Hee-jae Jung

Protective Effect of the Fruit Hull of Gleditsia sinensis on LPS-Induced Acute Lung Injury Is Associated with Nrf2 Activation

The fruit hull of Gleditsia sinensis (FGS) has been prescribed as a traditional eastern Asian medicinal remedy for the treatment of various respiratory diseases, but the efficacy and underlying mechanisms remain poorly characterized. Here, we explored a potential usage of FGS for the treatment of acute lung injury (ALI), a highly fatal inflammatory lung disease that urgently needs effective therapeutics, and investigated a mechanism for the anti-inflammatory activity of FGS. Pretreatment of C57BL/6 mice with FGS significantly attenuated LPS-induced neutrophilic lung inflammation compared to sham-treated, inflamed mice. Reporter assays, semiquantitative RT-PCR, and Western blot analyses show that while not affecting NF-κB, FGS activated Nrf2 and expressed Nrf2-regulated genes including GCLC, NQO-1, and HO-1 in RAW 264.7 cells. Furthermore, pretreatment of mice with FGS enhanced the expression of GCLC and HO-1 but suppressed that of proinflammatory cytokines in including TNF-α and IL-1β in the inflamed lungs. These results suggest that FGS effectively suppresses neutrophilic lung inflammation, which can be associated with, at least in part, FGS-activating anti-inflammatory factor Nrf2. Our results suggest that FGS can be developed as a therapeutic option for the treatment of ALI.

Herbal Formula, PM014, Attenuates Lung Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD), which is characterized by airway obstruction, leads to, as the two major forms of COPD, chronic bronchitis and emphysema. This study was conducted to evaluate the effects of herbal formula, PM014, in a murine model of COPD. Balb/c mice were treated once with each herb extract in PM014 or PM014 mixture via an oral injection. Lipopolysaccharide (LPS) or elastase/LPS were administrated to the mice to induce a disease that resembles COPD. PM014 treatment significantly attenuated the increased accumulation of immune cells in bronchoalveolar lavage fluid (BALF) compared to control mice. In addition, the TNF-α and IL-6 levels in BALF were decreased in the PM014 mice. Furthermore, histological analysis demonstrated that PM014 attenuated the hazardous effects of lung inflammation. These data suggest that PM014 exerts beneficial effects against forms of COPD such as lung inflammation.

Screening of herbal medicines for the recovery of cisplatin-induced nephrotoxicity

The goal of this study was to quantitatively determine the recovery effects of herbal medicines (HM) on the cisplatin-induced nephrotoxicity. In the present study, the recovery effects of 239 HM on HEK 293 cells that had been damaged by cisplatin were evaluated by a mitochondrial activity MTS assay. After the first round of screening, candidate HM were selected based on a recovery rate of greater than 20%. The efficacy of the selected herbs was then determined by dose response kinetic analysis. Of the extracts evaluated, 7 HM (Paeonia suffruticosa (PS), Curcuma longa (CL), Centipeda minima (CM), Loranthus parasiticus (LP), Pulsatilla dahurica (PD), Sinapis alba (SA), and Scutellaria barbata (SB)) had a strong recovery effect on cisplatin-induced damage in HEK 293 cells. An LDH assay showed that LP, CM, SB, CL, SA, and PS had the best recovery effect, whereas a comet assay indicated that PS, SB, SA, PD, and CL had the best recovery effect. Taken together, these results suggest that SB, CL, PS, and SA are the best candidate HM for the recovery of cisplatin-induced nephrotoxicity. Therefore, additional studies should be conducted to determine if these HM possess novel therapeutic agents that can be used for the prevention or treatment of renal disorders.

A Randomized Pilot Study of Acupuncture as an Adjunct Therapy in Adult Asthmatic Patients

