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Bo Li,
De-Yun Kong,
Yun-Heng Shen,
Hu Yuan,
Rong-Cai Yue,
Yi-Ren He,
Lu Lu,
Lei Shan,
Hui-Liang Li,
Ji Ye,
Xian-Wen Yang, Juan Su,
Run-Hui Liu,
Wei-Dong Zhang
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ABSTRACT: Pseudolaridimers A (1) and B (2), two unprecedented heterodimers formed via a [4 + 2] Diels-Alder cycloaddition between a cycloartane triterpenoid unit and a labdane diterpenoid unit, were isolated from the cones of Pseudolarix amabilis. Their structures were established by extensive analysis of HRESIMS and NMR spectra. The absolute configuration of 1 was determined by single crystal X-ray diffraction (CuK(α)) of its methyl esterified derivative. Pseudolaridimer A (1) showed strong cytotoxicity against HCT116, ZR-75-30, and HL-60 human tumor cell lines, with IC(50) values 9.62, 7.84, 8.29 μg/mL, respectively. Pseudolaridimer B (2) only exhibited potent inhibition against the HL-60 cell line with an IC(50) value of 7.50 μg/mL.
Organic Letters 10/2012; · 5.86 Impact Factor
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Sheng Lin,
Zhong-Xiao Zhang,
Tao Chen,
Ji Ye,
Wei-Xing Dai,
Lei Shan, Juan Su,
Yun-Heng Shen,
Hui-Liang Li,
Run-Hui Liu,
Xi-Ke Xu,
Hui Wang,
Wei-Dong Zhang
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ABSTRACT: HPLC-PDA-MS and TLC analysis were used to look for minor cytotoxic chlorinated valepotriates from whole plants of Valeriana jatamansi (syn. Valeriana wallichii DC.). This resulted in isolation of 15 chlorinated valepotriates, designated as chlorovaltrates A-O, together with six known analogues, (1S,3R,5R,7S,8S,9S)-3,8-epoxy-1,5-dihydroxyvalechlorine, volvaltrate B, chlorovaltrate, rupesin B, (1S,3R,5R,7S,8S,9S)-3,8-epoxy-1-O-ethyl-5-hydroxyvalechlorine, and (1R,3R,5R,7S,8S,9S)-3,8-epoxy-1-O-ethyl-5-hydroxyvalechlorine. Their structures were elucidated by spectroscopic methods including homo- and heteronuclear two-dimensional NMR experiments. Chlorovaltrates K-N, chlorovaltrate and rupesin B showed moderate cytotoxicity against lung adenocarcinoma (A 549), metastatic prostate cancer (PC-3M), colon cancer (HCT-8) and hepatoma (Bel 7402) cell lines with IC(50) values of 0.89-9.76μM.
Phytochemistry 10/2012; · 3.35 Impact Factor
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Planta Medica 09/2012; 78(14):E23. · 2.15 Impact Factor
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ABSTRACT: A rapid and sensitive liquid chromatography-tandem mass spectrometry method has been developed and validated for the determination of 1-acetoxy-6α-hydroxyeriolanolide, 1β-hydroxyalantolactone and ivangustin from Herba Inula extract in rat plasma. Plasma samples were pretreated by protein precipitation with methanol. Chromatographic separation was accomplished on a TOSOH TSKgel ODS column with mobile phase consisting of methanol and 0.3% formic acid (80:20, v/v). The detection was carried out by multiple-reaction monitoring mode under positive electrospray ionization. The quantification was performed using the transitions of m/z 309.1/185.0 for 1-acetoxy-6α-hydroxyeriolanolide, m/z 249.0/231.1 for 1β-hydroxyalantolactone and ivangustin and m/z 285.0/193.0 for diazepam, respectively. Calibration curves were linear over the concentration range of 4-800 ng/mL for 1-acetoxy-6α-hydroxyeriolanolide, 8-500 ng/mL for 1β-hydroxyalantolactone and ivangustin. The limit of detection (LOD) was 1 ng/mL for 1-acetoxy-6α-hydroxyeriolanolide, 1.6 ng/mL for 1β-hydroxyalantolactone and ivangustin (S/N=3). The intra-day and inter-day precisions (RSD%) for the three compounds were less than 7.8% and 8.6%, and the accuracy (RE%) ranged from -4.6 to 6.8%. The method was successfully applied to pharmacokinetic studies of the three sesquiterpene lactones after oral administration of 300 mg/kg Herba Inula extract to rats, the t(½) of 1-acetoxy-6α-hydroxyeriolanolide, 1β-hydroxyalantolactone and ivangustin was 9.65±1.43, 14.88±0.82 and 13.93±2.74 (h). The AUC((0-t)) of 1-acetoxy-6α-hydroxyeriolanolide, 1β-hydroxyalantolactone and ivangustin was 1102.46±247.04, 808.92±117.53 and 990.35±275.49 (ng h/mL), respectively.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 07/2012; 903:40-5. · 2.78 Impact Factor
