Phytochemical properties, biological activities and medicinal use of Centaurium erythraea Rafn.

ETHNOPHARMACOLOGICAL RELEVANCE: Centaurium erythraea is an important medicinal plant in many countries, e.g. Morocco, Algeria, Italy, Spain, Portugal, and countries of Balkan Peninsula. It is used in folk medicine to treat various illnesses. It is also used as an antiapoplectic, anticoagulant, anticholagogue, antipneumonic, hematocathartic, and as a hypotensive agent. AIM OF THE REVIEW: In this review, previous reports on the taxonomy, botanical description, geographic distribution, ethnomedicinal applications, phytochemistry, pharmacological properties, and toxicity of Centaurium erythraea were critically summarized. MATERIALS AND METHODS: Scientific search engines including PubMed, ScienceDirect, SpringerLink, Web of Science, Scopus, Wiley Online, SciFinder, and Google Scholar were consulted to collect data on C. erythraea. The data presented in this work summarized the main reports on C. erythraea phytochemical compounds, ethnomedicinal uses, and pharmacological activities. RESULTS: C. erythraea is used in traditional medicine to treat various diseases such as diabetes, fever, rhinitis, stomach ailments, urinary tract infections, dyspeptic complaints, loss of appetite, and hemorrhoids, and as diuretic. The essential oils and extracts of C. erythraea exhibited numerous biological properties such as antibacterial, antioxidant, antifungal, antileishmanial, anticancer, antidiabetic, anti-inflammatory, insecticidal, diuretic, gastroprotective, hepatoprotective, dermatoprotective, neuroprotective, and inhibitory agent for larval development. Phytochemical characterization of C. erythraea revealed the presence of several classes of secondary metabolites such as xanthonoids, terpenoids, flavonoids, phenolic acids, and fatty acids. CONCLUSIONS: Ethnomedicinal studies demonstrated the use of C. erythraea for the treatment of various disorders. Pharmacological reports showed that C. erythraea especially its aerial parts and roots exhibited potent, and beneficial activities. These findings confirmed the link between the traditional medicinal use and the results of the scientific biological experiments. Considering these results, further investigation using diverse in vivo pharmacological assays are strongly recommended to validate the results of its traditional use. Toxicological tests and pharmacokinetic studies are also required to validate the safety and efficacy of C. erythraea and its bioactive contents.

Changes in beneficial bioactive compounds in eight traditional herbal liqueurs during a one-month maceration process.

BACKGROUND: Herbs are rich in various beneficial bioactive compounds and they can be used for many different purposes. One of the most common is maceration of herbs in alcohol. Different substances respond differently to extraction in prepared solutions. It is very important to enhance the highest proportion of beneficial ingredients during the maceration process in a herbal liqueur. A comparative analysis of numerous different phenolic compounds from eight of the most frequently used herbs for making aperitifs in Europe was performed. RESULTS: In the comparison among all studied herbs, the highest phenolic content was found with Artemisia absinthium (wormwood) (14.61 mg g-1 ) and Mentha piperita (peppermint) (13.89 mg g-1 ), while the lowest content was found with Centaurium erythraea (common centaury) (3.96 mg g-1 ). Salvianolic acid isomers and caffeic acid derivatives were the greatest contributors to the total phenolic content in lemon balm, wormwood, peppermint, fennel and sage. These compounds contain more hydroxyl groups and they were better extracted at the beginning of the maceration process. Caraway and common centaury contain more flavonols (quercetin and kaempferol derivatives), with higher chemical stability and fewer hydroxyl groups in their structure. CONCLUSION: The compositions of eight herbal liqueurs were highly related to the presence of different herbal ingredients and their solubility in the extract over time. Most flavonol derivatives were extracted over a longer time and the two liqueurs (common centaury and caraway) therefore had the highest phenolic contents after 3 weeks of maceration. © 2019 Society of Chemical Industry.

Centaurium Erythraea Extracts Exert Vascular Effects through Endothelium- and Fibroblast-dependent Pathways.

