Kinetic Studies on Radical Scavenging Activity of Kaempferol Decreased by Sn(II) Binding.

Sn(II) binds to kaempferol (HKaem, 3,4',5,7-tetrahydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) at the 3,4-site forming [Sn(II)(Kaem)2] complex in ethanol. DPPH• scavenging efficiency of HKaem is dramatically decreased by SnCl2 coordination due to formation of acid inhibiting deprotonation of HKaem as ligands and thus reduces the radical scavenging activity of the complex via a sequential proton-loss electron transfer (SPLET) mechanism. Moderate decreases in the radical scavenging of HKaem are observed by Sn(CH3COO)2 coordination and by contact between Sn and HKaem, in agreement with the increase in the oxidation potential of the complex compared to HKaem, leading to a decrease in antioxidant efficiency for fruits and vegetables with Sn as package materials.

Alkaline earth metal ion coordination increases the radical scavenging efficiency of kaempferol.

Flavonoids are used as natural additives and antioxidants in foods, and after coordination to metal ions, as drug candidates, depending on the flavonoid structure. The rate of radical scavenging of the ubiquitous plant flavonoid kaempferol (3,5,7,4'-tetrahydroxyflavone, Kaem) was found to be significantly enhanced by coordination of Mg(ii), Ca(ii), Sr(ii), and Ba(ii) ions, whereas the radical scavenging rate of apigenin (5,7,4'-trihydroxyflavone, Api) was almost unaffected by alkaline earth metal (AEM) ions, as studied for short-lived ß-carotene radical cations (ß-Car˙+) formed by laser flash photolysis in chloroform/ethanol (7 : 3) and for the semi-stable 2,2-diphenyl-1-picrylhydrazyl radical, DPPH˙, in ethanol at 25 °C. A 1 : 1 Mg(ii)-Kaem complex was found to be in equilibrium with a 1 : 2 Mg(ii)-Kaem2 complex, while for Ca(ii), Sr(ii) and Ba(ii), only 1 : 2 AEM(ii)-Kaem complexes were detected, where all complexes showed 3-hydroxyl and 4-carbonyl coordination and stability constants of higher than 109 L2 mol-2. The 1 : 2 Ca(ii)-Kaem2 complex had the highest second order rate constant for both ß-Car˙+ (5 × 108 L mol-1 s-1) and DPPH˙ radical (3 × 105 L mol-1 s-1) scavenging, which can be attributed to the optimal combination of the stronger electron withdrawing capability of the (n - 1)d orbital in the heavier AEM ions and their spatially asymmetrical structures in 1 : 2 AEM-Kaem complexes with metal ion coordination of the least steric hindrance of two perpendicular flavone backbones as ligands in the Ca(ii) complex, as shown by density functional theory calculations.

Copper(II) Coordination and Translocation in Luteolin and Effect on Radical Scavenging.

Luteolin differs as a radical scavenger dramatically from apigenin in response to Cu(II) coordination despite a minor structural difference. Coordination of Cu(II) increases the radical scavenging efficiency of luteolin, especially at low pH, while decreases the efficiency of apigenin at both low and higher pH as studied by ABTS•+ radical scavenging. Luteolin forms a 1:1 complex with Cu(II) binding to 4-carbonyl and 5-phenol for pH <6 and to 3',4'-catechol for pH >6. Apigenin forms a 1:2 complex independent of pH coordinated to 4-carbonyl and 5-hydroxylyl. Cu(II) coordinated to luteolin, as studied by pH jump stopped-flow, translocates with rate constants of 11.1 ± 0.3 s-1 from 4,5 to 3',4' sites and 1.0 ± 0.1 s-1 from 3',4' to 4,5 sites independent of Cu(II) concentration, pointing toward the dissociation of Cu(II) from an intermediate with two Cu(II) coordination as rate determining. 3',4'-Catechol is suggested to be a switch for Cu(II) translocation with deprotonation initiating 4,5 to 3',4' translocation and protonation initiating 3',4' to 4,5 translocation. For dicoordinated apigenin, the coordination symmetry balances an electron withdrawal effect of Cu(II) resulting in a decrease of phenol acidity and less radical scavenging efficiency compared to parent apigenin. Compared to that of parent luteolin, the radical scavenging rate of both 4,5 and 3',4' Cu(II)-coordinated luteolin is enhanced through increased phenol acidity by electron withdrawal by Cu(II), as confirmed by density functional theory (DFT) calculations. Coordination and translocation of Cu(II) accordingly increases the antioxidant activity of luteolin at pH approaching the physiological level and is discovered as a novel class of natural molecular machinery derived from plant polyphenols, which seems to be of importance for protection against oxidative stress.

Cisplatin and photodynamic therapy exert synergistic inhibitory effects on small-cell lung cancer cell viability and xenograft tumor growth.

Lung cancer is the leading cause of cancer death worldwide. Small-cell lung cancer (SCLC) is an aggressive type of lung cancer that shows an overall 5-year survival rate below 10%. Although chemotherapy using cisplatin has been proven effective in SCLC treatment, conventional dose of cisplatin causes adverse side effects. Photodynamic therapy, a form of non-ionizing radiation therapy, is increasingly used alone or in combination with other therapeutics in cancer treatment. Herein, we aimed to address whether low dose cisplatin combination with PDT can effectively induce SCLC cell death by using in vitro cultured human SCLC NCI-H446 cells and in vivo tumor xenograft model. We found that both cisplatin and PDT showed dose-dependent cytotoxic effects in NCI-H446 cells. Importantly, co-treatment with low dose cisplatin (1 µM) and PDT (1.25 J/cm2) synergistically inhibited cell viability and cell migration. We further showed that the combined therapy induced a higher level of intracellular ROS in cultured NCI-H446 cells. Moreover, the synergistic effect by cisplatin and PDT was recapitulated in tumor xenograft as revealed by a more robust increase in the staining of TUNEL (a marker of cell death) and decrease in tumor volume. Taken together, our findings suggest that low dose cisplatin combination with PDT can be an effective therapeutic modality in the treatment of SCLC patients.

Human behaviors determine health: strategic thoughts on the prevention of chronic non-communicable diseases in China.

BACKGROUND: In the last three decades, people's living standards have significantly increased along with the rapid growth of the national economy of China. However, the prevalence of unhealthy behaviors and unfavorable lifestyles (e.g., smoking, excessive use of alcohol, physical inactivity, and unhealthy diets) also steadily increased, which may contribute to the growing epidemic of chronic non-communicable diseases (CNCDs) such as diabetes, coronary heart disease, stroke, and cancers. PURPOSE: To briefly summarize the major studies from China concerning epidemic and burden of CNCDs and unhealthy lifestyles, and propose intervention strategies toward unhealthy lifestyles and behaviors aiming for effective control of the growing epidemic of CNCDs in China. METHODS: We first review the major national studies addressing the epidemic and burden of CNCDs and unhealthy behaviors in China. Then, we aim to develop the preventive strategies against the increasing epidemic of CNCDs by focusing on the intervention campaign toward health unfavorable behaviors and lifestyles. RESULTS: CNCDs have posed major challenges to public health and the ongoing reform of health care system in China. Unhealthy lifestyles and behaviors (e.g., smoking, excessive alcohol consumpsion, physical inactivity, and imbalanced diets) are responsible for the growing epidemic of CNCDs. Adherence to healthy behaviors and lifestyles is critical for maintaining physical and mental health. CONCLUSION: Active implementation of the population-wide intervention program of health education and promotion by targeting unhealthy behaviors and lifestyles may help to constrain the growing epidemic of CNCDs in China.