Revealing the missing puzzle piece of concentration in regulating Zn electrodeposition.

Despite achievements in suppressing dendrites and regulating Zn crystal growth, secondary aqueous Zn batteries are still rare in the market. Existing strategies mainly focus on electrode modification and electrolyte optimization, while the essential role of ion concentration in liquid-to-solid electrodeposition is neglected for a long time. Herein, the mechanism of concentration regulation in Zn electrodeposition is investigated in depth by combining electrochemical tests, post hoc characterization, and multiscale simulations. First, initial Zn electrodeposition is thermodynamically controlled epitaxial growth, whereas with the rapid depletion of ions, the concentration overpotential transcends the thermodynamic influence to kinetic control. Then, the evolution of the morphology from 2D sheets to 1D whiskers due to the concentration change is insightfully revealed by the morphological characterization and phase-field modeling. Furthermore, the depth of discharge (DOD) results in large concentration differences at the electrode-electrolyte interface, with a mild concentration distribution at lower DOD generating (002) crystal plane 2D sheets and a heavily varied concentration distribution at higher DOD yielding arbitrarily oriented 3D blocks. As a proof of concept, relaxation is introduced into two systems to homogenize the concentration distribution, revalidating the essential role of concentration in regulating electrodeposition, and two vital factors affecting the relaxation time, i.e., current density and electrode distance, are deeply investigated, demonstrating that the relaxation time is positively related to both and is more sensitive to the electrode distance. This work contributes to reacquainting aqueous batteries undergoing phase transitions and reveals a missing piece of the puzzle in regulating Zn electrodeposition.

Asymmetric Electrode Design for High-Area Capacity and High-Energy Efficiency Hybrid Zn Batteries.

Compared to Zn-air batteries, by integrating Zn-transition metal compound reactions and oxygen redox reactions at the cell level, hybrid Zn batteries are proposed to achieve higher energy density and energy efficiency. However, attaining relatively higher energy efficiency relies on controlling the discharge capacity. At high area capacities, the proportion of the high voltage section can be neglected, resulting in a lower energy efficiency similar to that of Zn-air batteries. Here, a high-loading integrated electrode with an asymmetric structure and asymmetric wettability is fabricated, which consists of a thick nickel hydroxide (Ni(OH)2) electrode layer with vertical array channels achieving high capacity and high utilization, and a thin NiCo2O4 nanopartical-decorated N-doped graphene nanosheets (NiCo2O4/N-G) catalyst layer with superior oxygen catalytic activity. The asymmetric wettability satisfies the wettability requirements for both Zn-Ni and Zn-air reactions. The hybrid Zn battery with the integrated electrode exhibits a remarkable peak power density of 141.9 mW cm-2, superior rate performance with an energy efficiency of 71.4% even at 20 mA cm-2, and exceptional cycling stability maintaining a stable energy efficiency of ≈84% at 2 mA cm-2 over 100 cycles (400 h).

Reacquainting the Sudden-Death and Reaction Routes of Li-O2 Batteries by Ex Situ Observation of Li2O2 Distribution Inside a Highly Ordered Air Electrode.

The unclear Li2O2 distribution inside an air electrode stems from the difficulty of conducting observation techniques inside a porous electrode. In this work, an integrated air electrode is prepared with highly ordered channels. The morphological composition and distribution of Li2O2 inside the real air electrode are clearly observed for the first time. The results show that the toroidal Li2O2 is constrained by the channel size and exhibits a larger diameter on the separator side at high currents. In contrast to the reported single-factor experiments, the coupling effects of charge transfer impedance and concentration polarization on sudden death are analyzed in-depth at low and high currents. The growth model suggests that toroidal Li2O2 exhibits a high dependence on the electrode surface structure. A new route is proposed in which the Li2O2/electrode interface of a toroid is controlled partially by the second single-electron reduction.

Self-Activated Formation of Hierarchical Co3 O4 Nanoflakes with High Valence-State Conversion Capability for Ultrahigh-Capacity Zn-Co Batteries.

Cobalt-based materials are attracting increasing interest in alkaline Zn batteries due to the high theoretical capacity. However, the practical utilization is restricted by the poor microstructure and insufficient valence-state conversion. Herein, a self-activated formation of hierarchical Co3 O4 nanoflakes with high valence-state conversion capability is designed. This electrode not only exhibits the optimized microstructure with large reaction surfaces, but also shows excellent valence-state conversion capability. Consequently, this battery delivers an ultrahigh capacity of 481.4 mAh g-1 and an energy density of 818.3 Wh kg-1 based on the active material, which shines among reported Co-based materials. Besides, the capacity can retain 41.9% with even 20× current density increases, and it can operate with a capacity decay of 20% after the 1000th cycle. This strategy greatly enhances the performance and durability of integrated air electrodes, raising the attention of boundary design for other electrochemical energy conversion and storage devices.