Centaurium erythraea is a plant used in traditional medicine for several cardiovascular disorders, namely hypertension, but there is no scientific evidence able to provide a molecular basis for its claimed antihypertensive effects. After a preliminary screen of extracts obtained from sequential extraction of C. erythraea aerial parts, effects of the methanolic fraction (MFCE) on changes in perfusion pressure of isolated rat mesenteric vascular bed (MVB) and in rat cardiac fibroblasts proliferation were investigated, gathering information on the mechanisms involved in endothelium-dependent effects and their dependence on a pro-proliferative stimulus. The HPLC-DAD determination of the phenolics content of MFCE revealed the presence of 22 phenolic compounds. MFCE reduced (63.3 ± 3.9%; n = 4) perfusion pressure in MVB and almost completely abrogated the Ang II-induced increase in cardiac fibroblasts proliferation. Reduction of the perfusion pressure caused by MFCE was endothelium-dependent and occurred in parallel with an increase in NO release. These effects were inhibited by muscarinic receptor antagonists, by L-NAME (a NO synthase inhibitor), and by ODQ (a soluble guanylate cyclase inhibitor). Experiments revealed that effects required the involvement of K+ channels, being inhibited by tetraethylamonium (TEA; a Ca2+ activated K+ channels inhibitor) and by glibenclamide (an ATP-sensitive K+ channels inhibitor). In conclusion, extracts from C. erythraea, particularly the compounds present in the MFCE, induce endothelium-dependent vasodilation and prevent fibroblast proliferation induced by angiotensin II, which can account for the claimed antihypertensive effects of C. erythraea in traditional medicine.

Bioactivities of Centaurium erythraea (Gentianaceae) Decoctions: Antioxidant Activity, Enzyme Inhibition and Docking Studies.

Centaurium erythraea is recommended for the treatment of gastrointestinal disorders and to reduce hypercholesterolemia in ethno-medicinal practice. To perform a top-down study that could give some insight into the molecular basis of these bioactivities, decoctions from C. erythraea leaves were prepared and the compounds were identified by liquid chromatography-high resolution tandem mass spectrometry (LC-MS/MS). Secoiridoids glycosides, like gentiopicroside and sweroside, and several xanthones, such as di-hydroxy-dimethoxyxanthone, were identified. Following some of the bioactivities previously ascribed to C. erythraea, we have studied its antioxidant capacity and the ability to inhibit acetylcholinesterase (AChE) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). Significant antioxidant activities were observed, following three assays: free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) reduction; lipoperoxidation; and NO radical scavenging capacity. The AChE and HMGR inhibitory activities for the decoction were also measured (56% at 500 µg/mL and 48% at 10 µg/mL, respectively). Molecular docking studies indicated that xanthones are better AChE inhibitors than gentiopicroside, while this compound exhibits a better shape complementarity with the HMGR active site than xanthones. To the extent of our knowledge, this is the first report on AChE and HMGR activities by C. erythraea decoctions, in a top-down analysis, complemented with in silico molecular docking, which aims to understand, at the molecular level, some of the biological effects ascribed to infusions from this plant.

HPLC-DAD-ESI/MSn phenolic profile and in vitro biological potential of Centaurium erythraea Rafn aqueous extract.

Centaurium erythraea Rafn is a food flavouring used in both food and beverage industries. Despite the existence of some works on this species, only few focus their attention on its common form of consumption (infusion). Thus, we intended to explore the chemical composition and the biological properties of infusions from C. erythraea aerial parts. Phenolic compounds were identified by HPLC-DAD-ESI/MSn, twenty-two flavonoid derivatives being reported for the first time. Concerning to the biological potential, the best scavenging activity was observed for the superoxide anion radical. Moreover, this extract revealed to have some effect on the inhibition of 5-lipoxygenase, no cytotoxicity against RAW 264.7 macrophage cells line, and a weak potential to decrease the nitric oxide levels in this cell system. The results suggest that C. erythraea aerial parts could be valuable sources of health benefits compounds, contributing to its valorisation and its further application in functional foods.

