Application of fingerprint combined with QAMS in quality evaluation of Aurantii Immaturus Fructus / 中草药

Objective: This paper aims to provide the experimental foundation for quality control of Aurantii Immaturus Fructus from different habitats by analyzing the multi-component qualitatively and quantitatively. Methods: Fingerprint pattern and QAMS were combined in this experiment, and HPLC analysis was performed on a Waters X-Brige C18 (200 mm × 4.6 mm, 5 μm) column with mobile phase composed of acetonitrile (A) -0.1% methanoic acid solution at a flow rate of 1.0 mL/min in gradient elution mode. The column temperature was maintained at 30 ℃, the injection volume was 10 μL, and the detection wavelengths were set at 283 and 330 nm. Results: The HPLC-UV fingerprint of Aurantii Immaturus Fructus from different habitats was established with 21 common peaks, 9 of them were identified as narirutin, naringin, hesperidin, neohesperidin, naringenin, hesperetin, sinensetin, nobiletin and tangeretin, and the similarity of 23 batches of samples were greater than 0.9, CA and PCA show the classification is consistent with the habitats distribution of the medicine. Then, the QAMS result showed some differences with neohesperidin to be the internal standard. Conclusion: From the perspective of composition, there are some differences in the quality of Aurantii Immaturus Fructus from different habitats, and the method of QAMS is accurate, efficient and feasible, which has obvious advantages than standard curve method and external standard method. In a word, it can be applied to quality evaluation and provides the experimental foundation for quality control of Aurantii Immaturus Fructus from different habitats.

Chemical constituents of Schoenoplectus tabernaemontani / 中草药

Objective: To study the chemical constituents of the rhizomes of Schoenoplectus tabernaemontani. Methods: Compounds were isolated and purified by a combination of column chromatography including silica gel, polyamide and Sephadex LH-20. Their structures were elucidated by physiochemical properties and NMR analysis. Results: Twelve compounds were obtained from water extract of the rhizome of S. tabernaemontani and identified as 5,7,2',4'-tetrahydroxy-3, 5'-dimethoxyflavone (1), tricin (2), hesperetin (3), quercetin (4), luteolin (5), eriodictyol (6), apigenin (7), naringenin (8), chrysin (9), 5,7-dihydroxychromone (10), catechin (11) and tricin-7-O-β-D-glucoside (12), respectively. Conclusion: Compound 1 is a new flavone named schoenin. Compounds 2-5 and 7-12 are isolated from the Cyperaceae for the first time. Compound 6 is isolated from the genus Scirpus for the first time.

Hesperetin derivative-12 (HDND-12) regulates macrophage polarization by modulating JAK2/STAT3 signaling pathway / 中国天然药物

Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as macrophage polarization, of which play an important role in the pathogenesis of many diseases. Numerous studies have proved that Hesperidin (HDN), a traditional Chinese medicine, extracted from fruit peels of the genus citrus, play key roles in anti-inflammation, anti-tumor, anti-oxidant and so on. However, the role of HDN in macrophage polarization has never been reported. Additional, because of its poor water solubility and bioavailability. Our laboratory had synthesized many hesperidin derivatives. Among them, hesperidin derivatives-12 (HDND-12) has better water solubility and bioavailability. So, we evaluated the role of HDND-12 in macrophage polarization in the present study. The results showed that the expression of Arginase-1 (Arg-1), interleukin-10 (IL-10), transforming growth factor β (TGF-β) were up-regulated by HDND-12, whereas the expression of inducible Nitric Oxide Synthase (iNOS) was down-regulated in LPS- and IFN-γ-treated (M1) RAW264.7 cells. Moreover, the expression of p-JAK2 and p-STAT3 were significantly decreased after stimulation with HDND-12 in M1-like macrophages. More importantly, when we taken AG490 (inhibitor of JAK2/STAT3 signaling), the protein levels of iNOS were significantly reduced in AG490 stimulation group compare with control in LPS, IFN-γ and HDND-12 stimulation cells. Taken together, these findings indicated that HDND-12 could prevent polarization toward M1-like macrophages, at least in part, through modulating JAK2/STAT3 pathway.

