Material Attribute Research in Quality Control of Traditional Chinese Medicine Pills： A Review / 中国实验方剂学杂志

As intelligent production of traditional Chinese medicine （TCM） has been inevitable， informatization and automation of the production process have become the precondition for realizing intelligent manufacturing of TCM， of which the accumulation of critical material attribute and the critical quality attribute are the basis. The study of material properties is of great significance to achieve the quality control of the final product in the process， but there is a lack of systematic induction and summary of the research on the attribute of TCM pills. Therefore， the authors analyzed and summarized the attributes of raw materials， excipients and intermediates in the pill unit process according to the classification of powder properties， rheological properties and texture properties. What’s more， the impact of material attributes on the quality of the final product was summarized. Besides， this review summarized the attribute characterization techniques involved in the pill process and provided some suggestions for the characterization of product quality attributes. Finally， based on the concept of quality by design （QbD）， the authors proposed that the study of material attribute should be combined with process analytical technology （PAT）， and the focus of drug quality control should be moved forward to guide equipment upgrading， so as to realize intelligent continuous manufacturing of TCM pills.

Feasibility of low-dose radiation CT scanning for liver 3D modeling printing / 医学研究生学报

Objective In the wide clinical practice of liver 3D printing, its related high-dose CT radiation has been somehow neglected and resulted in unnecessary radiation injury to the patients. This study was to explore the feasibility of liver 3D modeling printing with the low-dose radiation CT scanning technique.　Methods　This retrospective study included 40 patients undergoing liver 3D modeling printing from January 2016 to June 2018, who were equally randomized into a low-dose radiation group (100 kVp, by automated tube current modulation [ATCM] and adaptive statistical iterative reconstruction [ASIR]) and a normal-dose radiation group (120 kVp, 250 mA by filter back projection [FBP]), both with contrast agent Iohexol at 300 mgI/m1. We obtained the values of three-phase enhanced CT scanning of the abdominal aorta, portal vein and liver parenchyma, background noise (BN), volume CT dose index (CTDI), dose length product (DLP), contrast noise ratio (CNR) and effective radiation dose (ED). We input the CT DICOM data into the 3D printer for liver modeling printing and subjectively assessed the results. Results There were statistically significant differences between the low-dose and normal-dose radiation groups in the CTDI, DLP and ED (P 0.05). The ED was decreased about 35.8% in the low-dose group as compared with that in the normal-dose group ([2.58 ± 0.79] vs [4.02 ± 0.26] mSv, P 0.05). Conclusion Low-dose radiation CT scanning technology can meet the clinical requirement of liver 3D modeling printing and significantly reduce the patient’s exposure to CT radiation.

A new strategy to intervene tumor metabolism: regulatory targets for amino acid metabolism and advances in drug research / 药学学报

Reprogramming of metabolism is one of the most critical features in tumorigenesis and tumor growth. Many types of cancer show an increased demand for specific amino acids, rely on exogenous supplies, or alter amino acid metabolic pathways, leading to changes in corresponding amino acid levels to meet the need of tumorigenesis. Therefore, if the level of tumor growth-dependent amino acids can be effectively controlled, a new treatment strategy can be developed from the perspective of cell metabolism. At present, remarkable progress has been made in this field. This paper outlines the amino acid metabolic pathways closely related to tumorigenesis and tumor growth, and summarizes the corresponding regulatory mechanisms and active molecules. Finally, the direction of the field is discussed and prospected for future development.

Vitellaria paradoxa nutshells from seven sub-Saharan countries as potential herbal medicines for treating diabetes based on chemical compositions, HPLC fingerprints and bioactivity evaluation / 中国天然药物

The aim of the study was to determine the feasibility of the Vitellaria paradoxa nutshell as a new medicinal resource for treating diabetes. A total of forty-one compounds were identified by HPLC-DAD-Q-TOF-MS and phytochemical methods in V. paradoxa nutshell methanol extract. Based on HPLC fingerprints, four characteristic constituents were quantified and the origin of twenty-eight V. paradoxa nutshells from seven sub-Saharan countries was compared, which were classified into three groups with chemometric method. Twenty-eight samples contained high total phenolic content, and exhibited moderate-higher antioxidant activity and strong α-glucosidase inhibitory activity. Furthermore, all fractions and isolated compounds were evaluated for their antioxidant and α-glucosidase inhibitory activities, and α-glucosidase inhibitory action mechanism of four characteristic constituents including protocatechuic acid, 3, 5, 7-trihydroxycoumarin, (2R, 3R)-(+)-taxifolin and quercetin was investigated via molecular docking method, which were all stabilized by hydrogen bonds with α-glucosidase. The study provided an effective approach to waste utilization of V. paradoxa nutshell, which would help to resolve waste environmental pollution and provide a basis for developing potential herbal resource for treating diabetes.

