• 대한한방내과학회지
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• 제27권2호
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• pp.394-406
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• 2006

Backgrounds and Objectives: Asthma is considered to be an inflammatory disease characterized by airway hyperresponsiveness and Pulmonary eosinophilia. And it is known the structure and function of IL-5, its receptor and the mechnism IL-5 triggered eosinophil accumulation and inflammaion of the airways. At this point of view, we assume which oriental materia medics can the splenocyte inhibit from secreting the IL-S in vitro. Material and Methosds: We used the splenocyte of mouse 8 weeks after its birth, and then cnltivated those into the 2 experimental groups and control group for 48 hours. The culture medium of experimental groups were made of $1{\mu}g/ml,\;10{\mu}g/ml$, oriental materia medics, representative. And the culture media of control group was given no oriental materia medica. Then, we assayed the quantity of cytokine-expression by the Sandwich ELISA. The quantifies of cytokine-expression of the experimental groups were compared with that of the control group which was standardized These method were used for the all of oriental materia medica treated. Results: In this study, we demonstrated that 12 oriental materia medica that inhibit the splenocyte from secreting the IL-5 in both $1{\mu}g/ml,\;and\;10{\mu}g/ml$ culture media. Those were Equiseti Herbs, Sophorae Subprostratae Radix, Moutan Radicis Cortex. Trichosanthis Radix, Buddleiae Flos. Cyperi Rhizoma. Benincasae Semen, Armeniacae Semen. Zedoariae Rhizoma, Astragali Semen, Dolichoris Semen. Lilii Bulbus, Asparagi Radix, Atractylodes Rhizoma White, Polygonati Officinallis Rhizoma. Conculusions: These findinga indicate that some oriental materia medica, specially Antipyretics, Herbs for Resolving Phlegm, Relieving Cough and Calming Wheezing and Herbs for Tonifring and Invigorating effects inhibit the splenocyte from secreting the IL-5. And further study experimented in vivo is needed for treating IL-5-driven inflammatory disease including asthma.

• 한국약용작물학회지
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• 제27권4호
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• pp.247-258
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• 2019

Background: Astragali radix (A) and Lithospermi radix (L) have long been used as traditional medicines due to their known anti-inflammatory effects. This study aimed at evaluating, their optimal mixing ratio and their functional compounds by investigating the inhibitory effects of mixed extracts of A and L and their active compounds on matrix metalloproteinases (MMPs). Methods and Results: A and L extracts were obtained by extraction at $80^{\circ}C$ using 50% and 70% fermented alcohol, respectively, and then mixed at a ratio of 5 : 5, 6 : 4, 7 : 3 and 8 : 2 (w/w). The activities of MMP-1, MMP-3, and MMP-13 were evaluated in interleukin-1beta ($IL-1{\beta}$)-induced SW1353 cells. The extract mixtures showed synergistic inhibitory effects on MMP-3 and MMP-13, higher than the effects of the individual A and L extracts. The 7 : 3 mixture (ALM16) showed the most effective MMPs inhibitory activity, while among the active ingredients, calycosin-7-O-${\beta}$-D-glucoside and lithospermic acid exhibited excellent MMPs inhibitory activity. Additionally, an HPLC method was established for simultaneous quantification of the effective components of the extract mixtures, and validated by measuring the linearity, precision and accuracy of the limit of detection (LOD) and limit of quantification (LOQ). Conclusions: ALM16 showed the most effective MMPs inhibitory activity. Calycosin-O-${\beta}$-D-glucoside, calycosin and lithospermic acid were identified as useful candidates, as they were the major functional compounds in the MMP inhibitory activity. Summarily, ALM16 might be a highly effective in osteoarthritis management, owing to its because it exhibits a protective effect on cartilage via excellent inhibition of MMPs.