S-Allylmercapto-N-acetylcysteine ameliorates elastase-induced chronic obstructive pulmonary disease in mice via regulating autophagy.

Autophagy-impairment is involved in the pathological process of chronic obstructive pulmonary disease (COPD), and relates to inflammation and emphysema in lung injury. This study aimed to elucidate the protective effect of S-Allylmercapto-N-acetylcysteine (ASSNAC) against COPD via regulating the autophagy. Firstly, porcine pancreatic elastase (PPE)-induced COPD model in A549 cells was established, and ASSNAC was verified to alleviate the autophagy-impairment from the results of western blotting analysis of LC3BⅡ/Ⅰ and monodansylcadaverine (MDC) staining of autophagosome. Secondly, Balb/c mice were stimulated by PPE to induce the COPD model in vivo. The histological analysis of lung tissues presented that ASSNAC could alleviate the lung injury induced by PPE. Thirdly, the secretions of NO, TNF-α and IL-1ß in serum and BALF were reduced by ASSNAC compared with the PPE group. Finally, the mechanism of therapeutic effects of ASSNAC against COPD through regulating the autophagy-impairment was clarified. That is, ASSNAC inhibits the phosphorylation of PI3K/Akt/mTOR signaling pathways. In a word, this research provides a reference for ASSNAC to be an effective drug for pulmonary diseases.

S-allylmercaptocysteine inhibits mucin overexpression and inflammation via MAPKs and PI3K-Akt signaling pathways in acute respiratory distress syndrome.

Cytokine storm is an important cause of acute respiratory distress syndrome and multiple organ failure. Excessive secretion and accumulation of mucins on the surface of airway cause airway obstruction and exacerbate lung infections. MUC5AC and MUC5B are the main secreted mucins and overexpressed in various inflammatory responses. S-allylmercaptocysteine, a water-soluble organic sulfur compound extracted from garlic, has anti-inflammatory and anti-oxidative effects for various pulmonary diseases. The aim of this work was to investigate the therapeutic effects of SAMC on mucin overproduction and inflammation in 16HBE cells and LPS-induced ARDS mice. Results show that SAMC treatment ameliorated inflammatory cell infiltration and lung histopathological changes in the LPS-induced ARDS mice. SAMC also inhibited the expressions of MUC5AC and MUC5B, decreased the production of pro-inflammatory markers (IL-6, TNF-α, CD86 and IL-12) and increased the production of anti-inflammatory markers (IL-10, CD206 and TGF-ß). These results confirm that SAMC had potential beneficial effects on suppressed hyperinflammation and mucin overexpression. Furthermore, SAMC exerted the therapeutic effects through the inhibition of phosphorylation of MAPKs and PI3K-Akt signaling pathways in the 16HBE cells and mice. Overall, our results demonstrate the effects of SAMC on the LPS-induced mucin overproduction and inflammation both in the 16HBE cells and mice.

Preparation of Ergosterol-Loaded Nanostructured Lipid Carriers for Enhancing Oral Bioavailability and Antidiabetic Nephropathy Effects.

In our previously studies, we confirmed that ergosterol could ameliorate diabetic nephropathy by suppressing the proliferation of mesangial cells and the accumulation of extracellular matrix (ECM). However, the therapeutic application of ergosterol may be confined due to poor aqueous solubility and low oral bioavailability. We aim to prepare ergosterol-loaded nanostructured lipid carriers (ERG-NLCs) to enhance the solubility and oral bioavailability of ergosterol. ERG-NLCs were prepared using glyceryl monostearate and decanoyl/octanoyl-glycerides by hot emulsification-ultrasonication method and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) analysis, entrapment efficiency (EE), and drug loading (DL) capacity studies. The prepared ERG-NLCs were spherical, with particle size of 81.39 nm and negative zeta potential of 30.77 mV. Ergosterol was successfully encapsulated in NLCs with a high EE of 92.95% and a DL capacity of 6.51%. In pharmacokinetic study, Cmax and AUC0-∞ of ergosterol in ERG-NLCs were obviously enhanced, and the relative oral bioavailability of ERG-NLCs was 277.56% higher than that of raw ergosterol. Moreover, the in vitro pharmacodynamic study indicated that ERG-NLCs inhibited high-glucose-stimulated mesangial cells over proliferation and ECM accumulation more effectively compared to raw ergosterol. In conclusion, the validated ERG-NLCs showed that NLCs mediated delivery could be used as potential vehicle to enhance solubility, oral bioavailability and therapeutic efficacy of ergosterol.

