Tight junctions (TJs) play a key role in regulating permeability to liquids, ions and larger solutes through the paracellular route. To demonstrate TJ structure changes by measuring paracellular flux is challenging for understanding biological functions of tight junction and designing delivery system for highly hydrophilic macromolecular drugs. In the present study, we tested two long wavelength emitting silver nanoclusters (AgNCs), Ag2S(BSA)-NCs (λex/em at 500/1050 nm) and Ag(GSH)-NCs (λex/em at 488/640 nm), for their suitability as novel paracellular permeation indicators on a MDCK monolayer. Ag2S(BSA)-NCs exhibited marginal cytotoxicity and passed through the cell monolayer exclusively via the paracellular pathway. However, Ag(GSH)-NCs could be taken inside the cells possibly through endocytosis. AgNCs together with Eu-DTPA were used in the double probe strategy for detecting the change of TJ pore path parameters (i.e. pore size r and retention capacity ε/τ) upon TJ opening with EDTA or vanadyl acetylacetonates, respectively. The AgNCs/Eu-DTPA probe set was found to give the same results as our previous work using the short wavelength emitting AuNCs and Eu-DTPA probe set, suggesting future potential applications of AgNCs to the in vivo studies of TJ alternations upon stresses. This work reinforced the use of a double probe set for study of the TJ structure change.

Based on electron and proton transfer events occurring in biological respiration, a mitochondria-based biocell is constructed by combining with artificial nanochannels. In this biocell, mitochondria transfer electrons to the working electrode and pump protons into the electrolyte through the tricarboxylic acid cycle. The nanochannels provide passages for protons to transport along the transmembrane concentration gradient to consume electrons on the counter electrode, forming a continuous and stable current. Furthermore, the proton transmembrane transport behavior could be modulated by regulating the permeability area and surface charge of nanochannels. A high-performance biocell is obtained when equipped with the optimized nanochannels, which produces a current of ≈3.1 mA cm−2, a maximum power of ≈0.91 mW cm−2, and a lifetime over 60 h. This respiratory-based biocell shows great potential for the efficient utilization of bioelectricity.

•Amyloid-modulating dimethylphenylenediamine was conjugated into vanadyl complexes.•The new vanadyl complexes showed reduced toxicity and improved anti-diabetic effects.•The new vanadyl complexes up-regulated peroxisome proliferator-activated receptor α/γ.•The new vanadyl complexes affected Tau phosphorylation in brain.Vanadium compounds are promising anti-diabetic agents. However, reducing the metal toxicity while keeping/improving the hypoglycemic effect is still a big challenge towards the success of anti-diabetic vanadium drugs. To improve the therapeutic potency using the anti-oxidative strategy, we synthesized new N,N-dimethylphenylenediamine (DMPD)-derivatized nitrilotriacetic acid vanadyl complexes ([VO(dmada)]). The in vitro biological evaluations revealed that the DMPD-derivatized complexes showed improved antioxidant capacity and lowered cytotoxicity on HK-2 cells than bis(maltolato)oxidovanadium (IV) (BMOV). In type II diabetic mice, [VO(p-dmada)] (0.15 mmol kg− 1/day) exhibited better hypoglycemic effects than BMOV especially on improving glucose tolerance and alleviating the hyperglycemia-induced liver damage. These insulin enhancement effects were associated with increased expression of peroxisome proliferator-activated receptor α and γ (PPARα/γ) in fat, activation of Akt (v-Akt murine thymoma viral oncogene)/PKB (protein kinase-B) in fat and liver, and inactivation of c-Jun NH2-terminal protein kinases (JNK) in liver. Moreover, [VO(p-dmada)] showed no tissue toxicity at the therapeutic dose in diabetic mice and the oral acute toxicity (LD50) was determined to be 1640 mg kg− 1. Overall, the experimental results indicated that [VO(p-dmada)] can be a potent insulin enhancement agent with improved efficacy-over- toxicity index for further drug development. In addition, the results on brain Tau phosphorylation suggested necessary investigation on the effects of vanadyl complexes on the pathology of the Alzheimer's disease in the future.New N,N-dimethylphenylenediamine-derivatized nitrilotriacetic acid vanadyl complexes exhibited low toxicity and improved anti-diabetic effects than bis(maltolato)oxidovanadium in db/db diabetic mice.Download high-res image (176KB)Download full-size image

