• Journal of Life Science
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• v.23 no.8
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• pp.1057-1063
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• 2013

Citri Pericarpium is one of the most commonly used traditional herbal medicines in Korea, China, and Japan. Its extracts have many properties including the treatment of indigestion and inflammatory respiratory syndromes such as bronchitis and asthma. However, the underlying molecular mechanisms of anti-cancer activity and molecular targets are not fully understood. In this work, we investigated the anti-proliferative activity of Citri Pericapium (EMCP) methanol extract on reactive oxygen species (ROS) production and the association of these effects with apoptotic cell death using U937 human leukemia cells in vitro. EMCP treatment decreased cell proliferation in a dose-dependent manner following an increase of the sub-G1 phase, the down-regulation of Bax proteins, the activation of caspases, the degradation of poly (ADP-ribose) polymerase proteins (PARP), and the induction of ROS generation. However, the quenching of ROS generation by N-acetyl-L-cysteine administration, a scavenger of ROS, reversed the EMCP-induced apoptosis effects. In addition, heme oxygenase-1 expression also recovered by inhibiting the nuclear translocation of phosphorylated NF-E2-related factor 2. Taken together, our data indicate that ROS are involved as key mediators in the early molecular events in the EMCP-induced apoptotic pathway.

• Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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• v.61 no.12
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• pp.674-680
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• 2018

Background and Objectives The representative mucin genes in the human airway are MUC5AC and MUC5B, which are regulated by several inflammatory and anti-inflammatory substances. Triptolide (TPL), udenafil, betulinic acid, changkil saponin, and glucosteroid are some of the many anti-inflammatory substances that exist. TPL is a diterpenoid compound from the thunder god vine, which is used in traditional Chinese medicine for treatment of immune inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, nephritis and asthma. However, the effects of TPL on mucin expression of human airway epithelial cells have yet to be reported. Hence, this study investigated the effect of TPL on lipopolysaccharide (LPS)-induced MUC5AC and MUC5B expression in human airway epithelial cells. Subjects and Method The NCI-H292 cells and the primary cultures of human nasal epithelial cells were used to investigate the effects of TPL on LPS-induced MUC5AC and MUC5B expression using real-time polymerase chain reaction, enzyme immunoassay, and Western blot. Results TPL significantly decreased the LPS-induced MUC5AC and MUC5B mRNA expression and protein production. TPL also significantly decreased the nuclear factor-kappa B (NF-kB) phosphorylation. Conclusion These results suggest that TPL down regulates MUC5AC and MUC5B expression via inhibition of NF-kB activation in human airway epithelial cells. This study may provide important information about the biological role of triptolide on mucus-secretion in airway inflammatory diseases and the development of novel therapeutic agents for controlling such diseases.

• Natural Product Sciences
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• v.8 no.1
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• pp.1-15
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• 2002

An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.

• The Journal of Internal Korean Medicine
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• v.33 no.4
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• pp.418-428
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• 2012

Objectives : Ojeok-san, a traditional herbal formula, has been used for the treatment of cold illness and its related symptoms such as headache, nausea and indigestion. This study was performed to compare effects of water (OJSW) and 70% ethanol extracts (OJSE) of Ojeok-san on inflammation and its related diseases atopy, asthma and obesity in vitro. Methods : We performed HPLC to investigate contents of index components of OJSW and OJSE. We investigated the effects of OJSW and OJSE with an in vitro model, using 5 cell lines, specifically RAW 264. 7, HaCaT, MC/9, BEAS-2B and 3T3-L1. Results : HPLC analysis displayed that the contents of index components were higher in OJSE than OJSW. In lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, OJSE significantly inhibited productions of interleukin (IL)-6, nitrite and prostaglandin $E_2$ ($PEG_2$). In TNF-${\alpha}$/IFN-${\gamma}$-treated HaCaT keratinocytes, OJSE significantly lowered levels of macrophage-derived chemokine (MDC) as well as regulated and normal T cell expressed and secreted (RANTES). OJSE also had a protective effect on inflammatory response by decreasing RANTES secretion in TNF-${\alpha}$-stimulated BEAS-2B cells. Conclusions : We conclude that OJSE could be more appropriate to enhance the biological activities against inflammation and its related diseases, and could be applied as a bioactive material for developing the potent anti-inflammatory agents.

