xi'an Jiaotong-Liverpool University, Suzhou 215123, China d Department of Human Nutrition, The University of Agriculture Peshawar, Khyber Pakhtunkhwa 25120, Pakistan e Department of Food Science, University of Otago, Dunedin 9016, New Zealand f Institute of Basic Medical Sciences, Khyber Medical University, Peshawar 25100, Pakistan b c

a r t i c l e

i n f o

Article history: Received 8 July 2018 Received in revised form 9 October 2018 Accepted 6 December 2018 Available online xxxx Edited by Johannes van Staden

a b s t r a c t Moringa oleifera (Moringa), a perennial deciduous tropical plant belonging to the Moringaceae family, is rich in many bioactive compounds. Moringa is also considered as a remedy to fight malnutrition. It possesses many pharmacological properties such as anti-cancer, anti-diabetic, anti-inflammatory and antioxidant. It is possible that the pharmacological properties of Moringa is closely associated with the presence of its bioactive compounds including flavonoids. Therefore, this review will summarize the bioactive compounds and medicinal properties of Moringa, which provides a reference for its potential application as a functional food. © 2018 SAAB. Published by Elsevier B.V. All rights reserved.

Keywords: Moringa oleifera Evaluation Pharmacological Phytochemicals Functional food

1. Introduction Medicinal plants have been used as a natural source of biologically active compounds (Ji et al., 2009; Zhang and Ma, 2018). Some of these biologically active compounds possess beneficial effects, which can be used to improve human health. One of such medicinal plants is Moringa oleifera. It is usually referred as Moringa in the literature, is a cruciferous plant belonging to the genus Moringa under the family Moringaceae. Since 150 B.C., Moringa has been used for health purposes in the diet (Mahmood et al., 2010). Among the 13 cultivars of Moringa (M. arborea, M. rivae, Moringa oleifera, M. longituba, M. stenopetala, M. concanensis, M. pygmaea, M. borziana, M. ruspoliana, M. drouhardii, M. hildebrandtii, M. ovalifolia and M. peregrine) (Mahmood et al., 2010), M. oleifera is the most most-studied species and most-used species because of its phytochemical and pharmacological properties related to human health. Moringa oleifera is native to Indian subcontinent, but

⁎ Corresponding author at: PhD, FRSPH, ANutr, Department of Health and Environmental Sciences, Xiʼan Jiaotong-Liverpool University, Suzhou, China. E-mail address: [email protected] (Z.F. Ma). 1 These authors contributed equally to this work and shared the joint-first authorship.

now it is widely grown in other regions of the world including Africa, Europe and Asia. This is because Moringa is able to grow in hot and humid and dry environment including less fertile soils. Moringa is also usually known as ‘horseradish tree’ or ‘drumstick tree’ (Kou et al., 2018). In the 1990s, the cultivation of Moringa became popular because of the recognition that Moringa was a useful plant. It is a multi-purpose tree because all parts of Moringa can be used for different purposes (Kou et al., 2018). Since then, Moringa has been known as one of the most economically valued crop, particularly in the developing countries for food, industrial, agricultural and medicinal uses (Leone et al., 2015). For example, Moringa can be used to address food security in countries where hunger is a major problem. This is because the flowers, pods, leaves and seeds of Moringa are regarded as food sources that contain good nutritional values (Kou et al., 2018). Since Moringa leaves are rich in nutrients such as proteins and vitamins, they can be eaten fresh or cooked in order to be used to prevent malnutrition in populations (Leone et al., 2015). Given its rich source of bioactive compounds and nutritional characteristics, there is an increasing exploration and understanding of Moringa with reference to human health. Therefore, the aim of this mini-review is to gather information on Moringa, particularly its pharmacological properties and potential health benefits.

https://doi.org/10.1016/j.sajb.2018.12.002 0254-6299/© 2018 SAAB. Published by Elsevier B.V. All rights reserved.

Please cite this article as: Z.F. Ma, J. Ahmad, H. Zhang, et al., Evaluation of phytochemical and medicinal properties of Moringa (Moringa oleifera) as a potential functional food..., South African Journal of Botany, https://doi.org/10.1016/j.sajb.2018.12.002

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2. Phytochemical constituents of Moringa Phytochemicals are regarded as secondary metabolites present in plants, which accumulate in high concentrations but play little or no role in the growth and development of plants. However, throughout the history, humans have been using phytochemicals as medicine to cure and protect against different diseases. The use of phytochemicals as drugs dates back to Hippocrates, who prescribed willow tree leaves to abate fever. Even today, around 80% population in the developing world uses phytochemicals as traditional medicine for health care (Kim, 2005). On the basis of their chemical structure, plant based phytochemical are divided into five classes namely polyphenols, carotenoids, alkaloids, terpenoids, and sulfur containing compounds (Bohn et al., 2012). Majority of these phytochemicals are also present in Moringa tree. Indeed, the diverse biological activities and disease preventive potential of Moringa is largely believed to be due the presence of these phytochemicals. Therefore, future research holds great promise to harness and exploit the chemical diversity of Moringa phytochemicals as a means of combating diseases and improving health. Polyphenols are one of the major groups of phytochemicals characterized by the presence of either one (phenolic acids) or more than one phenol rings (flavonoids) in their chemical structure. Moringa has been found to be a rich source of polyphenols (flavonoids, phenolic acids and tannins). Folin–Ciocalteau assay is the most commonly used method to quantify total phenolic content in Moringa. Based on this assays, highest concentration was found in the leaves where total phenolic contents ranges from 2000 to 12,200 mg GAE/100 g (Leone et al., 2015). Flowers and seeds also contain polyphenols but much less concentration than leaves (Alhakmani et al., 2013). Total phenolic contents also depend on geographical location and environmental conditions. For example, cultivars grown in Pakistan have much higher total phenolic contents compared to the one grown in India, Thailand, Nicaragua and USA. An important drawback of Folin–Ciocalteu assay is that it is non-specific, meaning that it can detect all phenolic containing molecules in a sample including those found in extractable proteins. In order to identify individual polyphenols (flavonoids and phenolic acids) in Moringa, advance chromatography techniques such as HPLC, GC–MS and LC–MS are increasingly used. Recent studies reported the presence of different flavonoids and phenolic acids in different parts of Moringa tree based on advance chromatography techniques. Quercetin and kaempferol glycosides (glucosides, rutinosides and malonyl glucosides) are the most common flavonoids present in different parts of Moringa tree except roots and seeds (Saini et al., 2016). In the leaves, quercetin and kaempferol are found in the concentration range of 0.46–16.64 and 0.16–3.92 mg/g dry weight, respectively (Amaglo et al., 2010; Bennett et al., 2003; Siddhuraju and Becker, 2003). Other flavonols such as myricetin (Sultana and Anwar, 2008), rutin (Bajpai et al., 2005) and epicatechin (Zhang et al., 2011) were also detected in Moringa but in much lesser quantities. Geographical variations in flavonoids concentration have also been observed among different varieties (Coppin et al., 2013). Predominant phenolic acids present in different parts of Moringa include gallic acid (Oboh et al., 2015; Singh et al., 2009), caffeic acid (Bajpai et al., 2005), chlorogenic acid (Vongsak et al., 2013), coumaric acid and ellagic acid (Leone et al., 2015). Moringa leaves also contain an appreciable amount of tannins. These are complex polyphenol molecules that can bind to and precipitate protein, amino acids, alkaloids and other organic molecules in aqueous solutions. Tannins concentration varies in different parts of moringa tree with highest concentration found in dried leaves (20.7 mg/g) (Teixeira et al., 2014). Small amount of tannins can also be found in seeds (Mohammed and Manan, 2015). Glucosinolates are heterogeneous group of sulfur and nitrogen containing glycosidic compounds present abundantly in many plants family. Several different glucosinolates compounds have been reported in different parts of Moringa plant including roots, stem, leaves and pods. The most common glucosinolate in Moringa is 4-(α-L-rhamnopyranosiloxy) benzyl glucosinolate also known as

