Lan Shen

Shanghai University of Traditional Chinese Medicine, Shanghai, Shanghai Shi, China

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Publications (79)

  • Qianqian Dong · Xiao Lin · Lan Shen · Yi Feng
    [Show abstract] [Hide abstract] ABSTRACT: Ischemia-reperfusion (IR) injury is one of the common ischemic diseases in organs such as brain, heart, kidney, liver, and intestine, which often leads to cell apoptosis and organ failure. The study of herbal polysaccharides for IR injury has a long time, and has laid a solid foundation for the next research work. The purpose of this review is to objectively appraise the current experimental research situation of treating IR injury in organs by polysaccharides from traditional Chinese medicines. Twenty-four kinds of polysaccharides that show effective treatment in organ ischemia were mentioned on the review. The results indicate that herbal polysaccharides provide a good prospect in prevention and treatment of IR injury, and these kinds of polysaccharides have various mechanisms of action, including (i) modifying the function of neurosystem, (ii) reducing the infarct volume, malondiadehyde (MDA) content, and levels of pro-inflammatory cytokines, (iii) elevating the activities of superoxide dismutase (SOD) and myeloperoxidase (MPO) and increasing the levels of anti-inflammatory cytokine. As the polysaccharides from traditional Chinese medicines are a promising solution for IR injury, it is necessary to review the reported researches so as to point out the direction of application and exploitation in the future.
    Article · Jul 2016 · International journal of biological macromolecules
  • JinZhi Li · Xiao Lin · Fei Wu · [...] · Yi Feng
    [Show abstract] [Hide abstract] ABSTRACT: To develop a novel co-processed tablet excipient based on calcium carbonate and hydroxypropyl methylcellulose (HPMC), the central composite design-response surface methodology (CCD-RSM) was applied to optimize the amount of HPMC and the solid content of feed suspensions used for co-spray drying by choosing powder and tablet properties as the evaluation indicators. Significant and adequate regression models were developed for each property. An increase in % HPMC improved powder bulk density, tablet tensile strength, and various tableting parameters. However, a high content of HPMC had a negative influence on tablet disintegration time. In addition, the median particle size of the product increased with both factors. However, they had little effect on the fast elastic stretch of tablets. Numerical optimization determined the optimal parameters as HPMC in the feed solid: 6.7% (w/w) and the solid content of the feed: 42% (w/v). The experimental values of the optimized co-processed excipient were mostly close to the model-predicted values. The tablet tensile strength and disintegration time were 3.28 MPa and 8.91 min, respectively. The combined use of CCD, RSM, and the desirability functions can provide an insight into the object studied and the results achieved are helpful for further development of novel co-processed excipients.
    Article · Oct 2015 · RSC Advances
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    Qiang Wang · Lan Shen · Shi-Yu Ma · [...] · Yi Feng
    [Show abstract] [Hide abstract] ABSTRACT: Ligusticum chuanxiong (LC)–Gastrodia elata (GE) compatibility is widely used in the clinic for the treatment of migraine. It has been shown that the changes of neurotransmitters in the central nervous system are closely related to the pathogenesis of migraine; whether LC–GE compatibility might affect the neurotransmitters in migraine rats has not yet been studied. In this study, high performance liquid chromatography-fluorescence detector methods for quantification of serotonin (5-hydroxytryptamine, 5-HT) and excitatory amino acids (EAAs) in rat brain were developed. The 5-HT was measured directly, while EAAs were determined by using dansyl chloride as precolumn derivative reagent. The validation of the methods, including selectivity, linearity, sensitivity, precision, accuracy, recoveries, and stability were carried out and demonstrated to meet the requirements of quantitative analysis. Compared with the model group, the expression of 5-HT in migraine rat brain was enhanced from 30 minutes to 120 minutes and glutamate (L-Glu) was suppressed from 30 minutes to 60 minutes in an LC–GE (4:3) group compared with the model group (p < 0.05, p < 0.01, respectively). These findings showed that the analytical methods were simple, sensitive, selective, and low cost, and LC–GE 4:3 compatibility could have better efficacy for treating migraine through upregulating 5-HT levels and downregulating L-Glu levels.
