Amla

Emblica officinalis (of the family Euphorbiaceae), also known as Amla or Amla churna (the latter referring to the dried fruits) and is a component of some Ayurveda combination therapies such as Chyawanprash^[1] and Triphala.^[2] This plant is synonymous with Phyllanthus emblica and Amla is sometimes used interchangeably with Anwala, Amlaj, or Amlaki.^[3][4] It is also known as Indian gooseberry.^[5]

The fruits are traditionally used in Egypt for improving memory, as a stimulant, and restoratives for all organs^[6][7] while in general it is used for the treatment or prevention of diarrhea, jaundice, inflammation, cerebral insufficiency and mental disorders^[8] while other claims include usage as an appetite stimulant or for the treatment of diabetes.^[9] Among some ayurvedic texts (Charaka Samhita and Sushruta Samhita), this herb is referred to as the "best among the sour fruits" or "the best among rejuvenative herbs".^[4]

The fruits appear to also be well known in regards to their taste, which is described as being a relative balance of five major senses (sweet, sour, pungent, bitter, and astringent).^[9]

Emblica officinialis (Amla) is a fruit-bearing plant that has traditionally been used for whole-body medicinal purposes, and appears to be fairly well acclaimed in traditional medicine. The dried fruit powder is referred to as Amla Churna and is the commonly supplemented part

When consuming the fruits themselves, emblica officinalis contributes:

• 77+/-3kcal per 100g (assuming a 80.3+/-0.8% moisture content)^[10]
• 0.5+/-0.1g dietary protein per 100g^[10]
• 18.7+/-0.8g dietary carbohydrate per 100g^[10] some of which are conjugated to phenolics^[11]
• Trace fatty acids^[10]
• 6.1+/-0.6g dietary fiber per 100g^[10]

Similar to most fruits, Amla fruits are mostly carbohydrate with a decent fiber content and next to no protein nor fatty acids

The components of emblica officinalis include (fruit unless otherwise specified):

• Phyllemblin^[9]
• Emblicanin A and B (major tannoids)^[9] which can be hydrolyzed to form gallic acid and ellagic acid with glucose (Emblicanin A) or ellagic acid with glucose (Emblicanin B)
• Punigluconin and pedunculagin^[9]
• Putranjivain A^[12]
• Progallin A (leaves)^[13]
• Tannin structures elaeocarpusin and chebulagic acid (also found in Dimocarpus Longan)^[12] and various configuations of these tannic acids with gallic acid^[12]
• β-glucogallin (1-O-galloyl-β-d-glucose)^[14]
• Gallic Acid^[15]
• Mucic acid 3-O-gallate^[16][12]
• Quercetin at 2.6+/-1.6mg/100g (no detectable kaempferol, Myricetin, chlorogenic acid, ferulic acid, nor apigenin)^[10]
• Phytosterols including β-sitosterol (12.12+/-1.90mg/100g), stigmasterol (0.70+/-0.21mg/100g), and campesterol (0.26+/-0.02mg/100g)^[17] as well as trihydroxysitosterol and 5α,6β,7α-7α-acetoxysitosterol^[18]
• Carotenoids including lutein (49+/-27mg/100g) and β-carotene (32+/-19mg/100g)^[10]
• Vitamin C (2% of fruit juice^[17] or 575+/-452mg/100g of the fruits (wet weight)^[10])
• Vitamin E at 0.16 ± 0.05mg/100g fruit wet weight^[10]
• Calcium (42+/-12mg/100g), Sodium (13+/-4mg/100g), Phosphorus (21+/-5mg/100g), Potassium (151+/-37mg/100g or 1.16+/-0.05%), Magnesium (13+/-2mg/100g), Manganese (0.71+/-0.06mg/g) Iron (0.16+/-0.04mg/100g), Copper (0.04+/-0.03mg/100g), chloride (25.6+/-2.3mg/g) and Zinc (0.14+/-0.08mg/100g)^[10][19] with the content varying depending on analysis technique

Appears to be particularly rich in vitamin C, with some other unique bioactives. Most of the bioactives seem to belong to the class of tannin structures, which are large antioxidant structures particularly high in a few select plants or fruits

