Protoberberine alkaloids: A review of the gastroprotective effects, pharmacokinetics, and toxicity.

BACKGROUND: Stomach diseases have become global health concerns. Protoberberine alkaloids (PBAs) are a group of quaternary isoquinoline alkaloids from abundant natural sources and have been shown to improve gastric disorders in preclinical and clinical studies. The finding that PBAs exhibit low oral bioavailability but potent pharmacological activity has attracted great interest. PURPOSE: This review aims to provide a systematic review of the molecular mechanisms of PBAs in the treatment of gastric disorders and to discuss the current understanding of the pharmacokinetics and toxicity of PBAs. METHODS: The articles related to PBAs were collected from the Web of Science, Pubmed, and China National Knowledge Infrastructure databases using relevant keywords. The collected articles were screened and categorized according to their research content to focus on the gastroprotective effects, pharmacokinetics, and toxicity of PBAs. RESULTS: Based on the results of preclinical studies, PBAs have demonstrated therapeutic effects on chronic atrophic gastritis and gastric cancer by activating interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) pathway and suppressing transforming growth factor-beta 1 (TGF-ß1)/phosphoinositide 3-kinase (PI3K), Janus kinase-2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK) pathways. The major PBAs exhibit similar pharmacokinetic properties, including rapid absorption, slow elimination, and low bioavailability. Notably, the natural organ-targeting property of PBAs may account for the finding of their low blood levels and high pharmacological activity. PBAs interact with other compounds, including conventional drugs and natural products, by modulation of metabolic enzymes and transporters. The potential tissue toxicity of PBAs should be emphasized due to their high tissue accumulation. CONCLUSION: This review highlights the gastroprotective effects, pharmacokinetics, and toxicity of PBAs and will contribute to the evaluation of drug properties and clinical translational studies of PBAs, accelerating their transfer from the laboratory to the bedside.

[Adsorption Cd2+ from Solution by EDTA-modified Silicate Nanoparticles].

Silicate nanoparticles(nSiO2) are a kind of widely used engineering material. In order to improve the Cd2+ adsorption ability, the EDTA-modified nSiO2 nanoparticles were prepared by grafting method and characterized by TEM, N2 adsorption-desorption, FTIR, and TGA. The effects of solution pH, contact time, temperature and ionic strength were examined. The adsorption mechanism was further investigated by XPS. The results showed that the EDTA-nSiO2 nanoparticles possessed excellent stability, and were successfully prepared. Cd2+ adsorption was mainly controlled by solution pH. The raw nSiO2 had limited Cd2+ adsorption ability, while the EDTA-modified nSiO2 particles had significantly improved adsorption performance. At high pH, the Cd2+ adsorption rate increased and kept balance above pH 4.0. The Cd2+ adsorption was an endothermic spontaneous process which could be finished within 1 h. Langmuir model could be used to describe the adsorption isotherm. The temperature ranged from 293-313 K during the process, while the maximum adsorption was observed at higher temperature. Higher ionic strength could inhibit the Cd2+ adsorption. The Cd2+ adsorption decreased from 0.433 to 0.294 mmol·g-1, when NaCl concentration varied from 0 to 100 mmol·L-1. The desorption of Cd2+ from the EDTA-nSiO2 nanoparticles was carried out with distilled water, 0.1 mol·L-1 NaCl and 0.1 mol·L-1 HCl. The maximum Cd2+ desorption of 94.36% was obtained at 0.1 mol·L-1 HCl. Based on the results of thermodynamics, pH, ionic strength, and XPS analysis, it could be concluded that Cd2+ adsorption was a multiple process dominated by chemical chelating reaction, physical adsorption and ion exchange. This study indicated that the EDTA-nSiO2 is an effective engineering nanomaterial that could be used in Cd2+ adsorption.

(E)-N'-[1-(4-Chloro-phen-yl)ethyl-idene]-2-hydroxy-benzohydrazide.

In the title compound, C(15)H(13)ClN(2)O(2), the dihedral angle between the two benzene rings is 7.0 (1)°. An intra-molecular N-H⋯O hydrogen bond is present and inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into chains along [001].