• 대한한의학방제학회지
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• 제27권1호
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• pp.17-29
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• 2019

Inflammatory and oxidative stimuli play a critical role not only in the process of transforming normal cells into cancer cells, but also in the proliferation process of cancer cells. Sipyukmiryukieum (SYMRKU), a traditional Korean herb-combined remedy, is composed of 16 kinds of herbal medicines, which were recorded for "Ongjeo" treatment in "Dongeuibogam". In this study, we investigated the inhibitory effect of SYMRKU against inflammatory and oxidative responses in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Our results showed that SYMRKU significantly inhibited LPS-induced secretion of pro-inflammatory mediators including nitric oxide (NO) and prostaglandin $E_2$ without showing any significant cytotoxicity. Consistent with these results, SYMRKU down-regulated LPS-induced expression of their regulatory enzymes such as inducible NO synthase and cyclooxygenase-2. SYMRKU also inhibited LPS-induced production and expression of pro-inflammatory cytokines such as tumor necrosis factor-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6. In addition, SYMRKU significantly reduced the production of reactive oxygen species by LPS and showed a strong, which was associated with induction of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 expression. Although further studies are needed to fully understand the anti-inflammatory effects associated with the antioxidant capacity of SYMRKU, the findings of the current study suggest that SYMRKU may have potential benefits by inhibiting the onset and/or treatment of inflammatory and/or oxidative diseases.

• 대한수의학회지
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• 제63권3호
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• pp.27.1-27.9
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• 2023

Lespedeza cuneata (LC) is a perennial plant used in herbal medicine to treat numerous diseases, including prostatic hyperplasia, diabetes, early atherosclerosis, and hematuria. Reference collections of bioactive compounds of LC are crucial for the determination of their pharmacological properties. However, little is known regarding its anti-oxidative and anti-inflammatory effects in alveolar macrophage (MH-S) cells. This study examined whether LC can inhibit reactive oxygen species and Coal fly ash (CFA) induced inflammation in MH-S cells. The anti-oxidative effects of LC were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, anti-inflammatory effects were examined using nitric oxide (NO) assay, and cytotoxicity was analyzed using methyl thiazolyl tetrazolium assay. The expression of inflammatory cytokine genes was assessed through a reverse-transcription polymerase chain reaction. Our results revealed that LC exhibited high radical scavenging activity and a dose-dependent (7.8-1,000 ㎍/mL) inhibition of oxidation as compared to ascorbic acid and Trolox. It also inhibited CFA-induced NO production in MH-S cells. Moreover, it suppressed the CFA exposure-mediated expression of pro-inflammatory mediators and cytokines, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. These results suggest that LC is a potent antioxidant and anti-inflammatory agent that can be useful as a nutraceutical product.

• 대한한방내과학회지
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• 제27권4호
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• pp.864-878
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• 2006

목적 : 인삼은 다양한 생물학적 작용이 있다. 그 중 항염증작용과 관련하여 염증성 사이토카인 분비 및 저산소 유도인자-1${\alpha}$ 활성화 조절 효과를 살펴보고자 한다. 방법 : phorbol myristate acetate (PMA)+A23187에 유도된 세포에서 염증성 cytokines 분비의 변화와 인간의 mast cell인 HMC-1 cells에서 hypoxia-inducible factor-1 (HIF-1)${\alpha}$의 작용을 관찰하였다. 결과 : PMA+A23187은 대조군과 비교해서 interleukin $(IL)-1{\beta}$, IL-6와 tumor necrosis factor $(TNF)-{\alpha}$의 분비를 증가시킨다. 또한 증가된 cytokines IL-1, IL-6, $TNF-{\alpha}$가 인삼의 처리에 의해 두드러지게 억제하는 것을 확인하였다. 인삼(5 ${\mu}g/ml$)은 $IL-1{\beta}$, IL-6, $TNF-{\alpha}$의 분비를 약 105.1${\pm}$9.7%, 95${\pm}$9.4%, 29.7${\pm}$4.5%,(P<0.05)로 최대로 억제하였고, PMA+A23187에 유도된 vascular endothelial growth factor (VEGF)와 granulocyte macrophage-colony stimulating factor (GM-CSF)의 분비를 41.3%와 75.7%로 각각 억제하였다. 그리고 저자는 인삼이 PMA+A23187로 유도된 HIF-1${\alpha}$ 발현과 HIF-1에 대해 DNA binding activity를 억제하고 있음을 관찰하였다. 결론 : 인삼이 HIF-1에서 염증반응을 억제함을 나타내고, 이는 인삼이 염증성 질환을 치료하는데 유익한 효과가 있음을 의미한다.