Ergosterol attenuates cigarette smoke extract-induced COPD by modulating inflammation, oxidative stress and apoptosis in vitro and in vivo.

Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). CS heightens inflammation, oxidative stress and apoptosis. Ergosterol is the main bioactive ingredient in Cordyceps sinensis (C. sinensis), a traditional medicinal herb for various diseases. The objective of this work was to investigate the effects of ergosterol on anti-inflammatory and antioxidative stress as well as anti-apoptosis in a cigarette smoke extract (CSE)-induced COPD model both in vitro and in vivo Our results demonstrate that CSE induced inflammatory and oxidative stress and apoptosis with the involvement of the Bcl-2 family proteins via the nuclear factor kappa B (NF-κB)/p65 pathway in both 16HBE cells and Balb/c mice. CSE induced epithelial cell death and increased the expression of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), malondialdehyde (MAD) and the apoptosis-related proteins cleaved caspase 3/7/9 and cleaved-poly-(ADP)-ribose polymerase (PARP) both in vitro and in vivo, whereas decreased the levels of superoxide dismutase (SOD) and catalase (CAT). Treatment of 16HBE cells and Balb/c mice with ergosterol inhibited CSE-induced inflammatory and oxidative stress and apoptosis by inhibiting the activation of NF-κB/p65. Ergosterol suppressed apoptosis by inhibiting the expression of the apoptosis-related proteins both in vitro and in vivo Moreover, the usage of QNZ (an inhibitor of NF-κB) also partly demonstrated that NF-κB/p65 pathway was involved in the ergosterol protective progress. These results show that ergosterol suppressed COPD inflammatory and oxidative stress and apoptosis through the NF-κB/p65 pathway, suggesting that ergosterol may be partially responsible for the therapeutic effects of cultured C. sinensis on COPD patients.

Metabolism and pharmacokinetics studies of allyl methyl disulfide in rats.

1. Allyl methyl disulfide (AMDS) is one of the main compounds in garlic, whereas its metabolism has not been studied yet. 2. In this work, we first identified the metabolites of AMDS in rat erythrocytes and rats using GC-MS. The transformation mechanism study among different metabolites was then conducted. The apparent kinetics of AMDS in rat erythrocytes and pharmacokinetics of AMDS by oral administration in rats were also studied. 3. The metabolic pathway study showed that AMDS was mainly metabolized in rats to allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO2) through mechanisms of reduction, methylation and oxidation. The transformation mechanism study indicated that AMDS was firstly reduced to allyl mercaptan (AM) in rat erythrocytes, and then methylated to allyl methyl sulfide (AMS) by S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and finally oxidized to AMSO and AMSO2 by liver microsomes. The half-life of AMDS in rat erythrocytes was 6.285 ± 0.014 min while the half-lives of its active metabolites AMSO and AMSO2 in vivo were 18.17 and 17.50 h, respectively. Also, the large AUCs of the two active metabolites were observed, indicating potential applications of AMDS for certain pharmacological effects.

Pharmacokinetics behaviors of l-menthol after inhalation and intravenous injection in rats and its inhibition effects on CYP450 enzymes in rat liver microsomes.

1. l-Menthol, as a kind of monocyclic terpene, is widely used in inhalation formulations, food and tobacco. The purpose of this study was to investigate the pharmacokinetic behavior of l-menthol as well as its influence on the activities of cytochrome P450 enzymes. 2. The pharmacokinetic behaviors of l-menthol after inhalation (50 mg/kg) and intravenous injection (10 mg/kg) were investigated. A rat liver microsomal model was adopted to elucidate the inhibitory effect of l-menthol on CYP1A2, CYP2C11, CYP2D1/2, CYP2D4, CYP2E1 and CYP3A1 using phenacetin, tolbutamide, omeprazole, dextromethorphan, chlorzoxazone and testosterone as probe drugs, respectively. 3. The plasma concentration reached the Cmax within 1.0 h (inhalation) and descended with the T1/2 of 8.53 and 6.69 h for inhalation and i.v. administration, respectively. IC50 for inhibition of l-menthol on CYP 450 enzymes were 4.35 µM for 2D4, 8.67 µM for 1A2, 13.02 µM for 3A1, 14.78 µM for 2D1/2, 234.9 µM for 2C11 and 525.4 µM for 2E1, respectively. 4. The results illustrate the pharmacokinetic process of l-menthol in rats and provide information for further rational applications. l-Menthol had moderate inhibitions on CYP2D4 and 1A2, which might affect the disposition of medicines primarily dependent on these pathways.

