• Journal of Ginseng Research
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• 제45권6호
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• pp.617-630
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• 2021

Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural nontoxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun Nterminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

• 생명과학회지
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• 제31권2호
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• pp.158-163
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• 2021

본 연구에서는 풋사과의 열수추출물(GAHW)과 에탄올추출물(GAE), 그리고 애사과 열수추출물(UAHW)을 제조하고 LPS로 활성화된 RAW264.7세포주를 이용하여 이들의 항염증 활성을 연구하였다. 모든 추출물이 세포생존율에는 영향을 미치지 않고 nitric oxide (NO) 생산을 저해하였으며, iNOS의 발현도 감소시켰다. 반면, UAHW만이 COX-2의 발현을 저해하였다. 또한 모든 추출물이 모든 MAPKs의 인산화를 감소시켰다. 모든 추출물이 ROS의 생산을 농도의존적으로 감소시켰으며, GAHW와 GAE에 의해 HO-1의 발현이 증가됨을 확인하였다. 또한, 사과 flavonoid인 phloretin과 phloridzin의 항염증 활성을 연구하였다. Phloretin은 농도의존적으로 NO의 생산을 저해하였으나, phloridzin은 NO 생산에 아무 영향이 없었다. 또한, phloretin은 iNOS와 COX-2 단백질의 발현을 감소시킨 반면, phloridzin은 두 단백질 발현에 영향을 주지 못하였다. 따라서, 이러한 연구결과는 사과 추출물은 MAPK 경로와 HO-1 경로를 조절함으로써 항염증 활성을 가지며, phloretin이 사과의 항염증 활성을 담당하는 파이토케미칼의 하나가 될 수 있음을 제시한다.

• 생약학회지
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• 제51권4호
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• pp.244-254
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• 2020

Atractylodes macrocephala is a perennial herb and is a member of the Compositae family. This plant is known to contain various bioactive constituents indicating anti-inflammatory, neuroprotective, anti-oxidant, immunological enhancement, and gastroprotective effects. In this investigation, we isolated four compounds with similar chemical structures from A. macrocephala, and evaluated their anti-inflammatory effects. Among the four compounds, compound 2(atractylenolide II) showed the second-best inhibitory effect on the lipopolysaccharide(LPS)-induced production of nitric oxide in RAW264.7 macrophages and BV2 microglial cells. Compound 2 also inhibited the LPS-induced the production of prostaglandin E2(PGE2), and the expression of inducible nitric oxide synthase(iNOS) and cyclooxygenase(COX)-2 proteins in both cells. In addition, compound 2 suppressed the production of pro-inflammatory cytokines including interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. These inhibitory effects were contributed by inactivation of nuclear factor kappa B(NF-κB) and mitogen-activated protein kinases(MAPKs) pathways by treatment with compound 2. This compound did not induce the expression of heme oxygenase(HO)-1 protein indicating that the anti-inflammatory effect of compound 2 was independent with HO-1 protein. Taken together, these results suggested that atractylenolide II can be a candidate material to treat inflammatory diseases.

• 한국식품과학회지
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• 제49권2호
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• pp.203-208
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• 2017

고지방식사를 섭취한 쥐의 신장에서 가압볶음 무말랭이 추출물의 산화방지, 항염증 효과를 확인하였다. 실험군은 chow diet와 증류수를 경구 투여하는 NOR group, 고지방식사와 증류수를 경구 투여하는 CON group, 고지방식사와 237 mg/kg bw/day농도의 DR과 RDR를 각각 경구 투여하는 DR group, RDR group으로 나누어 12주간 사육하였다. 신장의 산화스트레스 지표인 ROS, $ONOO^-$, 그리고 지방질과산화물의 농도를 확인한 결과 CON group이 NOR group에 비해 유의적으로 증가하였다. 반면 DR group과 RDR group에서 유의적으로 감소하였다. 체내 산화방지 지표인 글루타싸이온의 농도와 산화방지단백질의 발현은 DR group과 RDR group 모두 CON group에 비해 증가하였다. NF-${\kappa}B$ 발현은 CON group이 NOR group에 비해 증가하였으나 DR group과 RDR group은 모두 감소하였다. RDR group은 DR group에 비해 $ONOO^-$ 및 지방질과산화물 농도가 감소하였고 글루타싸이온 농도와 산화방지 관련 단백질 발현 중 Nrf2, HO-1, 카탈레이스, 그리고 GPx가 증가하였고 염증반응 전사인자인 NF-${\kappa}B$의 발현이 낮아졌다. RDR group의 산화스트레스 개선효과는 유의적으로 높은 것으로 확인되었다. 따라서 가압볶음무말랭이를 차로 제조하여 섭취할 때 고지방식사로 유도된 신장의 산화스트레스를 억제할 수 있을 것으로 사료되며, 그 효과는 무말랭이보다 높은 것으로 확인되었다.

