Research progress on chemical constituents and pharmacological effects of Ajania plants / 中国中药杂志

Ajania belonging to the subtribe Artemisiinae of Anthemideae(Asteraceae) is a genus of semi-shrubs closely related to Chrysanthemum. There are 24 species of Ajania in northwestern China, most of which are folk herbal medicines with strong stress tolerance. Modern medical studies have demonstrated that the chemical constituents of Ajania mainly include terpenoids, flavonoids, phenylpropanoids, alkynes, and essential oils. These compounds endow the plants with antimicrobial, anti-inflammatory, antitumor, antimalarial, antioxidant, and insecticide effects. In this study, we reviewed the research progress in the chemical constituents and pharmacological activities of Ajania, aiming to provide reference for the further research and development of Ajania.

The pulmonary pharmacokinetics and anti-inflammatory effect of anemoside B4 after intratracheal and intravenous administration / 药学学报

Anemoside B4 (B4), a main triterpenoid saponin from a traditional Chinese medicine plant, Pulsatilla chinensis, is a novel anti-inflammatory agent for protection from acute lung injury. We investigated the pulmonary availability and anti-inflammatory efficacy of B4 after intratracheal and intravenous dosing with a view to evaluating the suitability of inhalation delivery. All animal studies were performed under the guidelines approved by the Animal Care and Use Committee of Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences (Approval No: SLXD-20181113046). In vitro evaluation of the aerodynamic characteristics and droplet size distribution showed that the aerosols generated by a commercially available nebulizer were well deposited in the respiratory tract. Following intratracheal administration, B4 underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 103%. Compared to intravenous delivery, intratracheal administration dramatically increased the drug availability in lung tissue of rats by more than 1 000-fold, leading to improved and prolonged concentrations of B4 in lung tissue up to 48 h. In addition, the intratracheal administration of B4 resulted in dose-dependent and prolonged anti-inflammatory efficacy in a lipopolysaccharide (LPS)-induced lung injury model in mice. The present results demonstrate that inhalation delivery of B4 is a promising approach to treat pulmonary inflammation with once-daily dosing.

The ethyl acetate extraction of Pileostegia tomentella (ZLTE) exerts anti-cancer effects on H1299 cells via ROS-induced canonical apoptosis / 中国天然药物

Lung cancer is the leading cause of cancer death and the most common malignant tumor, the long-term survival of which has stagnated in the past several decades. Pileostegia tomentella Hand. Mazz is a traditional Chinese medicine called "Zhongliuteng" (ZLT) in the pharmacopeia, which has been proved to possess a potent anti-tumor effect on various cancers. In this study, the effects of ZLT N-butanol extraction (ZLTN) and ZLT ethyl acetate extraction (ZLTE) on the viability of non-small cell lung cancer cell (NSCLC) lines H1299 and A549 were evaluated. Here, we firstly reported that ZLTE significantly inhibited H1299 cells growth without affecting the release of lactate dehydrogenase (LDH). In addition, ZLTE induced caspase-dependent apoptosis in a concentration-dependent manner and increased the expression cleaved-PARP and decreased pro-caspase-3, pro-caspase-7, pro-caspase-8, and pro-caspase-9. Moreover, ZLTE increased the level of cellular reactive oxygen species (ROS) in H1299 cells to lead to apoptosis, which was reversed by N-acetyl-cysteine (NAC). Taken together, our results revealed that ZLTE induced caspase-dependent apoptosis via ROS generation, suggesting that ZLTE is a promising herbal medicine for the treatment of NSCLC.

Chemical Components in Pinelliae Rhizoma by UPLC-Q-TOF-MS/MS / 中国实验方剂学杂志

Objective: To identify the chemical constituents of Pinelliae Rhizoma(BX)by ultrahigh-pressure liquid chromatography coupled with electrospray time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Method: Chromatograpic separation was performed on a shim-pack xR-ODS Ⅲ column (2.1 mm×75 mm,1.6 μm) using a gradient elution program with mixtures of acetonitrile and 0.1% formic acid-water as mobile phases at a flow rate of 0.25 mL·min-1. UPLC-Q-TOF-MS/MS was developed for rapid and high-throughput screening of the preliminary chemical profile of BX in positive ion modes. Result: Ninety chemical components were found in BX,according to the accurate Charge-mass Ratio and the MS/MS data,retention time of reference standard,references or databases,the fragmentation regularities of mass spectra. Eighty were identified preliminarily,including 7 alkaloids,8 poly-alcohols,12 fatty glycerides,5 flavonoids,12 lysophosphatidylcholines (LPCs),10 alcohol amines,11 amino acids,11 amides and 4 other type. Conclusion: LPCs were first found in BX. Because BX has certain toxicity,it is found that BX contains LPCs by analyzing the chemical constituents of BX,which can cause inflammatory reaction and neuronal myelin sheath loss and degeneration. Therefore,the analysis of the chemical composition of BX can explain the causes of the toxicity and provide a foundation for the basic research and quality control of the potency of BX.

