Eriobotrya japonica

Eriobotrya japonica (Common Loquat) is a plant whose fruits are commonly consumed for their taste and other parts (seeds, leaves, flowers) used in Traditional Chinese Medicine for treatment of cough and respiratory distress; it appears to be rich in Ursolic Acid like triterpenoids.

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Summary

All Essential Benefits/Effects/Facts & Information

Eriobotrya japonica is the plant which bears the fruits we refer to as 'Loquat', or specifically the common or wild Loquat. While the fruits themselves are sold as a food product with no medicinal history, the seeds have been added to alcoholic drinks which are thought to promote longevity while the leaves have been ingested on an as-needed basis to treat cough, sputum, and throat inflammation associated with sickness.

The leaves themselves are a good source of triterpenoid molecules, with some unique ones including tormentic acid (and some variants) and euscaphic acid although the majority of these triterpenoids are just Ursolic Acid and a variety of methoxylated or polyhydroxylated variants. It seems to have a wider variety of triterpenoids rather than a high level of any one triterpenoid, and this class of molecules seems to underlie most of the benefits associated with the leaf extracts. There is not a good idea of what molecules are in the seeds, and it is though that they are also a source of triterpenoids since no unique molecules are known in them.

The benefits of this plant right now tend to be associated with either high or undisclosed doses of the seeds, suggesting that they probably don't apply to oral ingestion of standard doses in humans. The only roles where supplementation may be useful are in control of diabetes and possibly in reducing ulcer formation, but both of these claims can be achieved if not easily outperformed by using isolated ursolic acid or other supplements. There is not enough research into the variety of triterpenoid variations (the polyhydroxylated or methyoxylated variants) to know if they possess unique properties or not.

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How to Take

Recommended dosage, active amounts, other details

There is currently not enough information to recommend an ideal supplemental dose of this plant for any of its recommended supplemental purposes, although one study referencing the 'recommended human dose' for the seeds used a rat dose of 40mg/kg (ie. abouto 3-5g of the seeds for adults).

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Scientific Research

Table of Contents:

  1. 1 Sources and Composition
    1. 1.1 Sources
    2. 1.2 Composition
    3. 1.3 Formulations and Variants
  2. 2 Longevity
    1. 2.1 Rationale
  3. 3 Neurology
    1. 3.1 Neuroprotection
    2. 3.2 Analgesia
    3. 3.3 Memory and Learning
  4. 4 Cardiovascular Health
    1. 4.1 Absorption
    2. 4.2 Atherosclerosis
  5. 5 Interactions with Glucose Metabolism
    1. 5.1 Absorption
    2. 5.2 Insulin
    3. 5.3 Blood Glucose
    4. 5.4 Type II Diabetes
  6. 6 Obesity and Fat Mass
    1. 6.1 Adipogenesis
  7. 7 Bone and Joint Health
    1. 7.1 Dental Health
  8. 8 Inflammation and Immunology
    1. 8.1 Interferons and Immunoglobulins
    2. 8.2 Macrophages
    3. 8.3 Mast Cells
    4. 8.4 Allergies
    5. 8.5 Virology
  9. 9 Interactions with Hormones
    1. 9.1 Estrogen
    2. 9.2 Cortisol
  10. 10 Peripheral Organ Systems
    1. 10.1 Stomach
    2. 10.2 Liver
    3. 10.3 Lungs
    4. 10.4 Kidneys
  11. 11 Interactions with Cancer Metabolism
    1. 11.1 Mechanisms
    2. 11.2 Invasion and Metastasis
    3. 11.3 Breast Cancer
    4. 11.4 Leukemia
    5. 11.5 Sarcoma
    6. 11.6 Adjuvant Usage
  12. 12 Safety and Toxicology
    1. 12.1 General

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1Sources and Composition

1.1. Sources

Eriobotrya japonica (of the family rosaceae) is a Food Product known as Loquat, Biwa, or Pipa (English, Japanese, and Chinese respectively) and is also sometimes called Japanese or Chinese Plum (despite not belong to the genera of fruits known as plums, the prunus fruits). The food product is a fruit weighing 20-80g with a thin and tough skin yet an internal pulp varying in color from white to deep orange to salmon pink.[1]

The term 'Loquat' refers to the genera (eriobotrya) rather than the species (eriobotrya japonica), and this particular species is called common or wild Loquat (with a variant, eriobotrya japonica var. zaozhong known as 'Zaozhong 6' Loquat) and is the most commonly sold Loquat;[2] others include Tibet Loquat (eriobotrya elliptica), Oak leaf (eriobotrya prinoides) and Daduhe Loquat (eriobotrya prinoides var. dadunensis), Taiwan (eriobotrya deflexa) and Hengchun Loquat (eriobotrya deflexa var. koshunensis), Bengel Loquat (eriobotrya bengalensis), Fragrant Loquat (eriobotrya fragrans), Guangxi Loquat (eriobotrya kwangsiensis), Obovata Loquat (eriobotrya obovata), and Big flower Loquat (eriobotrya cavaleriei).[2]

Eriobotrya japonica is one of various species in the genera (Eriobotrya) that refers to Loquat fruits, and it the most commonly sold species in this family for the purposes of being consumed

The leaves that this plant bears appear to be a Traditional Chinese Medicine by the name of pipaye and for the treatment of lung-related diseases including cough, asthma, and chronic bronchitis as well as for headache, lower back pain, and dysmenorrhea[3][4] as well as to quell the stomach and reduce vomiting during sickness.[5] The flowers also appear to have a similar history, being used for cough and sputum amongst other lung-related issues.[6]

This plant appears to have historical usage for the treatment of lung related disorders and some other possibly inflammation related disorders (headache and lower back pain)

1.2. Composition

The fruits that this plant bears contain:

  • Total sugars of 7.8-11.4% total weight[7] which are mostly fructose (39-53% total sugars) and glucose (38-50%) with trace sorbitol and sucrose[7]

  • Vitamin A[8] and other carotenoids including β-carotene (7.8µg/g; 44% total carotenoids), ζ-carotene (0.1µg/g; 0.5% total carotenoids), neurosporene (1.1µg/g; 6% total carotenoids), β-cryptoxanthin (4.8µg/g; 27% total carotenoids), 5,6-monoepoxy-β-cryptoxanthin (0.6µg/g; 3% total carotenoids), violaxanthin (1.6µg/g; 9% total carotenoids), and auroxanthin (0.9µg/g; 5% total carotenoids)[9]

  • Epicatechin[1]

  • Chlorogenic Acid (13.7-52.0% of total phenolics and higher after ripening;[1] measured at 46.4mg/100g wet weight in storebought fruit[10]) and neochlorogenic acid (higher in ripe fruits[1])

  • Cyanidin glucosides at 21.8mg/100g wet weight[10]

  • Caffeic acids such as 3-caffeoylquinic acid (9.55-20.7mg/100g fresh ripe fruit weight[1]), 4-caffeoylquinic acid (0.52-4.33mg/100g fresh ripe fruit weight[1]), and 5-caffeoylquinic acid (32.92-90.7mg/100g fresh ripe fruit weight[1])