• 한국자원식물학회지
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• 제31권5호
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• pp.466-477
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• 2018

본 연구는 헛개나무 잎, 줄기, 뿌리로부터 얻어진 메탄올 추출물의 항염증 효과를 구명하기 위해서 수행되었다. LPS로 염증이 유도된 RAW264.7 세포 내 부위별 추출물을 동시에 처리하여 염증 매개성 물질인 NO 생성량 분석 결과 $40{\mu}g/m{\ell}$농도에서 뿌리(94.7%)와 줄기(42.6%)에서는 효과가 있는 반면 잎에서는 효과가 없는 것으로 확인되었다. 이 중 탁월한 효과를 보인 뿌리 추출물(RE)의 항염증 효과 및 관련 분자적 기전을 확인하였다. 그 결과, 염증 반응의 주요 경로인 NF-kB 및 MAPK 신호전달경로에서 RE가 LPS로 유도된 NF-kB의 핵 이동을 억제하고, ERK, JNK, p38의 인산화를 억제함으로써 iNOS, COX-2의 발현이 감소되고, NO와 pro-inflammatory cytokine (IL-6, $IL-1{\beta}$, $TNF-{\alpha}$)의 생성이 억제됨을 확인하였다. 또한 RE는 대식세포에서 Nrf2를 활성화시켜 항염증성 단백질인 HO-1 발현을 유도하여 항염증 효과를 나타내었다. 또한, RE로부터 주요 성분을 분리한 후 NMR과 MS 기기를 이용하여 구조 동정된 27-O-protocatechuoylbetulinic acid 화합물에서도 높은 항염증 효과를 확인하였다. 이러한 연구결과는 헛개나무뿌리와 그 주요성분은 의약품 소재 및 기능성 식품 등의 기능성 소재로 활용될 수 있는 기초적인 정보를 제공할 것으로 생각된다.

• 동의생리병리학회지
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• 제27권1호
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• pp.83-91
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• 2013

Pruritus is a unpleasant symptom in the skin that provokes the act of or desire to scratch. Mast cells are important effector cells in allergic reactions such as pruritus and inflammation. The purpose of this study was undertaken to investigate the synergic anti-pruritic and anti-inflammatory effects of Scutellariae Radix (SB) plus Flos Loncerae (FL) extracts in rat peritoneal mast cells (RPMCs), pruritogen-induced scratching mice and 2,4-dinitrofluorobenzene (DNFB)-induced allergic mice. We investigated the effect of SB, FL and SB plus FL extracts on the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, and histamine in RPMCs, on the scratching behavior in ICR mice, and skin clinical serverity and inflammatory mediators in DNFB-induced allergic hairless mice. RPMCs stimulated with PMA plus A23187 or compound 48/80 significantly increased TNF-${\alpha}$, IL-$1{\beta}$ or histamine production compared with media control. However, TNF-${\alpha}$ IL-$1{\beta}$ or histamine levels increased by PMA plus A23187 or compound 48/80 treatment were significantly inhibited by SB, FL in a dose-dependent manner. Especially, SB plus FL pretreatment had a synergic inhibitory effects on stimulator-induced cytokines (TNF-${\alpha}$ and IL-$1{\beta}$) and histamine production. Moreover, SB plus FL administration had a synergic inhibitory effects on the scratching behavior induced by pruritogen (compound 48/80, histamine, serotonin, substance P) in ICR mice. Furthermore, SB plus FL administration had a synergic inhibitory effects on skin damage, inflammatory mediators, leukocyte and mast cell infiltration induced by DNFB in hairless mice. These results suggest that SB plus FL administration has a potential use as a medicinal plant for treatment against itching and inflammation-related skin disease.