A Nucleoside/Nucleobase-Rich Extract from Cordyceps Sinensis Inhibits the Epithelial-Mesenchymal Transition and Protects against Renal Fibrosis in Diabetic Nephropathy.

Cordyceps Sinensis, a traditional Chinese medicine and a healthy food, has been used for the treatment of kidney disease for a long time. The aim of present study was to isolate a nucleoside/nucleobase-rich extract from Cordyceps Sinensis (CS-N), determine the contents of nucleosides and nucleobases, and explore its anti-diabetic nephropathy activity. CS-N was isolated and purified by using microporous resin and glucan columns and the unknown compounds were identified by using HPLC-DAD and LC-MS. The effects of CS-N on the epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) depositions, and the MAPK signaling pathway were evaluated in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-exposed HK-2 cells. CS-N significantly attenuated the abnormity of renal functional parameters, ameliorated histopathological changes, and inhibited EMT and ECM accumulation by regulating p38/ERK signaling pathways. Our findings indicate that CS-N exerts a therapeutic effect on experimental diabetic renal fibrosis by mitigating the EMT and the subsequent ECM deposition with inhibition of p38 and ERK signaling pathways.

Yifei Tongluo, a Chinese Herbal Formula, Suppresses Tumor Growth and Metastasis and Exerts Immunomodulatory Effect in Lewis Lung Carcinoma Mice.

This study was aimed to investigate the anti-tumor, anti-metastasis and immunomodulatory effects of Yifei Tongluo (YFTL), a Chinese herbal formula, in Lewis lung carcinoma mice and to explore the underlying mechanisms. LLC cells were inoculated subcutaneously in C57BL/6 mice to establish the Lewis lung carcinoma model. We observed that YFTL effectively inhibited tumor growth and prolonged the overall survival of tumor-bearing mice. Additionally, YFTL treatment resulted in a significantly decreased number of surface lung metastatic lesions compared with the model control group. Meanwhile, TUNEL staining confirmed that the tumors from YFTL-treated mice exhibited a markedly higher apoptotic index. The results suggest that Akt and mitogen-activated protein kinase (MAPKs) pathways may be involved in YFTL-induced apoptosis. The results show that YFTL also inhibited the vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2, MMP-9, N-cadherin, and Vimentin expression, but increased E-cadherin expression. Mechanistic studies indicated that YFTL could suppress the angiogenesis and the epithelial-mesenchymal transition (EMT) of the tumor through Akt/ERK1/2 and TGFß1/Smad2 pathways. In addition, YFTL also showed immunomodulatory activities in improving the immunosuppressive state of tumor-bearing mice. Therefore, our findings could support the development of YFTL as a potential antineoplastic agent and a potentially useful anti-metastatic agent for lung carcinoma therapy.

Protective effect of methylallyl sulfone in the development of cigarette smoke extract-induced apoptosis in rats and HFL-1 cells.

Although the organosulfur compounds from garlic have shown diverse pharmacological activities, the prototype drug was almost undetectable in vivo. As known, methylallyl sulfone (AMSO2) is the main metabolite of some active organosulfur compounds derived from garlic. The purpose of this article was to study the protective effect of AMSO2 on cigarette smoke extract (CSE) induced cell apoptosis in lungs in vivo and in vitro. The male rats were injected intraperitoneally with 900 µL of 100% CSE 3 times for three successive weeks. The rats from treatment groups were injected intraperitoneally with AMSO2 (50 mg/kg/day or 100 mg/kg/day) or DEX (1 mg/kg/day) for 21 days. We observed that pretreatment of AMSO2 effectively reversed apoptosis and oxidative stress in rats induced by CSE. Moreover, CSE-induced apoptosis in the HFL-1 cells was significantly suppressed by pretreated AMSO2 (400 µM) and DEX (0.1 mg/mL). Mechanistic studies suggested that this activity may arise from its effects on the regulation of p38 MAPK, Nrf-2 and Bcl-2/Bax signaling pathways. Overall, the metabolite of active organosulfur compounds AMSO2 might be a potential candidate for the treatment of CSE-induced apoptosis in rats.

