Artichoke Extract

Artichoke Extract is a term used to refer to plant extracts from Cynara Scolymus, and apparently has a short history of medicinal use to treat dyspepsia (related to its choleretic effects)^[1] for gout,^[2] and for anti-diabetic actions.^[3] It should be noted that Cynara Scolymus is referring to Globe Artichoke, a perennial thistle of the Asteraceae plant family, and that this is the same plant bulb (capitlua) that is commonly eaten as a vegetable in North America, Europe, and the Mediterranean.^[4][5]

Other 'Artichokes' include Stachys affinis (Chinese Artichoke) Helianthus tuberosus (Jerusalem Artichoke), the latter of which is also a food product but is a tuber (resembling a Yucca, or a Potatoe covered in tree bark).

Artichoke extract refers to the species Cynara Scolymus, which is the same as the edible Artichoke commonly eaten as a vegetable in the west

Artichoke extract contains:

• Luteolin (27.71-215.52mg/kg) and the glycoside Luteolin-7-O-Glucopyranoside, the latter being known as Cynaroside.^[6] These two are seen as the active Luteolin compounds, and are named after Cynara due to this
• Other Luteolin compounds such as Luteolin 7-O-rutinoside, Luteolin 7-O-glucoside, and Luteolin 7-O-glucuronide;^[4] all Luteolin compounds collectively range from 24.6-73.8g/kg, or 2.5-7.4% (variance depending on cultivar) and most being 7-O-glucoside^[4]
• Caffeoylquinic acids including Cynarin (aka. 1,3-dicaffeoylquinic acid)^[6] and others such as 1-O-caffeoylquinic acid, 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, 5-O-caffeoylquinic acid, and Caffeic acid.^[4] Total caffeoylquinic acids range from 3139.02-7270.11mg/kg (0.3-0.7%)^[4]
• Chlorogenic Acid (aka. 5-O-caffeoylquinic acid)^[7][6] ranging from 106.39-423.94mg/kg (0.01-0.04%)^[4]
• Apigenin (as 7-O-glucuronide, 7-O-glucoside, and 7-O-rutinoside)^[4] with total Apigenin compounds ranging from 43.74-6477.68mg/kg (0.004-0.650%)^[4]
• Sterols including Beta-Sitosterol, Stigmaterol, and Campesterol^[8]
• If the fiber component is not removed, then an Inulin content^[9] of 30.6-36.7% dry weight.^[10]
• If not otherwise removed, a mineral content including Potassium (14.1-25.3g/kg), Magnesium (0.8-2g/kg), Calcium (3.1-5.5g/kg), and Sodium (0.8-2.6g/kg); all highly affected by genotype, cultivar, and season^[11]
• Microminerals of Zinc (16.7-40.4mg/kg), Copper (4.7-10.5mg/kg), Manganese (8.5-14mg/kg), and Iron (34.3-82.2mg/kg)^[11]

The total phenolic content of Artichoke is actually higher in the leaves than in the head (edible capitula).^[4]

Luteolin and Caffeoylquinic acids are seen as the main bioactives of Artichoke extract

Some studies have investigated the effects of Artichoke Extract and its ability to reduce food intake, usually in combination with Phaseolus Vulgaris (White Kidney Bean Extract), where Artichoke appears to be ineffective while the latter is somewhat effective at reducing food intake.^[12] This inefficacy with Artichoke Extract has been noted elsewhere.^[13]

The combination of the two extracts has been shown to reduce food intake in obese (BMI greater than 35) persons without highly abnormal health parameters. When subjects were prompted to adhere to a caloric limit each day, those given 100mg White Kidney Bean Extract and 200mg Artichoke (BONVIT® at 30-60% caffeoylquinic acid) over 8 weeks where the supplemented group reported less hunger which may have underlied improvements in glucose levels and BMI.^[14]

Does not appear to reduce voluntary food intake in rodents, and is confounded in some research where White Kidney Bean Extract does so

Artichoke extract appears to induce secretion of cholephilic compounds bile canaliculi,^[15] which then leads to accumulation of bile acids in the intestines.^[1] This increase of bile acids in the intestines has been demonstrated (in rodents) to be the cause of cholesterol reducing effects associated with artichokes.^[16]

In rats given 100, 200, or 400mg/kg Artichoke extract (80% bioactives), bile flow into the intestines appears to be increased in a dose-dependent manner. In comparison to 20mg/kg Dehydocholic acid (DHCA), 400mg/kg was not significantly different, 100mg/kg was not significantly different than control, and 200mg/kg was in between.^[1]

The mechanism underlying cholesterol-reducing effects of Artichoke seem to be its bile acid secreting effects, which simultaneously reduce plasma cholesterol and increase fatty acid absorption (both due to increased intestinal fatty acids)

