Anti-photoaging effect and the mechanism of Coreopsis tinctoria okanin against UVB-induced skin damage in mice.

Long-term exposure to ultraviolet radiation may cause photoaging of skin tissues. Coreopsis tinctoria Nutt. riches a variety of flavonoids with strong antioxidant activities. In the present study, the main antioxidant flavonoid was isolated from C. tinctoria and identified as okanin by Mass spectrum and Nuclear Magnetic Resonance Spectroscopy. Okanin was found to effectively reduce the malondialdehyde content, increase various intracellular antioxidant enzyme activities, relieve epidermal hyperplasia and dermal damage caused by UVB irradiation, and increase the collagen fibers' content in the dorsal skin tissue of mice. Immunohistochemical analysis showed that okanin effectively counteracted the photoaging effect of UVB-induced by down-regulating IL-1, IL-6, TNF-α, and COX-2, and up-regulating COL-1, COL-3, and HYP expression. In addition, okanin can inhibit skin photoaging by regulating TNF-ß/Smad2-3, MAPK, P13K/AKT, and NF-κB signaling pathways. In particular, the three key markers of photoaging, MMP (MMP-1/-3/-9), were down-regulated and five collagen synthesis genes (COL1A1, COL3A1, COL5A2, COL6A1, and COL7A1) were up-regulated, underlines the direct anti-photoaging mechanism of okanin in preventing collagen degradation and promoting collagen synthesis. The current investigation provides new insights into the great potential of okanin in alleviating skin photoaging and lays theoretical references for the development ofanti-photoaging products.

Optimizing Coreopsis tinctoria Flower Extraction and Inhibiting CML Activity: Box-Behnken Design.

BACKGROUND: Chronic myelogenous leukemia (CML) is an uncommon type of cancer of the bone marrow associated with high mortality. Although several effective therapies have been developed to reduce symptoms in patients with CML, many of these methods are associated with side effects. Coreopsis tinctoria Nutt. (C. tinctoria) is a natural medicinal material that possesses antioxidant and anticancer activities. Yet, its effect in treating leukemia has still not been fully explored. OBJECTIVE: To optimize the C. tinctoria flower extraction process and investigate whether these extracts can impair CML cell survival. METHODS: The extraction process of C. tinctoria was optimized by the Box-Behnken design response surface method. K562 cells were treated with different volumes (0, 10, 25, 50, and 100 µL) of C. tinctoria flower extracts. The effect of C. tinctoria extract on cell morphology and cell apoptosis was assessed by light microscopy, laser confocal microscopy, and flow cytometry. RESULTS: We established the following optimized C. tinctoria flower extraction conditions: temperature of 84.4°C, extraction period of 10 mins, solid-liquid ratio of 1:65, and times 4. These conditions were applied for C. tinctoria flower extraction. Pre-incubation of extracts prepared under the aforementioned optimal conditions with K562 cells induced cell cytotoxicity and cell apoptosis. CONCLUSION: C. tinctoria flower extracts exert obvious anti-leukemia effects in vitro and may be a potential drug candidate for leukemia treatment.

UPLC-quadrupole time-of-flight-tandem mass spectrometry combined with chemometrics and network pharmacology to differentiate Coreopsis tinctoria Nutt.

Coreopsis tinctoria Nutt. (C. tinctoria) is a traditional medicinal plant, primarily found in plateau areas with altitudes exceeding 3000 m. The efficacy of C. tinctoria appears to be intricately tied to its quality. However, there is a scarcity of studies focused on evaluating the quality of C. tinctoria from diverse geographical locations. In this study, we used ultra-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry to analyze and identify the prevalent chemical components in 12 batches of C. tinctoria sourced from Xinjiang, Qinghai, Tibet, and Yunnan provinces in China. By using cluster analysis and discriminant analysis of partial least squares, we assessed the similarity and identified varying components in the 12 batches of C. tinctoria. Subsequently, their quality was further evaluated. Utilizing network pharmacology, we identified potential active components for the treatment of diabetes mellitus. The findings revealed the presence of 16 flavonoids, 3 phenylpropanes, 2 sugars, 2 amino acids, and 7 hydrocarbons in the analyzed samples. Through variable importance screening, 17 constituents were identified as quality difference markers. Marein and flavanomarein emerged as pivotal markers, crucial for distinguishing variations in C. tinctoria. In addition, network pharmacology predicted 187 targets for 9 common active components, including marein and flavanomarein. Simultaneously, 1747 targets related to diabetes mellitus were identified. The drug-component-disease target network comprised 91 nodes and 179 edges, encompassing 1 drug node, 9 component nodes, and 81 target nodes. In summary, marein and flavanomarein stand out as key biomarkers for assessing the quality of C. tinctoria, offering a scientific foundation for the quality evaluation of C. tinctoria Nutt.