As an emerging nanomaterial, graphene quantum dots (GQDs) have shown enormous potential in theranostic applications. However, many aspects of the biological properties of GQDs require further clarification. In the present work, we prepared two sizes of GQDs and for the first time investigated their membrane permeabilities, one of the key factors of all biomedical applications, and transport mechanisms on a Madin Darby Canine Kidney (MDCK) cell monolayer. The experimental results revealed that under ∼300 mg L−1, GQDs were innoxious to MDCK and did not affect the morphology and integrity of the cell monolayer. The Papp values were determined to be 1–3 × 10−6 cm s−1 for the 12 nm GQDs and 0.5–1.5 × 10−5 cm s−1 for the 3 nm GQDs, indicating that the 3 nm GQDs are well-transported species while the 12 nm GQDs have a moderate membrane permeability. The transport and uptake of GQDs by MDCK cells were both time and concentration-dependent. Moreover, the incubation of cells with GQDs enhanced the formation of lipid rafts, while inhibition of lipid rafts with methyl-β-cyclodextrin almost eliminated the membrane transport of GQDs. Overall, the experimental results suggested that GQDs cross the MDCK cell monolayer mainly through a lipid raft-mediated transcytosis. The present work has indicated that GQDs are a novel, low-toxic, highly-efficient general carrier for drugs and/or diagnostic agents in biomedical applications.

Vanadium compounds exhibit effective hypoglycemic activity in both type I and type II diabetes mellitus. However, there was one argument that the hypoglycemic action of vanadium compounds could be attributable to the suppression of feeding—one common toxic aspect of vanadium compounds. To clarify this question, we investigated in this work the effect of a vanadyl complex, BSOV (bis((5-hydroxy-4-oxo-4H-pyran-2-yl)methyl-2-hydroxy-benzoatato) oxovanadium (IV)), on diabetic obese (db/db) mice at a low dose (0.05 mmol/kg/day) when BSOV did not inhibit feeding. The experimental results showed that this dose of BSOV effectively normalized the blood glucose level in diabetic mice without affecting the body weight growth. Western blotting assays on the white adipose tissue of db/db mice further indicated that BSOV treatment significantly improved expression of peroxisome proliferator-activated receptor γ (PPARγ) and activated AMP-activated protein kinase (AMPK). In addition, vanadium treatment caused a significant suppression of phosphorylation of c-Jun N-terminal protein kinase (JNK), which plays a key role in insulin-resistance in type II diabetes. This is the first evidence that the mechanism of insulin enhancement action involves interaction of vanadium compounds with JNK. Overall, the present work indicated that vanadium compounds exhibit antidiabetic effects irrelevant to food intake suppression but by modulating the signal transductions of diabetes and other metabolic disorders.

Vanadium compounds are promising agents in the therapeutic treatment of diabetes; however, their mechanism of action has not been clearly elucidated. The current study investigated the effects of vanadium compounds, vanadyl acetylacetonate [VIVO(acac)2] and sodium metavanadate (NaVVO3), on peroxisome proliferator-activated receptors (PPARs), especially PPARγ, which are important targets of anti-diabetic drugs. Our experimental results revealed that treatment of NIT-1 β-pancreas cells with vanadium compounds resulted in PPARγ activation and elevation of PPARγ protein levels. Vanadium compounds did not increase PPARγ transcription but ameliorated PPARγ degradation induced by inflammatory stimulators TNF-α/IL-6. Vanadium compounds induced binding of PPARγ to heat shock protein (Hsp60). This PPARγ-Hsp60 interaction might cause inhibition of PPARγ degradation, thus elevating the PPARγ level. In addition, modulation of PPARγ phosphorylation was also observed upon vanadium treatment. The present work demonstrated for the first time that vanadium compounds are novel PPARγ modulators. The results may provide new insights for the mechanism of anti-diabetic action of vanadium compounds.