Artichoke, at 0.25ng/mL, appears to inhibit the HMG-CoA reductase enzyme by approximately 30% (with Atorvastatin as active control reducing activity by 50% at this concentration).^[17]

Artichoke extract at 26mg/kg in rats (1.6g human dose) was unable to acutely reduced the spike in triglycerides from Pluronic F-127 and in response to a 10-day high fat diet in rats it also appeared to fail in isolation.^[17] When artichoke was paired with turmeric (contains curcumin) and Prickly Pear at 80mg/kg and 22mg/kg (5.6 and 1.5g human doses), however, the combination appeared to rival Atorvastatin (statin drug) at 10mg/kg on all serum parameters; adding garlic to the mixture did not provide further benefit.^[17]

Lacklustre results in rats given oral Artichoke extract in isolation; combination therapy may be more effective

In human interventions, a study of 18 moderately hyperlipidemic patients consuming the juice made from artichoke leaves (20mL; 2.5% fiber, 0.7% glucydes) in conjunction with a standard hypolipidemic diet for 6 weeks reported an increase in triglycerides associated with treatment only and a decrease in total cholesterol and LDL-C that occured in both groups (due to the diet intervention).^[18] In comparison to this low dose study, one study using a 450mg Extract capsule (25-35:1 concentration) four times daily (1,800mg total) in persons with high cholesterol (7.3mmol/L or more) was associated with an 18.6% reduction in total cholesterol, 22.9% reduction in LDL-C, and no significant influence on either HDL-C (despite the ratio being improved) or Triglycerides.^[19] A third study (double-blind) with 1280mg Artichoke extract also suggests cholesterol reducing properties with 75 adults with high cholesterol over 12 weeks, but only the difference between artichoke (4.2% reduction) and placebo (2% increase) was significant; the reduction of total cholesterol from baseline to final was not significant, nor was any alteration in LDL-C, HDL-C, or triglycerides.^[20] This latter study used 1280mg of a 4-6:1 extract, so it is possible it was underdosed.

Only one study has currently noted increases in HDL-C with 500mg Artichoke extract,^[21] which is in contrast to previous studies using both lower^[18] and higher^[19][20] doses. Similar to this, only one study has been conducted noting a reduction in triglycerides, where 15 diabetics given 6g artichoke powder hidden in crackers experienced a 10% reduction in triglycerides after 90 days;^[22] all other studies note either no net effect or an increase in triglycerides (according to one study^[18]).

Summarizing all the above, a Cochrane Meta-anlaysis on the topic was only able to find 3 studies fitting inclusion criteria and deemed the ability of Artichoke extract to reduce cholesterol levels preliminary but promising.^[23]

Appears to have potential to reduce circulating cholesterol levels, but relative to other compounds the body of literature is quite small. The potency of Artichoke Extract is minimal, even at higher doses, and seems unreliable

Flavonoids from Artichoke appear to be able to increase iNOS gene expression in human endothelial cells,failing to acutely increase NO production in vitro and instead requiring a prolonged incubation time.^[6] These benefits appeared to come mostly from Luteolin and its glycoside, Luteolin-7-O-glucopyranoside.^[6]

In vitro, Artichoke extracts have been shown to prevent oxidation of LDL (into oLDL)^[24] and reduce the oxidative effects of oLDL on the endothelium and immune cells (monocytes) in vitro.^[25]

Mechanistically, Artichoke flavonoids appear to induce Nitric Oxide and exert anti-oxidative properties

6 week consumption of artichoke juice in conjunction with a standard AHA hypolipidemic diet recorded decreases in VCAM-1 and ICAM-1 (30.3% and 16.8%) with no change in E-selectin, these changes were accompanied by an increase in blood flow (36%) despite no significant changes in lipoproteins.^[18]

Has been shown to increased blood flow, suggesting the above mechanisms are relevant after oral ingestion

Rats fed 500, 1000, or 1500mg/kg Artichoke extract (from flowering buds) one hour prior to an oral glucose tolerance test was able to reduce subsequent glycemia for 6 hours post-ingestion (with the increase being attenuated 24%, 29.5%, and 41% respectively); thin mice found benefit with all doses whereas obese mice required the highest dose.^[26] Similar results have been shown in humans, where boiled artichoke seems to reduce postprandial (after meal) glucose spikes in healthy controls while it was much less effective in persons with metabolic syndrome; this study was conducted with a related species of Artichoke (cardunculus rather than scolymus).^[27]

Acutely, Artichoke may reduce glucose spikes after a meal with more efficacy in lean individuals and much less in obese persons; reasons unknown