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ABSTRACT: To establish a determination method for contents of chlorogenic acid and vitexin 2"-rhamnoside in Crataegi Fructus extracts by HPLC.
The chromatographic column was SHISEIDO CAPCELL PAK C18 (4.6 mm x 250 mm, 5 microm); mobile phase was methanol(A) and THF-acetic acid-water (10:2:76, B), with gradient elution, flow speed was 1.0 mL x min(-1); detection wavelength was 330 nm; temperature of column was 25 degrees C.
Chlorogenic acid and vitexin 2"-rhamnoside showed good linear relationships within the ranges of 1.34-164.8 and 1.18-148.7 mg x L(-1), with the recovery rates being 100.4% and 98.8%, and RSD being 1.5% and 1.3% respectively.
The present method is so simply, accurate and highly repeatable that it can be used to effectively determine the contents of chlorogenic acid and vitexin 2"-rhamnoside in Crataegi Fructus extracts.
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 03/2012; 37(6):829-31.
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ABSTRACT: In the rapid development of nanoscience and nanotechnology, many researchers have discovered that metal oxide nanoparticles have very useful pharmacological effects. Cuprous oxide nanoparticles (CONPs) can selectively induce apoptosis and suppress the proliferation of tumor cells, showing great potential as a clinical cancer therapy. Treatment with CONPs caused a G1/G0 cell cycle arrest in tumor cells. Furthermore, CONPs enclosed in vesicles entered, or were taken up by mitochondria, which damaged their membranes, thereby inducing apoptosis. CONPs can also produce reactive oxygen species (ROS) and initiate lipid peroxidation of the liposomal membrane, thereby regulating many signaling pathways and influencing the vital movements of cells. Our results demonstrate that CONPs have selective cytotoxicity towards tumor cells, and indicate that CONPs might be a potential nanomedicine for cancer therapy.
International Journal of Nanomedicine 01/2012; 7:2641-52. · 3.13 Impact Factor
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Juan Su,
Pu You,
Jun-Peng Zhao,
Shou-Long Zhang,
Shao-Hua Song,
Zhi-Ren Fu,
Li-Wei Ye,
Xiao-Yuan Zi,
Dong-Fu Xie,
Ming-Hua Zhu,
Yi-Ping Hu
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ABSTRACT: Hepatocellular carcinoma (HCC), the most common primary malignant tumor of the liver, often associated with the dysregulation of transcriptional pathways involved in cell growth and differentiation. The hematopoietically expressed homeobox protein (Hhex) is an important transcription factor throughout liver development and is essential to liver bud formation and hepatoblast differentiation. Here, we report a relationship between Hhex expression and HCC. First, adenovirus-mediated Hhex delivery into the hepatoma cell line, Hepa1-6, resulted in decreased expression of several proto-oncogenes (c-Jun and Bcl2), increased expression of some tumor suppressor genes (P53 and Rb), and enhanced expression of a cluster of hepatocytic and bile ductular markers. Second, Hhex expression significantly attenuated Hepa1-6 tumorigenicity in nude mice. Third, we report a correlation between Hhex expression and the differentiation state of human HCC. In 24 cases of clinical specimens, there was a significant difference in Hhex expression between poorly differentiated HCC and well-differentiated HCC (P < 0.001). Taken together, these results indicate that Hhex is a potential candidate molecular marker for HCC pathological evaluation, suggesting a need to evaluate Hhex as a potential target for therapeutic intervention.
