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Tags: Food and Nutrition , Healthy Drinks , Healthy Eating Tips. Loading More Posts Featured Collection. Close Close. Larger, more robust clinical trials are needed to shed some light on this potential use.

In a clinical trial on 38 healthy people, drinking a beverage with added chlorogenic acids daily for 16 weeks improved performance in some cognitive functions motor and psychomotor speed, executive function, and shifting attention [ 49 ]. In mice treated with a neurotoxic drug scopolamine , chlorogenic acid improved short-term and working memory and reversed cognitive impairments by inhibiting acetylcholinesterase [ 18 ].

In mice and cultured brain cells, chlorogenic acid improved the survival of brain cells containing dopamine. Indeed, chlorogenic acid prevented the toxic effects of a protein involved in this condition alpha-synuclein in dopamine-containing brain cells [ 17 , 51 ].

Although the results are promising, most of the studies have been done in mice. Further clinical research is needed to determine if chlorogenic acid helps improve and preserve cognitive function. In a study of 45 people, gargling twice daily for 2 weeks using a green coffee bean extract mouthwash reduced the salivary concentration of a microbe that causes cavities and gum disease Streptococcus mutans [ 52 ].

This was caused by the inhibition of the bacterial enzyme sortase A [ 53 ]. Chlorogenic acid killed bacteria in test tubes by disrupting their bacterial membranes [ 54 ]. A single clinical trial and some animal and cell-based research cannot be considered conclusive evidence that chlorogenic acid helps with bacterial infections.

More clinical trials on larger populations are required to confirm these preliminary results. No clinical evidence supports the use of chlorogenic acid for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts.

However, the studies should not be interpreted as supportive of any health benefit. Multiple rodents and cell studies showed that chlorogenic acid exhibits antioxidant and anti-inflammatory properties [ 55 , 56 , 57 , 58 , 41 , 59 , 60 ].

The antioxidant activity may be attributed to the increased production of antioxidant proteins such as glutathione and vitamins C and E. Additionally, chlorogenic acid reduced oxidative stress by lowering the levels of oxidative proteins and reactive oxygen species [ 58 , 41 , 59 ]. Do not under any circumstances attempt to replace conventional cancer therapies with chlorogenic acid or any other supplements.

If you want to use it as a supportive measure, talk to your doctor to avoid any unexpected interactions. The topical application of chlorogenic acid prevented skin tumor growth in mice [ 62 ].

In mice fed high doses of bile acids, supplementing their diet with chlorogenic acid prevented the development of colon cancer [ 63 ]. Most of the studies examined the effects of green coffee bean extracts, which contain a number of other active molecules in addition to chlorogenic acid.

The specific contribution of chlorogenic acid to the effects observed is thus difficult to speculate. Further studies using chlorogenic acid alone are needed to conclusively establish its effects. Importantly, many studies were conducted in mice.

Further studies in humans are needed to validate their preliminary results. Although side effects have rarely been reported, many of the studies evaluated chlorogenic acid supplementation in the short term. Long-term testing is needed to assess the possible side effects. Furthermore, a number of studies, particularly on green coffee bean extract, were sponsored by companies commercializing this product.

The results are not necessarily invalid, but caution must be used when evaluating industry-funded research. This list does not cover all possible side effects.

Contact your doctor or pharmacist if you notice any other side effects. Call your doctor for medical advice about side effects. In the US, you may report side effects to the FDA at FDA or at www. In Canada, you may report side effects to Health Canada at Allergy to green coffee bean extract, the natural source of chlorogenic acid, has been reported.

Symptoms were primarily asthma attacks. However, coffee compounds other than chlorogenic acid seem to be responsible for this effect [ 69 , 70 ].

Because green coffee bean extract contains caffeine, it may cause some of its unwanted effects. You may want to avoid it late in the evening to prevent sleep disturbances. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.

Due to its potential blood pressure-lowering effect, chlorogenic acid may cause blood pressure to drop too low in people already taking medication with this effect.

Chlorogenic acid may enhance the effects of metformin , a medication used to treat high blood sugar levels. However, this effect was only observed at much higher concentrations than those achieved by human blood after chlorogenic acid consumption [ 71 ].

Consult your doctor if you are taking any drugs especially blood pressure-lowering and antidiabetic drugs before supplementing with chlorogenic acid. Because chlorogenic acid is not approved by the FDA for any condition, there is no official dose. Users and supplement manufacturers have established unofficial doses based on trial and error.