    Full-text Article · Oct 2015 · Journal of Food and Drug Analysis
  • Xiao Lin · ChunXia Yao · Fei Wu · [...] · Lina Wang
    [Show abstract] [Hide abstract] ABSTRACT: Drug delivery to ischemic myocardium is an enormous challenge. This work aimed to characterize cardiac delivery behaviors of mono-polyethylene glycosylated (PEGylated) conjugates and long-circulating liposomes (L-Lps) with Radix Ophiopogonis polysaccharide (ROP) as drug. The results showed that compared to native ROP, 32-, 52-, and 45-fold increases in blood half-life were achieved by 20-kDa PEG mono-modified ROP (P20k-R), 40-kDa PEG mono-modified ROP (P40k-R), and ROP-loaded L-Lp, respectively. With comparable blood pharmacokinetics, ROP-loaded L-Lp showed both significantly higher targeting efficacy and drug exposure in infarcted myocardium than P40k-R. With regard to P20k-R, both its targeting efficacy and its level in infarcted myocardium at 3 hours postdose were comparable to P40k-R, but its level in blood and myocardium reduced obviously faster. As a whole, the results indicate that both loading in L-Lps and mono-PEGylation are effective in targeting drug to ischemic myocardium, but the former appears to induce stronger effects.
    Article · Sep 2015 · International Journal of Nanomedicine
  • JinZhi Li · Fei Wu · Xiao Lin · [...] · Yi Feng
    [Show abstract] [Hide abstract] ABSTRACT: This work aimed to investigate the novel application of hydroxypropyl methylcellulose (HPMC) to improving the direct compaction properties of tablet fillers by co-spray drying. Commonly used three types of fillers were investigated. Two representatives were chosen for each type, i.e., (i) water-soluble small molecules: lactose and mannitol; (ii) water-insoluble small molecules: calcium carbonate and anhydrous dibasic calcium phosphate; and (iii) macromolecules: corn starch (practically insoluble in cold water) and chitosan (sparingly soluble in water). Except for chitosan, improvements on both powder properties (e.g., flowability and hygroscopicity) and tableting properties (e.g., tableting ratio, yield pressure, tensile strength, and Esp) were achieved for the rest five fillers by co-spray drying with a small amount of HPMC. This is mainly attributed to the homogeneous distribution of plastic and nonhygroscopic HPMC macromolecules on the surface of the primary and composite particles. In addition, changes induced by spray drying, such as agglomeration, spheroidization, porosity increase, amorphous formation, and gelatinization, also contribute to some degree to the improvements. The above results, together with the data of lubrication sensitivity and tablet disintegration, show that such a novel application of HPMC is effective and promising.
    Article · Aug 2015 · RSC Advances
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    Xinyuan Xu · Jianying Li · Xiang Sun · [...] · Lan Shen
    Full-text Dataset · Jul 2015
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    Xinyuan Xu · Jianying Li · Xiang Sun · [...] · Lan Shen
    [Show abstract] [Hide abstract] ABSTRACT: Cancer cells use glucose and glutamine as the major sources of energy and precursor intermediates, and enhanced glycolysis and glutamimolysis are the major hallmarks of metabolic reprogramming in cancer. Oncogene activation and tumor suppressor gene inactivation alter multiple intracellular signaling pathways that affect glycolysis and glutaminolysis. N-Myc downstream regulated gene 2 (NDRG2) is a tumor suppressor gene inhibiting cancer growth, metastasis and invasion. However, the role and molecular mechanism of NDRG2 in cancer metabolism remains unclear. In this study, we discovered the role of the tumor suppressor gene NDRG2 in aerobic glycolysis and glutaminolysis of cancer cells. NDRG2 inhibited glucose consumption and lactate production, glutamine consumption and glutamate production in colorectal cancer cells. Analysis of glucose transporters and the catalytic enzymes involved in glycolysis revealed that glucose transporter 1 (GLUT1), hexokinase 2 (HK2), pyruvate kinase M2 isoform (PKM2) and lactate dehydrogenase A (LDHA) was significantly suppressed by NDRG2. Analysis of glutamine transporter and the catalytic enzymes involved in glutaminolysis revealed that glutamine transporter ASC amino-acid transporter 2 (ASCT2) and glutaminase 1 (GLS1) was also significantly suppressed by NDRG2. Transcription factor c-Myc mediated inhibition of glycolysis and glutaminolysis by NDRG2. More importantly, NDRG2 inhibited the expression of c-Myc by suppressing the expression of β-catenin, which can transcriptionally activate C-MYC gene in nucleus. In addition, the growth and proliferation of colorectal cancer cells were suppressed significantly by NDRG2 through inhibition of glycolysis and glutaminolysis. Taken together, these findings indicate that NDRG2 functions as an essential regulator in glycolysis and glutaminolysis via repression of c-Myc, and acts as a suppressor of carcinogenesis through coordinately targeting glucose and glutamine transporter, multiple catalytic enzymes involved in glycolysis and glutaminolysis, which fuels the bioenergy and biomaterials needed for cancer proliferation and progress.