  • Hydroxybenzoic acid (2.24-8.15mg/100g fresh weight of ripe fruits[1]) and protocatechuic acid[1]

  • Ferulic acid[1] and 5-feruloylquinic acid (higher in ripe fruit, reaching 2.81-14.52mg/100g fresh weight[1])

  • Vitamin C at 10.3-19.2mg/100g fresh weight[7]

The fruits have a variable phenolic content of 81.8-173.8mg/100g fresh pulp (has been noted to be much higher at 240.5-545.3mg/100g gallic acid equivalents (GAEs) elsewhere[7]), and decrease during growth only to increase during ripening.[1] The carotenoid content is in the range of 23.4-496.3µg/g fresh weight (β-carotene equivalents)[7][9] which is mostly -carotene (30-60%)[11] and the flavonoids at 23.6-77.5mg/100g rutin equivalents (REs) fresh weight.[7]

Unlike other parts of Loquat (seeds, peel, and leaves), there does not appear to be a detectable catechin or procyanidin content in the fruits.[10]

The phenolics in the fruits appear to be mostly small weight phenolic compounds (caffeic and ferulic acids) as well as chlorogenic acid, and while there is a carotenoid and flavonoid content they are highly variable

The leaves of Loquat (Eriobotryae folium) contain:

  • Euscaphic acid,[12][13][14] 1β-hydroxyeucsaphic acid,[15] and a ferulic acid derivative known as 3-O-trans-feruloyleuscaphic acid[16][17]

  • Ursolic Acid (16mg/g dry weight in one study[18] but elsewhere at 1.969-5.675mg/g;[12] usually 50% of total triterpenoids[14]), 2α,19α-Dihydroxy-3-oxo-urs-12-en-28-oic acid, 2α,3α,19α-trihydroxyolean-12-en-28-oic acid (0.992-2.972mg/g[12]), and 2α-hydroxyursolic acid (4.6mg/g dry weight[18]),[13] and 2α,3α-dihydroxyursolic acid (0.615-1.190mg/g[12]). An ursolic acid lactone is also present in low levels[15]

  • Corosolic acid (1.887-5.396mg/g dry weight[12]) and 3-epicorosolic acid[15]

  • Oleanolic acid[13] at 1.7mg/g dry weight in one study[18] and 0.530-1.637mg/g elsewhere;[12] also α-hydroxyoleanolic acid[14] and δ-oleanolic acid[15]

  • Maslinic acid[13] at 800µg/g dry weight in one study[18] and 0.869-1.890mg/g elsewhere[12]

  • Betulinic acid and methyl betulinate[15]

  • Arjunic acid[14] and methyl arjunolate[15] (named after Terminalia arjuna)

  • Pomolic acid[13]

  • Tormentic acid (20mg/g in the callus but not detectable in the leaves in one study[18] but at 0.579-1.858mg/g elsewhere[12]) as well as 3-O-p-coumaroyltormentic acid (cis and trans isomers)[3][18] at 2.9mg/g in the callus yet only 200µg/g in the leaves[18] and 23-O-coumaroyltormentic acid (both isomers)[19]

  • Hyptadienic acid[3][18] and Nerolidiol glycosides[20][21]

  • Cinchonain IIb (flavonolignan)[22] and Cinchonain Id 7-O-glucoside[22][23]

  • Glycosides of Vomifoliol (Megastigmane; aka. 3-oxo-α-ionol) including Eriojaposide A (6R,9R isomer with 9-O-β-xylopyranosyl-(1"→6')-β-glucopyranoside[16][22]) and B (6R,9R isomer with 9-O-α-rhamnopyranosyl-(1"→6')-β-glucopyranoside[16]) as well as a 3-oxo-α-ionyl-9-O-glucoside (6R,9R isomer),[22] (6S,9R)roseoside (glucoside),[22]9-O-apiosyl (1→6) glucoside and an apiofuranosyl variant,[16][22]xylosyl (1→6) glucoside,[22] and Citroside A[16]

  • (-)-Epigallocatechin-3-O-gallate (EGCG)[22]

  • Quercetin as 3-Sambubioside and 3-rhamnoside[24]

  • Kaempferol as 3-rhamnoside[24] and the acetylated flavonoid kaempferol-3-O-α-L-(2″,4″-di-E-p-coumaroyl)-rhamnoside[25][26]

  • Naringenin (as 8-C-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside)[23]

  • Chlorogenic Acid and methyl chlorogenate,[24] a variant with higher antioxidative properties[27]

  • Procyanidin B2[22] and C1[22] as well as other oligomers[22][23]

  • Ferulic acid[20]

  • β-sitosterol[16]

When comparing species of the eriobotrya genera against one another, the japonica species appears to have either comparable or lower flavanoid and phenolic content in their leaves;[2] being measured at 31.47-47.5mg/g phenolics as gallic acid equivalents (GAEs) and 109.3+/-4.8mg/g flavonoids as rutin equivalents (REs) based on dry weight of the leaves.[2][28] Relative to other plants in Traditional Chinese Medicine, eriobotrya japonica appears to have a high phenolic content behind only dioscorea bulbifera and tussilago farfara.[28]

The ethyl acetate extract has been known to concentrate the pentacyclic triterpenoids, where a metabolic extract (20.1% yield) can be fractioned into an ethyl acetate extract (24% yield; 5% total dry weight) results in higher levels of ursolic acid (9.7%), euscaphic acid (4.9%), corosolic acid (4.4%), 3-O-trans-coumaroyltormentic acid (4.0%), 1β-hydroxyeuscaphic acid (2.9%), oleanolic acid (2.7%), maslinic acid (1.7%), 2α,3α,23α-trihydroxyolean-12-en-28-oic acid (1.3%), 3-O-cis-coumaroyltormentic acid (0.8%), 3-epicorosolic acid, methyl ursolate, and methyl arjunolate (each 0.2%) and ursolic acid lactone, betulinic acid, methyl betulinate, and δ-oleanolic acid (each 0.1%).[15]

For the most part, the leaves contain either triterpenoids (of which ursolic acid is by far the largest in amount and has a bunch of hydroxylated and acetylated variants) and the vomifoliol glycosides; there are also the common catechins and the procyanidins that they form

The flower of loquat tends to contain:

  • Oleanolic acid (0.38-0.51mg/g dry weight[29]) and 2β,3β,23α-trihydroxyolean-12-en-28-acid[30]

  • Ursolic acid (2.15-2.68mg/g dry weight[29]) and 2α,3α,19α-trihydroxyurs-5,12-dien-28-acid[30]

  • Amygdalin (1.23-1.56mg/g dry weight[29])

The flowers have a total flavonoid content of 1.59+/-0.24mg/g and total phenolic content of 7.89+/-0.87mg/g dry weight;[6] they appear to be concentrated in methanolic and ethanolic extracts and less in ethyl acetate and acetone extracts, and antioxidant potential of the flowers generally correlates with the flavonoid and phenolic content.[6]

The flowers contain both triterpenoids and flavonoid components, with most (but not all) of the antioxidant potential probably coming from the flavonoids

The seeds of loquat tend to possess:

  • Proteins at 4.9% dry weight[31]

