Huangqin decoction mitigates hepatic inflammation in high-fat diet-challenged rats by inhibiting TLR4/NF-κB/NLRP3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic hepatopathy worldwide, in which ectopic steatosis (5%) and inflammatory infiltration in the liver are the principal clinical characteristics. Huangqin decoction (HQD), a Chinese medicine formula used in the clinic for thousands of years, presents appreciable anti-inflammatory effects. Nevertheless, the role and mechanism of HQD against inflammation in NAFLD are still undefined. AIM OF THE STUDY: The objective of this study was to evaluate the curative efficacy and unravel the involved mechanism of HQD on a high-fat diet (HFD)-induced NAFLD. MATERIALS AND METHODS: First, HPLC was utilized to analyze the main chemical components of HQD. Then, NAFLD model was introduced by subjecting the rats to HFD for 16 weeks, and HQD (400 and 800 mg/kg) or polyene lecithin choline (PLC, 8 mg/kg) was given orally from week 8-16. Pharmacodynamic indicators including body weight, liver weight, liver index, as well as biochemical and histological parameters were assessed. As to mechanism exploration, the expressions of TLR4/NF-κB/NLRP3 pathway and molecular docking between major phytochemicals of HQD and key targets of TLR4/NF-κB/NLRP3 pathway were investigated. RESULTS: Seven main monomeric constituents of HQD were revealed by HPLC analysis. Of note, HQD could effectively attenuate the body weight, liver weight, and liver index, rescue disorders in serum transaminases and lipid profile, correct hepatic histological abnormalities, and reduce phagocytes infiltration into the liver and pro-inflammatory cytokines release in NAFLD rats. Mechanism investigation discovered that HQD harbored inhibitory effects on TLR4/NF-κB/NLRP3 pathway-regulated liver inflammation. Further exploration found that seven phytochemicals in HQD exhibited better binding modes with TLR4/NF-κB/NLRP3 pathway, in which baicalein, baicalin and liquiritin presented the highest affinity and docking score for protein TLR4, NF-κB, and NLRP3, respectively. CONCLUSIONS: These findings confirmed that HQD ameliorated hepatic inflammation in NAFLD rats by blocking the TLR4/NF-κB/NLRP3 pathway, with multi-components and multi-targets action pattern.

[Distribution of surface components in spray-dried powder of binary system of berberine hydrochloride and dextran based on hydrodynamic size].

The present study explored the correlation between the hydrodynamic size(i.e., hydrated particle size) and the surface component distribution of spray-dried powder based on the binary system model of berberine hydrochloride and dextran. A variety of mixture solutions containing substances of different proportions were prepared, and the hydrated particle sizes of the solutions were measured by laser light scattering technique. Then the effects of molecular weight and mixing proportion on the particle size were analyzed. After the solutions were spray-dried, the surface components of spray-dried powder were determined by X-ray photoelectron spectroscopy. The changes of hydrated particle size of the two substances in different solutions were measured with the altered solution environments, and the distribution of surface components after spray-drying was observed. The results of particle size measurement showed that different solution environments would change the hydrodynamic size of substances. Specifically, the particle size of berberine hydrochloride increased with the increase in ionic strength and solution pH, while the particle size of dextran decreased with the increase in ionic strength and increased with the increase in solution pH. The results of surface components of the spray-dried powder indicated that berberine hydrochloride was prone to accumulate on the surface of particles during spray-drying because of its large hydrodynamic size. Therefore, hydrodynamic size is considered an important factor affecting the surface component distribution of spray-dried powder. As revealed by scanning electron microscopy of the particle morphology of spray-dried powder, the particles of berberine hydrochloride spray-dried powder were irregularly elliptic, and the particles of dextran and mixture spray-dried powders were irregularly spherical with the shrunken surface. Finally, the FT4 powder rheometer and DVS instrument were used to determine the stability, adhesion, and hygroscopicity of the powder. The results showed that when berberine hydrochloride was enriched on the surface, the adhesion of the mixture increased and the fluidity became worse, but the hygroscopicity was improved to a certain extent. In addition, as found by hygroscopic kinetic curve fitting of spray-dried powder, the hygroscopic behaviors of all spray-dried powder conformed to the double exponential function.