glucomoringin (Maldini et al., 2014). Glucomoringin is commonly present in stem, flowers, pods, leaves and seeds (Amaglo et al., 2010). The highest concentration found in the seeds where it can reach up to concentration of 8620 mg/100 g followed by leaves (78 mg/100 g) (Maldini et al., 2014). The predominant glucosinolate in Moringa roots is benzyl glucosinolate (glucotropaeolin) (Bennett et al., 2003). Considerable variations have been reported in glucosinolate concentration of Moringa plants from different geographical regions (Bennett et al., 2003). In plants, breakdown of glucosinolates by the enzyme myrosinase produces glucose, isothiocyanates, nitriles, and thiocarbamates which are also present in Moringa (Waterman et al., 2014; Waterman et al., 2015). Carotenoids are a group of phytochemicals that gives fruits and vegetables their characteristic red, yellow or orange color. Fresh Moringa leaves are rich source of β-carotene (also known as pro vitamin A) with contents (6.6–17.4 mg/100 g) much higher than those found in carrots, pumpkins and apricots (Kidmose et al., 2006). Dried leaves contain even high β carotene contents (23.31–39.6 mg/100 g) of dry weight (Glover-Amengor et al., 2017; Joshi and Mehta, 2010). Apart from β carotenoids, several other carotenoids have been identified in foliage, flowers and immature pods (fruits) of commercially grown Moringa cultivars in India (Saini et al., 2014). Among these, All-Elutein was the pre-dominant carotenoid in foliage and fruits, accounting for more than 50% of total carotenoids. All-E-luteoxanthin, 13-Z-lutein, all-E-zeaxanthin and 15-Z-b-carotene were also been found but in lesser quantities. Alkaloids are nitrogen containing organic compounds present in plants and derived from amino acids metabolism. Though uncommon, presence of several alkaloids has been confirmed in Moringa. Of these, N,α-L-rhamnopyranosyl vincosamide is the most commonly isolated indol alkaloid from Moringa leaves (Cheraghi et al., 2017; Panda et al., 2013). The leaves are also shown to contain unusual glycosides of a pyrol alkaloid namely pyrrolemarumine 4″-O-α-L-rhamnopyranoside (marumosides A) and 4′-hydroxyphenylethanamide (marumosides B) (Sahakitpichan et al., 2011). However, the actual amount of these alkaloids in Moringa leaves has never been quantified so far. 3. Studies of Moringa in relation to human health Many studies reported diverse pharmacological properties of Moringa using its leaves, seeds and pods, but most of these studies are unable to provide conclusive data on the relationship between Moringa and its health benefits. Similar to other plants (Cao et al., 2018; Ma and Zhang, 2017; Ma and Lee, 2016; Ravichanthiran et al., 2018; Zhang et al., 2018), one of the possible reasons is that limited high quality human intervention studies that investigated its effects on human health. 3.1. Effects on biomarkers of oxidative stress Many studies have reported the antioxidant potential of different extracts of Moringa leaves, seeds and pods. In a recent in vitro study, the antioxidant activity of hydroethanolic extract of Moringa leaves was investigated. The results showed strong antioxidant activity of Moringa leaves using nitric oxide (NO) scavenging assay (IC50 = 120 μg/ml) and deoxyribose degradation assay (IC50 = 178 μg/ml). This study further showed that the antioxidant potential of Moringa leaves could be attributed to the presence of total phenolic content, total flavonoid content, carotenoids, lycopene, ascorbic acid and anthocyanins in the leaves (Vats and Gupta, 2017). Strong scavenging activity of aqueous extract of Moringa leaves was also found using 2,2-diphenyl-1picrylhydrazyl (DPPH) free radical, superoxide, nitric oxide radical and lipid peroxidation (LPO) assays. Interestingly, the free radical scavenging effect of Moringa leaf extract was comparable to reference antioxidants (Sreelatha and Padma, 2009). In another in vitro study, methanolic extract of Moringa leaves showed strong antioxidant activity using xanthine oxidase assay (IC50 = 30 μL) and 2-deoxyguanosine assay (IC50 = 40 μL) (Atawodi et al., 2010).

Please cite this article as: Z.F. Ma, J. Ahmad, H. Zhang, et al., Evaluation of phytochemical and medicinal properties of Moringa (Moringa oleifera) as a potential functional food..., South African Journal of Botany, https://doi.org/10.1016/j.sajb.2018.12.002