Off-line coupling of new generation centrifugal partition chromatography device with preparative high pressure liquid chromatography-mass spectrometry triggering fraction collection applied to the recovery of secoiridoid glycosides from Centaurium erythraea Rafn. (Gentianaceae).

A purification sequence including a Gilson CPC 250 PRO device coupled to PrepHPLC hyphenated with a MS triggering fraction collector was applied to isolate secoiridoid glycosides from a complex methanolic extract of Centaurium erythraea. This species is widely used for ethnomedicinal purposes around the Mediterranean Sea. The solvent system ethyle acetate/ethanol/water 7.5/3/5 was determined using shake-flask method targeting swertiamarin, the major secoiridoid of the extract. Optimization of CPC experimental parameters enabled the injection of 4g of extract with a flow rate of 40mL/min at 3000rpm to provide a secoiridoid glycosides enriched fraction. 130mg of this latter was submitted to a second step of purification by preparative HPLC (gradient water/formic acid (19:1) (A) and methanol (B) as follows: 0min, 85% A; 8min, 60% A; 12min, 55% A; 35min, 55% A; 40min, 10% A; 50min, 10% A; 52min, 85% A; 55min, 85% A) to give swertiamarin (36mg, yield 27.7%, purity 98.2%). Other secoiridoid glycosides (sweroside, gentiopicroside, secologanol, secoxyloganin) were also isolated in minor amounts. As these monoterpene derivatives are responsible for several biological activities, their quick recovery with high yield and purity may serve as a model for further scale-up and industrial development.

Chemodiversity of two closely related tetraploid Centaurium species and their hexaploid hybrid: Metabolomic search for high-resolution taxonomic classifiers.

Species within the genus Centaurium readily hybridize and polyploid complexes are often seen in natural populations. We describe phytochemical profiles of newly discovered allohexaploid hybrid, here named Centaurium pannonicum, and its parental tetraploid species C. erythraea and rare C. littorale ssp. compressum. Our aim was to examine chemodiversity of these taxa in the area of Vojvodina (North Serbia) and to perform metabolomics search for chemical classifiers which would provide high resolution discrimination of parental and hybrid individuals. In sum, UHPLC-MS/MS Orbitrap metabolomics fingerprinting revealed seventy compounds in methanol extracts. Despite the lack of qualitative chemical novelty in hybrid plants, UHPLC-qqqMS targeted metabolomics approach, aimed at three secoiridoid compounds and seventeen phenolics, pointed to considerable differences in quantitative composition of these dominant compounds among the plant taxa studied. In addition to the difference in the ploidy levels, the hybrid taxon was well distinguished from both parental species based on metabolite profiles, and, for most individuals, positioned intermediately to the parental taxa in both PCA and hierarchical clustering. After optimizing and comparing several statistical learning methods, it was possible to narrow the number of taxonomic classifiers to five (three xanthones, one secoiridoid glycoside, and one phenolic acid), while increasing the differentiation resolution. The presented metabolomics approach will certainly, along with morphometrics and molecular genetics studies, have high impact on further elucidation of complex relationships among taxa within the genus Centaurium.