Application of metabolomics and related technologies in research and development field of traditional Chinese medicine / 中国中药杂志

Internal environment of metabolism of traditional Chinese medicine (TCM) is a dynamic process, which is in line with the "holistic-dynamic-comprehensive-analytic" characteristics of metabonomics, therefore metabonomics have a unique advantage to reveal the metabolic pattern of TCM. The application of metabonomics in TCM has great practical significance in understanding the pharmacodynamic/toxic effect material basis, mechanisms and guiding for determination of dosage and treatment course; At the same time, the scientific compatibility of TCM prescription, the germplasm resources of TCM and the preclinical safety/toxicity can be widely researched. At present, metabolomics has become a leading technology in many industries and fields including the research and development of TCM. The core of metabolomics is analytical technology, because comprehensive metabolite profiles or accurate identification of known metabolites can be obtained from complex biological samples only by appropriate analytical techniques. At the same time, a series of bioinformatics/chemical informatics/stoichiometry methods are needed to process the data, so as to obtain the potential law and information in the mass data. In this paper, the concept of metabolomics, relevant analytical techniques, data processing methods and applications were explained and analyzed clearly. In addition, the core problems and countermeasures of metabolomics were summarized, and the future development of metabolomics was prospected as well.

In vivo metabolism of three coumarins from Chimonanthi Radix based on UHPLC-QTOF-MS/MS / 中国中药杂志

Scopolin (SC-1), scopoletin (SC-2) and isofraxidin (IS-1) are the main active constituents in Chimonanthi Radix. However, the in vivo metabolism of SC-1, SC-2 and IS-1 have not been comprehensively clarified. In this study, the in vivo metabolic profiles of these three coumarins in the rat plasma, urine and feces were analyzed. Ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS/MS) method was applied to characterize the prototypes and metabolites of SC-1, SC-2 and IS-1 in rat feces, urine, and plasma after intravenous administration. A total of 11 metabolites of the three parent compounds were tentatively identified. The main metabolic pathways were analyzed by identification of metabolites, and it was found that these three coumarins underwent multiple in vivo metabolic reactions including glucuronidation, sulfonation, isomerism and reduction. In this study, the analysis of metabolites of three coumarins basically demonstrated their in vivo metabolic process, providing basis for the further pharmacokinetics and pharmacological evaluations of SC-1, SC-2 and IS-1.

Primary hypothalamic lymphoma with extensive ventricular enhancement and hydrocephalus

@#Primary central nervous system lymphoma (PCNSL) is an aggressive malignancy arising exclusively in the central nervous system (CNS). PCNSL represents 1-5% of intracranial neoplasms and approximately 1% of all non-Hodgkin lymphomas.1,2 The clinical manifestation varies, depending on the location and size of the tumor. Biopsy is usually required in the diagnosis of PCNSL, and chemotherapy and/or radiotherapy were the most commonly used therapy.3 Here we report a rare case of primary hypothalamic lymphoma with extensive ventricular enhancement and hydrocephalus

Ramsay Hunt syndrome presenting with abducens nerve palsy followed by V, VII, VIII, IX, and X nerve palsies

@#Ramsay Hunt syndrome, associated with varicella zoster virus infection is characterized by herpes zoster oticus, facial nerve palsy, and cochleovestibular symptoms. Ramsay Hunt syndrome associated cranial polyneuropathy occasionally occurs with involvement beyond VII and VIII. We represent a patient of Ramsay Hunt syndrome who presented with only VI involvement at the first visit followed by cranial polyneuropathy. Varicella zoster virus infection was confirmed by the detection of varicella zoster virus-DNA in cerebrospinal fluid.

Three new triterpenoids isolated from the aerial parts of Ilex cornuta and protective effects against HO-induced myocardial cell injury / 中国天然药物

In the present study, three new triterpenoids, 23-hydroxyurs-12, 18-dien-28-oic acid 3β-O-α-L-arabinopyranoside (1), 23-hydroxyurs-12, 18-dien-28-oic acid 3β-O-β-D-glucuronopyranoside-6-O-methyl ester (2), and urs-12, 18-dien-28-oic acid 3β-O-β-D-glucuronopyranoside-6-O-methyl ester (3), and a known triterpenoid, 3β-hydroxy-urs-2, 18-dien-28-oic acid (4, randialic acid B), were isolated from the aerial parts of Ilex cornuta. Their structures were identified by the spectroscopic analyses (IR, ESI-MS, HR-ESI-MS, and 1D and 2D NMR) and chemical reactions. Compound 4 showed significant cell-protective effects against HO-induced H9c2 cardiomyocyte injury. Compounds 1-4 did not show any significant DPPH radical scavenging activity.

