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Background:Nuezhenide (NZD), an iridoid glycoside isolated from Ilex pubescens Hook. & Arn. var. kwangsiensis Hand.-Mazz., used as a traditional Chinese medicine for clearing Hook. & Arn. var. kwangsiensis Hand.-Mazz., used as a traditional Chinese medicine for clearing away heat and toxic materials, displays a variety of biological activities such as anti-tumor, antioxidant, and other life-protecting activities. However, a few studies involving anti-inflammatory activity and the mechanism of NZD have also been reported. In the present study, the anti-inflammatory and antioxidative effects of NZD are illustrated.Objective:This study aims to test the hypothesis that NZD suppresses LPS-induced inflammation by targeting the NF-κB pathway in RAW264.7 cells.Methods:LPS-stimulated RAW264.7 cells were employed to detect the effect of NZD on the release of cytokines by ELISA. Protein expression levels of related molecular markers were quantitated by western blot analysis. The levels of ROS, NO, and Ca2+were detected by flow cytometry. The changes in mitochondrial reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were observed and verified by fluorescence microscopy. Using immunofluorescence assay, the translocation of NF-κB/p65 from the cytoplasm into the nucleus was determined by confocal microscopy.Results:NZD exhibited anti-inflammatory activity and reduced the release of inflammatory cytokines such as nitrite, TNF-α, and IL-6. NZD suppressed the expression of the phosphorylated proteins like IKKα/β, IκBα, and p65. Besides, the flow cytometry results indicated that NZD inhibited the levels of ROS, NO, and Ca2+in LPS-stimulated RAW264.7 cells. JC-1 assay data showed that NZD reversed LPS-induced MMP loss. Furthermore, NZD suppressed LPS-induced NF-B/p65 translocation from the cytoplasm into the nucleus.Conclusions:NZD exhibits anti-inflammatory effects through the NF-κB pathway on RAW264.7 cells.

Various drug transporters are widely expressed throughout the intestine and play important roles in absorbing nutrients and drugs, thus providing high quality targets for the design of prodrugs or nanoparticles to facilitate oral drug delivery. In particular, intestinal carnitine/organic cation transporter 2 (OCTN2) and mono-carboxylate transporter protein 1 (MCT1) possess high transport capacities and complementary distributions. Therefore, we outline recent developments in transporter-targeted oral drug delivery with regard to the OCTN2 and MCT1 proteins in this review. First, basic information of the two transporters is reviewed, including their topological structures, characteristics and functions, expression and key features of their substrates. Furthermore, progress in transporter-targeting prodrugs and nanoparticles to increase oral drug delivery is discussed, including improvements in the oral absorption of anti-inflammatory drugs, antiepileptic drugs and anticancer drugs. Finally, the potential of a dual transporter-targeting strategy is discussed., Graphical abstract In this review, we outline the recent developments in transporter-targeting oral drug delivery, especially on intestinal carnitine/organic cation transporter 2 (OCTN2) and monocarboxylate transporter protein 1 (MCT1).Image, graphical abstract

Inflammation is a complex physiological process that poses a serious threat to people’s health. However, the potential molecular mechanisms of inflammation are still not clear. Moreover, there is lack of effective anti-inflammatory drugs that meet the clinical requirement. Procyanidin A1 (PCA1) is a monomer component isolated from Procyanidin and shows various pharmacological activities. This study further demonstrated the regulatory role of PCA1 on lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in RAW264.7 cells. Our data showed that PCA1 dramatically attenuated the production of pro-inflammatory cytokines such as NO, iNOS, IL-6, and TNF-α in RAW264.7 cells administrated with LPS. PCA1 blocked IκB-α degradation, inhibited IKKα/β and IκBα phosphorylation, and suppressed nuclear translocation of p65 in RAW264.7 cells induced by LPS. PCA1 also suppressed the phosphorylation of JNK1/2, p38, and ERK1/2 in LPS-stimulated RAW264.7 cells. In addition, PCA1 increased the expression of HO-1, reduced the expression of Keap1, and promoted Nrf2 into the nuclear in LPS-stimulated RAW264.7 cells. Cellular thermal shift assay indicated that PCA1 bond to TLR4. Meanwhile, PCA1 inhibited the production of intracellular ROS and alleviated the depletion of mitochondrial membrane potential in vitro. Collectively, our data indicated that PCA1 exhibited a significant anti-inflammatory effect, suggesting that it is a potential agent for the treatment of inflammatory diseases.

