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Two novel pectic polysaccharides (FDP and DDP) from fresh/dried Dendrobium officinale prevent alcohol-induced liver injury by attenuating oxidant stress and inflammatory cytokine response. “Fresh” pectin exhibits more promising hepatoprotection.

Background: Borneol can enhance the blood-brain barrier (BBB) permeability of some drugs and suppress the efflux transport of P-glycoprotein (P-gp), which will contribute to the brain delivery of salvianic acid A (SAA). Objective: The study aimed to develop an approach to improve the brain targeting delivery of SAA with the aid of borneol. Methods: “Borneol” was involved in SAA via esterified prodrug SAA borneol ester (SBE) and combined administration (SAA-borneol, SAA-B). Subsequently, the blood-brain transport of SAA through brain/blood distribution and P-gp regulation via expression and function assay were investigated in rats. Results: The SBE and SAA-B-treated group received a three-fold brain concentration and longer t1/2 and retention period of active SAA than that of SAA alone (20.18/13.82 min vs. 6.48 min; 18.30/17.42 min vs. 11.46 min). In addition, blood to brain transport of active SAA in SBE was altered in comparison to that of SAA-B, ultimately resulting in a better drug targeting index (9.93 vs. 3.63). Further studies revealed that SBE-induced downregulation of P-gp expression occurred at the later stage of administration (60 min, P < 0.01), but SBE always showed a more powerful drug transport activity across BBB represented by Kp value of rhodamine 123 than SAA-B (30, 60 min, P < 0.05). Conclusion: The comparative results indicate that SBE exhibits prominent efficiency on SAA's targeting delivery through improved blood/brain metabolic properties and sustained inhibitory effect of “borneol” on P-gp efflux. Therefore, prodrug modification can be applied as a more effective approach for brain delivery of SAA.

In this study, the physico-chemical properties of tomato powder produced by an optimized freeze drying process (FDP) were evaluated. With the lycopene content as the dependent variable, the optimum FDP conditions (i.e., thermal cracking time of 62 s, ascorbic acid addition amount [0.13%], and particle size [Dv90] of 163 μm) were obtained through response surface methodology (RSM). The results showed that the content of lycopene in the prepared tomato powder was higher than that in two commercial products. Aldehydes were the main components among 25 kinds of aromatic substances detected in tomato powder. The values of a * and a */b *, the hydration properties including water holding capacity (WHC) and oil binding capacity (OBC), and the content of total acid, ascorbic acid, and soluble solids were improved compared to commercial spray dried and freeze dried samples. All the above results suggested that FDP was an adequate procedure for the production of high-quality tomato powder.

Infectious diseases associated with drug-resistant bacteria increasingly threaten public health. Effective antibacterial nanoplatforms are of special importance for treating bacterial infections. In this work, a novel magnetic Fe3O4–Au–PDA hybrid microcapsule with both photothermal (PTT) and photodynamic (PDT) anti-bacterial functions was developed. First, the Fe3O4@Au/PDA core/shell microspheres with hollow nature were obtained by a simple in situ redox–oxidize polymerization method. Then, they were etched in acid to improve the hollow interior and porous shell. Finally, the tetracarboxyzinc phthalocyanine (ZnPc) was used as the photosensitizer to be loaded into the above Fe3O4–Au–PDA hybrid microcapsule. Owing to the dual-mode photothermal Au–PDA hybrid shell and the ZnPc photosensitizer, the final Fe3O4–Au–PDA/ZnPc hybrid microcapsule serves as a wonderful photothermal/photodynamic (PTT/PDT) synergistic therapy agent. The experimental results show that the Fe3O4–Au–PDA/ZnPc microcapsule possesses excellent photothermal sterilization effect (808 nm laser irradiation) against Escherichia coli, and the experimental results further demonstrate good photodynamic behavior under Xenon lamp irradiation. The product exhibits much higher antibacterial performance by combining the PTT/PDT treatment, which demonstrates that this work provides a novel dual-mode phototheranostic nano-agent for an effective treatment of bacterial infections.

A rapid and robust preparation method of six isoflavones from ethanol aqueous extract of Iris tectorum Maxim (I. tectorum) was established by using macroporous resin column chromatography and preparative high-performance liquid chromatography (Prep-HPLC). After separation by AB-8 resins, total flavonoids content increased from 10.60% in the crude extract to 54.20% with a recovery yield of 75.12%. Subsequently, the extracts were purified by Prep-HPLC, and the purities were more than 82.2% after assessment by analytical HPLC and characterization by mass spectrometry. The established method is expected to be used for preparing available quantities of pure isoflavones from I. tectorum.