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Administration of Moringa leaves at a dose of 50 and 100 mg/day to carbon tetrachloride (CCl4)-intoxicated rats for a period of 2 weeks decreased lipid peroxides and increased glutathione (GSH) concentrations, along with a decrease in activities of superoxide dismutase (SOD) and catalase (CAT) enzymes in the liver and kidney, compared to control. In addition, the antioxidant activity of Moringa leaves in the group treated with 100 mg/dl per day showed a comparable effect to a group treated with a standard treatment of vitamin E at 50 mg/dL per day (Verma et al., 2009). In another study, diet supplemented with Moringa leaf powder in goats increased GSH, CAT and SOD, and decreased LPO in the liver of goats (Moyo et al., 2012). The effect of Moringa leaf and fruit (pod) extracts was also investigated on oxidative stress biomarkers in Swiss albino rats. Treatment with aqueous extract of Moringa leaves increased GSH and reduced malondiadehyde (MDA) level in mice erythrocytes in a dose dependent manner. In addition, ethanolic extract of pod showed enhanced free radical scavenging capacity and strong reducing power (Luqman et al., 2012). In humans, the effect of Moringa leaf extract on low-density lipoprotein (LDL) oxidation was determined using ex vivo essay. For this purpose, human plasma was collected and incubated with different concentrations of leaf extract of Moringa (1, 10, 30 and 50 μg/ml) at 37 °C for 1 h. Vitamin E was used as standard antioxidant in the control group. Freshly prepared CuSO4 solution was added to LDL solution—isolated from human plasma—to initiate oxidation reduction reaction of LDL. The results showed that oxidation of plasma LDL was inhibited dose-dependently in the presence of Moringa leaf extract, which was evident from increased lag-time of conjugated diene formation and decreased formation of thiobarbituric acid reactive substances (TBARS). Moreover, TBRAS formation was completely blocked when incubated with high concentrations of Moringa leaf extract. This study showed that Moringa leaf extract can decrease the initiation and propagation of lipid peroxidation (Chumark et al., 2008). Similarly, it has been shown that daily supplementation of Moringa leaf powder (7 g) by postmenopausal women for 3 months significantly increased serum levels of retinol, ascorbic acid, GSH and SOD, with a decrease in serum MDA (Kushwaha et al., 2014). The above studies suggest that Moringa possesses strong antioxidant properties, and therefore can be beneficial for the prevention of oxidative stress induced diseases. 3.2. Anti-cancer effect Studies have reported the chemopreventive properties of Moringa by inhibiting the growth of human cancer cells (Karim et al., 2016). The anti-cancer effect of Moringa leaves, bark and seed extracts was tested against breast (MDA-MB-231) and colorectal (HCT-8) cancer cell lines of humans. Treatment with Moringa leaf and bark extracts reduced colony formation, cell motility, and showed low cell survival, high apoptosis as well as G2/M enrichment in these cells. However, no anticancer effect of Moringa seed on breast and colorectal cancer cell lines was observed in this study (Al-Asmari et al., 2015). In another study, aqueous extract of Moringa leaves inhibited cancer proliferation and progression in human cancerous lung cells (A549) by inducing apoptosis, DNA fragmentation, and increasing oxidative stress (Tiloke et al., 2013). Treatment with aqueous extract of Moringa leaves inhibited tumor cell growth, induced apoptosis and decreased reactive oxygen species (ROS) levels in lung cancer cells and some other types of cancer cells, suggesting that Moringa leaves has the potential to decrease proliferation and invasion of cancer cells (Jung, 2014). The antiproliferative and apoptosis properties of Moringa leaf extract were determined using human tumor (KB) cell line. The study showed that Moringa leaves inhibited cell proliferation of KB cells in a dose-dependent manner. The observed antiproliferative property of Moringa leaves was further demonstrated by induction of apoptosis, morphological changes, and DNA fragmentation (Sreelatha et al., 2011). Similarly, aqueous extract of Moringa leaves on survival of human cancer pancreatic cells (Panc-1, p34, and COLO 357) inhibited

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the growth of these cells, particularly with a dose of ≥0.75 mg/ml. Interestingly, treatment with Moringa leaf extract at a dose of 2 mg/ml reduced Panc-1 cell survival by 98%. This study also showed that treatment of Panc-1 cells with Moringa leaves extract inhibited nuclear factor kappa B signaling pathway proteins and enhanced the efficiency of cisplatin chemotherapy in these cancer cells (Berkovich et al., 2013). In a recent study, ethanol extract of Moringa leaves showed strong anticancer activity against diethyl nitrosamine-induced hepatocellular carcinoma in Wistar rats, mainly by inducing apoptosis and improving antioxidant activity (Sadek et al., 2017). In another study, aqueous extract of Moringa seeds provided cytotoxic effect to human peripheral blood mononuclear cells and showed no effect on hemolytic activity of erythrocytes (Araujo et al., 2013). Also, oral consumption of methanolic and hydromethanolic extracts of Moringa leaves at a dose of 500 mg/dl for 15 days delayed the growth of tumors and increased life span in mice (Purwal et al., 2010). 3.3. Effects on biomarkers of inflammation The anti-inflammatory activity of ethanolic extract of Moringa pods was investigated against pro-inflammatory mediators secreted by lipopolysaccharide (LPS)-induced murine macrophage cells. The Moringa extract inhibited mRNA expression and concentrations of interleukine-6 (IL-6), tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenease-2 in a dosedependent manner. This effect was also in-part mediated by inhibiting phosphorylation of inhibitor kappa B protein and mitogen-activated protein kinases (Muangnoi et al., 2012). In another study, butanol extract of Moringa seeds showed anti-inflammatory activity against ovalbumin-induced airway inflammation in pigs, by modifying Type-1 and 2 helper T-cells cytokines (Mahajan et al., 2009). Similarly, ethyl acetate extract of Moringa leaves has been shown to inhibit human macrophage cytokine production (TNF-α, IL-6 and IL-8), induced by smoking and by LPS (Kooltheat et al., 2014). Both Moringa leaf concentrate and isothiocyanates decreased the gene expression and production of inflammatory markers in RAW macrophage cell system (Waterman et al., 2014). Specifically, both decreased expression of iNOS and IL-1β and production of NO and TNF-α at 1 and 5 μM (Waterman et al., 2014). Similarly, in a recent study, isothiocyanates isolated from Moringa seed extract showed anti-inflammatory activity in LPS-stimulated murine macrophages by decreasing production of NO and inflammatory gene expression (iNOS, IL-1β, and IL-6) (Jaja-Chimedza et al., 2017). In another study, the anti-inflammatory effect of Moringa leaf extract and its active component (quercetin) was investigated in mice fed with high fat diet. The results showed that short-term treatment of both Moringa extract and quercetin inhibited the release of TNF-α, IL-6 and expressions of nuclear factor kappa B, iNOS, interferon gamma and C-reactive protein in high fat diet-fed mice compared to the group fed with only high-fat diet (Das et al., 2013). 3.4. Hepatoprotective effect Several studies have shown the hepatoprotective property of Moringa. For example, leaf extract of Moringa has been shown to protect against liver damage by decreasing tissue histopathology, aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), as well as by decreasing LPO and increasing GSH in mice fed with high fat diet (Das et al., 2012). Ethanolic extract of Moringa leaves also showed hepatoprotective activity against liver damage induced by antitubercular drugs (isoniazid, rifampicin, and pyrazinamide) in rats by decreasing the serum levels of AST, ALT, ALP, and bilirubin, and by inhibiting LPO in the liver (Pari and Kumar, 2002). In another study, the hepatoprotective activity of Moringa leaf extract was investigated against liver injury induced by Artesunateamodiaquine (AS-AQ) – an antimalarial drug – in Wistar rats. Moringa

