[Show abstract][Hide abstract] ABSTRACT: Background:
A large number of experimental studies using young adult subjects have shown that ginseng (Panax ginseng C.A. Meyer) protects against ischemia heart disease. However, ginseng has not been explored for its anti-I/R effect and mechanism of action in the aged myocardium. The present study was designed to evaluate the effects of the long-term consumption of ginseng extract on myocardial I/R in an in vivo rat model and explore the potential underlying mechanism.
Methods and results:
Young (6-mo-old) and intermediate-aged (18-mo-old) rats were gavaged with either standardized ginseng extract (RSE) at 80 mg/kg or vehicle for 90 days. The rats were sacrificed after LAD coronary artery ligation was performed to induce 30 min of ischemia, followed by 90 min of reperfusion. The myocardial infarct size was measured. Left ventricular function was evaluated using pressure-volume loops. The levels of survival, apoptotic and longevity protein expression were assessed through Western blot analysis. Myocardial pathology was detected through H&E or Masson's trichrome staining. We observed higher infarct expansion with impairment in the LV functional parameters, such as LVSP and LVEDP, in aged rats compared with young rats. Enhanced Akt phosphorylation and eNOS expression in RSE-treated aged hearts were accompanied with reduced infarct size, improved cardiac performance, and inducted survival signals. In contrast, p-Erk and caspase 7 were significantly downregulated in aged rats, suggesting that cardiomyocyte apoptosis was suppressed after RSE treatment. RSE also inhibited caspase-3/7 activation and decreased Bax/Bcl-2 ratio. Consistent with the results of apoptosis, Sirt1 and Sirt3 were significantly increased in the RSE-treated aged heart compared with vehicle-treated I/R, suggesting that the anti-aging effect was correlated with the anti-apoptotic activity of RSE.
These findings suggest that the long-term consumption of ginseng extract reduced the susceptibility of intermediate-aged hearts to acute ischemia reperfusion injury in rats. These effects might be mediated through the activation of Akt/eNOS, suppression of Erk/caspase 7 and upregulation of Sirt1 and Sirt3 in intermediate-aged rats.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Mitochondrial dysfunction is a prominent feature of ischemia heart disease but the underlying mechanism of dynamics (fusion/fission) is still unclear. Here we investigated a novel function and underlying mechanism of Rg1 on an in vitro cardiomyocyte model of hypoxia/reoxygenation (H/R).
Cellular cytotoxicity was evaluated by MTT, mitochondrial viable staining, and cardiac marker detection. Mitochondrial function was evaluated by ATP content measurement, MMP determination, ROS, OCR and ECAR assay. Mitochondrial dynamics was investigated by Live-cell imaging with time-lapse fluorescence microscopy and morphological features were evaluated by the high-content image analysis. Mitochondrial fusion and fission-related proteins, GDH were determined by Western blot, RT-PCR and immunofluorescence.
Rg1 moderated GDH dysregulation and then protected against H/R-induced cellular damage and mitochondrial dysfunction in a dose-dependent manner. Rg1 significantly increased mitochondrial length, reduced the number of cells with fragmented mitochondria and up-regulated the MFN2 expression finally leading to preventing the imbalance of mitochondrial dynamics following H/R. Knock-down of MFN2 by specific siRNA completely abolished the ability of Rg1 to cell survival by H/R.
Rg1 through modulation of GDH and MFN2 maintained mitochondrial dynamics that resulted in protection against H/R-induced cardiomyocyte injury. All these results put forward a new protective mechanism of Rg1 on the therapeutic potential in cardiac I/R disorders.