The purpose of this study was to optimize the preparation conditions of podophyllotoxin liposomes (PPT-Lips), and to investigate their effects on PC3 cells. PPT-Lips were prepared by using a thin-film dispersion method. In order to achieve maximum drug encapsulation efficiency (EE), the process and formulation variables were optimized by response surface methodology (RSM). The optimum preparation conditions were cholesterol to lecithin ratio of 3.6:40 (w/w), lipid to drug ratio of 15.8:1 (w/w), and the ultrasonic intensity of 35% (total power of 400 W). The experimental EE of PPT-Lips was 90.425%, which was consistent with the theoretically predicted value. The characterization studies showed that PPT-Lips were well-dispersible spherical particles with an average size of 106 nm and a zeta potential of –10.1 mV. A gradual and time-dependent pattern of PPT from liposomes was found in in vitro drug release with a cumulative release amount up to 70.3% in 24 h. Results of cell viability experiments on PC3 cells demonstrated that PPT-Lips exhibited more effective anticancer activity in comparison with free PPT. Therefore, PPT-Lips represent an efficient and promising drug delivery system for PPT.

An efficient separation method of scopolamine from Hindu Datura extracts was successfully developed by combining liquid–liquid extraction, macroporous resins, and crystallization. First, the extraction solution was successively performed with liquid–liquid extraction by acid water and carbon tetrachloride. Secondly, D151 resin was selected from six tested resins, and the separation parameters were optimized. Finally, scopolamine hydrobromide was obtained after crystallization at −20°C overnight. Through one run of above combined treatments, the content of scopolamine increased from 3.02% (w/w) to 99.12% (w/w). In addition, the products were assessed by high-performance liquid chromatography (HPLC).

Extractable phenols, total flavonoid, total anthocyanin, antioxidant activity and in vitro digestibility of cooked black rice (BR) following high hydrostatic pressure (HHP) treatments (200–500 MPa/15 min) during 40 days of storage at 4 °C were evaluated in this study. Results showed that extractable phenols significantly (p

Metal–organic framework (MOF)-derived nanostructures exhibit wonderful characteristics and possess broad application potential by modulating the complex composition and inner nanostructure. Although various MOF-based nanocomposites have been successfully developed, a facile method that can easily modulate the structure-dependent chemical components of the MOF-derived hybrids remains a challenge. By coating zeolitic imidazolate framework-8 (ZIF-8) with Au/polydopamine (Au/PDA) via in situ redox-oxidation polymerization of HAuCl4 and dopamine, it was found that the ZIF-8 templates were simultaneously etched off to give Au/PDA hybrid microcapsules with a cubic shape. This one-step sacrificial templating process followed a competing chelation between gold ions and Zn2+ cations to 2-methylimidazole and PDA; thus, both the hollow and the yolk-like hybrid cubic microcapsules were controllably obtained by varying the synthetic dynamics. Owing to the hollow nature, penetrated PDA shell, well-distributed Au nanocrystals, and unique stable nanostructure, the non-spherical Au/PDA hybrid cubic microcapsules showed high performance in catalyzing the reduction of 4-nitrophenol as well as adsorption/release of ibuprofen as a model drug. Moreover, this simple strategy offers a controllable design in developing multifunctional nanocomposites with definite inner nanostructures and activities for nanocatalysis, drug delivery, energy storage etc.

The purpose of this study was to investigate the effect of okra polysaccharides with similar molecular weight on intestinal ecology. After extraction, ethanol precipitation, deproteinization and purification, two polysaccharide fractions, named as water-extracted polysaccharides (WEP) and alkaline-extracted polysaccharides (AEP), were obtained. According to the results of high performance liquid chromatography, AEP contained mannose, rhamnose, galacturonic acid and galactose, while WEP was composed of galactose, rhamnose, fructose, arabinose, glucose, galacturonic acid and mannose. The compositions of intestinal microbiota were affected by the change of daily substrates. Meanwhile, the concentration of ammonia and gastrointestinal transit time decreased, the total short chain fatty acid (SCFA) levels, moisture of caecum content increased. These findings suggested that the effect of okra polysaccharides on intestinal microbiota was achieved by the output of detrimental compounds and the supply of nutrients. Besides, AEP supported a more pivotal role in manipulating gut microbiota than WEP.

