Research progress in quality studies and antiviral effect of Qingyan Dropping Pills / 国际生物医学工程杂志

Qingyan Dropping Pills have the effects of relieving wind and heat, detoxifying, and promoting the pharynx. It is commonly used in traditional Chinese medicines to treat acute and chronic pharyngitis, as well as sore throats and dry throats caused by surgery. Recently, many studies have shown that Qingyan Dropping Pills have certain effects on bacteriostasis, anti-inflammatory, antioxidant, and antiviral activities. As the coronavirus disease 2019 (COVID-19) pandemic enters the post-epidemic era, the regular use of drugs for COVID-19 pandemic symptoms has become a new trend. Therefore, there is a good market prospect to explore and develop Chinese patent medicines with antiviral effects. A preliminary study on the herbal formula and material basis of Qingyan Dropping Pills revealed that they have potential for antiviral applications. In this paper, the research on the quality study and antiviral effect of Qingyan Dropping Pills was reviewed, and the research direction of its secondary development was discussed to provide ideas and references for the new use of old traditional Chinese medicines.

The underlying mechanism of autophagy regulating liver injury with obstructive jaundice in Sprague-Dawley rats / 中华肝胆外科杂志

Objective:To investigate the effect of autophagy on liver injury with obstructive jaundice in Sprague-Dawley (SD) rats and its underlying mechanism.Methods:Thirty-five healthy male SD rats, SPF grade, aged 6-8 weeks, weighting 200-300 g, were divided into 5 groups with 7 rats in each group, including sham group (simple free common bile duct, without ligation, intraperitoneal injection of normal saline), obstructive jaundice (OJ) group (established by common bile duct ligation, intraperitoneal injection of normal saline), OJ group with 3-MA, OJ group with Rapamycin, and OJ group with 3-MA and VX-765. Morphological changes in liver tissues were analyzed with HE staining. Expression of autophagy-related protein Atg5 was detected by immunohistochemistry staining. Liver function was analyzed by automatic biochemical instrument and the level of serum interleukin (IL)-18 was detected using ELISA assay. Protein levels of autophagy related-proteins and endoplasmic reticulum stressed (ERs)-related apoptosis proteins were detected by Western Blot.Results:The relative expression of autophagy related protein Atg5 in OJ group was significantly higher than that in sham group [(5.0±1.0) vs. (2.8±1.3), t=-3.00, P<0.05]. Compared with sham group, the activity of autophagy was enhanced and the protein levels of Caspase-1/p-65 and IL-18 were significantly increased in OJ group. At the same time, apoptosis was induced by activating ERs. In OJ group, the autophagy inducer 3-MA improved the expression levels of Caspase-1/p-65 and IL-18, and aggravate liver injury. While after applying the autophagy agonist Rapamycin in OJ rat models, the expression of Caspase-1/p-65 and IL-18 was repressed and liver damage was also reduced. In addition, in rat OJ groups with 3-MA, inhibition of Caspase-1 by VX-765 could down regulate the expression of Caspase-1/p-65 and IL-18, and protect against liver injury. Conclusions:Both ERs related apoptosis and autophagy were activated after ligation of common bile duct. Besides, activation of autophagy could reduce OJ-induced liver injury in SD rats by inhibiting the Caspase-1/p-65 inflammatory pathway.

c-MYC-mediated TRIB3/P62+ aggresomes accumulation triggers paraptosis upon the combination of everolimus and ginsenoside Rh2

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.

Conditional reprogramming: next generation cell culture

Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming (CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR co-cultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase (ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years' development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.

Small molecules for fat combustion: targeting obesity

Obesity is increasing in an alarming rate worldwide, which causes higher risks of some diseases, such as type 2 diabetes, cardiovascular diseases, and cancer. Current therapeutic approaches, either pancreatic lipase inhibitors or appetite suppressors, are generally of limited effectiveness. Brown adipose tissue (BAT) and beige cells dissipate fatty acids as heat to maintain body temperature, termed non-shivering thermogenesis; the activity and mass of BAT and beige cells are negatively correlated with overweight and obesity. The existence of BAT and beige cells in human adults provides an effective weight reduction therapy, a process likely to be amenable to pharmacological intervention. Herein, we combed through the physiology of thermogenesis and the role of BAT and beige cells in combating with obesity. We summarized the thermogenic regulators identified in the past decades, targeting G protein-coupled receptors, transient receptor potential channels, nuclear receptors and miscellaneous pathways. Advances in clinical trials were also presented. The main purpose of this review is to provide a comprehensive and up-to-date knowledge from the biological importance of thermogenesis in energy homeostasis to the representative thermogenic regulators for treating obesity. Thermogenic regulators might have a large potential for further investigations to be developed as lead compounds in fighting obesity.