Discuss with your doctor if chlorogenic acid may be useful as a complementary approach in your case and which dose you should take. Different manufacturers produce green coffee bean supplements that may have more or less chlorogenic acid. The user-recommended dose for chlorogenic acid ranges from mg to 3, mg per day, depending on the specific supplement.

The opinions expressed in this section are solely those of chlorogenic acid users, who may or may not have medical or scientific training. Their reviews do not represent the opinions of SelfHacked. SelfHacked does not endorse any specific product, service, or treatment. Do not consider user experiences as medical advice.

Never delay or disregard seeking professional medical advice from your doctor or other qualified healthcare providers because of something you have read on SelfHacked. We understand that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.

The most common uses for the extract were to lose weight and to lower blood pressure. Many of the users were satisfied with the results obtained. The main adverse effects reported were anxiety , rapid heartbeat, and insomnia.

Note, however, that these effects are most likely due to the caffeine content of green coffee bean extract. Mild weight loss possibly due to both caffeine and chlorogenic acid was also reported by some users not taking chlorogenic acid for this purpose.

Health Benefits of Chlorogenic Acid. Animal and Cell Research Lack of Evidence. Oxidative and Inflammatory Stress. Joe Cohen flipped the script on conventional and alternative medicine… and it worked. Frustrated by the lack of good information and tools, Joe decided to embark on a learning journey to decode his DNA and track his biomarkers in search of better health.

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On the other hand, to investigate the composition of plants in the proper way the matrix solid-phase dispersion technique MSPD and its variant, the sea sand disruption method SSDM , are increasingly recommended Dawidowicz and Wianowska ; Dawidowicz et al.

The mechanism of ultrasounds in liquids relies in the mechanical effect caused by the implosion of cavitation bubbles generating macro-turbulence, high-velocity inter-particle collisions and perturbation in micro-porous particles of the natural materials which accelerates diffusion and enhances the mass transfer Srinath and Maheswari Due to the possibility of using these phenomena to reduce extraction time and increase yield of heat-sensitive compounds at lower processing temperatures, the increasing interests in application of ultrasounds to plants and plant products extraction have been observed Dent et al.

In addition, the ultrasound-assisted solvent extraction UASE technique provides the greater opportunity of enhancing its extraction ability. Apart from the careful choice of an appropriate solvent characteristic of the conventional techniques, the process can be further optimized and this is an important part of the UASE process.

During the optimization ultrasounds frequency, their amplitude, number of the applied extraction cycles, irradiation time and nominal output power are taken into consideration. It is worth noting that in addition to the low overall process temperature, the use of high-frequency sonication also reduces the degradation of compounds extracted from plants.

Another advantageous feature of UASE, that is equally important, is the cost of equipment necessary for the technique. The cost is low as the process is most often performed in ultrasonic baths being in each laboratory.

Yet the process can be realized in a different way applying an ultrasonic disintegrator. In this case the ultrasound emitting tip is directly immersed in the extraction mixture and the process is called the focused ultrasound assisted solvent extraction FUASE Tena et al.

FUASE, compared to UASE, by some researchers is considered to be even more reproducible and faster mainly due to a few times greater ultrasonic power Martinez-Moral and Tena It should be emphasized, however, that regardless of the extraction way, both variants can generate reactive oxygen species that they can cause degradation of some compounds and their lower concentrations in extracts if the sonication is continued over a long period.

This reduces the generation of oxidising species from the decomposition of water, because alcohols are much more stable in terms of homolytic cleavage.

The validity of this statement is confirmed by the following two examples documenting the relatively fast and effective isolation of 5-CQA from various matrices at room temperature. Li et al. During the experiments the influence of four extraction variables solvent type, its volume and concentration as well as extraction time on the yield of 5-CQA was examined.

An increase of extraction efficiency was also observed with the increase of the ratio of solvent volume to the sample the ratio of 20 was optimal and the number of extraction cycles. It was proved that, in comparison to the conventional extraction techniques, triplicate extraction of 5-CQA for 30 min using a fresh extractant each time reveals the highest 5-CQA yield.

The optimized UASE process was applied by the researchers for the extraction of 5-CQA from bark of E. ulmodies and four other traditional Chinese herbs and found that independently of the plant matrix type the isolation efficiency of UASE is very high and the obtained results highly reproducible.

Saleh et al. In this light, the advantages of using UASE to isolate CQAs from plants, also on an industrial scale, are clear. Not only the processing time is shorter at much lower costs, but also the extraction efficiency is higher due to preventing the thermal degradation of the compounds and guaranteeing the greater contact area between solid and liquid phase, compared with the traditional extraction methods.