  • Lipids at 2.4% dry weight[31]

  • Sugars (carbohydrate) at 72.1% dry weight[31]

  • A mostly insoluble fiber content of 7% dry weight[31]

  • An ash content of 2.1% dry weight[31]

  • Amygdalin at 20mg/g dry weight[31]

  • Catechins such as (+)-catechin (2.16mg/g), epicatechin (0.68mg/g), epigallocatechin (0.12mg/g), and epicatechin gallate (0.09mg/g)[31]

  • Chlorogenic acid (0.04mg/g)[31]

Despite traditional usage of the seeds (particularly ethanolic extracts), there are not many unique constituatives in them relative to the leaf extracts; they do seem to be higher in carbohydrates than many seeds, however

1.3. Formulations and Variants

There appears to be an anti-acne compound formulation known as BC-AF which consists of eriobotrya japonica, saliva miltiorrhiza, and glycyrrhiza uralensis (Licorice).[32]

Some traditional chinese medicines have been paired together in the form of an anti-acne medication

It appears that loquat leaves can be fermented with camellia sinensis tea leaves (primary source of Green Tea Catechins) in a 1:9 ratio,[33] and when this occurs it develops synergism in inhibiting carbohydrate uptake;[34] the IC50 for inhibiting maltose uptake via inhibiting the maltase enzyme (65µg/mL) is three-fold higher than either plant alone, and this is thought to associated with the unique bioactives theasinensin A (IC50 142µM), theasinensin (225µM), strictinin (398µM) and 1,6-digalloylglucose (337µM), although it seems most of the inhibitory effects were attributed to currently not known molecules.[34] It does, however, appear to accelerate the production of Theaflavins gallates and thearubigins relative to fermenting camellia sinensis alone, without affecting the Caffeine content of the green tea.[35][36]

There also appears to be inhibitory effects on the sucrase enzyme (IC50 of 200µg/mL) which was mostly due to camellia sinensis but was still greater than it alone (IC50 350-430µg/mL) suggesting slight enhancement.[34] There also appears to be an inhibitory effect on lipid absorption (thought to be due to pancreatic lipase inhibition at around an IC50 value of 1.081mg/mL), and when given to rats at mg/kg prior to a soybean emulsion noted a significant reduction in lipid spikes in serum.[36]

This combination has been used successfully to reduce serum glucose spikes following oral ingestion of maltose (with 50mg/kg of the hot water extract of the combination) by 23.8%[37] and the suppression of insulin spikes following said meal was said to be 16-fold higher than the reference drug arcabose;[37] when given alongside the diet, the combination in rats appears effective in reducing obesity and high blood triglycerides.[36]

Fermenting one part loquat leaves alongside nine parts green tea leaves appears to synergistically increase how effective the green tea leaves are at inhibiting maltose and sucrose uptake from the intestines. In a sense, the fermentation process of green tea (to make it black tea) may be enhanced when 10% of the leaves are loquat


2Longevity

2.1. Rationale

The 70% ethanolic extract of the seeds of eriobotrya japonica incubated in fibroblast at 0.5-2% of medium noted that the bradykinin-induced calcium efflux seen in senescent cells (which normally have attenuated calcium release in response to stimulators[38][39]) was restored to levels seen in young cells and increase the number of overall cells in culture that responded to bradykinin, although it failed to have a per se influence on young cells at the same concentration.[40]

Due to restoring a biomarker that is impaired with aging to levels seen in youthful control, the seed extract of eriobotrya japonica is thought to have antiaging properties


3Neurology

3.1. Neuroprotection

In PC12 cells incubated with Aβ1-42 (neurotoxic protein fibril), a 5% ethanolic leaf extract preincubated for 24 hours is able to preserve cell viability in a concentration dependent manner in the range of 5-100μg/mL, reaching a protective effect similar to 100μM Vitamin C.[41]

The antioxidant effects cause some general neuroprotective effects; no in vivo evidence at this point in time and practical significance of this information is not known

3.2. Analgesia

An n-butanolic leaf extract (0.7% yield of dry leaves) at 250-500mg/kg oral ingestion appears to possess anti-nocioceptive properties in a battery of tests (tail immersion, hot plate, acetic acid writhing, and formalin) with a potency either comparable to or slightly lesser than the reference drugs of tramadol (intravenous injections of 10mg/kg) and indomethacin (oral);[42] the leaf extract appears to be antagonistic with opioid drugs in reducing pain acutely (30 minutes after oral intake), with no interaction at later times (60-120 minutes).[42]

While components of the leaf may have respectable analgesic effects, this is limited to a high oral dose of a very limited concentration and likely does not apply to oral supplementation of this plant (seeds or leaves)

3.3. Memory and Learning

Eriobotrya japonica leaf extract (5% ethanolic) fed to mice at the dose of 100-300mg/kg for three weeks prior to injections of Aβ1-42 (and then administered for another week) is able to attenuate the learning deficits seen by attenuating the 65% reduction in step-through latency (Aβ1-42 control) to 21% and 14% (100mg/kg and 300mg/kg, respectively).[41]

Alongside the neuroprotective effects are anti-amnesiac effects in a model of brain damange from protein fibrils (related to Alzheimer's disease); the dose is not an impractically high dose, suggesting that it may be relevant


4Cardiovascular Health

4.1. Absorption

Eriobotrya japonica leaves appear to inhibit pancreatic lipase with an IC50 value of 4.5mg/mL, which is weaker than camellia sinensis (IC50 of 2.245mg/mL) although it appears to be synergistic when fermented alongside camellia sinensis at a 1:9 ratio (IC50 of 1.081mg/mL);[36] this synergism also manifested during an oral triglyceride load, with the leaves of loquat by themselves at 200mg/kg inhibiting the subsequent AUC in serum by a minimal 2.2% (camellia sinensis by itself 35%) and the mixture by 62%.[36]

Appears to be able to inhibit fat absorption by an incredibly small amount, and practically speaking this is probably too small to exert any appreciable effect in the body

4.2. Atherosclerosis

The water extract of multiple parts (fruit, peel, seeds) show antioxidative properties in reducing LDL oxidation with comparable potency, although the seed ethanolic extract seemed to be most potent.[10]

General antioxidant effects beget a reduction in lipid peroxidation, but the practical significance of this information is currently not known


5Interactions with Glucose Metabolism

5.1. Absorption

The leaves of eriobotrya japonica appear to inhibit sucrase (IC50 values of 2.81mg/mL and 2.87mg/mL basic and fermented leaves, respectively) and maltase (2.24mg/mL and 10.5mg/mL basic and fermented leaves, respectively) activity in vitro, although it appears that they are more notable in enhancing the inhibitory actions of camellia sinensis when fermented in a 1:9 ratio (loquat:green tea).[34] When looking at the α-amylase enzyme, a water extract of the leaves failed to show any inhibitory properties up to 1mg/mL.[43]

Not overly significant inhibitory effects on carbohydrate (disaccharide) uptake from the intestines, as assessed by its inhibitory effects on the enzymes that break down sucrose and maltose