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leaf extract decreased both serum AST values similar to Siliphos® (standard hepatoprotectant) and hepatocyte degeneration in AS-AQ intoxicated rats (Okumu et al., 2017). Administration of Moringa seed extract also showed hepatoprotective property against CCl4-induced liver fibrosis in rats by decreasing serum activities of AST, ALT and globulin level (Hamza, 2010). In another study, Moringa leaf extract showed protective action against acetaminophen-induced hepatotoxicity in mice in a dose-depended manner by decreasing the levels of serum AST, ALT, gamma-glutamyl transpeptidase, as well as by increasing antioxidant enzymes in the liver (Karthivashan et al., 2015). Moringa leaf abstracts have also shown a decrease in the level of serum ALT, AST, ALP, as well as an increase in GSH level in acetaminophen-induced hepatotoxic rats (Fakurazi et al., 2008). 3.5. Effects on biomarkers of diabetes Diabetes is a metabolic disorder, characterized by high fasting and postprandial blood glucose concentration. It is important to keep blood glucose concentration within recommended ranges to avoid or control the complications of diabetes. Many studies have reported the antidiabetic properties of Moringa (Gupta et al., 2012; Khan et al., 2017; Omodanisi et al., 2017; Tang et al., 2017; Yassa and Tohamy, 2014). The hypoglycemic and antidiabetic effects of aqueous extract of Moringa leaves was investigated in normal and streptozotocin (STZ)-induced sub, mild and severely diabetic albino rats. Oral administration of Moringa leaf extract caused a maximum reduction of 26.7% in fasting blood glucose level (FBG), and a maximum reduction of 30% in glucose tolerance after 3 h of glucose consumption. Furthermore, treatment of severely diabetic rats with the same dose of Moringa leaf extract for 21 days showed a maximum reduction of 69.2% and 51.2% in FBD and postprandial blood glucose level, respectively. Interestingly, the blood glucose lowering effects of Moringa leaves treated rats were similar to the rats treated with a reference drug (Glipizide, 2.5 mg/kg body weight), and no toxic effect of high doses of the extract (10–15 times greater than the most effective dose) was observed in rats as measured using LD50 experiment (Jaiswal et al., 2009). In another study, the effect of oral administration of Moringa leaf powder on glucose tolerance was investigated in Wistar and Goto-Kakizaki (GK) rats with type-2 diabetes. Moringa leaves improved glucose tolerance in GK and Wistar rats compared to both controls after glucose consumption, and also reduced gastric emptying in GK rats. This study suggested that hypoglycemic effect of Moringa leaves might be due to presence of quercetin-3glucoside and fiber contents, probably by inhibiting glucose uptake and slowing gastric emptying rate (Ndong et al., 2007). Furthermore, hypoglycemic effect of Moringa leaf extract was investigated in alloxan-induced diabetic rats. It was found that administration of Moringa extract improved glucose tolerance and insulin secretion. In addition, Moringa extract improved glycogen synthase activities, glycogen contents and glucose uptake in the liver and muscle tissues. This study showed that the hypoglycemic effects of Moringa leaves observed in rats could be due to enhanced insulin secretion, and improved glycogen synthesis and glucose uptake in the liver and muscles (Olayaki et al., 2015). Aqueous extract of Moringa leaves showed potential hypoglycemic effects in alloxan-induced diabetic rats by minimizing gluconeogenesis, and by regenerating damaged hepatocytes and pancreatic β-cells (Abd El Latif et al., 2014). Moringa seed extract also showed antidiabetic effects in STZ-induced diabetes rats by reducing high levels of immunoglobulin (IgA, IgG), fasting blood glucose and glycosylated hemoglobin (HbA1c). In addition, Moringa seed treatment also restored both kidney and pancreatic tissues to its normal structure in diabetic rats, compared to diabetic control rats (Al-Malki and El Rabey, 2015). In a recent study, Moringa leaf extract showed hypoglycemic effect in STZ-induced diabetic rats, and the authors suggested that this effect might be due to the presence of cryptochlorogenic acid, quercetin 3-β-D-glucoside,

and kaempferol 3-O-glucoside in Moringa leaves (Irfan et al., 2017). Methanol extracts of Moringa pods also showed a decrease in blood glucose concentration and an increase in insulin levels in STZ-induced diabetic rats after 21 days of treatment compared to untreated diabetic rats (Gupta et al., 2012). Limited studies have been conducted on the antidiabetic role of Moringa in human subjects. In an intervention study, regular consumption of Moringa leaf powder (7 g) in the daily diet of post-menopausal women for 3 months showed a significant decrease (13.5%) in fasting blood glucose concentration (Kushwaha et al., 2014). Similarly, the hypoglycemic effect of Moringa leaf powder was investigated in type-2 diabetic human subjects (30–60 years of age). The results showed that administration of Moringa leaves for 40 days significantly decreased both fasting and postprandial blood glucose concentrations in the diabetic subjects (28% and 26%, respectively) (Kumari, 2010). Furthermore, Arun and his team also evaluated the antidiabetic property of Moringa leaf powder in type-2 diabetic patients aged 40–58 years. They found that Moringa treatment caused a significant reduction in postprandial blood glucose levels from baseline value of 210 mg/dl to 191, 174 and 150 mg/dl, respectively after the first, second and third month of supplementation. Glycated hemoglobin level was also decreased from baseline value of 7.81% to 7.4% after the 90 days supplementation period (Arun Giridhari et al., 2011). In a recent randomized controlled crossover study, the effect of cookies-containing Moringa leaf powder (5% w/w) on postprandial glycemia in 20 healthy subjects was investigated. Moringa-containing cookies decreased blood glucose compared to isocaloric control cookies made from 100% wheat flour (Ahmad et al., 2018). In addition, the consumption of Moringa-containing cookies caused no adverse effects on gastrointestinal symptoms of the study subjects. The study provided evidence of hypoglycemic effect of Moringa leaf powder when incorporated into cookies in healthy subjects, and suggested that more research is required to understand the benefits of long-term consumption of Moringa containing foods for reducing the risk of diabetes and other chronic diseases (Ahmad et al., 2018). In a recent review, the mechanism behind the glucose lowering effect of Moringa were identified to be inhibition of intestinal glucose, improved insulin secretion, and decrease in insulin resistance (Muhammad et al., 2016). The above studies have proved the blood glucose lowering potential of Moringa plant. However, most of the studies were conducted in animals, and only few studies are available in human. Future long-term randomized controlled studies are needed to further investigate the anti-diabetic effect of Moringa plant parts (leaves, seed and pods) in humans. 3.6. Effects on biomarkers of cardiovascular disease Various studies have shown the hypolipidemic properties of Moringa. For example, the hypolipidemic effect of Moringa leaves was investigated in rabbits fed with high-cholesterol diet for 3 months. Daily consumption of Moringa leaf extract (100 mg/kg bw) significantly decreased cholesterol levels by 50% and atherosclerotic plaque formation in internal carotid by 86.52% in the rats compared to control group. These observed effects were similar to simvastatin (reference drug) treated group (5 mg/kg bw) (Chumark et al., 2008). In another study, daily consumption of aqueous extract of Moringa leaves (1 g/kg bw) for 30 days by rats fed with high-fat diet significantly decreased serum cholesterol by 14.35% compared to control group. Moringa leaves treatment also decreased the levels of cholesterol in the liver and kidney by 6.40% and 11.09%, respectively (Ghasi et al., 2000). Similarly, daily consumption of methanolic extracts of Moringa leaves at different doses (150, 300, or 600 mg/kg bw) for 30 days by rats fed with highfat diet decreased serum lipids in a dose dependent manner compared to controls. Moringa leaf extracts at doses of 300 and 600 mg/kg bw significantly decreased triglyceride, cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), atherogenic index, and increased high-density lipoprotein (HDL) in rats fed with high-fat diet

Please cite this article as: Z.F. Ma, J. Ahmad, H. Zhang, et al., Evaluation of phytochemical and medicinal properties of Moringa (Moringa oleifera) as a potential functional food..., South African Journal of Botany, https://doi.org/10.1016/j.sajb.2018.12.002