• 생명과학회지
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• 제26권12호
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• pp.1458-1465
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• 2016

본 연구는 oxidative stress에 의한 세포죽음 분석의 이상적인 모델로 사용되는 HT22세포를 이용하여 천문동 에탄올추출물의 glutamate에 의한 oxidative toxicity에 대한 신경보호 효과를 살펴보았다. 이를 위해 cell viability, lactate dehydrogenase (LDH), 그리고 세포죽음형태, reactive oxygen species (ROS), mitochondria membrane potential (MMP) 등에 대한 flow cytometry 및 Western blot분석을 이용하였다. 천문동 추출물의 처리는 cell viability 및 LDH분석에서 glutamate에 의한 cell toxicity를 저하시키며, 특히 apoptotic cell death를 현저히 감소시켰다. ROS 및 MMP분석 결과, 천문동 추출물은 ROS의 형성을 저하시키며 glutamate에 의해 저하된 MMP를 현저히 회복시켜 주었다. 이와 관련된 단백질 발현을 보면, 천문동 추출물은 PARP 및 HO-1의 발현을 억제하였다. 이상의 결과는 천문동 추출물이 HT22해마세포에서 ROS형성저해 및 MMP회복에 의해 세포죽음을 완화시켜 보호작용을 하는 것으로 사료되며 oxidative toxicity관련 질환에 적용 가능할 것으로 보여 진다.

• 동의생리병리학회지
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• 제17권4호
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• pp.905-913
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• 2003

Oriental medicine explains aging as the weakening of Kidney-ai, and Kidney-strengthening herbal medicines such as Yukmijihwang-tang have been studied for anti-aging effects. In Western Medicine, the hypothesis that reactive oxidant species(ROS) contribute to the aging process is generally accepted. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective constituent of Yukmijihwang-tang in decreasing ROS production in oxidative-stressed cells. The purpose of this study is to confirm the anti-oxidant effect of MCR on PC12 cells, the expression of Heme oxygenase (HO), Macrophage migradon inhibitory factor (MIF), Catechol-O-methyltransferase (COMT) using real time RT PCR. PC12 cells were treated without or with hydrogen peroxide in the presence or absence of MCR using MTS assay. Hydrogen peroxide decreased the viability of PC12 cells by 53% and MCR did not influence that of stressed PC 12 cells irrespective of dose or incubation period. However, MCR showed an inhibitory effect on production of ROS in stressed cells, both dose and incubation time dependently. In particular, 1 ㎎/㎖ of MCR for 24 h culture almost returned to normal level. In the quantiation of anti-aging related gene expression, MCR at 1 ㎎/㎖ increased the expression of HO by 370%, MIF by 180% and COMT by 280% through real time RT PCR. In conclusion, MCR treatment protected PC12 cells from hydrogen peroxide and decreased ROS production and enhanced anti-oxidative gene expression such as HO, COMT and MIF, which suggests that MCR is involved in controlling anti-aging of nerve cells through elimination of cytotoxic stimuli.

• 한방재활의학과학회지
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• 제29권2호
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• pp.115-133
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• 2019

Objectives The purpose of this study was to evaluate the effects of Curcumae Longae Rhizoma pharmacopuncture on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods Osteoarthritis was induced by injection of MIA ($50{\mu}L$ with 80 mg/mL) into knee joint cavity of rats. Rats were divided into 6 groups. Normal group was injected by normal saline into knee joint cavity only. Control group was induced for osteoarthritis by MIA and orally administered with distilled water. Normal Saline group was induced for osteoarthritis by MIA and injected with normal saline $100{\mu}L$. Positive comparison group was injected with MIA and orally administered with indomethacin 5 mg/kg. Curcumae Longae Rhizoma pharmacopuncture low concentration (CL) group was induced for osteoarthritis by MIA and injected with Curcumae Longae Rhizoma pharmacopuncture low concentration $100{\mu}L$. Curcumae Longae Rhizoma pharmacopuncture high concentration (CH) group was induced for osteoarthritis by MIA and injected with Curcumae Longae Rhizoma pharmacopuncture high concentration $100{\mu}L$. Curcumae Longae Rhizoma pharmacopuncture was injected at ST35 and EX-LE4 each group (CL, CH). After that, hind paw weight distribution was measured and oxidative stress biomarker in serum, liver function biomarker in serum, western blot analysis were measured. Histological analysis of knee joint tissue was performed by hematoxylin and eosin staining, Safranin-O staining and Masson's trichrome staining. Results Hind paw weight distribution was significantly improved in both group. alanine aminotransferanse and aspartate aminotransferase were decreased significantly in CH group compare with Indomethacin threated group. Antioxidant enzyme glutathione peroxidase, Catalase and heme oxygenase-1 were increased in CH group compare with control group. Inflammatory cytokine cyclooxygenase-2, inducible nitric oxide synthase and interleukin-1 beta were decreased significantly in CH group. Histological analysis result shows that protective effects of joint and cartilage were observed in both CH and CL groups in a concentration-dependent. Conclusions The result suggest that Curcumae Longae Rhizoma pharmacopuncture has anti-oxidation effect, anti-inflammatory effect and also can prevent progression of osteoarthritis and protect joint cartilage.

