Comparison of extraction processes, characterization and intestinal protection activity of Bletilla striata polysaccharides.

We optimized the extraction process of Bletilla striata polysaccharides using orthogonal design, Box-Behnken design (BBD), and genetic algorithm-back propagation (GA-BP), then compared and evaluated them to confirm that the combination of BBD and GA-BP neural networks was capable of increasing polysaccharide yields and antioxidant activity. The optimal extraction parameters were as follows: liquid-to-solid ratio of 15 mL/g, extraction power of 450 W, and extraction time of 34 min. Under these conditions, the polysaccharide yield and antioxidant activity were 8.29 ± 0.50 % and 26.20 ± 0.28 (mM FE/mg). Subsequently, the polysaccharide was purified to obtain purified Bletilla striata polysaccharides 1 (pBSP1) with a Mw of 255.172 kDa. Scanning electron microscope (SEM), ultraviolet-visible detector (UV), fourier transform infrared spectrometer (FTIR), high performance liquid chromatography (HPLC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and periodate oxidation were used to analyze the structure of pBSP1. The results showed pBSP1 had a smooth surface and a rough interior, with a composition of α-D conformation glucose (18.23 %) and ß-D conformation mannose (53.77 %), and an amorphous crystal structure. According to the results of thermogravimetric and rheological tests, pBSP1 exhibits good thermal stability and viscoelastic behavior. Furthermore, pBSP1 protected lipopolysaccharide (LPS)-induced GES - 1 and Caco2 cells, the results showed pBSP1(400 µg/mL) lowered TEER synthesis in Caco2 cells as well as apoptosis and reactive oxygen species (ROS) production in both cells, indicating that pBSP1 may have an intestine protective effect.

Pharmacognostic standardization and machine learning-based investigations on Akebia quinata and Akebia trifoliata.

Currently, Akebiae Caulis is being used in clinical practice, but there are few reseaches on its different varieties. To ensure the accuracy and effectiveness of clinical practice, this study distinguished the Akebia quinata (Thunb.) Decne. and Akebia trifoliata (Thunb.) Koidz, using organoleptic evaluation, microscopic observation, fluorescence reaction, physicochemical properties, thin-layer chromatography, IR spectroscopy, HPLC, four machine learning models, and in vitro antioxidant methods. Analysis of the powders of these two varieties using optical microscopy revealed the presence of starch granules, cork cells, crystal fibers, scalariform vessels, and wood fibers. Scanning electron microscopy revealed the presence of scalariform vessels, pitted vessels, wood fibers, and calcium oxalate crystals. Several tissues, including the cork layer, fiber population, cortex, phloem, pith, xylem, and ray, were found in the transverse section. In addition, thin-layer chromatography was used to identify two components: oleanolic acid and calceolarioside B; 11 common peaks were identified in 15 batches of SAQ and 5 batches of SAT by using HPLC. Support vector machine, BP neural networks, and GA-bp neural networks were able to predict 100% accurately of the different origins of stem of Akebia quinate (Thunb.) Decne (SAQ) and Akebia trifoliata (Thunb.) Koidz (SAT). Extreme learning machine achieved a correct rate of 87.5%. Meanwhile, Fourier-transform infrared spectroscopy fingerprint identified nine characteristic absorption peaks of the secondary metabolites of SAQ and SAT. 2,2-Diphenyl-1-1-picrylhydrazyl experiment revealed that the IC50 values of SAQ and SAT extracts were 155.49 and 128.75 µg/ml, respectively. For the 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) assay, the IC50 value of SAT extract was found to be 269.24 µg/ml, which was lower than that of SAQ extract (IC50 = 358.99 µg/ml). This study successfully used different methods to differentiate between A. quinata (Thunb.) Decne. and A. trifoliata (Thunb.) Koidz., to help decide on which type to use for clinical application.

Artificial neural network model- and response surface methodology-based optimization of Atractylodis Macrocephalae Rhizoma polysaccharide extraction, kinetic modelling and structural characterization.