Optimization of preparation method of hepatoprotective active components from Coreopsis tinctoria Nutt. and its action mechanism in vivo.

Capitula of Coreopsis tinctoria are widely used as a flower tea with great health benefits due to rich content of flavonoids and phenolic acids. The hepatoprotective effect of C. tinctoria and its bioactive basis have seldom been investigated until now. In the present study, capitula of C. tinctoria were extracted with a method optimized by response surface methodology (RSM) and BoxBehnken design (BBD) and further purified by macroporous resin HPD-300 to obtain a fraction (CE) enriched with flavonoids and phenolic acids. The contents of the four most abundant compounds, isookanin-7-O-ß-d-glucoside (1), quercetigetin-7-O-ß-d-glucoside (2), okanin (3), and marein (4), were determined by HPLC as 9.98, 5.21, 41.78 and 1.85 mg/g, respectively. Seventy-four compounds including fifity-five flavonoids, fifteen organic acids (twelve of them were phenolic compounds), and three coumarins were tentatively identified in CE by LC-HRMS/MS. In vivo hepatoprotective effect and potential mechanism of CE were studied with a high-fat diet-induced NASH mouse model. CE administration decreased the amount of weight gain, hepatic lipid, and sequentially improved dyslipidemia, inflammation, oxidative stress, and IR in HFD-fed mice. Molecular data revealed that CE inhibited hepatic inflammation by reducing NFκB/iNOS/COX-2/NLRP3/MAPK in the liver tissues and ameliorated oxidative stress by activating the Nrf2/HO-1 pathway. Modulation of inflammation and oxidative stress with CE may represent a promising target for the treatment of NAFLD and provide insight into the mechanism by which CE protects against obesity.

Supercritical CO2 extraction, chemical composition, and antioxidant effects of Coreopsis tinctoria Nutt. oleoresin.

Coreopsis tinctoria Nutt. was used to extract oleoresin through supercritical CO2 extraction technology. The extraction conditions were optimized using response surface methodology, and the chemical composition of C. tinctoria Nutt. oleoresin (CTO) was analyzed. Under the optimal conditions, the antioxidant activity of oleoresin was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH˙) and 2,2'-azino-bis-(3-ethylbenzo-thiazoline-6-sulphonic acid)diammonium salt (ABTS˙+) free radical scavenging assays. The optimal extraction conditions were a 27.5 MPa extraction pressure, a 45°C extraction temperature, and a 3 h extraction time. Under these extraction conditions, oleoresin yield was up to 3.163%. Compared to steam distillation extraction, the CTO extracted using supercritical CO2 had more abundant components. The EC50 of CTO for DPPH˙ and ABTS˙+ free radical scavengers was 1.54 and 1.07 mg/mL, respectively.

Study on the metabolism profile of flavanomarein in Coreopsis tinctoria Nutt.

Coreopsis tinctoria Nutt. (family Asteraceae) is a popular medicine-food plant, which improves chronic diseases such as hyperlipemia, hypertension, and diabetes. Flavanomarein is the main active component of Coreopsis tinctoria Nutt, in which the blood concentration of volunteers is low and bioavailability is poor. Thus, the understanding of flavanomarein metabolites and metabolic pathways is significant to clarify its effectiveness. This study systematically studied the metabolites of flavanomarein by oral and injection. The biological samples (feces, urine, and plasma) were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry in negative ion mode. The metabolic law of flavanomarein in the liver was further verified by a liver microsomal incubation experiment in vitro. A total of 12 metabolites were identified by oral administration while 15 metabolites were detected by injection. It was shown that metabolic pathways include acetylation, hydroxylation, glucuronidation, methylation, dehydrogenation, and so forth. The liver extraction rate of flavanomarein was 0.08, which means the metabolic stability of flavanomarein is well in rats' liver microsomes. It is a systematic study on the metabolism of flavanomarein and provides a metabolic rationale for further in-depth in vivo biotransformation.

The Antitumor Effect and Mechanism of Total Flavonoids From Coreopsis Tinctoria Nutt (Snow Chrysanthemum) on Lung Cancer Using Network Pharmacology and Molecular Docking.