[Effect of N-acetyl-L-cysteine on bioavailability and brain distribution of curcumin by nasal delivery].

Curcumin( Cur) is a natural active substance extracted from the roots or tubers of traditional Chinese medicinal materials. It has anti-inflammatory and anti-tumor activities on brain diseases. Due to the poor stability,low solubility,poor absorption and low bioavailability of curcumin,N-acetyl-L-cysteine( NAC) was used as an absorption enhancer and mixed with curcumin to improve the absorption of curcumin in the body. In this paper,curcumin was smashed by airflow pulverization,and Cur-NAC mixtures were prepared by being grinded with liquid. Then,the raw material and the product were analyzed by differential scanning calorimetry( DSC),X-ray diffraction( XRD) for structural characterization. The dissolution was determined by high performance liquid chromatography( HPLC) analysis. The characteristic peaks of the samples prepared by grinding method were similar to those of the raw materials,while the melting temperature and the accumulated dissolution degree were not significantly changed. The crystal forms of the products were not changed,and no new crystal form was formed after grinding. After the administration of intranasal powder,blood samples were collected from the orbit,while the whole brain tissues were removed from the skull and dissected into 10 anatomical regions. The concentrations of curcumin in these samples were determined by UPLC-MS/MS. The concentrations of curcumin in plasma and brain were compared at different time points. After intranasal administration of two drugs,it was found that the concentration of curcumin after sniffing up the mixtures in plasma was high,and the concentration of the drug in the olfactory bulb,hippocampus,and pons was increased significantly. Within 0. 083-0. 5 h,the olfactory bulb,piriform lobe and hippocampus remained high concentrations,the endodermis,striatum,hypothalamus and midbrain reached high concentrations within 1-3 h; and the cerebellum,pons and brain extension maintained relatively high concentrations within 3-7 h. The experiment showed that nasal administration of Cur-NAC mixtures can significantly improve the bioavailability of curcumin,and lead to significant differences in brain tissue distribution.

[Study on essential oil separation from Forsythia suspensa oil-bearing water body based on vapor permeation membrane separation technology].

To investigate the feasibility of vapor permeation membrane technology in separating essential oil from oil-water extract by taking the Forsythia suspensa as an example. The polydimethylsiloxane/polyvinylidene fluoride (PDMS/PVDF) composite flat membrane and a polyvinylidene fluoride (PVDF) flat membrane was collected as the membrane material respectively. Two kinds of membrane osmotic liquids were collected by self-made vapor permeation device. The yield of essential oil separated and enriched from two kinds of membrane materials was calculated, and the microscopic changes of membrane materials were analyzed and compared. Meanwhile, gas chromatography-mass spectrometry (GC-MS) was used to compare and analyze the differences in chemical compositions of essential oil between traditional steam distillation, PVDF membrane enriched method and PDMS/PVDF membrane enriched method. The results showed that the yield of essential oil enriched by PVDF membrane was significantly higher than that of PDMS/PVDF membrane, and the GC-MS spectrum showed that the content of main compositions was higher than that of PDMS/PVDF membrane; The GC-MS spectra showed that the components of essential oil enriched by PVDF membrane were basically the same as those obtained by traditional steam distillation. The above results showed that vapor permeation membrane separation technology shall be feasible for the separation of Forsythia essential oil-bearing water body, and PVDF membrane was more suitable for separation and enrichment of Forsythia essential oil than PDMS/PVDF membrane.

[Adsorption characteristics of proteins on membrane surface and effect of protein solution environment on permeation behavior of berberine].

In order to explore the adsorption characteristics of proteins on the membrane surface and the effect of protein solution environment on the permeation behavior of berberine, berberine and proteins were used as the research object to prepare simulated solution. Low field NMR, static adsorption experiment and membrane separation experiment were used to study the interaction between the proteins and ceramic membrane or between the proteins and berberine. The static adsorption capacity of proteins, membrane relative flux, rejection rate of proteins, transmittance rate of berberine and the adsorption rate of proteins and berberine were used as the evaluation index. Meanwhile, the membrane resistance distribution, the particle size distribution and the scanning electron microscope (SEM) were determined to investigate the adsorption characteristics of proteins on ceramic membrane and the effect on membrane separation process of berberine. The results showed that the ceramic membrane could adsorb the proteins and the adsorption model was consistent with Langmuir adsorption model. In simulating the membrane separation process, proteins were the main factor to cause membrane fouling. However, when the concentration of proteins was 1 g•L⁻¹, the proteins had no significant effect on membrane separation process of berberine.