Medical Oncology 06/2011; 29(2):1059-67. · 2.14 Impact Factor
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ABSTRACT: Investigation of the ethanol extract of the whole plant of Ainsliaea macrocephala led to the isolation of five new sesquiterpenoids, namely ainsliadimer C (1), ainsliadimer D (2), ainsliaolide B (3), ainsliatone B (4), and ainsliaolide C (5), together with seventeen known sesquiterpenes and sesquiterpene glycosides (6- 22). Their structures were elucidated by spectroscopic methods. The relative stereochemistry of ainsliadimers C (1) and D (2) were further confirmed by single crystal X-ray diffraction analysis. Total extract of A. macrocephala and compounds 1- 22 were tested for inhibitory activity against the production of nitric oxide in RAW 264.7 cells stimulated by LPS, as well as for cytotoxicity against RAW 264.7 macrophages. Of all samples tested, purified compounds 4, 7, and 12 strongly inhibited the production of nitric oxide with IC50 values of 8.78, 2.50, and 7.11 µM, and simultaneously showed low cytotoxicity against RAW 264.7 macrophages.
Planta Medica 03/2011; 77(13):1545-50. · 2.15 Impact Factor
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ABSTRACT: Polyacetylenes are main toxic ingredients in Bupleurum longiradiatum, a poisonous plant that has ever been misused as substitutes for Chaihu (Bupleuri Radix). For the first time, a high-performance liquid chromatography method coupled with diode array detector and mass spectrometry (HPLC-DAD-MS) was developed for qualitative and quantitative analysis of nine polyacetylenes in Bupleurum species. All references, including two new polyacetylenes, were isolated from B. longiradiatum and purified using a semi-preparation HPLC chromatography. The analysis was performed on a TSKgel ODS-100V C18 column (3 μm, 150 mm x 4.6 mm i.d.) using a gradient system of acetonitrile and water, with diode array detection (254 nm). The method was validated for linearity, precision, accuracy, limit of detection and quantification. A total of 27 Bupleurum samples were examined with this method, which showed a great variety in the distribution and contents of the polyacetylenes. It was found that polyacetylenes (1-8) were the main ingredients in B. longiradiatum, while a few kinds of polyacetylenes (5-8) were also identified in B. smithii, B. smithii var. parvifolium, B. bicaule and B. angustissimum. However, no polyacetylenes (1-9) were detected in the authentic Chaihu samples and the other Bupleurum species. The results indicated that the toxic B. longiradiatum could readily be distinguished from other medicinal Bupleurum species based on the polyacetylene profiles, and the guidelines and quality control of polyacetylenes for Chaihu are useful. The acute toxicity of the ethanol extract of B. longiradiatum and its fractions was also investigated.
Journal of chromatography. A 02/2011; 1218(8):1131-8. · 4.19 Impact Factor
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ABSTRACT: Inhibition of cytochrome P450 (CYP) is a major cause of herb-drug interactions. The CYP1A2 enzyme plays a major role in the metabolism of drugs in humans. Its broad substrate specificity, as well as its inhibition by a vast array of structurally diverse herbal active ingredients, has indicated the possibility of metabolic herb-drug interactions. Therefore nowadays searching inhibitors for CYP1A2 from herbal medicines are drawing much more attention by biological, chemical and pharmological scientists. In our work, a pharmacophore model as well as the docking technology is proposed to screen inhibitors from herbal ingredients data. Firstly different pharmaphore models were constructed and then validated and modified by 202 herbal ingredients. Secondly the best pharmaphore model was chosen to virtually screen the herbal data (a curated database of 989 herbal compounds). Then the hits (147 herbal compounds) were continued to be filtered by a docking process, and were tested in vitro successively. Finally, five of eighteen candidate compounds (272, 284, 300, 616 and 817) were found to have inhibition of CYP1A2 activity. The model developed in our study is efficient for in silico screening of large herbal databases in the identification of CYP1A2 inhibitors. It will play an important role to prevent the risk of herb-drug interactions at an early stage of the drug development process.