Centaurium erythraea methanol extract protects red blood cells from oxidative damage in streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Centaurium erythraea Rafn (CE) is a traditional medicinal herb in Serbia with antidiabetic, digestive, antipyretic and antiflatulent effects AIM OF THE STUDY: To investigate the potential protective effects of the methanol extract of the aerial parts of CE against glyco-oxidative stress in red blood cells (RBCs) in rats with experimentally induced diabetes. MATERIAL AND METHODS: Diabetes was induced in Wistar rats by intraperitoneal (i.p.) injection of multiple low-dose streptozotocin (STZ) (40mg/kg, for five consecutive days), with the 1st day after the last STZ injection taken as the day of diabetes onset. The methanol extract of CE (100mg/kg) was administered orally and daily, two weeks before the first STZ injection, during the 5-day treatment with STZ, and for four weeks after the STZ injections (pre-treated group) or for four weeks after diabetes onset (post-treated group). The effect of CE extract administration on the redox status of RBCs was evaluated by assessing lipid peroxidation, the ratio of reduced/oxidized glutathione (GSH/GSSG), the level of S-glutathionylated proteins (GSSP) and the enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in RBCs four weeks after diabetes onset. The major biochemical parameters of diabetes, protein glycation/glycosylation of erythrocytes and parameters which correlate with their aggregation and deformability were also evaluated. RESULTS: Daily application of CE extract to STZ-induced diabetic rats provided important antidiabetic effects, observed in both pre-treated and post-treated groups of diabetic rats as elevated serum insulin concentration, reduction of blood glucose and glycated hemoglobin concentrations and an improved lipid profile. Antioxidant effects of CE extract were detected in RBCs of diabetic rats and observed as decreased lipid peroxidation and ameliorated oxidative damage as a result of increased SOD, CAT and GR activities, an improved GSH/GSSG ratio and reduced GSSP levels. Moreover, the CE extract protected RBC proteins from hyperglycemia-induced damage by reducing non-enzymatic glycation and enzymatic glycosylation processes. CE extract was more effective when applied before diabetes induction (pre-treated group). CONCLUSIONS: The results of this study show that the Centaurium erythraea methanol extract protects RBCs in diabetic animals from oxidative damage. They provide additional support for the application of this traditionally used plant in diabetes management.

Nonprenylated Xanthones from Gentiana lutea, Frasera caroliniensis, and Centaurium erythraea as Novel Inhibitors of Vascular Smooth Muscle Cell Proliferation.

Aberrant proliferation of vascular smooth muscle cells (VSMC) plays a major role in restenosis, the pathological renarrowing of the blood vessel lumen after surgical treatment of stenosis. Since available anti-proliferative pharmaceuticals produce unfavorable side effects, there is high demand for the identification of novel VSMC proliferation inhibitors. A natural product screening approach using a resazurin conversion assay enabled the identification of gentisin (1) from Gentiana lutea as a novel inhibitor of VSMC proliferation with an IC50 value of 7.84 µM. Aiming to identify further anti-proliferative compounds, 13 additional nonprenylated xanthones, isolated from different plant species, were also tested. While some compounds showed no or moderate activity at 30 µM, 1-hydroxy-2,3,4,5-tetramethoxyxanthone (4), swerchirin (6), and methylswertianin (7) showed IC50 values between 10.2 and 12.5 µM. The anti-proliferative effect of 1, 4, 6, and 7 was confirmed by the quantification of DNA synthesis (BrdU incorporation) in VSMC. Cell death quantification (determined by LDH release in the culture medium) revealed that the compounds are not cytotoxic in the investigated concentration range. In conclusion, nonprenylated xanthones are identified as novel, non-toxic VSMC proliferation inhibitors, which might contribute to the development of new therapeutic applications to combat restenosis.

Polybrominated diphenyl ethers (PBDEs) in herbaceous Centaurium erythraea affected by various sources of environmental pollution.

Polybrominated diphenyl ethers (PBDEs) are persistent xenobiotics with harmful effects on humans and wildlife. Their levels in the environment and accumulation in biota must be carefully controlled especially in species harvested from wild populations and commonly used as medicines. Our objective has been to determine PBDE concentrations (BDEs 28, 47, 66, 85, 99, 100, 153, 154, 183 and 209) in Centaurium erythraea collected at sites with various levels of environmental pollution. PBDE congener profiles in C. erythraea were dominated by BDE209, which accounted for 47-89% of the total PBDE burden in the plants. Principal Component and Classification Analysis, which classifies the concentration of PBDEs in C. erythraea, allowed us to distinguish the pattern of these compounds characteristic for the origin of pollution: BDEs 28, 47, 66, 85, 99, 100 for lignite and general chemical industry and the vicinity of an expressway and BDEs 183 and 209 for a thermal power plant and ferrochrome smelting industry. Careful selection of sites with C. erythraea for medicinal purposes is necessary as this herb can accumulate PBDEs while growing at polluted sites.

