Artificial Octopus-Limb-Like Adhesive Patches for Cupping-Driven Transdermal Delivery with Nanoscale Control of Stratum Corneum.

Drug delivery through complex skin is currently being studied using various innovative structural and material strategies due to the low delivery efficiency of the multilayered stratum corneum as a barrier function. Existing microneedle-based or electrical stimulation methods have made considerable advances, but they still have technical limitations to reduce skin discomfort and increase user convenience. This work introduces the design, operation mechanism, and performance of noninvasive transdermal patch with dual-layered suction chamber cluster (d-SCC) mimicking octopus-limb capable of wet adhesion with enhanced adhesion hysteresis and physical stimulation. The d-SCC facilitates cupping-driven drug delivery through the skin with only finger pressure. Our device enables nanoscale deformation control of stratum corneum of the engaged skin, allowing for efficient transport of diverse drugs through the stratum corneum without causing skin discomfort. Compared without the cupping effect of d-SCC, applying negative pressure to the porcine, human cadaver, and artificial skin for 30 min significantly improved the penetration depth of liquid-formulated subnanoscale medicines up to 44, 56, and 139%. After removing the cups, an additional acceleration in delivery to the skin was observed. The feasibility of d-SCC was demonstrated in an atopic dermatitis-induced model with thickened stratum corneum, contributing to the normalization of immune response.

Boston Ivy Disk-Inspired Pressure-Mediated Adhesive Film Patches.

Boston ivy (Parthenocissus tricuspidata) climbs brick walls using its tendril disks, which excrete a sticky substance to perform binding and attachment. While the cellular structures and adhesive substances involved have been identified for decades, their practical applicability as an adhesive has not yet been demonstrated. A Boston ivy disk-inspired adhesive film patch system is reported in which structural and compositional features of the Boston ivy disk are mimicked with a form of thin adhesive film patches. In analogy to the sticky disk of a mature ivy in which porous microchannels are occupied by catechol-containing microgranules on the bound site, 3,4-dihydroxylphenylalanine bolaamphiphile nanoparticle (DOPA-C7 NP)-coated alginate microgels are two-dimensionally positioned into the cylindrical holes that are periodically micropatterned on the flexible stencil film. Finally, it is demonstrated that the pressurization of the patch breaks the microgels filled in the holes, releasing the polysaccharides and leading to crosslinking with DOPA-C7 NPs via ligandation with combined Ca2+ and Fe3+ ions, thus enabling development of a pressure-mediated adhesion technology.

Change in Perfusion Angiography During Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma Predicts Short-Term Outcomes.

OBJECTIVE. The purpose of this study is to quantitatively assess perfusion reductions occurring in hepatocellular carcinoma (HCC) during transcatheter arterial chemoembolization (TACE) using 2D perfusion angiography and to evaluate the relationships between various 2D perfusion angiography parameter changes and short-term tumor response. SUBJECTS AND METHODS. This prospective study included 172 patients (144 men and 28 women; mean [± SD] age, 65.4 ± 10.2 years) who underwent TACE for HCC between November 2015 and November 2017. Two-dimensional perfusion angiography was performed before and after TACE. Pre- and postprocedural CT images were also reviewed. Index lesions were defined as all discrete lesions 1.5 cm or larger. The tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors. Periprocedural 2D perfusion angiography parameters, including the arrival time, time to peak, wash-in rate, width, AUC, and mean transit time, were compared using the Wilcoxon signed rank test. Correlations between 2D perfusion angiography parameter changes and objective tumor response were evaluated using multivariate logistic regression analysis. RESULTS. A total of 187 lesions meeting the inclusion criteria were identified in 172 patients. All analyzed 2D perfusion angiography parameters were significantly different after versus before TACE (p < 0.001). A significant relationship between periprocedural change in AUC and short-term tumor response was found (odds ratio, 1.535; 95% CI, 1.314-1.793; p < 0.001). CONCLUSION. Two-dimensional perfusion angiography could objectively quantify perfusion reductions and predict short-term tumor response to TACE in patients with HCC.

