Da-Young Jung

Hepatoprotective and Antioxidative Activities of Cornus officinalis against Acetaminophen-Induced Hepatotoxicity in Mice

The fruit of Cornus officinalis Sieb. et Zucc. is commonly prescribed in Asian countries as a tonic formula. In this study, the hepatoprotective effect of ethanolic extracts of the fruit of C. officinalis (ECO) was investigated in a mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice with ECO (100, 250, and 500 mg/kg for 7 days) significantly prevented the APAP (200 mg/kg) induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, and LDH). Parallel to these changes, ECO treatment also prevented APAP-induced oxidative stress in the mice liver by inhibiting lipid peroxidation (MDA) and restoring the levels of antioxidant enzymes (SOD, CAT, and HO-1) and glutathione. Liver injury and collagen accumulation were assessed using histological studies by hematoxylin and eosin staining. Our results indicate that ECO can prevent hepatic injuries associated with APAP-induced hepatotoxicity by preventing or alleviating oxidative stress.

Ursolic acid reduces prostate size and dihydrotestosterone level in a rat model of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is characterized by hyperplasia of prostatic stromal and epithelial cells, which can lead to lower urinary tract symptoms. The prevalence of BPH increases in an age-dependent manner. We investigated the protective effect of ursolic acid in BPH development using a testosterone-induced BPH rat model. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP), for a period of four weeks. Ursolic acid was administrated daily by oral gavage at a dose level of 5mg/kg during the four weeks of TP injections. Animals were sacrificed on the scheduled termination, before prostates were weighed and subjected to histopathological examination. TP and dihydrotestosterone (DHT) levels in the serum and prostate were also measured. BPH-induced animals displayed an increase in prostate weight with increased testosterone and DHT levels in both the serum and prostate. However, ursolic acid treatment resulted in significant reductions in prostate weight and testosterone and DHT levels in both the serum and prostate, compared with BPH-induced animals. Histopathological examination also showed that ursolic acid treatment suppressed TP-induced prostatic hyperplasia. These findings indicate that ursolic acid may effectively inhibit the development of BPH and it may be a useful agent in BPH treatment.

Protective effects of allantoin against ovalbumin (OVA)-induced lung inflammation in a murine model of asthma

Asthma is characterized by difficulty in breathing because of the constriction of the smooth muscles of the bronchi, as a result of inflammation. In the present study, we focus on the protective effects of allantoin against ovalbumin (OVA)-induced lung inflammation in a murine allergic model, and assess cytokine release, eosinophilia, and mucus hypersecretion. Allantoin treatment led to significant reduction in the levels of Ig(immunoglobulin)E and T-helper-2-type cytokines, such as IL(interleukin)-4 and IL-5, in bronchoalveolar lavage (BAL) fluid. Airway inflammatory-cell infiltration was remarkably alleviated in allantoin-treated asthma groups, compared with the control group. Moreover, allantoin-treated asthma groups exhibited a marked decrease in cytokine mRNA expression in lung tissues, compared with the control group. The effectiveness of allantoin was similar to that of montelukast, used as a positive control. These results support the utility of allantoin as a protective agent against asthma.

Alpinia katsumadai seed extract attenuate oxidative stress and asthmatic activity in a mouse model of allergic asthma

Allergic asthma is a chronic inflammatory disorder of the airways characterized by biphasic airway obstruction. Oxidative stress plays an important role in the development of asthmatic conditions. Thus, identification of oxidative stress markers in bronchoalveolar lavage fluid (BALF) and lung tissue from ovalbumin (OVA)-sensitized mice could provide new insights into both the pathogenesis of the disease and the possible use of anti-oxidants to alleviate disease severity. In this study, we investigated the effect of an ethanolic extract of Alpinia katsumadai seeds (AK) on a murine model of OVA-induced asthma model. The anti-oxidant and anti-asthmatic effects of AK on OVA-induced murine airway reaction were determined through observation of Th2-type cytokine levels, eosinophil recruitment, and lung histopathology. AK was found to significantly inhibit increases in Th2-type cytokines and mRNA expression such as IL-4 and IL-5 in BALF and lung tissue, and effectively suppressed IgE, IgG2a, eosinophilia, and mucus hypersecretion in the asthmatic mouse model. Also, the generation of reactive oxygen species (ROS) in BALF was diminished by AK treatment. These findings indicate that oxidative stress may play a crucial role in the pathogenesis of OVA-induced asthma model and that AK may have applications in the treatment of asthma.

