Synthesis, Spectroscopic Study and Radical Scavenging Activity of Kaempferol Derivatives: Enhanced Water Solubility and Antioxidant Activity.

Kaempferol (Kae) is a natural flavonoid with potent antioxidant activity, but its therapeutic use is limited by its low aqueous solubility. Here, a series of Kae derivatives were synthesized to improve Kae dissolution property in water and antioxidant activity. These compounds included sulfonated Kae (Kae-SO3), gallium (Ga) complexes with Kae (Kae-Ga) and Kae-SO3 (Kae-SO3-Ga). The compound structures were characterized by high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy and thermal methods (TG/DSC). The results showed that a sulfonic group (-SO3) was successfully tethered on the C3' of Kae to form Kae-SO3. And in the metal complexation, 4-CO and 3-OH of the ligand participated in the coordination with Ga(III). The metal-to-ligand ratio 1:2 was suggested for both complexes. Interestingly, Kae-SO3-Ga was obviously superior to other compounds in terms of overcoming the poor water-solubility of free Kae, and the solubility of Kae-SO3-Ga was about 300-fold higher than that of Kae-Ga. Furthermore, the evaluation of antioxidant activities in vitro was carried out for Kae derivatives by using α,α-diphenyl-ß-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) free radical scavenging. The results showed that Kae-SO3-Ga was also optimal for scavenging free radicals in a dose-dependent manner. These data demonstrate that sulfonate kaempferol-gallium complex has a promising future as a potential antioxidant and as a potential therapeutic agent for further biomedical studies.

Synthesis, characterization and anticancer activity of kaempferol-zinc(II) complex.

According to the previous studies, the anticancer activity of flavonoids could be enhanced when they are coordinated with transition metal ions. In this work, kaempferol-zinc(II) complex (kaempferol-Zn) was synthesized and its chemical properties were characterized by UV-VIS, FT-IR, (1)H NMR, elemental analysis, electrospray mass spectrometry (ES-MS) and fluorescence spectroscopy, which showed that the synthesized complex was coordinated with a Zn(II) ion via the 3-OH and 4-oxo groups. The anticancer effects of kaempferol-Zn and free kaempferol on human oesophageal cancer cell line (EC9706) were compared. MTT results demonstrated that the killing effect of kaempferol-Zn was two times higher than that of free kaempferol. Atomic force microscopy (AFM) showed the morphological and ultrastructural changes of cellular membrane induced by kaempferol-Zn at subcellular or nanometer level. Moreover, flow cytometric analysis indicated that kaempferol-Zn could induce apoptosis in EC9706 cells by regulating intracellular calcium ions. Collectively, all the data showed that kaempferol-Zn might be served as a kind of potential anticancer agent.

Silk fibroin-based coating with pH-dependent controlled release of Cu2+ for removal of implant bacterial infections.

The implantation of medical devices is frequently accompanied by the invasion of bacteria, which may lead to implant failure. Therefore, an intelligent and responsive coating seems particularly essential in hindering implant-associated infections. Herein, a self-defensive antimicrobial coating, accompanied by silk fibroin as a valve, was successfully prepared on the titanium (Ti-Cu@SF) for pH-controlled release of Cu2+. The results showed that the layer could set free massive Cu2+ to strive against E. coli and S. aureus for self-defense when exposed to a slightly acidic condition. By contrary, a little Cu2+ was released in the physiological situation, which could avoid damage to the normal cells and showed excellent in vitro pH-dependent antibiosis. Besides, in vivo experiment confirmed that Ti-Cu@SF could work as an antibacterial material to kill S. aureus keenly and display negligible toxicity in vivo. Consequently, the design provided support for endowing the layer with outstanding biocompatibility and addressing the issue of bacterial infection during the implantation of Ti substrates.

[Modulation of polysaccharide extracted from Laminaria on phase compositions of urinary crystal calcium oxalate].

The influence of sulfate polysaccharide (SPS) isolated from marine algae Laminaria japonica aresch on the growth of urinary crystal calcium oxalate (CaO(xa)) was investigated by means of X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and atomic absorption spectroscopy. SPS can stabilize thermodynamic metastable calcium oxalate dihydrate (COD) crystals. As the concentration of SPS increases from 0 to 0.60 mg x mL(-1), the mass percentage of COD crystals increases from 0 to 100%, and the relative supersaturation of calcium oxalate increases from 1.0 to 19.6. The ability of SPS to stabilize the existence of COD in aqueous solution and to increase the concentration of soluble calcium ions is favorable to the inhibition of CaO(xa) stone. Indicating that SPS is a potential green drug for prevention and cure of CaO(xa) urinary stones.

[Chemical structure of dicarboxylic acids and their capacity inhibiting of calcium oxalate crystal growth].