Combined Therapy with Transarterial Chemoembolization and Radiofrequency Ablation for Hepatocellular Carcinoma: Does the Degree of Ethiodized Oil Accumulation within the Tumor Affect the Therapeutic Efficacy?

PURPOSE: To evaluate the effects of the degree of ethiodized oil accumulation achieved by transarterial chemoembolization followed by radiofrequency (RF) ablation on the treatment efficacy for a single intermediate-sized hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 153 consecutive patients who underwent chemoembolization and RF ablation for a single intermediate-sized HCC (2-5 cm) were included. On the basis of the degree of ethiodized oil accumulation in HCC on cone-beam CT images, patients who underwent chemoembolization and RF ablation were classified into 2 groups: compact accumulation (≥ 75%) and noncompact accumulation (< 75%). The rates of cumulative local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) were compared between groups. RESULTS: Of the 153 patients, 89 were classified into the compact ethiodized oil accumulation group and 64 in the noncompact ethiodized oil accumulation group. There were no significant differences in patient demographic or HCC characteristics between groups except for the incidence of liver cirrhosis (P = .038) and the tumor margin morphology (P = .008). The cumulative LTP rate was significantly lower in the compact accumulation group than in the noncompact accumulation group (P = .013). There were no significant differences in the incidences of complications, DFS rates (P = .055), or OS rates (P = .184). CONCLUSIONS: The degree of ethiodized oil accumulation does not play a role in decreasing the OS or DFS rate after chemoembolization and RF ablation for intermediate-sized HCC; however, it may contribute to reducing the rate of LTP.

Evaluation of Hepatoprotective Effect of Curcumin on Liver Cirrhosis Using a Combination of Biochemical Analysis and Magnetic Resonance-Based Electrical Conductivity Imaging.

In oriental medicine, curcumin is used to treat inflammatory diseases, and its anti-inflammatory effect has been reported in recent research. In this feasibility study, the hepatoprotective effect of curcumin was investigated using a rat liver cirrhosis model, which was induced with dimethylnitrosamine (DMN). Together with biochemical analysis, we used a magnetic resonance-based electrical conductivity imaging method to evaluate tissue conditions associated with a protective effect. The effects of curcumin treatment and lactulose treatment on liver cirrhosis were compared. Electrical conductivity images indicated that liver tissues damaged by DMN showed decreased conductivity compared with normal liver tissues. In contrast, cirrhotic liver tissues treated with curcumin or lactulose showed increased conductivity than tissues in the DMN-only group. Specifically, conductivity of cirrhotic liver after curcumin treatment was similar to that of normal liver tissues. Histological staining and immunohistochemical examination showed significant levels of attenuated fibrosis and decreased inflammatory response after both curcumin and lactulose treatments compared with damaged liver tissues by DMN. The conductivity imaging and biochemical examination results indicate that curcumin's anti-inflammatory effect can prevent the progression of irreversible liver dysfunction.

Trial Comparing a Combined Regimen of Amikacin and Ciprofloxacin to Ciprofloxacin Alone as Transrectal Prostate Biopsy Prophylaxis in the Era of High Fluoroquinolone-Resistant Rectal Flora.