[Show abstract][Hide abstract] ABSTRACT: Traditional Tibetan medicine (TTM) is an old traditional medical system, which is an effective and natural method of improving physical and mental health, and has been widely spread in the western part of China for centuries. Halenia elliptica (H. elliptica) D. Don, known as “Jiadiranguo” (Tibetan medicine name) is one of the most important herbal medicine in TTM that is from the genus Halenia (family: Gentianaceae). The whole herb can be used as a medicine to treat hepatobiliary diseases and xeransis, and possesses many biological and pharmacological activities including heat clearing, bile benefiting, liver soothing, digestion promoting, blood nursing, detoxification activities, and so on. In modern research, H. elliptica can be used to treat acute or chronic hepatitis, especially hepatitis B. In addition, the chemical compounds of the herb have potent antihepatitis B virus (anti-HBV) activity in vitro. As an important TTM, further studies on H. elliptica can lead to the development of new drugs and therapeutics for various diseases, and more attention should be paid on the aspects of how to utilize it better.
[Show abstract][Hide abstract] ABSTRACT: A sensitive, precise and selective ultra-high performance liquid chromatography method coupled with triple-quadrupole mass spectrometry was developed and validated for the determination of trace amounts of sinomenine (ng/mL) in minute volumes of human plasma. Fifty microliter plasma samples were precipitated using methanol to extract sinomenine. Separation was carried out on a C18 column with a water and acetonitrile mobile phase gradient with formic acid as an additive. The mass spectrometry data were obtained in the positive ion mode, and the transition of multiple reactions was monitored at m/z 330.2→181.0 for sinomenine quantification. The working assay range for sinomenine was linear from 0.1173 to 15.02 ng/mL with the lower limit of quantification of 0.1173 ng/mL. The precision and accuracy of the method was less than 15% in intra-day and inter-day experiments with a matrix effect of less than 6.5%. After validation, the quantitative method was applied to analyze sinomenine levels in human plasma after transdermal delivery of the Zhengqing Fengtongning Injection. The results showed that some samples contained sinomenine within the concentration range 0.4131-4.407 ng/mL.
[Show abstract][Hide abstract] ABSTRACT: Fish oil is a popular nutritional product consumed in Hong Kong. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the two main bioactive components responsible for the health benefits of fish oil. Market survey in Hong Kong demonstrated that various fish oil capsules with different origins and prices are sold simultaneously. However, these capsules are labelled with same ingredient levels, namely EPA 180 mg/g and DHA 120 mg/g. This situation makes the consumers very confused. To evaluate the quality of various fish oil capsules, a comparative analysis of the contents of EPA and DHA in fish oil is crucial.
A gas chromatography-mass spectrometry (GC-MS) method was developed for identification and determination of EPA and DHA in fish oil capsules. A comprehensive validation of the developed method was conducted. Ten batches of fish oil capsules samples purchased from drugstores of Hong Kong were analyzed by using the developed method.
The present method presented good sensitivity, precision and accuracy. The limits of detection (LOD) for EPA and DHA were 0.08 ng and 0.21 ng, respectively. The relative standard deviation (RSD) values of EPA and DHA for precision tests were both less than 1.05%; and the recovery for accuracy test of EPA and DHA were 100.50% and 103.83%, respectively. In ten fish oil samples, the contents of EPA ranged from 39.52 mg/g to 509.16 mg/g, and the contents of DHA ranged from 35.14 mg/g to 645.70 mg/g.
The present method is suitable for the quantitative analysis of EPA and DHA in fish oil capsules. There is a significant variation in the contents of the quantified components in fish oil samples, and there is not a linear relationship between price and contents of EPA and DHA. Strict supervision of the labelling of the fish oil capsules is urgently needed.
Full-text · Article · Dec 2014 · Lipids in Health and Disease
[Show abstract][Hide abstract] ABSTRACT: Anthraquinones are active components of herbal medicine, and consequently it is necessary to develop a selective, convenient, and green preconcentration method for these compounds. A rhein-functionalized resin was synthesized by a condensation reaction followed by characterization by infrared spectroscopy, transmission electron microscopy, solid carbon-13 nuclear magnetic resonance, and elemental analysis. The rhein-functionalized resin was employed for solid-phase extraction with HPLC-MS for the determination of anthraquinones in the extracts of Polygonum cuspidatum. Emodin, chrysophanol, and physcion were selectively concentrated by a simple absorption and desorption procedure. The results indicated that this new material has application for separating and enriching anthraquinones from herbal medicine, which is significant for pharmaceutical analysis.