[Pharmacokinetics of α-asarone after intranasal and intravenous administration with PLA-α-asarone nanoparticles].

PLA-α-asarone nanoparticles were prepared by using organic solvent evaporation method, and their in vivo distribution and brain targeting after intranasal administration were studied as compared with intravenous administration. The results showed that brain targeting coefficient of PLA-α-asarone nanoparticles after intranasal and intravenous administration was 1.65 and 1.16 respectively. The absolute bioavailability, brain-targeting efficiency and the percentage of nasal-brain delivery of PLA-α-asarone nanoparticles were 74.2%, 142.24 and 29.83%, respectively after intranasal administration. The results of fluorescence labeling showed that the fluorescent intensity of coumarin-6 in the brain tissue was the highest after intranasal administration of PLA-α-asarone fluorescent nanoparticles, achieving the purpose of brain-targeted drug delivery. The fluorescent intensity of coumarin-6 in liver tissue after intravenous administration of PLA-α-asarone nanoparticles was much higher than that after intranasal administration, indicating that intranasal administration of PLA-α-asarone nanoparticles could decrease drug-induced hepatotoxicity. In addition, the fluorescent intensity of coumarin-6 in lung tissue was weaker after intranasal administration, which solved the shortcomings of intranasal administration of α-asarone dry powder prepared by airflow pulverization method. In vivo studies indicated that PLA-α-asarone nanoparticles after intranasal administration had a stronger brain targeting as compared with intravenous administration.

Preparation and Physicochemical and Pharmacokinetic Characterization of Ginkgo Lactone Nanosuspensions for Antiplatelet Aggregation.

The aim of this study was to investigate the potential of nanosuspensions (NSs) in improving the dissolution and absorption of poorly water-soluble ginkgo lactones (GLs), including ginkgolide A, ginkgolide B, and ginkgolide C. Liquid GL-NSs were prepared by a combined bottom-up and top-down approach with response surface methodology design, followed by freeze-drying solidification. Physicochemical characterization of the prepared freeze-dried GL-NSs was performed by photon correlation spectroscopy, scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. In vitro dissolution and in vivo bioavailability of ginkgolide A, ginkgolide B, and ginkgolide C in freeze-dried GL-NSs were evaluated with GLs coarse powder as control. Their inhibitory effects on platelet aggregation were also comparatively analyzed. GLs existed in an amorphous state in the prepared freeze-dried GL-NSs. The particle size, polydispersity index, zeta potential, and redispersibility index of freeze-dried GL-NSs were around 286 nm, 0.26, -25.19 mV, and 112%, respectively. The particle size reduction resulted in much more rapid and complete dissolution of ginkgolides from GL-NSs than coarse powder. Comparison with GLs coarse powder, freeze-dried GL-NSs showed a significant decreased Tmax, 2-fold higher peak concentration, and 2-fold higher area under plasma concentrations curve for 3 ginkgolides and exhibited significantly higher antiplatelet aggregation effect.

[Studies on preparation by SPG membrane emulsification method and in vitro characterization of tetradrine-tashionone II(A)-PLGA composite microspheres].

Tetradrine-tashionone II(A)-PLGA composite microspheres were prepared by the SPG membrane emulsification method, and the characterization of tetradrine-tashionone II(A) -PLGA composite microspheres were studied in this experiment. The results of IR, DSC and XRD showed that teradrine and tashionone II(A) in composite microspheres were highly dispersed in the PLGA with amorphous form. The results of tetradrine-tashionone II(A) -PLGA composite microspheres in vitro release experiment showed that the cumulative release amounts of tetradrine and tashionone II(A) were 6.44% and 3.60% in 24 h, and the cumulative release amounts of tetradrine and tashionone II(A) were 89.02% and 21.24% in 17 d. The process of drug in vitro release accorded with the model of Riger-Peppas. Tetradrine-tashionone II(A) -PLGA composite microspheres had slow-release effect, and it could significantly reduce the burst release, prolong the therapeutic time, decrease the dosage of drugs and provide a new idea and method to prepare traditional Chinese medicine compound.