The microwave assisted solvent extraction MASE is considered as a novel and alternative method for isolation of CQAs from plants and related products using microwave heating. The principle of microwave heating, conversely to the conventional heating, is based on direct absorption of microwave energy and its conversion into thermal energy when the microwaves are passed through the medium Eskilsson and Bjorklund ; Kaufmann and Christen The conversion of electromagnetic energy to heat occurs via two mechanisms, specifically, by dipole rotation and ionic conduction, i.

by means of reversal of dipoles and displacement of charged ions present in both the sample and the solvent. These two mechanisms usually occur simultaneously which converts microwave energy into thermal one effectively.

Dipole rotation takes place when the dipolar molecules attempt to follow the electric field in the same alignment. The induced oscillation leads to collisions between the dipoles and the surrounding molecules and thus creates heat. Ionic conduction refers to the migration of ions under the influence of the electric field produced by microwaves.

In this case heat is generated due to the resistance of the medium to flow ions Eskilsson and Bjorklund It should be added that in both mechanisms the generated thermal energy is immediately redistributed in the medium, which leads to homogeneous heating of the medium.

The MASE effectivity can be affected by a large variety of factors, such as frequency and power of microwaves, duration of microwaves irradiation, moisture content and particle size of plant samples, type and concentration of solvent, ratio of solid to liquid, extraction temperature and number of extraction cycles.

Of these factors, solvent is regarded to be one of the most important parameters, which affects not only the solubility of compounds but also the absorption of microwaves energy. The higher the dielectric constant and dielectric loss, the higher is the solvent capacity to absorb microwave energy and the faster solvent heating.

It should be added, however, that both polar and non-polar solvents can be used in MASE. Moreover, by combining solvents differing in their dielectric constant, the extractant properties and its selectivity can be modified.

Therefore, the isolation of the compounds from plants can be carried out without the need for the use of organic extractants, in the so-called solventless mode. Other advantages of MASE are improved extraction efficiency and shortened extraction time, resulting in decreased costs and environmental impact.

Due to these strong benefits, MASE is considered as a good alternative to traditional extraction processes of plant metabolites. A serious concern that might stand to be true when using MASE for CQAs isolation can be explained by the fact that the amount of microwave energy generated in the system can be sometimes so hight that it easily can cause a loss of thermally unstable compounds and consequently a decrease in their extraction efficiency.

The following examples show, however, that the skillfully conducted CQAs extraction process by MASE using the appropriate volume of water in several short extraction cycles can give a higher CQAs yield compared to the conventional extraction techniques.

The MASE applicability for CQAs extraction from green coffee beans was described in Upadhyay et al. During the investigations the influence of four extraction variables solvent type, extraction time, extraction temperature and microwave power on the extraction efficiency of 5-CQA was tested.

Among the examined solvents ethanol, methanol and water , water proved to be the best extractant giving the highest yield of 5-CQA. This is due to the fact that the dielectric constant and polarity of water are higher than those of the alcohols.

It was observed that extending the extraction time from 2 to 5 min resulted in the increased extraction efficiency. However further extension of the time resulted in reduction of 5-CQA yield.

Taking into account the effect of extraction temperature on the total CQAs yield, it was shown that the highest yield was obtained at the temperature of 50 °C. Finally, testing the effect of microwave power it was noticed that the total CQAs yield was increased with the increase the microwave power up to W.

Comparing the MASE results with those of the conventional extraction techniques, the authors concluded that the optimized MASE procedure isolates 5-CQA equally effectively as the conventional techniques. At the same time the authors stressed that the application of MASE reduced both time and solvent consumption.

Therefore MASE can be recognized as a more environmentally friendly process providing high quality extracts rich in CQAs. According to some researchers, the performance of MASE is highly influenced by the solid to liquid ratio.

Generally, a larger solvent volume can dissolve compounds of interest more effectively and lead to a higher extraction yield. As shown in Li et al. increased with the improvement of the solvent volume i. the reduction of the solid to liquid ratio.

The 5-CQA yield increased steadily when the plant mass was kept constant and the liquid volume was raised. That is to say, the extraction yield of plant constituents depends on how the solid to liquid ratio is regulated. Therefore in MASE the plant sample extraction is typically conducted in multiple steps, using the consecutive extraction cycles with a fresh portion of the extractant.

This practice helps to improve the extraction yield and prevents prolonged heating of the sample in the same solvent volume. In addition, the use of fresh portions of extractant prevents the saturation of the solvent with analytes, increasing their mass transfer and extraction kinetics Routray and Orsat In other words, MASE can extract compounds more rapidly, thus the heat-sensitive compounds are shortly exposed to potentially harmful conditions and in consequence, their yields can be higher in comparison to those obtained by the conventional extraction methods.

