• Title/Summary/Keyword: drug efficacy

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Cross-resistance Between Rifampicin and Rifabutin and Its Relationship with rpoB Gene Mutations in Clinically Isolated MDR-TB Strains (다제내성 결핵 균주에서 리팜핀과 리파부틴간의 교차내성률 및 rpoB 유전자 돌연변이와의 연관성)

  • Kim, Byoung Ju;Oh, Seung Hwan;Cho, Eun Jin;Park, Seung Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.2
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    • pp.171-179
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    • 2006
  • Background : Despite the emerging danger of MDR-TB to human beings, there have only been a limited number of drugs developed to treat MDR-TB since 1970. This study investigated the cross-resistance rate between rifampicin (RFP) and rifabutin (RBU) in order to determine the efficacy of rifabutin in treating MDR-TB. In addition, the results of rifabutin were correlated with the rpoB mutations, which are believed to be markers for MDR-TB and RFP resistance. Methods : The MICs of RBU were tested against 126 clinical isolates of MDR-TB submitted to the clinical laboratory of National Masan TB Hospital in 2004. Five different concentrations ($10-160{\mu}g/ml$) were used for the MICs. The detection of the rpoB mutations was performed using a RFP resistance detection kit with a line probe assay(LiPA), which contains the oligonucleotide probes for 5 wide type and 3 specific mutations (513CCA, 516GTC, and 531TTG) The rpoB mutation was determined by direct sequencing. Results : The rate of cross-resistance between RFP and RBU was 70.5%(74/105) at $20{\mu}g/ml$ RBU(ed note: How much RFP?) Most mutations (86.3%) occurred in the 524~534 codons. The His526Gln, His526Leu, Leu533Pro, Gln513Glu, and Leu511Pro mutations(Ed note: Is this correct?) were associated with the susceptibilty to RBU. Conclusion : Based on the cross-resistance rate between RFP and RBU, RBU may be used effectively in some MDR-TB patients. Therefore, a conventional drug susceptibility test for RBU and a determination of the critical concentration are needed. However, rpoB gene mutation test may be have limited clinical applications in detecting RBU resistance.

The Effect of Pleurodesis with Doxycycline in the Rabbit (토끼에서 Doxycycline을 이용한 흉막유착 효과)

  • Won, Kyoung-Sook;Park, Keon-Uk;Jeon, Won-Ho;Baik, Jae-Jung;Jeong, Yeon-Tae;Suh, Jung-Il;Son, Jin-Hee
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.5
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    • pp.531-536
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    • 1994
  • Background: The intrapleural instillation of tetracycline for pleural sclerosis had been most commonly used in patients with symptomatic malignant pleural effusion or recurrent pneumothorax for a long time. Unfortunately, at a time of expanding use of this agent, the production of injectable tetracycline hydrochloride used for pleurodesis was discontinued by its sole manufacturer in mid-1991 because the manufacturer was unable to meet US Food and Drug Administration purity standards. So we performed a preliminary study of doxycycline, as a alternative pleural sclerosant on rabbit pleura and compared its efficacy with that of tetracycline. Method: Eighteen New Zealand white rabbits weighing 2 to 3kg(mean 2.6kg) were devided into three groups. In each groups, one tetracycline(20 mg/ml/kg) and two doxycycline solutions(7 mg/ml/kg and 20 mg/ml/kg) instillated into the right pleural space through an 18-gauge angiocath with care to prevent pneumothorax. All rabbits were sacrificed after 28 days. Results: 1) In the group of tetracycline 20 mg/ml/kg(six rabbits), five rabbits showed partial pleural symphysis with several fibrous bands, and one rabbit died on 22th day. 2) In the group of doxycycline 7 mg/ml/kg(six rabbits), three rabbits showed partial pleural symphysis and the other three rabbits showed complete pleural symphysis without necrosis of underlying parenchymal lung tissue. 3) In the group of doxycycline 20 mg/ml/kg(six rabbits), two rabbits showed complete pleural symphysis without lung necrosis, another two rabbits showed complete pleural symphysis with lung necrosis, and the other two rabbits died on 4th and 13th day, respectively. Conclusion: We concluded that doxycycline is a highly effective sclerosing agent having stronger pleurodesis effect with that of tetracycline by dose base and its optimal dosage was considered as 7 mg/ml/kg with minimal complications.