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compared to controls (Jain et al., 2010). Also, oral administration of hydroalcoholic extract of Moringa leaves at doses of 100 and 200 mg/kg bw for 28 days to hyperlipidemia rats decreased total cholesterol, triglycerides, LDL, VLDL, atherogenic index, and increased the level of HDL (Rajanandh et al., 2012). Furthermore, oral administration of Moringa pod powder at a dose 200 mg/kg bw for 120 days to hyperlipidemia rabbits decreased serum total cholesterol, triglyceride, phospholipids, LDL, VLDL, cholesterol to phospholipid ratio, and atherogenic index. Treatment with Moringa pod also decreased lipid profile of liver, heart and aorta and increased the excretion of fecal cholesterol (Mehta et al., 2003). The anti-dyslipidemia property of Moringa leaf powder was also investigated in 35 hyperlipidemia human subjects. The result showed that daily consumption of Moringa leaf powder (4.6 g) by the subjects for 50 days showed a significant decrease in total cholesterol by 1.6% and a mild increase in HDL by 6.3% compared to control group (Nambiar et al., 2010). In another study, daily consumption of Moringa leaf powder (8 g) for 40 days by type-2 diabetic subjects decreased total cholesterol (by 14%), triglycerides (by 14%), LDL cholesterol (by 29%), and VLDL cholesterol (by 15%) compared to control group (Kumari, 2010). Limited research data are available on the role of Moringa as anti-hypertensive agent. The ethanolic extracts of Moringa seeds and pods showed hypotensive activity at a dose of 30 mg/kg in rats. Thiorcarbamate, isothiocyanate glucosides and hydroxybenzoate isolated from the extracts were considered as the active components for blood pressure lowering activity (Faizi et al., 1998). Similarly, it has been reported that the blood glucose lowering effect of Moringa leaves could be due to the presence of several bioactive compounds including nitrile, mustard oil glycosides and thiocarbamate glycosides (Faizi et al., 1994; Faizi et al., 1995). Acute administration of Moringa leaf extract also decreased arterial blood pressure in monocrotaline (MCT)-induced pulmonary hypertensive rats in a dose dependent manner, reaching statistical significance at a dose of 4.5 mg/kg bw. Interestingly, chronic treatments with Moringa extract reversed the MCT-induced changes in the rats (Chen et al., 2012). In a recent study, consumption of Moringa seeds showed antioxidant and anti-inflammatory property in hypertensive rats by decreasing vascular oxidative stresses in aortas and by improving endothelial function of resistance arteries in hypertensive rats. This study provided evidence that consumption of Moringa seeds can be used to treat high blood pressure and other cardiovascular diseases associated with oxidative stress and inflammation (Randriamboavonjy et al., 2017). In humans, daily intake of Moringa leaf powder (4 g) capsules for 1 month in type-2 diabetes subjects showed a decrease in systolic and diastolic blood pressure by 5 mmHg (Taweerutchana et al., 2017). Although this decrease in blood pressure was not significant, however, a recent meta-analysis has shown that every 5 mmHg decrease in the systolic blood pressure results decrease in cardiovascular risk and all-cause mortality (Bundy et al., 2017; Taweerutchana et al., 2017). Although the above several studies show the hypotensive property of Moringa, more research is needed to further evaluate and confirm the blood pressure lowering potential of Moringa. 4. Conclusions Moringa oleifera has shown to exhibit several medicinal properties which are attributed to its phytochemicals, though the underlying mechanisms remain to be unclear. Therefore, future studies should explore the possible mechanisms of actions of these phytochemicals and the potential of considering M. oleifera plant as a functional food for the prevention and management of chronic diseases. Declaration of interest The authors declare that no conflict of interest exists among the authors.

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Acknowledgements This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. References Abd El Latif, A., El Bialy Bel, S., Mahboub, H.D., Abd Eldaim, M.A., 2014. Moringa oleifera leaf extract ameliorates alloxan-induced diabetes in rats by regeneration of beta cells and reduction of pyruvate carboxylase expression. Biochemistry and Cell Biology 92, 413–419. Ahmad, J., Khan, I., Johnson, S.K., Alam, I., Din, Z.U., 2018. Effect of incorporating Stevia and Moringa in cookies on postprandial glycemia, appetite, palatability, and gastrointestinal well-being. Journal of the American College of Nutrition 37, 133–139. Al-Asmari, A.K., Albalawi, S.M., Athar, M.T., Khan, A.Q., Al-Shahrani, H., Islam, M., 2015. Moringa oleifera as an anti-cancer agent against breast and colorectal cancer cell lines. PLoS One 10, e0135814. Alhakmani, F., Kumar, S., Khan, S.A., 2013. Estimation of total phenolic content, in-vitro antioxidant and anti-inflammatory activity of flowers of Moringa oleifera. Asian Pacific Journal of Tropical Biomedicine 3, 623–627. Al-Malki, A.L., El Rabey, H.A., 2015. The antidiabetic effect of low doses of Moringa oleifera Lam. Seeds on streptozotocin induced diabetes and diabetic nephropathy in male rats. BioMed Research International 13. Amaglo, N.K., Bennett, R.N., Curto, R.B.L., Rosa, E.A., Turco, V.L., Giuffrida, A., Curto, A.L., Crea, F., Timpo, G.M., 2010. Profiling selected phytochemicals and nutrients in different tissues of the multipurpose tree Moringa oleifera L., grown in Ghana. Food Chemistry 122, 1047–1054. Araujo, L.C., Aguiar, J.S., Napoleao, T.H., Mota, F.V., Barros, A.L., Moura, M.C., Coriolano, M.C., Coelho, L.C., Silva, T.G., Paiva, P.M., 2013. Evaluation of cytotoxic and antiinflammatory activities of extracts and lectins from Moringa oleifera seeds. PLoS One 8, e81973. Arun Giridhari, V., Malathi, D., Geetha, K., 2011. Anti diabetic property of drumstick (Moringa oleifera) leaf tablets. International Journal of Health and Nutrition 2, 1–5. Atawodi, S.E., Atawodi, J.C., Idakwo, G.A., Pfundstein, B., Haubner, R., Wurtele, G., Bartsch, H., Owen, R.W., 2010. Evaluation of the polyphenol content and antioxidant properties of methanol extracts of the leaves, stem, and root barks of Moringa oleifera Lam. Journal of Medicinal Food 13, 710–716. Bajpai, M., Pande, A., Tewari, S.K., Prakash, D., 2005. Phenolic contents and antioxidant activity of some food and medicinal plants. International Journal of Food Sciences and Nutrition 56, 287–291. Bennett, R.N., Mellon, F.A., Foidl, N., Pratt, J.H., Dupont, M.S., Perkins, L., Kroon, P.A., 2003. Profiling glucosinolates and phenolics in vegetative and reproductive tissues of the multi-purpose trees Moringa oleifera L. (horseradish tree) and Moringa stenopetala L. Journal of Agricultural and Food Chemistry 51, 3546–3553. Berkovich, L., Earon, G., Ron, I., Rimmon, A., Vexler, A., Lev-Ari, S., 2013. Moringa oleifera aqueous leaf extract down-regulates nuclear factor-kappa B and increases cytotoxic effect of chemotherapy in pancreatic cancer cells. BMC Complementary and Alternative Medicine 13, 212. Bohn, S.K., Ward, N.C., Hodgson, J.M., Croft, K.D., 2012. Effects of tea and coffee on cardiovascular disease risk. Food and Function 3, 575–591. Bundy, J.D., Li, C., Stuchlik, P., Bu, X., Kelly, T.N., Mills, K.T., He, H., Chen, J., Whelton, P.K., He, J., 2017. Systolic blood pressure reduction and risk of cardiovascular disease and mortality: a systematic review and network meta-analysis. JAMA Cardiology 2, 775–781. Cao, Y., Ma, Z., Zhang, H., Jin, Y., Zhang, Y., Hayford, F., 2018. Phytochemical properties and nutrigenomic implications of Yacon as a potential source of prebiotic: current evidence and future directions. Food 7, 59. Chen, K.H., Chen, Y.J., Yang, C.H., Liu, K.W., Chang, J.L., Pan, S.F., Lin, T.B., Chen, M.J., 2012. Attenuation of the extract from Moringa oleifera on monocrotaline-induced pulmonary hypertension in rats. Chinese Journal of Physiology 55, 22–30. Cheraghi, M., Namdari, M., Daraee, H., Negahdari, B., 2017. Cardioprotective effect of magnetic hydrogel nanocomposite loaded N,alpha-L-rhamnopyranosyl vincosamide isolated from Moringa oleifera leaves against doxorubicin-induced cardiac toxicity in rats: in vitro and in vivo studies. Journal of Microencapsulation 34, 335–341. Chumark, P., Khunawat, P., Sanvarinda, Y., Phornchirasilp, S., Morales, N.P., PhivthongNgam, L., Ratanachamnong, P., Srisawat, S., Pongrapeeporn, K.U., 2008. The in vitro and ex vivo antioxidant properties, hypolipidaemic and antiatherosclerotic activities of water extract of Moringa oleifera Lam. Leaves. Journal of Ethnopharmacology 116, 439–446. Coppin, J.P., Xu, Y., Chen, H., Pan, M.-H., Ho, C.-T., Juliani, R., Simon, J.E., Wu, Q., 2013. Determination of flavonoids by LC/MS and anti-inflammatory activity in Moringa oleifera. Journal of Functional Foods 5, 1892–1899. Das, N., Sikder, K., Ghosh, S., Fromenty, B., Dey, S., 2012. Moringa oleifera Lam leaf extract prevents early liver injury and restores antioxidant status in mice fed with high-fat diet. Indian Journal of Experimental Biology 50, 404–412. Das, N., Sikder, K., Bhattacharjee, S., Majumdar, S.B., Ghosh, S., Majumdar, S., Dey, S., 2013. Quercetin alleviates inflammation after short-term treatment in high-fat-fed mice. Food and Function 4, 889–898. Faizi, S., Siddiqui, B.S., Saleem, R., Siddiqui, S., Aftab, K., Gilani, A.-U.H., 1994. Isolation and structure elucidation of new nitrile and mustard oil glycosides from Moringa oleifera and their effect on blood pressure. Journal of Natural Products 57, 1256–1261. Faizi, S., Siddiqui, B.S., Saleem, R., Siddiqui, S., Aftab, K., Gilani, A.H., 1995. Fully acetylated carbamate and hypotensive thiocarbamate glycosides from Moringa oleifera. Phytochemistry 38, 957–963.