5.2. Insulin

In isolated pancreatic β-cells (INS-1) the leaf extract at 320µg/mL is able to stimulate insulin secretion to 260% of baseline, a potency comparable to 1μg/mL glibenclamide.[44] It was noted cinchonain Ib was a causative agent by increasing insulin secretion in the presence of glucose to 122-214% in the concentration range of 10-320µg/mL, and there was a mild increase in plasma insulin (150%) for the four hours following oral ingestion of 108mg/kg cinchonain Ib with no significant influence on blood glucose.[44]

The leaf extract overall suppresses insulin secretion, which was thought to be due to the epicatechin (more prominent than cinchonain Ib in the leaf) since it suppressed insulin secretion in vitro to 57-94% of baseline in the same 10-320µg/mL range.[44]

Despite cinchonain Ib being an insulin secretagogue, the leaf extract appears to suppress the release of insulin from the pancrease by a small amount after oral ingestion possibly related to the epicatechin content

In diabetic rats (alloxan and streptozotocin), supplementation of the total triterpenoid fraction at 100-300mg/kg daily for one week is able to increase insulin concentrations relative to diabetic control by 53-84% (27-43% normalization to nondiabetic control).[45] The flavonoid fragment may be slightly more effective at this particular property, with 300-450mg/kg reducing fasting insulin (44-57% normalization to nondiabetic control) with a similar potency to gliclazide.[46]

May attenuate the reductions in insulin that are seen in some animal models of diabetes

5.3. Blood Glucose

In otherwise normal mice, the triterpenoids (mostly tormentic and corosolic acid) fed over the course of a week can reduce fasting blood glucose (measured in eye socket blood) by 36-44% in the dosage range of 100-300mg/kg, the higher dose being comparable to 50mg/kg gliclazide.[45] The total flavonoids also show blood glucose reducing properties in this context, but require higher doses (300-450mg/kg, with 150mg/kg ineffective) and are less effective than gliclazide.[46]

The leaf extract (25.9% total triterpenoids; 8.7% ursolic acid and 8.2% tormentic acid) fed to mice at 200-1,000mg/kg alongside a high fat diet for four weeks (after a six week high fat run in period) was able to prevent further weight gain associated with reduced food intake, and reduced circulating glucose and improve responses to an oral glucose tolerance test;[5] while this study noted an increase in liver PPARα in a dose-dependent manner, the increase in AMPK activity of the liver was only present at the lowest dose.[5]

There may be a reduction in blood glucose secondary to attenuating weight gain seen in rodents during a high fat diet, which is known to cause a species-dependent increase in both body weight and parameters such as blood glucose

5.4. Type II Diabetes

Supplementation of eriobotrya japonica (200-1,000mg/kg of an extract with 85.35% total triterpenoids) for four weeks to mice who became obese on a high fat diet was able to reduce fat with no apparent dose-dependence noted, although the improvements in the adipokine profile and insulin sensitivity appeared to be slightly dose-dependent.[47] The potency appeared to be comparable to 10mg/kg rosiglitazone at the highest dose tested for reducing blood glucose and insulin as well as improving insulin sensitivity.[47]

In type II diabetic rats (Otsuka Long-Evans Tokushima) and mice (KK-Ay) given the seed extract at 10% of the diet over the course of four months failed to modify weight gain or either hepatic or plasma lipids yet reduced circulating basal insulin concentrations (halved the difference between diabetic state and control) and significantly abrogated the increase in glucose seen in control groups.[31]

In regards to potential bioactives, amgygladin at doses found in the seed but taken by itself (0.2-2% of the diet) has failed to show any benefit to fasting glucose or insulin[31] and a nerolidol glyoside has noted acute (2-4 hours) reductions in blood glucose in alloxan-induced diabetic rats but not normal rats when ingested at 25-75mg/kg.[21] The total triterpenoid fraction (100-300mg/kg) appears to be effective when isolated from the leaves[45] (particularly euscaphic acid[48]) and the flavonoids (150-450mg/kg) also appear effective;[46] in the context of reducing blood glucose and improving insulin in animal models of diabetes, the triterpenoids (100-300mg/kg) and the flavonoids (150-450mg/kg) seem equipotent.[45][46]

The seeds and leaves appear to have protective effects when given to diabetic animals, with higher than normal doses of these components having comparable efficacy to some antidiabetic drugs (rosiglitazone, gliclazide). This may be mostly due to the triterpenoids of the plant with special reference towards ursolic, euscaphic, and corosolic acids


6Obesity and Fat Mass

6.1. Adipogenesis

Isolated corosolic acid from eriobotrya japonica at 15-45µg/mL appears to increase glucose uptake into adipocytes by 8.1-18.6% over control cells in the absence of insulin (and to a level significantly lesser than insulin at 1nM as reference), and was augmented in the presence of insulin.[49] Despite the increased glucose uptake, corosolic acid appears to suppress fat accumulation and proliferaiton associated with suppressing PPARγ and C/EBPα expression.[49]

Corosolic acid has some interesting benefits to adipocytes, but the high concentration required (for triterpenoids at least) paired with the relatively low levels of this in eriobotrya japonica leaves suggest that this mechanism is not relevant following oral ingestion


7Bone and Joint Health

7.1. Dental Health

In cultured gingival fibroblasts, a 70% ethanolic eriobotrya japonica leaf extract (7.39% Ursolic Acid) was able to suppress an LPS-induced increase in inflammation as assessed by nitrite, TNF-α, and IL-6 when pretreated at 20–80μg/mL; it reached a similar antiinflammatory effect as 2-8μM isolated ursolic acid.[50]

Potential antiinflammatory effects of the triterpenoids may precede anti-inflammatory activities in the gums


8Inflammation and Immunology

8.1. Interferons and Immunoglobulins

Injections of the hydrophilic (water soluble) leaf extract into mice is able to increase the secretion of IFN-γ from the spleen over the next 48 hours when 1-10μg is injected into mice, although there is a suppression at 100μg and while IL-17 is also stimulated it lasts for less than 24 hours; this was also seen with the water insoluble components, but these insoluble components also suppressed TGF-β.[51]

When measuring the serum, it appears that both extracts reduce circulating TGF-β without significantly influencing IL-17, and an increase in IFN-γ is seen in lung tissue.[51] The increase in IFN-γ from mitogens is also enhanced when whole human blood is incubated with the leaf extract of eriobotrya japonica at 1-100μg/mL with peak efficacy around 1-10μg/mL.[52]

There is an increase in interferons that positively influence immunity, and an increase has been detected in the lungs following administration of the leaf extract

8.2. Macrophages

The leaf extracts (methanolic at 12.5–75µg/mL) of eriobotrya japonica appear to suppress NF-kB activity and MAPK phosphorylation (JNK, ERK, and p38) in macrophages stimulated with LPS and secondary to that suppress iNOS and COX-2 induction, reducing nitrite formation from 9-fold (LPS control) to 2-fold[53] while 500µg/mL of the n-butanolic extract of the leaves (0.7% yield) has been noted to inhibit NF-kB translocation (from LPS) and suppressed nitrite formation by 87.7%.[42] These effects also occur in alveolar macrophages[54] and are thought to underlie some antitussive properties of eriobotrya japonica.