Coreopsis tinctoria Nutt (C. tinctoria), also known as Snow Chrysanthemum, is rich in polyphenols and flavonoids. It has important pharmacological effects such as lowering blood lipids, regulating blood glucose, and anti-tumor effect. However, its anti-tumor mechanism has not yet been investigated thoroughly. This study aimed to explore the anti-tumor effect of total flavonoids extracted from C. tinctoria (CTFs) on lung cancer and the possible mechanism. The components of CTFs were analyzed using Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The active components of CTFs were screened according to oral bioavailability (OB) and drug-likeness (DL). Totally, 68 components of CTFs were identified and 23 active components were screened. Network pharmacological analysis on the active components identified 288 potential targets associated with lung cancer. After protein-protein interaction (PPI) network topology analysis, 17 key protein targets including Akt1, MAPK1, TP53, Bcl-2, Caspase-3, Bax, GSK3B and CCND1 were screened. The molecular docking results showed that the active components of CTFs had good binding activity with key targets. GO and KEGG analysis of candidate targets found that the main enrichment was in PI3K/Akt-mediated intrinsic apoptotic pathways. Finally, according to the results of network pharmacology, the potential molecular mechanism of CTFs intervention in lung cancer was validated experimentally in vitro and in vivo. The experimental validation results demonstrated that the antitumor activity of CTFs on lung cancer may be related to inhibiting the PI3K-Akt signaling pathway and activating the mitochondrial-mediated apoptosis pathway.

Comparison of Metabolome and Transcriptome of Flavonoid Biosynthesis in Two Colors of Coreopsis tinctoria Nutt.

Coreopsis tinctoria Nutt. (C. tinctoria) has a long history of application and high economic and medicinal value. Flavonoids, the main active components of C. tinctoria, are widely studied in pharmacology and food development. However, the flavonoid biosynthesis pathway in C. tinctoria is unclear. In this study, we comprehensively compared the transcriptomes and metabolite profiles of two colors of C. tinctoria flowers (LS and JS) at different flowering stages. A total of 165 flavonoids (46 flavonoids, 42 flavonols, 22 anthocyanins, 18 chalcones, 12 dihydroflavonols, nine isoflavones, eight dihydroflavonoids, six flavanols, and two tannins) were identified in LS and JS at different flowering stages. Thirty-three metabolites (11 anthocyanins, 11 flavonols, seven flavonoids, two dihydroflavonols, one dihydroflavone, and one chalcone) were found to be statistically significantly different in the LS vs. JS groups. LS flowers accumulated higher levels of 10 anthocyanins (seven cyanidins and three pelargonidins) than JS flowers. Furthermore, candidate genes related to the regulation of flavonoid and anthocyanin synthesis were identified and included 28 structural genes (especially F3H, Cluster-28756.299649, and 3GT, Cluster-28756.230942) in LS and JS, six key differentially expressed transcription factors (especially MYB90a, Cluster-28756.143139) in LS and JS, and 17 other regulators (mainly including transporter proteins and others) in LS. Our results provide valuable information for further studies on the mechanism underlying flavonoid biosynthesis in C. tinctoria.

Mechanisms of Coreopsis tinctoria Nutt in the treatment of diabetic nephropathy based on network pharmacyology analysis of its active ingredients / Mecanismos de Coreopsis tinctoria Nutt. En el tratamiento de la nefropatía diabética basado en el análisis farmacológico de red de sus principios activos

SUMMARY: Coreopsis tinctoria Nutt. (C. tinctoria Nutt.) can protect diabetic kidneys, but the mechanisms are unclear. This work is to investigate the potential mechanisms of C. tinctoria Nutt. in the treatment of diabetic nephropathy based on network pharmacology analysis of its active ingredients. Twelve small molecular compounds of C. tinctoria Nutt. and targets related to diabetic nephropathy were docked by Discovery Studio 3.0. DAVID database was used for GO enrichment and KEGG pathway analysis. Cytoscape 3.6.1 was used to construct active ingredient-target network. Cell viability was detected with MTT. Glucose consumption was analyzed with glucose oxidase method. Protein expression was measured with Western blot and immunofluorescence. Electron microscopy observed autophagosomes. The core active ingredients of C. tinctoria Nutt. included heriguard, flavanomarein, maritimein, and marein. Twenty-one core targets of the 43 potential targets were PYGM, TLR2, RAF1, PRKAA2, GPR119, INS, CSF2, TNF, IAPP, AKR1B1, GSK3B, SYK, NFKB2, ESR2, CDK2, FGFR1, HTRA1, AMY2A, CAMK4, GCK, and ABL2. These 21 core targets were significantly enriched in 50 signaling pathways. Thirty- four signaling pathways were closely related to diabetic nephropathy, of which the top pathways were PI3K/AKT, insulin, and mTOR, and insulin resistance. The enriched GO terms included biological processes of protein phosphorylation, and the positive regulation of PI3K signaling and cytokine secretion; cellular components of cytosol, extracellular region, and extracellular space; and molecular function of protein kinase activity, ATP binding, and non-membrane spanning protein tyrosine kinase activity. In vitro experiments found that marein increased the expression of phosphorylated AKT/AKT in human renal glomerular endothelial cells of an insulin resistance model induced by high glucose, as well as increased and decreased, respectively, the levels of the microtubule-associated proteins, LC3 and P62. C. tinctoria Nutt. has many active ingredients, with main ingredients of heriguard, flavanomarein, maritimein, and marein, and may exert anti-diabetic nephropathy effect through various signaling pathways and targets.

