Latest ArticlesFifteen alkaloid compounds were isolated from the 70% aqueous alcohol extract of Stephania tetrandra S. Moore by silica gel, reversed phase silica gel, Sephadex LH-20 column chromatography and semi-preparative high performance liquid chromatography. They were identified as tetrandraside A (1), (Z)-N-formyl-nornuciferin (2), (E)-N-formyl-nornuciferin (3), salutaridine (4), salutaridine N-oxide (5), (E)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2 propenamide (6), dauriporphine (7), sinomenine (8), liriodenine (9), α-magnoflorine (10), (1S)-4'-β-glucosylcoclaurine (11), tetrandrine (12), fangchinoline (13), tetrandrine 2'-β-oxide (14), and tetrandrine 2'-α-oxide (15), respectively, by MS, NMR and single crystal diffraction. Among them, compound 1 is a new alkaloid glycoside. Compounds 2-11 were obtained from this plant for the first time. These compounds showed obvious cytotoxic activity against drug-resistant lung cancer cell line H1299, and compound 9 had the best activity, with an IC50 of 5.38 μmol·L-1.
An ultra-high performance liquid chromatography method for the determination of 8 constituents in Qingzao Jiufei Decoction was established and the basis of related chemical substances with antioxidant activity in Qingzao Jiufei Decoction was explored. The separation was performed on a Waters Cortecs RP Shield C18 (150 mm × 2.1 mm, 1.6 μm) using UHPLC-DAD as the mobile phase was water (containing 0.1% phosphoric acid) – acetonitrile with flow rate of 0.30 mL·min-1 by gradient elution ① determining 5 constituents (amygdalin, liquiritin, liquiritin apioside, rutin and isoquercitrin) at the wavelength of 210 nm, 237 nm and 358 nm. Under gradient elution ②, 3 constituents (glycyrrhizin, glycyrrhizic acid and sesamin) were determined at the wavelength of 210 nm and 265 nm. The IC50 of 10 batches of Qingzao Jiufei Decoction scavenging 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS+) free radicals obtained through test and Probit model was analyzed for correlation with the contents of 8 constituents. The established methods had a good linear relationship (r > 0.999), good repeatability and stability. The recovery rate was between 82.8% and 112.4%. In a series of concentration range, the higher the concentration of Qingzao Jiufei Decoction, the stronger the free radical scavenging effect. There was a significant correlation between the content of rutin and glycyrrhizic acid and the IC50 of scavenging free radicals. The content determination methods established in this experiment provide a basis for a reasonable and scientific evaluation of the quality of Qingzao Jiufei Decoction. Qingzao Jiufei Decoction has antioxidant activity, which is significantly positively correlated with the content of rutin and glycyrrhizic acid.
A quantitative analysis method for ten principal components (phenylethanol, iridoids and triterpenes) of raw Ligustri Lucidi Fructus and its wine-steamed product was developed using liquid chromatography tandem triple quadrupole mass spectrometry (LC-QQQ-MS) to study their pharmacokinetic behavior in vivo. The results of methodological investigation were in accord with the criteria of biological analysis. After a single administration to rats of the water extracts of Ligustri Lucidi Fructus and its wine-steamed product, the plasma concentration of each component at different time points was measured and the pharmacokinetic parameters were determined. The AUC0-24 h and Cmax of the phenylethanol components (salidroside, tyrosol, hydroxytyrosol) were the greatest, suggesting that these components are the main pharmacological substances of Ligustri Lucidi Fructus. In addition, the tmax values of the eight major components were even lower with administration of the wine-steamed product, suggesting that these components are rapidly absorbed. However, the tmax values of specnuezhenide and oleanolic acid were greater with administration of the wine-steamed product, indicating that these two components were more slowly absorbed. A secondary peak phenomenon of tyrosol and hydroxytyrosol were observed in two sample groups, whereas the secondary peak phenomenon of salidroside occurred only with the wine-steamed product. This result suggests that the effect of wine-steamed product could persist for a long period. Meanwhile, the relative bioavailability of specnuezhenide and oleanolic acid was greater than 100% with administration of the wine-steamed product, consistent with the Traditional Chinese Medicine theory of the wine-steamed product being more effective than the raw material. The results reveal the different pharmacokinetic parameters and relative bioavailability of each component of Ligustri Lucidi Fructus and its wine-steamed product, and also demonstrate the variation and correlation of various components in vivo and in vitro, providing an experimental basis for the selection of quality control indexes, mechanisms of processing and the metabolic rule in vivo of Ligustri Lucidi Fructus. These experiments were approved by the Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medicine Science.