Centauries as underestimated food additives: antioxidant and antimicrobial potential.

Methanol extracts of aerial parts and roots of five centaury species (Centaurium erythraea, C. tenuiflorum, C. littorale ssp. uliginosum, C. pulchellum, and Schenkia spicata) were analysed for their main secondary metabolites: secoiridoid glycosides, a group of monoterpenoid compounds, and phenolics (xanthones and flavonoids), and further investigated for antioxidant capacity and antimicrobial activity. The results of ABTS, DPPH, and FRAP assays showed that above ground parts generally displayed up to 13 times higher antioxidant activity compared to roots, which should be related to higher phenolics content, especially flavonoids, in green plant organs. Secoiridoid glycosides showed no antioxidant activity. All the tested extracts demonstrated appreciative antibacterial (0.05-0.5 mg ml(-1)) and strong antifungal activity (0.1-0.6 mg ml(-1)). Our results imply that above ground parts of all centaury species studied, could be recommended for human usage as a rich source of natural antioxidants and also in food industry as strong antimicrobial agents for food preservation.

Chemical characterization of Centaurium erythrea L. and its effects on carbohydrate and lipid metabolism in experimental diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: Centaurium erythrea L. fam. Gentianaceae (CE) has been traditionally used for centuries in folk medicine of Balkans as a bitter medicinal herb for digestive complications and for treating febrile conditions and diabetes. The aim of this study was to gain insight into the chemical composition and underlying biochemical mechanism of action of the antihyperglycemic and antilipidemic activities of the dry extract of Centaurium erythrea L., wildly growing and traditionally used medicinal plant in the Republic of Macedonia. MATERIALS AND METHODS: An ultrasonic methanol maceration of the aerial parts of the dried plant was performed and the extract was freeze-dried. HPLC-DAD-ESI-MS(n) was carried out on 150 mm × 4.6mm, 5 µm RP-18 Eclipse XDB column, at 40 °C. Mobile phase: water with 1% formic acid (A) and methanol (B) with linear gradient starting with 10% B was used to reach 15% at 5 min, 40% B at 25 min, 55% of B at 50 min and 100% at 60 min, with flow rate of 0.4 mL min(-1). Normal and streptozotocin (STZ) hyperglycemic Wistar rats were used for assessment of the antihyperglycemic and antilipidemic activity by measurement of the key carbohydrate-related enzymes and substrates, as well as lipid state of the organism. RESULTS: HPLC-DAD-ESI-MS(n) analyses revealed presence of four different secoiridoids, seven flavonoid glycosides and seven xanthones in the freeze-dried extract of CE representing 53%, 25% and 22% of all compounds, respectively. The short-term (12 days) treatment of the STZ-diabetic rats with CE-extracts resulted in a 74% reduction of the produced hyperglycemia, which is only 6% less than the reduction caused by glibeclamide (GLB, positive control). The CE-extract had a significant impact on the hepatic carbohydrate metabolism enhancing the direct synthesis of glycogen, normalizing phosphorylase a activity and reducing the activity of glucose-6-phosphatase, which further causes reduction in production of blood glucose level. The long-term (45 days) treatment showed that the HbA1c in CE-treated group of animals was even lower than in the GLB-treated groups. The antilipidemic assessment of the CE-extract revealed decrease of total cholesterol, triglycerides, HDL and LDL level in the blood of the normal and STZ-hyperglycemic rats. CONCLUSION: The obtained results indicate that treatment with CE extract in STZ-diabetic rats regulates the elevated level of blood glucose and carbohydrate-related disturbances slightly better than the effect of glibenclamide. There was also regulation of the serum lipid status in diabetic rats. Identified groups of bitter compounds in the extract (flavonoides, iridoids and xanthones) probably have influence on the expressed antihyperglycaemic effect.