No preview · Article · Sep 2014 · Analytical Letters
[Show abstract][Hide abstract] ABSTRACT: Aim
To study the hepatoprotective effect of methanol extract of Gentiana veitchiorum (MGV) against CCl4-induced oxidative stress and liver injury in mice.
The acute hepatic model was developed by injection of 20% CCl4 in mice. ICR mice were divided into six groups, including control, CCl4, CCl4+ silymarin, and CCl4+ MGV (100, 200, and 400 mg·kg−1) groups. Hepatic enzymes including AST, ALT and ALP levels in serum, and antioxidant enzymes, including SOD, CAT and GPX activity in liver tissue, were determined. Histopathological examination and Western blot analysis were performed.
Oral administration of MGV at 200 and 400 mg·kg−1 for 15 days dose-dependently inhibited the serum elevations of AST, ALT, and ALP, and recovered the reduction of SOD, CAT, and GPX in liver tissue. Hematoxylin and eosin staining examination performed in liver tissues suggested that MGV treatment ameliorated histopathological changes in CCl4-induced mice. Western blotting analysis implied that MGV increased HO-1 expression and recovered TNF-α alternation.
G. veitchiorum can protect the liver against CCl4-induced damage in mice, and this hepatoprotective effect was due at least in part to its ability through scavenging CCl4-associated free radical activities. The study provided in vivo evidence that G. veitchiorum can be used as a safe, cheap, and effective agent to reduce acute liver damage, supporting its folk medicine use
No preview · Article · Jul 2014 · Chinese Journal of Natural Medicines
[Show abstract][Hide abstract] ABSTRACT: To establish an HPLC-ELSD fingerprint of the whole herbs of Morina nepalensis and perform the correlation analysis of chemical components of the herb and nitric oxide (NO) production inhibition.
HPLC-ELSD assay was performed to evaluate 10 batches of M. nepalensis herbs. The chromatographic conditions were as following: Eclipse XDB C18 column (4.6 mm x 150 mm, 5 microm), water (A) and acetonitrile (B) as a gradient mobile phases, flow rate 1.0 mL x min(-1), and column temperature at 35 degress C. Evaporative light-detection conditions: atomization temperature at 104 degrees C, the flow rate of N2 2.8 L x min(-1) and 10 microL sample injection. Chromatographic fingerprint was developed, and the inhibition activity of production of NO in lipopolysaccharide-induced macrophages was also analyzed. The similarity and correlation analysis between the HPLC-ELSD fingerprints and NO production inhibition were carried out by PLS method.
The common mode for M. nepalensis herb fingerprint was established, including 15 common characteristic peaks. Among them, 7 peaks were positively correlated with the NO production inhibition. According to the assessment on the similarity of 10 batches of samples, a similarity of over 0.90 were shown in HPLC-ELSD fingerprint and all samples were separated into two groups.
This method can be used to assess the quality of M. nepalensis, which provides a reliable method for scientific assessment and quality control.
No preview · Article · Sep 2013 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
[Show abstract][Hide abstract] ABSTRACT: A saponin-enriched fraction was prepared from the EtOH extract of the whole plant of Morina nepalensis var. alba Hand-Mazz. It showed α-glucosidase inhibitory activity, from which two new triterpene saponins (1 and 2), along with one known saponin (3), were isolated. The structures of the new saponins were identified by spectroscopic analysis, including extensive 1D and 2D NMR techniques and hydrolysis followed by chromatographic analysis. The three saponins were assayed for α-glucosidase inhibitory activities.
No preview · Article · Aug 2013 · Natural product research
[Show abstract][Hide abstract] ABSTRACT: Ginseng (Panax ginseng C.A. Meyer) is widely used in Asian communities for treating cardiovascular diseases. However, the mechanism by which it protects the myocardium in ischemia-reperfusion (I/R) injury remains unclear. In this study, we aim to investigate whether a standardized ginseng extract (RSE) protects rodent hearts against I/R injury and if glucocorticoid and/or estrogen receptor-mediated activation of Akt and Erk1/2 (the reperfusion injury salvage kinase pathway, RISK) and subsequent nitric oxide (NO) synthesis signaling are involved in this effect.