Pressurized liquid extraction PLE is known under different names, such as accelerated solvent extraction ASE , pressurized solvent extraction PSE , enhanced solvent extraction ESE , pressurized hot water extraction PHWE , subcritical water extraction or superheated water extraction SWE.

The technique has gained popularity due to its lower organic solvents consumption, and even their complete elimination, and significantly shorter extraction times required for full isolation of bioactive compounds from plants.

These are the reasons explaining also why it is described as a green extraction technique Mustafa and Turner In PLE a sample enclosed in the stainless steel extraction vessel is extracted in an inert atmosphere with a solvent at high pressure and at a temperature exceeding the boiling point of the solvent under the atmospheric pressure.

Due to the increase of solubility and mass transfer and, also decrease of viscosity and surface tension of solvents, higher extraction yields compared to the conventional extraction methods are observed. The technique has proven to be an equivalent or superior alternative to the extraction of different analytes from various matrices Carabias-Martinez et al.

For isolation of polar compounds PLE is also considered a potential technique alternative to the supercritical fluid extraction Kaufmann and Christen Alonso-Salces et al. No significant changes in the extraction efficiency of compounds were found studying the effect of extraction time and pressure.

However, according to Erdogan et al. This observation is consistent with the findings of other researchers Lou et al. In other cases, the pressure does not affect the extraction efficiency because the purpose of pressurizing the extraction vessel is to prevent the solvent from boiling at the extraction temperature and to ensure that the solvent remains in an intimate contact with the sample.

Luthria showed that not only the type of plant matrix but also the size of plant particles, the solid-to-liquid ratio, and especially the volume of extractant used to flush the extraction vessel after completion of the process so-called the flush volume affects the extraction yield of phenolics from the parsley flakes Petroselinum crispum Fuss.

One of the characteristics of PLE is to promote the use of water as an extractant of less polar bioactive compounds.

The efficiency of this approach is mainly affected by temperature as the polarity of water under pressure changes with temperature. At lower temperatures the water polarity is high but with the temperature increase it decreases so that the polarity of pressurized water resembles the polarity of polar organic liquids.

Due to the elimination of the use of organic solvents, this approach seems to be milder compared to conventional techniques, avoiding the production of artifacts. A more thorough analysis of the application of water under the PLE conditions for extraction of natural compounds reveals, however, that this approach is not free from drawbacks.

In Wianowska et al. In Dawidowicz and Typek it was found that heating of the 5-CQA water solution in the PLE apparatus leads even to formation of 4,5-dicaffeoylquinic acid and the presence of other isomers of dicaffeoylquinic acids cannot be excluded.

These examples indicate the need for a thorough qualitative and quantitative study of the composition of natural extracts not only at the final stage of extract production, but also at the initial stages of determining optimal extraction conditions.

This is important because due to the proven susceptibility of CQAs to the negative effects of high temperature, light, pH and the extractant type, it is not possible to find the PLE conditions under which the transformation of 5-CQA would be completely imposible.

The selection of optimal extraction conditions should be a compromise in conditions that guarantee the highest 5-CQA yield and the lowest amount of 5-CQA derivatives.

It seems that the best choice will be the use of a short-lasting PLE process, giving a lower number and quantity of CQA derivatives. At present, supercritical fluid extraction SFE is increasingly used in numerous industries applications including food decaffeination of coffee , pharmaceutical extraction of pharmacologically active substances , cosmetics obtaining essential oils and fuel.

This is due to the fact that the obtained extracts are free from all inorganic compounds. The relatively low temperature of the process does not cause degradation of proteins, vitamins and other active ingredients of the plant and thus does not reduce their health and organoleptic quality.

In addition, the entire process runs without air, the product obtained has no chance of undergoing any oxidative changes. SFE has several advantages over the conventional extraction techniques: it is a flexible process due to the possibility of adjustment of the solvent power or selectivity of the supercritical fluid SCF , it allows protection of polluting organic solvents, and it eliminates the expensive cost of postprocessing of the extract for solvent reduction.

SCF of any substance is present where the temperature and pressure are above its critical point, forming a homogenous phase with both liquid-like and gas-like properties. Due to its gas-like low viscosity and high diffusivity, a SCF, when used as a solvent, can easily penetrate plant materials with a rapid mass transfer rate.

In addition, the density of a SCF can be altered by adjusting the pressure and temperature, hence SCF density is said to be tunable. The most commonly used solvent in SFE is carbon dioxide CO 2 in its supercritical fluid state, due to the following factors: it is readily available, it is a reusable gas, and it has a low critical temperature of SFE, due to the chemical character of superctricial CO 2 , is a technique commonly used to extract non-polar pharmacologically active compounds from plants.