• 생명과학회지
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• 제32권10호
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• pp.771-777
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• 2022

파킨슨병에서의 도파민 신경세포의 사멸 원인은 다양하며 별개의 유전적 요소와 환경적 요소들이 관여한다. 드물게 발생하는 유전성 파킨슨병에서 parkin의 돌연변이와 기능 상실은 주로 소포체 스트레스를 통해 중뇌 흑질의 도파민 신경세포를 특이적으로 손상시킨다. 상대적으로 일반적인 특발성 파킨슨병에서는 살충제 노출이 역학적으로 중요하다. 그러나 환경독성물질에의 노출과 유전성 파킨슨병의 연관성에 대해서는 잘 알려진 바가 없다. 본 연구에서는 잘 확립된 중뇌 유래의 도파민 신경세포주인 N27-A를 사용하여 특발성 파킨슨병과 유전성 파킨슨병 사이의 공통된 발병 기작의 증거를 확인하였다. 특발성 파킨슨병을 유발하는 유기염소계 살충제인 디엘드린은 BiP/Grp78, 헴산화효소-1과 같은 소포체 스트레스 반응 표지자를 발현 유도하였고, 특히 parkin 단백질의 발현을 증가시켰다. 디엘드린이 N27-A 세포를 사멸시키는 과정에서 소포체 스트레스 특이적 세포사를 매개하는 Caspase-12의 활성화가 유의미하게 증가하였다. 흥미롭게도 디엘드린에 의한 N27-A 세포의 사멸이 소포체 단백질인 parkin과 Bcl-2의 과발현시 유의미하게 억제되었다. 본 연구 결과, 소포체 스트레스의 누적이 특발성, 유전성 파킨슨병의 공통의 발병 기작일 가능성이 있으며, 몇 가지 소포체 관련 단백질들이 디엘드린에 의한 도파민 신경세포 손상으로부터 보호 효과를 가지는 것으로 보인다.

• 동의신경정신과학회지
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• 제21권2호
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• pp.125-140
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• 2010

Objectives : The purpose of this study is to examine from various angles the protective effect of Gastrodia elata Blume (GEB) against nerve cell death induced by $\beta$-amyloid by using the cell line SH-SY5Y, which is commonly utilized for toxicity testing in nerve cells, and to find out its mechanism of action. Methods : To begin with, as a result of assessing the rate of cell survival by employing MTT reduction assay, the treatment with $\beta$-amyloid at different concentrations caused cytotoxicity, which was inhibited by preprocessing GEB extract. In addition, after $\beta$-amyloid was processed with the cell SH-SY5Y, apoptosis progressed, which was reduced effectively by processing GEB extract. Results : When cytotoxicity was caused by using hydrogen peroxide, a representative ROS, in order to examine the antioxidant effect of GEB, its protective effect was also observed. Apart from ROS, reactive nitrogen species (RNS) are also known to play a crucial role in nerve cell death. The treatment with the NO donor SNAP increased the production of nitric oxide and the expression of iNOS, which was also inhibited by GEB extract. Meanwhile, as an attempt to find out the mechanism of action explaining the antioxidant effect, the intracellular antioxidant enzyme expressions were measured by RT-PCR, which showed that GEB extract increased the expressions of heme oxygenase-1, GAPDH and $\gamma$-glutamate cysteine ligase. Lastly, GEB extract had a protective effect against impaired memory induced by scopolamine in animal models (in vivo). Conclusions : These findings indicate that GEB has a protective effect against the death of cranial nerve cells, suggesting possibilities for the prevention and treatment of AD.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6651-6661
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• 2015

Breast cancer is a global health concern and is a major cause of death among women. In Oman, it is the most common cancer in women, with an incidence rate of 15.6 per 100,000 Omani females. Various anticancer remedies have been discovered from natural products in the past and the search is continuing for additional examples. Cytotoxic natural compounds may have a major role in cancer therapy either in potentiating the effect of chemotherapy or reducing its harmful effects. Recently, a few studies have reported advantages of using crude camel milk in treating some forms of cancer. However, no adequate data are available on the lyophilised camel's milk responsibility for triggering apoptosis and oxidative stress associated with human breast cancer. The present study aimed to address the role of the lyophilised camel's milk in inducing proliferation repression of BT-474 and HEp-2 cells compared with the non-cancer HCC1937 BL cell line. Lyophilized camel's milk fundamentally repressed BT-474 cells growth and proliferation through the initiation of either the intrinsic and extrinsic apoptotic pathways as indicated by both caspase-3 mRNA and its action level, and induction of death receptors in BT-474 but not the HEp-2 cell line. In addition, lyophilised camel's milk enhanced the expression of oxidative stress markers, heme-oxygenase-1 and reactive oxygen species production in BT-474 cells. Increase in caspase-3 mRNA levels by the lyophilised camel's milk was completely prevented by the actinomycin D, a transcriptional inhibitor. This suggests that lyophilized camel's milk increased newly synthesized RNA. Interestingly,it significantly (p<0.003) repressed the growth of HEp-2 cells and BT-474 cells after treatment for 72 hours while 24 hours treatment repressed BT-474 cells alone. This finding suggests that the lyophilised camel's milk might instigate apoptosis through initiation of an alternative apoptotic pathway.