Protective Effect of Bergenin against Cyclophosphamide-Induced Immunosuppression by Immunomodulatory Effect and Antioxidation in Balb/c Mice.

In this study, the aim was to investigate the effect of bergenin on immune function and antioxidation in cyclophosphamide (Cy)-induced immunosuppressed mice. Firstly, we estimated its effect on immune organs. Histological analysis and indexes of immune organs showed that cyclophosphamide exhibited spleen and thymus injury compared with the normal control, which was alleviated by bergenin. Secondly, bergenin also enhanced the humoral immune function through increasing the level of IgM and IgG in serum. Thirdly, bergenin also enhanced the cellular immune function. The results indicate that bergenin increased peritoneal macrophage functions, the proliferation of T and B lymphocytes, NK and CTL cell activities, and T (CD4⁺ and CD8⁺) lymphocyte subsets. Besides, bergenin also had the ability to modulate the Th1/Th2 balance. Moreover, bergenin prevented the Cy-induced decrease in numbers of peripheral RBC, WBC and platelets, providing supportive evidence for their anti-leukopenia activities. Finally, bergenin also reversed the Cy-induced decrease in the total antioxidant capacity including activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). In conclusion, bergenin protected against Cy-induced adverse reactions by enhancing humoral and cellular immune functions and augmenting antioxidative activity and could be considered as a potential immunomodulatory agent.

S-allylmercaptocysteine suppresses the growth of human gastric cancer xenografts through induction of apoptosis and regulation of MAPK and PI3K/Akt signaling pathways.

Gastric cancer remains as a common lethal malignancy worldwide. Developing novel anti-gastric cancer drugs with minimal side effects is necessary to address this public health issue. S-allylmercaptocysteine (SAMC), one of the water-soluble organosulfur garlic derivatives, has been demonstrated as a suppressive agent against tumors. In this study, we examined the effect of SAMC on human gastric carcinoma growth in vivo and explored the underlying mechanism. Human gastric cancer SGC-7901 cells were inoculated subcutaneously in BALB/c nude mice. When xenograft tumors reached about 100 mm3, mice were treated with SAMC for 30 days. We observed that SAMC administration in mice effectively delayed the growth of SGC-7901 xenografts without signs of toxicity. TUNEL staining confirmed that the tumors from SAMC-treated mice exhibited a markedly higher apoptotic index. Mechanistic studies suggested that this activity may arise from its effects on the caspase activation and modulation of MAPK and PI3K/Akt signaling pathways. Taken together, these data support development of SAMC as a potential agent for gastric cancer therapy.

Diallyl trisulfide suppresses tumor growth through the attenuation of Nrf2/Akt and activation of p38/JNK and potentiates cisplatin efficacy in gastric cancer treatment.

Diallyl trisulfide (DATS), a garlic organosulfide, has shown excellent chemopreventive potential. Cisplatin (DDP) is widely used to treat solid malignant tumors, but causing serious side effects. In the current study, we attempted to elucidate the chemopreventive mechanisms of DATS in human gastric cancer BGC-823 cells in vitro, and to investigate whether DATS could enhance the anti-tumor efficacy of DDP and improve quality of life in BGC-823 xenograft mice in vivo. Treatment with DATS (25-400 µmol/L) dose-dependently inhibited the viability of BGC-823 cells in vitro with an IC50 of 115.2±4.3 µmol/L after 24 h drug exposure. DATS (50-200 µmol/L) induced cell cycle arrest at G2/M phase in BGC-823 cells, which correlated with significant accumulation of cyclin A2 and B1. DATS also induced BGC-823 cell apoptosis, which was accompanied by the modulation of Bcl-2 family members and caspase cascade activation. In BGC-823 xenograft mice, administration of DATS (20-40 mg·kg-1·d-1, ip) dose-dependently inhibited tumor growth and markedly reduced the number of Ki-67 positive cells in tumors. Interestingly, combined administration of DATS (30 mg·kg-1·d-1, ip) with DDP (5 mg/kg, every 5 d, ip) exhibited enhanced anti-tumor activity with fewer side effects. We showed that treatment of BGC-823 cells with DATS in vitro and in vivo significantly activated kinases such as p38 and JNK/MAPK and attenuated the Nrf2/Akt pathway. This study provides evidence that DATS exerts anticancer effects and enhances the antitumor efficacy of DDP, making it a novel candidate for adjuvant therapy for gastric cancer.