Antioxidant and cardioprotective effects of Ilex cornuta on myocardial ischemia injury / 中国天然药物

Previous studies have indicated that the Ilex genus exhibits antioxidant, neuroprotective, hepatoprotective, and anti-inflammatory activities. However, the pharmacologic action and mechanisms of Ilex cornuta against cardiac diseases have not yet been explored. The present study was designed to investigate the antioxidant and cardioprotective effects of Ilex cornuta root with in vitro and in vivo models. The anti-oxidative effects of the extract of Ilex cornuta root (ICR) were measured by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging and MTT assays as well as immunoassay. Furthermore, a rat model of myocardial ischemia was established to investigate the cardioprotective effect of ICR in vivo. Eight compounds were isolated and identified from ICR and exhibited DPPH free-radical scavenging activities. They also could increase cell viability and inhibit morphological changes induced by HO or NaSO in H9c2 cardiomyocytes, followed by increasing the SOD activities and decreasing the MDA and ROS levels. In addition, it could suppress the apoptosis of cardiomyocytes. In the rat model of myocardial ischemia, ICR decreased myocardial infarct size and suppressed the activities of LDH and CK. Furthermore, ICR attenuated histopathological alterations of heart tissues and the MDA levels, while increasing SOD activities in serum. In conclusion, these results suggest that ICR has cardioprotective activity and could be developed as a new food supplement for the prevention of ischemic heart disease.

Study on differences of Ainsliaea fragrans from different sources based on UFLC-Q-TOF-MS/MS and PCA analysis / 中国中药杂志

A rapid and accurate method of UFLC-Q-TOF-MS/MS combined with multivariate statistical analysis was established for the identification of Ainsliaea fragrans from different origins in this study. The A. fragrans from different producing areas of Jiangxi, Yunnan, Henan and Jiangsu were determined by UFLC-Q-TOF-MS/MS in the negative ion mode. And the data of the study were analyzed by the Markerview and other software for the PCA and OPLS-DA cluster analysis as well as t test. The results of the principal component analysis(PCA)showed that the main components from different origins were well distinguished. And the results of multivariate statistical showed the differences and similarities between different producing areas. Besides, 40 different compounds were identified in the negative ion mode. This method for identifying A. fragrans from different producing areas has the advantages of rapid accuracy and simplicity, which laid the foundation for the evaluation of the quality of the A. fragrans.

An unusual presentation of infective endocarditis: Transient encephalopathy with reversible lesions in corpus callosum and white matter

Clinical mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinicradiologicalsyndrome, which has been reported to be associated with many conditions and the mostcommon pathogens are virus. However, bacteria are rare pathogens for MERS. We report a 20-year-oldman diagnosed with definite infective endocarditis, who presented with transient encephalopathy withreversible lesions in the entire corpus callosum and bilateral white matter on magnetic resonance imaging(MRI). The blood culture indicated a Staphylococcus aureus infection. His neurological manifestationimproved and imaging abnormalities faded after receiving a combination of intravenous immunoglobulin,methylprednisolone, and antibiotics. Clinicians should be aware of transient encephalopathy withreversible callosal lesions as a potential unusual presentation of infective endocarditis.

Lignan glycosides and sucrose esters from roots of Securidaca inappendiculata / 中国中药杂志

Nine compounds, including five lignan glycosides (1-5), three sucrose esters (6-8), and one organic acid ester (9), were isolated from the ethanol extract of the roots of Securidaca inappendiculata by various chromatographic methods including silica gel, MPLC and preparative HPLC. Their structures were elucidated as acernikol-4″-O-β-D-glucopyranoside (1), (7R, 8S)-dihydrodehydrodiconiferyl alcohol 9-O-β-D-glucopyranoside (2), (7R, 8S)-dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranoside (3), (7R, 8S)-dihydrodehydrodiconiferyl alcohol 9'-O-β-D-glucopyranoside (4), (7R, 8S)-5-methoxydihydrodehy-drodiconiferyl alcohol 4-O-β-D-glucopyranoside (5), 3, 6'-O-diferuloylsucrose (6), 3-O-feruloyl-6'-O-sinapoylsucrose (7), sibricose A5 (8), and mehyl ferulate (9) on the basis of 1H-, 13C-NMR and MS experiments. Compounds 1-5, 8, and 9 were isolated from the Securidaca genus for the first time. Compounds 2, 3, and 7 exhibited weak cytotoxic activities against Hela and MCF-7 cell lines.