To isolate polar compounds, the SCF should be enriched with a suitable polar solvent so-called the co-solvent. The co-solvent effect is associated with the modification of intermolecular interactions forces and the increase in the density of extractants.

Azevedo et al. Experiments of Machmudah et al. These researchers proved that the counter-current extraction in flow mode is more effective compared to both batch and co-current extraction with CO 2. In Wu et al. This study showed that as far as the change in ethanol concentration and extraction pressure can significantly affect the recovery of chlorogenic acid, the temperature effect is negligible.

Chlorogenic acids are thermally unstable compounds, so the lack of temperature influence on the SFE process efficiency makes this method an attractive alternative to the conventional extraction techniques.

In the last few years, enzymatic extraction has gained research interest due to the fact that the method is completely ecologicall and the obtained extract is of high quality that allows it to be used for the production of medicines, dietary supplements and specialized cosmetics.

The basic principle of this method is that the enzymes hydrolyze the plant cell wall and disrupt it completely under optimum experimental conditions, to release components. Yet, this method in not free from drawbacks and the main problem is the selection of an appropriate enzyme that will enable the extraction of the desired compound.

In addition, the activity of enzymes is strictly dependent on the temperature and pH of the environment, thus these parameters must be constantly monitored during the process. As an example of the use of enzymatic process for the isolation of CQAs from natural materials, the work of Torres-Mancera et al.

The researchers proved that after a few hours stiring of coffee pulp with enzymes in darkness, at 40 °C chlorogenic acid can be effecivelly separated from the waste material using a small amount of ethyl acetate. As it was stated before for faster CQAs isolation from plants, temperature is usually applied.

Yet as it was proved in Wianowska et al. Thus the challenge in the CQAs analysis in plants is to obtain an extract whose composition would exactly reflect the true composition and concentrations of CQAs, so important for researchers studying plant metabolism.

Taking into account the fact that temperature is the main factor responsible for CQAs degradation, it would be more advantageous to use the extraction techniques at ambient temperature.

According to Dawidowicz and Wianowska , Wianowska et al. In addition, it is very simple, quick and cheap. More importantly, it proved to isolate effectively different compounds from various plant matrices. MSPD consist in direct mechanical blending of biological sample with the solid material i.

octadecyl modified silica C18 which helps to disrupt plant cells. After a few minutes of vigorous homogenization, the crushed plant material is transferred into a SPE tube and the released plant constituents are eluted with an appropriate eluent.

Instead of C18 sorbent, sand can be applied in the MSPD process. In this case the method is called the sea sand disruption method SSDM. There are many examples of procedures in which this method is successfully applied for release of various compounds from different plant matrices, including CQAs Teixeira and Da Costa ; Teixeira et al.

In addition, there are the examples proving that the amounts of compounds released by this method are higher than those revealed by the conventional approaches, although the reasons explaining this fact given by the authors are different.

Teixeira et al. leaves and proved that both SSDM and MSPD disclose higher extraction efficiency. According to the authors, higher MSPD and SSDM yields are due to better sample destruction which, by exposing the plant cell components to a solvent, tend to yield richer extracts.

Applying MSPD and PLE for the isolation of phenolics including CQAs from the field horsetail Equisetum arvense L. Oniszczuk et al. This statement, however, was not supported by experimental proves. and hawthorn Crataegus L. flowers, nettle Urtica dioica L. and yerba maté Ilex paraguariensis A.

Finally, it is worth mentioning that in addition to the C18 sorbent and sand, other materials are tested as dispersive agents. In Xu et al.

The results proved that the proposed method provides good precision and high recoveries of monoCQAs as well as diCQAs. Moreover, according to the authors, the method possesses many practical advantages, including rapidity, high sensitivity and less consumption of samples and organic solvents.

One of the typical problems of CQAs quantitative analysis in plants and plant products is the very limited number of commercially available standards of these compounds.

Moreover, some commercial standards are incorrectly described at a regio-isomer level Clifford et al. Therefore, to overcome this problem without compromising the quality of the results, two approaches are typically used.

In the first one the use of surrogate standards such as a green coffe extract or artichoke extracts characterized by LC—MS fragmentaion and relative retention times is considered. In the second, the compounds are isolated from plant extracts by different chromatographic procedures, and then subjected to meticulous purification.

Romero-Gonzalez and Verpoorte studied the application of centrifugal partition chromatography with gradual reduction of the ionic strength of the mobile phase in order to separate the various CQAs subfamilies present in green coffee beans extracts in the reversed-phase mode.