Preparation and evaluation of posaconazole-loaded enteric microparticles in rats.

OBJECTIVES: Posaconazole (POS) is an antifungal compound which has a low oral bioavailability. The aim of this study was to prepare POS enteric microparticles to enhance its oral bioavailability. METHODS: POS enteric microparticles were prepared with hypromellose acetate succinate (HPMCAS) via the spray drying method. The solvent mixtures of acetone and ethanol used in the preparation of the microparticles were optimized to produce the ideal POS enteric microparticles. Multivariate data analysis using a principal component analysis (PCA) was used to find the relationship among the HPMCAS molecular characteristics, particle properties and drug release kinetics from the spray dried microparticles. KEY FINDINGS: The optimal spray solvent mixtures were critical to produce the POS microparticles with the defined polymer entanglement index, drug surface enrichment, particle size and drug loading. The HPMCAS molecular characteristics affected the microscopic connectivity and diffusivity of polymer matrix and eventually influenced the drug release behavior, and enhanced the bioavailability of POS. CONCLUSIONS: These studies suggested that the selection of suitable solvent mixtures of acetone and ethanol used in the spray drying of the microparticles was quite important to produce the entangled polymer structures with preferred polymer molecular properties of polymer coiling, overlap concentration and entanglement index. Additional studies on particle size and surface drug enrichment eventually produced HPMCAS-based enteric microparticles to enhance the oral bioavailability of POS.

Protective Effect of Flavonoids from Ziziphus jujuba cv. Jinsixiaozao against Acetaminophen-Induced Liver Injury by Inhibiting Oxidative Stress and Inflammation in Mice.

This study was aimed to investigate the chemical composition, antioxidant activities and hepatoprotective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao (ZJF). The composition of ZJF was analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography-mass spectrometry (LC-MS), and antioxidant properties were investigated by biological assays in vitro. The hepatoprotective activity of ZJF was evaluated in acetaminophen (APAP)-treated BALB/c mice. Results indicate that ZJF displayed significant antioxidant capacity. Pretreatment with ZJF significantly decreased APAP-elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TB). Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were enhanced with ZJF administration, while malondialdehyde (MDA) level and glutathione (GSH) depletion were reduced. Meanwhile, ZJF reversed the suppression of nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and up-regulated the protein expression of NAD(P)H: quinone oxidoreductase 1(NQO1) in liver damage mice. Furthermore, ZJF attenuated APAP-induced inflammatory mediator production, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß). Expression of p65 showed that ZJF dampened nuclear factor-κB (NF-κB) activation. The results strongly indicate that the hepatoprotective role of ZJF in APAP-induced hepatotoxicity might result from its induction of antioxidant defense via activation of Nrf2 and reduction of inflammation via inhibition of NF-κB.

Preparation and optimization of resveratrol nanosuspensions by antisolvent precipitation using Box-Behnken design.

Resveratrol, a natural polyphenolic component, has inspired considerable interest for its extensive physiological activities. However, the poor solubility of resveratrol circumscribes its therapeutic applications. The purpose of this study was to optimize and prepare resveratrol nanosuspensions using the antisolvent precipitation method. The effects of crucial formulation and process variables (drug concentration, stabilizer, and surfactant contents) on particle size were investigated by utilizing a three-factor three-level Box-Behnken design (BBD) to perform this experiment. Different mathematical polynomial models were used to identify the impact of selected parameters and to evaluate their interrelationship for predictive formulation purposes. The optimal formulation consisted of drug 29.2 (mg/ml), polyvinylpyrrolidone (PVP) K17 0.38%, and F188 3.63%, respectively. The morphology of nanosuspensions was found to be near-spherical shaped by scanning electron microscopy (SEM) observation. The X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) analysis confirmed that the nanoparticles were in the amorphous state. Furthermore, in comparison to raw material, resveratrol nanosuspensions showed significantly enhanced saturation solubility and accelerated dissolution rate resulting from the decrease in particle size and the amorphous status of nanoparticles. Meanwhile, resveratrol nanosuspensions exhibited the similar antioxidant potency to that of raw resveratrol. The in vivo pharmacokinetic study revealed that the C max and AUC0→∞ values of nanosuspension were approximately 3.35- and 1.27-fold greater than those of reference preparation, respectively. Taken together, these results suggest that this study provides a beneficial approach to address the poor solubility issue of the resveratrol and affords a rational strategy to widen the application range of this interesting substance.