Mango

Mangifera indica (of the family anacardiaceae) is the botanical name for the common mango, with mangifera being the family of plants which provide fruits referred to as mangoes. Mangoes overall are at times called "the king of fruits".^[1]

At times other fruits may be erronously called mangos due to visual or culinary similarities despite not being in this family, irvingia gabonensis (African mango) being an example.

One particular molecule known as mangiferin (synonymous with C-glucosylxanthone), a xanthone, was named after it's discovery in mangos where it exists in both the fruits^[2] and leaves.^[3] It is not necessarily unique to mango fruits as it can be detected in coffee leaves^[4] and honeybush,^[5] but due to its various mechanisms it is thought to be the major bioactive in mango that differentiates it from other fruits that do not contain it.

One other supplement that contains appreciable levels of mangiferin is salacia reticulata.

Mangifera indica refers to the common mango which can be bought in stores as a food product, although this particular fruit also has the leaves from the plant used in dietary supplements. Both the fruit and the leaves are thought to confer benefits to health due to having similar components (albeit in differing quantities)

Mango fruits (mangifera indica unless otherwise specified) contain the following noncaloric bioactives:

• Mangiferin at variable concentrations, with some sources citing up to 0.2mg/g dry weight,^[6] slightly above 13mg/g dry weight,^[7] or undetectable^[6]
• Carotenoids including α-carotene, β-carotene, cryptoxanthin, and zeaxanthin with no detectable lycopene and drastically lower levels in dried fruit relative to fresh^[8]
• Gallotannins at lower concentrations (0.2mg/g dry weight)^[9]

Lupeol, found in the peel, is undetectable in the pulp.^[7]

The fruit (pulp) of the mango has a surprisingly low concentration of the major bioactives, as it seems to be concentrated in the peel of the fruit and other parts of the plant (leaves and kernels). Consuming the entire fruit may still confer some effects however (due to more overall mass ingested)

Other parts of the mango plant (mangifera indica unless otherwise specified) contain:

• Mangiferin in the peels (4.94-15.23mg/g), kernels (6.40-8.98mg/g), bark (12.33-18.33mg/g), and leaves (36.9-67.20mg/g favoring young leaves),^[3] thought to be the major bioactive compound
• Isomangiferin in the bark only (0.79mg/g) and 6-O-galloylmangiferin in the bark only (1.67mg/g)^[3] and possibly also in a gallated form^[9]
• Lupeol (peels) at less than 1mg/g dry weight^[7]
• Gallic acid in low levels in the bark (0.24mg/g) and leaves (0.43-3.49mg/g favoring young leaves)^[3] with higher levels of other gallated molecules such as methyl gallate (up to 17.95mg/g in young leaves, 12.68mg/g in kernels, and 15.46mg/g in peels), tetra-O-galloylglucoside (7.22mg/g in the peels), and penta-O-galloylglucoside (up to 23.81mg/g in the young leaves, 17.71mg/g in peels, and 50.03mg/g in the kernels)^[3]
• _Maclurin_itself^[9] and in the forms of 3-C-β-D-glucoside (1.97mg/g in the peels and 0.63mg/g in young leaves) and gallated versions of the aforementioned glucoside present in peels almost exclusively (3.37-4.05mg/g)^[3]
• Quercetin pentosides in the leaves at 1.33-4.93mg/g favoring young leaves^[3] with some detectable in the kernels and peel (likely at lower concentrations as to be undetectable^[3]) in the forms of 3-O-galactoside, 3-O-glucoside, and 3-O-xyloside^[9]
• Kaempferol in the peels and kernel in the form of 3-O-glucoside^[9]
• Isoquercitrin isomers in the leaves only, 2.12-11.42mg/g favoring young leaves^[3]
• Iriflophenone as 3-C-β-D-glucoside (8.30-118.04mg/g in the leaves favoring young leaves and 2.05mg/g in the peels and bark) and gallated versions thereof present at lower concentrations in the leaves (around 1.16-7.45 in young leaves)^[3]