Vanadium compounds are promising agents in the therapeutic treatment of diabetes mellitus, but their mechanism of action has not been fully elucidated. The current work investigated the effects of vanadyl acetylacetonate, VO(acac)2, on peroxisome-proliferator-activated receptor γ (PPARγ) and adiponectin, which are important targets of antidiabetic drugs. The experimental results revealed that vanadyl complexes increased the expression and multimerization of adiponectin in differentiated rat adipocytes. VO(acac)2 caused activation of p38 mitogen-activated protein kinase (MAPK) and AMP-activated protein kinase (AMPK) and elevation of PPARγ levels. The specific inhibitors SB203580 (p38 MAPK inhibitor) and T0070907 (PPARγ inhibitor) decreased the expression of adiponectin; however, compound C (AMPK inhibitor) did not significantly reduce the expression of adiponectin. In addition, vanadyl complexes induced protein–protein interaction between PPARγ and a vanadium-binding chaperone, heat shock protein 60 kDa. Overall, our results suggest that vanadyl complexes may upregulate PPARγ by suppressing PPARγ degradation, and thus stimulate adiponectin expression and multimerization. The present work has provided new insights into the mechanism of the antidiabetic actions of vanadium compounds.

Gadolinium (Gd) compounds have important applications as MRI contrast and potential anticancer agents. The present study investigated the mechanisms of the proapoptotic effect of gadolinium chloride (GdCl3) on hepatoblastoma cell line (Hep G2) tumor cells. The experimental results indicated that GdCl3 induced apoptosis of Hep G2 at high concentration and with long time incubation; however, unlike the actions on normal cell lines, GdCl3 did not cause any oxidative stress on tumor cells. Cytochrome c (Cyt c) and apoptosis inducing factor release, Bax translocation, collapse of mitochondria membrane potential, caspase 3 and 8 activation, and Bid cleavage were observed along with a sustained activation of extracellular signal-regulated kinase (ERK) and c-Jun NH2 terminal kinase (JNK). Addition of ERK and JNK inhibitor attenuated the effect of GdCl3 induced apoptosis and Cyt c release. All the results suggested a novel mechanism that GdCl3 induced Hep G2 cell death through intrinsic and external death pathways without significant elevation of reactive oxygen species generation. The present work provided new insight to understand the mechanisms of the biological effects of GdCl3 and implications for the development of anticancer Gd agents.

To improve the nutritional value of chickpea food, selenium (Se)-rich chickpea sprouts were produced by germination of chickpea seeds for 6 days at 28 centigrade in the presence of various concentrations of Na2SeO3 in germination solution. High concentrations of selenite were found to inhibit the growth of chickpea sprout and the biosynthesis of isoflavones formononetin and biochanin A. However, chickpea sprouts could tolerate up to ∼50 mg/L of Na2SeO3, under which condition the product chickpea sprouts contained a high Se content (2.14 μg/g dry weight) and a moderate high content of isoflavones (601.56 μg biochanin A/g dry weight and 578.11 μg formononetin/g dry weight). Se was incorporated in chickpea sprout in the form of selenomethionine. Thus, Se-enriched chickpea sprouts may serve as a convenient dietary source of Se and of isoflavones, including formononetin and biochanin A.