Atractylodis Macrocephalae Rhizoma (AMR) is the dried rhizome of Atractylodes macrocephala Koidz, which is widely used in the development of health products. AMR contains a large number of polysaccharides, but at present there are fewer applications for these polysaccharides. In this study, the effects of different extraction methods on the Atractylodis Macrocephalae Rhizoma polysaccharide (AMRP) yield were investigated, and the conditions for ultrasound-assisted extraction were optimized by response surface methodology (RSM) and three neural network models (BP neural network, GA-BP neural network and ACO-GA-BP neural network). The best conditions were a liquid-to-solid ratio of 17 mL/g, ultrasonic power of 400 W, extraction temperature of 72 °C, and extraction time of 40 min, which yielded 31.31% AMRP. The kinetic equation of AMRP was determined and compared with the results predicted by three neural network models. It was finally determined that the extraction conditions, kinetic processes and kinetic equation predicted by the GA-ACO-BP neural network were optimal. In addition, AMRP was characterized using SEM, FTIR, HPLC, UV, XRD, and NMR, and the structural study revealed that AMRP has a rough exterior and a porous interior; moreover, it contains high levels of glucose (5.07%), arabinose (0.80%), and galactose (0.74%). AMRP has three crystal structures, consisting of two ß-type monosaccharides and one α-type monosaccharide. Additionally, the effectiveness of AMRP as an antioxidant was demonstrated in an in vitro experiment.

Network Pharmacology, Molecular Docking, and Molecular Dynamic-Based Investigation on the Mechanism of Compound Chrysanthemum in the Treatment of Asthenopia.

As a clinical empirical prescription for ophthalmology, compound chrysanthemum has been used gradually and has a good effect on eye fatigue. However, the detailed mechanisms of antiasthenopia have not been studied. In order to clarify the mechanisms of the compound chrysanthemum in the treatment of asthenopia, network pharmacology was combined with experimental study in this paper. A total of 593 genes and 39 active chemicals were identified, and both were considered to be essential to the advancement of asthenopia research. The results of the molecular docking analysis demonstrated a certain affinity between PRKACA, PRKCA, PRKCB, and their related compounds; molecular dynamic simulations assessed the stability of these receptors and ligands. The effects of compound chrysanthemum extract on ciliary muscle were studied in vitro and in vivo. By using the MTT assay, compound chrysanthemum extracts (50, 100, 200, 400, and 800 g·mL-1) showed no effect on the proliferation of rCSMCs for 24 and 48 hours. It raised nitric oxide and decreased Ca2+ in ciliary muscle cells isolated from the eyeballs of rats. Besides, compound chrysanthemum extract had a direct relaxing effect on the isolated gastric smooth muscle of rats by reducing the contractile tension. Furthermore, in vivo experiment results showed that, compared to the incandescent lamp-irradiated rats (model group), SD rats treated with compound chrysanthemum extracts (660 mg·kg-1 and 1320 mg·kg-1, orally) displayed considerably retracted pupils and increased NO content. It is also found that compound chrysanthemum extract can downregulate the mRNA expression of PKA and PKC in the calcium signaling pathway. Overall, our results suggested that compound chrysanthemum extract may lessen visual fatigue through multiple components, multiple targets, and multiple pathways.

A pharmacokinetics-pharmacodynamics study of single-dose total glucosides of paeony capsule on reducing serum total bile acid in hepatic injury rats.

CONTEXT: Total Glucosides of Paeony (TGP) capsule possesses various hepatoprotective activities. No study is available concerning TGP's concentration-effect relationship on hepatoprotection. OBJECTIVE: To establish a pharmacokinetics-pharmacodynamics (PK-PD) modelling on TGP capsule's hepatoprotection after a single oral administration in hepatic injury rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into five groups (n = 6): control, model (hepatic injury), treated-H (2.82 g/kg), treated-M (1.41 g/kg), and treated-L (0.705 g/kg) groups. All treated groups rats were intragastrically administered a single dose. An LC-MS/MS method was applied to determine paeoniflorin (Pae) and albiflorin (Alb) in rat serum. The effects of single-dose TGP on serum alanine transaminase (ALT), aspartate transaminase (AST) and total bile acid (TBA) were evaluated in hepatic injury rats. RESULTS: Single dose (2.82, 1.41, or 0.705 g/kg) TGP capsule could real-time down-regulate serum TBA but not ALT and AST in hepatic injury rats within 20 h. An inhibitory effect Sigmoid Emax of PK-PD modelling was established using Pae and Alb as PK markers and serum TBA as effect index. Pharmacodynamic parameters were calculated. For treated-H, treated-M and treated-L group, respectively, E0 were 158.1, 226.9 and 245.4 µmol/L for Pae, 146.1, 92.9 and 138.4 µmol/L for Alb, Emax were 53.0, 66.0, and 97.1 µmol/L for Pae, 117.4, 249.7 and 60.0 µmol/L for Alb, and EC50 were 9.3, 5.2 and 2.7 µg/mL for Pae, 2.3, 0.8, and 0.8 µg/mL for Alb. DISCUSSION AND CONCLUSIONS: Serum TBA is a sensitive effect index for TGP's single dose PK-PD modelling, and it is potential for further multi-dose studies of TGP' effect on hepatic injury. The study provides valuable information for TGP's mechanistic research and rational clinical application.