    Full-text Article · Jul 2015 · Oncotarget
  • Shiyu Ma · Lan Shen · Meiwan Chen · [...] · Yi Feng
    [Show abstract] [Hide abstract] ABSTRACT: Liuwei Dihuang Pills (LDPs) are a well-known prescription of nourishing yin especially for invigorating kidney-yin. According to the deviation of the structural imbalance of intestinal flora in kidney-yin deficiency patients and the study about polysaccharides having significant added value on intestinal probiotics, it is indicated that there is a possible correlation between intestinal flora metabolism and the mechanism of LDPs intervening in kidney-yin deficiency. In this study, LDPs, a nourishing medicine with rich polysaccharides, are used as the research object. First of all, the kidney-yin deficiency hyperthyroidism rat model was established and evaluated. The appearance of the rats' behavioral, T3, T4, FT3, FT4 and renal histopathology indexes were detected. After LDP treatment for 21 days, the original model of manic rats became more tame and gentle, the T3, T4, FT3 and FT4 values decreased, which gradually approached those contents of the control group rats, and renal pathological sections were shown to be better. Then, we adopted a metabonomics study on urine and excrement of kidney-yin deficiency hyperthyroid rats. 11 metabolites and 18 metabolites were chosen as potential biomarkers among the urine metabonomics study and fecal metabonomics study, respectively. According to the changes of the biomarkers' content, it is speculated that the disorders of metabolism and intestinal flora metabolism occurred after modeling. At the same time, we monitored intestinal flora diversity and metabolic behavior in model rats and LDP-treated rats. Hyperthyroidism caused metabolic disorders of the carboxylic acid cycle, glycometabolism, and amino acid metabolism. Also the energetic metabolism increased the amount of undigested food debris which promoted the growth of the gut microbiome, which may closely relate to the development of the disease. After 21 days of LDP treatment, it was found that LDPs could change the metabolic abnormality, balance structure and quantity of intestinal bacteria, and adjust the diversity of the intestinal flora. The mechanism of LDPs intervening in the metabolism of kidney-yin deficiency hyperthyroidism and the effect of intestinal flora metabolism had a certain connection.
    Article · Jun 2015 · RSC Advances
  • Qiang Wang · Lan Shen · Shiyu Ma · [...] · Yi Feng
    [Show abstract] [Hide abstract] ABSTRACT: The two herbs Ligusticum chuanxiong (LC) Hort. (Umbelliferae) and Gastrodia elata (GE) Blume (Orchidaceae), are widely used in the clinic for the treatment of migraine. This article aims to understand the effects of LC and GE on blood-brain barrier (BBB) permeability in migraine rats. Serotonin, excitatory amino acids (EAAs) and matrix metalloproteinase-9 (MMP-9) were determined at different sampling times to assess BBB disruption during a migraine attack. BBB permeability was examined by fluorescence imaging and Evans blue dye (EBD) extravasation. The results showed that the expression of serotonin in migraine rat brain was enhanced from 30 min to 120 min and glutamate (Glu) was suppressed from 30 min to 60 min in LC-GE group compared with the model group (p < 0.05 or 0.01), while the MMP-9 levels in migraine rat blood was increased at 30 min as well as decreased at 120 min in LC-GE group compared with the model group (p < 0.05 or 0.01). EBD levels in rat brain were significantly lower at 30-60 min and 120-150 min in LC-GE group than that of the model group (p < 0.05 or 0.01). Our findings demonstrated that LC and GE might decrease BBB permeability and maintain its integrity through regulating serotonin, EAAs and MMP-9 in migraine rats.