International Journal of Molecular Sciences 01/2011; 12(5):3250-62. · 2.60 Impact Factor
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ABSTRACT: The liquorice plant has long been used in both Eastern and Western cultures. Glycyrrhizin is the major triterpenoid saponin in liquorice root, and glycyrrhetinic acid (GA) is its predominant metabolite and a pharmacologically active form of glycyrrhizin. We have assessed the ability of GA to inhibit the enzyme cytochrome P450 3A (CYP3A). A Lineweaver-Burk plot showed that GA was a mixed inhibitor of CYP3A, with an IC₅₀ of 7.25 μmol/l, a K(m) of 4.3 μmol/l and a K(i) of 6.4 μmol/l by non-linear regression analysis. CYP3A activity was also affected by intragastric administration of GA, which resulted in increases in area under the plasma concentration-time curve (AUC)(₀-t) and in apparent elimination half-time (t₁/₂) and significant decreases in body clearance, as well as in the formation of 1-hydroxy-midazolam after intragastric or intravenous administration of midazolam (p < 0.05). An increase in C(max) after intragastric administration (p < 0.05) was also observed. These results suggest the likelihood of an interaction between GA and CYP3A-metabolised drugs in humans and indicate that liquorice root should be used with caution when taken concomitantly with other drugs that interact with CYP3A.
Pharmacology 10/2010; 86(5-6):287-92. · 1.79 Impact Factor
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Juan Su,
Pu You,
Wen-Lin Li,
Xin-Rong Tao,
Hai-Ying Zhu,
Yu-Cheng Yao,
Hong-Yu Yu,
Qing-Wang Han,
Bing Yu,
Fang-Xia Liu,
Jun Xu,
Joseph T Y Lau,
Yi-Ping Hu
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ABSTRACT: During early stage of embryonic development, the liver bud, arising from the foregut endoderm, is the beginning for the formation of future liver three-dimensional structure. While the gene expression profiles associated with this developmental stage have been well explored, the detailed cellular events are not as clear. Epithelial-mesenchymal transition (EMT) was thought to be essential for cell migration in the early vertebrate embryo but seldom demonstrated in human liver development. In this study, we tried to identify the cell populations with both stem cell and EMT features in the human liver bud. Our in situ studies show that the phenotype of EMT occurs at initiation of human liver development, accompanied by up-regulation of EMT associated genes. A human liver bud derived stem cell line (hLBSC) was established, which expressed not only genes specific to both mesenchymal cells and hepatic cells, but also octamer-binding protein 4 (OCT4) and nanog. Placed in appropriate media, hLBSC differentiated into hepatocytes, adipocytes, osteoblast-like cells and neuron-like cells in vitro. When transplanted into severe combined immunodeficiency mice pre-treated by carbon tetrachloride, hLBSC engrafted into the liver parenchyma and proliferated. These data suggests that there are cell populations with stem cell and EMT-like properties in the human liver bud, which may play an important role in the beginning of the spatial structure construction of the liver.
The international journal of biochemistry & cell biology 09/2010; 42(12):2047-55. · 4.89 Impact Factor
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ABSTRACT: The effects of nuciferine, a major active aporphine alkaloid from the leaves of Nelumbo nucifera Gaertn, on a cytochrome P450 1A2 (CYP1A2) probe substrate were investigated in vitro and in vivo.