The chemical composition and antitumor activity of essential oil were compared for four parts of the Arisaema Amuremse Maxim. Chemical constituent of essential oil in every parts of Arisaema Amuremse Maxim was identified by GC-MS analysis systematically. Arisaema Amuremse Maxim had 114 kinds of essential oils. Tubers, petioles, leaves, and fruits were identified 53, 48, 5 and 21 species essential oil, respectively. The antiproliferative activity against Hep2, HCT-116, A549, SW480, HepG2 cell lines had been investigated by MTT assay. The essential oil of tubers, petioles, leaves and fruits all had strong antiproliferative activity. The IC 50 was 19.60μg·mL-1, 17.60μg·mL-1, 23.80μg·mL-1, and 30.23μg·mL-1, respectively. Among them, the essential oil of tubers and petioles had stronger antitumor activity. The essential oil of tubers, petioles, leaves and fruits had strong antiproliferative activity. This study was of great significance to increase the medicinal parts of Arisaema Amuremse Maxim.

OBJECTIVE To investigate inhibitory effect of semen litchi drug serum on proliferation of human hepatoma HepG2 cells and its effect on the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9). STUDY DESIGN An experimental study. PLACE AND DURATION OF STUDY College of Pharmacy, Guangxi University of Chinese Medicine, China, from June 2017 to January 2018. METHODOLOGY Semen litchi drug serum with concentrations of 0 mg/kg (control group), 3 g/kg (low dose group), 6 g/kg (medium dose group) and 12 g/kg (high dose group) was used to act on HepG2 cells at the logarithmic phase. Inhibitory effect of semen litchi drug serum on cell growth, expression of VEGF and MMP-9 mRNA and protein was detected. RESULTS Inhibitory effect of semen litchi drug serum on the proliferation of HepG2 cells significantly increased with the increase of drug concentration, which was dose-time dependent. Expression levels of VEGF and MMP-9 mRNA in HepG2 cells after 48 hours of treatment by semen litchi low-dose group, medium-dose group, and high-dose group were lower than those in control group (all p

BACKGROUND The aim of this study was to assess the hypoglycemic effect of Cyclocarya paliurus extract (CPE) on diabetes mellitus (DM) mice. MATERIAL AND METHODS A DM mouse model was established to test FBG, TC, and TG. The DM mice were divided into 3 groups: a DM group, a DM+CPE (0.5 g/Kg) group, and a DM+CPE (1.0 g/Kg) group. The FBG and body weight were measured. The glucose tolerance ability was determined by OGTT test. FINS was measured to calculate ISI and IRI. Serum MDA, SOD, and GSH-Px levels were detected. NIT-1 cells were cultured in vitro and divided into 4 groups: a control group, a STZ group, a STZ+CPE (80 μg/mL) group, and a STZ+CPE (160 μg/mL) group. Cell apoptosis and ROS content were assessed by flow cytometry. Cell proliferation was detected by EdU staining. RESULTS Compared with the control group, FBG, TC, and TG were significantly increased in the DM group. CPE gavage obviously reduced FBG level, increased body weight, enhanced glucose tolerance, elevated FINS level and ISI, and reduced IRI, all in a dose-dependent manner. CPE gavage reduced serum MDA content and increased SOD and GSH-Px enzyme activities in DM mice. STZ markedly enhanced ROS production, induced apoptosis, and inhibited proliferation in NIT-1 cells. CPE treatment clearly reduced ROS production and apoptosis, enhanced cell proliferation, and alleviated STZ damage to NIT-1 cells. CONCLUSIONS CPE has the effects of decreasing blood glucose and insulin resistance, and enhancing glucose tolerance in DM mice, which may be related to its effects of reducing oxidation and reduced apoptosis, and relieving STZ in pancreatic beta cell injury.

Procyandin A2 (PCA2) is a polyphenolic compound which is isolated from grape seeds. It has been reported that PCA2 exhibits antioxidative and anti-inflammatory effects, but its molecular mechanism is still poorly understood. This study tests the hypothesis that PCA2 suppresses lipopolysaccharide (LPS)-induced inflammation and oxidative stress through targeting the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and NF-E2-related factor 2 (Nrf2) pathways in RAW264.7 cells. PCA2 (20, 40, 80 μM) exhibited no significant cytotoxicity in RAW264.7 cells and showed an inhibitory effect on an LPS-induced nitrite level. Pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), nitric oxide (NO), and reactive oxygen species (ROS) were suppressed by PCA2 with a concentration range of 0-80 μM. The mRNA levels of TNF-α and IL-6 were inhibited by PCA2 (80 μM). The hallmark-protein expression of the NF-κB (p-IKKα/β, p-IκBα, and p-p65) and MAPK (p-p38, p-JNK, and p-ERK) pathways were decreased by PCA2 in LPS-stimulated RAW264.7 cells. In addition, immunofluorescence results indicated that PCA2 (80 μM) promoted the translocation of NF-κB/p65 from the cytoplasm into the nucleus. PCA2 upregulated the expressions of Nrf2 and HO-1 and downregulated the expression of Keap-1. Simultaneously, PCA2 (80 μM) reversed LPS-induced Nrf2 translocation from the nucleus into the cytoplasm. Collectively, PCA2 protect cells against the damage from inflammation and oxidative injury, which suggest a potential therapeutic strategy for inflammatory and oxidative stress through targeting NF-κB, MAPK, and Nrf2 pathways in RAW264.7 cells.