RESUMEN: Coreopsis tinctoria Nutt. (C. tinctoria Nutt.) puede proteger riñones diabéticos, sin embargo los mecanismos son desconocidos. Este trabajo se realizó para investigar los potenciales mecanismos de C. tinctoria Nutt. en el tratamiento de la nefropatía diabética basado en el análisis de farmacología en red de sus principios activos. Doce compuestos moleculares pequeños de C. tinctoria Nutt. y los objetivos relacionados con la nefropatía diabética fueron acoplados por Discovery Studio 3.0. La base de datos DAVID se utilizó para el enriquecimiento GO y el análisis de la vía KEGG. Se usó Cytoscape 3.6.1 para construir una red de ingrediente-objetivo activa. La viabili- dad celular se detectó mediante MTT. El consumo de glucosa se analizó con el método de glucosa oxidasa. La expresión proteica fue determinada mediante Western blot e inmunofluorescencia. En la microscopía electrónica se observó autofagosomas. Los principales ingredientes activos de C. tinctoria Nutt. incluyeron heriguard, flavanomarein, maritimin y marein. Veintiún de los 43 objetivos potenciales fueron PYGM, TLR2, RAF1, PRKAA2, GPR119, INS, CSF2, TNF, IAPP, AKR1B1, GSK3B, SYK, NFKB2, ESR2, CDK2, FGFR1, HTRA1, AMY2A, CAMK4, GCK y ABL2. Estos 21 objetivos principales se enriquecieron significativamente en 50 vías de señalización. Treinta y cuatro vías de señalización estuvieron estrechamente relacionadas con la nefropatía diabética, de las cuales las principales vías fueron PI3K/ AKT, insulina y mTOR, y resistencia a la insulina. Los términos GO enriquecidos incluyeron procesos biológicos de fosforilación proteica, la regulación positiva de la señalización de PI3K y la secreción de citoquinas; componentes celulares del citosol, región extracelular y espacio extracelular; y la función molecular de la actividad de la proteína quinasa, la unión de ATP y la actividad de la proteína tirosina quinasa que no se extiende por la membrana. Los experimentos in vitro encontraron que la mareína aumentaba la expresión de AKT/AKT fosforilada en células endoteliales glomerulares renales humanas en un modelo de resistencia a la insulina inducida por niveles elevados de glucosa, así como aumentaron y disminuyeron respectivamente, los niveles de las proteínas asociadas a los microtúbulos, LC3 y P62. C. tinctoria Nutt. tiene muchos principios activos, con ingredientes principales de heriguard, flavanomarein, maritimain y marein, y puede ejercer un efecto de nefropatía antidiabética a través de distintass vías de señalización y objetivos.

Physiological changes and transcript identification in Coreopsis tinctoria Nutt. in early stages of salt stress.

