Dicaffeoylquinic Acid Derivatives Research Articles

Light-Emitting Diodes and Liquid System Affect the Caffeoylquinic Acid Derivative and Flavonoid Production and Shoot Growth of Rhaponticum carthamoides (Willd.) Iljin.

Plant in vitro cultures can be an effective tool in obtaining desired specialized metabolites. The purpose of this study was to evaluate the effect of light-emitting diodes (LEDs) on phenolic compounds in Rhaponticum carthamoides shoots cultured in vitro. R. carthamoides is an endemic and medicinal plant at risk of extinction due to the massive harvesting of its roots and rhizomes from the natural environment. The shoots were cultured on an agar-solidified and liquid-agitated Murashige and Skoog's medium supplemented with 0.1 mg/L of indole-3-acetic acid (IAA) and 0.5 mg/L of 6-benzyladenine (BA). The effect of the medium and different treatments of LED lights (blue (BL), red (RL), white (WL), and a combination of red and blue (R:BL; 7:3)) on R. carthamoides shoot growth and its biosynthetic potential was observed. Medium type and the duration of LED light exposure did not affect the proliferation rate of shoots, but they altered the shoot morphology and specialized metabolite accumulation. The liquid medium and BL light were the most beneficial for the caffeoylquinic acid derivatives (CQAs) production, shoot growth, and biomass increment. The liquid medium and BL light enhanced the content of the sum of all identified CQAs (6 mg/g DW) about three-fold compared to WL light and control, fluorescent lamps. HPLC-UV analysis confirmed that chlorogenic acid (5-CQA) was the primary compound in shoot extracts regardless of the type of culture and the light conditions (1.19-3.25 mg/g DW), with the highest level under R:BL light. BL and RL lights were equally effective. The abundant component was also 3,5-di-O-caffeoylquinic acid, accompanied by 4,5-di-O-caffeoylquinic acid, a tentatively identified dicaffeoylquinic acid derivative, and a tricaffeoylquinic acid derivative 2, the contents of which depended on the LED light conditions.

Correction to: Insulin secretion and α-glucosidase inhibitory effects of dicaffeoylquinic acid derivatives

Correction to: Insulin secretion and α-glucosidase inhibitory effects of dicaffeoylquinic acid derivatives

Insulin secretion and \u03b1-glucosidase inhibitory effects of dicaffeoylquinic acid derivatives

In this study, we investigated the effects of dicaffeoylquinic acid derivatives, including 1,4-di-O-caffeoylquinic acid (1,4-DCQA), 3,4-di-O-caffeoylquinic acid (3,4-DCQA), 3,5-di-O-caffeoylquinic acid (3,5-DCQA), 4,5-di-O-caffeoylquinic acid (4,5-DCQA), and 1,5-di-O-caffeoylquinic acid (1,5-DCQA) on glucose-stimulated insulin secretion (GSIS) activity and α-glucosidase activity were compared in rat INS-1 pancreatic β-cells. The α-glucosidase inhibitory activities of dicaffeoylquinic acid derivatives were as follows: 1,4-DCQA > 1,5-DCQA > 3,4-DCQA > 4,5-DCQA > 3,5-DCQA. In INS-1 cells, dicaffeoylquinic acid derivatives showed no cytotoxic effect at any concentration (2.5–10 μM). In addition, the GSIS activities of dicaffeoylquinic acid derivatives were as follows: 4,5-DCQA > 3,4-DCQA > 1,4-DCQA > 3,5-DCQA > 1,5-DCQA. Treatment of INS-1 cells with 4,5-DCQA resulted in a marked increase in protein expression of extracellular signal-regulated protein kinases (ERK), insulin receptor substrate-2 (P-IRS-2), Akt, phosphoinositide 3-kinase (P-PI3K), and pancreatic and duodenal homeobox-1 (PDX-1), which might be related to its GSIS activity in INS-1 cells. These findings indicate that the location of the dicaffeoyl functional group influences the anti-diabetic activity of quinic acid.

