• 생명과학회지
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• 제24권3호
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• pp.260-265
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• 2014

귤나무(Citrus unshiu)의 과피를 말린 한약재인 진피(Aurantii Nobilis Pericarpium; ANP)는 오래 전부터 대한민국을 비롯한 동아시아에서 위장관 운동 관련 질환의 치료에 전통적으로 쓰여 왔다. 본 연구에서는 진피 주정 추출물(ANP-E)을 제조하여 실험하였는데, 우선 ANP-E는 5 g/kg의 고용량을 mouse에 경구 투여하였을 때에도 급성독성을 나타내지 않았다. ANP-E가 위장관 운동 기능에 미치는 영향을 파악하고 이를 cisapride의 효과와 비교하기 위하여, mouse를 대상으로 위장관 이송률을 측정하는 실험을 수행하였다. Cisapride는 20세기 말까지 다양한 위장관 운동 저해 상황에서 임상적으로 광범위하게 적용되었던 최고의 위장관 운동 촉진제였으나, 치명적인 부작용으로 인하여 2000년 이후 시장에서 철수된 약물이다. 실험 결과, ANP-E는 정상 및 위장관 운동 저해 상황에서 모두 용량 의존적으로 위장관 운동을 촉진시키는 것으로 나타났다. ANP-E의 위장관 운동 촉진 효과를 cisapride와 비교해 보면, 정상 mouse에서는 cisapride와 거의 대등한 위장관 이송률 수치를 나타내었으며, 특히 위장관 운동 저해 상황에서는 cisapride보다 약효 및 안전성 측면에서 모두 비교 우위를 점하는 강력한 위장관 운동 기능개선 효과를 보였다. 이상과 같은 결과들은, ANP-E가 인간의 위장관 운동 기능 저해 상황을 개선할 수 있는 새롭고 강력한 신약 후보 물질이자, 아직 시장에 출현하지 않고 있는 cisapride의 대체 의약품으로서 개발 가능함을 시사하고 있다.

• International Journal of Oral Biology
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• 제42권4호
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• pp.183-190
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• 2017

Ficus carica L. (common fig), one of the first plants cultivated by humans, originated in the Mediterranean basin and currently grows worldwide, including southwest Asia and South Korea. It has been used as a traditional medicine for treatment of metabolic, cardiovascular, and respiratory diseases as well as hemorrhoids and skin infections. Its pharmacological properties have recently been studied in detail, but research on the anti-cancer effect of its latex has been only been studied on a limited basis on several cell lines, such prostate cancer, breast cancer, and leukemia. In this study, we investigated the anti-cancer activity of the latex of Ficus carica L.and its underlying mechanism in FaDu human hypopharynx squamous carcinoma cells. (See Ed. note above) We confirmed through SDS-PAGE analysis and gelatinolytic activity analysis that the latex of Ficus carica contains cysteine protease ficin. Our data showed that the latex inhibited cell growth in a dose-dependent manner. In addition, the latex treatment markedly induced apoptosis in FaDu cells as determined by FACS analysis, elevated expression level of cleaved caspase-9, -3 and PARP (poly (ADP-ribose) polymerase), and. increased the expression of Bax (pro-apoptotic factor) while decreasing the expression of Bcl-2 (anti-apoptotic factor). Taken together, these results suggested that latex containing the ficin inhibited cell growth and induced apoptosis by caspase and the Bcl-2 family signaling pathway in FaDu human hypopharynx squamous carcinoma cells. These findings point to the potential of latex of Ficus carica to provide a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.