Coreopsis tinctoria Nutt. (C. tinctoria) is a special tea ingredient that adapts to certain salt stresses and shares the functions of chrysanthemum. With annual expansion of the cultivation area of C. tinctoria in Xinjiang (China), soil salinity may become a constraint for chrysanthemum cultivation. To investigate the response of C. tinctoria to salt stress, physiological and transcriptional changes in C. tinctoria in the early stages of low (50 mM NaCl) and high (200 mM NaCl) salt stress were analyzed and identified. The results showed that the contents of osmotic regulators (free proline, soluble sugar, and soluble protein) and antioxidant enzymes (catalase and peroxidase) under salt stress increased to various extents compared with those of the control (CK) within 72 h, and the increase was higher under 200 mM NaCl treatments. De novo RNA-seq was used to analyze changes in the transcripts under 50 and 200 mM NaCl treatments for up to 48 h. In total, 8,584, 3,760, 7,833, 19,341, 13,233, and 9,224 differentially expressed genes (DEGs) were detected under 12 h, 24 h, and 48 h for 50 and 200 mM NaCl treatments, respectively. Weighted correlation network analysis (WGCNA) was used to analyze the correlations between all DEGs and physiological indexes. We found that the coexpression modules blue2 and Lightskyblue4 highly correlated with osmotic regulators and CAT and identified 20 and 30 hub genes, respectively. The results provide useful data for the further study of salt tolerance in C. tinctoria.

Isolation, purification and structural characterization of two pectin-type polysaccharides from Coreopsis tinctoria Nutt. and their proliferation activities on RAW264.7 cells.

Coreopsis tinctoria Nutt. (C.tinctoria) is an annual herb of the Compositae family with many health benefits, such as clearing heat, antioxidant and anticancer activity. In this paper, two polysaccharides were isolated from C.tinctoria, named CTAP-1 and CTAP-2, respectively. Structure of CTAP-1and CTAP-2 were elucidated by high-performance gel permeation chromatography, chemical derivative analyses, GC-MS and NMR techniques. Results reveal that they both CTAP-1 and CTAP-2 consisted of predominant amounts of galacturonic acid residues along with small amounts of arabinose, rhamnose and galactose.Both them contain homogalacturonan and rhammnogalcturan I regions in different ratio, suggesting their pectin-type features. The proliferation activities of CTAP-1 and CTAP-2 on RAW264.7 cells in vitro were detected. Results show both them have the significant proliferation effect on RAW264.7 cells when the concentration from 40 to 200 µg/mL. Given their structural characteristics and proliferation activities, the pectins are expected to be potential natural immune modulators, which need further study.

Okanin in Coreopsis tinctoria Nutt is a major quorum-sensing inhibitor against Chromobacterium violaceum.

ETHNOPHARMACOLOGICAL RELEVANCE: Coreopsis tinctoria Nutt has various medical and functional properties and its flower is widely used as health-care tea to decrease blood glucose and to lower blood lipids. However, the quorum sensing (QS) inhibition activity of Coreopsis tinctoria Nutt flower remains unclear. AIM OF THE STUDY: To assess inhibitory activity against quorum sensing by Chromobacterium violaceum, to identify the chemical composition of the extracts and to disclose the action mechanism of separated compound. MATERIAL AND METHODS: Violacein inhibition assays were performed in 96-wells microplates. The compounds extracted from Coreopsis tinctoria Nutt flower were separated and purified by various chromatography techniques. Respectively, thin layer chromatography (TLC, GF254), mass spectrometer (Agilent 1100 Series LC/MSD Trap SL), Medium-pressure automatic purification system (Buscisepacore C 620, Switzerland), High performance liquid chromatography (HPLC, Shimadzu LC-20AD, Japan), Liquid preparation Chromatography (Waters2545, USA). The chemical structures were identified by nuclear magnetic resonance (NMR, Bruker AV-500, Germany) technique. The inhibitory mechanism of okanin against C. violaceum quorum sensing was detected by quantitative real-time PCR (qRT-PCR). RESULTS: Quorum sensing regulates production of bacterial virulence factors, thereby making it an intriguing target for attenuating bacterial pathogenicity. In this study, anti-QS activity of Coreopsis tinctoria Nutt methanol fraction (CTM) was investigated against C. violaceum ATCC12472. CTM showed an inhibitory effect on the QS-mediated virulence factors production such as violacein in C. violaceum without effect on growth rate. Also, okanin was isolated from CTM and its potential of anti-QS was confirmed after observing a significant reduction of violacein production in C. violaceum. An attempt was made to assess the effect of okanin on vioABCDE expression in C. violaceum to disclose acting mechanisms. CONCLUSIONS: The results of this study contribute to validate an inhibitory effect of Coreopsis tinctoria Nutt flower on quorum sensing by Chromobacterium violaceum and to determine the compound responsible for inhibition. Also, the inhibitory effect was achieved in tandem with the down-regulation of vio operon.