There is an increase in TNF-α and IL-12p70 secretion in whole human blood stimulated with mitogens from 1µg/mL of the leaf extract, while the increase in TNF-α persists up to 10-100µg/mL while IL-12p70 does not; this is indicative of possibly stimulatory effects on macrophages, and reversed the suppression of corticosteroid induced immunosuppression of these cytokines.[52]

May have some currently unexplored modulatory effects on macrophages, since it has been noted to reduce macrophage activation in models of bronchitis and systemic inflammation yet also has a per se stimulatory effect on macrophages and reduces corticosteroid-induced suppression of them

8.3. Mast Cells

A water extract of the leaves of eriobotrya japonica (12.5% yield) in isolated HMC-1 (mast) cells stimulated with the antigen PMA noted that at 100-1,000µg/mL the leaf extract attenuated IL-8 secretion while 1,000µg/mL was required to attenuate TNF-α and IL-6 secretion associated with NF-kB inhibition.[55] Elsewhere, 100-1,000µg/mL of the leaf extract has been found to mildly attenuate the release of histamine in response to an antigen.[56]

This same extract was later found to attenuate compound 48/80 induced anaphylaxis as mortality was halved at 100mg/kg injections and prevented at 500mg/kg, with the preventative effects only occurring when administered prior (as administration of even 1,000mg/kg 20 minutes after compound 48/80 was ineffective).[56]

Potential anti-allergic properties of the leaves and seeds, but this requires quite a high concentration in vitro and the limited animal evidence suggests that a large dose of the supplement is required to exert these antiallergic effects; may not be relevant to standard supplemental doses

8.4. Allergies

The seed extract of eriobotrya japonica (70% ethanolic with 13% yield) given at an unspecified dose ('5 times greater than the calculated human equivalent'; which according to this study[57] may be 1,250mg/kg) alongside sensitization to antigens (DTNB and oxazolone) and daily thereafter noted a suppression of ear edema by 11.3-19.2% when the rats were reintroduced to the antigens.[58]

Oral ingestion of higher than normal doses of the seed ethanolic extract appear to have mild anti-allergic effects when it comes to contact dermatitis

8.5. Virology

When testing triterpenoids in inhibiting the activation of Epstein-Barr virus, it seems that they had an inhibitory property comparable to the reference (EGCG from Green Tea Catechins).[18]


9Interactions with Hormones

9.1. Estrogen

Eriobotrya japonica leaf extract has been noted to possess estrogenic effects at a concentration of 100µg/mL which was as potent as 100ng/mL 17β-estradiol in a yeast assay.[59]

Potential interactions with estrogenic signalling of currently unknown relevance to the human body

9.2. Cortisol

The dichloromethane methane of eriobotrya japonica leaves 11β-HSD1 is inhibited (IC50 of 43+/-3µg/mL) preferentially over 11β-HSD2 (88+/-5µg/mL), although both inhibitory effects were weaker than the reference of glycyrrhetinic acid from Licorice.[60]

1,000mg/kg of a leaf extract (85.35% triterpenoids) but not 200-500mg/kg given to mice for four weeks after being fed a high fat diet was able to mildly decrease expression of the 11-β-hydroxysteroid dehydroxygenase 1 (11β-HSD1) gene in the liver and white adipose tissue, despite the expression of this gene not necessarily being altered with the onset of obesity and insulin resistance.[47] This was replicated with the reference drug of 10mg/kg rosiglitazone.[47]

The enzyme that reduces cortisone into the active cortisol appears to be mildy hindered at high oral doses of this leaf, likely not highly relevant to oral supplementation of this leaf


10Peripheral Organ Systems

10.1. Stomach

A 70% ethanolic extract of the seeds from eriobotrya japonica (dose unspecified) for 14 days with the last dose an hour before indomethacin induced stomach ulceration was able to attenuate the ulceration and oxidative changes[61] and elsewhere the same extract and timing given 15mL of either the human dose (37.5mg per 15mL; or 250mg/kg) or two concentrated forms (three and five times the aforementioned dose) noted reductions in the ulcer index in response to aspirin (31-71% protection), histamine (28-71%), serotonin (60-75%), pylorus ligature (25-43%; nonsignificant), and Alcohol with or without additional hydrochloric acid (39-60% and 34-49%) where the most effective dose of 112.5mg (750mg/kg) was equally effective as Teprenone (25mg/kg twice daily).[57]

Higher than average doses of the ethanolic seed extract appear to be respectably protective against gastric ulceration from a variety of sources based on the limited animal evidence available

10.2. Liver

The leaf extracts of eriobotrya japonica are known to possess antioxidative properties per se (IC50 for reducing lipid peroxidation was 30.35µg/mL) and higher potency with a water extract (10.08µg/mL) or partial ethanolic (15.62µg/mL), all of which appeared to outperform Vitamin E as reference (40.24µg/mL).[62] These antioxidant effects are thought to partially explain hepatoprotective effects against oxidative toxins, such as in rats given hepatotoxicity from dimethylnitrosamine (carcinogen) followed up by oral ingestion of various seed extracts in unspecified doses where there were protective effects (reduced liver enzymes and fibrosis) with all fragments with most potency coming from the 70% ethanolic extract.[63]

Methyl chlorogenate has been noted to suppress NF-kB activity in the liver of rats subsequently given an inflammatory agent via injections (t-butylhydroperoxide), with 2-10mg/kg of methyl chlorogenate suppressing NF-kB activity in a dose-dependent manner and the higher dose not being significantly different than control.[27]

In rats consuming a diet that induces fatty liver (a methionine-choline deficient diet) also given the 70% ethanolic seed extract of eriobotrya japonica (12% yield) at 270mg daily (approximately 2,450-3,000mg/kg) for 15 weeks, there was a full and partial attenuation of changes in the liver enzymes AST and ALT, respectively.[64] The seed extract was also associated with reductions in oxidative stress in liver tissue, fat accumulation in the liver, and subsequent fibrosis.[64]

There are standard protective effects in the liver which may be related to the antioxidant properties of this compound; currently it has not been compared to reference drugs in an assessment of potency

In rats fed a diabetic and obesogenic diet given the seed extract (10% of the diet) which was sufficient to reduce blood glucose and insulin levels, there was no significant influence on hepatic fatty acids or cholesterol concentrations.[31]

The dose that appears to exert beneficial effects towards glucose metabolism has failed to exert any appreciable benefit to cholesterol and lipid content of the liver

10.3. Lungs

One study measuring IFN-γ concentrations have noted an increase in lung tissue following injections of 1-10μg of the water soluble extract from eriobotrya japonica leaves[51] and oral ingestion of 150-450mg/kg of the total triterpenoids has been noted to increase lung activity of the superoxide dismutase (SOD) enzyme.[65]

A possible immunostimulatory effect involving an increase in IFN-γ has been reported in the lung tissue, and oral ingestion of high doses of the triterpenoids has been confirmed to increase antioxidant enzyme status in lung tissue