Authentic compound-free strategy for simultaneous determination of primary coumarins in Peucedani Radix using offline high performance liquid chromatography-nuclear magnetic resonance spectroscopy-tandem mass spectrometry

Herein, a strategy is proposed for the simultaneous determination of primary coumarins in Peucedani Radix (Chinese name: Qianhu). The methodology consists of three consecutive steps: 1) Semi-preparative LC in combination with a home-made automated fraction collection module to fragment the universal metabolome standard into ten fractions (Frs. I-X); 2) LC-accurate MS/MS and quantitative H NMR spectroscopy conducted in parallel to acquire the qualitative and quantitative data of each fraction; 3) Robust identification and quantification of components by use of LC coupled to multiple reaction monitoring. In this final step, the most significant fractions (Frs. III-X) were pooled to serve as the pseudo-mixed standard solution. Meticulous online parameter optimization was performed to obtain the optimal parameters, including ion transitions and collision energies. Concerns were particularly paid onto pursuing the parameters being capable of monitoring -specific isomers, notably praeruptorin E 3'-isovaleryl-4'-angeloylkhellactone. The quantitative performance of the method was validated according to diverse assays. Eleven primary coumarins (-) were unambiguously identified and absolutely quantified, even though no external reference compound was used. Above all, the integrated strategy not only provides a feasible pipeline for the quality assessment of Peucedani Radix, but more importantly, shows the potential for authentic compound-free quantitative evaluation of traditional Chinese medicines.

Developing Key Technologies in R&D and Quality Research of Chinese Medicine / 世界科学技术-中医药现代化

Quality assurance is the key to the clinical efficacy,industrial development and international development of Chinese medicine.This article,themed “developing key technologies in R&D and quality research of Chinese medicine”,introduced the advances in constructing state key laboratory of Chinese medicine,the location of overseas innovative platform,systemic research of Chinese medicine (effectiveness,safety,stability,controllability,systematicness) and R&D of innovative Chinese medicine.We also discussed how to apply advanced technologies in drug evaluation,and how to utilize the basis of scientific research and academic advances in the development of innovative drugs,thereby ensuring the safety,efficiency and controllability of drugs.

Research progress of the studies on the roots of Peucedanum praeruptorum dunn [Peucedani radix]

As a commonly employed traditional Chinese medicine, Peucedani Radix [Qian-hu in Chinese], which consists of the dried roots of Peucedanum praeruptorum Dunn, has a long history of application for the treatment of cough with thick sputum and dyspnea, nonproductive cough and upper air-way infections in traditional medicinal practice. The current review aims to summarize the research progress on the botany, phytochemistry, chemical analysis, pharmacological assay, and pharmacokinetic profile of this famous herbal drug. All available information on this traditional medicine was obtained via electronic search [using ACS, PubMed, Web of Science, Google Scholar, Baidu Scholar, and CNKI]. Phytochemical investigations revealed that angular-type pyranocoumarins [APs], mainly [+/-]- praeruptorin A [Pd-Ia], [+]-praeruptorin A, [+/-]-praeruptorin B, [+]-praeruptorin B [Pd-II] and [+]-praeruptorin E [PdIII], were the main active components in Qian-hu, while some other types of ingredients were also identified from this herb. The crude extract and pure compounds from Peucedani Radix exhibited a wide spectrum of in vitro and in vivo pharmacological activities, including vasorelaxant, cardioprotective, hepatoprotective, anti-tumor and anti-platelet aggregative effects. Conversely to the well-defined chemical constituents and activities, the properties of absorption, pharmacokinetics, and metabolism were rarely characterized. However, further investigations are wistful for the development of new drugs and therapies for various diseases, especially cardiovascular disorders. Collectively, the present review on the phytochemistry, chemical analysis, pharmacological evaluation, and pharmacokinetic profile of Peucedani Radix will provide meaningful information for further studies and commercial exploitation of the herbal medicine

Advances in Proliferation Model of Vascular Smooth Muscle Cells and Inhibitory Effects and Mechanisms of Chinese Herbal Medicine / 世界科学技术-中医药现代化