Vanadium complexes are potent hypoglycemic agents and of great potential for therapeutical treatment of diabetes. In the present work, a novel vanadium compound, bis ((5-hydroxy-4-oxo-4H-pyran-2-yl)methyl benzoatato) oxovanadium (IV) (BBOV) has been synthesized. Treatment of STZ-induced diabetic rats with BBOV restored the blood glucose to normal level and ameliorated glucose tolerance. The hypoglycemic effect of BBOV is similar to that of bis (maltolato) oxovanadium but is less toxic in median lethal dose. Overall, the present work will provide useful information for further development of new anti-diabetic vanadium compounds.

The molecular mechanisms of vanadium toxicity suggest that incorporation of antioxidant groups in the structure of vanadium complexes could be a preferable strategy in designing novel hypoglycemic vanadium complexes with proper efficacy and safety. By conjugating a pyrone skeleton to provide a coordination group and antioxidative motifs, we synthesized a novel complex of bis ((5-hydroxy-4-oxo-4 H-pyran-2-yl) methyl 2-hydroxy- benzoatato) oxovanadium (IV) (BSOV). Evaluation of the anti-diabetic effects of BSOV using streptozotocin (STZ)-induced diabetic rats with bis (maltolato) oxovanadium (BMOV) as a positive control showed that BSOV effectively lowered blood glucose level, ameliorated damages of hepatic and renal function in diabetic rats and improved lipid metabolism. The signs of potential alteration of renal function caused by BSOV and BMOV were observed and are discussed. Overall, the experimental results suggest BSOV as a potent hypoglycemic agent and further studies using this strategy for anti-diabetic agents.Study on the rational design and synthesis of a novel complex, BSOV, and the evaluation of its anti-diabetic effects.

Endoplasmic reticulum (ER) stress induced by free fatty acids (FFA) is important to β-cell loss during the development of type 2 diabetes. To test whether vanadium compounds could influence ER stress and the responses in their mechanism of antidiabetic effects, we investigated the effects and the mechanism of vanadyl bisacetylacetonate [VO(acac)2] on β cells upon treatment with palmitate, a typical saturated FFA. The experimental results showed that VO(acac)2 could enhance FFA-induced signaling pathways of unfolded protein responses by upregulating the prosurvival chaperone immunoglobulin heavy-chain binding protein/78-kDa glucose-regulated protein and downregulating the expression of apoptotic C/EBP homologous protein, and consequently the reduction of insulin synthesis. VO(acac)2 also ameliorated FFA-disturbed Ca2+ homeostasis in β cells. Overall, VO(acac)2 enhanced stress adaption, thus protecting β cells from palmitate-induced apoptosis. This study provides some new insights into the mechanisms of antidiabetic vanadium compounds.

Gadolinium (Gd) and its complexes are utilized widely in industrial and clinical diagnoses. As a rare earth metal ion, free gadolinium (Gd3+) in the human body poses neurotoxic risks during its in vivo release and retention. In the central nervous system, astrocytes play a pivotal role in processing toxic metal ions. The present study evaluates the effects of Gd on cellular calcium homeostasis, a common mechanism that causes cell death, and on unfolded protein responses (UPRs), a mechanism for cell survival in response to toxic stimuli in mammalian cells. The experimental results indicate that the influx of extracellular Ca2+ increases greatly after the exposure of astrocytes to Gd; however, no cell deaths were observed. Further evidence suggests the up-regulated expression of the endoplasmic reticulum (ER)-resident chaperone protein GRP78 by ER stress-mediated signal transductions, specifically the activation of ATF6, eIF2a, and IRE1. These results suggest that Gd promotes Ca2+ influx, thus triggering UPRs, which can be closely associated to the resistance of astrocytes to Gd-induced cytotoxicity.