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Prevalence and Clinical Outcome of Penicillin-resistant Pneumococcal Pneumonia (폐렴구균에 의한 지역사회 획득 폐렴에서 페니실린 내성률과 내성에 따른 임상경과에 관한 연구)

  • Hong, Ji Hyun;Lee, Hyung Seok;Jung, Seung Hyun;Kim, Gyu Won;Eom, Kwang-Seok;Lee, Jae Myung;Jang, Seung Hun;Kim, Dong Gyu;Hyoen, In Gyou;Lee, Myoung Koo;Park, Yong Bum;Jung, Ki-Suck;Lee, Young Kyoung
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.3
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    • pp.295-303
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    • 2003
  • Backgroung : The incidence of penicillin-resistant streptococcus pneumoniae(PRSP) accounts for almost 70% of all pneumococcal pneumonia cases in Korea. It is still unclear as to whether the efficacy of penicillin or equally active beta-lactam agents is compromised in PRSP pneumonia. This study investigated the prevalence of PRSP in community-acquired pneumonia and its clinical course. Methods : A total of 42 patients with community-acquired pneumococcal pneumonia were evaluated from July 1999 to May 2001. The cultured strains of Streptococcus pneumoniae were divided into susceptible, intermediately resistant, and resistant strains by an E-test, and the effect of the clinical course was investigated. Results : From a total of 42 patients, 22 (52.4%) patients had an intermediate resistance (MIC $0.1-1{\mu}g/m{\ell}$) and six (14.3%) showed a high resistance ($MIC{\geq}2.0{\mu}g/m{\ell}$) with current penicillin susceptibility categories. However, according to the classification of the DRSPTWG (Drug Resistant Streptococcus pneumoniae Therapeutic Working Group), there were 11 cases (26.2%) of intermediate resistance and no case of high resistance. Under empirical antimicrobial treatment, there was no difference in the clinical outcome between the penicillin susceptible and resistant group. Conclusion : The clinical outcome of PRSP pneumonia with empirical therapy was acceptable. These results suggest that the current MIC breakpoint for penicillin resistance in Streptococcus pneumoniae has been set at a very low level and penicillin resistance according to the NCCLS classification does not significantly influence the outcome of the empirical treatment for pneumococcal pneumonia.

Serotypes and Antimicrobial Susceptibility of Streptococcus pneumoniae (폐구균의 혈청형 분포와 항생제 감수성에 관한 연구)

  • Choi, Kyoung-Min;Kim, Jeong-Hyun;Shin, Kyoung-Mi;Yeon, Soo-In;Shin, Jeon-Soo;Yong, Dong-Eun;Lee, Kyoung-Won;Kim, Dong-Soo
    • Pediatric Infection and Vaccine
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    • v.10 no.2
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    • pp.159-166
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    • 2003
  • Purpose : Streptococcus pneumoniae is part of the normal flora but is also responsible for causing many invasive diseases such as pneumonia, meningitis, and sepsis in addition to noninvasive diseases such as otitis in children. Multi-drug resistant strains has raised a lot of concern worldwide and thus the importance of prevention has been emphasized. We have analyzed the current serotypes and antibiotic sensitivity of each serotype as a baseline study to estimate the efficacy of the pneumococcal vaccine in Korean children. Methods : One hundred sixteen cases of pneumococcus cultured at Yonsei Medical Center from September 2001 to January 2003 were analyzed. The serotyping was done with the Quellung reaction and penicillin resistance was tested using the oxacillin disc diffusion method. Results : Pneumococcus were cultured from the sputum in 76 cases(65.5%), from the blood in 13 cases(11.2%), from the ear discharge in 12 cases(10.3%), from the throat in 7 cases(6.0%), from the nasal cavity in 2 cases(1.7%), and one case(0.9%) each from the cerebrospinal fluid, eye discharge, peritoneal fluid, post-operational wound, brain abscess, and catheter tip. Serotyping was possible with 98 cases and the following serotypes were found; 15 cases of type 19F(15.3%), 11 cases of 19A(11.2%), 8 cases of 11A(8.2%), 7 cases each of 6A, 14 and 3(7.1%), 6 cases each of 35, 6B and 23F(6.1%). Eighty two cases(70.7%) out of 116 cases were penicillin resistant and serotypes 19F, 19A, 11A, 23F, 6A, 9V constituted the majority, 48 cases(59.8%). These serotypes showed resistance to cotrimoxazole (74.4%), tetracycline(69.5%), and erythromycin(90.3%) as well. In the 22 cases cultured from children, 19A and 19F were found in 25.0%, 6A, 6B, and 23F in 10.0%, 11A, 14, 19, and 29 in 5.0%. Fifty percent(10/20) of the clinical isolates were represented in the current 7-valent pneumococcal protein conjugate vaccine, and 85%(17/20) when the cross-reacting serotypes were included. Penicillin resistance was found in 86.4%(19/22). Conclusion : The percentage of serotypes included in the 7 valent pneumococcal protein conjugate vaccine found in our study was 40.8% which was less than other prior studies. In anticipation of a change of pneumococcal serotypes, a nationwide multicenter study is needed before the initiation of pneumococcal vaccines in Korea.