HPLC fingerprints research on decoction pieces of Citri Reticulatae Pericarpium based on chemometrics methods combined with orthogonal partial least square discriminate analysis / 中草药

Objective To establish an HPLC method for the fingerprints analysis of decoction pieces of tangerine peel, so as to provide reference for the quality control of it. Methods Fingerprints of 17 batches of decoction pieces of tangerine peel were established by HPLC and evaluated by cluster analysis (CA), principal component analysis (PCA) and orthogonal partial least square discriminate analysis (OPLS-DA). Results The method of fingerprint of decoction pieces of tangerine peel was established, the similarities were greater than 0.9. There were 25 common peaks in the HPLC fingerprint, of which variable importance projection (VIP) of 14 peaks were greater than 1. Compared with the spectrogram of reference substances, peak 13 was narirutin, peak 14 was hesperidin, peak 23 was nobiletin, peak 24 was 3,5,6,7,8,3’,4’-heptamethoxy flavone, and peak 25 was hesperetin. Conclusion This simple and reliable method can be used for the identification and quality control of decoction pieces of Citri Reticulatae Pericarpium.

Enhanced water solubility, antioxidant activity, and oral absorption of hesperetin by D-α-tocopheryl polyethylene glycol 1000 succinate and phosphatidylcholine / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Hesperetin, an abundant bioactive component of citrus fruits, is poorly water-soluble, resulting in low oral bioavailability. We developed new formulations to improve the water solubility, antioxidant activity, and oral absorption of hesperetin. Two nano-based formulations were developed, namely hesperetin-TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) micelles and hesperetin-phosphatidylcholine (PC) complexes. These two formulations were prepared by a simple technique called solvent dispersion, using US Food and Drug Administration (FDA)-approved excipients for drugs. Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) were used to characterize the formulations’ physical properties. Cytotoxicity analysis, cellular antioxidant activity assay, and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations. The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility, which increased to 21.5- and 20.7-fold, respectively. The hesperetin-TPGS micelles had a small particle size of 26.19 nm, whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm. In addition, the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2- and 3.9-fold, respectively. Importantly, the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration (Cmax) from 2.64 μg/mL to 20.67 and 33.09 μg/mL and also increased the area under the concentration–time curve of hesperetin after oral administration to 16.2- and 18.0-fold, respectively. The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin, indicating these formulations’ potential applications in drugs and healthcare products.

Hesperetin inhibits PM2.5-induced apoptosis in H9c2 cells by attenuating oxidative stress and mitochondrial damage / 中华心血管病杂志