The total phenolic content is greatest in leaves, with young leaves generally having more of all bioactives relative to older leaves, with lowest concentrations in the peels of the fruit and bark of the plant the fruit is borne from.^[3] The quantities of bioactives seems quite variable, most notably iriflophenone 3-C-β-D-glucoside being reported as low as 8.30mg/g in one cultivar's old leaves and as high as 118.04mg/g in another cultivar's young leaves.^[3]

As a general statement the major bioactives in mango leaves (most common supplemental form) seem to be mangiferin and iriflophenone quantitatively speaking, while the phenolic acid known as gallic acid itself is present in low levels but is also conjoined to many other molecules (ie. gallated) in appreciable quantities

Sequential ethanolic extractions may be able to increase the mangiferin concentration of a mango leaf extract up to 62% on a dry weight basis.^[10]

There are tablets known as 'Vimang' (brand name) tablets which appears to be a mango water extract derived from the stem bark, which have been tested in vitro^[11] and in vivo.^[12]

Mangiferin in isolation (30mg/kg orally) appears to be absorbed from the intestines and can be detected in plasma within 15 minutes reaching a C_max of 15.23+/-6.0µg/mL at the T_max of 40 minutes.^[13] The volume of distribution was 7.21mL suggesting tissue binding, and overall AUC_0-∞ was 155.03+/-17.98.^[13] Elsewhere, when mangiferin was administrated at three doses (17.5, 35, and 70mg/kg) intragastrically a lower range of C_max values were reported (0.119-0.190µg/mL).^[14]

When administered in a polyherbal formulation containing other herbs (salacia oblonga and roxburghii) the C_max of 30mg/kg mangiferin is increased (44.16+/-23.12µg/mL) while the T_max is delayed (3 hours).^[13] Similar increases in C_max values have been reported with a Zhimu decoction (21.52µg/mL) and Zhim-Huanbai decoction (16.26µg/mL) when the dose of mangiferin is controlled for, also associated with delayed T_max values.^[14]

After oral ingestion of mangiferin in relatively large doses (30mg/kg in the rat being an estimated 330mg in a 150lb human) there are low levels of mangiferin detectable in plasma. The absorption of mangiferin seems to be influenced by administration of various herbs

Following oral administration of mangiferin to rats at 30mg/kg (via salacia family herbs) it has been detected in most tested organs including the stomach (55.2-332.9ng/mL), heart (203-526ng/mL), small intestine (121-754ng/mL), liver (75.5-128.5ng/mL), lungs (12.7-60ng/mL), kidney (23.1-143.3ng/mL), and spleen (21.7-36.3ng/mL) with very small quantities (0.5-1.1ng/mL) reaching the brain.^[13]

Peak concentrations are found in the stomach after 30 minutes which then decrease progressively over 180 minutes, and both the liver and kidneys accumulate then in a time dependent manner over 180 minutes (likely due to eliminating mangiferin from the body); other tissues reach peak concentrations after about one hour.^[13]

Mangiferin has been noted to increase secretion of neuronal growth factor (NGF) at the concentrations of 1-5µg/mL, with 50µg/mL not being significantly more effective than 5µg/mL and this increase being noted alongside an increase in cellular proliferation of glioblastoma cells.^[15]

When tested in vitro, mango leaf extracts appear to protect neurons from glutamate-induced damage with maximal efficacy at 2.5µg/mL (56% protection) although when mangiferin was tested in isolation it's maximal efficacy was at 12.5µg/mL (64% protection).^[16]

In rats given amnesia via AF64A (cholinergic toxin^[17]), oral administration of an extract from mango pulp at doses in the range of 12.5-200mg/kg noted that all doses were equally effective in ablating cognitive deficit while 50-200mg/kg preserved cholinergic neurons; the potency of all treatments being comparable to 250mg/kg Vitamin C and likely due to exerting an antioxidative effect.^[18]