Objective. This trial aimed to evaluate the feasibility of estimating the effectiveness of acupuncture on asthmatic patients under conventional medical management. Participations and Methods. A prospective randomized, patient/assessor-blinded, sham acupuncture–, and waiting list–controlled pilot trial was conducted. Forty-five eligible asthmatic participants underwent a 1-week run-in period and were then randomized into one of three groups: an active acupuncture group, a sham acupuncture group, and a waiting list group. They were instructed to maintain the use of antiasthmatic medications. Needling was administered three times per week for 4 weeks with a 2-week follow-up in the active and sham acupuncture groups. The primary outcome was daily morning peak expiratory flow (PEF) and the secondary outcomes included forced expiratory volume one second (FEV1), quality of life questionnaire for adult Korean asthmatics (QLQAKA), transition dyspnea index (TDI), serum eosinophil count, and total serum immunoglobulin E (IgE). Results. No significant differences in the between- or within-group values of weekly average PEF (recorded daily in the morning) and FEV1 were found. For QLQAKA and TDI, the active acupuncture group showed a significant improvement over the waiting list group at 2, 4, and 6 weeks after randomization. Discussion. Acupuncture as an adjunct therapy to conventional medical care does not seem to affect pulmonary function in asthmatic patients. However, 12 sessions of acupuncture treatment during 4 weeks showed a favorable effect on the quality of life in adult asthmatic patients. Further large trials assessing the effectiveness of acupuncture on the quality of life and symptoms in asthmatic patients are needed.

Traditional medicine Taeeumjowitangkagambang exerts antiobesity and hypolipidemic effects via antioxidant enzyme enhancement

Taeeumjowitangkagambang (ETJKB) is a traditional Korean medicine that has been clinically used for obesity with little mechanistic understanding. The present study investigated antiobesity and hypolipidemic effects of ETJKB in high fat diet fed rats as well as a 3T3‐L1 pre‐adipocyte differentiation model. ETJKB significantly inhibited the lipidogenesis in 3T3‐L1 adipocytes in a concentration‐dependent manner as well as reduced the cellular adipokine leptin level. Daily oral gavage of ETJKB to rats fed a high fat diet significantly attenuated body weight gain and abdominal and epididymal fat weights. ETJKB treatment also reduced the levels of total cholesterol, low density lipoprotein (LDL) and triglyceride as well as increased high density lipoprotein (HDL) in serum compared with the untreated control. Similarly, the ETJKB treatment decreased the levels of total lipid, triglyceride and cholesterol in liver tissue in high fat diet fed rats. Interestingly, ETJKB significantly increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px) and catalase in liver tissue, while decreasing the hydroxyl radical, thiobarbituric acid reactive substances (TBARS), carbonyl concentration. An improvement of antioxidant enzymes was associated with improved body weight control and healthier lipid profiles and therefore may play an important role in the antiobesity and hypolipidemic effects of ETJKB. Copyright

The anti-inflammatory effects of Alisma herb extract on allergic asthma mouse model

Asthma is a complex chronic inflammatory disorder in the airway accompanying airway hyperresponsiveness, airway obstruction and airway wall remodeling. Alisma canaliculatum (AC) is a constituent of Cheong-Sang-Bo-Ha-Tang (CSBHT) which had been frequently prescribed to treat the respiratory disease in traditional Korean medicine. Here, we investigated the precise mechanism of the anti-inflammatory activity of AC extract using ovalbumin-induced mouse asthma model. AC extract administration improved the mouse AHR, and alleviated the thickened airway epithelium. These effects may mediate by the inhibitory effect of AC extract on nuclear factor kappa B (NF-κB) activation. And the inhibitory effect regulated the inducible nitric oxide synthase (iNOS) expression at the transcription level. We determined the AC extract metabolites through UPLC/ESI-QTOF-MS and identified 10-O-methyl-alismoxide, 11-deoxyalisol C, 4-12-dihydroxyguaian-6,10-diene, alismol, alismoxide, alisol B, alisol B 23-acetate, alisol C 23-acetate, and alisolide. This study provides the full understanding about the anti-asthmatic effect of AC extract for the first time.

The Multi-Targeted Effects of Chrysanthemum Herb Extract Against Escherichia coli O157:H7

The Chrysanthemum lavandulifolium extract, which includes chrysoeriol, sudachitin, and acacetin, has excellent antibiotic effects on Escherichia coli O157:H7 (E. coli O157). A notable point is that the antibiotic targets of the herb extract are similar to the targets of commonly used antibiotic drugs, including bacterial cell wall biosynthesis, bacterial protein synthesis, and bacterial DNA replication and repair. In addition, the herbal antibiotic inhibits the etiological factors that contribute to the pathogenic property. The herbal sample was extracted and fractionated and then inoculated through a disk diffusion method to confirm its antibiotic effect against E. coli O157. Total RNA was isolated from the affected bacterial cells, and its expression level was analyzed through a microarray analysis. To confirm the accuracy of the microarray data, a real‐time PCR was performed. Three active compounds, chrysoeriol, sudachitin, and acacetin, were identified with a high‐performance liquid chromatography‐electrospray ionization/mass spectrometry chromatogram, and the disk diffusion study confirmed that chrysoeriol and sudachitin contribute to the antibiotic properties of the herb extract. The results demonstrate that the multi‐target efficacy of the herbal sample may indicate the potential for the development of more effective and safer drugs that will act as substitutes for existing antibiotics. Copyright