Objective@#To investigate the effects of hesperetin on fine particulate matter (PM2.5) induced apoptosis in H9c2 cells and related mechanisms.@*Methods@#H9c2 cells were divided into 4 groups: control group (cells were cultured without intervention), PM2.5 group (cells were treated with 800 µg/ml PM2.5), hesperetin group (H group, cells were treated by 40 µmol/L hesperetin for 1 h at 37 ℃), and hesperetin+PM2.5 group (H+PM2.5 group, cells were pretreated with hesperetin before PM2.5 treatment). Cells were cultured for corresponding interval. Apoptotic cells were detected by Annexin Ⅴ-FITC/PI apoptosis detection kit and Hoechst staining. The intracellular reactive oxygen species (ROS) levels were measured by DCFH-DA Fluorescence Probe and mitochondrial membrane potential (MMP) was detected with JC-1 staining, respectively in these groups. Apoptotic related protein and phosphorylated MAPK expression levels were determined by Western blot.@*Results@#(1) Flow cytometry results showed that the apoptosis rate of PM2.5 group ((48.94±3.20)%) was significantly higher than that of control group ((8.13±1.40)%, P<0.01), which was significantly reduced in H+PM2.5 group ((34.80±2.21)%) (P=0.003 2 vs. PM2.5 group, P<0.01 vs. control group). The number of Hoechst 33258 positive apoptotic cells was distinctly less in H+PM2.5 group than in PM2.5 group. (2) The ROS levels was significantly higher in PM2.5 group ((49.69±5.05)%) than in control group (10.57±1.33)%, P<0.01), which was significantly reduced in H+PM2.5 group ((35.08±3.90)%) (P=0.000 2 vs. PM2.5 group, P<0.01 vs. control group). (3) Green fluorescence indicating the JC-1 monomer form, which represented MMP loss of H9c2 cells, was significantly higher in PM2.5 group ((20.28±4.69)%) than in control group ((10.50±2.72)%, P<0.01), which was significantly decreased in H+PM2.5 group ((13.41±2.89)%) (P<0.01 vs. PM2.5 group, P=0.029 4 vs. control group). (4) The expression levels of Bcl-2 protein of H9c2 cells was lower in PM2.5 group ((76.94±4.52)%) than in control group (100%, P=0.000 9), which was significantly upregulated in H+PM2.5 group ((92.95±6.82)%) (P=0.027 5 vs. PM2.5 group, P=0.15 vs. control group). The expression levels of cleaved caspase-3 protein of H9c2 cells was significantly higher in PM2.5 group ((243.98±17.94)%) than in control group (100%, P=0.000 2), which was significantly downregulated in H+PM2.5 group ((200.45±4.31)%) (P=0.015 vs. PM2.5 group, P<0.01 vs. control group). (5) The expression levels of phosphorylated p38 MAPK protein of H9c2 cells was higher in PM2.5 group ((118.90±4.78)%) than in control group(100%, P=0.002 7), which could be significantly downregulated in H+PM2.5 group ((103.30±1.27)%) (P=0.01 vs. PM2.5 group, P=0.05 vs. control group). The expression levels of phosphorylated ERK protein of H9c2 cells was higher in PM2.5 group ((163.50±4.98)%) than in control group (100%, P<0.01), which was significantly downregulated in H+PM2.5 group ((139.10±2.72)%) (P=0.001 6 vs. PM2.5 group, P<0.01 vs. control group).@*Conclusions@#Hesperetin protects H9c2 cells from PM2.5 stimulation through reducing oxidative stress and protecting mitochondrial function, regulating the expression of apoptotic associated proteins as well as MAPK signal pathway, thus inhibiting H9c2 cells apoptosis.

The anti-inflammatory effect of hesperetin on lung damage induced by paraquat in rats / 中华劳动卫生职业病杂志

Objective@#To investigate the anti-inflammatory effect of hesperetin (HSP) on lung damage induced by paraquat (PQ) in rats by detecting the levels of inflammatory makers in rat lung tissues.@*Methods@#140 Wistar male rats were randomly divided into negative control group, HSP control group, HSP control group, paraquat model group, pirfenidone (PDF) positive control group, and 100, 200, 400 mg/kg HSP treatment groups. All groups were exposed to 50mg/kg paraquat by oral gavage except for the negative control group and HSP control group. After 24 hours, the rats in each group were given drug intervention once daily. 10 rats were randomly sacrificed at 7th day and 28th day after exposure to paraquat respectively. 3 rats were randomly selected from them and HE, Masson staining were used to observe the pathological changes in the lungs of each group. Each group randomly selected 6 rats at two time points to detect the levels of TGF-β1, TNF-α, IL-4, IL-10, IL-1β and IFN-γ in rat lung tissues.@*Results@#Histopathological examination found that the lung injury were reduced in the rats of PDF positive control group and all HSP treatment groups. Compared with the negative control group, the levels of TGF-β1, IL-1β, TNF-α, IL-4, and IL-10 in rat lung tissues were significantly increased (P<0.05, P<0.01) after PQ exposure at two points in time, and there was no significant difference in the level of IFN-γ in lung tissues compared with the negative control group (P>0.05) . The levels of TGF-β1, IL-1β, IL-4, IL-10 and TNF-α in the lung tissues of rats on the 7th day in different dose treatment groups of HSP were reduced compared with those in the PQ model group with varying degrees (P<0.05, P<0.01) . The level of IFN-γ in lung tissues of rats were not significantly different from that of model group (P>0.05) . The levels of TGF-β1 and TNF-α in lung tissue of rats on the 28th day in PDF positive control group and different dose treatment groups of HSP were reduced compared with those in the PQ model group with varying degrees (P<0.05, P<0.01). The levels of IFN-γ in the rat lung tissues were increased compared with those in the PQ model group (P<0.05). Besides, there were no significant in the levels of IL-1β, IL-4 and IL-10 in lung tissues compared with PQ model group (P>0.05).@*Conclusion@#HSP can reduce lung damage induced by PQ in rats by inhibiting the release of inflammatory factors and promoting the secretion of anti-inflammatory factors.