Metal contents in Centaurium erythraea and its biometry at various levels of environmental pollution.

In this investigation we focus on the influence of pollution on concentration of elements in the medicinal Centaurium erythraea. This herb is collected from wild populations and also provides important information as monitor of environmental quality. Concentrations of Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, N, Ni, P, Pb, V and Zn in Centaurium erythraea and in the soil in which this plant grew were measured together with biometrical features of the species from sites affected by various levels of pollution. C. erythraea from sites polluted by lignite mining and industrial combustion had the highest concentrations of Cd, Co and Zn (principal component and classification analysis, PCCA). C. erythraea from sites influenced by ferrous-chromium and thermal power plants had the highest concentrations of Cr and Fe as well as Cu, Mn and Ni and the highest length of shoots and number of leaves, shoots, nodes, flowers and flowers on the main shoot. These luxurious growth forms were probably related to the highest concentrations of N, P and Fe in the soil and concentrations of N and K accumulated by C. erythraea on these sites as revealed by the established models. Controlling the collection of C. erythraea for medicinal purposes is recommended as this species is able to accumulate increased levels of metals from polluted sites. The medical quality of C. erythraea may be negatively related to the degree and type of pollution of the environment and should not be based on the luxurious growth of individuals which may contain hazardous levels of metals.

Volatile organic compounds from Centaurium erythraea Rafn (Croatia) and the antimicrobial potential of its essential oil.

GC and MS were used for the analysis of Croatian Centaurium erythraea Rafn essential oil (obtained by hydrodistillation) and headspace (applying headspace solid-phase microextraction). The headspace contained numerous monoterpene hydrocarbons (the major ones were terpinene-4-ol, methone, p-cymene, γ-terpinene and limonene). Oxygenated monoterpenes were present in the headspace and oil, while 1,8-cineole, bornyl acetate and verbenone were present only in the headspace. High headspace percentages of toluene and naphthalene were found, followed by hemimellitene. Lot of similarities were observed with Serbian C. erythraea oil [neophytadiene (1.4%), thymol (2.6%), carvacrol (6.1%) and hexadecanoic acid (5.7%)], but different features were also noted such as the presence of menthol, menthone and phytone. The oil fractionation enabled identification of other minor compounds not found in total oil such as norisoprenoides, alk-1-enes or chromolaenin. The essential oil showed antimicrobial potential on Escherichia coli, Salmonella enteritidis, Staphylococcus aureus and Bacillus cereus. On the other hand, no antibacterial activity of the oil was observed on Pseudomonas fluorescens and Lysteria monocytogenes.

Centaurium cachanlahuen (Mol) Robinson, a Chilean native plant with a vasodilatory effect / Centaurium cachanlahuen (Mol) Robinson una planta nativa chilena con efecto vasodilatador

Centaurium cachanlahuen (Mol.) Robinson is a chilean native plant widely used in traditional medicine for the treatment of many diseases, including cardiovascular disorders. Studies carried out in normal and hypertensive rats suggested that extract of Centaurium cachanlahuen has antihypertensive effect. In this work, we aim to evaluate the effect of aqueous and hydroalcoholic extracts of Centaurium cachanlahuen on the vascular reactivity using rat aorta rings precontrated with phenylephrine (0.1 uM). Results showed that both aqueous (3 mg/mL) and hydroalcoholic extracts (3 mg/mL) produced rat aorta vasodilatation that was higher (P < 0.001) in the hydroalcoholic extract compared to the aqueous extract. This effect had an important endothelium-dependent component that was mediated by nitric oxide (NO), as supported by the inhibition of the response in the presence of N-nitro-L-arginine (L-NNA, 100 uM), a nitric oxide synthase (NOS) inhibitor. We suggest that xanthones present in the plant may play a key role in the vasodilator effect of Centaurium cachanlahuen extracts. The present study provides experimental evidence supporting the folkloric use of Centaurium cachanlahuen as hypotensive agent.