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Comparisons of 12-Hour and 24-Hour Sustained-Release Theophyllines in the Management of Asthma (천식치료에서 서방형 Theophylline의 1일 1회 제형과 1일 2회 제형의 비교)

  • Lee, Yang-Deok;Park, Seoung-Ju;Lee, Heung-Bum;Lee, Yong-Chul;Rhee, Yang-Keun
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.3
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    • pp.293-299
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    • 2001
  • Background : Sustained-release theophylline, which is generally prescribed as a twice-daily equal-dose regimen, is one of the more common asthma treatments. The development of a sustained-release drug delivery technology that enables improved control of the theophylline blood levels represents a significant advancement in both the efficacy and safety of dosing. Method : A crossover study was conducted with 25 adult chronic asthmatic patients requiring daily bronchodilator therapy. The study group included thirteen males and twelve females with ages ranging from 19 to 71 years. The overall approach was to place the patients first on the twice-daily preparation($Etheophyl^{(R)}$) for 28 days at 8 AM and 8 PM, and measure the pulmonary function and theophylline level on the 28th day. The patients were subsequently switched to the once-daily preparation($Uniphyl^{(R)}$) in the same daily dose at 8 PM on the 29th day and the same parameters were measured on the 56th day. Results : The mean serum levels of theophylline were $8.18{\pm}1.66\;{\mu}g/ml$ in the $Etheophyl^{(R)}$-treated period and $8.00{\pm}1.75\;{\mu}g/ml$ in the $Uniphyl^{(R)}$-treated period. ln addition, the $FEV_1$ showed $71.40{\pm}7.48$ percent in the $Etheophyl^{(R)}$-treated and $69.18{\pm}9.00$ percent in the $Uniphyl^{(R)}$-treated period. Thus there were no significant differences between the once-daily and twice-daily preparation. Conclusion : The results indicated little clinical differences between the two medications. The two drugs are equally effective in controlling asthma over the four weeks of treatment.

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A study of serotyping of Streptococcus pneumoniae by multibead assay (다중구슬 분석법에 의한 폐구균 혈청형 결정 연구)

  • Cho, Ky Young;Lee, Jung Ah;Cho, Sung Eun;Kim, Nam Hee;Lee, Jin A;Hong, Ki Sook;Lee, Hoan Jong;Kim, Kyung Hyo
    • Clinical and Experimental Pediatrics
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    • v.50 no.2
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    • pp.151-156
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    • 2007
  • Purpose : Streptococcus pneumoniae is a major etiologic agent for pneumonia, meningitis, otitis media, and sepsis among young children. Multi-drug resistant strains have raised great concern worldwide, thus the importance of prevention with vaccines has been emphasized. However, vaccines may force the appearance of pneumococcal infections by nonvaccine serotypes. Thus, distribution of pneumococcal serotypes should be monitored to estimate vaccine efficacy. We used a new and efficient multibead assay in determining pnemococcal serotypes. Methods : From January to February 2005, 643 children were recruited from ten day care centers to isolate pneumococci from their oropharynx. Pneumococcal serotyping was performed on 62 pneumococcal isolates from 60 children by multibead assay. This immunoassay required two sets of latex particles coated with pneumococcal polysaccharides and serotype-specific antibodies. Twenty four newly developed monoclonal antibodies specific for common serotypes and a pool of polyclonal rabbit sera for some of the less common serotypes were used. Results : The most prevalent pneumococcal serotypes were serotype 6A, 19A, 19F, 23F, and 11A/D/F which accounted more than 50 precent of all the 62 pneumococcal isolates. We found that multibead assay can be performed very rapidly and objectively. Conclusion : This multibead immunoassay was very useful in serotyping clinical isolates of S. pneumoniae because it was simple, reliable and fast.