Structures and physicochemical properties of vortioxetine salts.

In the present work, novel salts of the multimodal antidepressant drug vortioxetine (VT) were crystallized with pharmaceutically acceptable acids, aiming to improve the solubility of VT. The acids for VT were selected based on ΔpKa being greater than 2 or 3. Salts of hydrobromic acid (HBr), hydrochloric acid (HCl), p-hydroxybenzoic acid (PHBA), saccharin (SAC) and L-aspartic acid (ASP) were reported. All salts were characterized by single-crystal X-ray diffraction, FT-IR, powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The acidic proton is transferred to the secondary N atom on the piperazine ring of VT, forming the charge-assisted hydrogen bond N+-H...X- (X = Cl, Br, O). Solubility and intrinsic dissolution rate (IDR) experiments were carried out in distilled water (pH = 7.0) to compare the solubilities of the salts with that of VT. The VT-ASP-H2O (1:1:2) salt showed 414 times higher solubility and 1722 times faster IDR compared with VT. VT-ASP-H2O (1:1:2) is a high solubility salt that is stable in a slurry experiment at 298 K in 95% ethanol. The experimental data for the VT-ASP-H2O (1:1:2) salt identify it as a promising drug candidate.

[Crystal structure and crystal form stability of trelagliptin succinate].

In order to investigate trelagliptin succinate's stability in solution, recrystallization and suspension methods in polar solvent (mainly in water and 95% alcohol) were used to study the crystal form transformation of trelagliptin succinate. Single crystal X-ray diffraction, powder X-ray diffraction and thermalgravimetric analysis, and differential scanning calorimetry were used to characterize the structure of the solid state form before and after transformation. The results showed that trelagliptin succinate can easily convert to trelagliptin hemi-succinate mediated by solvent, especially by polar solvent, namely trelagliptin hemi-succinate is more stable than trelagliptin succinate in solution.

Crystal structures of vortioxetine and its methanol monosolvate.

Vortioxetine, C18H22N2S, (1), systematic name 1-{2-[(2,4-di-methyl-phen-yl)sulfan-yl]phen-yl}piperazine, a new drug used to treat patients with major depressive disorder, has been crystallized as the free base and its methanol monosolvate, C18H22N2S·CH3OH, (2). In both structures, the vortioxetine mol-ecules have similar conformations: in (1), the dihedral angle between the aromatic rings is 80.04 (16)° and in (2) it is 84.94 (13)°. The C-S-C bond angle in (1) is 102.76 (14)° and the corresponding angle in (2) is 103.41 (11)°. The piperazine ring adopts a chair conformation with the exocyclic N-C bond in a pseudo-equatorial orientation in both structures. No directional inter-actions beyond normal van der Waals contacts could be identified in the crystal of (1), whereas in (2), the vortioxetine and methanol mol-ecules are linked by N-H⋯O and O-H⋯N hydrogen bonds, generating [001] chains.

Quetiapine N-oxide-fumaric acid (2/1).

THE TITLE COMPOUND (SYSTEMATIC NAME: 2-{2-[4-(dibenzo[b,f][1,4]thia-zepin-11-yl)piperazin-1-yl 1-oxide]eth-oxy}ethanol-fumaric acid (2/1)), C(21)H(25)N(3)O(3)S·0.5C(4)H(4)O(4), is one of the oxidation products of quetiapine hemifumaric acid. In the tricyclic fragment, the central thia-zepine ring displays a boat conformation and the benzene rings are inclined to each other at a dihedral angle of 72.0 (2)°. The piperazine ring adopts a chair conformation with its eth-oxy-ethanol side chain oriented equatorially. In addition to the main mol-ecule, the asymmetric unit contains one-half mol-ecule of fumaric acid, the complete mol-ecule being generated by inversion symmetry. In the crystal, O-H⋯O hydrogen bonds link the components into corrugated layers parallel to bc plane.

Moxifloxacinium chloride monohydrate.