Screening of the active fractions from the Coreopsis tinctoria Nutt. Flower on diabetic endothelial protection and determination of the underlying mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: The Coreopsis tinctoria Nutt. flower (CTF) has been used traditionally in China for treating hypertension and diabetes as well as reducing body weight and blood fat. However, the vascular protection effect of the CTF has not been studied to date. AIM OF THE STUDY: This study aimed to screen and identify bioactive fractions from the CTF with a diabetic endothelial protection effect and to clarify the underlying mechanism. MATERIALS AND METHODS: The vascular protection effect of Fraction A was studied in high-fat diet and streptozocin-induced diabetic models. The endothelial protection effect of Fraction A-2 was further studied in an in vitro vascular endothelial dysfunction model induced by high glucose. In a high glucose-induced human umbilical vein endothelial cell (HUVEC) model, Fractions A-2-2 and A-2-3 were screened, and their detailed mechanisms of endothelial protection were studied. Liquid chromatography mass spectrometry (LC-MS) was used to identify the main components in Fractions A-2-2 and A-2-3. RESULTS: Fraction A treatment significantly improved the endothelium-dependent vasodilation of the mesenteric artery induced by acetylcholine in diabetic rats. The maximum relaxation was 79.82 ± 2.45% in the control group, 64.36 ± 9.81% in the model group, and 91.87 ± 7.38% in the Fraction A treatment group (P < 0.01). Fraction A treatment also decreased rat tail pressure compared with the model group at the 12th week. The systolic blood pressure was 152.7 5 ± 16.99 mmHg in the control group, 188.50 ± 5.94 mmHg in the model group, and 172.60 ± 14.31 mmHg in the Fraction A treatment group (P < 0.05). The mean blood pressure was 128.50 ± 13.79 mmHg in the control group, 157.00 ± 6.06 mmHg in the model group, and 144.80 ± 11.97 mmHg in the Fraction A treatment group (P < 0.05). In an in vitro vascular endothelium-dependent vasodilation dysfunction model induced by high glucose, Fraction A-2 improved the vasodilation of the mesenteric artery. The maximum relaxation was 82.15 ± 16.24% in the control group, 73.29 ± 14.25% in the model group, and 79.62 ± 13.89% in the Fraction A-2 treatment group (P < 0.05). In a high glucose-induced HUVEC model, Fraction A-2-2 and Fraction A-2-3 upregulated the expression of IRS-1, Akt, and eNOS and increased the levels of p-IRS-1Ser307, p-Akt Ser473, and p-eNOSSer1177 and also decreased the expression of NOX4, TNF-α, IL-6, sVCAM, sICAM, and NF-κB (P < 0.01). With the intervention of AG490 and LY294002, the above effects of Fraction A-2-2 and Fraction A-2-3 were inhibited (P < 0.01). LC-MS data showed that in Fraction A-2-2 and Fraction A-2-3, there were 10 main components: flavanocorepsin; polyphenolic; flavanomarein; isochlorogenic acid A; dicaffeoylquinic acid; coreopsin; marein; coreopsin; luteolin-7-O-glucoside; and 3',5,5',7-tetrahydroxyflavanone-O-hexoside. CONCLUSION: The protective effect of the CTF on diabetic endothelial dysfunction may be due to its effect on the JAK2/IRS-1/PI3K/Akt/eNOS pathway and the related oxidative stress and inflammation. The results strongly suggested that Fraction A-2-2 and Fraction A-2-3 were the active fractions from the CTF, and the CTF might be a potential option for the prevention of vascular complications in diabetes.

The chemical components of Coreopsis tinctoria Nutt. and their antioxidant, antidiabetic and antibacterial activities.

Seventeen compounds were isolated from the capitula of Coreopsis tinctoria Nutt. with various column chromatographic methods and semi-preparative HPLC. Their structures were identified by the spectroscopic data and comparison with literatures as 2'-hydroxy-4,4'-dimethoxy-chalcone; (1), isoliquiritigenin (2), eriodictyol (3), naringenin (4), maritimetin (5), butin (6), taxifolin (7), luteolin (8), 7,3',4'-trihydroxyflavone (9), 8,3',4'-trihydroxyflavone-7-O-ß-d-glucoside (10), quercetin (11), quercetagitin-7-O-ß-d-glucoside (12), quercetin-7-O-ß-d-glucoside (13), 3,4-dihydroxybenzoic acid (14), caffeic acid (15), coreoside B (16), and myo-inositol (17). Compounds 1, 4, 9, 10 and 17 were isolated from C. tinctoria Nutt. for the first time. Compounds 7 and 12 possessed the highest antioxidant activity (IC50 = 64.37 and 32.86 µg/ml, respectively) among the tested compounds (IC50 value of positive control was 5.34 µg/ml). Compound 7 exhibited potent PTP1B enzymatic inhibition with an IC50 value of 7.73 µg/ml (IC50 value of positive control is 1.46 µg/ml). Furthermore, compound 5 showed strong antibacterial activity against the Gram-positive bacterium, S. aureus.