Nuciferine and recombinant human CYP1A2 were incubated together to study the impact of nuciferine on CYP1A2 in vitro. Nuciferine was administered orally to Wistar rats at a dose of 20 mg/kg to further estimate the impact of nuciferine on CYP1A2 in vivo. A probe substrate, phenacetin, was used to index the activity of CYP1A2.
The IC50 value for nuciferine was determined to be 2.12 mmol/l. When phenacetin was intravenously coadministered with nuciferine compared with phenacetin alone, the elimination rate constant and total body clearance of phenacetin were decreased by 24.0% (P < 0.01) and 43.0% (P < 0.05), respectively. The mean residence time, apparent elimination half-time and area under the plasma concentration-time curve were increased by 22% (P < 0.005), 26.9% (P < 0.02) and 74.6% (P < 0.05), respectively. Similarly, when phenacetin was coadministered orally with nuciferine, the apparent elimination half-time in the nuciferine pretreated group was increased by 16.7% (P < 0.05) and the elimination rate constant was decreased by 15.4% (P < 0.05).
The results suggest that nuciferine inhibited CYP1A2 activity in vitro and caused changes in the pharmacokinetic parameters of phenacetin in vivo.
The Journal of pharmacy and pharmacology. 05/2010; 62(5):658-62.
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ABSTRACT: Eight new polyacetylenes (1-8) and six known polyacetylenes were isolated from the entire parts of Bupleurum longiradiatum, a poisonous plant. The structures of the new compounds were determined by spectroscopic data interpretation. The absolute configuration of the known compound bupleurotoxin (9) was established by the modified Mosher's method. All isolates were also tested for their cytotoxicity against a human leukemia cell line (HL-60).
Journal of Natural Products 12/2009; 72(12):2153-7. · 3.13 Impact Factor
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Chemistry & Biodiversity 10/2009; 6(10):1751 - 1757. · 1.80 Impact Factor
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ABSTRACT: A phytochemical investigation of the bulbs of Crinum asiaticum L. var. sinicum Baker resulted in the isolation of two new alkaloids, asiaticumines A and B (1 and 2, resp.), together with 21 known compounds, including nine alkaloids, four amides, five phenolic compounds, and three flavonoids. All 23 compounds were isolated for the first time from Crinum asiaticum L. var. sinicum Baker. Their structures were elucidated by spectroscopic methods. In addition, ten alkaloids, 1-10, were evaluated for their cytotoxic activities against human tumor cell lines A549, LOVO, HL-60, and 6T-CEM. Compounds 3, 4, and 7-10 selectively showed remarkable inhibition against one or more of the tested cell lines.
Chemistry & Biodiversity 10/2009; 6(10):1751-7. · 1.80 Impact Factor
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ABSTRACT: There is increasing evidence that human mesenchymal stem cells (hMSCs) can be a valuable, transplantable source of hepatocytes. Most of the hMSCs preparations used in these studies were likely heterogeneous cell populations, isolated by adherence to plastic surfaces or by density gradient centrifugation. Therefore, the participation of other unknown trace cell populations cannot be rigorously discounted. Here we report the isolation and establishment of a cloned human MSC line (chMSC) from human bone marrow primary culture, through which we confirmed the hepatic differentiation capability of authentic hMSCs. chMSCs expressed markers of mesenchymal cells, but not markers of hematopoietic stem cells. In vitro, chMSCs can differentiate into either mesenchymal cells or cells exhibiting hepatocyte-like phenotypes. When transplanted intrasplentically into carbon tetrachloride-injured livers of SCID mice, EGFP-tagged chMSCs engrafted into the host liver parenchyma, exhibited typical hepatocyte morphology, form a three-dimensional architecture, and differentiate into hepatocyte-like cells expressing human albumin and alpha-1-anti-trypsin. By confocal microscopy, ultrafine intercellular nanotubular structures were visible between adjacent transplanted and host hepatocytes. We postulate that these structures may assist in the phenotype conversion of chMSCs, possibly by exchange of cytoplasmic components between native hepatocytes and transplanted cells. Thus, a clonal pure population of hMSCs, which can be expanded in culture, may have potential as a cellular source for substitution damaged cells in hepatic injury.