No preview · Article · Mar 2011 · Journal of ethnopharmacology
[Show abstract][Hide abstract] ABSTRACT: Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) (PL) is a naturally occurring yellow pigment found in the plants of the Plumbaginaceae, Droseraceae, Ancistrocladaceae, and Dioncophyllaceae families. It has been reported that PL exhibits anticarcinogenic, anti-inflammatory, and analgesic activities. However, the mechanism underlying its anti-inflammatory action remains unknown. In the current study, we investigated and characterized the anti-inflammatory and analgesic effects of PL orally administrated in a range of dosages from 5 to 20 mg/kg. We also examined the role of nuclear factor κB (NF-κB) and proinflammatory cytokines and mediators in this effect. The results showed that PL significantly and dose-dependently suppressed the paw edema of rats induced by carrageenan and various proinflammatory mediators, including histamine, serotonin, bradykinin, and prostaglandin E(2). PL reduced the number of writhing episodes of mice induced by the intraperitoneal injection of acetic acid, but it did not reduce the writhing episode numbers induced by MgSO(4) in mice or prolong the tail-flick reaction time of rats to noxious thermal pain. Mechanistic studies showed that PL effectively decreased the production of the proinflammatory cytokines interleukin 1β, interleukin 6, and tumor necrosis factor α. It also inhibited the expression of the proinflammatory mediators inducible nitric-oxide synthase and cyclooxygenase 2, whereas it did not inhibit the expression of cyclooxygenase 1. Further studies demonstrated that PL suppressed inhibitor of κBα phosphorylation and degradation, thus inhibiting the phosphorylation of the p65 subunit of NF-κB. This study suggests that PL has a potential to be developed into an anti-inflammatory agent for treating inflammatory diseases.
Full-text · Article · Dec 2010 · Journal of Pharmacology and Experimental Therapeutics
[Show abstract][Hide abstract] ABSTRACT: Ginseng is the most popular herb used for treatment of ischemic heart diseases in Chinese community; ginsenosides are considered to be the major active ingredients. However, whether ginsenosides can enhance the coronary artery flow of ischemic heart and, if so, by what mechanisms they do this, remains unclear.
Isolated rat hearts with ischemia/reperfusion injury in Langendorff system were employed for examining the effect of total ginsenosides (TGS) on coronary perfusion flow (CPF). In addition, human aortic endothelial cells (HAECs) were used for mechanistic study. Levels of various vasodilative molecules, intracellular calcium concentration ([Ca²+](i)), and expressions and activation of proteins involving regulation of nitric oxide (NO) signaling pathways in heart tissues and HAECs were determined.
TGS dose-dependently and significantly increased CPF and improved systolic and diastolic function of the ischemia/reperfused rat heart, while inhibitors of NO synthase (NOS), soluble guanylate cyclase (sGC), heme oxygenase (HO), cyclooxygenase (COX), and potassium channel abolished the vasodilation effect of TGS. Positive control verapamil was effective only in increasing CPF. TGS elevated levels of NO and 6-keto-prostaglandin F₁α, a stable hydrolytic product of prostacyclin I₂ (PGI₂), in both coronary effluents and supernatants of HAECs culturing medium, and augmented [Ca²+](i) in HAECs. TGS significantly up-regulated expression of phosphoinositide 3-kinase (PI3K) and phosphorylations of Akt and endothelial NOS (eNOS) as well.
TGS significantly increased CPF of ischemia/reperfused rat hearts through elevation of NO production via activation of PI3K/Akt-eNOS signaling. In addition, PGI₂, EDHF and CO pathways also partially participated in vasodilation induced by TGS.