The aim of this study was to determine the effect of Astragalus polysaccharide (APS) on the expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in mice with Lewis transplantable lung cancer. It was an experimental study carried out from June 2017 to January 2018 at the College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China. Forty male SPF-level C57BL/6J mice were selected and inoculated with Lewis lung cancer cell suspension in the right axilla of the mice to establish a lung-cancer mouse model. The mice were randomly divided into a model control group and APS groups with high, middle and low dosages, respectively, 10 in each group. After inoculation of Lewis tumor cell suspension for 2 days, mice in the model control group were injected intraperitoneally with 50 mL/kg of 0.9% sodium chloride solution, whereas, mice in the APS groups with high, middle and low dosages were intraperitoneally injected with APS at 100, 50, 25 mg/kg, respectively. The research results showed that APS can effectively inhibit the growth and metastasis of Lewis lung cancer in mice, improve immune organ function, inhibit the protein expression of VEGF and EGFR in tumor tissues, and have a concentration-effect relationships.

Objectives A system of stearic acid (SA)-modified Bletilla striata polysaccharide (BSP) micelles was developed for the targeted delivery of docetaxel (DTX) as a model anticancer drug (DTX-SA-BSP). Methods Particle size, zeta potential and DTX release in vitro were measured in release media at different pH values. Quantitative cellular uptake, cytotoxicity assay in vitro and antitumour efficacy in vivo were also evaluated. Cell apoptosis was assessed by flow cytometry. Key findings DTX-SA-BSP copolymer micelles displayed pH-dependent properties in the respects of particle size, zeta potential and in vitro release behaviour ranging from pH 5.0 to pH 7.4. DTX-SA-BSP copolymer micelles showed higher release rate at pH 5.0 than that at pH 6.0 and 7.4. In vitro cytotoxic effect of DTX-SA-BSP copolymer micelles was higher than that of DTX injection. The results of high-performance liquid chromatography determination confirmed that DTX cellular uptake of micelles was enhanced compared with that of DTX injection. Anticancer activity in vivo further confirmed the enhanced tumour targeting and anticancer efficacy of DTX-SA-BSP copolymer micelles. Conclusions The above results show that DTX-SA-BSP copolymer micelles have pH sensitivity. SA-BSP copolymers are a promising carrier for delivering hydrophobic anticancer drugs.

Celiac disease (CD) is one of the most common human intestinal malabsorption diseases. The only effective treatment for patients with CD is to follow a gluten-free (GF) diet strictly. Nowadays, the increasing incidence of CD promotes worldwide interests for various desirable GF products. However, baking without gluten, the key ingredient for bread structure and quality, is a big challenge for all bakers and cereal researchers. Several approaches have been applied to understand and improve gluten-free bread (GFB) elaboration and further studies are still required. The main focus of this review is to discuss the approaches for GFB improvements in recent 5 years, including the use of novel alternative flours, functional ingredients, processing aids, additives, innovative techniques, and their combinations.

The aim of this study was to prepare dissolving microneedles (DMNs) patches containing tranexamic acid (TA) for the treatment of melasma. Polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) were preferred as matrix materials through the compatibility experiment. In the in vitro permeation study, the transdermal amount of TA was significantly promoted through dissolving microneedles with the cumulative release was 44.43 ± 6.55%. By comparison, the release of TA solution assisted with solid microneedles (SMNs) was merely 11.31 ± 2.30% (p 0.05). Pharmacokinetics study indicated the bioavailability of dissolving microneedles was more than 1.3 times compared with oral administration. In pharmacodynamics investigation, TA dissolving microneedles obviously reduced melanin deposition in the skin of melasma guinea pigs after 8 consecutive administrations. In particular, the combination of tranexamic acid and licorice extract (LIC) dissolving microneedles worked better than tranexamic acid alone. Accelerated stress conditions including high temperature, high humidity, as well as photostability were designed to prove that TA microneedles maintained good pharmaceutical stability. In conclusion, tranexamic acid dissolving microneedles showed reliable quality and remarkable effect. Moreover, the combination of tranexamic acid and licorice extract had a synergistic therapy in melasma.