Background: Macamides, the main active components contained in maca, have attracted increasing attention due to their various bioactivities. In this study, crude macamide extract (CME) and purified macamide extract (PME) were prepared by enzyme-assisted extraction and macroporous resin separation, and the anti-fatigue effects of CME and PME were evaluated in a forced swimming model.; Results: The composition analysis results revealed that both CME and PME mainly contain eight kinds of macamide. Based on the results of a weight-loaded forced swimming test, compared with a control group, CME and and PME groups could prolong exhaustive swimming time, increase levels of liver glycogen (LG) and muscle glycogen (MG), accelerate fatty acid oxidation in serum to provide energy, eliminate the accumulation of blood lactic acid (BLA) and blood urea nitrogen (BUN), and decrease the serum biomarkers for muscle damage, such as lactate dehydrogenase (LDH) and creatine kinase (CK). Histological analysis also indicated that CME and PME attenuated damage to skeletal muscle and the myocardium in mice during exercise.; Conclusion: Two macamide extracts have a beneficial effect on relieving physical fatigue by attenuating the damage of skeletal muscle and myocardium during exercise, and a better effect was observed in the PME group. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.

Currently, there are few studies on acid-soluble pectin from okra, especially in biological activity for antioxidant and anti-inflammatory. In this study, the antioxidant properties of acid-soluble okra pectin components and their anti-inflammatory were explored. Firstly, two acid-soluble okra pectic fractions, namely crude acid-soluble okra pectin (CAOP) and acid-soluble okra pectin (AOP), were obtained and exhibited structural and compositional variation. The two pectic fractions contained a low degree of esterification (42.0-46.5%) and a relatively high uronic acid content (31.6-37.3%). AOP was composed of galacturonic acid (79.1 mol/%), galactose (4.3 mol/%), rhamnose (14.5 mol/%) and xylose (2.1 mol/%), and the molecular weight was 92.8 kDa. Morphological and thermal properties of acid-soluble okra pectin components were also investigated. Compared to CAOP, AOP expressed better antioxidant activity, and suppressed the NO production in LPS-induced RAW 264.7 macrophages. All the above results indicated that AOP had the potential to act as a natural antioxidant or a functional anti-inflammatory food, which would broaden the development and utilization of okra resources.

BACKGROUND The poor palatability, low digestibility, and unpleasant color of parboiled rice (PR) have severely hampered its acceptance by consumers. It is hence necessary and urgent to develop a new method for producing high-quality PR. In the current study, the effect of high hydrostatic pressure (HHP) pre-soaking on the color, textural properties, and the degree of retrogradation of PR was investigated. RESULTS With HHP from 100 to 500 MPa, the water adsorption rate increased and cooking time decreased. Parboiled rice samples presented higher lightness scores (L) and had lower color intensity (B). Compared with a control group, PR samples treated with high-pressure pre-soaking showed a reduction of hardness values from 0.69% to 32.99%, and gumminess values also decreased from 8.58% to 33.62%. The differential scanning calorimetry (DSC) results indicated that the enthalpy values of PR samples decreased after high pressure pre-soaking. The molecular structure of PR characterized by Fourier transform infrared spectrometry confirmed that HHP pre-soaking could decrease the retrogradation level. CONCLUSION The findings outlined above suggest that the texture and retrogradation properties of PR were improved after high-pressure pre-soaking. © 2021 Society of Chemical Industry.

Background Protecting the intestinal mucosa from being destroyed helps reduce the inflammation caused by acute pancreatitis (AP). In this study, whether okra pectin (OP) could attenuate the inflammation of AP through protecting the intestinal barrier was investigated. Results OP was obtained from crude okra pectin (COP) through the purification by DEAE cellulose 52 column. Supplementation with OP or COP in advance reduced the severity of AP, as revealed by lower serum amylase and lipase levels, abated pancreatic edema, attenuated myeloperoxidase activity and pancreas histology. OP or COP inhibited the production of pancreatic proinflammatory cytokines, including tumor necrosis factor-α and interleukin-6. In addition, the upregulation of AP-related proteins including ZO-1, occludin, the antibacterial peptide-defensin-1 (DEFB1) and cathelicidin-related antimicrobial peptide (CRAMP), as well as the histological examination of colon injuries, demonstrated that OP or COP provision could effectively maintain intestinal barrier function. Ultimately, dietary OP or COP supplementation could inhibit AP-induced intestinal inflammation. For the above, the effect of OP was better than COP. Conclusion Dietary OP supplementation could be considered as a preventive method that effectively interferes with intestinal damage and attenuates inflammatory responses trigged by AP. © 2020 Society of Chemical Industry.