Vanadium compounds have been regarded as promising in therapeutic treatment of diabetes and in cancer prevention. In the present work, we studied the effects of vanadium compounds on mitochondria to investigate the mechanisms of toxicity. Mitochondria were isolated from rat liver and incubated with a variety of vanadium compounds, i.e. VOSO4, NaVO3, and vanadyl complexes with organic ligands. Our studies indicated that VO2+, VO3-, VO(acac)2 and VOcit (1–100 μM) could induce mitochondrial swelling in a concentration dependent manner and disrupt mitochondrial membrane potential (Δψm) in a time dependent manner, which is quite different from the rapid Δψm collapse caused by Ca2+ or CCCP (carbonyl cyanide m-chlorophenylhydrazone, a mitochondrial uncoupling reagent). Release of cytochrome c (Cyt c) was observed and could be inhibited by cyclosporin A (CsA), an inhibitor of the mitochondrial permeability transition pore (PTP). Interestingly, VOdipic caused release of Cyt c without mitochondrial swelling and Δψm disruption, an action previously only observed on the Bax protein, suggesting a potentially role of VOdipic in regulating PTP opening. In addition, all the vanadium compounds tested stimulated mitochondrial production of reactive oxygen species (ROS). Antioxidants, i.e. vitamin C and E, significantly delayed the Δψm disruption. Overall, our experimental evidence indicated vanadium compounds exhibited multiple actions on mitochondria. Vanadium compounds did induce oxidative stress on mitochondrial and thus caused PTP opening, which led to collapse of Δψm and Cyt c release as the initiation of cell apoptosis.

Calmodulin (CaM) is a multifunctional Ca2+-binding protein regulating the activity of many enzymes in response to fluctuation of the intracellular Ca2+ level. It has been shown that a CaM Q41C/K75C mutant (CaMSS) with a disulfide bond in the N-terminal domain exhibits greatly reduced affinity to Ca2+. In the present study, the experimental results revealed a unique metal binding pattern in CaMSS towards La3+ and Ca2+ separately: the mutant protein binds Ca2+ at site I, III and IV; however, it binds La3+ at site I, II and IV. A putative mechanism was proposed which is the conformation of site II (or site III) of CaMSS could be altered and thus loses its metal ion affinity in response to metal binding in the opposite terminal domain possibly through the long range domain interaction. The present work may offer new perspectives for understanding the mechanisms of specific metal ion affinity in CaM and for CaM-based protein design.

Gadolinium (Gd3+) complexes are important contrast agents in medical magnetic resonance imaging (MRI) and of great potential value in brain research. In order to better understand the mechanisms of the action of Gd3+ on neurons in the complex central nervous system (CNS), the neurotoxic actions of GdCl3 have been investigated in both neuron monoculture and astrocyte-neuron co-culture systems. Measurements of lactate dehydrogenase release showed that GdCl3 causes significant cell death of monocultured neurons as a result of reactive oxygen species (ROS) generation and down-regulation of brain-derived neurotrophic factor (BDNF). However, GdCl3 does not affect the viability and BDNF expression of astrocytes. Both co-culturing of neurons with astrocytes and addition of BDNF ameliorated GdCl3-induced neurotoxicity by decreasing ROS generation and facilitating recovery of BDNF levels. The results obtained suggest that astrocytes in the CNS may protect neurons from GdCl3-induced impairment through secreting BDNF and thus up-regulating BDNF expression and interfering with Gd3+-induced cell signaling in neurons. A possible molecular mechanism is suggested which should be helpful in understanding the neurotoxic actions of gadolinium probes.

Ca2+ binds to calmodulin (CaM) and triggers the interaction of CaM with its target proteins; CaM binding proteins (CaMBPs) can also regulate the metal binding to CaM. In the present paper, La3+ binding to CaM was studied in the presence of the CaM binding peptides, Mastoparan (Mas) and Mas X, using ultrafiltration and titration of fluorescence. Ca2+ binding was used as an analog to understand La3+ binding in intact CaM and isolated N/C-terminal CaM domain of metal-CaM binary system and metal-CaM–CaMBPs ternary system. Mas/Mas X increased binding affinity of La3+ to CaM by 0.5 ∼ 3 orders magnitude. The metal ions binding affinity to the C-terminal or the N-terminal CaM domain suggested that in the first phase of binding process both Ca2+ and La3+ bind to C-terminal of CaM in the presence of Mas/Mas X. In the presence of CaM binding peptides, La3+ binding preference was substantially altered from the metal-CaM binary system where La3+ slightly preferred binding to the N-terminal sites of CaM. Our results will be helpful in understanding La3+ interactions with CaM in the biological systems.