Discovery of new acetylcholinesterase inhibitors with small core structures through shape-based virtual screening.

Targeting acetylcholinesterase (AChE) using small molecule inhibitors is considered to be the most successful therapeutic strategy in the treatment of Alzheimer's disease (AD). Herein we present a shape-based virtual screening to identify new cores for the designing of AChE inhibitors. Ten active hits are identified and the most active hit, 5169-0032 and T5369186, showed comparable AChE inhibitory activity to tacrine. Prediction of physicochemical properties and ADME/T risk indicates their potential in druggability and safety. The two compounds provide new core and can serve as a promising fragment to design potent AChE inhibitors.

[Pharmacokinetic study on dry powder inhalation administration of α-asarone in rats].

To study the pharmacokinetic characteristics and absolute bioavailability of α-asarone through dry powder inhalation in rats, and compare with that through oral administration and intravenous injection. A HPLC method was established for the determination of α-asarone in rat plasma to detect the changes in plasma concentrations of α-asarone through dry powder inhalation (20 mg · kg(-1)), oral administration (80 mg · kg(-1)) and intravenous injection (20 mg · kg(-1)) in rats. DAS 2.0 software was used to calculate the pharmacokinetic parameters. The absolute bioavailability of α-asarone was calculated according to AUC(0-t)) of administration routes and administration doses. According to the results, α-asarone showed good linear relations (r = 0. 999 4) at concentrations between 0.282-14.1 mg · L(-1), with the limit of detection (LOD) at 0.212 mg · L(-1). Through dry powder inhalation, oral administration and intravenous injection of α-asarone, the metabolic processes of α-asarone in rats conformed to one, two and three compartment models respectively, with the elimination half-life of (95.48 ± 48.28), (64.34 ± 27.59), (66.99 ± 29.76) min. According to the bioavailability formula, the absolute bioavailability of α-asarone through dry powder inhalation and oral administration were 78.32% and 33. 60%, respectively. This study showed that significant increase in elimination half-life and absolute bioavailability of α-asarone through dry powder inhalation, which lays a theoretical foundation for preparing α-asarone dry powder inhalers.

[Study of pretreatment on microfiltration of huanglian jiedu decoction with ceramic membranes based on solution environment regulation theory].

To optimize the pretreatment of Huanglian Jiedu decoction before ceramic membranes and verify the effect of different pretreatments in multiple model system existed in Chinese herb aqueous extract. The solution environment of Huanglian Jiedu decoction was adjusted by different pretreatments. The flux of microfiltration, transmittance of the ingredients and removal rate of common polymers were as indicators to study the effect of different solution environment It was found that flocculation had higher stable permeate flux, followed by vacuuming filtration and adjusting pH to 9. The removal rate of common polymers was comparatively high. The removal rate of protein was slightly lower than the simulated solution. The transmittance of index components were higher when adjust pH and flocculation. Membrane blocking resistance was the major factor in membrane fouling. Based on the above indicators, the effect of flocculation was comparatively significant, followed by adjusting pH to 9.

[Studies on baicalin ethylcellulose microspheres for intranasal administration].

In this study, solvent evaporation method was used to preparing baicalin ethylcellulose microspheres for intranasal administration. The prepared microspheres were round with certain rough surface. The average drug loading and entrapment efficiency was (33. 31 ± 0. 045)% , (63. 34 ± 0. 11)% , respectively. As the characteristic crystalline peaks of baicalin were observed in the microspheres sample, the result of X-ray diffractometric analysis indicated that the baicalin was present in crystalline form after its entrapment in ethylcellulose matrix. By investigating the thermogram of microspheres sample, it was found that endothermic peak of baicalin was shifted from 211. 8 °C to 244. 2 °C and associated with the first broad endothermic peak of ethylcellulose. This could confirm that baicalin was loaded into ethylcellulose, nor simply physical mixture. The powder flowability test exhibited that the specific energy of microspheres was 3. 57 mJ . g-1 and the pressure drop was 2. 22 mBar when air kept the speed of 2 mm . s-1 through the powder bed with the force was 15 kPa. The consequence of the baicalin in vitro released from microspheres showed that the pure baicalin sample displayed faster (90%) release than microspheres sample (75%) in 7 h. Fitting model for release curve before 7 h, the results showed that the pure baicalin sample and the microsphere sample accorded with first order model (R2 = 0. 990 4) and Riger-Peppas model(R2 = 0. 961 2), respectively. Ex vivo rabbit nasal mucosa permeability experiment revealed that the value of cumulative release rate per unit area of the microsphere sample was 1. 56 times that of the pure baicalin sample. This provided the foundation for the in vivo pharmacokinetic study.