In this study, the preparation of molecularly imprinted polymers for bilobalide (BBMIPs) was successfully achieved by bulk polymerization with methacrylamide (MAM), trimethylolpropane triacrylate (TMPTA), and acetonitrile (ACN) as functional monomer, cross-linker, and solvent, respectively. After Gaussian software simulation and single factor experiments, the prepared MIPs with a molar ratio of 1:4:15 for BB-MAM-TMPTA were systematically characterized. The hydrogen bonding interaction between BB and MAM was confirmed by a combination of FTIR and NMR analysis. Thermal gravimetric analysis results displayed that MIPs have excellent thermal stability under high temperature. Additionally, the average pore size and surface area of MIPs were found to be higher than those of NIPs through nitrogen adsorption results. The results of static adsorption and kinetic adsorption suggested that the adsorption equilibrium concentration was 0.6 mg/mL and the equilibrium time was 5 h, and the Langmuir and pseudo-second-order kinetic models were proven to fit with static and kinetic adsorption behaviors, respectively. Meanwhile, the selective adsorption study revealed that MIPs show high adsorption and great selectivity towards BB in comparison with other substances having similarly structure. MIPs also possessed a good performance on reusability, maintaining a high recovery rate after being reused 5 times. The application experiment further indicated that MIPs can effectively separate BB from low purity samples. Therefore, the prepared MIPs had a great potential for BB separation.

Cooking properties and retrogradation process of black rice (BR) with high hydrostatic pressure (HHP, 200–400 MPa/15 min) soaking were evaluated in this study. Results showed that the water absorption capacity of BR with HHP soaking was higher than that of control one. The HHP soaking also generated the lower leached amylose and hardness, while the higher springiness, cohesiveness, and resilience for cooked BR. In addition, the DSC data revealed that the enthalpy of cooked BR was influenced by HHP treatment, and the degree of retrogradation was decreed from 91% to 71% (storage for 21 days). Furthermore, the analysis of X-ray diffraction (XRD) revealed that the HHP treatment weakened the intensity of the peak of the 14 day-retrograded samples and decreased the relative crystallinity from 19.92% to 15.94% (storage for 21 days). These findings suggest that the HHP soaking could be a potentially applicable pretreatment for producing cooked BR with high quality.

An efficient preparation procedure has been proposed for the synthesis of 5,6-di-O-cinnamyl-l-ascorbic acid ester (5,6-CA–AA) and 2-O-cinnamyl-l-ascorbic acid ester (2-CA–AA) via ascorbic acid (AA) and cinnamic acid (CA), and their anti-oxidant and antibacterial activities were also investigated. Among the factors affecting the synthesis efficiency of 5,6-CA–AA and 2-CA–AA, reaction solvent and substrate molar ratio were very important, resulting in 76 and 54% total yield, respectively. Further studies indicated that 5,6-CA–AA maintained the inherent inhibitory ability of AA in α, α-diphenyl-β-picrylhydrazyl radical scavenging assay. Also, it had stronger scavenging activity against hydroxyl radicals than that of standard tert-butylhydroquinone (EC50: 7.84 vs. 8.38 mM). In addition, 5,6-CA–AA and 2-CA–AA possessed comparable antibacterial activity to that of CA. Significantly, the application of ascorbyl cinnamate could retard the lipid oxidation of peanut oil and pork, and the corresponding perioxide value and thiobarbituric acid reactive substance content decreased by 32.0 and 56.5%, respectively. Moreover, the microbial reproduction of the pork treated with mixed ascorbyl cinnamate was attenuated to some extent. These investigations will pave the way for designing more efficient bifunctional derivatives of AA and CA.