Centaurium cachanlahuen (Mol) Robinson es una planta nativa chilena ampliamente utilizada en medicina tradicional para el tratamiento de varias enfermedades, que incluyen alteraciones cardiovasculares. Estudios llevados a cabo en ratas normales e hipertensas sugieren que el extracto de Centaurium cachanlahuen tiene efecto antihipertensivo. El propósito de este trabajo fue evaluar el efecto de extractos acuosos e hidroalcohólicos de Centaurium cachanlahuen sobre la reactividad vascular de aorta de rata precontraída con fenilefrina (0.1 uM). Tanto el extracto acuoso (3 mg/mL) como el extracto hidroalcohólico (3 mg/mL) produjeron relajación de aorta de rata, la cual fue de mayor magnitud (P < 0.001) con el extracto hidroalcohólico respecto del extracto acuoso. El efecto observado tuvo un importante componente mediado por óxido nítrico (NO), tal como lo demuestra la inhibición de esta respuesta en presencia de N-nitro-L-arginina (L-NNA, 100 uM), un inhibidor de la óxido nítrico sintasa (NOS). Se sugiere que las xantonas presente en la planta pueden jugar un papel clave en el efecto vasodilatador observado por los extractos de Centaurium cachanlahuen. Este estudio constituye una evidencia experimental que apoya el uso popular de Centaurium cachanlahuen como agente hipotensor.

Two new acetylated flavonoid glycosides from Centaurium spicatum L.

Two new acetylated flavonol glycosides, quercetin 3-O-[(2,4-diacetyl-α-L-rhamnopyranosyl)-(1→6)]-2,4-diacetyl-ß-D-galactopyranoside (1) and quercetin 3-O-[(2,4-diacetyl-α-L-rhamnopyranosyl)-(1→6)]-3,4-diacetyl-ß-D-galactopyranoside (2), in addition to two known acetylated quercetin glycosides quercetin 3-O-[(2,3,4-triacetyl-α-L-rhamnopyranosyl)-(1→6)-ß-D-galactopyranoside (3) and quercetin 3-O-[(2,3,4-triacetyl-α-L-rhamnopyranosyl)-(1→6)-3-acetyl-ß-D-galactopyranoside (4), were isolated from the aerial part of Centaurium spicatum (L.) Fritsch (Gentianaceae). Structure elucidation, especially the localization of the acetyl groups, and complete (1)H and (13)C NMR assignments of these biologically active compounds were carried out using one- and two-dimensional NMR measurements, including (1)H- and (13)C-NMR, DEPT-135, H-H COSY, HMQC and HMBC, in addition to HR-FAB/MS experiments.

Centaurium erythrea (Gentianaceae) leaf extract alleviates streptozotocin-induced oxidative stress and ß-cell damage in rat pancreas.

ETHNOPHARMACOLOGICAL RELEVANCE: Centaurium erytrea is used in traditional medicine for treat urine retention, abdominal colic and diabetes mellitus. The aim of the present study was to evaluate the possible protective effects of Centaurium erythrea leaf extract (CE) against pancreas ß-cells' damage and antioxidant defense systems in streptozotocin induced diabetes rats. MATERIALS AND METHODS: Experimental diabetes was induced by a single dose of STZ (65 mg/kg) administered by intraperitoneal way. The oxidative stress was measured by tissue MDA levels, protein carbonyl (PCO) content, reduced glutathione (GSH) content and by enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in pancreas. Biochemical observations were further substantiated with histological examination of pancreas. RESULTS: The increase in blood glucose and MDA levels with the decrease in GSH content and in enzymatic activities were the salient features observed in diabetic rats. Administration of CE (200mg/kg bw/day, i.p) for 30 days caused a significant reduction in blood glucose and MDA levels in STZ treated rats when compared with diabetic rats. Furthermore, diabetic rats treated with CE leaf extract showed a significant increase in the activities of both enzymatic and non-enzymatic antioxidants when compared to those of diabetic rats. Degenerative changes of pancreatic ß-cells in STZ treated rats were minimized to near normal morphology by administration of CE leaf extract as evidenced by histopathological examination. CONCLUSION: Results clearly indicate that Centaurium erythrea treatment exerts a therapeutic protective nature in diabetes by decreasing oxidative stress and pancreatic ß-cells' damage which may be attributed to its antioxidative potential.