Whitening effect of extracts from Matricaria chamomilla L. with B16F10 melanoma cells (B16F10 melanoma cell을 이용한 캐모마일(Matricaria chamomilla L.) 추출물의 미백 효과)

  • Jo, Jae-Bum;Kim, Myung-Uk;Lee, Eun-Ho;Kim, Ye-Jin;Cho, Eun-Bi;Kang, In-Kyu;Cho, Young-Je
    • Journal of Applied Biological Chemistry
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    • v.61 no.3
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    • pp.267-273
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    • 2018
  • Matricaria chamomilla L. has been used as a bath agent in Europe because of its sterilization effect on the skin. Flowers contain terpenes, flavonoids are effective in relieving inflammation. Matricaria chamomilla L. has been reported to have various drug efficacies such as sedation, anti-diabetic effect and anti-arthritic effect, but there is little research on the scientific efficacy of whitening effect. The purpose of this study was to examine the whitening effect of Matricaria chamomilla L. extract and to investigate the mechanism of inhibition of melanogenesis. The extracts were used to determine tyrosinase inhibitory activity. The tyrosinase inhibitory activity of extracts was ineffective for water extract but in 60% ethanol extract was shown in a concentration-dependent manner. B16F10 melanoma cell was measured using a powder obtained by lyophilization of 60% ethanol extract. The toxicity was observed at a concentration of $75{\mu}g/mL$. And concentration range was selected to be at most $50{\mu}g/mL$. The effect of tyrosinase, MITF, TRP-1 and TRP-2 on the expression of melanin protein was investigated in melanoma cells of B16F10 melanoma cells. As a result, it was confirmed that as the concentration of the extract increased, the melanogenesis level decreased and the protein expression level also decreased in a concentration dependent manner. Therefore, it was concluded that Matricaria chamomilla L. extract inhibited melanogenesis in cells. Based on the above results, it is expected that it will be used as a useful basic data for industrialization of whitening functional food of Matricaria chamomilla L.

A Study on Clinical Features and Pharmacologic Treatment Outcomes of Patients with Trigeminal Neuralgia (삼차신경통의 임상 소견과 약물 치료에 관한 연구)

  • Ko, Yu-Jeong;Kim, Kyun-Yo;Hur, Yun-Kyung;Choi, Jae-Kap
    • Journal of Oral Medicine and Pain
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    • v.34 no.2
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    • pp.207-216
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    • 2009
  • Trigeminal neuralgia is defined "a sudden, usually unilateral, severe, brief, stabbing, recurrent pain in the distribution of one or more branches of the fifth cranial nerve". The initial treatment of choice for trigeminal neuralgia is medical therapy. In patients with medically intractable pain or intolerable medication side effects, invasive therapeutic approaches are often necessary. Based on the amount of evidence and estimated efficacy, carbamazepine is the drug of choice in the management of trigeminal neuralgia. In case of insufficient or no response to carbamazepine, second-line drugs can be added. In this study, the author tried to review and analyzed the cases of 90 patients whom had visited for treatment of trigeminal neuralgia at the Department of Oral Medicine, Kyungpook National University Hospital from 2003 to 2008. The results were as follows: 1. Trigeminal neuralgia was significantly more common with advancing age, and nearly twice as common in women than men (ratio of 2.1:1) 2. The maxillary branch of the trigeminal nerve involved most often (51.1%), and the right side of the face is affected more commonly than the left (ratio of 2.9:1). 3. 85(94.4%) patients had experiences visiting medical or dental specialties before being referred to the Department of Oral Medicine. 4. 40(44.4%) patients with trigeminal neuralgia had systemic diseases. 5. Treatment with carbamazepine monotherapy was satisfactory initially in 69(76.7%) the patients, and the mean daily dose of carbamazepine was 402.9mg. On the other hand, 16(17.8%) patients expressed effectiveness after combination therapy of carbamazepine and other drugs. 6. Of the 69 patients who had a good initial response to carbamazepine monotherapy, 18 patients became resistant, so that combination therapy of carbamazepine and other drugs were necessary. 7. 54(60%) patients developed side effects such as dizziness, drowsiness, nausea, vomiting, blood dyscrasias, skin rash and constipation, and 11 of the patients decided to stop tmedicaion due to side effects.