Vanadium compounds have been recognized for their hypoglycemic effects; however, potential short and long-term vanadium toxicity has slowed the acceptance for therapeutic use. In the present work, three batches of vanadium-enriched chickpea sprout (VCS) were prepared by incubating chickpea seeds in presence of 200, 100, and 50 μg/ml of sodium orthovanadate (SOV). The effects of oral administration of chickpea sprout (CS) and VCS food for 8 weeks on streptozotocin-induced (STZ) diabetic rats were investigated. Both CS and VCS food was found to ameliorate some hyperglycemic symptoms of the diabetic rats, i.e. improve lipid metabolism, decrease blood glucose level, prevent body weight loss, and reduce impairment of diabetic related spatial learning and memory. Serum insulin was substantially elevated in treated diabetic rats, which is probably one important reason for the hypoglycemic effect. Compared with CS alone, VCS100 food exhibited remarkably enhanced effectiveness in alleviating diabetes induced hyperglycemia and memory loss. Moreover, vanadium-enriched chickpeas appeared to abolish the vanadium induced toxicity associated with administration of this metal for diabetes during the 8-week study period. This study suggested further work of the vanadium speciation in CS and novel hypoglycemic mechanism for the antidiabetic activity of vanadium agents. Vanadium containing (VCS) food could be a dietary supplement for the diabetic status.

Several vanadium compounds have been known for the hypoglycemic and anticancer effects. However, the mechanisms of the pharmacological and toxicological effects were not clear. In this work, we investigated the potential targets of vanadium in mitochondria. Vanadyl ions were found to bind to mitochondria from rat liver with a stoichiometry of 244±58 nmol/mg protein and an apparent dissociation constant (Kd) of (2.0±0.8)×10−16 mol/L. Using size exclusion chromatography, a vanadium-binding protein was isolated and identified to be the 60-kDa heat shock protein (HSP60) by mass spectrometry analysis and immunoassays. Additionally, binding of vanadyl ions was found to result in depolymerization of homo-oligomeric HSP60 (GroEL). HSP60 is an indispensable molecular chaperone and involved in many kinds of pathogenesis of inflammatory and autoimmune diseases, e.g. type 1 diabetes. Our results suggested that HSP60 could be a novel important target involved in the biological and/or toxicological effects of vanadium compounds.

Vanadium (III, IV, V)-dipicolinate complexes with different redox properties were selected to investigate the structure-property relationship of insulin-mimetic vanadium complexes for membrane permeability and gastrointestinal (GI) stress-related toxicity using the Caco-2 cell monolayer model. The cytotoxicity of the vanadium complexes was assayed with 3-(4,5-dimethylthiazoyl-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assays and the effect on monolayer integrity was measured by the trans-epithelial electric resistance (TEER). The three vanadium complexes exhibited intermediate membrane permeability (Papp = 1.4–3.6 × 10−6 cm/s) with low cellular accumulation level (<1%). The permeability of all compounds was independent of the concentration of vanadium complexes and excess picolinate ligands. Both V(III) and V(V)-dipicolinate complexes induced 3–4-fold greater reactive oxygen and nitrogen species (RONS) production than the V(IV)-dipicolinate complex; while the vanadium (III)-dipicolinate was 3-fold less damaging to tight junction of the Caco-2 cell monolayer. Despite the differences in apparent permeability, cellular accumulation, and capacity to induce reactive oxygen and nitrogen species (RONS) levels, the three vanadium complexes exhibited similar cytotoxicity (IC50 = 1.7–1.9 mM). An ion pair reagent, tetrabutylammonium, increased the membrane apparent permeability by 4-fold for vanadium (III and IV)-dipicolinate complexes and 16-fold for vanadium (V)-dipicolinate as measured by decrease in TEER values. In addition, the ion pair reagent prevented damage to monolayer integrity. The three vanadium (III, IV, V)-dipicolinate complexes may pass through caco-2 monolayer via a passive diffusion mechanism. Our results suggest that formation of ion pairs may influence compound permeation and significantly reduce the required dose, and hence the GI toxicity of vanadium-dipicolinate complexes.