• 대한한방내과학회지
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• 제27권3호
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• pp.639-652
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• 2006

Objective : The etiology of chronic prostatitis is likely multifactorial, resulting from either a cascade of events after an initiating factor or from a variety of etiologic mechanisms. There is substantiating evidence to support the role of the inflammatory responses in its pathogenesis, and the clinical value in the evaluation of therapeutic efficacy. Forsythiae Frucus has been traditionally used in treatment of inflammatory diseases, including of prostatitis and urinary tract inflammation. In this study, we investigated the effects of Forsythiae Frucus on inflammatory cytokines and cyto-pathological alternation in the rat model of chronic non-bacterial prostatitis induced by castration and $17{\beta}$-estradiol treatment. Methods : Two-month-old rats were treated with $17{\beta}$-estradiol after castration for induction of experimental non-bacterial prostatitis. which is similar to human chronic prostatitis in histopathological profiles. Forsythiae Frucus as an experimental specimen, and testosterone as a positive control, were administered orally. The prostates were evaluated by histopathologlcal parameters including the epithelial score and epithelio-stromal ratio for glandular damage. and the expression of inflammatory cytokine genes including interleukin (IL)-$1{\beta}$, IL-5, IL-12, tumor necrosis factor (TNF)-$\alpha$. eotaxin, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(cox-2). Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation. the rats treated with Forsythiae Frucus showed a diminished range of tissue damage. Epithelial score was improved in the Forsythiae Frucus group over that of the control (P<0.05). The epithelia-stromal ratio was lower in the Forsythiae Frucus group when compared to that of the control (P<0.05). In the reverse transcription-polymerase chain reaction (RT-PCR) of inflammatory cytosine genes. Forsythiae Frucus inhibited the expression of IL-$1{\beta}$, TNF-$\alpha$, iNOS, cox-2 genes, while it modulated the expression of IL-5, which is an anti-inflammatory cytokine. Conclusions : These findings suggest that Forsythiae Frucus may protect the glandular epithelial cells and also inhibit stromal proliferation in association with the immune modulation including the suppression of inflammatory cytokines and increase of anti-inflammatory cytokines. From theses results. we suggest that Forsythiae Frucus could be a useful remedy agents for treating chronic non-bacterial prostatitis.

• Restorative Dentistry and Endodontics
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• 제27권5호
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• pp.463-472
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• 2002

Bacterial lipopolysaccharide (LPS) plays a major role in stimulating the synthesis and release of the principal osteoclast-activating cytokines, namely, interleukin 1 and tumor necrosis factor-$\alpha$ from immune cells. Although rnonocytes/macrophages are the main producers of these cytokines, recent evidence has indicated that polymorphonuclear leukocytes (PMN) have the ability to release IL-1 and TNF-$\alpha$. Calcium hydroxide has been shown to be an effective medicament in root canal infections, reducing the microbial titre within the canal. It has been proposed that the therapeutic effect of Ca(OH)$_2$ may also be the result of direct inactivation of LPS. The purpose of this study was to investigate whether treatment of Porphyromonas endodontalis LPS with calcium hydroxide alters its biological action as measured by human PMN secretion of IL-1 and TNF-$\alpha$, and it was compared with Escherichia coli LPS. P. endodontalis ATCC 35406 was cultured in anaerobic condition, and LPS was extracted using the hot-phenol water extraction method and purified. Purchased E. coli LPS was also purified. 100 $\mu\textrm{g}$/ml of each LPS in pyrogen free water were incubated with 25mg/ml Ca(OH)$_2$ at 37$^{\circ}C$ for 7 days. The supernatants were subjected to ultrafiltration, and the isolates were lyophilized and weighed. PMNs were obtained from peripheral blood by centrifugation layered over Lymphoprep. The cells were resuspended (4$\times$10$^6$ cells/ml) in RPMI 1640 followed by treatment with various concentrations of LPS (0, 0.1, 1, 10$\mu\textrm{g}$/ml) for 24 hours at 37$^{\circ}C$ in 5% $CO_2$ incubator. The supernatants of cells were collected and the levels of IL-1$\alpha$, IL=1$\beta$ and TNF-$\alpha$ were measured by enzyme-linked immunosorbent assay. The results were as follows ; 1. The levels of IL-1$\alpha$, IL-1$\beta$, TNF-$\alpha$ from PMN treated with each LPS were significantly higher than those released from unstimulated PMN of the control group (p<0.05). 2. The levels of all three cytokines released from PMN stimulated with each calcium hydroxide treated LPS were significantly lower than those released from PMN stimulated with each untreated LPS (p<0.05), while they were not significantly different from those released from unstimulated PMN of the control group (p>0.05) 3. The levels of secretion for all three cytokines were affected in a dose-dependent manner in PMN stimulated with each LPS (p<0.05), but not in PMN stimulated with each calcium hydroxide treated LPS (p>0.05). 4. The levels of all three cytokines released from PMN stimulated with p. endodontalis LPS were significantly lower than those released from PMN stimulated with E coli LPS (p<0.05).