New advances in research of pharmacological effects of hesperetin and its derivatives / 中草药

Hesperetin is a dihydrogen flavonoid extracted from the Citrus fruits of the Rutaceae plants. It has many pharmacological effects, such as antibacterial, anti-inflammatory, anti-oxidant, antiviral, anti-allergy, regulating blood lipid, enhancing immunity, etc. In recent years, it is reported that hesperetin and its derivatives had anti-Alzheimer’s disease, anti-Parkinson’s disease, antihyperglycemic effect, inhibiting the venom thrombin, anti-fibrosis, ect. This paper mainly reviews some new pharmacological effects of hesperetin and its derivatives in the past five years, aiming to provide reference for further development and utilization of hesperidin and make it achieve better curative effect in other diseases.

A new alkaloid from Argyreia acuta / 中草药

Objective: To study chemical constituents of Argyreia acuta. Methods: The chemical constituents were isolated and purified by silica gel, macroporous resin adsorption, MCI GEL CHP 20P, Sephadex LH-20 chromatography, and preparative liquid chromatography. Their structures were identified by physicochemical properties and spectral analysis. Results: Ten compounds were isolated and identified as ethyl caffeate (1), hispidulin (2), quercetin (3), scopolin (4), paprazine (5), mannitol (6), hesperetin (7), ipalbidinium-4’-O-β-D-(6-O-trans-coumaroyl)-glucoside (8), nepitrin (9), and homoplantaginin (10). Conclusion: Compound 8 is a new compound named argyreiacutine, and compounds 2, 3, 6, 7, 9, and 10 are isolated from A. acuta for the first time.

Role of hesperetin intervention on cardiac function and ventricular remodeling after myocardial infarction / 中华急诊医学杂志

Objective To explore the effect of hesperidin on cardiac function and ventricular remodeling following myocardial infarction (MI) in mice.Methods Ligation of left anterior descending (LAD) was operated to establish MI model.Forty-two C57BL/6 mice were randomly (random number) divided into control and MI group;and 24 h after LAD ligation,mice in MI group were further divided into MI control and hesperetin group.Eight weeks later,cardiac function and structure changes were determined by the methods of hemodynamic measurement and echocardiography.HE staining was used to measure crosssectional area (CSA) of atrial myocytes,and PSR staining was applied for observe collagen deposition and calculation of collagen volume fraction (CVF).Real-time PCR was used to detect the mRNA expressions of cardiac hypertrophy markers (ANP,BNP and β-MHC) and cardiac fibrosis markers (Collagen Ⅰ,Collagen Ⅲ and CTGF).The contents of superoxide anion and hydroxy radical were detected by colorimetric method.Results Compared with control group,left ventricular posterior wall thickness (LVPWT) and interventricular septum thickness (IVST) were increased to be thicker,left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) were significantly lower,and ± dp/dtmax was remarkably reduced in MI control group (P ＜ 0.05).Compared with MI control group,hesperetin could increaseLVFS [(29.48±3.87)％ vs.(20.69±3.99) ％],LVEF [(46.40±1.68)％ vs.(30.51± 1.17) ％] and ±dp/dtmax [(3 344.33 ±269.57) mmHg/S vs.(2 205.19 ±224.17) mmHg/S;(2250.40±218.35) mmHg/S vs.(-1 566.91 ±217.37) mmHg/S];but could reduce LVPWT [(2.29±0.05) mm vs.(2.85±0.10)mm]andIVST[(1.44±0.09) mm vs.(1.89±0.06) mm].Compared with control group,CSA and CVF were significantly increased in MI control mice.However,hesperetin could reduce CSA and CVF.Compared with control group,the mRNA expressions of cardiac hypertrophy and cardiac fibrosis markers were significantly increased in MI control mice;but hesperetin could significantly inhibit the mRNA expressions of cardiac hypertrophy and cardiac fibrosis markers.Additionally,hesperetin could significantly reduce the contents of superoxide anion and hydroxy radical.Conclusion Hesperetin intervention can inhibit ventricular structure change,and improve hemodynamics and cardiac function after acute myocardial infarction via inhibiting the production of reactive oxygen species (ROS).