Developed validation for simultaneous determination of three Di-caffeoylquinic acid derivatives from the Leaf of Eribotrya japonica Lindl. by HPLC-DAD

The aim of this study was to developed HPLC simultaneous analysis method for the determination of Caffeoylquinic acid isolated from the leaf of Eribotrya japonica Lindl. extract. The phenolic compounds in E. japonica leaves were isolated and identified by HPLC, NMR, Mass etc. The quantitative analysis was carried out HPLC-DAD using C18 column with gradient elution of water and acetonitrile at 280 nM for 60 min. The method was successfully validated by specificity, LOD (linearity, limit of detection), LOQ (limit of quantification), precision and recovery. The three phenolic compounds were isolated from E. japonica leaves including 5-Caffeoylquinic acid (5-CQA), 4-Caffeoylquinic acid (4-CQA) and 3-Caffeoylquinic acid (3-CQA). In a quantitative analysis of three phenolic compounds were 3-CQA 7.82-14.48 µg/mL, 4-CQA 3.75-12.58 µg/mL and 5-CQA 3.60-7.82 µg/mL using the standard chemicals, respectively. The developed HPLC validation method would be applicable for simultaneous quantitative analysis of phenolic compounds in E. japonica leaves extracts.

Identification of Mushroom and Murine Tyrosinase Inhibitors from Achillea biebersteinii Afan. Extract.

Growing scientific evidence indicates that Achillea biebersteinii is a valuable source of active ingredients with potential cosmetic applications. However, the data on its composition and pharmacological properties are still insufficient. This study aims to optimize the extraction procedure of the plant material, evaluate its phytochemical composition, and compare anti-tyrosinase potential of A. biebersteinii extracts obtained by various methods. In order to identify compounds responsible for the tyrosinase inhibitory activity of A. biebersteinii, the most active anti-tyrosinase extract was fractionated by column chromatography. The fractions were examined for their skin lightening potential by mushroom and murine tyrosinase inhibitory assays and melanin release assay. HPLC-ESI-Q-TOF-MS/MS analysis of the total extract revealed the presence of several phenolic acids, flavonoids, flavonoid glucosides, and carboxylic acid. Among them, fraxetin-8-O-glucoside, quercetin-O-glucopyranose, schaftoside/isoschaftoside, gmelinin B, 1,3-dicaffeoylquinic acid (1,3-DCQA), and ferulic acid were found in the fractions with the highest skin lightening potential. Based on obtained qualitative and quantitative analysis of the fractions, it was assumed that the caffeoylquinic acid derivatives and dicaffeoylquinic acid derivatives are more likely responsible for mushroom tyrosinase inhibitory activity of A. biebersteinii extracts and fractions. Ferulic acid was proposed as the most active murine tyrosinase inhibitor, responsible also for the reduced melanin release from B16F10 murine melanoma cells.

The Metabolic Effects of Cynara Supplementation in Overweight and Obese Class I Subjects with Newly Detected Impaired Fasting Glycemia: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

Impaired fasting glucose (IFG) is a condition that precedes diabetes and increases the risk of developing it. Studies support the hypoglycemic effect of Cynara scolymus (Cs) extracts due to the content of chlorogenic acid, which is a potent inhibitor of glucose 6-phosphate translocase and of dicaffeoylquinic acid derivatives that modulate the activity of alpha-glucosidase. Given this background, we investigated whether a new highly standardized Cs extract could improve glycemic control, insulin sensitivity and other metabolic parameters (total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) Triglycerides, Apolipo protein B (ApoB), Apolipo protein A (ApoA), waist circumference, visceral adipose tissue (VAT) by dual-energy X-ray absorptiometry (DXA) in overweight subjects with newly diagnosed IFG. Fifty-four subjects (females/males 26/28, mean ± SD age 51.5 ± 6.2) were randomly assigned to the supplemented group (n = 27) and placebo (n = 27). After multiple testing correction, statistically significant interactions between time and group were observed for the primary endpoint glycemia (β = 0.36, p < 0.0001) and for the secondary endpoints HDL (β = −0.10, p < 0.0001), total cholesterol/HDL (β = 0.27, p < 0.0001), LDL (β = 0.15, p = 0.005), LDL/HDL (β = 0.23, p = 0.001), insulin (β = 1.28, p = 0.04), glycated hemoglobin (β = 0.21, p = 0.0002), A1c-derived average glucose (β = 0.34, p = 0.0002), ApoB (β = 6.00, p = 0.01), ApoA (β = −4.50, p = 0.04), ApoB/ApoA (β = 0.08, p = 0.003), waist circumference (β = 1.89, p = 0.05), VATβ = 222.37, p = 0.005). In conclusion, these results confirm that Cs supplementation has a significant effect on metabolic parameters in IFG patients.