• Journal of Life Science
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• v.30 no.4
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• pp.343-351
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• 2020

Sorbus commixta Hedl. has traditionally been used as a remedy for cough, asthma, and other bronchial disorders. In this study, three major triterpenoids-lupeol, β-sitosterol, and ursolic acid and a coumarin, scopoletin, were isolated from a CHCl₃-soluble fragment of the bark of S. commixta. Their structures were identified by spectroscopic analyses, including mass spectrometry (MS), 1D-, and 2D- nuclear magnetic resonance spectroscopy (NMR), as well as by comparing the data with data reported in the literature. Scopoletin was isolated from this plant for the first time. It is a nutraceutical compound contained in many plants that has been reported to exert diverse biological activities, including anti-inflammatory effects. This study examined the inhibitory effect of scopoletin on TNF-α-induced vascular endothelial inflammation. Unlike the marginal impact of other compounds against low-density lipoprotein (LDL) oxidation and vascular endothelial inflammation, scopoletin showed remarkable activity on LDL oxidation (IC₅₀ = 10.2 μM) and exerted vascular anti-inflammatory effects in EA.hy926 human endothelial cells activated by TNF-α. It suppressed the expression of adhesion molecules, such as ICAM-1, VCAM-1, and E-selectin, and blocked the adhesion between THP-1 monocytes and EA. hy926 endothelial cells. It also inhibited TNF-α-induced NF-κB translocation from the cytosol to the nucleus. Moreover, IκBα phosphorylation, which was increased by TNF-α treatment, was reduced after treatment with scopoletin. Thus, scopoletin inhibited TNF-α-induced vascular inflammation in endothelial cells by suppressing the NF-κB signaling pathway. These results demonstrate that owing to its anti-inflammatory activity in the vascular endothelium, scopoletin has the potential to inhibit atherosclerosis development.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.221-227
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• 2006

Background : Cough may be a consequence of bronchial hyperresponsiveness or inflammation. Empirical treatment is important in this context because it difficult to verify the obvious cause of cough using laboratory tests, Corticosteroid has a nonspecific anti-inflammatory effect, and can be used for cough management. However, its response rate has not yet been fully elucidated. This study investigated the short- term effects of inhaled corticosteroid on chronic cough Methods : Patients with chronic cough with a normal chest radiograph and a pulmonary function test were enrolled. Cases with a prior respiratory infection within 8 weeks, a history of bronchial asthma, objective wheezing on examination, subjective symptoms of gastroesophageal reflux or taking an ACE inhibitor were excluded. On the first visit, a methacholine bronchial provocation test, spontaneous sputum eosinophil count performed twice and a paranasal sinus radiograph were checked, and the patients were treated with budesonide turbuhaler $800{\mu}g/day$ for ten days. The primary outcome measure was a decrease in the cough score after treatment. Results : Sixty nine chronic coughers were finally analyzed. The final diagnoses by the routine tests were as follows: bronchial asthma 13.0%, eosinophilic bronchitis 18.8%, paranasal sinusitis 23.2% and non-diagnostic cases 53.6%. The following responses to the inhaled corticosteroid were observed: definite responders, 76.8%, possible responders, 2.9% and non-responders, 20.3%. The response rate was not affected by the final diagnosis even in the non-diagnostic cases. There were minimal adverse drug related effects during the empirical treatment. Conclusion : Routine objective tests such as methacholine provocation, sputum eosinophil count and simple radiographs were notare not suitable for diagnosing chronic cough Therefore, empirical treatment is important. Short term inhaled corticosteroid is effective and can guide a further treatment plan for chronic cough.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.888-899
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• 1995