An antioxidative effect of mango may persist in the brain following oral ingestion

Oral administration of a water extract from the stem bark of mangifera indica (125-500mg/kg) daily for a week prior to administration of formalin was able to reduce pain in a dose-dependent manner between 16.8-49.6% in a manner additive with Vitamin C (1mg/kg injection).^[19] The pain reducing effect is thought to be related to the mangiferin content, which was effective in isolation at the dosage range of 12.5-50mg/kg to a similar degree.^[19]

Administration of mangiferin via intraperitoneal administration at three doses (10, 50, and 100mg/kg) immediately after cognitive training in rats appears to improve memory recognition relative to control when tested a day later, with efficacy peaking at 50mg/kg and no effect when administered 6 hours after training.^[15]

Mangiferin (400mg/kg or 0.5% of the diet) fed to mice on a standard diet has been noted to prevent weight gain from a high fat diet noticeable after 5 weeks and halving weight after 16 weeks associated with an increase in metabolic rate.^[20] This effect was thought to be due to the observed increase in glucose oxidation associated with improved glucose tolerance (a tripling of glucose infusion rate) and glucose utilization of skeletal muscle.^[20] An activation of pyruvate dehydrogenase (PDH), a rate-limiting step in glucose oxidation that positively influences insulin sensitivity,^[21] was noted in vitro with an EC₅₀ of 216+/-35µM (15 minute incubation) and 184+/-32µM (24 hour).^[20]

10g of freeze-dried mango given to obese subjects over the course of 12 weeks in addition to their regular diets appeared to mildly reduce blood glucose (-4.1mg/dL; 4.3%) without significantly influencing body weight, lipids, or other biomarkers of glucose metabolism (HbA1c, insulin, or insulin sensitivity) over the entire group.^[22]

When mango peel is supplemented at 5-10% of the diabetic rat diet, the increase in blood glucose and other biomarkers of diabetes (urinary sugars, glomerular filtration rate, and serum lipids) appeared to be somewhat attenuated.^[23]

Mangiferin at oral doses of 50-200mg/kg in mice sensitized to ovalbumin appears to preserve the Th1 phenotype (assessed by the cytokines IFN-γ, IL-2 and IL-12) relative to the Th2 phenotype when compared to ovalbumin control, suggesting a mechanism for the observed antiallergic effects in the lung.^[24]

In subjects with rheumatism who were already assigned to methotrexate with NSAIDs and/or prednisone, the addition of 900mg mango extract (derived from stem bark) for 180 days appeared to improve scores based on the DAS-28 rating scale when compared to their baseline value; the control not given supplementation did not see further improvement and the group given the mango extract reduced NSAID usage.^[12]

Supplementation of mango stem extracts (300mg thrice daily) has been noted to reduce serum MDA by 58.4% and increase serum total antioxidant capacity by 55.9% after sixty days supplementation in elderly subjects who had higher baseline oxidation (relative to youthful controls).^[11]

Mangiferin in varying doses between 3-100mg/kg orally to mice appeared to increase gastrointestinal transit time in a manner not dose-dependent, with 30mg/kg and 100mg/kg increasing transit time by 89% and 93% respecitively; a comparable potency to the reference of 1mg/kg tegaserod injections although mangiferin did not promote fecal water weight (suggesting no ionic secretion).^[25] 30mg/kg mangiferin was found to reverse the reduction in intestinal motility caused by morphine, ondansetron, and capsaicin in a manner fully blocked by atropine suggesting cholinergic mechanisms.^[25]

Mango leaf ethanolic extracts (62% mangiferin) at 18.4g/kg twice daily over two weeks does not appear to be associated with any overt or histological signs of toxicity^[10] while chronic supplementation of 100-900mg/kg of this extract (17.2-155.2 times the clinical effective dose of 5.8mg/kg) over three months in mice showed alterations in blood cells and lipids that were deemed to not be overly clinically relevant.^[10]