Anti-Lipid Peroxidation, α-Glucosidase and α-Amylase Inhibitory Effects of the Extract of Capitula of Coreopsis tinctoria Nutt. and Protection Effects on High-Fat/High-Sugar and Streptozotocin-Induced Type 2 Diabetes in Mice.

Coreopsis tinctoria capitula (CTC) of the Compositae family has been used traditionally to treat various diseases in China, particularly type 2 diabetes mellitus (T2DM). This study evaluated the anti-lipid peroxidation, α-glucosidase and α-amylase inhibitory effects of CTC extracts, and analyzed its chemical composition by HPLC. Moreover, the antioxidant activity and protection effects of CTC extracts were investigated on high-fat/high-sugar and streptozotocin-induced T2DM mice. In vitro study, the ethyl acetate extract (EAE) and butanol extract (BE) of CTC exhibited anti-lipid peroxidation (IC50 : BHA>BE or EAE>ascorbic acid, p<0.05) and α-glucosidase inhibitory activity (IC50 : BE>EAE, p<0.05). In vivo, the BE at the dose of 600 mg/kg was intragastrically given to T2DM mice, which exhibited a certain extent of repair and improvement of the levels of CAT, GSH, GSH-PX , SOD, as well as plasma biomarkers, compared with those in the model group (p<0.05). These results demonstrated that CTC extracts have a positive effect to treat T2DM and it can be used for the treatment of T2DM in the future.

[Protective Effect of a Dihydroflavonol Glycoside from Coreopsis tinctoria Nutt. in Mouse Model of Alcoholic Acute Pancreatitis].

OBJECTIVE: To investigate the protective effect of (2R, 3R)-dihydroquercetin 7-O-ß-D-glucopyranose (C1) extracted from Coreopsis tinctoria Nutt. in a mouse model of alcoholic acute pancreatitis (FAEE-AP) induced byfatty acid ethyl ester (FAEE). METHODS: The 30 healthy SPF mice were randomly divided into control group, model group, low dose group, middle dose group and high dose group, 6 in each group. Alcoholic pancreatitis was induced by ethanol and palmitoleic acid administration (1.75 g/kg ethanol, 200 mg/kg palmitoleic acid, 2 times peritoneal injections). The three treatment groups were given C1 (0 h, 4 h, 8 h) at the dose of 12.5, 25 and 50 mg/kg, respectively. After 24 h of molding, the serum amylase, lipase and IL-6 levels were detected. The trypsin level in pancreatic tissue and myeloperoxidase (MPO) level in pancreatic and lung tissue were detected. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of pancreatic tissue and immunohistochemical (IHC) staining was used to detect the expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) in pancreatic tissue. RESULTS: The pancreatic histopathological scores, serum amylase and lipase activity, trypsin level in pancreatic tissue, serum IL-6 level, MPO level of pancreas and lung were significantly higher in the model group than in the control group (P < 0.01). Compared with the model group, the pancreatic histopathologies of the low dose group was significantly improved (P < 0.05), as well as the serum amylase and lipase activity, trypsin level of pancreas, serum IL-6 level, the pancreas andthe lung's MPO level decreased significantly (P < 0.05), and up-regulate that expression of Nrf2 in pancreatic tissue. CONCLUSION: 12.5 mg/kg of (2R, 3R) -dihydroquercetin 7-O-ß-D-glucopyranose (C1) improved the expression of Nrf2, reduced the expression of inflammatory factor IL-6, and protected acute pancreatitis caused by FAEE.

Classification of edible chrysanthemums based on phenolic profiles and mechanisms underlying the protective effects of characteristic phenolics on oxidatively damaged erythrocyte.