Seasonal variation of bioactive properties and phenolic composition of Cynara cardunculus var. altilis

Cynara cardunculus L. (cardoon) has several health benefits mainly attributed to its abundance in polyphenols. In this study, cardoon heads (capitula) were harvested in Greece during the flowering stage, and the hydroethanolic extracts were assessed in terms of phenolic compounds composition and antioxidant, cytotoxic, anti-inflammatory, and antimicrobial activities. The phenolic profile was evaluated by HPLC-DAD-ESI/MS to better understand the seasonal changes in the individual compound levels and how these changes correlate with bioactive properties. The main phenolic compounds identified were caffeoylquinic and dicaffeoylquinic acid derivatives. Immature heads (Car A: principal growth stage (PGS) 5) had the highest phenolic content (34.3 mg/g) and cytotoxic (GI50 of 69–268 µg/mL) and anti-inflammatory (IC50 of 183 µg/mL) activities. Sample Car D (PGS 6/7) revealed the highest antioxidant (IC50 of 23–227 µg/mL) and antifungal (MIC of 0.26–0.51 mg/mL) potential. Regarding the antibacterial activity, Car E (PGS 7) revealed the best results (MIC of 0.59–1.18 mg/mL). This study suggests that the maturity stage of the plant influences the phenolic composition and bioactivity.

Influence of the in vitro gastrointestinal digestion on the antioxidant activity of Artemisia gorgonum Webb and Hyptis pectinata (L.) Poit. infusions from Cape Verde

The phenolic profile and antioxidant activity of Cape Verde's Artemisia gorgonum Webb and Hyptis pectinata (L.) Poit. infusions before and after in vitro simulation of the gastrointestinal digestion were determined. The LC-UV/DAD fingerprinting analysis allowed the identification of 3-O-caffeoylquinic acid, chlorogenic acid, 3,5 dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid and other caffeoylquinic acids derivatives on A. gorgonum infusion, and of caffeoylquinic acid and quercetin derivatives on H. pectinata infusion. Despite some decrease in the chromatographic area of several peaks, no relevant qualitative alterations on the chromatographic profile were observed between the digested and undigested herbal infusions.Results obtained showed a decrease on the antioxidant capacity of both tested herbal infusions after the in vitro digestion. This decrease was more pronounced for H. pectinata than for A. gorgonum and was also more pronounced regarding the radical scavenging capacity than regarding the reducing capacity. After complete digestion the superoxide anion and the DPPH-radical scavenging capacities decreased ≈ 43 and 75% for H. pectinata and ≈ 31 and 70% for A. gorgonum.Despite the observed differences before and after simulated gastrointestinal digestion, both infusions still had antioxidant activity at the end of this process. Thus, the antioxidant potential of A. gorgonum and H. pectinata infusions from Cape Verde, prepared as traditionally used, seems to be kept in some extend throughout the digestive system.

Bioactive dicaffeoylquinic acid derivatives from the root extract of Calea urticifolia

Calea urticifolia (Mill.) DC., Asteraceae, is a native plant of the Yucatan Peninsula used in traditional medicine to treat inflammation and pain. The bioassay-guided purification of the ethanol root extract allowed the isolation of the main bioactive metabolites, which were identified as an inseparable mixture of thymol (1) and 3-methyl-4-isopropylphenol (2), together with 3,4-O-dicaffeoylquinic acid methyl ester (3), 3,4-O-dicaffeoyl-epi-quinic acid methyl ester (4), 3,5-O-dicaffeoyl-epi-quinic acid methyl ester (5) and 3,5-O-dicaffeoylquinic acid (6). The results showed that the analgesic activity detected in the root extract of C. urticifolia could be attributed mainly to the mixture of 1 and 2 and to the novel 3,4-O-dicaffeoyl-epi-quinic acid methyl ester (4). Alternatively, the similarity on the antiinflammatory and antioxidant activities of the dicaffeoylquinic acid derivatives 3–5 suggests that the former might be related to their ability as radical scavengers.

Potential health effects of the popular compound of artichoke: Cynarin (CYN)

Functional food components are usually related with disease prevention. Cynarin is one of the biologically active functional food components which is the major dicaffeoylquinic acid derivative found in artichoke. Although artichoke contains very low amount of cynarin, it still duplicates the effects of artichoke. Cynarin is one of the biologically active functional food components that have potential effects on choleretic and cholesterol lowering, hepatoprotective, anti-atherosclerotic, anti-HIV, antioxidative, anti-diabetic, anti-carcinogenic and immune modulator activity. To sum up, more molecular, clinical and epidemiological studies on cynarin is necessary to be able to use it as a disease preventive agent.

