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Background and Aims: Oral drug delivery is the most attractive pathway for ulcerative colitis [UC] therapy, since it has many advantages. However, this strategy has encountered many challenges, including the instability of drugs in the gastrointestinal tract [GT], low targeting of disease tissues, and severe adverse effects. Nanoparticles capable of colitis tissue-targeted delivery and site-specific drug release may offer a unique and therapeutically effective system that addresses these formidable challenges., Methods: We used a versatile single-step surface-functionalising technique to prepare PLGA/PLA-PEG-FA nanoparticles loaded with the ginger active compound, 6-shogaol [NPs-PEG-FA/6-shogaol]. The therapeutic efficacy of NPs-PEG-FA/6-shogaol was evaluated in the well-established mouse model of dextran sulphate sodium [DSS]-induced colitis., Results: NPs-PEG-FA exhibited very good biocompatibility both in vitro and in vivo. Subsequent cellular uptake experiments demonstrated that NPs-PEG-FA could undergo efficient receptor-mediated uptake by colon-26 cells and activated Raw 264.7 macrophage cells. In vivo, oral administration of NPs-PEG-FA/6-shogaol encapsulated in a hydrogel system [chitosan/alginate] significantly alleviated colitis symptoms and accelerated colitis wound repair in DSS-treated mice by regulating the expression levels of pro-inflammatory [TNF-α, IL-6, IL-1β, and iNOS] and anti-inflammatory [Nrf-2 and HO-1] factors., Conclusions: Our study demonstrates a convenient, orally administered 6-shogaol drug delivery system that effectively targets colitis tissue, alleviates colitis symptoms, and accelerates colitis wound repair. This system may represent a promising therapeutic approach for treating inflammatory bowel disease [IBD]., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Synthesized urushiol derivatives possessing different carbon atomic length in the alkyl side chain inhibited the growth of food spoilage and pathogenic microorganisms. Particularly, non-allergenic 3-pentylcatechol showed a broad antimicrobial spectrum on an agar plate. Most food spoilage and pathogenic microorganisms were sensitive to urushiol derivatives in the liquid culture. The morphologies of the microorganisms were changed after treatment of 3-pentylcatechol.

Negative symptoms in schizophrenia are associated with decreased dopaminergic activity in the prefrontal cortex (PFC). It is hypothesized that increasing dopamine levels would alleviate negative symptoms. Termination of dopamine activity in the PFC is mainly via catechol-O-methyl tranferase (COMT) activity. Hence, inhibition of COMT activity with entacapone should reverse PFC dopaminergic transmission. To assess the efficacy of entacapone addition to antipsychotic treatment in patients with residual schizophrenia, we conducted a double-blind, randomised, placebo-controlled study for 12 wk of treatment with entacapone or placebo. Clinical measures (PANSS, CGI and QLS) were obtained at baseline and at weeks 4, 8 and 12 and cognitive functions were assessed by the RBANSS. Significant improvement over time in PANSS and QLS scores was observed in both groups. However, entacapone did not demonstrate a beneficial effect compared to placebo. Therefore, this study does not support a therapeutic role for entacapone in residual schizophrenia.

Objectives: (S)-[6]-Gingerol is under investigation for a variety of therapeutic uses. Transforming growth factor (TGF)-β stimulates proteoglycan synthesis, leading to increased binding of low-density lipoproteins, which is the initiating step in atherosclerosis. We evaluated the effects of (S)-[6]-gingerol on these TGF-β-mediated proteoglycan changes to explore its potential as an anti-atherosclerotic agent., Methods: Purified (S)-[6]-gingerol was assessed for its effects on proteoglycan synthesis by [(35) S]-sulfate incorporation into glycosaminoglycan chains and [(35) S]-Met/Cys incorporation into proteoglycans and total proteins in human vascular smooth muscle cells. Biglycan level was assessed by real-time quantitative polymerase chain reactions and the effects of (S)-[6]-gingerol on TGF-β signalling by assessment of the phosphorylation of Smads and Akt by western blotting., Key Findings: (S)-[6]-Gingerol concentration-dependently inhibited TGF-β-stimulated proteoglycan core protein synthesis, and this was not secondary to inhibition of total protein synthesis. (S)-[6]-Gingerol inhibited biglycan mRNA expression. (S)-[6]-Gingerol did not inhibit TGF-β-stimulated glycosaminoglycan hyperelongation or phosphorylation of Smad 2, in either the carboxy terminal or linker region, or Akt phosphorylation., Conclusions: The activity of (S)-[6]-gingerol to inhibit TGF-β-stimulated biglycan synthesis suggests a potential role for ginger in the prevention of atherosclerosis or other lipid-binding diseases. The signalling studies indicate a novel site of action of (S)-[6]-gingerol in inhibiting TGF-β responses., (© 2013 Royal Pharmaceutical Society.)