According to the authors the manipulation of electrostriction in an aqueous solution, by changing the concentration of one or more salts, can constitute an effective method of performing a reversed-phase-like gradient elution in counter-current separations.

Owing to the proposed salting-out gradients is possible the fast single-column elution of single compounds largely differing in their distribution constants without experiencing significant column bleeding.

There are many analytical methods to identify and quantify chlorogenic acids in natural samples. According to our knowledge, however, there are no official and universally accepted methods of CQAs analysis. Therefore many laboratories develop and validate their own analysis methods, All the more that depending on the analytical technique chosen different approaches to sample preparation can be considered and, as it was stated before, nowadays there is a tendency to replace the conventional extraction techniques by newer and more effective processes.

It should be also remembered that even when using the same analytical technique, different equipment and different settings can be selected. A great example of how the change of apparatus can change the result of the CQAs analysis of the same sample carried out even by the same methodology in different laboratories is the work of Craig et al.

The fact that CQAs constitute a large family of compounds with various properties present in natural samples on different concentration levels, makes their analysis additionally more difficult.

Hence, frequently in the course of single run, only a few CQAs representatives with very similar properties are analyzed, for example monoCQAs or diCQAs, and even an individual compound i. Yet due to the application of modern highly selective, sensitive and accurate analytical techniques, this trend begins to change slowly towards the analysis of large numbers of CQAs in one single run.

The examples of currently applied methods of CQAs analysis are summarized in Table 1. They show that liquid chromatography LC and capillary electrophoresis CE with different detection systems are the most commonly applied.

Guan et al. In this method the laboratory-built CE-ED system was used. The inlet end of the capillary was held at a positive potential, and the outlet end was maintained at ground. All samples were injected electrokinetically, applying 18 kV for 6 s.

A three-electrode cell system consisting of a carbon-disk working electrode, a platinum auxiliary electrode, and a SCE saturated calomel electrode reference electrode was used in combination with amperometric detector.

By the migration time of the analyte as compared with the electropherogram of the standard solution, the active ingredient in the sweet potato samples can be identified and quantitatively determined.

The results obtained by Guan et al. Jiang et al. In the procedure the analyte zone after being separated by capillary electrophoresis was determined by indirect chemiluminescence of luminol—potassium hexacyanoferrate. In this system luminal was added into the running buffer solution and introduced at the head of separation quartz capillary, and potassium hexacyanoferrate was introduced at the end of capillary.

According to the authors, the proposed capillary electrophoresis-chemiluminescence system can avoid the electrolysis of chemiluminescence reagent, retain the stability of chemiluminescence baseline and prolong the working time of running and electrode buffer solutions.

A special mode of capillary electrophoresis employing a microemulsion as a carrier electrolyte, so-called the microemulsion electrokinetic chromatography MEEKC method, in which analytes can partition between the aqueous phase of microemulsion and its oil droplets acting as a pseudostationary phase, was employed by Tang et al.

The proposed MEEKC procedure with the PDA detection at nm, with the addition of tartrate for improving separation efficiency, was sufficient for separation and quantification of three monoCQAs and four diCQAs within 22 min.

Citing the authors of the report, the method proposed by them can be extensively used to determine individual CQA isomers in the honeysuckle or its preparations, and can provide more references for the quality evaluation and control of CQA related products. Another modification of capillary electrophoresis i.

micellar electrokinetic chromatography MEKC , in which the samples are separated by differential partitioning between the micelles pseudostationary phase and the surrounding aqueous buffer solution acting as a mobile phase, was proposed by Risso et al.

The electrophoretic conditions consisted of the sodium dodecyl sulphate SDS 70 mM -phosphate The separations were made on a fused-silica capillary with the effective and total lengths of The method was tested with both green and roasted coffee beans, and in both cases it was proved to be effective and selective.

According to the authors of the paper, the method can be used to monitor the presence of mono-CQA isomers in both natural and processed vegetables.

Numerous papers have been published on qualitative and quantitative analysis of CQAs in plants by liquid chromatography LC coupled with the spectroscopic detection techniques, such as ultraviolet UV , fluorescence FL nuclear magnetic resonance NMR and mass spectroscopy MS , and even near-infrared NIR spectroscopy.

Nowadays, the commonly observed trend of improving analytical abilities consists in using couplings with more than one separation and detection technique, e.