Effect and mechanism of hesperetin on P-selectin mediated breast cancer MDA-MB-231 metastasis / 中草药

Objective: To study the effect of hesperetin on the migration of P-selectin mediated MDA-MB-231 breast cancer cells and its mechanism. Methods: Using computer virtual docking to evaluate the capacity of hesperetin binding to P-selectin in vitro; MTS test was observed with different concentration of hesperetin or P-selectin on the growth capacity of MDA-MB-231; The effect of hesperetin on P-selectin secretion by activated platelet was detected by Elisa kit; Adhesion experiments examined hesperetin on P-selectin-mediated MDA-MB-231 and endothelial cell adhesion; Transwell experiment was performed to analyze the effect of P-selectin on MDA-MB-231 breast cancer cell migration affected by hesperetin; Western blotting investigated MDA-MB-231 cell surface glycoprotein Mucin-1, Integrin β3, β1 and matrix metalloproteinase expression of MMP-2 and MMP-9 protein expression influenced by hesperetin; impact of hesperetin on MDA-MB-231 cell integrin-matrix metalloproteinase signaling pathway was analyzed to clarify the anti-tumor metastasis mechanism of hesperetin. Results: Hesperetin inhibited P-selectin-induced MDA-MB-231 cell migration and reduced HUVEC-breast cancer cell adhesion. Hesperetin down-regulated the expression of β1 and β3 integrins, and MMP-2 and MMP-9 at protein levels in MDA-MB-231 cells. Conclusion: Hesperetin can inhibit the growth capacity of MDA-MB-231 breast cancer cells, block P-selectin-induced breast cancer MDA-MB-231 tumor cell migration and adhesion, and the mechanism for hesperetin is through competitive P-selectin binding to Mucin-1.Subsequently, hesperetin could block PI3K/AKT/Paxillin/FAK/Src signaling pathway and down-regulate P-selectin mediated Integrins, MMP-2, and MMP-9 expression.

Analysis on components exposing in rat plasma after oral administration of Baoerkang Powder / 中草药

Objective: To analyze the components exposing in rat plasma after oral administration of Baoerkang Powder, and to study the mechanism of Baoerkang Powder and pharmacokinetic behavior. Methods: Components absorbed in rat plasma after oral administration of Baoerkang Powder to rats were analyzed by UPLC tandem High-resolution mass spectrometer. The structures of Baoerkang Powder in rat plasma identified by comparing the retention time, molecular weight, and CID fragmentation patterns with their corresponding compounds reported in the literatures. Results: Twenty-three components in rat plasma were identified after oral administration of Baoerkang Powder to rats for 1 h, including five components confirmed by comparing retention time and information of mass with their reference substances, components confirmed were vitexin, liquiritigenin, hesperetin, glycyrrhetic acid, and ursolic acid. Conclusion: It is suggested that the method could be applied to quick analysis of the components exposing in rat plasma after oral administration of Baoerkang Powder, which is beneficial to studying its mechanism and pharmacokinetic behavior.

