Anti-depressant effect of curcumin-loaded guanidine-chitosan thermo-sensitive hydrogel by nasal delivery.

Curcumin, a polyphenol compound extracted from the roots of turmeric plants, possesses anti-depressant effect by regulating the levels of neuroendocrine immunological factors. The purpose of this study was to investigate the anti-depressant effect of curcumin through nasal delivery. The results of phase solubility, Fourier transform infrared spectra, Differential scanning calorimetry, X-ray powder diffractometry and 1H NMR spectra assays showed that curcumin/hydroxypropyl-ß-cyclodextrin complex had been obtained. The viscosity of hydrogel increased rapidly at the temperature range of 29-30 °C through the test of rheological property of Guanidine-Chitosan thermo-sensitive hydrogel. And the hydrogel had good mucoadhesion properties. The cumulative release rate of curcumin was 55% in 10 h in vitro drug release test. Curcumin-loaded (14.6, 29.2, or 58.4 µg/kg) thermo-sensitive hydrogel could reduce the immobility time of mice in force swimming test and tail suspension test, while could not increase the independent behavioral activity of mice. In addition, curcumin-loaded (14.6, 29.2, or 58.4 µg/kg) thermo-sensitive hydrogel could increase the concentration of Norepinephrine, Dopamine, 5-Hydroxytryptamine and their metabolites in hippocampus and striatum. In conclusion, thermo-sensitive hydrogel delivery system can be seen as a promising formulation of curcumin for the treatment of depression through nasal delivery.

[Advance in modern studies on compatibility of Coptidis Rhizoma and Evodiae Fructus].

In traditional clinical application, Coptidis Rhizome and Evodiae Fructus have been combined to treat various stomach heat and cold syndromes, gastritis, gastric ulcer and the like. With the application of modem instruments and the development of molecular pharmacologic theory, their chemical constituents and pharmacological effects have been sufficiently studied. In this paper, literatures from Pubmed were adopted, with particular emphasis on findings of international counterparts and studies on compatibility of main chemical components in Coptidis Rhizoma and Evodiae Fructus, in order to elaborate on the scientific comparability of Coptidis Rhizoma and Evodiae Fructus through chemical analysis, and pharmacological and biopharmaceutics studies and introduce the future development trend of the studies.

Paediatric drugs trials in China.

OBJECTIVE: Clinical trials of children's drugs are of great significance to rational drug use in children. However, paediatric drugs trials in China are facing complex challenges. At present, the investigation data on registration status of paediatric drug trials in China are still relatively lacking, and relevant research is urgently needed. METHODS: The advanced retrieval function is used to retrieve clinical trials data in the Clinical Trial.gov and Chinese Clinical Trial Registry databases in 22 April 2019. Fifteen key items were analysed to describe trial characteristics, including: registration number, study start date (year), mode of funding, type of disease, medicine type, research stage, research design, sample size, number of experimental groups, placebo group, blind method, implementation centre, child specific, newborn specific and participant age. RESULTS: A total of 1388 clinical trials of paediatric drugs conducted in China were registered. The number of paediatric drug trials grew steadily over time, from less than 20 per year before 2005 to more than 100 per year after 2012. Most clinical trials were postmarketing (n=800, 57.6%), single-centre (n=1045, 75.3%), intervention studies (n=1161, 83.6%) without blinded methods (1169, 84.2%) and funded by non-profit organisations (n=838, 60.4%). The number of clinical trials for antineoplastic agents (n=254, 18.3%), anti-infectives (n=156, 11.2%) and vaccines (n=154, 11.1%) is the largest. CONCLUSION: Paediatric drug trials in China made a significant progress in recent years. Innovative method and trial design optimisation should be encouraged to accelerate paediatric clinical research. Pharmaceutical companies need to be further stimulated to carry out more high-quality paediatric clinical trials with support of paediatric drug legislation.

Antidepressant-like effect of ethanol extract from Zuojin Pill, containing two herbal drugs of Rhizoma Coptidis and Fructus Evodiae, is explained by modulating the monoaminergic neurotransmitter system in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Zuojin Pill (ZJP), a traditional Chinese medicinal decoction, contains two herbal drugs: Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. in the ratio of 6:1 (w/w). Previous pharmacological studies have shown that two herbs in ZJP have the antagonistic effects on catecholamine secretion in bovine adrenal medullary cells. Furthermore, the alkaloids from the two herbs in ZJP may provide a protective effect for depression in individuals with a low expressing 5-HTT allele by increasing receptor concentration in serotonergic neurons. However, antidepressant effect has not been reported before and has not been fully clarified. AIM OF THE STUDY: The present study aimed to investigate the antidepressant potential of ethanol extract from ZJP and its monoaminergic mechanism in mice. MATERIALS AND METHODS: Seven alkaloids were determined from the ethanol extract of ZJP using High Performance Liquid Chromatography (HPLC) with the gradient mobile phase. The ethanol extract from ZJP was used to evaluate the antidepressant potential in mice. Mouse models of depression including the tail suspension test (TST) and the forced swim test (FST) were used to evaluate the effects of the ethanol extract from ZJP. A possible mechanism was explored in the tests of antagonism of reserpine-induced ptosis and hypothermia, and 5-HTP induced head twitch response in mice. The contents of monoamine neurotransmitters including norepinephrine (NE), serotonin (5-hydroxytryptamine or 5-HT) in hippocampus of mice and NE, 5-HT, dopamine (DA) in striatum of mice were determined by HPLC system with Electrochemical Detector (ECD). RESULTS: The results showed that intragastric administration of the ethanol extract from ZJP (5, 10, 20mg/kg) or fluoxetine (7.5mg/kg) significantly reduced the duration of immobility in TST and FST. However, the effect was not dose-dependent. Ethanol extract from ZJP (5, 10, 20mg/kg) also increased the accumulative number of the 5-HTP-induced head twitch response in mice. The mice were treated with the ethanol extract from ZJP (5, 10, 20mg/kg) or fluoxetine (7.5mg/kg), which could antagonize reserpine-induced ptosis and hypothermia, moreover, both of them could elevate the contents of NE, 5-HT in hippocampus as well as NE, 5-HT, DA in striatum significantly. CONCLUSION: These results indicate that the ethanol extract from ZJP produced antidepressant-like effect and the possible mechanism, at least in part, is via the central monoaminergic neurotransmitter system and 5-HT plays a major role.