    Article · Jun 2015 · Pharmazie
  • [Show abstract] [Hide abstract] ABSTRACT: Thymosin alpha 1 (Tα1), an immunoactive peptide, has been shown to inhibit cell proliferation and induce apoptosis in human leukemia, non-small cell lung cancer, melanoma, and other human cancers. However, the response and molecular mechanism of breast cancer cells exposed to Tα1 remain unclear. PTEN, a tumor suppressor gene, is frequently mutated in a variety of human cancers. In the present study, we aimed to investigate the biological roles of PTEN in the growth inhibition of human breast cancer cells exposed to Tα1. Using wild-type and mutant PTEN-expressing cells, we found a strong correlation between PTEN status and Tα1-mediated growth inhibition of breast cancer cells. The growth inhibition effect was more pronounced in breast cancer cells in which Tα1 enhanced PTEN expression, whereas endogenous PTEN knockdown reversed the growth inhibition effect of Tα1 in breast cancer cells. Further investigation revealed that PTEN up-regulation, which was induced by Tα1, can inhibit the activation of the PI3K/Akt/mTOR signaling pathway, leading to the growth inhibition of breast cancer cells. The addition of the synergy between Tα1 and the inhibition of PI3K/Akt/mTOR activation could strongly block cell viability in PTEN down-regulated breast cancer cells. PTEN-overexpressing cells not only up-regulated Bax and cleaved caspase-3/9 and PARP expression but also down-regulated Bcl-2 compared to the treatment with Tα1 alone. Together these findings suggest that PTEN mediates Tα1-induced apoptosis through the mitochondrial death cascade and inhibition of the PI3K/Akt/mTOR signaling pathway in breast cancer cells.
    Article · May 2015 · Apoptosis
  • Yan Guo · Qiao Pan · Jing Zhang · [...] · Lan Shen
    [Show abstract] [Hide abstract] ABSTRACT: Transcriptional co-activator with PDZ-binding motif (TAZ) has been reported to be associated with carcinogenesis. However, the cellular function of TAZ in human hepatocellular carcinoma (HCC) remains elusive. In this study, an immunohistochemistry analysis revealed that the expression of TAZ in cancer tissue samples from 180 HCC patients was significantly higher than that in adjacent normal tissues. In addition, TAZ overexpression was significantly correlated with aggressive tumor characteristics such as tumor size, TNM stage, lymph node or distant metastasis, histological differentiation and recurrent HCC (P<0.05). The Kaplan—Meier test showed that TAZ-positive expression was related to a poor prognosis compared to TAZ-negative expression (P<0.05). Furthermore, the expression level of TAZ was generally correlated with the invasiveness of cancer cells. The overexpression of TAZ in the Huh7 cell line, which endogenously expresses TAZ at low levels, significantly promoted cell proliferation, migration and invasion and inhibited apoptosis, whereas RNA interference—mediated knockdown of TAZ in the highly invasive cell line MHCC-97H significantly suppressed cell proliferation, migration and invasion in vitro and tumor formation in vivo.Taken together, these results suggest that TAZ plays an important role in the proliferation, apoptosis, migration and invasion of HCC cells and that the expression of TAZ in HCC patients is closely related to their prognosis. Thus, TAZ is a potential novel biomarker for predicting prognosis and guiding personalized therapeutic strategies. This article is protected by copyright. All rights reserved
    Article · Feb 2015 · Journal of Cellular Biochemistry
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    [Show abstract] [Hide abstract] ABSTRACT: Although PEGylation plays an important role in drug delivery, knowledge about the distribution behavior of PEGylated drugs in ischemic myocardia is rather limited compared to nanoparticles. This work therefore aims to characterize the targeting behavior of the anti-myocardial ischemic mono-PEGylated conjugates of Radix Ophiopogonis polysaccharide (ROP) in two clinically relevant animal models, ie, the myocardial infarction (MI) model and the ischemia/reperfusion (IR) model. To determine the effect of the molecular size of conjugates, two representative conjugates (20- and 40-kDa polyethylene glycol mono-modified ROPs), with hydrodynamic size being approximately and somewhat beyond 10 nm, respectively, were studied in parallel at three time points postdose after a method for determining them quantitatively in biosamples was established. The results showed that the cardiac distribution of the two conjugates was significantly enhanced in both MI and IR rats due to the enhanced permeability and retention effect induced by ischemia. In general, the cardiac targeting efficacy of the conjugates in MI and IR rats was approximately 2; however, different changing in targeting efficacy with time was observed between MI and IR rats and also between the conjugates. Although the enhanced permeability and retention effect-based targeting efficacy for mono-PEGylated ROPs was not high, they, as dissolved macromolecules, are prone to diffusion in the cardiac interstitium space, and thus, facilitate the drug to reach perfusion-deficient and nonperfused areas. These findings are helpful in choosing the cardiac targeting strategy.