The organic pollutants and heavy metal ions are critical harmful substances in waste water because they destroy the ecological systems and lead diseases to animals and human beings. Unfortunately, the simultaneously remove of them in one system is still a challenge due to their different treating mechanism. Herein, a novel magnetic h-Fe3O4@Au/Polydopamine (Au/PDA) hybrid hollow nanosphere which can both absorb the potentially toxic U(VI) ions and catalyze the reduction of the 4-nitrophenol is reported. By using a simple in situ redox-oxidizing polymerization method, the h-Fe3O4 hollow nanosphere is well encapsulated by the Au/PDA hybrid shell to form the dual-functional magnetic hollow nanocomposites. Owing to the hollow interior, uniform and functional PDA coating, and high active Au nanocrystals, the final h-Fe3O4@Au/PDA hollow nanosphere possesses high potential in nanocatalysis, heavy metal ions adsorption, and drug delivery. Because of the PDA protection, the h-Fe3O4@Au/PDA nanosphere can even keep 90% activity after 7 cycling catalytic reactions on reduction of 4-nitrophenol. Similarly, the h-Fe3O4@Au/PDA exhibits a good adsorption effect for U(VI) in nuclear waste and its adsorption capability reaches to 82.9 mg·g−1 by 6 successive adsorption–desorption experiments. Due to the facile magnetic separation, the h-Fe3O4@Au/PDA nanosphere can be easily collected by applying an external magnetic field. In summary, such a multifunctional recyclable h-Fe3O4@Au/PDA nanosphere with green and facile synthesis, easy manipulation, efficient adsorption performance and good catalytic activity possesses broad application potential in treatment of coexisting toxic water pollution.

A series of ginkgolide B derivatives (GBD) were designed for delivery of ginkgolide B (GB) across the blood–brain barrier to the brain. Three GBD had shown considerable brain-targeting ability in our previous study. Among them, the ginkgolide B pyrazine (PGB) derivative was selected as a promising novel GB derivative because of its highest brain distribution. Further investigations with regard to PGB and GB's effects on inhibiting the expression of P-gp and attenuating the efflux function of P-gp were reported in this study. They were considered a big step towards better understanding the relationship between GBD's brain-targeting behavior and P-gp regulation. Western blot analysis indicated that PGB was more effective in inhibiting the expression of P-gp than GB in rat brain microvessel endothelial cells (rBMECs) and rat cerebral cortexes and hippocampus. Moreover, the efflux function of P-gp via the transportation of rhodamine 123 was significantly inhibited in PGB-treated rat brains. Preventive medication with PGB induced a better protection of the integrity of the BBB in incomplete ischemia mice. Our findings revealed that an attenuated expression level and efflux function of P-gp and improved protective effect could be realized by the ginkgolide B derivative. These investigations will pave the way for designing more efficient brain-targeting derivatives of ginkgolide and some other central nervous system drugs.

Tetramethylpyrazine was introduced to the structure of danshensu (DSS) as P-glycoprotein (P-gp)-inhibiting carrier, designing some novel brain-targeting DSS-pyrazine derivatives via prodrug delivery strategy. Following the virtual screening, three DSS-pyrazine esters (DT1, DT2, DT3) were selected because of their better prediction parameters related to brain-targeting. Among them, DT3 was thought to be a promising candidate due to its appropriate bioreversible property in vitro release assay. Further investigation with regard to DT3's brain-targeting effects in vivo was also reported in this study. High-performance liquid chromatography-diode array detection (HPLC-DAD) method was established for the quantitative determination of DT3 and DSS in rat plasma, brain homogenate after intravenous injection. In vivo metabolism of DT3 indicated that it was first converted into DT1, DT2, then the generation of DSS, which could be the result of carboxylesterase activity in rat blood and brain tissue. Moreover, the brain pharmacokinetics of DT3 was significantly altered with 2.16 times increase in half-life compared with that of DSS, and its drug targeting index (DTI) was up to 16.95. Above these data demonstrated that DT3 had better tendency of brain-targeting delivery, which would be positive for the treatment of brain-related disorders.