Gastroprotective effect of small centaury (Centaurium erythraea L) on aspirin-induced gastric damage in rats.

The aim of this study was to determine the antiulcer and antioxidant activities of Centaurium erythraea L (small centaury) in aspirin (ASA) induced acute gastric ulcer model. The gastroprotective effect of the 50% aqueous-ethanolic small centaury (SC) extract was investigated in rats at a dose of ASA 200 mg/kg body weight. Twenty-one Sprague-Dawley albino rats were divided into three groups of seven rats each as follows: (1) control group; (2) acute ASA-treated group and (3) ASA plus SC group. At the end of the 4-h drug administration, ulcer index, oxidant and antioxidant levels were measured and compared between the groups. The percentage of lesion area to total gastric surface area (ulcer index) was significantly reduced (77%) in ASA plus SC group as compared with acute ASA-treated group. The oral administration of ASA decreased catalase (CAT), reduced glutathione (GSH), and increased lipid peroxidation (LPO) levels. Although myeloperoxidase (MPO) activity was increased by ASA, it was found to be lower in the ASA plus SC group. GSH and Vitamin A levels were determined higher in the ASA plus SC group compared with ASA group. These results suggest that SC extract protects against ASA-induced damage due to its antioxidizing activity.

Analysis of iridoids, secoiridoids and xanthones in Centaurium erythraea, Frasera caroliniensis and Gentiana lutea using LC-MS and RP-HPLC.

This study presents a new and validated HPLC method for the simultaneous determination of bioactive compounds in Centaurium erythraea, Frasera caroliniensis and Gentiana lutea. The iridoid loganic acid, four secoiridoids and 29 xanthones were separated on a RP-18 column, using aqueous o-phosphoric acid (0.085%, v/v) and acetonitrile as mobile phase. Phytochemical investigation of C. erythraea herb and F. caroliniensis roots resulted into isolation of 25 xanthones and three secoiridoids the structure of which was elucidated by spectroscopic means (NMR, MS and UV). 1,3,8-Trihydroxy-5,6-dimethoxyxanthone, isolated from C. erythraea, turned out to be a novel xanthone. The stability of the analytes was tested by subjecting samples to light, moisture and different temperatures. After six months of storage, decomposition of gentiopicroside and sweroside was observed. The swertiamarin content was nearly unchanged when stored at room temperature or in the refrigerator, but high temperature conditions reduced the content to 85%. In contrast, xanthones were stable under long-term, refrigerated and accelerated conditions. The established chromatographic method has been successfully applied for the quantification of the bioactive compounds in the three plants. The presence and distribution of polyoxygenated xanthones within the three members of the Gentianaceae family and their significance as analytical markers are discussed.

Antibacterial and antifungal screening of Centaurium pulchellum crude extracts and main secoiridoid compounds.

The main principles of C. pulchellum (Sw.) Druce, secoiridoid glycosides, have been studied as potent bioactive compounds. Here we scored their content in extracts of ten populations of this species. Antibacterial and antifungal assays of the extracts and pure secoiridoid glycosides were performed against eight bacterial strains and five fungal species. Methanol extracts from both aerial parts and roots exhibited excellent antibacterial (0.05-0.2 mg mL(-1)) and very good antifungal (0.1-2 mg mL(-1)) activity. Pure secoiridoid glycosides isolated from these extracts demonstrated very strong antibacterial (0.01-0.04 mg mL(-1)) and especially antifungal (0.001-0.1 mg mL(-1)) activity.