    Full-text Article · Jan 2015 · International Journal of Nanomedicine
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    Lin-Tao Jia · Rui Zhang · Lan Shen · An-Gang Yang
    [Show abstract] [Hide abstract] ABSTRACT: Cancers are characterized by aberrant cell signaling that results in accelerated proliferation, suppressed cell death, and reprogrammed metabolism to provide sufficient energy and intermediate metabolites for macromolecular biosynthesis. Here, we summarize the emerging "unconventional" roles of these regulators based on their newly identified interaction partners, different subcellular localizations, and/or structural variants. For example, the epidermal growth factor receptor (EGFR) regulates DNA synthesis, microRNA maturation and drug resistance by interacting with previously undescribed partners; cyclins and cyclin-dependent kinases (CDKs) crosstalk with multiple canonical pathways by phosphorylating novel substrates or by functioning as transcriptional factors; apoptosis executioners play extensive roles in necroptosis, autophagy, and in the self-renewal of stem cells; and various metabolic enzymes and their mutants control carcinogenesis independently of their enzymatic activity. These recent findings will supplement the systemic functional annotation of cancer regulators and provide new rationales for potential molecular targeted cancer treatments. Copyright © 2014. Published by Elsevier Ireland Ltd.
    Full-text Article · Nov 2014 · Cancer Letters
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    XiaoLi Shi · Xiao Lin · XiangWei Zheng · [...] · Lan Shen
    [Show abstract] [Hide abstract] ABSTRACT: Radix Ophiopogonis polysaccharide (ROP), a highly hydrophilic macromolecule, has a unique anti-ischemic action in the myocardium. One of the main problems with its use is its relatively short half-life in vivo. To solve this problem, injectable long-acting drug delivery systems, which combine mono-PEGylation (PEG, polyethylene glycol) with the in situ formation of poly(d,l-lactide-co-glycolide) copolymer (PLGA) depots, were tested in this study. Through a moderate coupling reaction between 20 kDa amino-terminated methoxy-PEG and excessive ROP with activated hydroxyls, a long-circulating and bioactive mono-PEGylated ROP was prepared and characterized. A reasonable and applicable range of PLGA formulations loaded with the mono-PEGylated ROP were prepared, characterized, and evaluated in vivo. Relative to ROP, the half-life of which was only 0.5 hours, the conjugate alone, following subcutaneous administration, showed markedly prolonged retention in the systemic circulation, with a mean residence time in vivo of approximately 2.76 days. In combination with in situ-forming PLGA depots, the residence time of the conjugate in vivo was prolonged further. In particular, a long-lasting and steady plasma exposure for nearly a month was achieved by the formulation comprising 40% 30 kDa PLGA in N-methyl-2-pyrrolidone. Long-lasting and steady drug exposure could be achieved using mono-PEGylation in combination with in situ formation of PLGA depots. Such a combination with ROP would be promising for long-term prophylaxis and/or treatment of myocardial ischemia. For high-dose and highly hydrophilic macromolecular drugs like ROP, more than one preparation technology might be needed to achieve week-long or month-long delivery per dosing.