• Journal of Ginseng Research
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• 제17권1호
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• pp.52-60
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• 1993

Panax ginseng has been extensively used in the traditional oriental medicine as a restorative, tonic and Prophylactic agent. Recently, several reports regarding to anticancer effects of Panax ginseng has accumulated. These studies emphasized the fact that the anticancer activities might be due to a glycoside group called ginsenoside or pan.u saponin which has a water soluble characteristic. However, the authors and collaborates demonstrated that a highly lipid soluble component in extract of Panax ginseng roots contains a considerable cytotoxic activities against marine leukemic cells (L1210, P388) and human censer cells (HRT-18, HT-29, HCT48). This study was devised to observe the cytotoxic activities of Petroleum-ether extract of Panax giuseng roots (crude GBD and its Partially Purified fraction from silicic acid column chromatography (7 : 3 GX) against sarcoma-180 (5-180) and Walker carcinosar- coma 256 (Walker 256) in vivo, and murine leukemic Lymphocytes (L1210) and human rectal cancer cells (HRT-18) and human colon cancer cells (HT-29 and HCT48) in vitro. Each cell-line was cultured in medium containing serial concentration of the crude GX or 7 : 3 GX in vitro. A highly lipid soluble compound in the extract of Panax ginseng root was cytocidal to murine leukemic cells and human colon and rectal cancer cells in vitro. In the meantime, ginseng saponin derivatives did not have cytotoxic effects at its corresponding concentration. The growth rates of the cancer cells in medium containing ginseng extracts were inhibited gradually to a significant degree roughly in proportion to the increase of the extract concentration. The cytotoxic activity of 7 : 3 GX was about 3 times more potent than that of crude GX, one unit of cytotoxic activity against L1210 cells being equivalent to 2.54 Ug and 058 Ug for the crude GX and 7 : 3 GX, respectively. The Ri value of the active compound on silica- gel thin layer chromatography with petroleum-ether/ethyl ether/acetic acid mixture (90 : 10 : 1, v/v/v) as a developing so lvent was 053. While, the Panaxydol and Panaxynol as active compounds were purified from Petroleum-ether extract of Panax ginseng root by Drs. Ahn and Kim, and author found out that the one unit of cytotoxic activity of the Panaxydol and Panaxynol against L1210 cells being equivalent to 056 Ug and 0.3918 respectively. The survival times of mice inoculated with S-180 cells were extended about 1.5 to 2 times by the 7 : 3 GX treatment compared with their control group. The significantly decreased hemoglobin values of rats after inoculation with Walker 256 were recovered to normal range by oral administration of the crude Gt The synthetic levels of protein, DNA and RNA in human colon and rectal cancer cells were significantly diminished by treatment with the crude GX, which can explain a part of the origin of its anticancer activity.

• Radiation Oncology Journal
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• 제28권2호
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• pp.99-105
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• 2010

목 적: 여러 통상적인 전뇌방사선치료 기법에서의 뇌와 수정체의 방사선 조사선량을 비교하고자 하였다. 대상 및 방법: 전뇌방사선치료를 위한 치료계획을 11명의 환자를 대상으로 컴퓨터단층촬영 영상을 이용하여 다음과 같이 수립하였다. 중심점이 조사영역의 중앙에 위치하고 가쪽눈구석(lateral bony canthus)에서 양측 빔이 평행한 통상적인 계획을 수립하고, 뇌에서 1 cm (렌즈에 대해서는 5 mm)의 여유로 차폐물을 생성하였다(P1). 이후 중심점을 가쪽눈구석으로 옮기고(P2), 조준기를 90도 회전시킨 후 5 mm 두께의 다엽조준기로 차폐를 하였다(P3). 각 환자의 모든 계획에서 P1의 중심점에 30 Gy를 처방하였다. 뇌와 수정체의 선량 지표들은 paired t-test를 이용하여 비교하였다. 결 과: 뇌의 $D_{max}$와 $V_{105}$는 P1에서 111.9%와 23.6%였다. 뇌의 $D_{max}$와 $V_{105}$는 P2와 P3에서 유의하게 감소하였는데, 그 값은 각각 107.2%와 4.5~4.6%였다(p<0.001). 수정체의 $D_{mean}$의 평균값은 P1에서 3.1 Gy, P2와 P3에서는 2.4~2.9 Gy였다(p<0.001). 결 론: 전뇌방사선치료 시 다른 복잡한 방법을 이용하지 않고, 중심점을 가쪽눈구석에 위치시키는 것만으로도 뇌와 수정체의 조사선량 측면에서 유리하였다.