LC—UV—MS, LC—MS—MS, LC—NMR—MS, and the like Jaiswal et al. In the case of plants in which CQAs are present on low concentration levels, and their precise analysis is essential, more integrated and sophisticated systems are applied that couple on-line the process of CQAs extraction with their analysis e.

focused ultrasound solid—liquid extraction FUSLE coupled to LC—MS FUSLE—LC—MS Tena et al. High-performance liquid chromatography HPLC is the most widely used analytical separation technique of CQAs. Though the more advanced form of LC i.

ultra-performance liquid chromatography UPLC utilizing a submicron analytical column becomes increasingly popular for the determination of plant extract compounds, due to the improved resolution there are obtained shorter retention times and higher sensitivity Shen et al.

In general, LC separations of CQAs are performed by the reversed phase system see Table 1. The most commonly applied columns are based on C18 stationary phases 0. A typical mobile phase consists of mixtures of methanol and water.

The data useful for identification of CQAs by means of LC are collected in Table 2. It should be remembered, however, that only a few CQAs standards are available commercially, and the precise analysis of the individual CQAs by means of conventional LC—DAD PDA systems is not easy due to the difficulty of distinguishing between the positional isomers especially when they are present at low concentrations.

Hence, nowadays most laboratories prefer the use of MS systems, and especially tandem MS, due to their higher selectivity and sensitivity. In order to improve the ionization capacity, formic acid is frequently added to the mobile phase comprising methanol as the organic modifier see Table 1.

Ionization is usually performed by electrospray ionization ESI source working in the negative and positive mode. Only one paper Lai et al. Regardless of the type of ionization source, for negative mode ionization, the optimal mobile phases descibed in the literature contain a lower concentrations of formic acid typically 0.

Comparing the sensitivity of both ionization modes, due to reduced chemical noise in the negative ionization mode, this mode is more sensitive than positive ionization. This is why the ESI ionization source, the most sensitive of all atmospheric pressure ionisation sources, typically operates in the negative mode.

The correctness of this statement is confirmed by the data comparing the CQAs ionization efficiency of ESI and APCI in both positive and negative mode Lai et al. For most MS applications for CQAs analysis see Table 1 , the tandem MS worked under relatively high collision energy conditions to 47 eV to generate second order mass spectra.

As for the most common MS analysers in the LC-based methods for the CQAs analysis in plants these are ion trap IP , triple quadrupole TQD and time of flight TOF Brolis et al. Tandem MS is very convenient for performing mass spectrometric quantification and identity confirmation, as it enables analysis in the mode of Selected Reaction Monitoring SRM , also called Multiple Reaction Monitoring MRM.

Typically 2 or 3 MRM transitions are selected for the analite. One transition so-called the precursor ion is selected for quantification, the additional ones so-called the products ions for confirmation purposes. As both precursor ion and products ions are specified and monitored, higly selective quantitative analysis that is low in unwanted compounds can be achieved compared to single ion monitoring.

Therefore the tandem MS analysis in MRM mode is ideal for sensitive and specific quantitation of a compound in very complex plant matrices. There are many papers dealing with the application of liquid chromatography—multi-stage spectrometric identification systems LC—MS n for qualitative and quantitative CQAs analysis in plant materials.

An example can be paper Paya et al. The team investigating the fragmentation behavior of 18 CQAs, that are not substituted at position 1, proved that the fragmentation patterns of chlorogenic acids are dependent upon the particular stereochemical relationships between the individual substituents on the quinic acid moiety Clifford et al.

In reference to the obtained results the authors stated that it is possible to discriminate between each of three isomers of p-coumaroylquinic acid, caffeoylquinic acid, feruloylquinic acid and dicaffeoylquinic acid.

More importantly, on the basis of the obtained information on fragmentation patterns, the authors have prepared a hierarchical key, which has become a tool widely used by scientists to facilitate the identification process of chlorogenic acids derivatives and conjugates when standards are not available.

The LC—MS n identification scheme of mono- and diacylochlorogenic acids is illustrated in Fig. The key stages of this protocol are as follows Clifford et al. In Clifford et al.

Using this protocol and LC—MS 4 the authors revealed that the caffeoyl residue at position 1 is the easiest to take apart from the molecule during fragmentation, followed by residues at positions 5, 3 and 4.

Nevertheless the MS fragmentation is insufficient to distinguish 1-CQA from 5-CQA. However, the greater hydrophobicity of 5-CQA and its commercial availability ensure that these two isomers can be distinguished by the retention time on the reversed phase columns.

Later the hierarchical key has been extended further for identification of 3,4,5-triacyl chlorogenic acids by Jaiswal and Kuhnert Due to the introduction of simple guidelines for regioisomer assignment, based on the successive sequencing of acyl fragmentation the researchers were able to determine eight quantitatively minor triacyl chlorogenic acids, most of which were not reported in nature previously.