Identification and screening of cardiac glycosides in Streptocaulon griffithii using an integrated data mining strategy based on high resolution mass spectrometry / 中国天然药物

The present study was designed to develop a practical strategy to tackle the problem of lacking standard compounds and limited references for identifying structure-related compounds in Streptocaulon griffithii Hook. f., especially those in trace concentrations, with a focus on antitumor activity. The cardiac glycosides (CGs)-enriched part was determined using in vitro bioactive assays in three cancer cell lines and then isolated using macroporous resins. The MS and MS/MS data were acquired using a high performance liquid chromatography coupled with hybrid quadrupole-time of flight (HPLC-Q-TOF-MS) system. To acquire data of trace compound in the extract, a multiple segment program was applied to modify the HPLC-Q-TOF-MS method. A mass defect filter (MDF) approach was employed to make a primary MS data filtration. Utilizing a MATLAB program, the redundant peaks obtained by imprecise MDF template calculated with limited references were excluded by fragment ion classification, which was based on the ion occurrence number in the MDF-filtered total ion chromatograms (TIC). Additionally, the complete cleavage pathways of CG aglycones were proposed to assist the structural identification of 29 common fragment ions (CFIs, ion occurrence number ≥ 5) and diagnostic fragment ions (DFIs, ion occurrence number < 5). As a result, 30 CGs were filtered out from the MDF results, among which 23 were identified. This newly developed strategy may provide a rapid and effective tool for identifying structure-related compounds in herbal medicines.

Identification and screening of cardiac glycosides in Streptocaulon griffithii using an integrated data mining strategy based on high resolution mass spectrometry / 中国天然药物

The present study was designed to develop a practical strategy to tackle the problem of lacking standard compounds and limited references for identifying structure-related compounds in Streptocaulon griffithii Hook. f., especially those in trace concentrations, with a focus on antitumor activity. The cardiac glycosides (CGs)-enriched part was determined using in vitro bioactive assays in three cancer cell lines and then isolated using macroporous resins. The MS and MS/MS data were acquired using a high performance liquid chromatography coupled with hybrid quadrupole-time of flight (HPLC-Q-TOF-MS) system. To acquire data of trace compound in the extract, a multiple segment program was applied to modify the HPLC-Q-TOF-MS method. A mass defect filter (MDF) approach was employed to make a primary MS data filtration. Utilizing a MATLAB program, the redundant peaks obtained by imprecise MDF template calculated with limited references were excluded by fragment ion classification, which was based on the ion occurrence number in the MDF-filtered total ion chromatograms (TIC). Additionally, the complete cleavage pathways of CG aglycones were proposed to assist the structural identification of 29 common fragment ions (CFIs, ion occurrence number ≥ 5) and diagnostic fragment ions (DFIs, ion occurrence number < 5). As a result, 30 CGs were filtered out from the MDF results, among which 23 were identified. This newly developed strategy may provide a rapid and effective tool for identifying structure-related compounds in herbal medicines.

GTS40, an active fraction of Gou Teng-San (GTS), protects PC12 from HO-induced cell injury through antioxidative properties / 中国天然药物

Oxidative stress, a predominant cause of apoptosis cascades triggered in neurodegenerative disorders, has been regarded as a critical inducement in the pathogenesis of Alzheimer's disease (AD). Gou Teng-San (GTS) is a traditional Chinese herbs preparation commonly utilized to alleviate cognitive dysfunction and psychological symptoms of patients with dementia. The present study aimed to investigate the protective effects of GTS40, an active fraction of GTS, on HO-induced oxidative damage and identify the potential active ingredients. Our results revealed that GTS40 exhibited radical scavenging activity, elevated cell viability, decreased the levels of intracellular reactive oxygen species (ROS), and stabilized mitochondrial transmembrane potential (MMP) in HO-treated PC12 cells. In addition, GTS40 blocked the apoptotic cascade by reversing the imbalance of Bcl-2/Bax and inhibiting the activity of caspase-3. Furthermore, an HPLC-QTOFMS method was developed to characterize major chemical constituents in GTS40. Our results revealed twenty-seven identified or tentatively characterized compounds through comparing their retention time (t) and MS spectra with reference standards. These results suggested that GTS40 was a promising active fraction that may be beneficial in the prevention and treatment of oxidative stress-mediated neurodegenerative disorders.

