Moringa

Moringa oleifera (of the family Moringaceae and synonymous with Moringa pterygosperma^[1]) is a drought-resistant wispy tree that grows in and has traditional usage as a food product in Asian countries^[2][3] and some African countries such as Zimbabwe^[4] and is commonly referred to as either Horse Radish tree (referring to the taste of its roots) or Drumstick tree (describing the shape of its pods)^[3] while less frequently referred to as 'The Tree of Life' or 'Miracle Tree' due to its economical importance and versatility (to be discussed)^[5][6] or Ben Oil Tree;^[7] some other cultural names being Zogale^[8] and Sahijan.^[9]

It is sometimes used for culinary purposes by wrapping the leaves around food products to preserve their quality and reduce bacterial contamination^[10] due to mixed antioxidant, antibacterial,^[11] and protease inhibiting properties.^[12]

More than anything, it appears to be renowned as an economically valuable tree and humanitarian potential (due to being both drought resistant and nutritive, as well as growing very fast reaching 3-5 meters tall within a year)^[2][13][14] and possibly detering mosquitoes as a repellant (an indirect anti-malarial measure).^[15] Moringa (specifically, a dehusked press cake) also appears to be effective in the removal of hydrophobic organic pollutants^[16] as well as minerals, surfactants,^[17][18] benzene and toluene,^[19] and may even have anti-cyanobacterial potential.^[20]

Moringa oleifera (Drumstick tree) is a tree that bears fruits, flowers, and leaves; beyond medicinal usage, it has a large degree of potential as an economical herb due to its resistance to drought and very rapid growth

The plant is used as an African folk medicine for the treatment of ascites, rheumatism, venomous bites and pneumonia^[21][22] and in other places (Phillipines) it is used for circulatory disorders, metabolic and endocrine disorders, and general nutritional deficiencies.^[5] It has some usage for the prevention of diabetes and glucose disturbances (Africa)^[23] wound healing,^[24] and as an aphrodisiac.^[25]

Most parts of this plant are said to hold some medicial properties even including the seeds,^[26] fruit pods,^[27] and flowers^[28] although the leaves are thought to be the main medicinal component. The leaves are also known to have the highest antioxidant potential of all plant parts.^[29]

Most traditional medicinal usage of this plant is related to it being an anti-inflammatory agent and tends to be focused on the leaf extracts of the plant

The plant moringa oleifera is both a vegetable as well as a medicinal herb, and as such a proper analysis would look at its macronutrient and nutritional profile in addition to isolated bioactives. In regards to a nutritional analysis:

The leaves contain:

• 20.72–25.29% protein by dry weight (5.4% wet weight)^[8][3] which is higher than other vegetable leafs^[30]
• Fatty acids 5.37-5.75% of dry weight (1.19–2.77% wet weight)^[3] again higher than other vegetable leafs^[31] with at least one source stating 12.5% dry weight^[8]
• Carbohydrates at 37.98%^[8] of which 12% (total weight) is sugars^[30]
• Dietary fiber at 13.71%^[8]
• An ash content in the range of 8.53-15.09% dry weight^[3][8]
• Calcium at 870-3,468mg/100g dry weight^[8][30]
• Phosphorus at 228-600mg/100g dry weight^[8][30]
• Magnesium at 300-831mg/100g dry weight^[8][30]
• Sodium at 0.05% leaf dry weight (50mg/100g)^[30]
• Potassium at 300mg/100g dry weight (0.3%)^[30]
• Copper at 960-1,170µg/100g dry weight^[8][30]
• Manganese at 11.28mg/100g^[8]
• Zinc at 2.04mg/100g^[8]
• Iron at 105mg/100g^[8]
• A phenolic content of 181.3–200.0mg/100g catechin equivalents^[3]
• Phytate (31.1mg/g dry weight)^[30]
• Oxalate (4.1mg/g dry weight)^[30]

The flowers contain:

• 1,931mg/100g gallic acid equivalents (phenolic content) at 8.69% by weight^[28]
• Protease enzymes^[32]

The seeds and their pods contain:

• 20-30% protein (pods)^[2]
• 35-45% fatty acids (seeds) which are mostly odorless and colorless^[26] and consists of mostly (73%) oleic acid with less than 1% polyunsaturated fatty acids, which gives the oils good oxidative stability^[33][26][34]
• A chitin binding protein^[35][36] and an α-Mannosidase (kernals)^[37]

The stem contains:

• Protein at 9.56-12.77% dry weight^[3]
• A 1.98-2.00% fatty acid content dry weight^[3]
• A 6.65-8.41% ash content dry weight^[3]
• Calcium at 780-1,562mg/100g dry weight^[3]
• 71.9–134.4mg/100g catechin equivalents (phenolic content)^[3]

The root contains:

• Protein at 5.29-7.07% dry weight^[3]
• Fatty acids at 1.00-1.38% dry weight^[3]
• An ash content of 2.91-6.48% dry weight^[3]
• Calcium at 761-2,247mg/100g dry weight^[3]
• 68.8–93.8mg/100g catechin equivalents^[3]

When looking at the overall macronutrient and phenolic contents, the stem and root portions of the plant appear to have less of all bioactives of interest (phenolics, proteins, and fatty acids) which supports the usage of the leaf extracts as the medicinal component. The flowers seem to have a high phenolic content, and similar to most seeds the seeds of moringa oleifera are mostly proteins and fatty acids

For medicinal bioactives, moringa oleifera (leaves unless otherwise specified) contains:

• Isothiocyanates such as 4-{(2'-O-acetyl-α-L-rhamnosyloxy)benzyl}isothiocyanate (RBITC; a 2'-acetylated glycoside of benzylisothiocyanate)^[38] and a 4'-acetylated variant (seeds)^[39] as well as a fully nonacetylated 4-(alpha-L-Rhamnosyloxy)benzyl isothiocyanate.^[39] The total glucosinolates in the leaves have been quantified in the 63-114mg/g dry weight range (favoring young leaves^[40]) which is higher than the root (43mg/g^[40]) but lower than seeds (200mg/g^[40]), with the leaves claimed^[41] to be higher than plants in the brassicaceae family of plants
• Moringine, which is a protonated Benzylamine^[42] as well as p-hydroxybenzoate^[43]
• The indole alkaloid N,α-L-rhamnopyranosyl vincosamide^[44]
• The pyrrole alkaloid pyrrolemarumine (4″-O-α-L-rhamnopyranoside) and its glycosides^[45]
• Marumosides A and B (glycosides of 4'-hydroxyphenylethanamide, which is literally Paracetamol)^[45]
• Carbamates known as Niazimin A-B and Niazicin A-B^[46] and thiocarbamate glycosides^[46] such as Niaziminin A-B^[47]
• The carbamate O-ethyl-4-{(alpha-L-rhamnosyloxy)-benzyl} carbamate^[43]
• The nitrile glycoside (mustard oil glycosides) known as Niazirin (70mg per gram crude extract, or 7% of the pods)^[48][47] and Niazirinin (the 4'-O-acetylated version of Niazirin)^[47]
• Nitrate at 5mM/100g dry weight^[30]
• Pterygospermin^[49][50]
• Crypto-chlorogenic acid (leaves at 0.01-0.1% dry weight^[51][52][53])
• Quercetin (795-975μg/g dry leaf weight^[54][55] and 845μg/g in flowers^[54]),^[56] Rutin,^[56] quercetin 3-O-βD-(600-O-malonyl)-glucoside,^[57] and the isomer Isoquercetin (0.01-0.12% of the leaves dry weight^[51][52][53])
• Kaempferol (216-2,100μg/g leaf dry weight^[54][55] and 2,802μg/g in flowers^[54]),^[56]its 3-glucoside Astragalin (0.02-0.16% of the leaves dry weight^[51][52][53]), and its rhamnoglucoside^[58]
• Procyanidins^[58]
• 4-O-caffeoylquinic acid, 5-O-caffeoylquinic acid, and glucosides thereof^[57]
• Protease inhibitors (leaves and seeds) with activity against serine proteases (trypsin and chymotrypsin) and bacterial proteases, but was ineffective against subtilisin, esperase, pronase E, and proteinase K^[12]

While the plant is a source of flavonoids, the main bioactives that appear to be somewhat unique to this plant include the isothiocyanate class of molecules (structurally similar to sulforaphane), the carbamates, and their glycosides; Niazirin and RBITC seem to be important components, and this plant does appear to have a small paracetamol content (as glycosides, interestingly)

A 70% ethanolic extract or 50% methanolic extract appears to be most suitable for phenolic and flavonoid extraction^[59][60] and 60 minutes of extraction at 90°C is also desirable;^[59] Myricetin does not appear to be present in leaves nor flowers.^[54]

It should be noted that the main bioactive of Moringa oleifera contains an isothiocyanate group (-N=C=S) which is similar to sulforaphane and this group is thought to be a hydrogen sulfide (H₂S) donating group;^[61] it so, then moringa oleifera has a possibility to increase H₂S signalling which underlies most benefits of garlic supplementation.