Chemical Constituents of the Leaves of Tussilago farfara and their Aldose Reductase Inhibitory Activity

The inhibitory activity of 37 medicinal plant extracts against aldose reductase (AR) activity was evaluated. The most potent AR inhibitory activity was found in the MeOH extract of the leaves of Tussilagofarfara (Compositae). Enzyme assay-guided fractionation of the extract led to the isolation of a new flavonoid glycoside, kaempferol 3-0-[3,4-0-(isopropylidene)-α-L-arabinopyranoside] (1), along with 15 known compounds (2-16), of which 3, 5, 13, 15, and 16 were isolated from T. faifara for the first time. The structures of 1-16 were elucidated based on MS and NMR data. Dicaffeoylquinic acid derivatives (7-12) showed potent AR inhibitory activity with IC(50)values ranging from 0.58 to 5.38 μM, whereas flavonoid glycosides 1, 3, 5, and 6 showed weak inhibitory activity with IC(50) values of 13.9, 15.1, 13.3, and 14.1 μM, respectively.

Four New Dicaffeoylquinic Acid Derivatives from Glasswort (Salicornia herbacea L.) and Their Antioxidative Activity.

Four new dicaffeoylquinic acid derivatives and two known 3-caffeoylquinic acid derivatives were isolated from methanol extracts using the aerial parts of Salicornia herbacea. The four new dicaffeoylquinic acid derivatives were established as 3-caffeoyl-5-dihydrocaffeoylquinic acid, 3-caffeoyl-5-dihydrocaffeoylquinic acid methyl ester, 3-caffeoyl-4-dihydrocaffeoylquinic acid methyl ester, and 3,5-di-dihydrocaffeoylquinic acid methyl ester. Their chemical structures were determined by nuclear magnetic resonance and electrospray ionization-mass spectroscopy (LC-ESI-MS). In addition, the presence of dicaffeoylquinic acid derivatives in this plant was reconfirmed by LC-ESI-MS/MS analysis. The isolated compounds strongly scavenged 1,1-diphenyl-2-picrylhydrazyl radicals and inhibited cholesteryl ester hydroperoxide formation during rat blood plasma oxidation induced by copper ions. These results indicate that the caffeoylquinic acid derivatives may partially contribute to the antioxidative effect of S. herbacea.

A dereplication strategy for the identification of new phenolic compounds from Anvillea radiata (Coss. &amp; Durieu)

Abstract Phenolic compounds were selectively extracted from aerial parts of Anvillea radiata using Accelerated Solvent Extraction (ASE) in two steps. Given the two molecular families (flavonoids and germacranolides) described as present in the plant material, a first extraction step using chloroform as the extraction solvent was carried out to remove the germacranolides, the most abundant compounds. The minor phenolic compounds were then selectively extracted and enriched from the plant residue by methanol. Characterization of twenty five phenolic compounds in the methanolic extract was performed using HPLC-DAD-ESI-MS/MS and HPLC-HRMS analyses. Seven compounds corresponded to chlorogenic acid and dicaffeoylquinic acid derivatives and eighteen flavonoids (from which five aglycones and thirteen glycosides) were identified and some of them for the first time. The presence of these phenolic compounds, identified in the whole aerial parts, was then followed in each organ (flower, leave and stem). The chromatographic profiles of the stem and leave were very close, while the flower one was more different. However most of the compounds identified in aerial parts were recovered in each organ, mainly difference on peak intensity could be observed. The most abundant compound in flowers was found to be a di-caffeoylquinic acid derivative while isorhamnetin and spinacitin diglucoside derivatives were the most abundant ones in stems and leaves.

Chemical constituents from Ainsliaea acerifolia as potential anti-obesity agents

Bioassay-guided isolation of an ethanolic extract of the aerial parts from Ainsliaea acerifolia using pancreatic lipase inhibitory assay led to the isolation of a new guaianolide-type sesquiterpene lactone (1), a new dicaffeoylquinic acid derivative (4), as well as eight known secondary metabolites. Structures of the two new compounds were elucidated on the basis of spectroscopic methods. All isolated compounds were evaluated for their inhibitory effects against pancreatic lipase, and compound 2 exhibited significant inhibitory activity with an IC50 value of 15.3±0.7μM. Furthermore, compound 2 also exhibited potent inhibitory effects against 3T3-L1 adipocyte cells.