[The influence of spray drying process conditions on physical, chemical properties and lung inhaling performance of Panax notoginseng saponins - tanshinone II A composite particles].

This study is to report the influence of conditions in spray drying process on physical and chemical properties and lung inhaling performance of Panax notoginseng Saponins - Tanshinone II A composite particles. According to the physical and chemical properties of the two types of components within the composite particles, three solvent systems were selected including ethanol, ethanol : acetone (9 : 1, v/v) and ethanol : acetone (4 : 1, v/v), and three inlet temperature: 110 degrees C, 120 degrees C, 130 degrees C to prepare seven different composite particle samples; each sample was characterized using laser diffraction, scanning electron microscopy (SEM), dynamic vapour sorption (DVS) and atomic force microscope (AFM), and their aerodynamic behavior was evaluated by a Next Generation Impactor (NGI). The results indicate that under the conditions of using the mixed solvent system of ethanol--acetone volume ratio of 9 : 1, and the inlet temperature of 110 degrees C, the resulting composite particles showed rough surface, with more tanshinone II A distributing in the outer layer, such composite particles have the best lung inhaling performance and the fine particle fraction (FPF) close to 60%. Finally it is concluded that by adjusting the conditions in co-spray drying process, the distribution amount and existence form of tanshinone II A in the outer layer of the particles can be changed so that to enhance lung inhaling performance of the drug composite particles.

[Preparation of panax notoginseng saponins-tanshinone H(A) composite method for pulmonary delivery with spray-drying method and its characterization].

OBJECTIVE: To prepare panax notoginseng saponins-tanshinone II(A) composite particles for pulmonary delivery, in order to explore a dry powder particle preparation method ensuring synchronized arrival of multiple components of traditional Chinese medicine compounds at absorption sites. METHOD: Panax notoginseng saponins-tanshinone II(A) composite particles were prepared with spray-drying method, and characterized by scanning electron microscopy (SEM), confocal laser scanning microscope (CLSM), X-ray diffraction (XRD), infrared analysis (IR), dry laser particle size analysis, high performance liquid chromatography (HPLC) and the aerodynamic behavior was evaluated by a Next Generation Impactor (NGI). RESULT: The dry powder particles produced had narrow particle size distribution range and good aerodynamic behavior, and could realize synchronized administration of multiple components. CONCLUSION: The spray-drying method is used to combine traditional Chinese medicine components with different physical and chemical properties in the same particle, and product into traditional Chinese medicine compound particles in line with the requirements for pulmonary delivery.

[Degradation of earthworm extracts prepared by wet superfine grinding in simulated gastrointestinal environment].

This is to report the study of degradation of earthworm extracts prepared by wet superfine grinding in simulated gastrointestinal environment. Enzymatic reactions were terminated by adjusting the solution pH or using membrane bioreactor principle. Earthworm protein concentration change was detected by Bradford method, the degraded state of protein was described with SDS-PAGE technology, and the degraded state of small molecule substances was detected by HPLC. The results showed that earthworm protein degraded completely in artificial gastric juice. High molecular weight protein degraded greatly in artificial intestinal fluid, while low molecular weight protein was not significantly degraded. Small molecular substances degradation did not degrade in artificial gastric juice, while they degraded obviously in artificial intestinal fluid, there is even new small molecule substance appeared. Finally it is concluded that the substance that having therapeutic effects in vivo may be some degraded peptide, amino acid and stable small molecules existed in artificial intestinal fluid.