BACKGROUND: To investigate whether addition of amikacin to fluoroquinolone (FQ) antimicrobial prophylaxis reduces infections after transrectal ultrasound-guided prostate biopsy (TRUSPB). METHODS: A total of 503 patients undergoing rectal swab were divided into three groups. Patients with FQ-sensitive rectal flora (group 1, n = 248) were administered ciprofloxacin before TRUSPB, and patients with FQ-resistant rectal flora were either administered ciprofloxacin (group 2, n = 97) or amikacin and ciprofloxacin (group 3, n = 158) before TRUSPB. RESULTS: Based on the rectal swab, FQ resistance was 54.9%, and extended-spectrum ß-lactamase (ESBL) positivity was 17.2%. The incidence of infectious complication in group 1 was 1.6%. Groups 2 and 3, with FQ-resistant rectal flora, tended to have increased infectious complications (5.2% and 4.4%, respectively) but the difference between those results is not statistically significant. The most common pathogens of infectious complications in patients with FQ-resistant rectal flora were FQ-resistant and ESBL-producing Escherichia coli. E. coli pathogens isolated in Group 3 were amikacin-susceptible species. The operation history and ESBL positivity of rectal flora increased the incidence of infectious complications (odds ratio [OR] = 3.68; P = 0.035 and OR = 4.02; P = 0.008, respectively). DM and antibiotics exposure were risk factors for FQ resistance (OR = 2.19; P = 0.002) and ESBL positivity of rectal flora (OR = 2.96; P = 0.005), respectively. CONCLUSION: Addition of amikacin to ciprofloxacin prophylaxis could not reduce infectious complications in patients with FQ-resistant rectal flora. Despite the amikacin sensitivity of infectious complications, single-dose amikacin addition to ciprofloxacin prophylaxis has limitations.

Nanoemulsion Vehicles as Carriers for Follicular Delivery of Luteolin.

Luteolin (3',4',5,7-tetrahydroxyflavone), a type of flavonoid found in medicinal herbs and vegetables, has been of great interest due to its antioxidative, anti-inflammatory, and anticarcinogenic effects. Despite these beneficial biological properties, the ease with which luteolin forms molecular crystals in conventional aqueous formulations has hampered much wider applications. In this study, we introduce an oil-in-water (O/W) nanoemulsion vehicle system for enhanced follicular delivery of luteolin. The luteolin-loaded nanoemulsion, which had an average hydrodynamic size of approximately 290 nm, was produced by the assembly of poly(ethylene oxide)-block-poly(ε-caprolactone) and lecithin at the O/W interface. The luteolin-loaded nanoemulsion showed outstanding stability against drop coalescence and aggregation. This was confirmed from the slight drop size increase after repeated freeze-thaw cycling and long-term storage. Moreover, in vivo hair growth evaluation demonstrated that the luteolin-loaded nanoemulsions fabricated in this study possessed the hair growth-promotion activity, which is comparable with the case of using a luteolin solution in an organic solvent.

Combined Therapy of Transcatheter Arterial Chemoembolization and Radiofrequency Ablation versus Surgical Resection for Single 2-3 cm Hepatocellular Carcinoma: A Propensity-Score Matching Analysis.

PURPOSE: To compare therapeutic outcomes of radiofrequency (RF) ablation combined with transcatheter arterial chemoembolization vs surgical resection (SR) for single 2-3 cm hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Seventy patients underwent combined chemoembolization/RF ablation therapy and 84 underwent SR. Local tumor progression (LTP), intrahepatic distant recurrence (IDR), disease-free survival (DFS), and overall survival (OS) rates, as well as major complications and duration of hospital stay, were compared between groups before and after propensity-score matching. RESULTS: LTP and IDR had developed in 9 (12.9%) and 24 (34.3%) patients in the combined treatment group and in 7 (8.3%) and 24 (28.6%) patients in the SR group (P = .262 and P = .252, respectively). The 1-, 3-, 4-, and 5-year DFS rates were similar between groups (82.6%, 53.2%, 53.2%, and 37.6%, respectively, vs 84.5%, 63.6%, 59.2%, and 52.1%, respectively; P = .278), and 1-, 3-, 4-, and 5-year OS rates were also comparable (94.2%, 81.2%, 74.1%, and 59.4%, respectively, vs 95.2%, 86.3%, 84.0%, and 80.3%, respectively; P = .081). After matching (n = 98), LTP, IDR, DFS, and OS rates were still similar (P = .725, P = .826, P = .484, and P = .578, respectively). Major complication rate was not significantly different (2.9% vs. 6.0%; P = .596); however, after matching, major complication rate was higher in SR group (2.0% vs. 6.1%; P < .001). Hospital stays were significantly longer in the SR group (16.6 ± 6.7 d vs 8.5 ± 4.1 d; P < .001). CONCLUSIONS: Before and after matching, there were no significant differences in long-term therapeutic outcomes between combined chemoembolization/RF ablation and SR groups. Therefore, combined chemoembolization/RF ablation therapy may be an alternative treatment for single 2-3 cm HCCs.