The total phenolic content of the fruits appears to be 3703+/-1244mGAE/100g (Gallic acid equivalents)^[10] and the total tannoid content (emblicanins, Punigluconin, gallic acid, rutin, and pedunculagin) consist of approximately 10-13% of the fruit by dry weight.^[20][9]

Despite the fruits having no detectable fatty acids, the seeds possess an oil that is rich in linoleic acid (44.0%) and oleic acid (28.4%).^[9]

The antioxidant potential of the herb does not seem to be altered with storage at 4°C for one years time.^[21]

There is an ayuvedic and mid-eastern combination formula known as Triphala or Itrifal Saghir which conists of equal parts of the seedless fruits from emblica officinalis, terminalia belerica, and terminalia chebula and appears to be taken at 10g overall (5g twice daily) after being mixed with almond oil and kneaded with frothless honey.^[22]

Emblica offinicalis appears to be of interest for longevity as, according to the Acharya Charaka (Ayurveda test), the fruits have been reported to be the best to increase longevity.^[23]

A study in drosophilia noted that daily consumption of feed with an Amla content was able to increase the days survived from 41.9 days to 76.8 days (83% increase), although a large variance was detected (76.8 days being the mean value, with +/-40.6 days for maximal and minimal values).^[23] This increase in longevity was met with an increase in fecundity.^[23]

Limited evidence to support the longevity promoting effects of Amla, but said preliminary evidence suggests surprisingly potent effects

Oral ingestion of 200mg/kg emblica officinalis daily over 14 days has been found to reduce concentrations of MAO-A in the brains of mice, and this was not accompanied by any alterations in locomotion.^[24]

Has been noted to reduce MAOA activity, which may cause an increase in neurotransmitters (catecholamines and serotonin implicated)

Emblica officinalis does not appear to interact with the acetylcholinesterase enzyme at concentrations up to 1mg/mL in vitro^[7] although the increase in this enzyme seen with anticholinergic treatment can be reduced with 600mg/kg of the herb (comparable potency to 200mg/kg Piracetam)^[25] or the increase seen with aging reduced by 13.5-23.7% with 50-200mg/kg oral ingestion of the fruit (although there was a 10.9-22.8% reduction in young mice as well).^[4]

Although it does not appear to directly inhibit the enzyme, but increases in the acetylcholine enzyme that may occur (either during aging or anticholinergic treatment) might be attenuated with the plant

Emblica officinalis appears scavenge free radicals with an IC₅₀ of 6.3µg/mL (DPPH), although this is less potent than both Terminalia Arjuna (3.1µg/mL) and chebula (2.2µg/mL) as well as the reference quercetin (4.5µg/mL)^[7] while being more potent than Anacyclus Pyrethrum (26.3µg/mL).^[7] Similar potencies have been noted elsewhere,^[26] suggesting that while Amla is potent there are plants and compounds with higher efficacy.

Thought to be secondary to these antioxidative effects, oral ingestion of 250mg/kg daily for six weeks alongside chronic alcohol ingestion is able to confer protective effects against mitochondrial dysfunction^[27] and pretreatment of 500-700mg/kg of the fruit extract before kainate administration (convulsant that induces seizures associated with prooxidative changes^[28]) can reduce the subsequent seizures and cogntive impairment.^[29] Similar protective effects are seen against PTZ-induced seizures.^[30]

Emblica officinalis appears to exert general antioxidative effects in brain cells, which are thought to underlie some of the protective effects. This has been confirmed with oral ingestion of the fruits in the standard dosages in rodents

It does not have any influence on COX1 activity up to 1mg/mL.^[7]

50-200mg/kg of oral fruit extract over 15 days to both young and old rats was able to dose-depedently reduce transfer and step-down latency in an elevated maze plus test in both age groups^[4] with 400mg/kg Piracetam being comparable potency to 200mg/kg Amla.^[4] This study is duplicated in Medline.^[3]

Animal evidence supports the usage of Amla as a nootropic in otherwise healthy and young animals, and the benefits also appear to extend to older animals. The nootropic potential seems similar to Piracetam

