Summary of Crataegus pinnatifida
Primary Information, Benefits, Effects, and Important Facts
Crataegus pinnatifida, also known as Chinese hawthorn, is a berry traditionally used to improve heart health.
Crataegus pinnatifida is sometimes recommended as a supplement to control lipid levels. Crataegus pinnatifida may be able to block lipid absorption in the intestines, but this effect is unreliable and needs further study.
Crataegus pinnatifida has a more powerful effect on restricting lipid absorption than orlistat, an anti-obesity drug. An ethanolic extract of Crataegus pinnatifida leaves was found to have a stronger anti-allergic effect than Montelukast, a brand name drug for asthma and allergy relief.
There have been no human studies done on Crataegus pinnatifida, and the two main effects of the plant, reduced lipid absorption and allergy relief, have not been linked to any bioactive compounds in the plant.
Though preliminary evidence suggests the fruit and leaves of Crataegus pinnatifida are a promising heart supplement, there is not enough evidence for its effects to specifically recommend the plant for supplementation.
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Things To Know & Note
Also Known As
Chinese Hawthorn, Shanzha, Shanlihong, Yixintong (tablets)
Do Not Confuse With
Undaria pinnatifida (source of fucoxanthin and a seaweed rather than a berry)
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Scientific Research on Crataegus pinnatifida
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Crataegus pinnatifida (of the family Rosaceae) is a medicinal food product native to Northern China (where it derives the common name of Chinese Hawthorn) but also found spreading across a similar latitude to Japan, South Korea, Europe, and parts of North America. It should be noted that while Crataegus pinnatifida is sometimes seen as the most important one, the term 'Chinese Hawthorn' may refer to up to 18 different species that have similar food properties some of which include C. brettschneideri (Fu hawthorn), C. scabrifolia (Yun’nan hawthorn), C. hupehensis (Hubei hawthorn), C. kansuensis Sarg. (Gansu hawthorn), C. cuneata Sieb. et Zucc. (wild hawthorn), C. songarica (Zhunger hawthorn), C. wilsonii Sarg. (Huazhong hawthorn), and C. altaica (loud) Lange. (A’ertai hawthorn) with the particular variant Crataegus pinnatifida Bge. var. major N.E.Br. (Shanlihong) having status in the Chinese Pharmacopeia.
The leaves and flowers, as well as the fruits independent of the stage of ripeness, have traditionally been used to treat congestive heart failure, high blood pressure, hypoxia, and hyperlipemia.
Novel compounds to Chinese Hawthorn include:
biphenyl-5-ol-3-O-β-D-glucoside and 3,4′-dimethoxy-biphenyl-5-ol-4-O-β-D-glucoside
The molecules novel to Crataegus pinnatifida have not yet been linked to any therapeutic benefits of the fruit or leaves
Whereas molecules that are common to some plants and have been noted elsewhere are:
Procyanidins (B2, B5, C1) at 2.96+/-0.14% of the dry fruit with an Oligomeric Procyanidin to Procyanidin ratio of 61.6%. The contents of these individually rather than collectively in another study (fresh fruit) were 1505mcg/g (B2), 339mcg/g (B5), and 684mcg/g (C1)
Quercetin (as 3-O-β-d-glucoside), Isoquercetin, Rutin (quercetin-3-O-rutinoside at 1.45% dry weight of fruits and 0.43% in the leaves, Isoquercitrin (Low at 41mcg/g in fresh fruits), and Hyperoside (aka. Quercetin-3-O-Galactoside) with the latter at 0.2% in the fruits (dry weight) or 56mcg/g (fresh weight) and highly variable at 0.16-0.82% in the leaves. A large triglycoside of Quercetin (α-L-rhamnopyranosyl(1-4)-α-L-rhamnopyranosyl-(1-6)-β-glucopyranoside) has also been noted
Beta-sitosterol and Daucosterol
Citric Acid (2-8.4% dry weight of fruits)
Quinic Acid (0.5-5.6% dry weight of fruits)
Malic Acid (0.3-1.1% dry weight of fruits)
Myo-inositol (0.1-0.3% dry weight of fruits)
There appears to be a relatively large Vitexin content (structurally related to the Apigenin molecule) and the Procyanidin class of molecules also have a large content. Quercetin structures are present in moderate amounts and may also contribute to the observed benefits
In general, all parts of the plant show anti-oxidant properties due to the high phenolic content. The leaves have most of this anti-oxidant content due to the epicatechin and Chlorogenic acid contents and can have up to 80% phenolic content on a dry weight basis.
The fruits confer most of the antioxidant properties from oligomeric procyanidins, where hawthorn procyanidins confer more direct protection from lipid peroxidation in vitro than an equal weight of Vitamin E.