Two new ortho benzoquinones from Uncaria rhynchophylla / 中国天然药物

The present study was designed to determine the chemical constituents of the stems and hooks of Uncaria rhynchophylla. The chemical constituents were isolated and purified from CH2Cl2 fraction by chromatography. Their structures were elucidated by spectroscopic analyses. Their cytotoxicity was tested using MTT method. Two new ortho benzoquinones, 3-diethylamino-5-methoxy-1, 2-benzoquinone (1) and 3-ethylamino-5-methoxy-1, 2-benzoquinone (2), together with a known compound isorhynchophyllic acid (3) were isolated from U. rhynchophylla. These compounds were evaluated for their cytotoxicity against cancer cells A549, HepG2 and A2780. Compounds 1 and 2 were new ortho benzoquinones and showed weak antiproliferative activities on A549, HepG2 and A2780 cells. Compound 3 significantly inhibited the proliferation of A549, HepG2 and A2780 cells with IC50 values being 5.8, 12.8 and 11.8 µmol·L(-1), respectively.

Identification of chemical constituents in Yangxue Qingnao granule by UPLC-Q-TOF/MSE / 药学学报

In order to clarify the chemical constituents in Yangxue Qingnao granule, we established a rapid ultra-performance liquid chromatography/orthogonal acceleration time-of-flight mass spectrometry (UPLCQ- TOF/MSE) method. According to the high resolution MS spectra data, fragmentation ion information and retention time, 142 peaks were identified or tentatively presumed by comparison with reference standards data and literature reports. The herbal sources of these peaks were assigned. The results implied that phenolic acids, alkaloids, anthraquinones, phthalides, monoterpene glycosides were included in the main components of Yangxue Qingnao granule. The method is rapid for systematically elucidation of the constituents of Yangxue Qingnao granule and the results would facilitate the quality control of Yangxue Qingnao granule for safe and efficacious use.

Identification and characterization of three new flavonoids from Rhododendron dauricum / 中国天然药物

The present study was designed to determine the major chemical constituents of the leaves of Rhododendron dauricum L. Compounds were isolated and purified by various chromatographic methods, and their structures were elucidated by physicochemical properties and spectral data. The present study identified two new C-methyl flavanones, 5, 7, 3', 5'-tetrahydroxy-6, 8-di-C-methyl flavanone (1) and 5, 4'-dihydroxy-8-C-methylflavanone-7-O-β-D-glucopyranoside (2), and one new flavonoid glycoside, quercetin-3-O-β-D-(6"-O-cinnamoyl)-galactoside (3), along with seven known compounds, including syzalterin (4), poriolin (5), farrerol-7-O-β-D-glucopyranoside (6), myrciacetin (7), quercetin-3-O-β-D-(6-p-hydroxy-benzoyl)-galactoside (8), quercetin-3-O-β-D-(6-p-coumaroyl)-galactoside (9), and 5, 7, 3', 5'-tetrahydroxyl flavanone (10). Compounds 1-3 were determined to be new flavonoids; compounds 4-6 were isolated from this species for the first time; and compounds 7-10 were reported for the first time from this genus.

YGS40, an active fraction of Yi-Gan San, reduces hydrogen peroxide-induced apoptosis in PC12 cells / 中国天然药物

In our previous study, we have elucidated the chemical profile of YGS40, a fraction of Yi-Gan San (YGS), used for the treatment of Alzheimer's disease (AD). Oxidative stress-induced apoptosis is implicated in neurodegenerative disorders such as AD. The aim of the present study was to explore the protective effects of YGS40 against hydrogen peroxide (H2O2)-induced apoptosis in PC12 cells and the underlying mechanisms. PC12 cells were exposed to 100 μmol·L(-1) of H2O2 for 12 h with or without YGS40 pretreatment. Cytotoxicity was determined by MTT (3, (4, 5-dimethylthiazole-2-yl) 2, 5-diphenyl-tetrazolium bromide) and lactate dehydrogenase (LDH) release assays; apoptosis was detected by Annexin V/propidium iodide coupled staining and by determining caspase-3 activity and Bax and Bcl-2 protein levels. Mitochondrial membrane potential (MMP) was assessed by the retention of rhodamine123; and the activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured using commercially available enzymatic kits. Pretreatment with YGS40 significantly prevented H2O2-induced cytotoxicity and protected the cells against H2O2-triggered apoptosis characterized by externalization of membrane phosphatidylserine and caspase-3 activation and the increased ratio of Bax/Bcl-2 in PC12 cells. Further studies showed that YGS40 suppressed H2O2-induced MMP loss, increased SOD activity, and decreased MDA level. These findings suggest that YGS40 may be beneficial for the prevention and treatment of oxidative stress-mediated disorders.