Full-text · Article · Nov 2010 · Phytomedicine: international journal of phytotherapy and phytopharmacology
[Show abstract][Hide abstract] ABSTRACT: Scutellarein-7-O-beta-D-glucuronide (SG) and apigenin-7-O-beta-D-glucuronide (AG) are two major bioactive constituents with known pharmacological effects in Erigeron multiradiatus. In this study, a simple method for preparative separation of the two flavone glucuronides was established with macroporous resins. The performance and adsorption characteristics of eight macroporous resins including AB-8, HPD100, HPD450, HPD600, D100, D101, D141, and D160 have been evaluated. The results confirmed that D141 resin offered the best adsorption and desorption capacities and the highest desorption ratio for the two glucuronides among the tested resins. Sorption isotherms were constructed for D141 resin under optimal ethanol conditions and fitted well to the Freundlich and Langmuir models (R(2) > 0.95). Dynamic adsorption and desorption tests was performed on column packed with D141 resin. After one-run treatment with D141 resin, the two-constituent content in the final product was increased from 2.14% and 1.34% in the crude extract of Erigeron multiradiatus to 24.63% and 18.42% in the final products with the recoveries of 82.5% and 85.4%, respectively. The preparative separation of SG and AG can be easily and effectively achieved via adsorption and desorption on D141 resin, and the method developed can be referenced for large-scale separation and purification of flavone glucuronides from herbal raw materials.
Full-text · Article · Nov 2009 · BioMed Research International
[Show abstract][Hide abstract] ABSTRACT: Erigeron multiradiatus (Lindl.) Benth is a traditional Tibetan medicine herb long used to treat various diseases related to inflammation. Our previous phytochemical studies on E. multiradiatus resulted in the isolation of scutellarin, which is a known flavone glucuronide with comprehensive pharmacological actions. In present study, we investigated the inhibition action of scutellarin on high glucose-induced vascular inflammation in human endothelial cells (ECV304 cells). Consistent with previous reports, exposure of ECV304 cells to high glucose for 24 h caused an increase of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1), and promoted cell adhesion between monocyte and ECV304 cells. However, pretreatment with scutellarin (0.1 and 1 microM) reversed these effects in a concentration-dependent manner. Scutellarin was able to inhibit the activation of NF-kappaB induced by high glucose in ECV304 cells. Furthermore, although oral administration of scutellarin (10 and 50 mg/kg) did not produce significant antihyperglycemic action, it lowered the serum MCP-1 levels significantly in alloxan-induced diabetic mice. Therefore, our results suggest that scutellarin has anti-inflammation effect that may afford some protection against hyperglycemia-induced vascular inflammatory both in vitro and in vivo.
Full-text · Article · Oct 2008 · Yakugaku zasshi journal of the Pharmaceutical Society of Japan
[Show abstract][Hide abstract] ABSTRACT: Erigeron multiradiatus (Lindl.) Benth., an herb that grows in the alpine and subalpine meadow of Qinghai-Tibet plateau, has been widely used as a folk remedy by the native people for treatment of various inflammatory ailments.
In order to isolate and identify the active components of Erigeron multiradiatus for anti-inflammatory activity, a preliminary phytochemical study and a bioassay-guided fractionation and purification process was performed.
The dry whole plant Erigeron multiradiatus was extracted with 50% ethanol and then separated into CHCl(3), n-BuOH, and aqueous fractions. The anti-inflammatory activities of each fraction were investigated using two in vivo inflammation models.
These results exhibited varying degrees of anti-inflammatory activities and the n-BuOH fraction showed the strongest anti-inflammatory activities. The n-BuOH fraction was then subjected to separation and purification using macroporous resins column chromatography and Sephadex LH-20 leading to two flavonoids glucuronides identified as scutellarein-7-O-beta-glucuronide and apigenin-7-O-beta-glucuronide. Furthermore, LC-MS/MS identification and quantification of isolated compounds were also performed.
Scutellarein-7-O-beta-glucuronide and apigenin-7-O-beta-glucuronide were considered as major components and principally responsible for the anti-inflammatory activity of Erigeron multiradiatus. Thus the results of our study provide a scientific basis for the utilization of Erigeron multiradiatus in traditional Tibetan medicine.