• 생명과학회지
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• 제29권11호
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• pp.1241-1250
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• 2019

본 연구에서는 섬애약쑥(Artemisia argyi H.)의 생리활성 규명을 위한 연구의 일환으로 6종의 용매(butanol, chloroform, ethyl acetate, ethyl ether, hexane, methanol)로 추출하여 총 페놀화합물과 플라보노이드 함량, 항산화 및 파골세포 분화 억제 활성을 검증하였다. 섬애약쑥 용매별 추출물의 총 페놀 및 플라보노이드 화합물은 methanol 추출물에서 함량이 가장 높고 다음으로 butanol 추출물이 높으며, ethyl ether 및 hexane 추출물은 여타추출물보다 그 함량이 낮았다. ABTS 및 DPPH 라디칼 소거활성과 FRAP법에 의한 항산화력을 측정한 결과 methanol 추출물의 항산화활성이 유의적으로 가장 높았고 hexane 추출물의 활성이 유의적으로 가장 낮았다. NO 생성억제능은 비교적 저농도인 $2.5{\mu}g/ml$에서 6종 추출물 모두 확인되었으며, $20{\mu}g/ml$ 농도에서는 ethyl acetate가 가장 활성이 높고 다음으로 butanol 추출물에서 높게 측정되었다. ROS 생성 억제능은 농도 의존적으로 활성이 증가하였으며, $20{\mu}g/ml$ 농도에서 ethyl acetate 추출물과 butanol 추출물이 다른 4종의 추출물 대비 활성이 높았다. TRAP 염색을 통해 용매별 추출물들의 파골세포 분화 활성을 확인한 결과 6종 추출물 모두에서 농도 의존적으로 분화 억제 활성이 증가하였으며, butanol 추출물에서 분화 억제 활성이 가장 높았다. 이상의 결과들을 종합하여 볼 때 섬애약쑥 용매별 추출물 중 butanol 추출물이 항산화 활성과 파골세포 분화억제 활성이 모두 높기 때문에 향후 골다공증의 치료 및 예방에 있어서 유효할 것으로 추정된다.

• Journal of Ginseng Research
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• 제45권3호
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• pp.408-419
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• 2021

Background: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. Methods: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. Results: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. Conclusion: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

• Journal of Ginseng Research
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• 제45권1호
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• pp.134-148
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• 2021

Background: Lung cancer has a high incidence worldwide, and most lung cancer-associated deaths are attributable to cancer metastasis. Although several medicinal properties of Panax ginseng Meyer have been reported, the effect of ginsenosides Rk1 and Rg5 on epithelial-mesenchymal transition (EMT) stimulated by transforming growth factor beta 1 (TGF-β1) and self-renewal in A549 cells is relatively unknown. Methods: We treated TGF-β1 or alternatively Rk1 and Rg5 in A549 cells. We used western blot analysis, real-time polymerase chain reaction (qPCR), wound healing assay, Matrigel invasion assay, and anoikis assays to determine the effect of Rk1 and Rg5 on TGF-mediated EMT in lung cancer cell. In addition, we performed tumorsphere formation assays and real-time PCR to evaluate the stem-like properties. Results: EMT is induced by TGF-β1 in A549 cells causing the development of cancer stem-like features. Expression of E-cadherin, an epithelial marker, decreased and an increase in vimentin expression was noted. Cell mobility, invasiveness, and anoikis resistance were enhanced with TGF-β1 treatment. In addition, the expression of stem cell markers, CD44, and CD133, was also increased. Treatment with Rk1 and Rg5 suppressed EMT by TGF-β1 and the development of stemness in a dose-dependent manner. Additionally, Rk1 and Rg5 markedly suppressed TGF-β1-induced metalloproteinase-2/9 (MMP2/9) activity, and activation of Smad2/3 and nuclear factor kappa B/extra-cellular signal regulated kinases (NF-kB/ERK) pathways in lung cancer cells. Conclusions: Rk1 and Rg5 regulate the EMT inducing TGF-β1 by suppressing the Smad and NF-κB/ERK pathways (non-Smad pathway).