The fruits themselves, as a food product, contain 5.5-18.4% fructose, 5.3-16.6% glucose, and 3-15.7% sorbitol dry weight; confering an approximate 1:1 fructose:glucose ratio and the total sugar content being approximately 22.86+/-3.68% in Crataegus pinnatifida specifically. When looking at extracts of the fruits, a hot water extract has 6.9% flavonoids and 2.2% Procyanidins by dry weight.
After intravenous administration of vitexin-4″-O-glucoside to rats at 20, 40, or 60mg/kg bodyweight noted a biological half-life around 0.5909-0.5984 hours with the 40-60mg/kg dose yet a much shorter half-life of 0.09+/-0.29 with 20mg/kg. Clearance was somewhat dose-dependent between 0.1180-0.1701kg/L/h and AUC increased from 169.5509+/-79.70mg/L/h (20mg/kg) to 245.7789+/-209.63mg/L/h and 352.8117+/-294.72mg/L/h, being dose-dependent at the two higher doses but non-linear at the lowest. Vitexin glycosides have also been studied after injections of the leaf extract of Hawthorne (6.1% Vitexin-4″-O-glucoside and 14% vitexin-2''-O-rhamnoside) where 10, 20, and 40mg/kg of the overall extract where a very short half-life was noted for both glycosides (just under 2 minutes).
Vitexin glycosides, which make up a major component of the leaves, seem to be rapidly deglycosylated (metabolized away from their sugar moieties) in serum after injections to rats
In regards to Hyperoside, injections of Hyperoside at 5, 10, or 20mg/kg had a half-life increasing with dose (0.2, 0.5, and 1.1 hours) and at the highest dose were only detectable for up to 4 hours (lower doses being detectable for up to 2 hours); Hyperoside injections followed non-linear kinetics.
Absorption of triglycerides from the intestines can be hindered with ingestion of the leaf extract of Crataegus pinnatifida, with 125-500mg/kg oral intake being given 30 minutes prior to an olive oil loading test reducing circulating lipid levels over the next 6 hours by 38-59% (125mg/kg), 62-87% (250mg/kg) and 95% at 2 hours relative to control (500mg/kg; 6 hour time point lower than control); when compared to Orlistat (12.5mg/kg) which reduced lipids by 81-89%, the highest dose of Crataegus outperformed Orlistat. This is possibly related to inhibition of pancreatic lipase (required for absorption of triglycerides in the diet), and an IC50 value of 324.0mcg/mL has been reported.
Cholesterol absorption may also be inhibited, being weakly synergistic with plant sterols.
The leaves may inhibit lipid absorption; actually appears to be very effective in doing so at high doses with more potency than Orlistat (but requiring a much higher oral dose)
In male mice who were given a high fat diet to induce high blood triglycerides and cholesterol, administration of 250mg/kg of the fruits of Crataegus pinnatifida for 7 days was able to improve the activity of PPARα and downstream proteins in the liver (but not adipose) of rats and thought to be a mechanism of hypolipidemic effects by increasing β-oxidation, with another study managing to abolish the hypolipidemic effects by coadministration with a PPARα antagonist (MK886) in vivo implicating this as a major role.
Individual components of Crataegus pinnatifida have suppressive effects on the HMG-CoA enzyme, and these compounds (rutin, chlorogenic acid, hyperoside, and quercetin) appear to be synergistic amongst themselves as evidenced by one in vitro study where the actual inhibition of 79.48% was the result of concentrations that mathematically had an additive sum of 50.01% inhibition. This was further tested in vivo, where 2.85mg/kg of a mixture of the four compounds in the ratios found in the fruits (0.16:0.32:1.42:0.95) outperformed any single compound in isolation at the 2.85mg/kg dosage.
Appears to have potent anti-lipidemic effects in rats, although at least one study suggests that this is due mostly to PPARα activation (of which species differences exist) and thus extrapolation to humans may be of lesser magnitude. Human studies will be needed to ascertain potency
Eriodectyol (100mcg/mL) has shown anti-thrombotic ability in a Zebrafish assay, where it prolonged clotting time to a similar degree as the active control Liquaemin (5U/mL; Anticoagulant drug).
Possibly potent anti-thrombus effects, but the dose seems quite high and this may not apply to oral Hawthorn ingestion due to currently unquantified Eriodectyol content in the leaves and fruits
A hot water extract of Crategus fruits (6.9% flavonoids, 2.2% Procyanidin) in vitro is able to greatly reduce TBARS (lipid peroxidation) and subsequent CuSO4-induced LDL cholesterol oxidation in a concentration-dependent manner with most potency between 0.5-1.0mg/mL; this extract also fully protected LDL from macrophage-induced oxidation at 0.05mg/mL or above despite proliferating macrophages in a dose-dependent manner.