Background: Topical inhaled steroids, budesonide(Bu) and beclomethasone dipropionate (BOP), are now established as effective drugs in the management of chronic asthma. These drugs have high topical anti-inflammatory effect with low systemic activity. This study was performed to determine the effects of two inhaled corticosteroids, Bu and BOP, on the adrenocortical supression in 44 patients with bronchial asthma or chronic obstructive pulmonary disease. Methods: The adrenocortical function was assessed by measurement of serum cortisol concentration at 8 o'clock in morning and free cortisol in 24-hour urine collection at interval in 44 patients. No steroid was administered during the pretreatment period of 10 days and the final 6 days of the study. Each subject inhaled BOP or Bu, in daily doses of 800 or 1,600 micrograms for 12 days. The dose was delivered by metered dose inhaler (MDI) or diskhaler or large spacing device attached to MDI. Results: The levels of serum cortisol and 24-hour urinary free cortisol were decreased during the treatment period in patients inhaled Bu delivered by MDI in daily doses of 800 and 1,600 micrograms. In contrast, serum cortisol level was decreased on 6 and 12th day of treatment period in patients with BDP diskhaler in daily doses of 800 micrograms. In daily doses of 1,600 micrograms, the serum cortisol and 24hour urine free cortisol levels were decreased on 6, 9 and 12th day of treatment period in patients with BDP disk haler. The serum cortisol and 24-hour urinary free cortisol levels were not significantly decreased during the treatment period in patients inhaled Bu delivered by large spacing device attached to a MDI. Conclusion: These results showed that 1) the endogenous cortisol secretion was suppressed after inhalation of BDP and Bu in daily doses of 800 and 1,600micrograms, 2) Bu with MDI suppressed the adrenocortical function more than BDP with diskhaler, in daily doses of 1600 micrograms. and 3)large spacing device attached to a MDI might decrease the risk of suppression in the hypothalamic -pituitary- adrenal axis.

• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.147-158
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• 1996

Background : Endobronchial tuberculosis(ET) is known to affect frequently young female and serious complication like bronchial stenosis would occur if early diagnosis and treatment for ET is not performed immediately. But ET shows normal chest roentgenogram in about 10% of patients, and is often confused with bronchial asthma because ET presents clinical features like cough, dyspnea, wheezing in history and physical examination. The pulmonary function test(PFT) feature of ET is not well known, but when we consider the fact that ET is pathophysiologically different from bronchial asthma, if there is any feature of PFT in ET, and we know it, PFT will be very helpful for diagnosis and follow up of ET. Methods : We performed both PFT and bronchoscopy in 68 ET patients who visited Boramae hospital, and were confirmed as ET by bronchoscopic biopsy and were followed prospectively from November 1991 to March 1995. After history taking and physical examination, we performed chest roentgenogram, complete blood count, sputum AFB stain and culture, and also performed PFT before anti-tuberculosis chemotherapy. PFT was classified as restrictive, if only PVC was reduced below 80%, and obstructive, if only FEV1 was reduced below 75%. In the case of both FVC and FEV1 were reduced, PFT was classified as restrictive if FEY1/FVC was greater than 75%, and mixed if FEV1/FVC was reduced below 75%. We repeated the PFT and bronchoscopy for 68 ET patients who were proven by biopsy in the first month and sixth month after starting anti-tuberculosis chemotherapy, and studied the feature and change of PFT of the ET and the relation between PFT and the bronchoscopic finding, and obtained following results. Results: 1) Number of male patients was 12, and that of female patient was 56, and mean age was $35.4{\pm}17yr$.(17-74yr). Clinical symptom was in the order of cough(86.8%), dyspnea(63.2%), fever(17.6%) and hemoptysis (10.3%), and the wheezing and stridor were audible among the 40 patients(58.4%) in the physical examination. 2) Hemoglobin level was below 12g/dl among 25 patients (36.8%), and WBC level was above $10,000/mm^3$ among 9 patients(13.2%) and ESR was above 20 among 46 patients (67.6%) and AFB stain and culture were positive among 50 patients(73.5%). 3) The dominant roentgenographic finding of ET was fibronodular feature in 35 patients(51.5%), pneumonic feature in 14 patients (20.6%), collapse in 11 patients(16.2%), mass-like lesion in 3 patients(4.4%), cavitary lesion in 2 patients(2.9%), and normal in 3 patients(4.4%). 4) PFT feature at the time of diagnosis of ET was normal in 16 patients(23.5%), restrictive pattern in 32 patients (47%), obstructive in 4 patients(5.8%), and mixed in 14 patients(23.5%). So restrictive pattern was the dominate feature of ET. 5) The PFT feature was little correlated with the gross finding of bronchoscopy, but the change of PFT during treatment of ET showed relatively good correlation with the change of bronchoscopic finding. 6) FVC(2.30L vs. 2.61L) and FEV1(1.74L vs. 2.06L) increased significantly (p < 0.01), but FEV1/FVC(82% vs. 83%) and PEF(3.45L/sec vs. 3.95L/sec) did not change significantly after 1 month of treatment (p > 0.01), and there was no significant change among all parameters during first and sixth month of treatment(p > 0.01). Conclusion : PFT may be useful in the diagnosis and treatment follow up of ET but further study would be needed to confirm it.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.3
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• pp.306-313
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• 2017