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.197-203
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• 2023

제주상사화(Lycoris chejuensis)는 우리나라에 자생하는 특산식물로 관상용으로의 가치가 높을 뿐만 아니라 다양한 약리성분을 함유하고 있어 약용적으로도 가치가 높은 식물이다. 그러나 종자번식이 이루어지지 않고 구근을 통해 번식이 이루어지며 소수의 개체가 자생하므로 산업적으로 활용하기에 어려움이 따른다. 따라서 본 연구는 식물의 종 특성을 벗어나 환경에 관계없이 대량화 할 수 있는 제주상사화 callus (LC)를 사용하였으며 미생물의 효소 작용을 이용하여 분자의 구조 수정을 유도하는 친환경 생물전환 기법인 biorenovation을 적용하여 활성을 증진시키고자 하였다. 이에 본 연구에서는 biorenovation 된 제주상사화 callus 추출물(LCB)의 항염증 활성을 마우스 대식세포인 RAW 264.7 세포에서 평가하였으며 앞서 LC 및 LCB가 세포의 생존에 미치는 영향을 조사한 결과 25, 50, 100 ㎍/mL 농도에서 LCB는 LC의 높은 세포독성을 감소하였음을 확인하였다. 또한 LCB는 세포 독성이 나타나지 않는 농도에서 nitric oxide 및 prostaglandin E₂를 효과적으로 억제하였으며 이들의 합성 효소인 inducible NO synthase, cyclooxygenase-2의 발현을 유의하게 억제함으로써 NO 및 PG E₂를 효과적으로 하향 조절함을 입증하였다. 뿐만 아니라 pro-inflammatory cytokines인 tumor necrosis factor-α와 interleukin-1β, interleukin-6의 발현 또한 유의하게 억제하는 것으로 확인되었다. 이러한 결과를 통해 LCB가 다양한 염증 인자를 표적으로 하는 항염증 소재로 적용될 수 있음을 제안한다.

• Journal of Ginseng Research
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• 제47권5호
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• pp.627-637
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• 2023

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

• 생명과학회지
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• 제25권1호
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• pp.113-120
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• 2015

골다공증은 골밀도(bone mineral density, BMD)가 평균 성인 정점에서 2.5 이상의 표준편차가 감소되는 뼈의 질환으로서 나이가 들어가면서 점차 증가하고 있다. 골다공증은 뼈를 흡수하는 파골세포와 뼈를 형성하는 조골세포로 이루어진 bone remodeling system의 불균형 때문에 발생한다. 이 불균형의 가장 큰 원인은 여성 폐경기 후에 따르는 에스트로겐 결핍 때문이다. 현재 골다공증의 치료에 사용되는 약들로는 호르몬 대체요법(hormone replacement therapy, HRT), biphosphonate, teriparatide 등이 있지만, 여러 가지 부작용 때문에 그들의 안정성과 실용성엔 의문의 여지가 있다. 더 안전한 대안을 찾기 위해 현재 천연물을 사용한 여러 가지 치료법이 연구되고 있다. Lactoferrin, isoflavone 등과 한약재를 이용한 많은 전통 치료법들이 있으며, 이는 뼈 흡수를 막거나, 뼈 동화를 일으킴으로써 골다공증 치료제로서의 가능성을 보여주고 있다. 그러나 대부분의 천연물 치료법은 지난 10여년간 괄목할만한 발전에도 불구하고 그 효능을 증명하기 위한 임상 예비단계에 머물고 있다. 따라서 천연물의 전임상 연구와 후속 임상 연구를 통해 새로운 골다공증 치료법으로 소개될 것이다.