There may be a mechanistic connection between Moringa oleifera and both sulforaphane and garlic, two relatively potent chemoprotective and heart healthy supplements. This requires confirmation

The seed oil, due to being approximately 73% oleic acid (a monounsaturated fatty acid) and less than 1% polyunsaturated fatty acids exhibits a high degree of oxidative stability, exceeding the stability of other oleic-acid rich oils such as olive oil, high-oleic sunflower, meadowfoam, macadamia, hybrid safflower, safflower, almond and apricot oils.^[33]

The leaves of moringa oleifera are said to have a hot taste (hot, radishy, and pungent) which begets the nickname of this tree being Horse Radish Tree.^[62]

The gum derived from moringa oleifera appears to have emulsifying properties which, under experimental conditions, exceeds that of gum acacia when at similar concentrations (2-4% of a 30% castor oil solution).^[63]

In mice administered rifampicin, an ethyl acetate fraction of the plant (dubbed the active fragment) at 0.1mg/kg coadministered acutely with rifampicin resulted in increased blood exposure of the drug as assessed by C_max (43%), half-life (505%), and AUC (512%).^[64] When looking at P450 enzymatic activity overall, there appears to be a suppression indicating enzymatic inhibition^[64] or at least preventing the known upregulation seen with rifampicin.^[65]

There do appear to be interactions with cytochrome P450 enzymes associated with moringa oleifera, but at this moment in time they are not fully elucidated

2,000mg/kg of the leaf extract (ethanolic) to mice is able to protect mice from pentylenetetrazol (PTZ) induced convulsions, although it is wholly ineffective against picrotoxin and strychnine.^[6]

250-2,000mg/kg of the ethanolic leaf extract causes dose dependent sedation^[6] and toxicology tests which failed to note toxicity have noted that a main side effect of doses of the water leaf extract (above 3,200mg/kg) are sedation and redued locomotion.^[66]

In rats given 250mg/kg of the ethanolic leaf extract, it appears that there is an increase in noradrenaline concentrations in the cerebral cortex (44%) and hippocampus (25.6%) relative to control but a nonsignificant change in the caudate nucleus.^[67]

There appears to be a statistically significant increase in dopamine concentrations of the caudate nucleus (25.8%) and hippocampus (18.9%) after ingestion of 250mg/kg of the ethanolic leaf extract, although concentrations in the cerebral cortex remain unchanged.^[67]

Serotonin concentrations in the rat brain following ingestion of 250mg/kg of the ethanolic leaf extract appear to be differentially effected, with a large (60.7%) increase in the cerebral cortex and a decrease (10.7%) in the caudate nucleus with no alterations in the hippocampus.^[67]

In a mouse model of scopolamine induced amnesiabefore testing in a passive shock avoidance paradigm and elevated plus maze, a specific extract of moringa oleifera (methanolic extract, but a Toluene-ethylacetate subfraction that was 0.26% yield) at 50-100mg/kg appears to exert protective effects of somewhat comparable potency as 100mg/kg Piracetam.^[68] Protective effects have been noted in hypoxia induced amnesia^[69] as well as in colchine-induced Alzheimer's disease in rats.^[70][67]

Alongside anti-amnesiac effects, a preservation of antioxidant biomarkers (higher SOD and Catalase, with less lipid peroxidation) has been noted in the cerebral cortex with 250mg/kg moringa oleifera leaf extract^[70] and the decrease in serotonin, noradrenaline, and dopamine seen with cochine (250mg/kg ethanolic extract) appears to be attenuated.^[67] Both the antioxidant effects and the preservation of monoamines are thought to underlie the antiamnesiac properties.^[71]

There appears to be anti-amnesiac properties associated with moringa oleifera leaf extracts, although the exact molecule underlying these benefits is not known and the potency not absolute

In mice given 250-2,000mg/kg of the leaf ethanolic extract, there appears to be increased learning and memory as assessed by Y-maze testing^[6] and in mice subject to a passive shock avoidance paradigm 50-100mg/kg of a methanolic extract subfraction (0.26% total leaf yield) was able to reduce the number of mistakes and latency.^[68]

Possible minor nootropic effects associated with the leaf extracts

In mice given 250-2,000mg/kg of the ethanolic leaf extract, it appeared that supplementation was able to cause a reduction in anxiety in a hole board test and elevated plus maze.^[6]