Objectives: We have investigated the anti-inflammatory and antinociceptive effects of (E)-4-(3,7-dimethylocta-2,6-dienylamino)phenol (LQFM-015), which was designed through molecular simplification strategy from 4-nerolidylcatechol., Methods: The possible anti-inflammatory and antinociceptive effects were assayed on carrageenan-induced paw oedema and pleurisy, acetic acid-induced abdominal writhing and formalin tests in mice., Key Findings:  LQFM-015 reduced the activity of PLA₂ enzyme in vitro by 18%. Docking studies into the catalytic site of PLA₂ were used to identify the binding mode of the LQFM-015. LQFM-015 showed a moderate antinociceptive effect, since this compound reduced the number of writhings by approximately up to 40% in the acetic acid-induced pain model; this antinociceptive activity also emerged in the second phase of the formalin-induced pain model (58% of inhibition). The anti-inflammatory action of LQFM-015 was confirmed in acute inflammation models, in which it reduced the formation of oedema to 52.78 ± 8.6 and 46.64 ± 5.2 at the second and third hour of carrageenan-induced paw oedema, respectively. Also in the carrageenan-induced pleurisy model, LQFM-015 reduced the migration of leucocytes by 26.0% and decrease myeloperoxidase activity by 50%. LQFM-015 showed different concentrations to inhibit 50% of isoenzyme cyclooxygenase activity (IC50); COX-1 IC50 = 36 μM) and COX-2 IC50 = 28 μM., Conclusions: LQFM-015 demonstrated inhibition of both PLA₂ and COX enzymes; thus, the moderate antinociceptive effect of this compound could be attributed to its anti-inflammatory activity., (© 2012 The Authors. JPP © 2012. Royal Pharmaceutical Society.)

Objective: This study investigated the use of a bioactive phytochemical, namely ginger extract (GE), for its antioxidant and antiulcer effects, and also for supporting probiotic growth and activity. Use of probiotics is limited in therapy because of their transience and inability to survive the adverse physiological conditions of the gastrointestinal tract. Packaging probiotics in a suitably designed pharmaceutical system with GE may facilitate their establishment in the stomach mucosa., Methods: A probiotic (Lactobacillus acidophilus) and GE were simultaneously and individually encapsulated/immobilized in alginate floating beads. The developed system was evaluated for diameter, buoyancy, entrapment, porosity, in-vitro viability/release and pharmacodynamics in a cold restraint stress induced gastric ulcer model in rats., Key Finding: The developed floating beads stayed in the stomach for more than 10 h and both agents were released slowly and over a prolonged period from these beads. Significant and promising results were obtained for the combination (synbiotic) system in terms of ulcer index, mucus secretion, oxidative stress and histopathological parameters, as compared with the individual agents. The developed system could completely revert the damage induced in ulcerated stomachs at physiological (ulcer index and mucus secretion), biochemical (oxidative stress) and histological levels., Conclusion: This study establishes that suitable packaging of GE and Lactobacillus acidophilus together in floating beads can help exploit their prospects as therapeutic curative agents rather than potential preventive agents., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)

A simple, precise, and accurate high-performance liquid chromatographic method was developed and validated to determine percent drug release of levodopa (LEV), carbidopa (CAR), and entacapone (ENT) from its combination dosage form. A mixture of acetonitrile and buffer was used as the mobile phase for reversed-phase liquid chromatographic separation for determination of the in vitro drug release of LEV, CAR, and ENT. A dissolution test was conducted at 75 rpm with United States Pharmacopeia (USP) apparatus-II (paddle) by using pH 5.5 phosphate buffer as a dissolution medium. Three formulations, differing in strength, were evaluated. The developed method was validated for specificity, linearity, precision, accuracy, and solution stability. The specificity of the method was determined in the presence of placebo interference. The method was linear over the drug concentration ranges of 4-210 microg/mL for LEV, 1-52 microg/mL for CAR, and 6-280 microg/mL for ENT. Precision was established by determination of system precision, method precision, and intermediate precision. Accuracy values for the method ranged from 96.8 to 104.3% for LEV, from 97.2 to 101.3% for CAR, and from 99.5 to 102.8% for ENT. The developed method was suitable for estimating percent drug release of LEV, CAR, and ENT in terms of the dissolution test.