Triterpenoid saponins from Patrinia scabra / 中国天然药物

AIM@#To study the chemical constituents and bioactivity of the roots of Patrinia scabra Bunge.@*METHODS@#The chemical constituents were isolated using various chromatographic methods, and the structures were elucidated on the basis of spectral analysis and chemical methods. In addition, cytotoxic activities toward HepG2 cells were tested by the MTT method.@*RESULTS@#A new triterpenoid saponin, 3-O-(4'-isovaleryl)-O-β-D-xylose-12,30-dihydroxy-oleanane-28,13-lactone-22-O- β-D-glucoside (1), along with two known triterpenoid saponins, acanthopanax saponin CP3 (2) and foetoside C (3), were isolated.@*CONCLUSION@#The aglycone of compound 1 was a new skeleton derivative of oleanolic acid. Compound 2 showed strong cytotoxicity to HePG2 cells (IC50 1.49 μmol·L(-1)).

Chemical profile of the active fraction of Yi-Gan San by HPLC-DAD-Q-TOF-MS and its neuroprotective effect against glutamate-induced cytotoxicity / 中国天然药物

Yi-Gan San (YGS), a traditional Chinese medicine for dementia-related symptoms, was previously fractionated. One active fraction, YGS40 exhibited a neuroprotective effect against glutamate-induced cytotoxicity. In the present study, high-performance liquid chromatography, coupled with diode-array detection and quadrupole time-of-flight mass spectrometry, was applied for the identification of its chemical constituents and for quantification studies. The chemical profile of YGS40 consisted of sixty-four identified or tentatively characterized compounds. The levels of the major marker compounds increased significantly in the mixed decoction compared with those in the single plant decoction. The results suggest the high precision of the analyses of most of the constituents in YGS40 and establish the quantitative variations of the major marker compounds between the single and mixed decoction processes.

Synthesis and cytotoxic activity of 3, 4, 11-trihydroxyl modified derivatives of bergenin / 中国天然药物

To synthesize a series of 3-, 4-, and/or 11-trihydroxy modified bergenin derivatives and evaluated their cytotoxic activity in vitro. The phenolic hydroxyl groups of bergenin were protected by benzyl groups with benzyl bromide. Treatment of dibenzyl bergenin with the corresponding acid in the presence of EDC·HCl and DMAP in CH2Cl2, followed by hydrogenation over Pd/C catalysts, afforded derivatives of bergenin esters. All of the target compounds were identified by IR, MS, and (1)H NMR. Twenty-six novel and three known derivatives of bergenin esters were synthesized. Their cytotoxicity values were evaluated by the MTT assay on the inhibition of DU-145 and BGC-823 cells in vitro. Several triply-substituted (3a, 4a, 5a, 6a, 7a) and doubly-substituted (8b, 9b) bergenin derivatives exhibited higher cytotoxic activity than bergenin. The result showed that the size of substituents and the lipophilicity of the bergenin esters displayed an important role on their cytotoxic activity.

Recent advances in chemistry and biology of gamboge / 中国中药杂志

Gamboge, the resin of Garcinia hanburyi has had a long history of use as the traditional dye as well as a complementary and alternative medicine. The antitumor activities of gamboge have been well demonstrated by inhibiting the growth and progression of cancer cells both in vitro and in vivo. In order to further clarify the mode of action of gamboge, there are three key questions needed to be answered, including what's in gamboge? How do the chemical components from gamboge work on cancer cells? How do biological systems work on the chemical components from gamboge after administration? In this review, we summarize the explorations of the answers toward these questions according to the recent progress in both of chemistry and biology research of gamboge. In addition, the implication in the future research and discovery of the caged G. xanthones as anticancer agents is also discussed.

Synthesis and in vitro cytotoxicity evaluation of baicalein amino acid derivatives / 中国天然药物

AIM@#To synthesize the baicalein amino acid derivatives and evaluate their cytotoxicity activities in vitro.@*METHODS@#Amino acids were subjected to methylation and aminoacylation reaction, then reacted with formaldehyde and baicalein to synthesize baicalein-8 benzyl amino acid derivatives. Through carboxyl group protection and aminoacylation of amino acid and benzyl protection of baicalein, derivatives of baicalein-6-O-amino acid esters were obtained. All of the target compounds were identified by IR, MS and (1)H NMR.@*RESULTS@#Thirteen novel derivatives were synthesized and characterized. Their cytotoxic activities were assessed by the MTT method on the inhibition of HepG2 cells in vitro.@*CONCLUSION@#Compounds 4c, 4d, 7a and 7b showed a significant increase in cytotoxicity compared with baicalein.