In rats given a hydroalcoholic extract of emblica officinalis (150-600mg/kg) for seven days intraperitoneally prior to scopolamine injections, supplementation was able to normalize the toxin-induced oxidative and learning changes with 600mg/kg being of comparable potency to 200mg/kg Piracetam.^[25] Elsewhere, the amnesiac effects of scopolamine or diazepam have been noted to be prevented with 200mg/kg oral Amla (comparable to 400mg/kg Piracetam).^[4]

Appears to have anti-amnesiac effects, of somewhat comparable potency to Piracetam as the reference drug

In isolation, Amla at 200-400mg/kg oral ingestion to mice for 14 days noted that the lower dose was effective in exerting antidepressant effects in forced swim and tail suspension tests (400mg/kg less effective) with a potency comparable to the reference drugs (15mg/kg imipramine, 20mg/kg phenelzine, and 20mg/kg fluoxetine).^[24] This is thought to be due to the suppressive effects of Amla on MAOA,^[24] an enzyme that degrades monoamines (catecholamines and serotonin, as well as GABA).

It has also shown anti-anxiety (anxiolytic) properties at 0.8-4mg/kg bodyweight in rats as assessed by elevated maze testing.^[31]

The compound supplement Rasayana Ghana (Emblica officinalis fruits with tribulus terrestris and Tinospora cordifolia in equal parts) at 260mg/kg appears to confer antidepressant effects as well as anxiolytic, although its potency is less than diazepam (2mg/kg for anxiolysis) and imipramine (5mg/kg for depression).^[32]

A combination supplement has noted weak anti-depressive and anxiolytic effects, and no evidence exists on Amla used in isolation

Gallic acid (one of the tannin structures in emblica officinalis^[33]) at 25-100mg/kg oral ingestion has been noted to have cardioprotective effects against the state of diabetes in rats in a dose-dependent manner^[34] and this has been noted with the juice of the fruits.^[35] This is thought to be due to the antioxidative effects of the plant, as cardioprotection has been noted in instances where blood glucose is not reduced.^[35]

Amla (100-500mg/kg over 30 days) has also shown cardioprotective effects against isoproterenol toxicity.^[36]

20-100µg/mL of the fruit extract appears to be protective against H₂O₂ induced endothelial cell death, associated with Akt activation without NF-kB^[37] and a similar concentration (1-100µg/mL) has been noted to inhibit LPS-induced coagulation.^[38]

Emblica officinalis has shown wound healing effects in isolated HUVEC cells at 0.1μg/mL over 48 hours of incubation, although this was also seen with isolated vitamin c at 0.01μg/mL, and 1μg/mL was able to promote endothelial cell migration with a potency comparable to 100ng/mL VEGF and possibly working vicariously through VEGF (as its mRNA was increased).^[21]

Emblica officinalis at 10μg/mL appears to enhance nitric oxide formation in isolated HUVECs to around 140% of control, with lower doses being ineffective.^[21] This was not related to the vitamin C content (not replicated by 1μg/mL vitamin C)^[21] and was noted in vivo when 75-300mg/kg of the fruits to rats over five weeks increased serum nitric oxide and eNOS activity in cardiac tissue.^[39]

The oxidation of LDL has been noted to be reduced with emblica officinalis fruits in vitro quite weakly, with an IC₅₀ of 136.3μg/mL.^[40]

Can be forced to inhibit LDL oxidation, but seems to occur at rather high concentrations and may not be biologically relevant

Oral administration of 50-200mg/kg Amla has been noted to reduce cholesterol in both young (13.6-27.5%) and old (7.6-23.4%) rats with the 100-200mg/kg dosage range over 15 days being comparable to the reference drug simvastatin (5mg/kg).^[4] Lower dose amla (10-40mg/kg) also seems effective over 100 days in rats, although to a lesser degree.^[17]

Serum triglycerides have been noted to be reduced in rats with 10mg/kg of the ethyl acetate fraction or 40mg/kg of fruit juice.^[17]

In rats given the fruits or leaves, there appear to be reductions in both cholesterol and triglycerides

Reductions have been noted in total cholesterol and LDL-C, as well as triglycerides, with oral intake of 3g of the fruits of emblica officinalis daily for 21 days; an increase in HDL-C was also seen at this dose, and it affected both healthy controls and the diabetics under investigation.^[41]