In isolated lung epithelial cells (A549) treated with the proinflammatory LPS, the leaf water extract of eriobotrya japonica appears to reduce the secretion of proinflammatory cytokines such as IL-1β (IC50 of 43.5+/-1.56µg/mL; normalized to control at 125µg/mL), TNF-α (33.6+/-1.4µg/mL; normalized to control at 64µg/mL), and IL-8 (35.4+/-1.4µg/ml; normalized to control at 500µg/mL) associated with NF-kB inhibition.[66] These effects were thought to simply be due to Ursolic Acid since it inhibited IL-8 production with an IC50 of 2+/-0.14µM (oleanolic ineffective).[66]

Total triterpenoids of eriobotrya japonica leaf (50-450mg/kg) fed to rats for 28 days after pulmonary fibrosis (induced by an injection of bleomycin A5) was able to alleviate fibrosis in the lungs and trachea, and this alleviation was associated with reductions in both protein content and mRNA of TNF-α and TGF-β1.[14] The doses of 50-450mg/kg were not significantly different than 1.2mg/kg dexamethasone (reference drug)[14] and this dose also appears to be effective in reducing LPS induced inflammation in the bronchus associated with reducing immune cell infiltration[67] and reducing macrophage activity and NF-kB activation in said macrophages.[68] In regards to LPS induced inflammation, all three doses tested (50, 150, and 450mg/kg) are either statistically comparable to each other and to 1.2mg/kg dexamethasome[67] or the two higher dsoes are while 50mg/kg is statistically protective but less so.[68]

Very high doses of the triterpenoids appear to be quite protective against damage in the lungs in response to inflammatory stimuli, but due to the high doses used this may not be practically reflective of oral supplementation of basic extracts

10.4. Kidneys

A 70% ethanolic extract of the seeds of eriobotrya japonica given at 15mL daily (dose unspecified but possibly in the range of 250-500mg/kg) was able to partially attenuate the increases in creatinine and BUN seen with adriamycin toxicity;[69] there was a partial abrogation of lipid peroxidation, and no influence on the reduction in albumin.[69]

Potential protective effects of unknown practical relevance


11Interactions with Cancer Metabolism

11.1. Mechanisms

A family of molecules that can inhibit apoptosis in the cell (inhibitors of apoptosis proteins, or IAP) has a subset which are X-linked inhibitor of apoptosis proteins (XIAPs) which can bind to caspase-9 from the mitochondria (on XIAP's BIR3 domain[70]) and prevent caspase-9 from inducing apoptosis. This process is normally inhibited by another protein from the mitochondrial called Smac/DIABLO which interacts with the BIR3 domain and prevents it from influence capsase-9.[71]

A acetylated flavonoid form eriobotrya japonica leaves known as kaempferol-3-O-α-L-(2″,4″-di-E-p-coumaroyl)-rhamnoside appears to bind to the BIR3 domain in an inhibitory manner (ie. is a Smac mimetic) with an IC50 of 10.4μM;[25] it is greatly dependent on the rhamnose sugar and the two coumaric acid moieties, and free Kaempferol does not appear to have this property.[25] Kaempferol itself, however, has been implicated in downregulating the protein content of XIAP[72][73] despite not directly binding to it.

A acetylated flavonoid in this plant appears to be a direct small molecule inhibitor of XIAP function, which may be involved in increasing apoptosis in cancer cells. Due to the unknown content of this molecule in the leaf, it is unknown how relevant this information is

Some triterpenoids in eriobotrya japonica leaves appear to be topoisomerase I inhibitors with most potency coming from 3-O-(E)-p-coumaroyltormentic acid (IC50 of 20.3μM) which was comparable to camptothecin (28.1μM) and stronger than ursolic acid (26.3μM), betulinic acid (36.5μM), oleanolic acid (64.3μM), and maslinic acid (80.6μM).[74]

Some triterpenoid structures may be inhibitors of topoisomerase I; practical significance of this data in regards to supplementation of this supplement is currently unknown

11.2. Invasion and Metastasis

Eriobotrya japonica is able to downregulate MMP2 and MMP9 and subsequently reduce invasion of B16F10 melanoma cells (concentration dependent up to 250-500µg/mL[75]) and MDA-MB-231 breast cancer cells (10-50µg/mL; up to 80% with the leaf extract[76]), which is thought to be due to ursolic acid and 2α-hydroxyursolic acid since they both suppressed MMP2 (to 10% of control) and MMP9 (25% of control) at 1.25µg/mL in a manner associated with reducing NF-kB translocation into the nucleus.[75]

Potential antiinvasive effects secondary to ursolic acid

11.3. Breast Cancer

Eriobotrya japonica (leaf extract with 17.2% yield) appears to have antiproliferative effects in MDA-MB-231 breast cancer cells with an IC50 of 4+/-0.2µg/mL, which was significantly better than its effects on other cancer cells such as cervical HeLa cells (23+/-1.1µg/mL), lung A549 cells (14+/-0.6µg/mL), and ovarian SK-OV-3 cells (306+/-14.2µg/mL).[59]

In vitro preliminary evidence suggests a respectable antiproliferative effect on the invasive breast cancer cell line

11.4. Leukemia

In leukemic cells (HL-60, U937, Jurkat and THP-1), isolated triterpenoids (ursolic, corosolic, oleanolic, and maslinic acids) have shown antiproliferative actions with most potency coming from corosolic and ursolic acids in the concentration range of 6.25-25μM.[77] Corosolic acid was further tested and was noted to induce apoptosis via inducing DNA fragmentation via oxidative stress in a mitochondrial dependent manner associated with increasing Bax translocation into the mitochondria.[77] An acetylated triterpenoid (3-O-(E)-p-coumaroyltormentic acid) has shown similar properties in HL-60 (EC50 of 6.9μM) with a potency comparable to ursolic acid (5μM) and betulinic acid (6.4μM) by inducing apoptosis via the mitochondrial pathway.[74]

Potential benefits which are mostly just secondary to ingestion of ursolic acid

11.5. Sarcoma

In mice bearing Meth-A tumors who are then injected with 0.1mg of an eriobotrya japonica hydrophilic extract, injections do not appear to induce IFN-γ secretion from the spleen with a single dose (seen in normal mice) but three repeated daily doses appeared to mildly stimulate IFN-γ production with no influence on IL-17 nor TGF-β1.[51]

Despite the above, injections of the water insoluble components greatly increased median lifespan from 27 days in control to 78 days while the water soluble extract failed to prolong lifespan.[51]

11.6. Adjuvant Usage

One study in hamsters where mucositis was induced using 5-fluorouracil, the 70% ethanolic seed extract (54mg; around 640mg/kg) taken daily for a week prior to the drug and continued until the end of the experiment was able to fully prevent leukocyte infiltration and lipid peroxide yet only appeared to attenuate the thickness of mucositis in the cheek tissue by approximately half.[78]

One study has noted benefits to oral mucositis, but it has not been investigated whether this adjuvant treatment benefits or hinders the usage of chemotherapeutics in treating cancer


12Safety and Toxicology

12.1. General

The n-butanolic extract of the leaves (0.7% total) yield appears to be acutely nontoxic up to 2,000mg/kg oral intake in mice,[42] and when looking at a 70% ethanolic extract (measured in dry leaf equivalents) the leaf appears to have an LD50 of 40.1g/kg bodyweight in mice.[79]