In adult male rats with chemically induced arthritis, a methanolic extract of the leaves (300-400mg/kg, but not 200mg/kg) is able to reduce pain perception (assessed by thermal and mechanical testing) with a potency comparable to 5mg/kg Indomethacin.^[21] Root extracts were similarly effective against thermal testing, but were ineffective against mechanical allodynia at all doses.^[21]

A leaf extract of moringa oleifera does not appear to inhibit intestinal lipase, suggesting no inhibition of dietary fat absorption.^[72]

A leaf extract appears to significantly inhibit cholesterol micelle formation (40% inhibition at 10mg/mL) and can directly bind to bile acids (no influence on pancreatic cholesterol esterase), suggesting an inhibitory effect on cholesterol absorption.^[72]

May inhibit cholesterol absorption from the intestines, but does not appear to be involved with fatty acids absorption inhibition

Isolated N,α-L-rhamnopyranosyl vincosamide (from the leaves) appears to reduce infarct size from isoproterenol in rats from 52% down to 20% when preloaded for seven days at the dose of 40mg/kg (most effective dose based on preliminary data).^[44]

10-100mg/kg of water extracts of moringa oleifera (leafs and pods), but not methanolic extracts, appear to cause an increase in hemoglobin in mice following a single oral dose.^[7]

When looking at the isothiocyanates and thiocarbamates of moringa oleifera, it was noted that the molecules with a cyanide and sulfur group (RBITC, Niaziminins A-B) were able to reduce blood pressure at a dose of 3mg/kg by 35-40% in anesthetized rats.^[47][73]

In a rat model of monocrotaline-induced pulmonary hypertension, injections of the leaf extract at 4.5mg/kg appear to cause a reduction in blood pressure associated with vasodilation and increased antioxidant potential.^[74]

A review^[75] notes a study which cannot be found online (Kumari 2010) suggesting that 8g of the leaf powder daily over the course of 40 days in type II diabetics is able to reduce total cholesterol (14%), LDL-C (29%), vLDL-C (15%), and triglycerides (14%) with a nonsignificant increase in HDL-C by 9%.

Limited evidence in human suggests that there may be a hypolipidemic effect of supplementation in diabetics

The leaf extract of moringa oleifera appears to inhibit intestinal sucrase with an IC₅₀ of 780+/-210µg/mL, with weak inhibitory potential against pancreatic amylase.^[72]

Potential inhibitory effects on sucrose absorption, although no apparent inhibition of starch absorption

200mg/kg of the water extract of the leaves appears to have hypoglycemic properties in otherwise normal rats, reducing fasting blood glucose by 26.7% over the course of eight hours after acute ingestion and reducing the spike in glucose from an oral glucose tolerance test by 29.9% relative to control.^[1] This was slightly less hypoglycemic than the reference drug glipizide (2.5mg/kg).^[1]

Moringa oleifera appears to have hypoglycemic properties in rats who do not have diabetes nor insulin resistance, and this appears to be a relatively large drop in blood glucose following acute oral ingestion

200mg/kg of the water extract of the leaves (determined to be more effective than 100mg/kg or 300mg/kg), when fed to diabetic rats over the course of 21 days, there appear to be time dependent decreases in fasting blood glucose reaching up to a 69.2% drop and a reduction in an oral glucose tolerance test after 21 days by 51.2%.^[1] This was comparable or slightly greater than the reference drug glipizide (2.5mg/kg).^[1]

10mg/kg of the leaf extract of moringa oleifera acutely administrated to alloxan induced diabetic rats appears to be of comparable or greater potency than glibenclamide^[76] and in dexamethasone induced insulin resistance, the alcoholic (125-250mg/kg) extract of the leaves appears to prevent insulin resistance from occurring in peripheral tissues although it had no effect on fasting glucose increased by dexamethasone.^[77]

Although not many mechanistic studies are conducted, one using the pods of moringa oleifera has noted less structural damage to the pancreas and its β-cells (alongside the standard antioxidant changes) suggesting a protective effect and preservation of insulin.^[78]

In animal research, moringa oleifera appears to have anti-diabetic properties due to a currently unknown mechanism (although usually said to be due to its antioxidant properties; unconfirmed). The potency, based on the preliminary and limited evidence, is comparable to reference drugs

In type II diabetics given a 75g oral glucose tolerance test, oral ingestion of moringa oleifera was able to reduce blood glucose by approximately 21% and this was not associated with an increase in serum insulin; the other two tested vegetables, Momordica charantia and Murrya koiengii, were ineffective.^[79]