The proliferation of vascular smooth muscle cells is closely related to the pathogenesis of a variety of diseases, such as atherosclerosis, hypertension, diabetes, vascular restenosis, and etc. A proper model for smooth muscle cell proliferation can be served as an important tool for exploring the molecular mechanisms of smooth muscle cell proliferation and the screening of potential inhibitory agents. Various factors can induce the proliferation of smooth muscle cells with different mechanisms and pathological significance. The ox-LDL, AGEs, angiotensin II (AngⅡ), high glucose, tumor necrosis factor (TNF) and etc. have been successfully applied in the establishment of smooth muscle cell proliferation model. This article summarized the most commonly used models for smooth muscle cell proliferation. The inhibitory effects of Chinese herbal medicine, especially the isolated pure compounds were discussed. It was aimed to provide references for the screening of smooth muscle cells based medications as well as studies on related research and development of Chinese herbal medicine.

Analysis on layout of traditional Chinese medicine industry based on location quotient / 中国中药杂志

To observe the layout and evolution of the traditional Chinese medicine (TCM) medical industry, classify the industry by region and conduct a preliminary study on its professional advantages, competitiveness and possible cause by using the theory of location quotient in regional economics, in order to provide suggestions for the layout of the TCM medical industry.

Inspirations from natural products based drug research and development for Chinese medicine research--analysis of natural products recoded in TTD / 药学学报

Natural product is an important source of new drug research and development (R&D). Traditional Chinese medicine (TCM) innovation is the key step for its modernization and internationalization. However, due to the complexity of TCM, there are many difficulties and confusions in this process. Target-based drug discovery is the mainstream model and method of R&D. TTD, short for therapeutic target database, is developed by National University of Singapore. Besides a large amount of information on drug targets, the database also contains considerable information related to natural products. This paper briefly introduces the TTD, analyzes the natural products derived drugs/compounds recorded in TTD, which we think might provide some inspiration for the innovation of TCM.

Application research of hot-melt extrusion in preparation of solid dispersion / 药学学报

Hot-melt extrusion (HME) is mainly used to enhance the dissolution rate and bioavailability of poorly water soluble drugs. It has many advantages, such as simple process, continuous operation, high efficiency, on-line monitoring and so on. HME provides an innovative approach, which has been concerned by pharmaceutical workers, for preparation of solid dispersion abroad. This article reviews recent advances on preparation of solid dispersion by HME in preparation processing, carrier materials and quality evaluation in order to further promote and apply HME in preparation of solid dispersion.

Chemical constituents from roots of Pueraria lobata / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents in the roots of Pueraria lobata.</p><p><b>METHOD</b>Various chromatographic methods were employed to separate of chemical constituents and the spectroscopic methods were used to elucidate the structure.</p><p><b>RESULT</b>Twenty-two compounds were isolated and characterized as beta-sitosterol palmitate (1), beta-sitosterol (2), lupeol (3), lupeone (4) , puerarol (5), diisobutyl phthalate (6), bis(2-ethylhexyl) phthalate (7), sophoracoumestan A (8), coumestrol (9), allantion (10), dadzein (11), formononetin (12), 3'-methoxy daidzein (13), ononin (14), 3'-hydroxy dadzein (15), genistin (16), dadzin (17), 8-methoxy ononin (18), sissotorin (19), (-)-puerol B 2-O-glucopyranoside (20), (6S,9R)-roseoside (21) and sucrose (22), respectively.</p><p><b>CONCLUSION</b>Compounds 1, 5-8, 15, 18, 21 and 22 were isolated from P. lobata for the first time, and componds 1, 5-7, 15, 18, 21 and 22 were isolated from the genus Pueraria for the first time.</p>

Analysis of Hospital's Non-price Competition in China and Possible Solutions / 中国药房

OBJECTIVE: To discuss the advantages and disadvantages of the non-price competition in Chinese hospital market and suggest some solutions. METHODS: Using the competition theory in health economics to analyze the situation in China and the advantages and disadvantages of the price competition as well as the causes accountable for the disadvantages. RESULTS & CONCLUSIONS: The government is suggested to understand the comparative (dis)advantages brought about by non-price competition and take possible solutions such as to clarify the role of market mechanism in regulating hospital performance, establish effective supervision system and referral system, and rationalize the income of physicians etc.