Elicitation of medicinally active dicaffeoylquinic acid derivatives from Helichrysum populifolium

Elicitation of medicinally active dicaffeoylquinic acid derivatives from Helichrysum populifolium

Identification of anti-HIV active dicaffeoylquinic- and tricaffeoylquinic acids in Helichrysum populifolium by NMR-based metabolomic guided fractionation

South Africa being home to more than 35% of the world's Helichrysum species (c.a. 244) of which many are used in traditional medicine, is seen potentially as a significant resource in the search of new anti-HIV chemical entities. It was established that five of the 30 Helichrysum species selected for this study had significant anti-HIV activity ranging between 12 and 21μg/mL (IC50) by using an in-house developed DeCIPhR method on a full virus model. Subsequent toxicity tests also revealed little or no toxicity for these active extracts. With the use of NMR-based metabolomics, the search for common chemical characteristics within the plant extract was conducted, which resulted in specific chemical shift areas identified that could be linked to the anti-HIV activity of the extracts. The NMR chemical shifts associated with the activity were identified to be 2.56–3.08ppm, 5.24–6.28ppm, 6.44–7.04ppm and 7.24–8.04ppm. This activity profile was then used to guide the fractionation process by narrowing down and focusing the fractionation and purification processes to speed up the putative identification of five compounds with anti-HIV activity in the most active species, Helichrysum populifolium. The anti-HIV compounds identified for the first time from H. populifolium were three dicaffeoylquinic acid derivatives, i.e. 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid as well as two tricaffeoylquinic acid derivatives i.e. 1,3,5-tricaffeoylquinic acid and either 5-malonyl-1,3,4-tricaffeoylquinic or 3-malonyl-1,4,5-tricaffeoylquinic acid, with the latter being identified for the first time in the genus.

Investigation of the photochemical changes of chlorogenic acids induced by ultraviolet light in model systems and in agricultural practice with Stevia rebaudiana cultivation as an example.

Mono- and diacyl chlorogenic acids undergo photochemical trans-cis isomerization under ultraviolet (UV) irradiation. The photochemical equilibrium composition was established for eight selected derivatives. In contrast to all other dicaffeoylquinic acid derivatives, cynarin (1,3-dicaffeoylquinic acid) undergoes a [2 + 2] photochemical cycloaddition reaction, constituting a first example of Schmidt's law in a natural product family. The relevance of photochemical isomerization in agricultural practice was investigated using 120 samples of Stevia rebaudiana leave samples grown under defined cultivation conditions. Ratios of cis to trans chlorogenic acids were determined in leaf samples and correlated with climatic and harvesting conditions. The data indicate a clear correlation between the formation of cis-caffeoyl derivatives and sunshine hours prior to harvesting and illustrate the relevance of UV exposure to plant material affecting its phytochemical composition.

Chemical analysis and antihyperglycemic activity of an original extract from burdock root (Arctium lappa).

In the present study, we obtained a dried burdock root extract (DBRE) rich in caffeoylquinic acids derivatives. We performed the chemical characterization of DBRE and explored its antihyperglycemic potential in both in vitro and in vivo experiments. Chemical analysis of DBRE using LC-MS and GC-MS revealed the presence of a great majority of dicaffeoylquinic acid derivatives (75.4%) of which 1,5-di-O-caffeoyl-4-O-maloylquinic acid represents 44% of the extract. In the in vitro experiments, DBRE is able to increase glucose uptake in cultured L6 myocytes and to decrease glucagon-induced glucose output from rat isolated hepatocytes together with a reduction of hepatic glucose 6-phosphatase activity. DBRE did not increase insulin secretion in the INS-1 pancreatic β-cell line. In vivo, DBRE improves glucose tolerance both after intraperitoneal and oral subchronic administration. In conclusion, our data demonstrate that DBRE constitutes an original set of caffeoylquinic acid derivatives displaying antihyperglycemic properties.

Determination of chokeberry (Aronia melanocarpa) polyphenol components using liquid chromatography–tandem mass spectrometry: Overall contribution to antioxidant activity

The type and content of plant polyphenols can be influenced by maturity. Korean chokeberry (Aronia melanocarpa) leaves of three different maturities (young, mature, and aged) were extracted with 70% aqueous methanol. The polyphenols in the leaves were analysed for the first time using high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) and comparison with reported data. Among the 12 characterised components, five flavonoids, 3, 4, and 10–12, and a dicaffeoylquinic acid derivative, 6, were characterised for the first time in chokeberry leaves. Each polyphenol component was validated and quantified using a representative polyphenol standard of the same group. The antioxidant activity of the three different mature leaf extracts was determined. The antioxidant activity was highest for young leaves, followed by mature and aged leaves. The results suggest that younger chokeberry leaves may be more favourable for processing a higher quality functional tea due to their higher polyphenol content.

Micropropagation of Helichrysum populifolium, which produces medicinally active dicaffeoylquinic acid derivatives

Micropropagation of Helichrysum populifolium, which produces medicinally active dicaffeoylquinic acid derivatives