No preview · Article · Aug 2008 · Journal of Ethnopharmacology
[Show abstract][Hide abstract] ABSTRACT: Salvianolic acid B (Sal B) is one of the major water-soluble compounds isolated from Radix Salviae Miltiorrhizae (Danshen in Chinese) that has been reported to be beneficial to treatment of diabetic complications. However, the mechanisms involved in these effects are not discussed in relation to mesangial proliferation via modulation of NF-kappaB. To explain this, human mesangial cells were pretreated with or without Sal B (0.1, 1, 10 microM) for 24 h and stimulated with high glucose (30 mM). Then the effects of Sal B on mesangial cells proliferation, extracellular matrix production and the possible mechanisms were evaluated by methylthiazoletetrazolium assay, flow cytometry assay, enzyme-linked immunosorbent assay, gelatin zymography assay and western blot assay. These results indicated that Sal B could inhibit high glucose-induced mesangial cells proliferation and extracellular matrix production in a dose-dependent manner, partially through modulating the cell-cycle progress and MMP-2 and MMP-9 activities via suppressing NF-kappaB activation, suggesting that Sal B may be a promising agent for treating diabetic nephropathy.
No preview · Article · Aug 2008 · Biological & Pharmaceutical Bulletin
[Show abstract][Hide abstract] ABSTRACT: An HPLC-DAD-MS method was developed for simultaneous determination of the five major active constituents in Erigeron multiradiatus (Wall.) Benth, namely 6'-O-cafferylerigeroside (1), scutellarin (2), apigenin-7-O-beta-d-glucuronide (3), apigenin (4) and kaempferol (5), respectively. They were identified by ESI-MS and comparisons with literature. A comprehensive validation of the method included tests of sensitivity, linearity, precision and accuracy. The linear regressions were acquired with r>0.999. The precision was evaluated by intra- and inter-day assays, and relative standard deviation (R.S.D.) values were reported within 2.7%. The recovery studies for the quantified compounds were observed in the range of 95.3-102.4% with R.S.D. values less than 2.3%. The overall procedure may be suitable for the qualitative and quantitative analyses of a large number of E. multiradiatus samples. Hierarchical clustering analysis based on the characteristics of the 5 investigated compound peaks in HPLC profiles showed that 18 samples were divided into 2 main clusters. The clusters corresponded to their content. The five constituents in E. multiradiatus are generally regarded as an index for the quality assessment of this herb.
No preview · Article · Jun 2008 · Journal of Pharmaceutical and Biomedical Analysis
[Show abstract][Hide abstract] ABSTRACT: Erigeron breviscapus (Vant.) Hand-mazz (EB), Erigeron multiradiatus (Lindl.) Benth (EM), and Aster brachytrichus Franch (AB), confused under the vernacular name "meiduoluomi" by native people and traditional healers, have been used for the treatment of meningitis, polyneuritis, hepatitis, adenolymphitis, and enteronitis in traditional Tibetan medicine. In this study, the antiinflammatory activity of methanol extracts of all three plants was investigated in the xylene-induced ear edema model, carrageenan-induced paw edema model, and cotton pellet-induced granuloma model. It was found that the methanolic extracts of both EB and EM had strong inhibitory effects on the acute phase of inflammation in carrageenan-induced paw edema in rats. On the other hand, the methanolic extract of EM showed stronger effects than those of EB in xylene-induced ear edema. In the chronic test, the methanolic extracts of EB and EM resulted in a significant reduction in granuloma weight in rats. In addition, myeloperoxidase (MPO) activity was strongly reduced in the EB-treated and EM-treated groups, which indicated that EB and EM can inhibit certain inflammatory modulator factors that cause neutrophil aggregation in inflamed tissue, e.g., nuclear factor-kappaB. However, the methanolic extracts of AB had no antiinflammatory effects in the tested models and MPO assay. The similar effects of EM and EB in tested models provided some scientific basis for the traditional usage of meiduoluomi in inflammatory disease. However, the results also suggest that further study is needed to investigate the antiinflammatory profile of AB and provide a scientific basis for the use of AB in inflammatory diseases.
Full-text · Article · Jun 2008 · Yakugaku zasshi journal of the Pharmaceutical Society of Japan