Benefits appear to extend to humans

Emblica officinalis fruits have been found to inhibit enzymes of carbohydrate absorption, including α-glucosidase (IC₅₀ of 1.0µg/mL) and α-amylase (IC₅₀ of 94.3µg/mL).^[40]

May be able to inhibit carbohydrate absorption enzymes, with the potency against α-glucosidase being fairly respectable

Glycation (a reduction between sugars and amino acids) has been noted to be reduced with the fruits, albeit with an IC₅₀ of 182.9µg/mL.^[40]

May reduce glycation at the concentrations that it also reduces LDL oxidation (ie. high enough that it might not be biologically relevant) which is thought to simply be due to antioxidative effects

A molecule in emblica officinalis known as β-glucogallin (1-O-galloyl-β-d-glucose) appears to inhibit the human aldose reductase enzyme with an IC₅₀ of 17µM^[42] which is thought to be biologically relevant since rodent interventions have noted protective effects (reduced oxidation and cataract formation) with a similar phenotype to aldose reductase inhibition.^[43][20]

May be inhibitory against aldose reductase

In diabetic rats given the hydromethanolic (20:80) extract of the leaves of emblica officinalis (100-400mg/kg bodyweight for 45 days) noted dose-dependent reductions in blood glucose and increases in serum insulin, with all groups being unable to outperform the reference drug (1mg/kg glibenclamide).^[44]

Reductions in plasma glucose have also been noted in a model of fluoride toxicity (known to have the side-effect of hyperglycemia^[45]) when 2.5-10% of the diet was comprised of amla fruits.^[46]

Rat studies with abnormally elevated blood glucose noted reductions with oral ingestion of both the leaves and fruits of emblica officinalis

Amla's effects on blood glucose in humans has been reviewed.^[47] It has been used in a combination supplement (alongside Bitter Gourd, Gurmur Leaves, Jamun Fruit and Holy basil) to reduce blood glucose in type II diabetics^[48] and elsewhere in type II diabetics with other herbs (Salacia oblonga and curcuma longa).^[49] Only one trial has been conducted using Amla in isolation (noted in the review,^[47] unable to be located online) where a 35g fresh amla fruit was consumed daily for two months noted that while there was no overall reduction in blood glucose that those with a baseline glucose over 150mg/dL experienced a statistically significant reduction.

Another study in uremic patients with 100mg emblica officinalis paired with 100mg EGCG (one of the green tea catechins) noted a reduction in fasting blood glucose without any influence on HbA1c, but is again confounded.^[50]

In diabetic and healthy humans given 1-3g of powdered emblica fruits daily for 21 days has noted reduction in postprandial glucose (highest dose being the only effect one in healthy controls, 3g being as effective as glibenclamide at 5mg twice daily) and fasting glucose (all groups and doses, with 3g being as effective as glibenclamide).^[41]

The majority of research on Emblica officinalis fruits has been confounded with the inclusion of other herbs that may also have hypoglycemic effects. Despite this lacklustre evidence, the lone study using a blinded protocol noted potency comparable to glibenclamide

Emblica officinalis has shown insulin sensitizing properties in adipocytes by increasing glucose uptake in the 50-200µg/mL range (dose-dependent)

^[51]

200μg/mL of the fruit extract (hydroalcoholic extract) appears to increase glucose uptake into adipocytes, and while comparable in potency to insulin it was antagonistic with incubated insulin.^[51]

Administration of amla (40mg/kg juice or 10mg/kg ethanolic extract) for 100 days to rats has failed to significantly reduce food intake or body weight.^[17]

In humans, Triphala (Amla with the two species of terminalia known as chebula and bellerica in equal ratios) at 5g twice daily over the course of three months in obese individuals without modifications to the diet (although diet was monitored to ensure it did not change significantly) noted that supplementation was associated with a 4.5% reduction in weight (4.37kg) and 3cm reduction in waist circumference while placebo did not alter their weight.^[22]

Emblica officinalis has been tested for its 5α-reductase inhibiting properties, and appears to be fairly potent as 1g of the crude fruit extract was as potent as 18.99+/-0.40mg finasteride.^[52] It was less potent than Carthamus tinctorius (1g being equivalent to 24.30+/-1.64mg finasteride), and these inhibitory effects were thought to underlie the hair growth promoting effects of topical application.^[52]