Journal of Cellular Biochemistry 09/2009; 108(3):693-704. · 2.87 Impact Factor
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ABSTRACT: An ultra performance liquid chromatography coupled with tunable UV detector (UPLC-TUV) and rapid resolution liquid chromatography coupled with time-of-flight tandem mass spectrometry (RRLC-Q-TOF) method was developed for the quality assessment of Niu Huang Jie Du Pill (NHJDP), a commonly used traditional Chinese medicine (TCM). Ten compounds were simultaneously identified by electrospray ion mass spectrometry (ESI/MS) and comparison with reference standards and literature data. All of them were quantified by UPLC method. Baseline separation was achieved on an ODS-140HTP C(18) column (2.3mum, 100mmx2.1mm I.D.) with linear gradient elution of acetonitrile-0.1% formic acid. This developed method provides good linearity (r(2)>0.9996), repeatability (RSD<3.63%), intra- and inter-day precisions (RSD<0.86%) with accuracies (97.88-101.56%) and recovery (98.88-101.92%) of 10 major constituents, namely baicalin, baicalein, wogonoside, wogonin, glycyrrhizic acid, liquiritin, rhein, emodin, chrysophanol and physcion. In addition, the principal component analysis (PCA) coupled with the UPLC fingerprint was applied to classify the NHJDP samples according to their manufacture corporation. This proposed method with high sensitivity and selectivity was successfully utilized to analyze 10 major bioactive compounds in 30 batches of NHJDPs, and the results demonstrate that this analytical method is simple and suitable for the original discrimination and quality control of this TCM.
Journal of pharmaceutical and biomedical analysis 09/2009; 51(3):565-71. · 2.45 Impact Factor
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ABSTRACT: Bacopa monniera (L.) Wettst (Scrophulariaceae), a reputed Ayurvedic medicinal plant of India, has been widely used as a brain tonic for centuries. In the present study, the methanol extract and different fractions of B. monniera were evaluated for antidepressant activity in the forced swimming test (FST) and tail suspension test (TST) in mice. The results showed that the methanol extract, EtOAc fraction, and n-BuOH fraction significantly reduced the immobility times both in FST and TST in mice after being administrated orally for 5 consecutive days. All tested samples, in the effective doses for FST and TST, showed no inhibitory effect against locomotor activity (LA) in mice.
03/2009; 47(4):340-343.
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ABSTRACT: Acetophenones in Cynanchum species, especially cynandione A and its derivatives, whose utilization and toxicity in herbal drugs and folk medicines has caused great interest in the chemical investigation, have extensive biological activities. In this paper, a facile method based on high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS(n)) was developed for the analysis of cynandione A derivatives in the roots of the Cynanchum wilfordii and C. auriculatum. ESI-MS/MS and ESI-MS(n) analysis of cynandiones A and B in negative ion mode were firstly performed employing two mass spectrometers each equipped with an ion-trap and a quadrupole time-of-flight (Q-TOF) mass analyzer. The results drawn from both instruments were similar to each other. Characteristic fragmentation pathways were proposed by comparing the spectra of two standards acquired in the experiments. The fragment ions at m/z 283 and 268 were obtained, and then were used as diagnostic ions to screen and identify cynandione A derivatives from the roots of above two species, together with an HPLC-MS(n) method. Total of 28 cynandione A derivatives comprising 4 reported and 24 novel components were identified or tentatively identified. Furthermore, breakdown curves were constructed to distinguish two types of isomers among these compounds. To our knowledge, this is the first report on characterization of acetophenones by HPLC-ESI-MS(n), which allows a rapid and complete analysis of cynandione A derivatives in roots of Cynanchum species.
Journal of pharmaceutical and biomedical analysis 02/2009; 49(3):715-25. · 2.45 Impact Factor