The Tumor Control According to Radiation Dose of Gamma Knife Radiosurgery for Small and Medium-Sized Brain Metastases from Non-Small Cell Lung Cancer

  • Park, Sue Jee;Lim, Sa-Hoe;Kim, Young-Jin;Moon, Kyung-Sub;Kim, In-Young;Jung, Shin;Kim, Seul-Kee;Oh, In-Jae;Hong, Jong-Hwan;Jung, Tae-Young
    • Journal of Korean Neurosurgical Society
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    • v.64 no.6
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    • pp.983-994
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    • 2021
  • Objective : The effectiveness of gamma knife radiosurgery (GKR) in the treatment of brain metastases is well established. The aim of this study was to evaluate the efficacy and safety of maximizing the radiation dose in GKR and the factors influencing tumor control in cases of small and medium-sized brain metastases from non-small cell lung cancer (NSCLC). Methods : We analyzed 230 metastatic brain tumors less than 5 mL in volume in 146 patients with NSCLC who underwent GKR. The patients had no previous radiation therapy for brain metastases. The pathologies of the tumors were adenocarcinoma (n=207), squamous cell carcinoma (n=18), and others (n=5). The radiation doses were classified as 18, 20, 22, and 24 Gy, and based on the tumor volume, the tumors were categorized as follows : small-sized (less than 1 mL) and medium-sized (1-3 and 3-5 mL). The progression-free survival (PFS) of the individual 230 tumors and 146 brain metastases was evaluated after GKR depending on the pathology, Eastern Cooperative Oncology Group (ECOG) performance score (PS), tumor volume, radiation dose, and anti-cancer regimens. The radiotoxicity after GKR was also evaluated. Results : After GKR, the restricted mean PFS of individual 230 tumors at 24 months was 15.6 months (14.0-17.1). In small-sized tumors, as the dose of radiation increased, the tumor control rates tended to increase (p=0.072). In medium-sized tumors, there was no statistically difference in PFS with an increase of radiation dose (p=0.783). On univariate analyses, a statistically significant increase in PFS was associated with adenocarcinomas (p=0.001), tumors with ECOG PS 0 (p=0.005), small-sized tumors (p=0.003), radiation dose of 24 Gy (p=0.014), synchronous lesions (p=0.002), and targeted therapy (p=0.004). On multivariate analyses, an improved PFS was seen with targeted therapy (hazard ratio, 0.356; 95% confidence interval, 0.150-0.842; p=0.019). After GKR, the restricted mean PFS of brain at 24 months was 9.8 months (8.5-11.1) in 146 patients, and the pattern of recurrence was mostly distant within the brain (66.4%). The small and medium-sized tumors treated with GKR showed radiotoxicitiy in five out of 230 tumors (2.2%), which were controlled with medical treatment. Conclusion : The small-sized tumors were effectively controlled without symptomatic radiation necrosis as the radiation dose was increased up to 24 Gy. The medium-sized tumors showed potential for symptomatic radiation necrosis without signifcant tumor control rate, when greater than 18 Gy. GKR combined targeted therapy improved the tumor control of GKR-treated tumors.

Anti-inflammatory effects of fruit and leaf extracts of Lycium barbarum in lipopolysaccharide-stimulated RAW264.7 cells and animal model (염증유도 RAW264.7 세포와 동물모델에서 구기자와 구기엽의 항염 효능)

  • Bae, Su-Mi;Kim, Ji-Eun;Bae, Eun-Young;Kim, Kyung-Ah;Ly, Sun Yung
    • Journal of Nutrition and Health
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    • v.52 no.2
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    • pp.129-138
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    • 2019
  • Purpose: Medicinal herbs have recently attracted attention as health beneficial foods and source materials for drug development. Recent studies have demonstrated that extracts of Lycium's fruits and roots have a range of physiologically active substances. The extract of Lycium's leaves has been reported to have excellent anti-oxidant and anti-microbial activity, but its anti-inflammatory efficacy is not known. The chlorophyll present in the leaves can act as an anti-oxidant or pro-oxidant depending on the presence of light. Therefore, this study analyzed the anti-inflammatory effects of Lycium's fruit extract (LFE), leaf extract (LLE), and leaf extract with chlorophyll removal (LLE with CR). Methods: This study examined the inhibitory effects of LFE, LLE, and LLE with CR on pro-inflammatory mediator production as well as on the expression of iNOS and COX-2 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and BALB/c mice. Results: LFE, LLE, and LLE with CR inhibited the production of pro-inflammatory mediators (NO, $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) and the expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. Furthermore, the administration of LLE and LLE with CR inhibited the serum pro-inflammatory cytokine levels and suppressed DNA damage in BALB/c mice. In particular, LLE with CR exhibited the highest anti-inflammatory activity. Conclusion: These results suggest that the fruit and leaves of Lycium are potential therapeutic agents against inflammation.