The efficacy of oral administration of the chelating agent catechol-3,6-bis(methyleiminodiacetic acid) (CBMIDA) for removing uranium from rats after intraperitoneal (i.p.) and intramuscular (i.m.) injections of depleted uranium (DU) was examined and the results with those by the i.p. injection of CBMIDA were compared. In Experiment 1, after a single i.p. injection of 8 mg kg(-1) of DU of rat's body weight, 35 8-week-old male rats were divided into seven groups consisting of five rats each. Three groups were administered with CBMIDA 240, 720 or 1200 mg kg(-1) of rat's body weight orally once a day, and three other groups received an i.p. injection of 240, 480 or 720 mg kg(-1) CBMIDA for 3 d, starting 30 min after DU injection on the first day. One DU group received no CBMIDA. The remaining five intact rats were used as a control group. Rats were killed 6 d after DU injection. In Experiment 2, the 35 male rats that received a single i.m. injection of 8 mg kg(-1) DU were divided into seven groups, and the rats of each group received the same doses of CBMIDA on the same schedules of treatment as those described in Experiment 1. The results obtained in Experiment 1 indicated that orally administered CBMIDA significantly increased the excretion of uranium at doses of 720 and 1200 mg kg(-1) and decreased uranium concentrations, particularly in the kidney, at all the doses tested, and the effects were almost equal to those of the i.p. injection. The lack of increases in creatinine and blood urea nitrogen in serum indicated that CBMIDA is efficacious in preventing the renal dysfunction caused by uranium. In Experiment 2, oral administration of CBMIDA significantly increased uranium excretion and significantly decreased uranium concentrations, particularly in the kidneys, at all the doses tested, and the effects were almost equal to those of the i.p. injection. However, these effects of CBMIDA on the i.m.-injected DU were lower than those of the i.p.-injected DU in Experiment 1. These results indicated that oral administration of CBMIDA has almost the same efficacy as that administered by the parenteral route. Additional study is necessary to obtain satisfactory effects for the clinical use of CBMIDA, particularly for wounds contaminated accidentally with uranium.

A simple and sensitive high-performance liquid chromatography method is developed for the simultaneous determination of (3,4-dihydroxyphenyl)-lactic acid (Dhpl) and protocatechuic aldehyde (Pal) in rat serum after oral administration of Radix Salviae miltiorrhizae extract. Serum samples are acidified with hydrochloric acid and extracted with ethyl acetate. Analysis of the extract is performed on a reversed-phase column and a mobile phase of 0.02% phosphoric acid-acetonitrile (91:9, v/v) with UV detection at 280 nm. Standard curves are linear in the range of 1.47-456.96 microg/mL for Dhpl and 0.124-7.936 microg/mL for Pal. For both regression coefficients, r(2) is greater than 0.993. Mean recovery is determined to be 75.23% and 84.06%, respectively, by analyzing serum standard containing 7.14, 57.12, and 228.48 microg/mL of Dhpl and 0.124, 0.992, and 3.968 microg/mL of Pal. The intraday precision (relative standard deviation) ranges from 3.91% to 12.03% at concentrations of 1.43, 57.12, and 228.48 microg/mL for Dhpl and 3.79% to 8.12% at concentrations of 0.124, 0.992, and 3.968 microg/mL for Pal. The interday precision (relative standard deviation) ranges from 5.06% to 9.93% for Dhpl and 3.05% to 10.00% for Pal, respectively, at the same three concentrations. This validated assay is applied to the determination of Dhpl and Pal concentrations and used to take a limited view of the pharmacokinetic profile in rat serum after oral administration of Radix Salviae miltiorrhizae extract.

Since various 4-alkylcatechols stimulate nerve growth factor (NGF) biosynthesis both in-vitro and in-vivo, delivery of these agents to the brain may provide beneficial effect for the treatment of neurodegenerative diseases such as Alzheimer's. Several dihydropyridine-pyridinium salt type redox chemical delivery systems (CDS) of 4-methylcatechol (4-methylcatechol) were prepared as potential brain selective targetry forms for 4-methylcatechol. After preliminary evaluation by in-vitro stability studies in various buffer solutions and biological media, a selected CDS was further investigated in the rat to determine its in-vivo distribution. Selective and sustained delivery of the compound of interest to the rat brain was achieved. Furthermore, the NGF stimulatory activity in the rat brain after peripheral administration of the selected CDS was evaluated by measuring the levels of pre-pro-NGF mRNA in the rat hippocampus and frontal cortex, by dot blot hybridization and analysis. Results showed the peripheral administration of the CDS to achieve a 1.7-fold increase in NGF mRNA compared to control in the rat hippocampus, and an approximately 1.4-fold increase in the frontal cortex.