We identified and analyzed the components and chemical constituents of hawthorn leaves of Crataegus pinnatifida Bge. (wild) and C. pinnatifida Bge. var major N. E. Br (cultivated) by using ultra high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MSE) combined with UNIFI data analysis platform and multivariate statistics. Fifty-eight chemical compounds were identified, including organic acids, flavonoids, triterpenoic acids, monoterpenes and sesquiterpenoids; among them, terpenoid content was the most abundant. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to identify the differential components of hawthorn leaves from two sources. The results show that there are differences in the chemical compositions of the two sources, including 24 flavonoids and terpenoids (including monoterpenoids, sesquiterpenoids and triterpenoid acids). The types of flavonoids (such as rutin, vitexin-2''-O-rhamnoside, isovitexin-2''-O-rhamnoside, hyperoside, quercetin-3-O-β-D-glucoside) and terpenoids (crataegolic acid, corosolic acid and ursolic acid) in C. pinnatifida were more varied than those found in C. pinnatifida Bge. var major N. E. Br, and their contents were relatively higher. This study provides a comprehensively analysis of the different chemical components of hawthorn leaves from two sources listed in the Chinese Pharmacopoeia, and provides a basis for the selection of raw materials and the potential development and utilization of hawthorn leaves.
ZSP1601, a novel pan-phosphodiesterase inhibitor is in development for the treatment of nonalcoholic steatohepatitis. A physiologically-based pharmacokinetic (PBPK) model was developed to predict the pharmacokinetics of ZSP1601 in human. The PBPK model following intravenous and oral dose of ZSP1601 in rats and dogs was firstly built using preclinical in vitro and in vivo data. The PBPK model in human was then built based on models in animal. The in vitro-in vivo extrapolation (IVIVE) method and some allometric scaling methods were used to predict the clearance in human, respectively. The PBPK models using IVIVE and allometry of unbound CL plus the rule of exponents methods predicted the pharmacokinetics of ZSP1601 in healthy Chinese subjects successfully. The predicted parameters Cmax and AUC following single oral dose administration were within 0.5-2 folds of the observed data. The model was optimized and the final model was used to predict the pharmacokinetics of ZSP1601 in North European Caucasian, Geriatrics, Obese and Morbidly Obese, respectively. Animal studies were approved by the Animal Management and Use Committee of Suzhou AppTec Inc., and the approved No. is SZ20140916.
According to the commonly used tablet compressibility, compactability and tabletability equation, the influence of pressure range on the fitting results and parameters of different compression equations was studied, and the optimal pressure range of different equations was determined. Plastic material microcrystalline cellulose (MCC) PH102, brittle material spray dried lactose and Chinese medicine Sanqi were used as experimental objects, the compression curves of tablets were obtained by the combination of dies with different diameters. For Heckel equation, the shape of Heckel section of different materials is not uniform, and the specified linear fitting range cannot be obtained, therefore, different distances between fitting pressure starting point and starting point were set to observe the influence of pressure range on R2 of Heckel equation. The Kawakita equation, Gurnham equation, Ryshkewitch-Duckworth (R-D) equation and Power equation are fitted in three different pressure ranges of 15-200, 15-300 and 15-400 MPa, respectively. In order to find the best linear region of Heckel equation, the 3D scatter diagram of "starting point of pressure, pressure range and R2" is drawn. The best linear pressure ranges of Heckel curves of MCC, lactose and Sanqi were 20-170, 20-220 and 10-90 MPa, respectively. It is proved that the 3D scatter diagram is an effective method to find the linear range of Heckel equation. The change of pressure range has little influence on the curve fitting effect and compression parameters of Kawakita equation, Gurnham equation and Ryshkewitch-Duckworth equation. The low pressure range of 15-200 MPa can meet the fitting requirements of Kawakita equation, Gurnham equation, R-D equation and Power equation for different materials. Therefore, only by optimizing the pressure range, can the good fitting effect be ensured and the obtained compression parameters be more reliable and interpretable.