Antioxidant and antiasthmatic effects of saucerneol D in a mouse model of airway inflammation.

Chronic airway inflammation is a hallmark of asthma, which is an immune-based disease. We evaluated the ability of saucerneol D, a tetrahydrofuran-type sesquilignan isolated from Saururus chinensis, to regulate airway inflammation in an ovalbumin (OVA)-induced airway inflammation model. Furthermore, we determined whether heme oxygenase (HO)-1 was required for the protective activity of saucerneol D. The airways of OVA-sensitized mice exposed to an OVA challenge developed eosinophilia and mucus hypersecretion and exhibited increased cytokine levels. Mice were administered saucerneol D orally at doses of 20 and 40mg/kg once daily on days 26-30. Saucerneol D administered orally significantly inhibited the number of OVA-induced inflammatory cells and the production of immunoglobulin E as well as Th2-type cytokines. Histopathology studies revealed a marked decrease in lung inflammation and goblet cell hyperplasia after saucerneol D treatment. In addition, saucerneol D induced HO-1 and led to a marked decrease in OVA-induced reactive oxygen species and malondialdehyde and an increase in superoxide dismutase and glutathione in lung tissues. These antioxidant effects were correlated with HO-1 induction. In our experiments, saucerneol D treatment reduced airway inflammation and suppressed oxidative stress in an OVA-induced asthma model.

Protective effects of Ulmus davidiana var. japonica against OVA-induced murine asthma model via upregulation of heme oxygenase-1

AIM OF THE STUDY Traditionally, the stem and root bark of Ulmus davidiana var. japonica (Ulmaceae) are Korean herbal medicines used for anti-inflammatory and anticancer therapy. In this study, we investigated the protective effects of Ulmus davidiana var. japonica ethanolic extract (UD) in a murine asthma model. Furthermore, we determined whether heme oxygenase (HO)-1 is required for the protective activity of UD. MATERIALS AND METHODS Airways of ovalbumin (OVA)-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. UD was applied 1h prior to OVA challenge. Mice were administered UD orally at doses of 100 and 200mg/kg once daily on days 18-23. Bronchoalveolar lavage fluid (BALF) was collected 48 h after the final OVA challenge. Levels of interleukin (IL)-4 and IL-5 in BALF were measured using enzyme-linked immunosorbent assays (ELISAs). Lung tissue sections 4 microm in thickness were stained with Mayers hematoxylin and eosin for assessment of cell infiltration and mucus production with PAS (periodic acid shift reagent) staining, in conjunction with ELISA, immunohistochemistry and Western blot analyses for HO-1 protein expression. RESULTS AND CONCLUSION Orally administered UD significantly inhibited the number of OVA-induced inflammatory cells and IgE production, along with reduced T-helper (Th)2 cytokine levels, such as IL-4 and IL-5, in BALF and lung tissue. In addition, UD induced a marked decrease in OVA-induced reactive oxygen species (ROS), inflammatory cell infiltration and mucus production in lung tissue. These effects were correlated with HO-1 mRNA and protein induction. Our results indicate that UD protects against OVA-induced airway inflammation, at least in part, via HO-1 upregulation.

The Fruits of Cudrania tricuspidata Suppress Development of Atopic Dermatitis in NC/Nga Mice

The fruits of Cudrania tricuspidata are a medicinal herb in Korea, known for its antiatherosclerotic and antiinflammatory effects. Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the influx of lymphocytes into the dermis. Using an animal model of AD, we assessed whether C. tricuspidata suppresses the development of AD‐like skin lesions. Cudrania tricuspidata was administered orally to NC/Nga mice with Dermatophagoides‐farinae‐induced AD‐like lesions for 49 days. The effects of C. tricuspidata were assessed by measuring clinical symptoms, swelling of the skin on the back and ears, and plasma concentrations of mTARC (mouse thymus and activation regulated chemokine), histamine and immunoglobulin E (IgE). We found that C. tricuspidata (60 mg/kg/day) inhibited the development of AD‐like skin lesions, reduced skin dermatitis scores and inhibited the histological changes induced by repeated application of D. farinae. In addition, C. tricuspidata inhibited the increases in plasma concentrations of mTARC, histamine and IgE induced by D. farinae. These findings indicate that C. tricuspidata inhibits the development of AD‐like skin lesions induced by repeated applications of D. farinae in sensitized NC/Nga by suppressing plasma concentrations of mTARC, histamine and IgE. Copyright