• Clinical and Experimental Pediatrics
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• 제50권9호
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• pp.882-890
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• 2007

목 적 : 제대혈액 내 줄기세포 자가 이식이 극소저출생 미숙아의 신경학적 손상을 방지할 수 있는지 알아보고자 하였다. 방 법 : 출생체중 1,500 g 미만, 제태연령 32주 이하인 미숙아 26명을 대상으로 하였다. 환자의 제대혈에서 단핵구만 분리한 후 생후 24-48시간 사이에 단핵구로서 평균 $5.87{\times}10^7/kg$개를 정맥주사 하였다. 평가 변수들로서는 저산소성-허혈성 뇌증의 예측 지표로 사용되는 유핵 적혈구수, 소변내의 uric acid/creatinine 비와 NSE, IL-6, $IL-1{\beta}$ 등과 신경세포 보호 작용이 있는 것으로 알려진 GDNF의 농도를 혈청 및 뇌척수액에서 측정하였다. 임상적으로는 생후 1개월의 두위 증가 정도와 함께 뇌 병변, 기관지폐이형성증, 미숙아 망막증, 괴사성 장염 등의 발생 정도를 평가하였다. 결 과 : 1) 소변내 uric acid/ceartinine 비는 줄기세포 자가 이식군과 대조군 사이에 차이가 없었으나 유핵 적혈구수의 감소는 줄기세포 이식군에서 빠르게 감소하는 경향을 보였다. 2) 제대혈 자가 줄기 이식 전후에 시행한 혈청 NSE와 IL-6는 생후 제 7일에 의미 있게 감소하였으나 뇌척수액에서는 통계학적인 의미를 보이지 않았다. 혈청 $IL-1{\beta}$는 생후 제 7일에 감소하고, 혈청 GDNF 농도는 줄기세포 이식 후 증가하는 경향을 보였으나 모두 통계학적인 의미는 없었고 뇌척수액에서도 차이를 보이지 않았다. 3) 생후 1개월에서의 두위 성장(2 cm 이상)은 줄기세포 이식군에서 11명(46%), 대조군은 3명(27%)이었다. 4) 생후 1개월에서의 뇌병변은 줄기세포 이식군 24명 중 3명에서 뇌실주위 연화증이 발생하였고 그 중 1명은 뇌실확장증을 동반하였으며 대조군에서는 11명 중 2명에서 뇌실주위 백질연화증과 뇌실확장증이 발생하였다. 5) 줄기세포 이식군에서 기관지폐이형성증 및 괴사성 장염이 각각 1명씩 발생하였고 대조군에서는 미숙아 망막증이 2명에서 발생하였다. 6) 줄기세포 이식군에서 신생아호흡곤란 증후군과 연관된 패혈증으로 2명이 사망하였으며 제대혈 줄기세포 자가 이식과는 연관관계가 없었다. 결 론 : 극소 저출생체중 미숙아에서 제대혈 자가이식술은 윤리적인 문제없이 쉽게 시행할 수 있는 안전하고 실용적인 신경손상 예방 및 치료법으로 기대된다. 향후 장기적인 신경학적 추적 검사 및 비침습적이며 정교한 평가 변수 확립이 필요하다.