Potential of Icariin Metabolites from Epimedium koreanum Nakai as Antidiabetic Therapeutic Agents.

The therapeutic properties of Epimediumkoreanum are presumed to be due to the flavonoid component icariin, which has been reported to have broad pharmacological potential and has demonstrated anti-diabetic, anti-Alzheimer's disease, anti-tumor, and hepatoprotective activities. Considering these therapeutic properties of icariin, its deglycosylated icaritin and glycosylated flavonoids (icaeriside II, epimedin A, epimedin B, and epimedin C) were evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. The results show that icaritin and icariside II exhibit potent inhibitory activities, with 50% inhibition concentration (IC50) values of 11.59 ± 1.39 µM and 9.94 ± 0.15 µM against PTP1B and 74.42 ± 0.01 and 106.59 ± 0.44 µM against α-glucosidase, respectively. With the exceptions of icaritin and icariside II, glycosylated flavonoids did not exhibit any inhibitory effects in the two assays. Enzyme kinetics analyses revealed that icaritin and icariside II demonstrated noncompetitive-type inhibition against PTP1B, with inhibition constant (Ki) values of 11.41 and 11.66 µM, respectively. Moreover, molecular docking analysis confirmed that icaritin and icariside II both occupy the same site as allosteric ligand. Thus, the molecular docking simulation results were in close agreement with the experimental data with respect to inhibition activity. In conclusion, deglycosylated metabolites of icariin from E. koreanum might offer therapeutic potential for the treatment of type 2 diabetes mellitus.

Povidone-iodine rectal cleansing and targeted antimicrobial prophylaxis using rectal swab cultures in men undergoing transrectal ultrasound-guided prostate biopsy are associated with reduced incidence of postoperative infectious complications.

PURPOSE: The aim of this study was to evaluate the effect of povidone-iodine rectal disinfection and targeted antimicrobial prophylaxis in men undergoing transrectal ultrasound-guided prostate biopsy based on rectal swab culture results. METHODS: From January 2011 to December 2015, we studied differences in infectious complications in men who received povidone-iodine rectal disinfection with targeted antimicrobial prophylaxis and those who received empirical prophylaxis before transrectal ultrasound-guided prostate biopsy. Clinical variables including demographics, prior antibiotic, rectal swab culture results, povidone-iodine rectal cleansing, antibiotic prophylaxis, and infectious complications were evaluated. Patients were divided into three groups as follows: Group A received no povidone-iodine rectal cleansing but received empirical antimicrobial prophylaxis; group B received povidone-iodine rectal cleansing and empirical antimicrobial prophylaxis; and group C received povidone-iodine rectal cleansing and targeted antimicrobial prophylaxis. RESULTS: Patients were divided into group A (n = 192; 13.2 %), group B (n = 579; 39.9 %), or group C (n = 679; 46.8 %). In groups A and B, all patients received fluoroquinolone antimicrobial prophylaxis. Group C patients received targeted antimicrobial prophylaxis according to antibiotic resistance of rectal flora, and 71.1 % of these received fluoroquinolone antimicrobial prophylaxis. Infectious complication rates were 3.6, 2.9, and 1.3 % in group A, group B, and group C, respectively. Incidences of acute prostatitis and bacteremia were significantly lower in group C (p = 0.041 and p = 0.049, respectively) than in the other groups. CONCLUSIONS: In the era of quinolone resistance, the combination of povidone-iodine rectal cleansing and targeted antibiotic prophylaxis may reduce the rate of infectious complications.