Another human study does note a reduction in glucose after 12 weeks of consuming 200mg Artichoke extract, but aside from being confounded with White Kidney Bean Extract it also reported weight loss due to appetite reduction (known to reduce blood glucose inherently)^[14] which mimicks previous animal research with the two compounds.^[12] The only other chronic studies not confounded with White Kidney Bean are one in type II diabetic persons, 6g of Artichoke powder (hidden in wheat crackers) was given for 90 days and associated with a 15% reduction in fasting glucose and 7.9% reduction in postprandial glucose relative to control^[22] and another where glucose was measured after supplementation with 1800mg 25-35:1 concentrated extract and no reductions were noted in hyperlipidemics.^[19]

Studies looking at long-term artichoke usage and glycemia are too hetereogeneous to come to conclusions, but it does not seem too promising

Artichoke extract appears to induce secretion of cholephilic compounds bile canaliculi,^[15] which then leads to accumulation of bile acids in the intestines.^[1]

In the colon, Inulin (a dietary fiber extracted from species of Artichoke) is able to proliferate the bacteria in the colon. Artichoke bacteria tends to have Inulins with a very high degree of polymerization relative to other Inulins^[28] (since 'Inulins' tend to have a chain length of 2-60) and have been reported to have a degree of polymerization of up to 200.^[29] Ingestion of 10g Inulin from Artichoke daily (average degree of polymerization of 55 or more) for 3 weeks in a sample of otherwise healthy persons was associated with an increase in colonic _Bifido_bacterium (2.82-fold increase) and, although attenuated, still persisted after cessation of dietary Inulin.^[9] An alteration in short-chain fatty acids (SCFAs) was also noted with Inulin ingestion, but these were not statistically significant.^[9]

The fiber component of Artichoke extract (not the polyphenols, fiber may not be in concentrated extracts) appears to have prebiotic properties

One study in persons with high cholesterol has noted decreases in liver enzymes associated with high dose (1,800mg of a 25-35:1 concentrated extract) of artichoke, where over 45 days a decrease was seen for y-GT (25.8%), AST (17.3%), and ALT (15.2%) with no influence on GLDH.^[19]

One in vitro study using the MDA-MB231 breast cancer cell line noted that the polyphenols of Artichoke (1/1 water/ethanolic extract of mostly caffeoylquinic acids) was able to induce 60% apoptosis at 600uM concentration over 24 hours; lower but significant degrees of cytotoxicity were seen in n BT549, T47D, and MCF-7 cancer cell lines but not MCF10A normal breast epithelial cells.^[30] 400uM abolished cell proliferation in MDA-MB231 cells over 6 days and reduced the invasive potential of these cells, and these effects were thought to be mediated via the chlorogenic acid content of Artichoke.^[30]

The active luteolin compounds are thought to be pro-erectile due to PDE5 inhibition, the mechanism of action of Viagra. Luteolin is a high affinity phosphodiesterase (PDE) inhibitor, but is non-selective and affects all 5 isozymes of PDE.^[32] The affinity for PDE4 in displacing other agonists (Rolipram) appears to have an EC₅₀ of 11.2uM^[32] and a previous study looking at IC₅₀ studies for inhibition noted that all isozymes had an IC₅₀ of around 10-20uM with Luteolin^[33] where the prevalent glycoside in Artichoke extract (Luteolin-7-Glucoside) inhibited mostly PDE2 and PDE4 with a weaker IC₅₀ of 40uM.^[33]

Although Luteolin compounds appear to inhibit the phosphodiesterase class of enzymes, it is not a specific inhibition of PDE5 (One of the mechanisms of action of Viagra) and less than desirable for a pro-erectile agent

UV rays (sunlight) tend to inherently damage melanin and protein constituents of hair follicles (correlated with color and structure of hair, respectively)^[34] which is thought to be mediated by an induction of oxidation (Reactive Oxygen Species; ROS) damaging sulfur linkages of proteins,^[35] inducing lipid peroxidation,^[36] and degrading melanin.^[37] These changes can be abrogated with anti-oxidant compounds, and this has been seen in vitro when hair follicles were treated with a shampoo-like solution containing Artichoke extract at 5%.^[38]

May protect hair from UV damage, but this may not be a unique effect of Artichoke and merely an effect of anti-oxidants in general

One in vitro study investigating DNA damage induced by ethyl methanesulfonate (EMS; known genotoxic agent) and assessed by comet assay (to detect DNA damage^[39][40]) noted that 0.62-5mg/mL was able to induce genetic damage in Chinese Hamster Ovarian (CHO) cells, with 5 mg/mL not being significantly different than 350uM EMS.^[41]

When incubated either before or after EMS, Artichoke extract appears to nonsignificantly enhance genotoxicity; when coincubated, 0.62mg/mL is associated with a 77% reduction of EMS-induced genotoxicity; suggesting competition at the genome (1.25 and 2.5mg/mL reducing genotoxicity by 17 and24.6%, respectively).^[41]

Interacts with DNA. Practical relevance of these results unknown