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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

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 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.

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.

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.

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.

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).