The seed extract given to mice over a period of four weeks at an oral dose of 8,000mg/kg has failed to exert any clinical signs of toxicology.[31]

At this moment in time there is insufficient evidence to suggest absolute safety but no reports of harm assocaited with the supplement; toxicity induced in animals appears to suggest that it is not acutely damaging

Scientific Support & Reference Citations

References

  1. Ding CK, et al Metabolism of phenolic compounds during loquat fruit development . J Agric Food Chem. (2001)
  2. Hong Y, et al Variation in contents of total phenolics and flavonoids and antioxidant activities in the leaves of 11 Eriobotrya species . Plant Foods Hum Nutr. (2008)
  3. Wu L, et al Processing technology investigation of loquat (Eriobotrya japonica) leaf by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry combined with chemometrics . PLoS One. (2013)
  4. Genetic Diversity and Utilization of Triploid Loquats (E. japonica Lindl)
  5. Shih CC, Lin CH, Wu JB Eriobotrya japonica improves hyperlipidemia and reverses insulin resistance in high-fat-fed mice . Phytother Res. (2010)
  6. Zhou C, et al Flavonoids, Phenolics, and Antioxidant Capacity in the Flower of Eriobotrya japonica Lindl . Int J Mol Sci. (2011)
  7. Xu HX, Chen JW Commercial quality, major bioactive compound content and antioxidant capacity of 12 cultivars of loquat (Eriobotrya japonica Lindl.) fruits . J Sci Food Agric. (2011)
  8. Tropical and subtropical fruits: composition, properties and uses
  9. Godoy HT, Amaya DB Carotenoid composition and vitamin A value of Brazilian loquat (Eriobotrya japonica Lindl.) . Arch Latinoam Nutr. (1995)
  10. Effect of loquat (Eriobotrya japonica) extracts on LDL oxidation
  11. Sadana JC Carotenoids of loquat (Eriobotrya japonica Lindl.) . Biochem J. (1949)
  12. Li EN, Luo JG, Kong LY Qualitative and quantitative determination of seven triterpene acids in Eriobotrya japonica Lindl. by high-performance liquid chromatography with photodiode array detection and mass spectrometry . Phytochem Anal. (2009)
  13. Studies on constituents of triterpene acids from Eriobotrya japonica and their anti-inflammatory and antitussive effects
  14. Yang Y, et al Antifibrosis effects of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. leaf in a rat model of bleomycin-induced pulmonary fibrosis . J Pharm Pharmacol. (2012)
  15. Banno N, et al Anti-inflammatory and antitumor-promoting effects of the triterpene acids from the leaves of Eriobotrya japonica . Biol Pharm Bull. (2005)
  16. Ito H, et al Megastigmane glycosides and an acylated triterpenoid from Eriobotrya japonica . J Nat Prod. (2001)
  17. A new triterpene ester from Eriobotrya japonica
  18. Taniguchi S, et al Production of bioactive triterpenes by Eriobotrya japonica calli . Phytochemistry. (2002)
  19. De Tommasi N, et al Constituents of Eriobotrya japonica. A study of their antiviral properties . J Nat Prod. (1992)
  20. Lee MH, Son YK, Han YN Tissue factor inhibitory sesquiterpene glycoside from Eriobotrya japonica . Arch Pharm Res. (2004)
  21. Chen J, et al Hypoglycemic effects of a sesquiterpene glycoside isolated from leaves of loquat (Eriobotrya japonica (Thunb.) Lindl.) . Phytomedicine. (2008)
  22. Ito H, et al Antitumor activity of compounds isolated from leaves of Eriobotrya japonica . J Agric Food Chem. (2002)
  23. Ito H, et al Polyphenols from Eriobotrya japonica and their cytotoxicity against human oral tumor cell lines . Chem Pharm Bull (Tokyo). (2000)
  24. Jung HA, et al Antioxidant flavonoids and chlorogenic acid from the leaves of Eriobotrya japonica . Arch Pharm Res. (1999)
  25. Pfisterer PH, et al In silico discovery of acylated flavonol monorhamnosides from Eriobotrya japonica as natural, small-molecular weight inhibitors of XIAP BIR3 . Bioorg Med Chem. (2011)
  26. Kawahara N, Satake M, Goda Y A new acylated flavonol glycoside from the leaves of Eriobotrya japonica . Chem Pharm Bull (Tokyo). (2002)
  27. Kwon HJ, et al Inhibition of NFkappaB by methyl chlorogenate from Eriobotrya japonica . Mol Cells. (2000)
  28. Song FL, et al Total phenolic contents and antioxidant capacities of selected chinese medicinal plants . Int J Mol Sci. (2010)
  29. Zhou C, et al Determination of oleanolic acid, ursolic acid and amygdalin in the flower of Eriobotrya japonica Lindl. by HPLC . Biomed Chromatogr. (2007)
  30. Cheng L, et al Studies on the triterpenoidal saponins from flowers of Eriobotrya japonica . Hua Xi Yi Ke Da Xue Xue Bao. (2001)
  31. Tanaka K, et al Hypoglycemic activity of Eriobotrya japonica seeds in type 2 diabetic rats and mice . Biosci Biotechnol Biochem. (2008)
  32. Li S, et al Repeated-dose (28 days) oral toxicity study in rats of an antiacne formula (BC-AF) derived from plants . Drug Chem Toxicol. (2011)
  33. Fermented tea produced by rubbing starting tea leaves and japanese medlar leaves and composition having extract contained in the fermented tea as the active ingredient
  34. Toshima A, et al Identification of alpha-glucosidase inhibitors from a new fermented tea obtained by tea-rolling processing of loquat (Eriobotrya japonica) and green tea leaves . J Sci Food Agric. (2010)
  35. Tanaka T, et al Increase of theaflavin gallates and thearubigins by acceleration of catechin oxidation in a new fermented tea product obtained by the tea-rolling processing of loquat ( Eriobotrya japonica ) and green tea leaves . J Agric Food Chem. (2009)
  36. Tanaka K, et al Hypotriacylglycerolemic and antiobesity properties of a new fermented tea product obtained by tea-rolling processing of third-crop green tea (Camellia sinensis) leaves and loquat (Eriobotrya japonica) leaves . Biosci Biotechnol Biochem. (2010)
  37. Tamaya K, et al Suppression of blood glucose level by a new fermented tea obtained by tea-rolling processing of loquat (Eriobotrya japonica) and green tea leaves in disaccharide-loaded Sprague-Dawley rats . J Sci Food Agric. (2010)
  38. IP3, IP3 receptor, and cellular senescence
  39. Grossmann A, Ledbetter JA, Rabinovitch PS Aging-related deficiency in intracellular calcium response to anti-CD3 or concanavalin A in murine T-cell subsets . J Gerontol. (1990)
  40. Muramoto K, et al Ameliorative effects of Eriobotrya japonica seed extract on cellular aging in cultured rat fibroblasts . J Nat Med. (2011)
  41. Kim MJ, et al Neuroprotective effects of Eriobotrya japonica against β-amyloid-induced oxidative stress and memory impairment . Food Chem Toxicol. (2011)
  42. Cha DS, Eun JS, Jeon H Anti-inflammatory and antinociceptive properties of the leaves of Eriobotrya japonica . J Ethnopharmacol. (2011)