The effect of dicarboxylic acids with a three C-C bonds distance on the crystallization of calcium oxalate (CaOxa) was investigated in silica gel system by means of X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). These acids include succinic acid, maleic acid, fumaric acid, malic acid, L-aspartic acid and tartaric acid. All the dicarboxylic acids can inhibit the aggregation of calcium oxalate monohydrate (COM) and induce the formation of calcium oxalate dehydrate (COD). But their ability to inhibit the growth and aggregation of COM, to diminish the specific surface area of COM and to induce COD formation were strengthened as the number of the substituted hydroxyl or amino group increased. The molecular mechanisms were discussed in terms of chemical structures of dicarboxylic acids. Only the dicarboxylic acids with a HOOC-CH(R)-CH2-COOH (R=OH or NH2) group were found to have the best inhibitory effect on the CaOxa urinary stones. The results could provide some clue to looking for new drugs for urinary stones in clinic.

[Application and research progress of composition analysis of urinary calculi].

The analyses of compositions of urinary stones can provide significant reference to the treatment and prevention of recurrence of urolithiasis. In the present paper, the application and research progress of composition analyses of various urinary stones such as calcium oxalates, phosphates, uric acid, urates, cystine etc. by means of modern instruments are summarized. These techniques include Raman spectroscopy, thermogravimetry analysis/differential thermal analysis (TGA/DTA), nuclear magnetic resonance (NMR), high-performance liquid chromatography (HPLC), Fourier infrared (FTIR) spectroscopy, etc.

The mechanism of kaempferol induced apoptosis and inhibited proliferation in human cervical cancer SiHa cell: From macro to nano.

Kaempferol has been identified as a potential cancer therapeutic agent by an increasing amount of evidences. However, the changes in the topography of cell membrane induced by kaempferol at subcellular- or nanometer-level were still unclear. In this work, the topographical changes of cytomembrane in human cervical cancer cell (SiHa) induced by kaempferol, as well as the role of kaempferol in apoptosis induction and its possible mechanisms, were investigated. At the macro level, MTT assays showed that kaempferol inhibited the proliferation of SiHa cells in a time- and dose-dependent manner. Flow cytometry analysis demonstrated that kaempferol could induce SiHa cell apoptosis, mitochondrial membrane potential disruption, and intracellular free calcium elevation. At the micro level, fluorescence imaging by laser scanning confocal microscopy (LSCM) indicated that kaempferol could also destroy the networks of microtubules. Using high resolution atomic force microscopy (AFM), we determined the precise changes of cellular membrane induced by kaempferol at subcellular or nanometer level. The spindle-shaped SiHa cells shrank after kaempferol treatment, with significantly increased cell surface roughness. These data showed structural characterizations of cellular topography in kaempferol-induced SiHa cell apoptosis and might provide novel integrated information from macro to nano level to assess the impact of kaempferol on cancer cells, which might be important for the understanding of the anti-cancer mechanisms of drugs. SCANNING 38:644-653, 2016. © 2016 Wiley Periodicals, Inc.

Morphology, particle size distribution, aggregation, and crystal phase of nanocrystallites in the urine of healthy persons and lithogenic patients.

BACKGROUND: The first step in urinary stone formation is the nucleation of urinary mineral from supersaturated urine. The formed nuclei then grow or/and aggregate to a pathological size. Thus, the nanocrystallites in urine may be related to the formation of urinary stones. METHODS: Nanocrystallites with a size of less than 1000 nm in the urine samples of 85 healthy persons and 65 lithogenic patients were comparatively investigated using laser scattering spectroscopy, TEM, and X-ray diffraction. RESULTS: Most of the nanocrystallites in healthy urine samples were spheroidal, less aggregated, well-dispersed, and with a narrow particle size distribution from about 20 to 350 nm. In contrast, most of the particles in lithogenic urines had sharply angled edges and tips, were aggregated, and had a broad particle size distribution from 1.1 to 1000 nm. More calcium oxalate dihydrate (COD) nanocrystallites were found in healthy urine; however, more calcium oxalate monohydrate (COM) nanocrystallites were found in lithogenic urine. CONCLUSIONS: The morphology, particle size, aggregation, and crystal phase of nanocrystallites in the urine of lithogenic patients are pronouncedly different from those of healthy persons. The results suggest, in ascending order of importance, that making nanocrystallites rounded, diminishing their size differentiation, and decreasing their aggregation in urine by physical and chemical methods maybe the means to prevent urinary stone formation. The most crucial among the four differences is the crystal phase differential of calcium oxalate (CaOxa). That is, the formation of COD nanocrystallites in urine can be considered as being relatively more favorable in preventing stone formation than the formation of COM nanocrystallites, which are in accord with those found for larger crystallites.