A review on moringa oleifera^[75] notes a study not available online (Kumari 2010) where supplementation of the leaf powder at eight grams daily noted reductions in fasting glucose (28%) and postprandial glucose (26%) relative to baseline over the course of 40 days, and a followup study in sixty type II diabetics supplemented with the leaf extract (dosage unspecified) over 90 days resulted in a decrease in HbA1c (0.4% points) and a time dependent decrease in post-prandial blood glucose by 9% (30 days), 17% (60 days), 29% (end of study).^[80]

There appears to be a reduction in post-meal glucose spikes seen with oral ingestion of moringa oleifera which is not due to a stimulation of insulin secretion

Isothiocyanates (such as sulforaphane^[81] or benzylisothiocyanate^[82]) are known to possess antiinflammatory properties and an isothiocyanate known as RBITC from moringa oleifera, when incubated with macrophages that are stimulated with LPS, is able to inhibit nitrite production in a concentration dependent manner with an IC₅₀ of 960+/-230nM;^[38] this was greater than its aglycone benzylisothiocyanate (2.08+/-0.28µM) and sulforaphane (2.86+/-0.39µM), and it appeared that RBITC was able to suppress iNOS and COX-2 induction by preventing the degradation of IκBα (and thus hindering NF-kB signalling) and reducing phosphorylation of ERK1/2 and JNK (but not p38), although the two pathways seemed independent of each other.^[38] The inhibitory effects of RBITC were additive with the reference MEK1 inhibitor U0126.^[38]

When looking at the plant extract overall though, concentrations of 31-250μg/mL are required (water extract of the pod) to suppress nitric oxide formation whereas 62μg/mL or above are required for the suppression of iNOS and COX-2 induction as well as TNF-α and IL-6 secretion.^[83]

Appears to suppress macrophage activation with a potency greater than sulforaphane and in the nanomolar range

In a model of cyclophosphamide induced immunosuppression (neutropenia or a loss of neutrophil function^[84]), 250-750mg/kg of the methanolic leaf extract appears to attenuate the degree of immunosuppression and preserve neutrophil phagocytosis.^[85] This is also seen with more reasonable (150-500mg/kg) of a 50% ethanolic extract.^[86]

Appears to be somewhat protective against neutrophil related immunosuppression in rats with the leaf extracts

One study using the methanolic extract of the leaves at 250-750mg/kg in mice has noted an increase in circulating antibody titre and immunoglobulins.^[85]

In a carrageenin model of edema where rats were orally supplemented with 750-1,000mg/kg of a root water extract 30 minutes prior to carrageenin injections, the lower dose was able to suppress edema when measured at one hour (53.5%), three hours (44.6%), and five hours (51.1%) while the higher dose was not more effective and 750mg/kg being somewhat comparable to Indomethacin (10mg/kg).^[22]

May have acute anti-inflammatory and anti-edemic properties when water extracts are orally ingested

When looking at extracts from moringa oleifera leaves (hot and cold water extract, a juice, and an ethanolic extraction) it was noted that the juice had a minimum inhibitory concentration (MIC) in the range of 229-458µg/mL against a variety of bacteria; this was slightly more potent than the ethanolic extract (458-916µg/mL) and water extracts (29.87-58.75mg/mL).^[11]

Currently unknown components in the leaves appear to possess somewhat respectable anti-bacterial properties

Moringa oleifera can be used to create high activated carbons^[87][88] which are able to sequester and remove cyanobacterial microcystin-LR quite effectively,^[89] and the seed extract also appears to be capable of suppressing cyanobacterial growth as 20-160mg of moringa oleifera extract per liter of water is able to suppress growth of Microcystis aeruginosa and cause the colony count to decline.^[20]

When cultured in the same water as cyanobacteria, moringa oleifera appears to be capable of reducing microcystin contamination at moderate concentrations

Moringa oleifera (80% hydroalcoholic extract) appears to have antiviral potential against hepatitis B (HBV) in vitro with a potency lesser than that of turmeric, Momordica charantia, and Cratoxylum formosum although 30μg/mL still appeared to reduce HBV cccDNA by more than 85%.^[90]

The leaves appear to be the most potent antioxidant part of the plant, with a methanolic extract sequestering free radicals with an EC₅₀ value of 200-387μg/mL^[3] and in a DPPH assay the IC₅₀ value for inhibition with the stem bark are most potent with the methanolic extract (54.34µg/mL) and lesser with petroleum (124.75µg/mL) and chloroform (112.08µg/mL) extracts.^[91]