Emblica officinalis appears to be a fairly respectable 5α-reductase inhibitor in preliminary testing

The increase in NF-kB expression in the liver of rats during the aging process is attenuated with oral intake of 10-40mg/kg of emblica officinalis.^[17]

10-40mg/kg of the fruit daily for 100 days in rats has been noted to reduce serum TBARS concentrations (22-36%)^[17]

β-glucogallin (1-O-galloyl-β-d-glucose) is an aldose reductase inhibitor with an IC₅₀ of 17µM and is able to inhibit sorbitol accumulation by 73% at 30µM.^[42] Aldose reductase is the first and rate-limiting enzyme of polyol synthesis^[53] and is upregulated in diabetes^[54][55] and contributes to pathology, thus its inhibition is desired for controlled symptoms of diabetes beyond blood glucose such as diabetic retinopathy or nephropathy.^[56]

LPS-induced inflammation can be inhibited by aldose reductase inhibitors (as seen with established ARIs^[57][58]) which extends to β-glucogallin as evidenced by a 10mg/kg injections of this molecule with equal potency as the reference drug (sorbinil).^[14]

The whole plant extract of emblica officinalis (either at 2% of the diet or 0.2% of isolated tannoid structures) is able to attenuate the rate of cataracht formation in diabetic rats and reduce buildup of sorbitol in the eyes, but without apparent affect on blood glucose or insulin.^[20]

Tannoids from emblica officinalis appear to inhibit aldose reductase and may reduce the progression of some diabetes comorbidities without affecting blood glucose or insulin, this includes the formation of cataracts and diabetic retinopathy

Liver cholesterol and triglyceride content have been noted to be reduced with 10mg/kg of the ethyl acetate fraction of amla or 40mg/kg of the fruit over 100 days in rats.^[17]

Oral feeding of 5-10% of the diet as Amla churna (dried fruit powder) to rats subsequently given the pro-oxidant hexachlorocyclohexane appeared to exert some protective effects via reducing oxidative damage.^[8]

The fruit pulp of emblica officinalis (water extract) at 10-300μg/mL in HeLa and SiHa cells (two cervical cancer cell lines) showed concentration dependent inhibition of AP-1 binding to DNA with up to 90% inhibition at the highest tested dose of 300μg/mL.^[5] It took up to 12 hours to manifest (suggestive of protein induction), and it was later found that cervical cancer cells that tested positive for HPV (which is known to activate AP-1 signalling^[59][60]) were sensitive to emblica officinalis since it could inhibit viral replication at concentrations as low as 30μg/mL.^[5]

Regardless of HPV infections, emblica officinalis appears to induce apoptosis in cervical cancer cells with a decrease in cells in the G0/G1 phase and an increase in sub-G1 phase.^[5]

Mostly appears to be anti-proliferative in cervical cancer cells that express HPV (Human papillomavirus)

Emblica officinalis appears to be recommended as a Thai rememdy for hair regrowth (fried in sesame seed oil, then topically applied), and topical application of 1% of the fruit extract in solution to mice was able to increase hair follicle count (91.7%) to a greater degree than 2% minoxidil (50%) but less than Clitoria Ternatea (117%) and Carthamus tinctorius (187%).^[52]

Appears to promote hair growth when topically applied, and its potency is greater than the reference drug of Rogaine

Secondary to its antioxidant properties emblica officinalis appears to be capable of protecting skin cells from UV radiation by reducing the increase in reactive oxygen species from 84+/-1.4% (control cells) down to 15+/-4% (at 0.5mg/mL), which outperformed pure vitamin c at the same concentration (64+/-2%).^[61] This protective effect has been noted at concentrations as low as 10-40μg/mL.^[62]

Appears to exert protective effects against oxidation in skin cells, and appears to be fairly potent at doing so

Triphala is a combination of three herbs, one of which includes emblica officinalis whereas the other two herbs come from the genus Terminalia (chebula and bellirica).^[63]

In rats, oral adminsitration of the hydromethanolic (20:80) extract up to 2,000mg/kg over 15 days has failed to cause any clinical signs of toxicity.^[44]