Simultaneous determination of liquiritin, hesperidin, and glycyrrhizin by HPLC-photodiode array detection and the anti-inflammatory effect of Pyungwi-san

A high-performance liquid chromatographic method was developed and validated to determine liquiritin, hesperidin, and glycyrrhizin levels in a traditional Korean medicine, Pyungwi-san (PWS). Reverse-phase chromatography using a C18 column operating at 40oC, and photodiode array detection at 254 nm and 280 nm, were used for quantification of the three marker components of PWS. The mobile phase using gradient flow consisted of two solvent systems. Solvent A was 1.0% (v/v) aqueous acetic acid and solvent B was acetonitrile with 1.0% (v/v) acetic acid. Calibration curves were acquired with r2 > 0.9999, and the relative standard deviation values (%) for intra- and inter-day precision were both less than 4.0%. The recovery of each compound was in the range 97.33–110.72%, with an relative standard deviation less than 6.0%. To provide information on the biological activity of PWS, anti-inflammatory action was evaluated. Production of nitric oxide and prostaglandin E2 were measured using the Griess reagent and enzyme-linked immunosorbent assay, respectively. PWS showed inhibitory effect on prostaglandin E2 production in LPS-treated RAW 264.7 cells.

Deletion of NAD(P)H:quinone oxidoreductase 1 represses Mre11-Rad50-Nbs1 complex protein expression in cisplatin-induced nephrotoxicity.

UNLABELLED The Mre11, Rad50, and Nbs1 (MRN) complex is a DNA double-strand break sensor involved in DNA damage repair. Herein, we explored whether deletion of NAD(P)H quinone oxidoreductase 1 (NQO1), a cytoprotective gene, affected MRN complex expression in the kidney after cisplatin-induced acute kidney injury (AKI). In vitro, cisplatin increased the expression of MRN complex proteins and NQO1 in NQO1-expressing ACHN cells in a time- and concentration-dependent manner. The expression of MRN complex proteins was relatively inhibited in NQO1-knockdown cells. In vivo, increased expression of renal MRN complex proteins was accompanied by upregulation of γ-H2A histone member X, a DNA damage marker, in cisplatin-treated wild-type mice. Although the NQO1-knockout (NQO1(-/-)) mice showed more severe cisplatin-induced renal damage, the renal expression of MRN complex proteins was lower than in NQO1-expressing mice; expression of poly[ADP-ribose] polymerase 1, which promotes MRN complex accumulation, was also lower in these animals. In addition, cisplatin-induced expression of DNA damage repair-related proteins, ataxia telangiectasia mutated and sirtuin1, markedly decreased in the NQO1(-/-) group, relative to the NQO1-expressing mice. These findings suggest that NQO1 deletion might be associated with decreased MRN complex expression, which might be partially responsible for the exacerbation of cisplatin-induced AKI in the absence of NQO1.

Growth arrest and DNA-damage-inducible 45 beta (GADD45β) deletion suppresses testosterone-induced prostate hyperplasia in mice

Aim: Growth arrest and DNA‐damage‐inducible 45 beta (GADD45&bgr;) is a member of the gene family associated with cell growth control, apoptosis, and DNA damage repair. The aim of present study was to determine the potential effects of GADD45&bgr; deletion on prostate hyperplasia progression. Main methods: LNCaP cells were incubated with testosterone propionate (1 &mgr;M) for 48 h and specific siRNA used to suppress GADD45&bgr; expression in vitro. For in vivo experiments, testosterone (3 mg/kg, IP) was injected into wild‐type (WT) and GADD45&bgr; knockout (GADD45&bgr;−/−) C57BL/6J mice for 21 consecutive days, and serum and prostate tissues subjected to biological and histochemical analyses. Key findings: GADD45&bgr;‐silenced LNCaP cells showed suppressed testosterone‐induced 5&agr;‐reductase 2 and androgen receptor expression compared to control LNCaP cells. Moreover, after 21 days of testosterone treatment, prostate weight and stromal tissue increment were relatively lower in GADD45&bgr;−/− than WT counterpart mice. Inhibition of testosterone‐induced 5&agr;‐reductase 2 and proliferating cell nuclear antigen expression in the GADD45&bgr;−/− group was confirmed via immunohistochemistry analyses. Significance: Although the exact correlation between GADD45&bgr; and prostate hyperplasia remains to be established, the present GADD45&bgr;deletion suppressed testosterone‐induced prostate hyperplasia which was accompanied by inhibition of 5&agr;‐reductase 2‐related protein expression.