Idiopathic pulmonary fibrosis is a fibrous disease. At present, its pathogenesis has not been fully elucidated and there is no drug with definite therapeutic effect. After four stages of development, antibody drugs are becoming a new hotspot in drug research and development with their own advantages. A number of drugs have entered the stage of clinical trials. Based on this, this review summarizes the antibody drugs for the clinical stage of clinical research of idiopathic pulmonary fibrosis, in order to summarize the development of antibody drugs, and provide certain bases and ideas for the development of antibody drugs.
Cardiac fibrosis is a vital pathological feature of various cardiovascular diseases, including myocardial infarction and heart failure. However, there have been few clinical interventions to treat cardiac fibrosis. Noncoding RNAs (ncRNAs) are a class of RNAs that do not encode proteins. ncRNAs participate in various cellular biological processes and regulate gene expression at transcription, post-transcription and epigenetic levels. Recent studies demonstrate that ncRNAs participate in the regulation of cardiac fibrosis by affecting the proliferation and transition of cardiac fibroblasts. ncRNAs can be used as potential intervention targets and biomarkers for cardiac fibrosis, provide new strategies and approach for treating and preventing fibrosis associated cardiovascular diseases. This review summarizes the function and mechanisms of ncRNAs in cardiac fibrosis.
Idiopathic pulmonary fibrosis (IPF) is an irreversible and highly mortal interstitial disease. The incidence of IPF is increasing around the world, which seriously harms human health and brings huge economic burden to the society. While traditional treatments can slow the progression of the disease, they are far to cure this disease. Clinically, pirfenidone and nintedanib are two main drugs that used for the treatment of IPF. However, severe adverse reactions were reported in some patients. Therefore, it is very important to explore novel therapeutic strategies to reverse fibrosis and regenerate lung. The repair and regeneration ability of stem cells has unique advantages in the treatment of pulmonary fibrosis. The structure and function of organoids produced by stem cells have similar characteristics with live organs. Therefore, lung stem cells play an important role in the discovery of novel anti-IPF drugs, and in the formation and development of lung tissue. In addition, organoids produced by stem cells also serve as a perfect model for regenerative medicine. In this review, we mainly summarize the role of stem cells and organoids in the repair and regeneration of pulmonary fibrosis, and hope to provide a reference for the development of clinical treatment of pulmonary fibrosis.
S-phase kinase-associated protein 2 (Skp2) is one of the components of E3 ubiquitin ligase, which can induce proteasome-mediated proteolysis or regulate labeled substrates to promote cell proliferation and migration and inhibit cell apoptosis and senescence by connecting the ubiquitin chains of K48 and K63 to different substrates. Skp2 is also a potential drug target in a variety of fibrotic diseases, is highly expressed in a variety of fibrotic diseases, and regulates the occurrence and progression of these diseases. This paper reviews Skp2's structure, downstream targets, and cellular regulation and then focuses on research progress on Skp2 in various fibrotic diseases, such as liver fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, corneal fibrosis, and cardiac fibrosis, which may help provide a new research approaches for clinical development of Skp2-targeted antifibrotic drugs.
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