Pharmacokinetics and tissue distribution of α-hederin sodium salt in rats / 中国中药杂志

To study the pharmacokinetics and tissue distribution characteristics of α-hederin sodium salt in rats. 100 mg•kg⁻¹ α-hederin sodium salt was given to the rats by intragastric administration, and LC-MS/MS method was used to determine its concentration at different time in plasma and tissues. Plasma and tissue samples were treated with methanol protein deposition method. Main pharmacokinetic parameters were as follows： tmax (0.97±1.23) h, Cmax (222.53±57.28) μg•L⁻¹, AUC0-t (1 262±788.9) h•μg•L⁻¹, T1/2 (17.94±9.50) h. α-hederin can be detected in heart, liver, spleen, lung, kidney, brain, muscle and adipose. The results showed that α-hederin sodium salt was absorbed fast and eliminated slowly in rats after oral administration. It was widely distributed in body tissues and livers kept the highest concentrations among various tissues at different time, so it can be speculated that α-hederin may have certain targeting property on livers.

Identification and characterization of two new xanthones from Cudrania fruticosa / 中国天然药物

The present study was designed to investigate the chemical constituents of the roots of Cudrania fruticosa Wight. Compounds were isolated by various column chromatographic methods including silica gel, polyamide, sephadex LH-20, and semi-preparative HPLC. Their structures were elucidated by a combination of 1D and 2D NMR techniques, mass spectrometry, and chemical methods. Two new xanthones, Cudraxanthone T and U (1-2), along with four known compounds (3-6) were isolated from the roots of Cudrania fruticosa Wight.

A high-performance liquid chromatography with circular dichroism detector for determination of stereochemistry of 6, 9-oxygen bridge dibenzocyclooctadiene lignans from kadsura coccinea / 中国天然药物

The stereochemistry of two 6, 9-oxygen bridge dibenzocyclooctadiene lignans from Kadsura coccinea, are difficult to separate and very unstable. The present study was designed to develop a high-performance liquid chromatography using circular dichroism detection for the analysis of the stereochemistry. A new 6, 9-oxygen bridge dibenzocyclooctadiene lignans named Kadsulignan Q was firstly found with an S-biphenyl configuration. The other compound was identified as Kadsulignan L with an R- biphenyl configuration. In order to obtain kinetic data on their reversible interconversion, the stability was measured at different deuterated solvents such as deuterated methanol, deuterated chloroform and deuterated dimethylsulfoxide. The lignans were more unstable and converted more easily in deuterated methanol than in deuterated chloroform and deuterated dimethylsulfoxide.

Effects of ultrahigh pressure extraction on yield and antioxidant activity of chlorogenic acid and cynaroside extracted from flower buds of Lonicera japonica / 中国天然药物

The present study was designed to establish and optimize a new method for extracting chlorogenic acid and cynaroside from Lonicera japonica Thunb. through orthogonal experimental designl. A new ultrahigh pressure extraction (UPE) technology was applied to extract chlorogenic acid and cynaroside from L. japonica. The influential factors, including solvent type, ethanol concentration, extraction pressure, time, and temperature, and the solid/liquid ratio, have been studied to optimize the extraction process. The optimal conditions for the UPE were developed by quantitative analysis of the extraction products by HPLC-DAD in comparison with standard samples. In addition, the microstructures of the medicinal materials before and after extraction were studied by scanning electron microscopy (SEM). Furthermore, the extraction efficiency of different extraction methods and the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities of the extracts were investigated. The optimal conditions for extracting chlorogenic acid and cynaroside were as follows: ethanol concentration, 60%; extraction pressure, 400 MPa; extraction time, 2 min; extraction temperature, 30 °C; and the solid/liquid ratio, 1 : 50. Under these conditions, the yields of chlorogenic acid and cynaroside were raised to 4.863% and 0.080%, respectively. Compared with other extraction methods, such as heat reflux extraction (HRE), ultrasonic extraction (UE), and Sohxlet extraction (SE), the UPE method showed several advantages, including higher extraction yield, shorter extraction time, lower energy consumption, and higher purity of the extracts. This study could help better utilize L. japonica flower buds as a readily accessible source of natural antioxidants in food and pharmaceutical industries.