An Angiotensin I Converting Enzyme Polymorphism Is Associated with Clinical Phenotype When Using Differentiation-Syndrome to Categorize Korean Bronchial Asthma Patients

In this study, genetic analysis was conducted to investigate the association of angiotensin I converting enzyme (ACE) gene polymorphism with clinical phenotype based on differentiation-syndrome of bronchial asthma patients. Differentiation-syndrome is a traditional Korean medicine (TKM) theory in which patients are classified into a Deficiency Syndrome Group (DSG) and an Excess Syndrome Group (ESG) according to their symptomatic classification. For this study, 110 participants were evaluated by pulmonary function test. Among them, 39 patients were excluded because they refused genotyping. Of the remaining patients, 52 with DSG of asthma (DSGA) and 29 with ESG of asthma (ESGA), as determined by the differentiation-syndrome techniques were assessed by genetic analysis. ACE insertion/deletion (I/D) polymorphism analysis was conducted using polymerase chain reaction (PCR). Students t, chi-square, Fisher and Hardy-Weinberg equilibrium tests were used to compare groups. No significant differences in pulmonary function were observed between DSGA and ESGA. The genotypic frequency of ACE I/D polymorphism was found to differ slightly between DSGA and ESGA (P = .0495). However, there were no significant differences in allelic frequency observed between DSGA and ESGA (P = .7006, OR = 1.1223). Interestingly, the allelic (P = .0043, OR = 3.4545) and genotypic (P = .0126) frequencies of the ACE I/D polymorphism in female patients differed significantly between DSGA and ESGA. Taken together, the results presented here indicate that the symptomatic classification of DSGA and ESGA by differentiation-syndrome in Korean asthma patients could be useful in evaluation of the pathogenesis of bronchial asthma.

Global transcriptome analysis of the E. coli O157 response to Agrimonia pilosa extract

Antibiotics are certainly beneficial to treat the bacterial infection. However, inappropriate use puts patients at danger for avoidable adverse drug reactions. This inappropriate use accelerates the emergence of resistance and potentially increases overall health-care costs. In oriental pharmacology, herbal medicines had been used as an antibiotic drug, but its antibiotic mechanism has not yet been proved completely. Here, we studied the antibiotic effects of Agrimonia pilosa on E. coli O157:H7. Especially, it is noteworthy that the antibiotic efficacy of the herb extract on three proven targets for a main antibiotic drug: bacterial cell wall biosynthesis, protein synthesis and DNA replication and repair. The results show the antibiotic effects through the inhibition of bacterial cell wall synthesis, folic acid synthesis, and multidrug efflux.

Anti-Inflammatory Effects of Ginsenoside Rg3 via NF-κB Pathway in A549 Cells and Human Asthmatic Lung Tissue

Objective. There is limited information of the anti-inflammatory effects of Rg3 on inflamed lung cells and tissues. Therefore, we confirmed the anti-inflammatory mechanism of ginsenoside Rg3 in inflamed human airway epithelial cells (A549) and tissues whether Rg3 regulates nuclear factor kappa B (NF-κB) activity. Methods. To induce the inflammation, IL-1β (10 ng/ml) was treated to A549 cells for 4 h. The effects of Rg3 on NF-κB activity and COX-2 expression were evaluated by western blotting analysis in both IL-1β-induced inflamed A549 cell and human asthmatic airway epithelial tissues. Using multiplex cytokines assay, the secretion levels of NF-κB-mediated cytokines/chemokines were measured. Result. Rg3 showed the significant inhibition of NF-κB activity thereby reduced COX-2 expression was determined in both IL-1β-induced inflamed A549 cell and human asthmatic airway epithelial tissues. In addition, among NF-κB-mediated cytokines, the secretion levels of IL-4, TNF-α, and eotaxin were significantly decreased by Rg3 in asthma tissues. Even though there was no significant difference, IL-6, IL-9, and IL-13 secretion showed a lower tendency compared to saline-treated human asthmatic airway epithelial tissues. Conclusion. The results from this study demonstrate the potential of Rg3 as an anti-inflammatory agent through regulating NF-κB activity and reducing the secretion of NF-κB-mediated cytokines/chemokines.