Flavonoids from the aerial parts of Houttuynia cordata attenuate lung inflammation in mice.

The aerial parts of Houttuynia cordata used for treating inflammation-related disorders contain flavonoids as major constituents. Since certain flavonoids possess anti-inflammatory activity, especially in the lung, the pharmacological activities of H. cordata and the flavonoid constituents were evaluated using in vitro and in vivo models of lung inflammation. The 70 % ethanol extract of the aerial parts of H. cordata inhibited the production of inflammatory biomarkers IL-6 and NO in lung epithelial cells (A549) and alveolar macrophages (MH-S), respectively. And the same plant material, administered orally (100 and 400 mg/kg), significantly inhibited lung inflammatory response in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury. From the extract, major flavonoids including afzelin, hyperoside and quercitrin were successfully isolated and they also attenuated LPS-induced lung inflammation in mice by oral administration. In particular, quercitrin showed most potent activity at 100 mg/kg. These results demonstrate for the first time that H. cordata and three flavonoid constituents have a therapeutic potential for treating lung inflammatory disorders.

Risk factors for and prophylactic effect of povidone-iodine rectal cleansing on infectious complications after prostate biopsy: a retrospective cohort study.

PURPOSE: To evaluate the risk factors and efficacy of a povidone-iodine enema on infectious complications after transrectal ultrasound-guided prostate biopsy. METHODS: A total of 814 males who underwent transrectal ultrasound-guided prostate biopsy from January 2011 to December 2013 were evaluated retrospectively. Clinical variables, including demographics, prior antibiotic, or quinolone exposure, rectal swab culture results, povidone-iodine rectal cleansing, antibiotic prophylaxis, and infectious complications, were evaluated. RESULTS: Overall, 16 of 814 (2.0%) patients developed infectious complications after prostate biopsy. Of the patients with infectious complications, five had fever, two had urinary tract infections, and nine had bacteremia or sepsis. Infectious complication rates were not significantly different between povidone-iodine rectal cleansing (n = 613) and no cleansing (n = 201) groups (1.5 vs. 3.5%, p = 0.083). However, povidone-iodine rectal cleansing reduced severe infectious complications such as bacteremia and sepsis (0.3 vs. 3.5%, p = 0.001). A rectal swab culture was performed in 552 patients, and extended-spectrum ß-lactamase (ESBL)-producing and quinolone-resistant Escherichia coli were detected in 4.5 and 7.8% of cultures, respectively. Quinolone and antibiotic exposure within 6 months prior to prostate biopsy were associated with quinolone resistance and ESBL positivity of rectal flora and infectious complications. CONCLUSIONS: In the era of quinolone resistance, a povidone-iodine enema may reduce the infectious complication rate by reducing bacterial load. Quinolone exposure prior to prostate biopsy was a risk factor for antibiotic resistance to rectal flora and infectious complications.

Alstonia scholaris R. Br. Significantly Inhibits Retinoid-Induced Skin Irritation In Vitro and In Vivo.

Topical retinoids inhibit matrix metalloproteinases and accelerate collagen synthesis, thereby triggering antiaging effects in the skin. However, topical retinoids can cause severe skin reactions, including scaling, erythema, papules, and inflammation. The present study demonstrates that the ethanolic bark extract of Alstonia scholaris R. Br. can significantly inhibit all-trans retinoic acid-induced inflammation in human HaCat keratinocyte cells. Furthermore, two representative retinoid-induced proinflammatory cytokines, monocyte chemoattractant protein-1 and interleukin-8, were significantly suppressed by A. scholaris extract (by 82.1% and 26.3% at 100 ppm, and dose-dependently across the tested concentrations) in vitro. In a cumulative irritation patch test, A. scholaris extract decreased retinol-induced skin irritation, while strengthening the ability of retinoids to inhibit matrix metalloproteinase-1 expression, which is strongly associated with aging effects. These results suggest that A. scholaris is a promising compound that may increase the antiaging function of retinoids while reducing their ability to cause skin irritation.