May reduce LDL oxidation, practical relevance of this following supplementation of Hawthorn is currently unknown
125-500mg/kg of the leaf extract of Crataegus pinnatifida (not the fruits, and thus without a significant carbohydrate content itself) may suppress carbohydrate absorption when given surcose when serum glucose is measured for up to 2 hours after ingestion; dose-dependence exists, but only the highest dose of 500mg/kg when measured at 30 minutes was statistically significnace (27%) while the active control of Tobutamide achieved 49% inhibition at this time point. This is related to inhibitory potential on the sucrase enzyme, which has had a reported IC50 value of 243.8mcg/mL.
Moderate to weak inhibitory potential on glucose uptake, failed to outperform the reference drug
30mcg/mL of a flavonoid concentration fraction (leaves) had various compounds that could inhibit triglyceride and fatty acid uptake in mature adipocytes, including vitexin-4′′-O-glucoside (32.82+/-4.31%), vitexin-2′′-O-rhamnoside (28.54+/-5.62%), Rutin (64.3+/-6.0%), and Hyperoside (79.1+/-9.8%). When incubated with preadipocytes over 14 days during differnetiation, those incubated with the leaf extract showed less expression of C/EBPα, PPARγ, SREBP 1c, aP2 and adiponectin (no influence on leptin) which suggest possible anti-proliferative effects.
Isolated components may inhibit triglyceride uptake into fat cells, but practical relevance of this after supplementation of Hawthorn is unknown
Flavonoids from Crataegus pinnatifida are able to suppress LPS-induced nitrate accumulation in macrophages in a concentration dependent manner up to 250mcg/mL (with 500-750mcg/mL suppressing to similar levels) and concentration dependent PGE2 suppression in vitro; this has been noted elsewhere with the hot water extract at 200-600mcg/mL dose-dependently reducing nitric oxide production, iNOS induction, and COX-2 mRNA induction with the latter being quantified at 45.5% attenuation (200mcg/mL), 80.2% (400mcg/mL), and 85.7% (600mcg/mL).
Due to these suppressive effects on macrophage activation, proinflammatory cytokines are reduced with one study quantifying these effects after 400mcg/mL of the water extract at 60.2% (TNF-α mRNA), 44.8% (IL-1β mRNA), and 34.4% (IL-6 mRNA) with no further decrease noted at 600mcg/mL. Hyperoside, a major active ingredient of Crataegus pinnatifida and structurally related to Quercetin, appears to exert these effects via NF-kB inhibition.
One study that wanted to measure macrophage-induced LDL oxidation noted that, when macrophages were incubated with a hot water extract of Crataegus pinnatifida, concentrations of 0.5-2mg/mL proliferated macrophages above that of control to about 120% of control at 1-2mg/mL (no significant difference between the two concentrations) and Hawthorn fruits have been found to protect macrophages from LPS-induced apoptosis from 45.7% (LPS control) to 61.8%(200mcg/mL water extract), 72.7% (400mcg/mL), and 83.4% (600mcg/mL) of control values.
Water extracts appear to have dose-dependent anti-inflammatory effects, but the IC50 values (concentration required to inhibit 50% of the measured phenomena) are not remarkably potent
One study conducting a scan for collagenase and gelatinase inhibitors noted that some Procyanidins from Crataegus pinnatifida were potent collagenase inhibitors. The Procyanidin with the structure epicatechin-(4β→8)-epicatechin-(4β→6)-epicatechin inhibited collagenase with an IC50 of 0.98+/-0.08uM, with others including a Procyanidin with 5 epicatechins found by (4β→8) bonds (IC50 21.4+?-1.9uM), the trimer epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin (11.3+/-1.3uM), and the most potent being another trimer epicatechin-(4β→6)-epicatechin-(4β→8)-epicatechin. This last trimer also potently inhibited gelatinase A (IC50 0.4+/-0.1uM) and Gelatinase B (2.3+/-0.9uM) both of which outperformed the active control of Chlorhexidine.
Procyanidins in Hawthorn appear to be very promising for therapeutic treatment of Arthritis, but this is currently preliminary
An ethanolic extract of Hawthorn Berries (0.14% Hyperoside) is able to reduce the inflammatory phenotype in careegnaan-induced paw edema at 50mg/kg (20.8% inhibition), 100 (23.0%), and 200mg/kg (36.3%) although all doses were weaker than 4mg/kg Indomethacin as active control.