This antioxidant property is not correlated with the phenolic content of the plant and is thought to be mostly due to the Vitamin C content;^[3] even when the phenolics reach high levels (using a flower extract which is 8.69% phenolics by weight) the scavenging potential is less than Vitamin C^[28] as vitamin C itself has shown a sequestering potential of 13.68µg/mL (IC₅₀ for DPPH assay) which exceeds that of all moringa oleifera extracts.^[91]

When compared to other medicinal plants, moringa oleifera appears to be less effective than Fenugreek, Holy basil, and Emblica officinalis.^[92]

Appears to be a respectable antioxidant in vitro when scavenging free radicals, but fails to outperform Vitamin C and is less potent than many other medicinal herbs

Components in the stem bark appear to be able to scavenge nitric oxide radicals, with IC₅₀ values of 93.32µg/mL (Petroleum ether extract), 65.12µg/mL (chloroform extract), and 54.83µg/mL (the ethyl acetate soluble fraction of methanolic extracts) all of which underperform relative to vitamin C (12.59µg/mL).^[91]

200mg/kg of the leaf water extract to rats over 21 days has failed to increase antioxidant enzymes (SOD, Catalase, Glutathione peroxidase) in normal rats, but was able to effectively normalize levels of these enzymes in diabetic rats;^[93] as diabetics tend to have lower antioxidant defenses leading to comorbidities.^[94][95]

Ten days supplementation of 175-350mg/kg of the leaf extract in rats, female rats appeared to experience a decrease in circulating T₃ (by around 30%) with an increase in T₄ (15%) while male rats did not experience any changes at either dosage.^[96]

The moringa oleifera leaves may have a suppressive effect on the conversion of T4 into active T3

In diabetic rats, moringa oleifera appears to be able to prevent the oxidative and inflammatory sequelae of diabetic retinopathy from occurring when supplemented over 24 weeks.^[97]

The seeds of Moringa oleifera are said to have beneficial effects in children with upper respiratory tract infections, which is thought to be in part due to a reported antipyretic effect and in part due to direct benefit to lung function.^[98] It has been reported to act similar to epherine (which relaxes the bronchiol tubes) due to the alkaloid Moringine having a structural similarity.^[99]

Mechanistically, the seeds have been noted to have anti-histamine properties by attenuating its release in response to an antigen and 400mg/kg (ethanolic extract) is able to reduce bronchospasms from acetylcholine with a potency comparable to 1mg/kg ketotifen.^[100][101]

The seeds of moringa oleifera appear to have anticholinergic and antiinflammatory properties in the airway, suggesting antiasthmatic properties

In persons with bronchiol asthma (not specifically allergic asthma), a pilot study using Moringa oleifera seeds at 3g (twice daily) for three weeks was associated with significant reductions in the symptoms of dyspnoea, wheezing, coughing, and chest tightness to less than half of baseline.^[99] This study also noted that, according to spirometry tests, that there were improvements in lung function by 32.97+/-6.03% (FVC) and 30.05+/-8.12% (FEV1).^[99]

Preliminary human evidence suggests an improvement in breathing and lung function associated with ingestion of the seeds

Serotonin is secreted in the stomach from enterochromaffin cells (EC cells)^[102] where it is involved in secretion of mucus;^[103] moringa oleifera (leaf water extract) can preserve the amount of these cells and their serotonin content in models of ulceration^[104] and 300mg/kg of this extract for 14 days prior to ulceration (deemed the most effective dose) works in a manner that is blocked by 5-HT₃ receptor antagonists.^[105]

Moringa oleifera appears to signal through the 5-HT₃ receptors in the stomach to exert protective effects in ulceration models against aspirin

An ethanolic extract of the root bark at 150-500mg/kg is able to reduce ulcer formation induced by plyoris-ligation by 82.58-86.15% (minimal dose-dependence) and from alcohol induced ulcer formation by 55.75-78.51%; the reference drug, omeprazole at 30mg/kg, was more effective.^[106] Similar protective effects against ulcers (usually from ethanol or aspirin) have been noted with an ethanolic extract of the leaves in the range of 200-500mg/kg^[107][108] although the fruits appear ineffective.^[108]

In vitro, the seeds of moringa oleifera appear to inhibit acetylcholine induced intestinal contractions with an EC₅₀ of 65.6mg/mL which is indicative of weak antispasmolytic effects.^[109]

In mice fed with the roots of moringa oleifera (100-200mg/kg of the ethanolic extract) for a week preceding induction of experimental colitis, supplementation appears to be equally or slightly less protective than the reference drug of 5mg/kg prednisone (IP injection) while 50mg/kg of moringa oleifera was paired with 50mg/kg of the rind of Citrus sinensis (the common orange) exerted synergistic protection exceeding prednisone on hyperemia and ulceration.^[110] Protective effects have been seen elsewhere with the leaf hydroalcoholic extract (50-200mg/kg) and chloroform extracts (100-200mg/kg) by reducing inflammation and and ulceration in the distal colon from acetic-acid.^[111]