Finally it was reported in Clifford et al. There are many reports Clifford et al. In the applied system a LC chromatograph with DAD was interfaced with an ion-trap mass spectrometer fitted with an ESI source operating in full scan. Using this method it was possible to distinguish twenty-nine chlorogenic acids.

Twenty-four of these twenty-nine CQAs were detected for the first time in this plant. Fourteen of them were not previously reported from any source. flower buds. Among the identified compounds there were three isomers each of p -coumaroylquinic acid, caffeoylquinic acid, feruloylquinic acid, dicaffeoylquinic acid and diferuloylquinic acid, and six isomers each of p -coumaroyl-caffeoylquinic acid, p -coumaroyl-feruloylquinic acid and caffeoylferuloylquinic acid.

Three of the six p -coumaroyl-feruloylquinic acids were not observed in nature previously. The same team of researchers profiled qualitatively herbal chrysanthemum by LC—MS 5 Clifford et al.

Besides partial characterization of minor components suggested the presence of five caffeoyl-hexose esters and caffeic acidβ- d -glucose, and eight caffeoylquinic acid glycosides and 16 dicaffeoylquinic acid glycosides that were not reported in nature previously. Studies on the CQAs composition in burdock roots Arctium lappa L.

described in Jaiswal et al. In reference to the results, the authors stated that despite revealing the significant differences in the MS fragmentation patterns of all CQAs regioisomers, the structure-diagnostic hierarchical keys that have been developed based on fragmentation preferences induced by characteristic hydrogen bonding arrays within the gas phase ions of CQAs in tandem MS spectra, UV spectrum, retention times, and relative hydrophobicity, are very useful tools for the identification of chlorogenic acids in the complex plant matrices.

The objective of this review paper is to give an overview of occurrence, properties, and methods that have been developed to improve the extraction and analysis of chlorogenic acids in plants and related products, with special attention paid to 5-O-caffeoylquinic acid as the compound of the chlorogenic acids family with many beneficial health effects.

Due to the potential biological activity of these compounds, recently there has been an increased interest in natural products rich in chlorogenic acids.

Consequently, more efficient extraction methods, leading to getting extracts with the enhanced CQAs content and the reduced content of their degradation products, are being sought.

On the other hand, taking into account the application of CQAs as pharmaceutical and food additives, the great structural similarity of CQAs and the deficiency of reference standards, more efficient and reliable analytical methods are constantly sought, in order to identify them exactly, especially when they are present at low concentrations in complex mixtures.

In the last few years a number of improvements in the strategy of extraction and analysis of CQAs in different natural samples was achieved. The application of newer, faster, more efficient and sophisticated extraction techniques, such as UASE, MASE, SFE or PLE, improved significantly the extraction yield of CQAs with significant reduction of organic solvents consumption.

The overall quality of the extracts was also improved. In addition, this resulted in reduction of manipulation errors, and in consequence, it led to improved reproducibility and repeatability of the analytical methods.

There are no official and universally accepted methods of CQAs analysis in plants and related products. The large number of compounds belonging to the CQAs family and the fact that these methods need to be applicable to many various plants make this desire difficult to accomplish.

Nevertheless nowadays two analytical techniques commonly applied for the analytical separation of CQAs can be distinguished.

These are capillary electrophoresis and liquid chromatography. This statement is supported by the fact that recently developed LC—MS n protocols, based on the determination of the same fragment ions belonging to similar structures of compounds forming the family so-called the fragmentation patterns , greatly facilitated CQAs identification without the need to isolate pure compounds.

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Also known by the trade name Benicar. All Rights Reserved. Privacy Policy. You are here: Welcome to the MPKB » Welcome to the MPKB » Health, food and drink » Chlorogenic acid. Table of Contents Foods with chlorogenic acid. MP patients should limit their daily coffee consumption to no more than two cups per day.

Teas Chocolate Health benefits of methylxanthines in cacao and chocolate. Chlorogenic acid and other things that affect immunopathology — discussion on the Marshall Protocol available to members and registered professionals online forum led by Joyce Waterhouse, PhD.

Food and drink , foods to avoid , drinks , IP. Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans. Am J Clin Nutr. doi: Pharmacologic immunosuppression of mononuclear phagocyte phagocytosis by caffeine.

Pharmacol Res Perspect. eCollection Dec. Quercetin, not caffeine, is a major neuroprotective component in coffee. Neurobiol Aging. Epub Jul 5. Bacteria-host communication: the language of hormones.

Proc Natl Acad Sci U S A. Epub Jul 7.