200mg/kg of the flavonoid extract fed to rats normalized LPS-induced inflammatory damage to hepatic tissue, with lower doses (50-100mg/kg) attenuating the damage.
Appears to have dose-dependent anti-inflammatory effects in rats following oral ingestion, but the one study comparing it to a reference drug (Indomethacin) noted that it was comparatively weaker
In rats with selenite-induced (prooxidative) cataracts, eye drops containing 1-2mg/mL leaf extract of Crataefus Pinnatifida was able to scavenge free radicals (IC50 5.98ug/mL), inhibit Nitric Oxide production (IC50 98.3ug/mL) and inhibit the aldose reductase enzyme (IC50 89.7ug/mL) while inducing the anti-oxidant enzymes SOD and Catalase; the potency of enzyme induction at was similar to the active control Pirenoxine (0.8mg/15mL) at the 2mg/mL concentration only.
Eye drops containing the leaf extract may be quite protective against free radical damage, moderately potent on Aldose Reductase (tied into diabetic retinopathy)
A study in mice using the ethanolic extract of Crataegus pinnatifida as either 100 or 200mg/kg (with preliminary studies finding doses higher than that equal to 200mg/kg) for 5 days prior to exposure to an antigen (ovalbumin) was associated with a dose-dependent reduction in immune cell infiltration into the lungs and Bronchoalveolar Lavage Fluid to comparable potency as the active control of 30mg/kg Montelukast (drug for treatment of allergic asthma). This was accompanied by reduced levels of total IgE and antigen-specific IgE and IgG1, decreased IL-4 and IL-5, and improved airway hyperresponsiveness all comparable to Montelukast; these protective effects were thought to be due to reducing MMP-9 induction in lung tissue.
At least one study suggest fairly potent anti-allergic effects of the ethanolic extract of Hawthorn
In a test of alcohol-induced stomach ulcers, Crataegus pinnatifida ethanolic extract can exert anti-ulcer effects at oral doses of 50mg/kg (36% protection), 100mg/kg (68%) and 200mg/kg (88%); the highest dose being significantly more protective than 20mg/kg Ranitidine as active control (70%) and assuming 100% is no detected damage.
May be protective against stomach ulcers following oral ingestion
In studying 125-500mg/kg of the leaf extract of Crataegus pinnatifida, there appears to be a slight acceleration of small intestinal transit time (22% higher than control at 500mg/kg), which may merely be secondary to the potent anti-lipid absorption effects noted in this study; no influence on gastric digestive time was noted.
A Traditional Chinese Medicine mixture of herbs using Chinese Hawthorn, Astragalus membranaceus, Morus alba, Alisma orientale, Salvia miltiorrhiza, and Pueraria lobata (2:2:2:2:1:1 ratio) given to rats at 222, 667, or 2,000mg/kg bodyweight for the last four weeks of a 10 week trial of chronic daily alcohol consumption (45.5% of the diet) noted a reduction in liver weight that peaked at the 667mg/kg group (107mg/kg human dose) which was thought to be due to reduced triglyceride accumulation as a reduction in serum triglycerides and partial normalization of lipoproteins was noted; this decrease in hepatic lipids was confirmed with histological examination. Serum ALT (liver enzyme indicative of damage) was fully normalized at 667mg/kg while all doses tested reduced AST to below control levels.
May help alleviate alcohol-induced liver damage, but although the combination therapy is seemingly potent the exact role of Hawthorn in this is uncertain
A hot water extract of Crataegus pinnatifida (mostly catechin, epicatechin, and hyperoside at 1.5%, 0.6%, and 0.6% respectively) in mouse JB6P+ epidermal cells (a cell line used to assess tumor promotion) noted that the increase in tumor promotion by TPA was attenuated with incubation of this extract at 0.1mg/mL (58% inhibition), 0.25mg/mL (65%), or 0.5mg/mL (88%) without inherently affecting proliferation without TPA. This preventative effect was mediated by inhibition of AP-1 and NF-kB activation (proinflammatory proteins), attenuation of oxidation (with 0.5mg/mL reducing H2O2 by 95%) and this was thought to occur in vivo when 50-200mg/mL (in an acetone base) was topically applied to mice prior to TPA, which effectively abolished the increase in water retention from TPA and greatly improved histological examination of skin thickness.
Possibly potent topical anti-carcinogen, not yet compared to an active control
50mg/kg of Chinese Hawthorn extract given to otherwise normal rats orally appeared to induce hair growth on the backs of rats; this was associated with an induction of Anagen phase (indicative of prolonging hair growth rates) and a greater ratio of Bcl-2:Bax, indicative of cell preservation rather than apoptosis.
One of the few oral supplements that appears to induce hair growth; does not appear to be androgen related
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