In mice subject to DMBA-induced kidney who recieved 200-400mg/kg of a hydroalcoholic extract of moringa oleifera (pods) for two weeks prior to DMBA, supplementation was able to dose-dependently reduce changes in oxidative status (with the higher dose normalizing GST and glutathione transferase) and fully normalized changes in renal enzymes (AST, ALP, ALT).^[112] The protective effect of moringa oleifera was greater than 0.5-1% Butylated hydroxyanisole (BHA; antioxidant).^[112]

Elsewhere, moringa oleifera appears to be protective against gentamicin-induced nephrotoxicity with 150-300mg/kg of the aqueous-ethanolic extract of the leaves.^[113]

The antioxidant effects of the leaf extracts appear to also occur in the kidney, where they may protect against oxidative toxins

When measuring urinary proteins and sugars in a rat model of diabetes, moringa oleifera appears to abolish all urinary proteins and sugars with 14 days of treatment with 200mg/kg of the water extract of the leaves.^[1]

The antioxidant properties (currently thought to be them at least) appear to underlie a reduction in urinary proteins and glucose in diabetic animals, suggesting protective effects that may attenuate the rate of kidney failure in diabetes

Oral ingestion of 1,000mg/kg of moringa oleifera leaves to rats appears to possess diuretic potential.^[109]

Appears to have some diuretic properties

In response to DMBA induced carcinogenesis, 14 days pretreatment with 200-400mg/kg of a pod extract appear to normalize glutathione transferase and GSH levels in the liver as well as liver enzymes with a potency exceeding 0.5-1% BHA.^[114] Antioxidant-mediated protection has also been noted against anti-tubercular drug induced toxicity (causing hepatic lipid peroxidation)^[115] and against acetominophen toxicity.^{[116][117][118]} The seed oil also appears to be somewhat hepatoprotective (again attributed to antioxidants) as is seen in a model of hepatitis in rats^[119] and one study has noted hepatoprotective effects against a high fat diet^[120] where the leaf extract (150mg/kg) as the early phases of liver damage from a high fat diet involves increased β-oxidation of fatty acids (in response to high dietary intake) causing lipid peroxidation.^[121][122]

In particular against acetominophen toxicity (which causes a production of NAPQI^[123] causing glutathione depletion and oxidative stress^[124]) moringa oleifera (both flower and leaf extracts) appears to work via preserving glutathione^[116] with 200-400mg/kg hydroalcoholic extracts (injection) having comparable potency to 7.35mM injections of N-acetylcysteine.^[117]

300mg/kg of the leaf extract of moringa oleifera appears to reduce the ability of ionizing radition to cause lipid peroxidation in the liver when preloaded for 15 days, fully preventing the increase in lipid peroxidation.^[125][126]

In a study assessing the possible toxicity of moringa oleifera (leaf water extract), it was noted that despite no abnormalities on testicular structure (assessed via histology) there was a transient decrease in sperm count at 250mg/kg oral intake over 60 days; this was not observed at higher doses of 500-1,000mg/kg and both morphology and motility of sperm was unaffected.^[66]

Moringa oleifera appears to be able to induce p53, p27Kip1, and p21WAF1/Cip1 protein levels in B16F10 melanoma cells, leading to reduced proliferation.^[127]

In isolated KB Cells (subtype of HeLa^[128]) the leaf extract of moringa oleifera appears to reduce proliferation and viability of these cells in the range of 100-200µg/mL, which underperformed relative to 10µg/mL cisplatin; this was associated with DNA fragmentation being induced from prooxidative effects.^[55]

A hot water extract of the leaves at 100-2,000μg/mL appears to reduce survival of pancreatic cancer cells in vitro, and in particular against Panc-1 cells (IC₅₀ of 1.1mg/mL), COLO 357 (IC₅₀ of 1.8mg/mL), and p34 cells (IC₅₀ of 1.5mg/mL).^[129]

This reduction in survival appears to be associated with a downregulation of NF-kB signalling and a downregulation of p65, phospho-IκBα and IκBα. NF-kB is known to protect pancreatic cancer cells from death^[130] and its suppression sensitized these cells to death from the chemotherapeutic cisplatin.^[129]

Appears to have anti-cancer properties in vitro against pancreatic cancer, but this occurs at a relatively high concentration and may not be optimal following oral ingestion of the supplement