  43. Kotowaroo MI, et al Screening of traditional antidiabetic medicinal plants of Mauritius for possible alpha-amylase inhibitory effects in vitro . Phytother Res. (2006)
  44. Qa'dan F, et al Cinchonain Ib isolated from Eriobotrya japonica induces insulin secretion in vitro and in vivo . J Ethnopharmacol. (2009)
  45. Lü H, et al Hypoglycemic and hypolipidemic effects of the total triterpene acid fraction from Folium Eriobotryae . J Ethnopharmacol. (2009)
  46. Lü H, et al Hypoglycemic effect of the total flavonoid fraction from folium Eriobotryae . Phytomedicine. (2009)
  47. Shih CC, et al Cell suspension culture of Eriobotrya japonica regulates the diabetic and hyperlipidemic signs of high-fat-fed mice . Molecules. (2013)
  48. Chen J, et al Euscaphic acid, a new hypoglycemic natural product from Folium Eriobotryae . Pharmazie. (2008)
  49. Zong W, Zhao G Corosolic acid isolation from the leaves of Eriobotrta japonica showing the effects on carbohydrate metabolism and differentiation of 3T3-L1 adipocytes . Asia Pac J Clin Nutr. (2007)
  50. Choi YG, et al Protective changes of inflammation-related gene expression by the leaves of Eriobotrya japonica in the LPS-stimulated human gingival fibroblast: microarray analysis . J Ethnopharmacol. (2011)
  51. Alshaker HA, et al Eriobotrya japonica hydrophilic extract modulates cytokines in normal tissues, in the tumor of Meth-A-fibrosarcoma bearing mice, and enhances their survival time . BMC Complement Altern Med. (2011)
  52. Matalka KZ, et al The differential effect of Eriobotrya japonica hydrophilic leaf extract on cytokines production and modulation . Cytokine. (2007)
  53. Uto T, et al Eriobotryae folium extract suppresses LPS-induced iNOS and COX-2 expression by inhibition of NF-kappaB and MAPK activation in murine macrophages . Am J Chin Med. (2010)
  54. Huang Y, et al Effect of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. leaf and MAPK signal transduction pathway on inducible nitric oxide synthase expression in alveolar macrophage of chronic bronchitis rats . Am J Chin Med. (2009)
  55. Kim SH, Shin TY Anti-inflammatory effect of leaves of Eriobotrya japonica correlating with attenuation of p38 MAPK, ERK, and NF-kappaB activation in mast cells . Toxicol In Vitro. (2009)
  56. Kim SH, et al Effect of leaves of Eriobotrya japonica on anaphylactic allergic reaction and production of tumor necrosis factor-alpha . Immunopharmacol Immunotoxicol. (2009)
  57. Yokota J, et al Gastroprotective activity of Eriobotrya japonica seed extract on experimentally induced gastric lesions in rats . J Nat Med. (2008)
  58. Sun G, et al Effect of orally administered Eriobotrya japonica seed extract on allergic contact dermatitis in rats . J Pharm Pharmacol. (2007)
  59. Kang SC, et al Evaluation of oriental medicinal herbs for estrogenic and antiproliferative activities . Phytother Res. (2006)
  60. Gumy C, et al Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 by plant extracts used as traditional antidiabetic medicines . Fitoterapia. (2009)
  61. Yokota J, et al Eriobotrya japonica seed extract and deep sea water protect against indomethacin-induced gastric mucosal injury in rats . J Nat Med. (2011)
  62. Yokota J, et al Scavenging of reactive oxygen species by Eriobotrya japonica seed extract . Biol Pharm Bull. (2006)
  63. Nishioka Y, et al Effects of extract derived from Eriobotrya japonica on liver function improvement in rats . Biol Pharm Bull. (2002)
  64. Yoshioka S, et al Effects of Eriobotrya japonica seed extract on oxidative stress in rats with non-alcoholic steatohepatitis . J Pharm Pharmacol. (2010)
  65. Huang Y, et al Anti-oxidative effect of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. leaf in chronic bronchitis rats . Life Sci. (2006)
  66. Lee CH, et al Eriobotrya japonica leaf and its triterpenes inhibited lipopolysaccharide-induced cytokines and inducible enzyme production via the nuclear factor-kappaB signaling pathway in lung epithelial cells . Am J Chin Med. (2008)
  67. Ge JF, et al Anti-inflammatory effect of triterpenoic Acids of Eriobotrya japonica (Thunb.) Lindl. Leaf on rat model of chronic bronchitis . Am J Chin Med. (2009)
  68. Huang Y, et al Effect of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. leaf on inflammatory cytokine and mediator induction from alveolar macrophages of chronic bronchitic rats . Inflamm Res. (2007)
  69. Hamada A, et al The effect of Eriobotrya japonica seed extract on oxidative stress in adriamycin-induced nephropathy in rats . Biol Pharm Bull. (2004)
  70. Liu Z, et al Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain . Nature. (2000)
  71. Wu G, et al Structural basis of IAP recognition by Smac/DIABLO . Nature. (2000)
  72. The flavonoid kaempferol sensitizes human glioma cells to TRAIL-mediated apoptosis by proteasomal degradation of survivin
  73. Jeong JC, et al Kaempferol induces cell death through ERK and Akt-dependent down-regulation of XIAP and survivin in human glioma cells . Neurochem Res. (2009)
  74. Kikuchi T, et al 3-O-(E)-p-coumaroyl tormentic acid from Eriobotrya japonica leaves induces caspase-dependent apoptotic cell death in human leukemia cell line . Chem Pharm Bull (Tokyo). (2011)
  75. Cha DS, et al Anti-metastatic properties of the leaves of Eriobotrya japonica . Arch Pharm Res. (2011)
  76. Kim MS, et al Loquat (Eriobotrya japonica) extracts suppress the adhesion, migration and invasion of human breast cancer cell line . Nutr Res Pract. (2009)
  77. Uto T, et al Anti-Proliferative Activities and Apoptosis Induction by Triterpenes Derived from Eriobotrya japonica in Human Leukemia Cell Lines . Int J Mol Sci. (2013)
  78. Takuma D, et al Effect of Eriobotrya japonica seed extract on 5-fluorouracil-induced mucositis in hamsters . Biol Pharm Bull. (2008)
  79. Li WL, et al Pharmacological studies on anti-hyperglycemic effect of folium eriobotryae . Am J Chin Med. (2007)
  80. Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators, et al Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial . JAMA. (2015)
  81. Taylor MJ1, et al Folate for depressive disorders . Cochrane Database Syst Rev. (2003)
  82. Godfrey PS1, et al Enhancement of recovery from psychiatric illness by methylfolate . Lancet. (1990)
  83. Kushwaha S1, Chawla P1, Kochhar A1 Effect of supplementation of drumstick (Moringa oleifera) and amaranth (Amaranthus tricolor) leaves powder on antioxidant profile and oxidative status among postmenopausal women . J Food Sci Technol. (2014)