Preparation of hesperetin nanocrystals: effect of solid state and particle morphology on the particle size reduction efficiency / 中国药学杂志

OBJECTIVE: Drug properties have important effect on the drug nanosuspenions/nanocrystal production and can determine the final particle size and production efficiency. A number of papers have referred to the optimizations of processes expecting the smaller achievable particle sizes as well as increased production efficiency. Aspects such as stabilizer selection are those most commonly described in the literature. The aims of this study are to systematically investigate the mechanism of nanocrystal formation and identify the physical properties that can affect the particle size reduction process. METHODS: The influence of drug properties such as degree of crystallinity and particle morphology on particle size reduction was systematically investigated by producing hesperetin as a model drug. Processes ie spray-drying, rotavapor, and quench-cooling were applied to modify the physical properties of hesperetin. Both unmodified drugs and modified drugs were used for production of nanosuspension. RESULTS: The nanosuspension with the smallest particle size was obtained from spray-dried hesperetin. CONCLUSION: An improved crystal morphology of modified starting material obtained through spray-drying may lead to a more efficient homogenization process. The drug exists in the nanosuspensions as crystalline, which means recrystallization has occurred as a result of the high pressure homogenization process.

Chemical constituents in flowers of Polygonum cuspidatum / 中草药

Objective: To investigate the chemical constituents in the flowers of Polygonum cuspidatum. Methods: The components were separated by means of solvent extraction, repeated chromatography with silica and Sephadex LH-20 column. The structures were determined by spectral analysis and physicochemical properties. Results: Sixteen compounds were isolated from the ethyl ether extract and methanol extract from the flowers of P. cuspidatum and identified as β-sitosterol (1), aloe-emodin (2), physcion (3), emodin (4), daucosterol (5), chrysophanol (6), luteolin (7), kaempferol (8), anthraglycoside B (9), rhein (10), apigenin (11), hesperetin (12), 4-hydroxyacetophenone (13), rutin (14), sucrose (15), and genistein (16). Conclusion: Compounds 2, 8, 12, 13, 15, and 16 are obtained from the flowers of P. cuspidatum for the first time.

Simultaneous determination of six constituents in rukuaixiao granules by UHPLC-MS/MS / 中国药学杂志

OBJECTIVE: To establish a UHPLC-MS/MS method for simultaneous determination of tangertin, hesperetin, 5-demethylnobiletin, nobiletin, vitexin, and narirutin in Rukuaixiao granules. METHODS: The analysis method was performed on a Waters ACQUITY UPLC® BEH C18 eolumn (2.1 mm×50 mm, 1.7 μm) with gradient elution of acetonitrile (containing 0.1% formic acid)-0.1% formic acid at a flow rate of 0.6 mL·min-1, and the column temperature was set at 50℃. Electrospray ionization (ESI) source with positive mode and the detector with multiple reaction monitoring (MRM) mode were adopted to determine the analytes by mass spectormeter. RESULTS: Satisfactory linearities were obtained for the six constituents in the investigated ranges (r>0.9958): The lower limit of quantitation (LOQ) was 0.80, 1.10, 1.30, 0.66, 2.00, 7.10 and 0.70 ng·mL-1, respectively. All the recoveries of samples were between 95.78%-101.35% with RSDs less than 2.1%. CONCLUSION: The method is simple, rapid, sensitive, and highly reproducible. It can be applied to the quality control of Rukuaixiao granules.

The relaxing effect of Poncirus fructus and its flavonoid content on porcine coronary artery / 한국실험동물학회지

Coronary artery disease is a common occurrence in human, and causes enormous social cost. Poncirus fructus (PF), the dried immature fruits of Poncirus trifoliata Rafinesquem, is used in the treatment of womb contraction and dyspepsia, as a prokinetic, and in improving blood circulation. This study was performed to investigate the effects of PF and some of its flavonoids components on the coronary from the pig. The arterial ring was suspended by a pair of stainless steel stirrups in an organ bath. The end of the upper stirrup was connected to an isometric force transducer. A dose-dependent induction of relaxation was observed by both water and 70% ethanol extracts of PF in the porcine coronary artery precontracted with U46619 (100 nM), a stable analogue of the potent vasoconstrictor thromboxane A2. The 70% ethanol extract showed more efficacy than the water extract. Pretreatment of the artery with L-NAME (100 microM), a nitric oxide synthase inhibitor, resulted in a significant reduction in the relaxation induced by PF extract. In addition, ODQ (10 microM), a soluble guanylate cyclase inhibitor, also significantly reduced the effects of PF extracts. Hesperidin, a flavonoid present in PF, induced very weak relaxation of the porcine coronary artery at a high concentration (100 microM), while its aglycone, hesperetin, demonstrated a dose-dependent relaxation. In conclusion, PF extracts induced relaxation in the porcine coronary artery, partially through the nitric oxide-cGMP pathway, and the aglycones of flavonoids might be also involved in the relaxation of the same artery.