Polymer-hybridized liposomes anchored with alkyl grafted poly(asparagine).

Polymer-hybridized liposomes (PHLs) of saturated lecithin were formed by association of poly(asparagines) grafted with alkyl chains (PAsn-g-Cn). The thermal, physical, and surface properties of the polymer-hybridized liposomes were examined with varying polymer concentration, alkyl chain length (C(8), C(12), C(18), C(22)), and degree of substitution (DS) in the polymer. The inclusion of the polymer raised the membrane fluidity of liposomes. By the incorporation of small amount of polymer, the membrane rigidity of liposomes dropped sharply and then increased close to the original level as the polymer concentrations increased in the cases of PAsn-g-C(18) and PAsn-g-C(22). Also, the membrane rigidity and stability of PHLs increased with alkyl chain length at the same polymer concentration. The surface charge of PHL associated with PAsn-g-C(22) was changed by DS of alkyl chains. The polymer bearing long alkyl chains (C(12), C(18), C(22)) formed PHLs well at low polymer concentration and the number of disk-shaped polymer-lipid mixed micelles increased with polymer concentration. The anchored polymers induced shifts in gel-to-liquid crystal transition temperature (Tc) of the vesicles and Tc varied with polymer concentration, alkyl chain length, and DS of the polymer.

Inhibition effect of Gynura procumbens extract on UV-B-induced matrix-metalloproteinase expression in human dermal fibroblasts.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynura procumbens Merr. (Asteraceae) has been used as a traditional remedy for various skin diseases in certain areas of Southeast Asia. AIM OF THE STUDY: In order to evaluate the protective activity of Gynura procumbens extract on skin photoaging and elucidate its mode of action. MATERIALS AND METHODS: Matrix-metalloproteinase (MMP)-1 and -9 expressions were induced by UV-B irradiation in human primary dermal fibroblasts. MMP-1 expression level was measured by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Zymography was employed for evaluating the enzymatic activity of MMP-9. Anti-inflammatory activity and anti-oxidative capacity of the extract were evaluated by ELISA and dichlorodihydrofluorescein diacetate (DCF-DA) assay. RESULTS: The ethanolic extract of Gynura procumbens inhibited MMP-1 expression up to 70% compare to negative control group. The enzymatic activity of MMP-9 was inhibited around 73% by the treatment of 20µg/mL of the extract. The extract markedly reduced the production of reactive oxygen species (ROS). Gynura procumbens extract showed an inhibitory effect on releasing pro-inflammatory cytokines (IL-6 and IL-8) in human HaCat keratinocyte. CONCLUSION: The ethanolic extract of Gynura procumbens inhibited MMP-1 and MMP-9 expressions induced by UV-B irradiation via inhibition of pro-inflammatory cytokine mediator release and ROS production.

Inhibitory effect of panduratin A isolated from Kaempferia panduarata Roxb. on melanin biosynthesis.

Hyperpigmentation disorders are associated with abnormal accumulation of melanin pigments, thus melanin synthesis inhibitors have been of great interest as target molecules for cosmetic and medicinal purposes. The aim of this study was to investigate the in vitro inhibitory effect of panduratin A, isolated from Kaempferia pandurata Roxb., on melanogenesis and its related enzymes such as tyrosinase, tyrosinase related protein-1 (TRP-1) and tyrosinase related protein-2 (TRP-2) in melan-a murine melanocytes. The IC(50) values of panduratin A for melanogenesis and tyrosinase were 9.6 µm and 8.2 µm, respectively, while those of arbutin as a positive control were 990 µm and 660 µm, respectively. In western blot analysis, panduratin A also significantly decreased tyrosinase, TRP-1 and TRP-2 protein levels. These results indicate that panduratin A effectively inhibits melanin biosynthesis, thus creating the possibility of developing a new skin-whitening agent.

Control over micro-fluidity of liposomal membranes by hybridizing metal nanoparticles.