Performance of Listed Companies after Merger & Acquisition in Medical Industry / 中国药房

OBJECTIVE:To evaluate the subsequent performance after the merger & acquisition (M&A) in the form of cash in medical industry during 3 years from 2000 to 2002.METHODS:Base on the financial data of the merging party and by means of principal component analysis and factor analysis,a scoring system was built for the evaluation of the performance of M&A so that the comparison of effect scores before and after M&A could be realized.RESULTS:The effect scores fluctuate dramatically after M&A,but finally reverted to the initial level before M&A.CONCLUSION:M&A in the form of cash failed to bring long-term profits to the entire medical industry.

Diversified Development of Chain Drugstore / 中国药房

OBJECTIVE:To provide references for the diversified development of chain drugstore.METHODS:The man?agement characteristics and the development tendency of chain drugstore were analyzed by using5competitive forces model together with examples.RESULTS&CONCLUSIONS:Chain drugstore should adhere to a long-term development,sparing no efforts to seek a road of development characteristic of their own and try to diversify its management forms,range of com?modities,services and brands,and standardize its administration,etc.

Systematic pharmacological evaluation of material basis for efficacy of Chinese herbal formula / 中草药

Systematic pharmacological evaluation of material basis for the efficacy of Chinese herbal formula is one of the key issues in Chinese materia medica(CMM),which is in urgent need of solution.However,its scientific connotation is still controversial in academic circles.The material basis for the efficacy of Chinese herbal formula is the total non-endogenous bioactive compound(derived either directly or indirectly from this formula) exerting the therapeutic effects,which is generated by the interaction of the formula with human body and reaches certain concentration in the target organs or tissues.Systematic evaluation of material basis for the efficacy of Chinese herbal formula is the cornerstone of modernization and internationalization of CMM,while the quality control of CMM is its prerequisite.

HPLC Determination of aristolochic acids in plants of Aristolochia L.by static pressurized liquid extraction / 中草药

Objective To optimize static pressurized liquid extraction(PLE) method for the extraction of aristolochic acids Ⅰ and Ⅱ(AAⅠ and AAⅡ) from Fructus Aristolochiae and study the influences of related factors.Methods The univariate design was introduced.The operational parameters,such as the type of solvent,particle size of the sample powder,extraction temperature,pressure,static time,flush volume,the number of cycles,and the amount of sample were optimized.Results The optimized result employed methanol as extraction solvent,particle size of 100—120 meshes,extraction temperature of 120 ℃,extraction pressure of 10.3 MPa,static time of 10 min,flush volume of 40%,1 cycle,and sample amount of 1.00 g.The method was applied for four species of traditional Chinese medicinal materials including Fructus Aristolochiae,Caulis Aristolochiae Manshuriensis,Radix Aristolochiae,and Radix Arsitolochiae Fangchi.Conclusion This method can be used to completely extract AAⅠ and AAⅡ from Fructus Aristolochiae in once extraction.The comparison shows that this static PLE method is better than ultrasonication and Soxhlet methods with higher extraction efficiency and less time-consuming.It is also better than the dynamic one in the extraction of AAs from Radix Aristolochiae.

Application of improved quality evaluation method to Fufang Danshen products / 中成药

AIM:To apply improved quality evaluation method for improving current quality criteria of Fufang Danshen products. METHODS:Considering both hydrophilic and lipophilic active components-danshensu,protocatechuic aldehyde,salvianolic acid B,cryptotanshinone and tanshinone ⅡA were selected as five markers. A HPLC method was developed to simultaneously determine their contents,which were used to compare the products from different companies,and different batches from the same company. Similarity factor method was used to evaluate the similarities of in-vitro dissolution profiles. Moreover,accelerated and long-term stability tests were performed to predict the shelf-life of Fufang Danshen products. RESULTS:All of the Fufang Danshen products passed the content requirements of Chinese Pharmacopeia. However,the content variations of the hydrophilic components were much higher than those of the lipophilic components. In dissolution tests,most of the hydrophilic components were dissolved completely while all of the lipophilic components could not be detected. The f2 values showed that there were no similar dissolution profiles among different brands of Fufang Danshen products. The contents of five markers degraded compatible with first-order kinetics processes in both the accelerated and long-term stability tests. The predicted shelf-life of Fufang Danshen products were shorter than those labelled on the products. CONCLUSION:It is suggested that more markers with defined content range instead of lower content limit are required for better control of Fufang Danshen products. Dissolution and stability tests need to be added into the quality control criteria in the Chinese Pharmacopeia.