Chemical constituents from Artemisiae Anomalae Herba / 中草药

Objective: To investigate the chemical constituents from Artemisiae Anomalae Herba (the aerial part of Artemisia anomala or A. actiflora). Methods: The chemical constituents from Artemisiae Anomalae Herba were isolated and purified by chromatography on silica gel and Sephadex LH-20 column, as well as preparative HPLC. Their structures were identified on the base of physicochemical properties and spectroscopic data analyses. Results: Fifteen constituents, including seven steroids and eight flavonoids, were isolated and identified as β-sitosterol (1), β-daucosterol (2), schleicheol 2 (3), α-spinasterol (4), 5α, 8α-epidioxy- ergosta-6, 22-dien-3β-ol (5), 5α, 8α-epidioxy-ergosta-6, 9(11), 22- trien-3β-ol (6), 22E-3β, 5α-dihydroxyergosta-7, 22-dien-6-one (7), naringenin (8), luteolin (9), kaempferol (10), chrysoeriol (11), diosmetin (12), jaceosidin (13), isorhamnetin 3-O-glucoside (14), and hesperetin-7-O-β-D-glucopyranoside (15). Conclusion: Compounds 5, 6, 12-14 are isolated from this plant for the first time, compound 3 is isolated from the plants of Artemisia L. for the first time, and compounds 7 and 15 are isolated from the plants in Compositae family for the first time.

Chemical constituents from Mentha haplocalyx / 中草药

Objective: To study the chemical constituents from Mentha haplocalyx. Methods: Compounds were isolated and purified by various chromatographic techniques, and their structures were identified by spectral analysis. Results: Eleven compounds were isolated and identified, including menthalignin (1), 5-hydroxy-6, 7, 8, 4'-tetramethoxyflavone (2), betulinic acid (3), hesperetin 7-O-β-D-glucopyranoside (4), gentisic acid 5-O-β-D-(6'-salicylyl)-glucopyranoside (5), linarin (6), acatin (7), 5-hydroxy-6, 7, 8, 3', 4'-pentamethoxyflavone (8), 5, 6, 4'-trihydroxy-7, 8-dimethoxyflavone (9), tilianin (10), and agastachoside (11). Conclusion: Compound 1 is a new lignan named menthalignan; compound 2 is a new natural product; compound 4 is isolated from the plants in Labiatae for the first time, and compounds 3 and 5 are firstly reported in the plants of Mentha L.

Hesperetin Stimulates Cholecystokinin Secretion in Enteroendocrine STC-1 Cells

Hesperetin (3',5,7-trihydroxy 4'-methoxyflavanone) and its glycoside hesperidin (hesperetin 7-rhamnoglucoside) in oranges have been reported to possess pharmacological effects related to anti-obesity. However, hesperetin and hesperidin have not been studied on suppressive effects on appetite. This study examined that hesperetin and hesperidin can stimulate the release of cholecystokinin (CCK), one of appetite-regulating hormones, from the enteroendocrine STC-1 cells, and then examined the mechanisms involved in the CCK release. Hesperetin significantly and dose-dependently stimulated CCK secretion with an EC50 of 0.050 mM and increased the intracellular Ca2+ concentrations ([Ca2+]i) compared to the untreated control. The stimulatory effect by hesperetin was mediated via the entry of extracellular Ca2+ and the activation of TRP channels including TRPA1. These results suggest that hesperetin can be a candidate biomolecule for the suppression of appetite and eventually for the therapeutics of obesity.