S-Adenosylhomocysteine (AdoHcy) hydrolase regulates biomethylation and homocysteine metabolism. It has been proposed to be a copper binding protein playing an important role in copper transport and distribution. In the present work, the kinetics of binding and releasing of copper ions was studied using fluorescence method. The dissociation constant for copper ions with AdoHcy hydrolase was determined by fluorescence quenching titration and activity titration methods using ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), and glycine as competitive chelators. The experimental results showed that copper ions bind to AdoHcy hydrolase with a Kd of ∼10−11 M. The association rate constant was determined to be 7 × 106 M−1 s−1. The releasing of copper ions from the enzyme was found to be biphasic with a k(1) of 2.8 × 10−3 s−1 and k(2) of 1.7 × 10−5 s−1. It is suggested that copper ions do not bind to the substrate binding sites because the addition of adenine substrate did not compete with the binding of copper to AdoHcy hydrolase. Interestingly, it was observed that EDTA could bind to AdoHcy hydrolase with a dissociation constant of K1=8.0×10−5 M and result in an increased affinity (Kd=∼10−17 M) of binding of copper ions to the enzyme.

The molecular mechanisms of vanadium toxicity suggest that incorporation of antioxidant groups in the structure of vanadium complexes could be a preferable strategy in designing novel hypoglycemic vanadium complexes with proper efficacy and safety. By conjugating a pyrone skeleton to provide a coordination group and antioxidative motifs, we synthesized a novel complex of bis ((5-hydroxy-4-oxo-4 H-pyran-2-yl) methyl 2-hydroxy- benzoatato) oxovanadium (IV) (BSOV). Evaluation of the anti-diabetic effects of BSOV using streptozotocin (STZ)-induced diabetic rats with bis (maltolato) oxovanadium (BMOV) as a positive control showed that BSOV effectively lowered blood glucose level, ameliorated damages of hepatic and renal function in diabetic rats and improved lipid metabolism. The signs of potential alteration of renal function caused by BSOV and BMOV were observed and are discussed. Overall, the experimental results suggest BSOV as a potent hypoglycemic agent and further studies using this strategy for anti-diabetic agents.Study on the rational design and synthesis of a novel complex, BSOV, and the evaluation of its anti-diabetic effects.Download full-size image

•A new method for nanomolar NAC determination with LOD of 50 nM was reported.•The combined mechanism for NAC quenching with static dominating was suggested.•DNA-Ag NC structure changed with addition of NAC, proved by spectroscopic studies.In this work, we reported a new, simple and sensitive method for determination of N-acetylcysteine (NAC) based on quenching of the red fluorescence of oligonuleotide-protected silver nanoculsters (Ag NCs) with the quantum yield of 68.3 ± 0.3%. This method was successfully used for the assay of NAC granules presenting a linear range from 100 nM to 1200 nM (LOD of 50 nM) with minimal interferences from potential coexisting substances. It is for the first time that quenching performance of the thiol-containing compound was found to follow a non-linear Stern–Volmer profile, indicative of a complicated quenching mechanism with static quenching dominating, in which DNA-template of Ag NCs was partly replaced by NAC, as elucidated by spectral investigations. This study extended the analytical application of silver nanoclusters as well as provided a more insightful understanding of the quenching mechanism of thiol-compounds on the fluorescence of Ag NCs.Download full-size image