    Full-text Article · Nov 2014 · International Journal of Nanomedicine
  • [Show abstract] [Hide abstract] ABSTRACT: Co-processed excipients withgelatinized or non-gelatinized starch were prepared by spray drying. Powder and tablet properties of corocessed excipients prepared were compared with those of physical mixtures and spray-dried lactose. Their applicability in traditional Chinese medicine (TCM) powder tableting was tested on two TCM extracts, i.e., the gardenia extract and the Herba Sedi extract. It was shown that gelatinizing starch before co-spray drying with lactose could improve the performance and efficiency of starch as a binder, resulting in remarkable improvement in physicomechanical properties of co-processed excipients prepared. Conpared to self-made and commercially available spray-dried lactose, co-processed excipients achieved better compactability and higher drug loading for TCM extracts. In conclusion, the lactose-gelatinized starch co-processed excipient, with excellent physicomechanical properties, is promising to be explored as a new excipient for direct tableting.
    Article · Nov 2014 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
  • [Show abstract] [Hide abstract] ABSTRACT: In the area of injectable long-acting formulations, the in situ forming system (ISFS) is an attractive alternative for its various superiorities. In this study, both hydrophilic and hydrophobic in situ forming systems, using Poloxamer and sucrose acetate isobutyrate (SAIB) or poly(D,L-lactide-co-glycolide) copolymer (PLGA) as carrier, respectively, were investigated for Radix Ophiopogonis polysaccharide (ROP), a natural anti-myocardial ischemic fructan. A reasonable and applicable range of formulations were selected from each carrier for in vivo study by investigating their rheological property. The results from in vivo evaluation show that relatively promising sustained behaviors were achieved by formulations 24% P407/10% P188, 40% PLGA30k/NMP, and 30% PLGA50k/NMP. Significant differences of drug release kinetics were observed between in situ thermally-induced Poloxamer-based hydrogels and in situ solvent exchange-induced hydrophobic PLGA depots. This suggests that different ISFS could be chosen to provide different application purpose for polysaccharide drugs. In the case of ROP, Poloxamer-based ISFS is promising for short-term acute therapies; however, PLGA-based ISFS might be promising for long-term precaution or/and cure of myocardial ischemia.
    Article · Sep 2014 · International Journal of Biological Macromolecules
  • Yi Feng · Yan-Long Hong · Jie-Chen Xian · [...] · Lan Shen
    [Show abstract] [Hide abstract] ABSTRACT: Traditional processes are mostly adopted in traditional Chinese medicine (TCM) preparation production and the quality of products is mostly controlled by terminal. Potential problems of the production in the process are unpredictable and is relied on experience in most cases. Therefore, it is hard to find the key points affecting the preparation process and quality control. A pattern of research and development of traditional Chinese medicine preparation process based on the idea of Quality by Design (QbD) was proposed after introducing the latest research achievement. Basic theories of micromeritics and rheology were used to characterize the physical property of TCM raw material. TCM preparation process was designed in a more scientific and rational way by studying the correlation among enhancing physical property of raw material, preparation process and product quality of preparation. So factors affecting the quality of TCM production would be found out and problems that might occur in the pilot process could be predicted. It would be a foundation for the R&D and production of TCM preparation as well as support for the "process control" of TCMIs gradually realized in the future.
    Article · Sep 2014 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: To evaluate in vivo pharmacokinetics of Ophiopogonis Radix polysaccharide MDG-1 oily suspension injection prepared with different prescriptions in rats, and explore the feasibility of the long-acting drug delivery of MDG-1 Injection by using the oily suspension drug release system. Method: MDG-1 microparticles were prepared by the anti-solvent precipitation method. Their size and size distribution were characterized. Castor oil with a high viscosity or aluminum stearate were added into soybean oil with a low viscosity, in order to prepare oily media with different viscosities, detect their rheological properties and screen out superior prescriptions for in vivo evaluation. Result: The average size of microparticles was 21.81 microm, and the span between them was 2.63. The in vivo evaluation was conducted for prescriptions of mixed oil (soybean oil/castor oil, 2: 3) and soybean oils gelled by 2% and 4% aluminium stearate. Among them, the prescription of soybean gelled by 4% aluminium stearate could significantly reduce C(max) and prolong the apparent t1/2, with the MDG-1 release time of several days. Conclusion: It is feasible to achieve the long-acting MDG-1 drug delivery by using oily media with a high viscosity.