Please cite this article as: Z.F. Ma, J. Ahmad, H. Zhang, et al., Evaluation of phytochemical and medicinal properties of Moringa (Moringa oleifera) as a potential functional food..., South African Journal of Botany, https://doi.org/10.1016/j.sajb.2018.12.002

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Z.F. Ma et al. / South African Journal of Botany xxx (2018) xxx

Faizi, S., Siddiqui, B.S., Saleem, R., Aftab, K., Shaheen, F., Gilani, A.-U.-H., 1998. Hypotensive constituents from the pods of Moringa oleifera. Planta Medica 64, 225–228. Fakurazi, S., Hairuszah, I., Nanthini, U., 2008. Moringa oleifera Lam prevents acetaminophen induced liver injury through restoration of glutathione level. Food and Chemical Toxicology 46, 2611–2615. Ghasi, S., Nwobodo, E., Ofili, J.O., 2000. Hypocholesterolemic effects of crude extract of leaf of Moringa oleifera Lam in high-fat diet fed wistar rats. Journal of Ethnopharmacology 69, 21–25. Glover-Amengor, M., Aryeetey, R., Afari, E., Nyarko, A., 2017. Micronutrient composition and acceptability of Moringa oleifera leaf-fortified dishes by children in Ada-East district, Ghana. Food Science and Nutrition 5, 317–323. Gupta, R., Mathur, M., Bajaj, V.K., Katariya, P., Yadav, S., Kamal, R., Gupta, R.S., 2012. Evaluation of antidiabetic and antioxidant activity of Moringa oleifera in experimental diabetes. Journal of Diabetes 4, 164–171. Hamza, A.A., 2010. Ameliorative effects of Moringa oleifera Lam seed extract on liver fibrosis in rats. Food and Chemical Toxicology 48, 345–355. Irfan, H.M., Asmawi, M.Z., Khan, N.A.K., Sadikun, A., Mordi, M.N., 2017. Antidiabeticactivity-guided screening of aqueous ethanol Moringa oleifera extracts and fractions: identification of marker compounds. Tropical Journal of Pharmaceutical Research 16, 543–552. Jain, P.G., Patil, S.D., Haswani, N.G., Girase, M.V., Surana, S.J., 2010. Hypolipidemic activity of Moringa oleifera Lam, Moringaceae, on high fat diet induced hyperlipidemia in albino rats. Revista Brasileira de Farmacognosia 20, 969–973. Jaiswal, D., Kumar Rai, P., Kumar, A., Mehta, S., Watal, G., 2009. Effect of Moringa oleifera Lam leaves aqueous extract therapy on hyperglycemic rats. Journal of Ethnopharmacology 123, 392–396. Jaja-Chimedza, A., Graf, B.L., Simmler, C., Kim, Y., Kuhn, P., Pauli, G.F., Raskin, I., 2017. Biochemical characterization and anti-inflammatory properties of an isothiocyanateenriched moringa (Moringa oleifera) seed extract. PLoS One 12, e0182658. Ji, H.-F., Li, X.-J., Zhang, H.-Y., 2009. Natural products and drug discovery. Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia? EMBO Reports 10, 194–200. Joshi, P., Mehta, D., 2010. Effect of dehydration on the nutritive value of drumstick leaves. Journal of Metabolomics and Systems Biology 1, 5–9. Jung, I.L., 2014. Soluble extract from Moringa oleifera leaves with a new anticancer activity. PLoS One 9, e95492. Karim, N.A., Ibrahim, M.D., Kntayya, S.B., Rukayadi, Y., Hamid, H.A., Razis, A.F., 2016. Moringa oleifera Lam: targeting chemoprevention. Asian Pacific Journal of Cancer Prevention 17, 3675–3686. Karthivashan, G., Arulselvan, P., Tan, S.W., Fakurazi, S., 2015. The molecular mechanism underlying the hepatoprotective potential of Moringa oleifera leaves extract against acetaminophen induced hepatotoxicity in mice. Journal of Functional Foods 17, 115–126. Khan, W., Parveen, R., Chester, K., Parveen, S., Ahmad, S., 2017. Hypoglycemic potential of aqueous extract of Moringa oleifera leaf and in vivo GC-MS Metabolomics. Frontiers in Pharmacology 8, 577. Kidmose, U., Yang, R.-Y., Thilsted, S., Christensen, L.P., Brandt, K., 2006. Content of carotenoids in commonly consumed Asian vegetables and stability and extractability during frying. Journal of Food Composition and Analysis 19, 562–571. Kim, H.S., 2005. Do not put too much value on conventional medicines. Journal of Ethnopharmacology 100, 37–39. Kooltheat, N., Sranujit, R.P., Chumark, P., Potup, P., Laytragoon-Lewin, N., Usuwanthim, K., 2014. An ethyl acetate fraction of Moringa oleifera Lam inhibits human macrophage cytokine production induced by cigarette smoke. Nutrients 6, 697–710. Kou, X., Li, B., Olayanju, J.B., Drake, J.M., Chen, N., 2018. Nutraceutical or pharmacological potential of Moringa oleifera Lam. Nutrients 10, 343. Kumari, D.J., 2010. Hypoglycaemic effect of Moringa oleifera and Azadirachta indica in type 2 diabetes mellitus. Bioscan 5, 211–214. Kushwaha, S., Chawla, P., Kochhar, A., 2014. Effect of supplementation of drumstick (Moringa oleifera) and amaranth (Amaranthus tricolor) leaves powder on antioxidant profile and oxidative status among postmenopausal women. Journal of Food Science and Technology 51, 3464–3469. Leone, A., Spada, A., Battezzati, A., Schiraldi, A., Aristil, J., Bertoli, S., 2015. Cultivation, genetic, ethnopharmacology, phytochemistry and pharmacology of Moringa oleifera leaves: an overview. International Journal of Molecular Sciences 16, 12791–12835. Luqman, S., Srivastava, S., Kumar, R., Maurya, A.K., Chanda, D., 2012. Experimental assessment of Moringa oleifera leaf and fruit for its antistress, antioxidant, and scavenging potential using in vitro and in vivo assays. Evidence-based Complementary and Alternative Medicine 2012. Ma, Z.F., Lee, Y.Y., 2016. Virgin coconut oil and its cardiovascular health benefits. Natural Product Communications 11, 1151–1152. Ma, Z., Zhang, H., 2017. Phytochemical constituents, health benefits, and industrial applications of grape seeds: a mini-review. Antioxidants 6, 71. Mahajan, S.G., Banerjee, A., Chauhan, B.F., Padh, H., Nivsarkar, M., Mehta, A.A., 2009. Inhibitory effect of n-butanol fraction of Moringa oleifera Lam seeds on ovalbumin-induced airway inflammation in a guinea pig model of asthma. International Journal of Toxicology 28, 519–527. Mahmood, K.T., Mugal, T., Haq, I.U., 2010. Moringa oleifera: a natural gift - a review. Journal of Pharmaceutical Sciences and Research 2, 775. Maldini, M., Maksoud, S.A., Natella, F., Montoro, P., Petretto, G.L., Foddai, M., De Nicola, G.R., Chessa, M., Pintore, G., 2014. Moringa oleifera: study of phenolics and glucosinolates by mass spectrometry. Journal of Mass Spectrometry 49, 900–910. Mehta, K., Balaraman, R., Amin, A.H., Bafna, P.A., Gulati, O.D., 2003. Effect of fruits of Moringa oleifera on the lipid profile of normal and hypercholesterolaemic rabbits. Journal of Ethnopharmacology 86, 191–195.