Saponins from roots of Securidaca inappendiculata with cytotoxic activities / 中国中药杂志

Seven acylated triterpene saponins were isolated from the roots of Securidaca inappendiculata by means of various chromatographic techniques such as silica gel, MPLC, preparative HPLC, and semi-preparative HPLC. Their chemical structures were identified as securioside A(1), securioside B(2), 3-O-β-D-glucopyranosyl presenegenin 28-O-β-D-xylopyranosyl-(1-->4)-α-L-rhamnopyranosyl-(1-->2)-[β-D-glucopyranosyl-(1-->3)]-4-O-[(E)-3,4-dimethoxycinnamoyl]-β-D-fucopyranosyl ester(3), 3-O-β-D-glucopyranosyl presenegenin 28-O-β-D-xylopyranosyl-(1-->4)-α-L-rhamnopyranosyl-(1-->2)-[β-D-glucopyranosyl-(1-->3) ] -4-O-[(E/Z)-3, 4-dimethoxycinnamoyl]-β-D-fucopyranosyl ester(3/4), 3-O-β-D-glucopyranosyl presenegenin 28-O-α-L-arabinopyranosyl-(1-->3)-β-D-xylopyranosyl-(1-->4)-α-L-rhamnopyranosyl-(1-->2)-4-O-[(E)-3,4-dimethoxycinnamoyl]-β-D-fucopyranosyl ester(5), polygalasa- ponin XLV(6), and polygalasaponin XLVI (7) on the basis of spectroscopic data analysis and physicochemical properties. Among them, compounds 5-7 were isolated from the plants in genus Securidaca for the first time and compounds 3, 3/4 were isolated from the species for the first time. The cytotoxicity assay showed that compounds 2, 3/4, 5 have moderate cytotoxic activities against Lewis lung carcinoma LLC cells with IC50 values of 41.10, 38.17, and 48.92 µmol · L(-1), respectively; compound 2 exhibited moderate cytotoxic activities against human breast cancer MCF-7 cells with an IC50 value of 47.93 µmol · L(-1).

Dissolution difference of ginsenosides from ultrafine granular powder and common powder traditional pieces of Panacis Quinquefolii Radix in vitro / 中国中药杂志

The dissolution of Panacis Quinquefolii Radix ultrafine granular powder and common powder, traditional pieces in water and simulated gastric juice in vitro was compared, and the effect of particles size of Panacis Quinquefolii Radix on the dissolution was studied. HPLC method was used for determination of five ginsenosides including Rg1, Re, Rb1, Rc and Rd from ultrafine granular powder and common powder, traditional pieces of Panacis Quinquefolii Radix at different points in time, furthermore, the dissolution curves of Panacis Quinquefolii Radix ultrafine granular powder and common powder, traditional pieces were obtained. The dissolution characteristics of the three Panacis Quinquefolii Radix forms were also compared in this study. According to the results, the dissolution rates of ginsenosides from ultrafine granular powder exceeded 90% of the total content with 5 min, significantly higher than that of the other two forms in water in vitro. At the same time, the dissolved amount of the ultrafine granular powder was fourteen percent higher than that of the traditional pieces and eight percent higher than that of the common powder. Under the condition of simulated gastric juice in vitro, the dissolution rates of ginsenosides from ultrafine granular powder were little lower than that of the other two, but the maximum dissolved amount of the former was fourteen percent higher than that of the common powder and five percent higher than that of the extracts. Therefore the conclusion is that micronization of Panacis Quinquefolii Radix contributed to dissolution of effective components.

Intestinal absorption of pulchinenosides from Pulsatilla chinensis in rats / 中国中药杂志

HPLC-ELSD was applied to explore the absorption mechanism of pulchinenosides (B3, BD, B7, B10, B11) in rats. The experimental results showed that the absorption rate constant, Ka value (B3, BD) and Permeability coefficient, Peff value (B3, B7) displayed significant difference (P <0.05) in various intestinal segments, The Ka value and Peff value of PRS was different from each other with the highest absorption in duodenum (duodenum > jejunum > colon > ileum); The PRS displayed excessive satuation as the concentration increased over 0.05-2.5 g · L(-1). There were no obvious linear correlations between Peff values and concentrations in duodenum (0.6007 ≤ R2 ≤ 0.7727); Ka and Peff value declined when the PRS was perfused with P-glycoprotein promoter digoxin, on the other hand, inclined when perfused with P-glycoprotein inhibitor verapamil with significant difference among PRS B3, BD, B7, B11 (P <0.05). All the above results demonstrated that B3, BD, B7 were greatly influenced by absorption sites, duodenum was the main absorption site; PRS didn't entirely transported in a concentration dependent manner, and the transporter-protein involved the transportation, so the intestinal absorption of the five pulchinenosides was not entirely passive diffusion; and PRS might be the substrates of P-glycoprotein.