The title compound {systematic name: 7-[(1S,6S)-8-aza-2-azonia-bicyclo-[4.3.0]non-8-yl]-1-cyclo-propyl-6-fluoro-8-meth-oxy-4-oxo-1,4-dihydro-quinoline-3-carb-oxy-lic acid chloride monohydrate}, C(21)H(25)FN(3)O(4) (+)·Cl(-)·H(2)O, crystallizes with two moxi-floxa-cinium cations, two chloride ions and two uncoordinated water mol-ecules in the unit cell. The crystal structure has a pseudo-inversion center except for the chloride ions. In both moxi-floxa-cinium cations, the quinoline rings are approximately planar, the maximum atomic deviations being 0.107 (3) and 0.118 (3) Å. The piperidine rings adopt a chair conformation while the pyrrolidine rings display a half-chair conformation. In the crystal, the carboxyl groups, the protonated piperidyl groups, the uncoordinated water mol-ecule and chloride anions participate in O-H⋯O, O-H⋯Cl and N-H⋯Cl hydrogen bonding; weak inter-molecular C-H⋯O and C-H⋯Cl hydrogen bonding is also present in the crystal structure.

[Analysis of content changes of volatile oil and beta-elemene in oil in Sarcandrae].

OBJECTIVE: To reveal the factors that affect the contents of volatile oil and beta-elemene in oil in Sarcandrae and to provide scientific basis for Sarcandrae's reasonable exploitation and quality assessment. METHOD: A GC method was established and the contents of volatile oil and beta-elemene were determined in Sarcandrae from different length of time to grow, different medicament portions, different collection periods and different length of time to dry. RESULT: The length of time to grow had no significant effect and the collection periods had effect on the volatile oil yield and content of beta-elemene. The volatile oil yield and content of beta-elemene were the highest in Sarcandrae harvested in December. The yield of volatile oil in different medicament portions descended in an order of roots, leaves and stems. The content of beta-elemene was the highest in leaves and the lowest in stems. With the increasing of the length of time to dry, the volatile oil yield and content of beta-elemene decreased calculated on an anhydrous basis. CONCLUSION: The established method is simple, accurate and repeatable. It can be used for the quality control of beta-elemene in Sarcandrae. The study provides a valuable basis for the quality assessment, the development and utilization of Sarcandrae.

Eprosartan mesylate, an angiotensin II receptor antagonist.

The title compound, eprosartan mesylate {systematic name: 2-butyl-1-(4-carb-oxy-benz-yl)-5-[(E)-2-carb-oxy-3-(thio-phen-2-yl)prop-1-en-yl]-1H-imidazol-3-ium methane-sulfonate}, C(23)H(25)N(2)O(4)S(+)·CH(3)O(3)S(-), one of the angiotensin II-receptor antagonists, is effective in regulating hypertension, induced or exacerbated by angiotensin II, and in the treatment of congestive heart failure, renal failure and glaucoma. In the eprosartan residue, which appears in this crystal in the cationic imidazolium form, the benzene ring plane is almost orthogonal to that of the imidazole ring, making a dihedral angle of 87.89 (2)°. The thio-phene ring forms dihedral angles of 66.54 (2) and 67.12 (2)° with the benzene and imidazole rings, respectively. The imidazolium NH group and the H atom of the aromatic carboxyl group participate in hydrogen bonds with the the O atoms of the anion, thus forming centrosymmetric aggregates made up of two cations and two anions each. The second carboxyl group further links the above-mentioned aggregates through a conventional centrosymmetric hydrogen-bonding motif into infinite chains along [011].

[Preparation of submicron emulsion of fresh Zhongjiefeng volatile oil].

OBJECTIVE: To prepare the submicron emulsion of fresh Zhongjiefeng volatile oil. METHOD: The Zhongjiefeng volatile oil submicron emulsion was obtained after passing the elementary emulsion through a high pressure homogenizer. The physical and chemical stability of the emulsion was evaluated with the stability parameter of centrifugation, appearance of emulsion and the pH. The formulation and processing factors were optimized by single factor reviewing and orthogonal experimental design. RESULT: By controlling various processing factors and optimizing formulation, the stable submicron emulsion of Zhongjiefeng volatile oil was prepared. Its mean particle diameter was 164-169 nm with PDI 0.084-0.107 and Zeta electric potential was -40 mV. CONCLUSION: The formulation and preparation technique of the emulsion is reasonable.