In the separation of strongly polar antioxidant compounds from natural products using high-speed counter-current chromatography that is target-guided by 2,2-diphenyl-1-picrylhydrazyl high-performance liquid chromatography experimentation, low adsorption ability is encountered due to the strong polarity of the target compounds. In this study, a strategy of novel partition coefficient value calculation was proposed for overcoming this problem. The partition coefficient value was expressed as the ratio of the antioxidant activities of the upper phase and the lower phase. This strategy was used in high-speed counter-current chromatography with a hydrophilic organic/salt-containing aqueous two-phase system for bioassay-guided separation of strongly polar antioxidant compounds from Lycium barbarum L. The antioxidant activity was determined via the radical scavenging activity method using 2,2-diphenyl-1-picrylhydrazyl radicals. A hydrophilic organic/salt-containing aqueous two-phase system of 95% EtOH - sat. (NH4)2SO4 (1:1.8, v/v) was successfully used to separate Lycium barbarum L. extract. Five fractions were collected via high-speed counter-current chromatography separation. The antioxidant activity of the third fraction was the highest. Three compounds were separated via MCI gel column chromatography and Sephadex LH-20 column chromatography from the third fraction, and their antioxidant activities were determined. The antioxidant activities of the three compounds were higher than that of the third fraction. These results demonstrate that this strategy can be used to separate strongly polar antioxidant compounds from natural products.

s Magnetic composite nanospheres carrying amino groups have attracted much interest due to their potential applications in the fields of catalysis, sensor, water purification, enzyme immobilization, DNA extraction, and drug delivery. In this paper, dedoped Fe 3 O 4 /polypyrrole (PPy) nanospheres with core–shell structure, high magnetization, superparamagnetism, and size meeting the demand of biorelated applications in vivo have been achieved by an in situ polymerization approach. The amount of the surface amino groups of Fe 3 O 4 /PPy is greatly enhanced by dedoping treatment due to liberation of the amino groups ever sheltered by the dopants, a situation that is responsible for facile conjugation of fluorescein and methotrexate (MTX) onto the magnetic composite through the EDC/NHS coupling chemistry to produce the desirable fluorescent Fe 3 O 4 /PPy/MTX targeting drug with a high MTX loading of ca. 109 μg mg −1 . The as-obtained magnetic targeting drug exhibits controlled drug release, enhanced intracellular drug retention, and specific targeting ability to HeLa cells, presenting a promising candidate for treatment of cancer cells overexpressing folate receptors.

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Aim: To investigate the mechanisms of paclitaxel resistance in hepatocellular carcinoma cells and find promising molecular target for HCC therapy. Materials and Methods: To investigate the effects of FHL1 on chemo resistance in HCC cells, we generated FHL1 knock-down stable cell lines with HepG2 and SMMC7721 cells. Cell viability assay, colony formation and xenograft experiments assay were performed to detect effect of FHL1 on Paclitaxel or Oxaliplatin resistance in vitro and in vivo. Caspase activity assay was performed to explore the activation of caspase-3 and caspase-9 in paclitaxel treated FHL1-knockdown HepG2 cells. Result: In the present study we have investigated that four-and-a-half LIM protein 1 (FHL1), which plays an important role in the development of cancer, is associated with both the chemo resistance of hepatocellular carcinomas cells in vitro and in vivo. Knockdown of FHL1 significantly enhanced the sensitivity of paclitaxel, but had no effects on sensitivity of oxaliplatin. Moreover, knockdown of FHL1 promoted the activation of caspase-3 and caspase-9, which were induced by paclitaxel. Interestingly, FHL1 negatively regulates the chemo resistance of HCC in xenografted nude mice. Conclusion: FHL1 promote paclitaxel resistance in hepatocellular carcinomas cells through regulating apoptosis induced by paclitaxel, suggesting that FHL1 may be a promising molecular target for HCC therapy.

Molecules of the title compound, [Sn2(C6H5)6(C6H2O4S)], lie on inversion centres with the central thiophene ring disordered equally over two orientations. The carboxylate groups are approximately coplanar with the thiophene ring [dihedral angle = 4.0 (1)°] and the Sn—O bond distance of 2.058 (4) Å is comparable to that in related organotin carboxylates.

Constructing novel materials with a hierarchical structure has become an increasingly hot research topic, because the hierarchical structures have wide potential applications in the fields of bionics, electronics, photocatalysis, solar cells, and lithium ion batteries. In this paper, we report on the fabrication of rhombohedral corundum-type indium oxide (rh-In2O3) hierarchical rod-aggregates by annealing oxyhydroxide (InOOH) counterparts prepared through a simple solvothermal route without surfactant. The formation mechanism of the InOOH hierarchical structures is suggested. The rh-In2O3 hierarchical crystals were tested in the role of sensing ammonia gas, and were found to show an excellent gas-sensitivity to NH3 as compared to the cubic bixbyite-type indium oxide (c-In2O3) analogues.