Purple bamboo salt (PuBS) is commonly used as a medicinal food in Korea and has beneficial potentials such as antioxidant and anti-inflammatory effects. Rubus coreanus is called Bokbunja, which is used as a traditional medicine for treating asthma, impotence, and allergic diseases in Korea. The aim of present study was to investigate the immunostimulatory effect of PuBS composed with Rubus coreanus (PuBS-R). We performed comparative analysis between PuBS and PuBS-R in Raw264.7 cells, which is a mouse macrophage cell line, and peritoneal macrophages isolated primarily from the mouse peritoneal cavity. We evaluated cytotoxicity and the immune cytokine response in PuBS- and PuBS-R-treated cells. Both PuBS and PuBS-R did not have any cytotoxicity in Raw264.7 cells up to $500{\mu}g/mL$. Gene and protein levels of immune cytokines such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), $interferon-{\gamma}$ ($IFN-{\gamma}$), interleukin (IL)-10, and IL-12 were significantly elevated by PuBS-R more than PuBS in Raw264.7 cells. Moreover, we evaluated the immunostimulatory effects of PuBS-R on mouse primary peritoneal macrophages. Protein levels of inducible nitric oxide synthase, $TNF-{\alpha}$, $IFN-{\gamma}$, IL-10, and IL-12 were significantly higher in PuBS-R-treated peritoneal macrophages than PuBS-treated peritoneal macrophages. These results suggest the potential immunostimulatory effect of PuBS-R for immunity against harmful infection.

• Korean Journal of Clinical Laboratory Science
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• v.48 no.3
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• pp.188-195
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• 2016

Neutrophils and lymphocytes are essential inflammatory cells in the pathogenesis of allergy. In this study, we evaluated the role of house dust mite (HDM) in the interaction between allergic lymphocytes and neutrophils. The extract of Dermatophagoides pteronissinus (DP) showed a stronger anti-apoptotic impact on neutrophil apoptosis in the coculture of allergic neutrophils with allergic lymphocytes when compared with that in allergic neutrophils alone. DP increased IL-6, IL-8, MCP-1, and GM-CSF in allergic lymphocytes, and the increased cytokines were inhibited by rottlerin-an inhibitor of the protein kinase C (PKC) ${\delta}$, as well as by SB202190-a p38 MAPK inhibitor. DP activated p38 MAPK in a time-dependent manner. The activation of p38 MAPK was suppressed by PAR2i, which is a protease-activated receptor (PAR) 2 inhibitor, and rottlerin. Both aprotinin-a serine protease inhibitor-and E64-a cysteine protease inhibitor-were not effective on cytokine secretion of lymphocytes. These results, despite increased cytokines in allergic lymphocytes via DP, did not show any differences between asthma and allergic rhinitis. Molecules, including cytokines, released by DP in lymphocytes inhibited the migration of neutrophils. This finding may further elucidate the pathogenic mechanism of allergic diseases due to HDM.