Mohammed, S., Manan, F.A., 2015. Analysis of total phenolics, tannins and flavonoids from Moringa oleifera seed extract. Journal of Chemical and Pharmaceutical Research 7, 135–137. Moyo, B., Oyedemi, S., Masika, P.J., Muchenje, V., 2012. Polyphenolic content and antioxidant properties of Moringa oleifera leaf extracts and enzymatic activity of liver from goats supplemented with Moringa oleifera leaves/sunflower seed cake. Meat Science 91, 441–447. Muangnoi, C., Chingsuwanrote, P., Praengamthanachoti, P., Svasti, S., Tuntipopipat, S., 2012. Moringa oleifera pod inhibits inflammatory mediator production by lipopolysaccharide-stimulated RAW 264.7 murine macrophage cell lines. Inflammation 35, 445–455. Muhammad, H.I., Asmawi, M.Z., Khan, N.A.K., 2016. A review on promising phytochemical, nutritional and glycemic control studies on Moringa oleifera Lam in tropical and sub-tropical regions. Asian Pacific Journal of Tropical Biomedicine 6, 896–902. Nambiar, V.S., Guin, P., Parnami, S., Daniel, M., 2010. Impact of antioxidants from drumstick leaves on the lipid profile of hyperlipidemics. Journal of Herbal Medicine and Toxicology 4, 165–172. Ndong, M., Uehara, M., Katsumata, S.-I., Suzuki, K., 2007. Effects of oral administration of Moringa oleifera Lam on glucose tolerance in Goto-Kakizaki and Wistar rats. Journal of Clinical Biochemistry and Nutrition 40, 229–233. Oboh, G., Ademiluyi, A.O., Ademosun, A.O., Olasehinde, T.A., Oyeleye, S.I., Boligon, A.A., Athayde, M.L., 2015. Phenolic extract from Moringa oleifera leaves inhibits key enzymes linked to erectile dysfunction and oxidative stress in rats' penile tissues. Biochemistry Research International 2015. Okumu, M.O., Ochola, F.O., Mbaria, J.M., Kanja, L.W., Gakuya, D.W., Kinyua, A.W., Okumu, P.O., Kiama, S.G., 2017. Mitigative effects of Moringa oleifera against liver injury induced by artesunate-amodiaquine antimalarial combination in wistar rats. Clinical Phytoscience 3, 18. Olayaki, L.A., Irekpita, J.E., Yakubu, M.T., Ojo, O.O., 2015. Methanolic extract of Moringa oleifera leaves improves glucose tolerance, glycogen synthesis and lipid metabolism in alloxan-induced diabetic rats. Journal of Basic and Clinical Physiology and Pharmacology 26, 585–593. Omodanisi, E.I., Aboua, Y.G., Oguntibeju, O.O., 2017. Assessment of the antihyperglycaemic, anti-inflammatory and antioxidant activities of the methanol extract of Moringa oleifera in diabetes-induced nephrotoxic male Wistar rats. Molecules 22. Panda, S., Kar, A., Sharma, P., Sharma, A., 2013. Cardioprotective potential of N,alpha-Lrhamnopyranosyl vincosamide, an indole alkaloid, isolated from the leaves of Moringa oleifera in isoproterenol induced cardiotoxic rats: in vivo and in vitro studies. Bioorganic and Medicinal Chemistry Letters 23, 959–962. Pari, L., Kumar, N.A., 2002. Hepatoprotective activity of Moringa oleifera on antitubercular drug-induced liver damage in rats. Journal of Medicinal Food 5, 171–177. Purwal, L., Pathak, A., Jain, U., 2010. In vivo anticancer activity of the leaves and fruits of Moringa oleifera on mouse melanoma. Pharmacology 1, 655–665. Rajanandh, M., Satishkumar, M., Elango, K., Suresh, B., 2012. Moringa oleifera Lam. A herbal medicine for hyperlipidemia: a pre-clinical report. Asian Pacific Journal of Tropical Disease 2, S790–S795. Randriamboavonjy, J.I., Rio, M., Pacaud, P., Loirand, G., Tesse, A., 2017. Moringa oleifera seeds attenuate vascular oxidative and nitrosative stresses in spontaneously hypertensive rats. Oxidative Medicine and Cellular Longevity 2017, 4129459. Ravichanthiran, K., Ma, Z., Zhang, H., Cao, Y., Wang, C., Muhammad, S., Aglago, E., Zhang, Y., Jin, Y., Pan, B., 2018. Phytochemical profile of brown rice and its nutrigenomic implications. Antioxidants 7, 71. Sadek, K.M., Abouzed, T.K., Abouelkhair, R., Nasr, S., 2017. The chemo-prophylactic efficacy of an ethanol Moringa oleifera leaf extract against hepatocellular carcinoma in rats. Pharmaceutical Biology 55, 1458–1466. Sahakitpichan, P., Mahidol, C., Disadee, W., Ruchirawat, S., Kanchanapoom, T., 2011. Unusual glycosides of pyrrole alkaloid and 4′-hydroxyphenylethanamide from leaves of Moringa oleifera. Phytochemistry 72, 791–795. Saini, R.K., Shetty, N.P., Giridhar, P., 2014. Carotenoid content in vegetative and reproductive parts of commercially grown Moringa oleifera L. cultivars from India by LC–APCI– MS. European Food Research and Technology 238, 971–978. Saini, R.K., Sivanesan, I., Keum, Y.-S., 2016. Phytochemicals of Moringa oleifera: a review of their nutritional, therapeutic and industrial significance. 3 Biotechnology 6, 203. Siddhuraju, P., Becker, K., 2003. Antioxidant properties of various solvent extracts of total phenolic constituents from three different agroclimatic origins of drumstick tree (Moringa oleifera Lam) leaves. Journal of Agricultural and Food Chemistry 51, 2144–2155. Singh, B.N., Singh, B.R., Singh, R.L., Prakash, D., Dhakarey, R., Upadhyay, G., Singh, H.B., 2009. Oxidative DNA damage protective activity, antioxidant and anti-quorum sensing potentials of Moringa oleifera. Food and Chemical Toxicology 47, 1109–1116. Sreelatha, S., Padma, P.R., 2009. Antioxidant activity and total phenolic content of Moringa oleifera leaves in two stages of maturity. Plant Foods for Human Nutrition 64, 303–311. Sreelatha, S., Jeyachitra, A., Padma, P.R., 2011. Antiproliferation and induction of apoptosis by Moringa oleifera leaf extract on human cancer cells. Food and Chemical Toxicology 49, 1270–1275. Sultana, B., Anwar, F., 2008. Flavonols (kaempeferol, quercetin, myricetin) contents of selected fruits, vegetables and medicinal plants. Food Chemistry 108, 879–884. Tang, Y., Choi, E.J., Han, W.C., Oh, M., Kim, J., Hwang, J.Y., Park, P.J., Moon, S.H., Kim, Y.S., Kim, E.K., 2017. Moringa oleifera from Cambodia ameliorates oxidative stress, hyperglycemia, and kidney dysfunction in type 2 diabetic mice. Journal of Medicinal Food 20, 502–510. Taweerutchana, R., Lumlerdkij, N., Vannasaeng, S., Akarasereenont, P., Sriwijitkamol, A., 2017. Effect of Moringa oleifera leaf capsules on glycemic control in therapy-naive