This study introduces a facile method to hybridize metal nanoparticles with lipid vesicles, which allows us to control over their membrane micro-fluidity. We have fabricated these hybrid liposomes by directly hybridizing metal nanoparticles with lipid bilayers solely consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC). For this, we have used the dehydration and rehydration method. Characterizing their morphology and micro-fluidity, in which we have used electron microscopy and fluorescence anisotropy spectroscopy, enables us to demonstrate that metal nanoparticles with different surface properties create interactions with either phosphorus end groups or hydrophobic tails of DPPC, thereby resulting in decrease in micro-fluidity of the assembled lipid membranes, especially for the hydrophobic layers. Our approach to hybridize metal nanoparticles in between lipid layers offers a flexible means that allows us to obtain a liposome system with more controllable membrane properties.

Cytoprotective effects of Glycyrrhizae radix extract and its active component liquiritigenin against cadmium-induced toxicity (effects on bad translocation and cytochrome c-mediated PARP cleavage).

Glycyrrhizae radix has been popularly used as one of the oldest and most frequently employed botanicals in herbal medicine in Asian countries, and currently occupies an important place in food products. Cadmium (Cd) induces both apoptotic and non-apoptotic cell death, in which alterations in cellular sulfhydryls participate. In the present study, we determined the effects of G. radix extract (GRE) and its representative active components on cell death induced by Cd and explored the mechanistic basis of cytoprotective effects of G. radix. Incubation of H4IIE cells with GRE inhibited cell death induced by 10 microM Cd. Also, GRE effectively blocked Cd (1 microM)-induced cell death potentiated by buthionine sulfoximine (BSO) without restoration of cellular GSH. GRE prevented both apoptotic and non-apoptotic cell injury induced by Cd (10 microM) or Cd (0.3-1 microM) + BSO. Inhibition of Cd-induced cell injury by pretreatment of cells with GRE suggested that the cytoprotective effect result from alterations in the levels of the protein(s) responsible for cell viability. GRE inhibited mitochondrial Bad translocation by Cd or CD+BSO, and caused restoration of mitochondrial Bcl(xL) and cytochrome c levels. Cd-induced poly(ADP-ribose)polymerase cleavage in control cells or in cells deprived of sulfhydryls was prevented by GRE treatment. Among the major components present in GRE, liquiritigenin, but not liquiritin, isoliquiritigenin or glycyrrhizin, exerted cytoprotective effect. These results demonstrated that GRE blocked Cd-induced cell death by inhibiting the apoptotic processes involving translocation of Bad into mitochondria, decreases in mitochondrial Bcl(xL) and cytochrome c, and poly(ADP-ribose)polymerase cleavage.

Hepatoprotective dibenzylbutyrolactone lignans of Torreya nucifera against CCl4-induced toxicity in primary cultured rat hepatocytes.

Three dibenzylbutyrolactone lignans, (-)-arctigenin, (-)-traxillagenin, and (-)-4'-demethyltraxillagenin, isolated from the bark of Torreya nucifera SIEB. et ZUCC. (Taxaceae) showed significant hepatoprotective activity in primary cultures of rat hepatocytes injured by carbon tetrachloride (CCl(4)). These lignans reduced the release of glutamic pyruvic transaminase into the culture medium from the CCl(4)-injured primary cultures of rat hepatocytes. Further investigation revealed that the three lignans significantly preserved the level of glutathione (GSH) and activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the CCl(4)-injured rat hepatocytes. The lignans also ameliorated lipid peroxidation as demonstrated by a reduction in malondialdehyde-related products. Moreover, these lignans significantly attenuated the GSH reduction caused by diethylmaleate which depletes GSH through the formation of stable conjugates. However, these lignans showed no effect on the GSH synthesis inhibited by buthionine sulfoximine. From these results, it can be concluded that arctigenin, traxillagenin, and 4'-demethyltraxillagenin may protect hepatocytes from CCl(4) injury by maintaining the GSH level.