In this study, phenolic profiles of chrysanthemums derived from five main species were determined for characterization of rationality of their application in tea, beverages and functional foods. A total of 41 phenolics including 3 phenolic acids, 17 flavones, 9 flavanones, 1 dihydroflavonol, 4 flavonols, 4 chalcones and 3 aurones were identified. The contents of 22 characteristic phenolics were simultaneously determined. Chrysanthemum morifolium cv. 'Qiju' (with abundant phenolics) and Coreopsis tinctoria Nutt. (with unique and abundant flavonoid aglycones and glycosides), exhibited excellent cellular antioxidant activities and strong market potentials. Chlorogenic acid, 3,5-dicaffeoylquinic acid and luteolin-7-O-glucoside largely contributing to cellular antioxidant activity of 'Qiju' by forming protective membrane around erythrocyte should be markers for quality control of 'Qiju'. Okanin, the gut microbial-produced metabolite of marein, possessed strong protective effect on oxidatively damaged erythrocyte via incorporating in membrane and entering cytoplasm. Okanin and marein should be markers for quality control of C. tinctoria.

Structural characterization of a polysaccharide from Coreopsis tinctoria Nutt. and its function to modify myeloid derived suppressor cells.

Coreopsis tinctoria Nutt. (C. tinctoria) is a natural plant with many health benefits, such as clearing heat and toxic materials. In this study, we investigate the effect of a polysaccharide from C. tinctoria, aiming at improving the tumor microenvironment, which is associated with non-resolving inflammation. Through combining ion-exchange and gel permeation chromatography, a polysaccharide named CTAP-3 is purified from the crude polysaccharides of C. tinctoria. The structure of CTAP-3 is characterized through high-performance gel permeation chromatography, chemical derivative analyses, GC-MS, FT-IR, and NMR. Results reveal that CTAP-3 consists of predominant amounts (87.2%) of galacturonic acid (GalA) residues, small amounts of arabinose (Ara) and rhamnose (Rham), and trace amounts of galactose (Gal). CTAP-3 is deduced to be native pectin-type polysaccharide containing a homo-galacturanan backbone consisting of α-(1 → 4)-linked GalAp and methyl-esterified α-(1 → 4)-linked GalAp residues in the ratio of 4:1. When myeloid-derived suppressor cells (MDSCs) are treated by CTAP-3, its suppressive effect on T cell proliferation is impaired. This result indicates that CTAP-3 is a candidate drug for improving the tumor microenvironment.

Evaluation of the Nitric Oxide and Nitrite Scavenging Capability, N-Nitrosamine Formation Inhibitory Activity, and Optimization of Ultrasound-Assisted Aqueous Two-Phase System Extraction of Total Saponins from Coreopsis tinctoria Flowering Tops by Response Surface Methodology.

Coreopsis tinctoria flowering tops (CTFs) is a popular health product as herbal tea or as a traditional medicinal herb that is rich in saponins and exerts substantial biological activity. In this study, an ultrasound-assisted aqueous two-phase system (ATPS) was utilized to extract total saponins from CTFs and optimize the extraction process by response surface methodology. Moreover, the nitric oxide and nitrite scavenging capability, and N-nitrosamine formation inhibitory activity of total saponins were evaluated. Results showed that the optimal conditions for total saponins were 37.76% (w/w) ammonium sulfate and 35.62% (w/w) ethanol in ATPS coupled with ultrasonic-assisted extraction. Under the optimal conditions, the maximum yield of total saponins of 33.4 g/kg can be obtained from the CTFs raw material. The nitric oxide radical scavenging, nitrite scavenging, and N-nitrosamine inhibitory activities (SC50) were 287.92 ± 7.42, 191.63 ± 7.69, and 1787.4 ± 51.26 µg/mL, respectively. The total saponins has a certain nitric oxide and nitrite scavenging capability, and N-nitrosamine formation inhibitory activity in vitro. Given these activities, research on saponins from CTFs provides profound and lasting implications for the novel applications of C. tinctoria.

Isolation, characterization and antimicrobial activities of polyacetylene glycosides from Coreopsis tinctoria Nutt.

Polyacetylene glycosides, (6Z, 12E)-tetradecadiene-8,10-diyne-1-ol-3(R)-O-ß-D-glucopyranoside (trivially named coreoside E) and (6Z, 12E)-tetradecadiene-8,10-diyne-1-ol-3(R)-O-ß-L-arabinopyranosyl-(1 â†’ 2)-ß-D-glucopyranoside (trivially named coreoside F), were isolated from buds of Coreopsis tinctoria Nutt., together with one known compound, coreoside B. Their chemical structures were elucidated by extensive spectroscopic analysis and on the basis of their chemical reactivities. Coreoside E exhibited high levels of antimicrobial activity against Staphylococcus aureus and Bacillus anthracis with minimum inhibitory concentrations of 27 ± 0.27 and 18 ± 0.40 µM, respectively, whereas coreoside F and coreoside B showed weak antimicrobial activity against S. aureus and B. anthracis.