The aim of this study was to investigate the anti-fatigue activity of polysaccharide fractions from Abelmoschus esculentus (L.) Moench (AE) in mice. After crude polysaccharide (CAEP) was extracted from AE and purified by DEAE cellulose-52 column, two polysaccharide fractions (AEP-1 and AEP-2) were obtained. The structural analysis suggested that AEP-1 and AEP-2 were a RG-I polysaccharide and an AG-II polysaccharide, respectively. According to the results of the weight-loaded swimming test, compared with the negative control group, the CAEP, AEP-1 and AEP-2 treatment groups could prolong the swimming time, decrease serum urea nitrogen (SUN) and blood lactic acid (BLA), and increase hepatic glycogen (HG) and muscle glycogen (MG), which indicated that okra polysaccharides have an effective anti-fatigue activity. Furthermore, our study exhibited the anti-fatigue mechanism of okra polysaccharide was correlated with retarding the accumulation of creatine kinase (CK) and lactate dehydrogenase (LDH) in serum, and enhancing succinate dehydrogenase (SDH), adenosine triphosphate (ATP) and adenosine triphosphatase (ATPase) levels. In addition, the anti-fatigue activity of AEP-1 was stronger than that of AEP-2, and significantly better than that of CAEP. Therefore, AEP-1 and AEP-2 may be the main active anti-fatigue functional substances of AE.

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder characterized by memory loss, language impairment, personality changes and intellectual decline. Taking into account the key pathological features of AD, such as low levels of acetylcholine, beta-amyloid (Aβ) aggregation, oxidative stress and dyshomeostasis of biometals, a new series of paeonol derivatives 5a–5d merging three different functions, i.e., antioxidant, anti-acetylcholinesterase (AChE) activity, metal chelating agents for AD treatment have been synthesized and characterized. Biological assays revealed that compared with paeonol (309.7 μM), 5a–5d had a lower DPPH IC50 value (142.8–191.6 μM). 5a–5d could significantly inhibit hydrogen peroxide-induced neuronal PC12 cell death assessed by MTT assay in the concentration range of 5–40 μM. AChE activity was effectively inhibited by 5a–5d, with IC50 values in the range of 0.61–7.04 μM. 5a–5d also exhibited good metal-chelating ability. All the above results suggested that paeonol derivatives may be promising multifunctional agents for AD treatment.

Tacrine is well-known drug for Alzheimer’s disease as an acetylcholinesterase inhibitor. Rember is a bright and promising AD drugs targeting tau protein, and it is currently in Phase III clinical trials. Phenothiazine, the key pharmacophore of Rember, can prevent tau filament formation. In this work, several tacrine-phenothiazine hybrids (T1–T26) were designed for inhibiting acetylcholinesterase and tau protein involved in Alzheimer’s disease. After initial screening with the help of computational chemistry software and Molegro Virtual Docker, three molecules (T5, T18, and T22) were selected for further synthesis and biological evaluation. Next, T5, T18, and T22 were synthesized and evaluated for their acetylcholinesterase and tau hyperphosphorylation inhibition. All the tested compounds had better acetylcholinesterase inhibitory activity compared with tacrine. Among them, compound T5 was found to be the most potent compound with IC50 89 nM. Meanwhile, T5 markedly prevented tau hyperphosphorylation induced by okadaic acid in N2α cell. Its P-tau level was decreased with 39.5 % inhibition when tested at 10−5 M, lower than that Rember (55.7 %). Besides acetylcholinesterase and tau hyperphosphorylation inhibition, T5 can also interact with fibrill beta amyloid using surface plasmon resonance, the data of KD were 5.51 × 10−8 M. All the above results indicated that tacrine-phenothiazine hybrids are potential multitarget directed ligands targeting acetylcholinesterase, tau protein, and beta amyloid.

A sensitive, simple and rapid liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of ginkgolide B (GB) and the prodrug of ginkgolide B (PGB) in rat plasma and brain tissue. Detection was performed on a triple quadrupole tandem mass spectrometry in multiple reaction monitoring mode using the electrospray ionization technique in negative ionization mode. The total run time was only 2.0 min. Good linearity was found between 1-200 ng/mL (r > 0.9993) for plasma samples and 0.5-50 ng/mL (r = 0.9995) for the brain tissue samples. The lower limits of quantification of PGB and GB were 1 ng/mL for plasma and 0.5 ng/mL for brain tissue. Intra-day and inter-day precision was less than 11.67%. Intra-day accuracy was in the range of -2.61-10.67%, inter-day accuracy was in the range of -2.36-8.98%. The mean recovery for PGB and GB was between 82.5 and 97.0%. The validated method was successfully applied to a pharmacokinetic study of PGB and GB in rats after intravenous administration.