    Article · Jul 2014 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
  • [Show abstract] [Hide abstract] ABSTRACT: Metabolic disorders such as hyperglycemia, dislipidemia, and insulin resistance often occur in obese populations long before the manifestation of type 2 diabetes mellitus (T2DM), cardiovascular disease, and cancer. The prevention of metabolic disorders in obese individuals might decrease the morbidity of diabetes and other metabolic diseases. Ophiopogon japonicus is a traditional Chinese medicine used for thousands of years to treat patients with diabetes. We showed in previous work that MDG-1, a polysaccharide extracted from Ophiopogon japonicus, could treat T2DM. To investigate whether MDG-1 can prevent metabolic disorders, metabonomic methods, together with multivariate analysis, were used to evaluate the role of MDG-1 in the prevention of metabolic disorders in a high-fat, diet-induced obesity (DIO) model. Thirty-six male C57BL/6 mice (8 weeks old) were randomly divided into a control group (normal chow), a model group (high-fat chow), and an MDG-1 group (high-fat chow dosed with 300 mg kg−1 MDG-1). After 16 weeks of treatment, urinary metabonomic studies were performed using ultra-performance liquid chromatography-time of flight mass spectrometry in combination with multivariate statistical analysis. Indices of body weight, food intake, fasting and fed blood glucose, oral glucose tolerance test (OGTT), and OGTT plasma insulin were collected. MDG-1 treatment was shown to exert mild ameliorative effects on bodyweight gain, fed blood glucose levels, OGTT, and the insulin resistance of DIO mice. In addition, 21 potential biomarkers of glucose, fatty acid, phospholipid and amino acid metabolism, the tricarboxylic acid cycle and purine metabolism were identified. Based on these compounds, it is suggested that MDG-1 could reduce glucose, the glucose-related products lactic acid and N-acetyl-D-glucosamine, and lipids, thus normalizing tricarboxylic acid cycle activity while decreasing purine, hence alleviating oxidative stress in DIO mice. Although there was no obvious alteration in visible biomedical indices, invisible metabolic disturbances did occur with MDG-1 supplementation, which may lead to the possible elucidation of the action of MDG-1 against metabolic disorders.
    Article · Jun 2014 · Analytical methods
  • Shiyu Ma · Lan Shen · Yu Zhai · [...] · Kefeng Ruan
    [Show abstract] [Hide abstract] ABSTRACT: The quantitative characterization and evaluation of the synchrony of multi-component release behavior are bottlenecks which urgently need to be solved in the study of multi-component release kinetics and the quality control of multi-component traditional Chinese medicine (MCTCM). MCTCM is made using original prescriptions and preparations. At present, MCTCM is generally evaluated using pharmacodynamics evaluation. However, this method lacks convenience and cannot clearly reveal the correlation between the whole dynamic process of drug release and in vivo absorption. It is also very limited by the preparation of MCTCM. In addition, there are various types of effective ingredients in MCTCM, which show distinctly different physicochemical properties. These differences may lead to the asynchrony of drug release between MCTCM and the original preparation, which thereby directly affects the efficacy. However, we can't find the core reason for this issue through the use of pharmacodynamics evaluation. The papers reported previously were confined to studying the release characteristics of one or a few components in MCTCM and the drug release evaluation method reported was too macroscopic to specifically identify the components which caused the integral asynchrony. In this paper, in order to reveal the MCTCM release synchronous characteristics, Fuzhenghuayu capsules were selected as the model, an original preparation used, and the integral release evaluation method based on a mathematics set was established in guiding the preparation of MCTCM. This method can not only be used in evaluating the release characteristics of MCTCM by the parameter of the asynchronous coefficient, but can also be used in adjusting the dose of the release unit by the relative error parameter. The results demonstrated that this evaluation method was feasible, stable and reproducible. Also the Fuzhenghuayu pellets guided by this method showed release synchrony and similar pharmacodynamics with the original capsules, and the drug release mechanism was mainly frame erosion. Through this study, we could then evaluate the quantifiable release characteristics of MCTCM and apply an integral synchronous evaluation method for MCTCM.
    Article · Apr 2014 · Analytical methods

Publication Stats

652 Citations


  • 2014
    • Shanghai University of Traditional Chinese Medicine
      • College of Chinese Materia Medica
      Shanghai, Shanghai Shi, China
  • 2013
    • Shanghai University
      Shanghai, Shanghai Shi, China
  • 2007
    • Fourth Military Medical University
      • Department of Biochemistry and Molecular Biology
      Xi’an, Liaoning, China