In a rat model of chemical induced colon carcinogenesis, oral ingestion of the pods of moringa oleifera at 1.5-6% of the rat diet for two weeks prior to toxicity (and continued throughout the study period) resulted in a dose-dependent reduction in colon tumors by 47% (1.5% of the diet), 53% (3% of the diet), and 71% (6% of the diet).^[131] These suppressive actions are thought to be related to antiinflammatory actions, as iNOS and COX2 expression were dose-dependently reduced.^[131]

In women during postpartum days 3-5 (after giving birth to preterm infants), supplementation of 250mg moringa oleifera leaf extract twice daily appears to increase milk production in a time dependent manner on the first day of supplementation (31% increase over placebo) as well as the second (48%) and third (165%) day.^[132]

Appears to be a galactogogue

Moringa oleifera appears to be traditionally used as an aborifacient to abort pregnancies in the early stages, and oral ingestion of 175mg/kg of the leaves to pregnant rats for 5-10 days was able to induce abortions in all drug-treated rats.^[9]

Appears to have quite potent anti-fertility actions in pregnant rats, and may be able to induce abortions

Topical application of an ethylacetate extract of the seeds appears to have wound healing properties (10% of solution when applied to rats)^[133] which is thought to be related to the ability of moringa oleifera to have protease-like activity (due to components in the leaves and roots, albeit more in the leaves) as well as have fibrinogenolytic and fibrinolytic activity.^[24] Fibrinogenolysis is known to accelerate wound healing as an endogenous protease that moringa oleifera mimicks, plasmin, cleaves fibrin into fibrin degradation products which inhibit excessive clotting and a hemostatic plug.^[134]

Topical application of the leaves of moringa oleifera may possess wound healing properties of unknown potency, which is currently thought to be related to the anticoagulant properties of the leaf extracts

The leaves of moringa oleifera at 3% in a facial cream applied to the cheeks twice daily for three winter months appeared to have general smoothness enhancing properties (more colour consistency and less fine wrinkling) associated with a higher hydration status of the skin.^[135]

May have some benefits to the smooth appearance of the skin related to a higher water content of the skin

Citrus sinensis is the botanical term for the common fruit known as an orange; the peel (rind) of an orange is at times considered slightly medicinal.

Combining 50mg/kg of the orange rind with 50mg/kg of the root extract from moringa oleifera appears to be synergistic in suppressing colitis in mice (when preloaded prior to the colitic toxin) and the combination, but neither plant in isolation, appears to be comparable or exceed the potency of 5mg/kg prednisone.^[110]

The water extracts of Moringa seeds, when injected into mice, have been noted to possess an acute LD₅₀ of 446.5mg/kg^[136] and injections of the leaf water extracts have noted an LD₅₀ of 1,585mg/kg in mice.^[66]

There is a known LD₅₀ value with injections of the water extracts which is fairly low (relative to supplemental dosages)

A water extract has failed to cause toxicity when orally administered up to this dose over 60 days^[66] although one study using the water extract at 3,000mg/kg daily noted genotoxic potential in PMBC immune cells (1,000mg/kg confirmed safe) despite no damage to organs.^[137] A leaf ethanolic extract has failed to exert any clinical signs of toxicity up to 6,400mg/kg acutely^[6] and a 50% ethanolic extract appears to be clinically nontoxic up to 2,000mg/kg.^[107] A methanolic extract of the leaves has found an increase in liver enzymes at 200-400mg/kg.^[138]

A water extract of the seeds, when fed orally to rats at 5.2mg/mL drinking water, failed to exert toxic effects over the course of 30 days.^[136] A seed methanolic extract is not acutely toxic up to 3,000mg/kg in rats (although 5,000mg/kg was damaging) and an LD₅₀ of 3,873mg/kg was noted; chronic ingestion noted no toxicity aside from elevated liver enzymes associated with 1,600mg/kg oral intake (400-800mg/kg confirmed safe).^[139] The genotoxicity seen with high doses of the leaf supplements has also been replicated with higher than normal levels of the seed oil.^[140]

The ethanolic extract of the root-bark appears to be safe acutely up to 2,000mg/kg in rats.^[106]

When looking at toxicology data, it appears that the standard recommended doses are free from all organ damage and toxicity. Higher doses (around 3-4 times the highest recommended supplemental dose) appear to be associated with genotoxic damage and even higher doses still cause apparent organ damage

It would be prudent to avoid any supplementation of this plant beyond the recommended dosages to avoid potential genotoxicity