This study was carried out to design and synthesize 10-O-nicotinate ginkgolide B (PGB) as a new prodrug of ginkgolide B (GB). The lipophilicity of PGB and GB was evaluated through the partition coefficient in 1-octanol–water system. The concentrations of PGB and GB in plasma and brain tissue were determined by liquid chromatography tandem mass spectrometry (LC–MS/MS) after intravenous administration of PGB or GB. After calculation and analysis, the drug-targeting index (DTI) of PGB was 7.45 and area under curve (AUC) value of GB decomposed from PGB was 2.45-fold higher than that of GB (parent drug) in brain. All the above results indicated that the brain targeting of GB was improved by prodrug strategy.

The preparation of new sulfonamide ligands derived from L-tartaric acid and camphor sulfonyl chloride are described. The employment in the titanium tetraisopropoxide-promoted enantioselective addition of diethylzinc to ketones has been studied. The best enantiomeric excess is up to 99% with 7 mol% catalyst loading at room temperature.

A new chiral ligand derived from natural tartaric acid was synthesized and was applied to the asymmetric addition of diethylzinc to aldehyde and ketones. Moderate to good enantioselectivities were obtained in the asymmetric addition of diethylzinc to ketones with 10% mol catalyst loading at room temperature.

Ginkgolide B, one of the important components of Ginkgo biloba extracts, has been revealed to exhibit great potential in therapy of cerebrovascular diseases. However the lack of permeability greatly limited it from further clinical application. Based on the prediction model for blood brain barrier (BBB) permeation, herein a potential brain-targeting analog ginkgolide B cinnamate (GBC) was successfully synthesized and characterized. After intravenous administration of GBC or GB, liquid chromatography tandem mass spectrometry (LC-MS/MS) was conducted to determine the analog in rat plasma and brain. The results showed that GBC had a significant increase in BBB permeability. A significant 1.61-times increase in half-life was observed for GBC and the drug targeting index (DTI) value was calculated to be 9.91. The experiment results matched well with the predicted one, which revealed that BBB permeability prediction model combined with in vivo study could be used as a quick, feasible and efficient tool for brain-targeting drug design.

Acetylcholinesterase (AChE) is one of the key targets of drugs for treating Alzheimer's disease (AD). Tacrine is an approved drug with AChE-inhibitory activity. In this paper, 3D-QSAR, molecular docking, and molecular dynamics were carried out in order to study 60 tacrine derivatives and their AChE-inhibitory activities. 3D-QSAR modeling resulted in an optimal CoMFA model with q(2) = 0.552 and r(2) = 0.983 and an optimal CoMSIA model with q(2) = 0.581 and r(2) = 0.989. These QSAR models also showed that the steric and H-bond fields of these compounds are important influences on their activities. The interactions between these inhibitors and AChE were further explored through molecular docking and molecular dynamics simulation. A few key residues (Tyr70, Trp84, Tyr121, Trp279, and Phe330) at the binding site of AChE were identified. The results of this study improve our understanding of the mechanisms of AChE inhibitors and afford valuable information that should aid the design of novel potential AChE inhibitors. Graphical Abstract Superposition of backbone atoms of the lowest-energy structure obtained from MD simulation (magenta) onto those of the structure of the initial molecular docking model (green).

A variety of camphor sulfonamide ligands were synthesized and employed in the addition of diethylzinc to aldehydes. The influences of substitution patterns, electronic property, reaction substrates, reaction solvents and temperature were studied. After optimization, the best reaction condition was determined and applied to this addition reaction, giving the corresponding products in high yields with up to 83% ee.

A new sulfonamide ligand based on l -tartaric acid was synthesized and was employed as a chiral ligand in the enantioselective addition of diethylzinc to aldehydes, giving rise to the best enantiomeric excess up to 83% with 5 mol % of catalyst loading. Moreover, the addition of diethylzinc to ketones can also be achieved with good to excellent enantioselectivities by employing 7 mol % of the catalyst under mild conditions.

To develop environmentally benign processes for C-C bond formation, electrochemistry is applied in a tin-mediated allylation reaction in water. In this electrochemical process, the corresponding homoallylic alcohols are prepared in excellent yields, while both tin salt and water can be recycled and electrode materials are not consumed.

The preparation of new sulfonamide ligands derived from L-tartaric acid and camphor sulfonyl chloride are described. The employment in the titanium tetraisopropoxide-promoted enantioselective addition of diethylzinc to ketones has been studied. The best enantiomeric excess is up to 99% with 7 mol% catalyst loading at room temperature.