Please cite this article as: Z.F. Ma, J. Ahmad, H. Zhang, et al., Evaluation of phytochemical and medicinal properties of Moringa (Moringa oleifera) as a potential functional food..., South African Journal of Botany, https://doi.org/10.1016/j.sajb.2018.12.002

Z.F. Ma et al. / South African Journal of Botany xxx (2018) xxx type 2 diabetes patients: a randomized placebo controlled study. Evidence-based Complementary and Alternative Medicine 2017, 6581390. Teixeira, E.M., Carvalho, M.R., Neves, V.A., Silva, M.A., Arantes-Pereira, L., 2014. Chemical characteristics and fractionation of proteins from Moringa oleifera Lam leaves. Food Chemistry 147, 51–54. Tiloke, C., Phulukdaree, A., Chuturgoon, A.A., 2013. The antiproliferative effect of Moringa oleifera crude aqueous leaf extract on cancerous human alveolar epithelial cells. BMC Complementary and Alternative Medicine 13, 226. Vats, S., Gupta, T., 2017. Evaluation of bioactive compounds and antioxidant potential of hydroethanolic extract of Moringa oleifera Lam from Rajasthan, India. Physiology and Molecular Biology of Plants 23, 239–248. Verma, A.R., Vijayakumar, M., Mathela, C.S., Rao, C.V., 2009. In vitro and in vivo antioxidant properties of different fractions of Moringa oleifera leaves. Food and Chemical Toxicology 47, 2196–2201. Vongsak, B., Sithisarn, P., Gritsanapan, W., 2013. Simultaneous determination of cryptochlorogenic acid, isoquercetin, and astragalin contents in Moringa oleifera leaf extracts by TLC-densitometric method. Evidence-based Complementary and Alternative Medicine 2013, 917609.

7

Waterman, C., Cheng, D.M., Rojas-Silva, P., Poulev, A., Dreifus, J., Lila, M.A., Raskin, I., 2014. Stable, water extractable isothiocyanates from Moringa oleifera leaves attenuate inflammation in vitro. Phytochemistry 103, 114–122. Waterman, C., Rojas-Silva, P., Tumer, T.B., Kuhn, P., Richard, A.J., Wicks, S., Stephens, J.M., Wang, Z., Mynatt, R., Cefalu, W., Raskin, I., 2015. Isothiocyanate-richMoringa oleifera extract reduces weight gain, insulin resistance, and hepatic gluconeogenesis in mice. Molecular Nutrition aand Food Research 59, 1013–1024. Yassa, H.D., Tohamy, A.F., 2014. Extract of Moringa oleifera leaves ameliorates streptozotocin-induced diabetes mellitus in adult rats. Acta Histochemica 116, 844–854. Zhang, H., Ma, Z., 2018. Phytochemical and pharmacological properties of Capparis spinosa as a medicinal plant. Nutrients 10, 116. Zhang, M., Hettiarachchy, N.S., Horax, R., Kannan, A., Praisoody, A., Muhundan, A., 2011. Phytochemicals, antioxidant and antimicrobial activity of Hibiscus sabdariffa, Centella asiatica, Moringa oleifera and Murraya koenigii leaves. Journal of Medicinal Plants Research 5, 6672–6680. Zhang, H., Ma, Z., Luo, X., Li, X., 2018. Effects of Mulberry fruit (Morus alba L.) consumption on health outcomes: a mini-review. Antioxidants 7, 69.

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