• Title/Summary/Keyword: herbal toxicity

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DNA and Proteomic Expression of Cervi parvum cornu Herbal-acupuncture Solution (CPC-HAS) in HepG2 carcinomar cells (녹용약침액(鹿茸藥鍼液)의 간암세포주(肝癌細胞柱)에 대한 DNA 및 단백질 발현(發顯))

  • Ryu, Sung-Hyun;Lee, Kyung-Min;Lee, Bong-Hyo;Lim, Seong-Chul;Jung, Tae-Young;Seo, Jung-Chul
    • Journal of Pharmacopuncture
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    • v.9 no.2
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    • pp.5-16
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    • 2006
  • Objective : It has long been known about the osteogenic effect of CPC-HAS on bone tissues. However, it has not been determined the effect of CPC-HAS on cancer cells. The purpose of this study is to screen the CPC-HAS mediated differentially expressed genes in cancer cells such as HepG2 hepatoma cells. Oligonucleotide microarray and proteomics approaches were employed to screen the differential expression genes. Methods : CPC-HAS was prepared by boiling and stored at $-70^{\circ}C$ until use. Cells were treated with various concentrations of CPC-HAS (0.1, 0.5, 1.5, 10, 20mg/ml) for 24 h. Cell toxicity was tested by MTT assay. To screen the differentially expressed genes in cancer cells, cells were treated with 1.5mg/ml of CPC-HAS. For oligonucleotide microarray assay, total RNA was used for gene expression analysis using oligonucleotide Genechip(Human genome Ul33 Plus 2.0., Affimatrix Co.). For proteomic analysis, total protein was analyzed by 2D gel electrophoresis and Q-TOF mass spectrometer. Results : It has no cytotoxic effects on both HepG2 cell in all concentrations(0.l, 0.5, 1.5, 10, 20mg/ml). In oligonucleotide microarray assay, the number of more than twofold differentially regulated known genes was 23 with 5 up-regulated and 18 down-regulated genes in HepG2 cells. In proteomic analysis, three spots were identified by 2D-gel electrophoresis and Q-TOF analysis. Two down-regulated proteins were aldehyde dehydrogenase 1 and enolase 1, and up-regulated protein was fatty acid binding protein 1 by 1.5mg/ml of CPC-HAS. Discussion : This study showed the screening of CPC-HAS mediated differentially regulated genes using combined approaches of oligonucleotide microarray and proteomic analysis. The screened genes will be used for the better understanding of the therapeutic effects of CPC-HAS on cancer fields.

Melatonin Attenuates Mitochondrial Damage in Aristolochic Acid-Induced Acute Kidney Injury

  • Jian Sun;Jinjin Pan;Qinlong Liu;Jizhong Cheng;Qing Tang;Yuke Ji;Ke Cheng;Rui wang;Liang Liu;Dingyou Wang;Na Wu;Xu Zheng;Junxia Li;Xueyan Zhang;Zhilong Zhu;Yanchun Ding;Feng Zheng;Jia Li;Ying Zhang;Yuhui Yuan
    • Biomolecules & Therapeutics
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    • v.31 no.1
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    • pp.97-107
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    • 2023
  • Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Clinical trial to evaluate the efficacy and safety of Tongxinluo in high risk group of cardiovascular diseases (심혈관질환 고위험군에 대한 통심락(通心絡)의 유효성 및 안전성 평가를 위한 임상시험)

  • Park, Seong Uk;Jung, Woo Sang;Moon, Sang Kwan;Go, Chang Nam;Cho, Ki Ho;Kim, Young Suk;Bae, Hyung Sup
    • The Journal of the Society of Stroke on Korean Medicine
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    • v.6 no.1
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    • pp.25-32
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    • 2005
  • Background and purpose: Arterial stiffness is an important, independent determinant of cardiovascular risk. Pulse wave velocity (PWV) has been used as a valuable index of arterial stiffness and as a surrogate marker for atherosclerosis. The Framingham risk score was developed using categorized risk factors to predict the 10 year absolute risk of developing coronary heart disease (CHD). This algorithm is established using recommended guidelines for blood pressure, total cholesterol, and high density lipoprotein cholesterol in addition to age, smoking history and history of diabetes. Tongxinluo(TXL) has been shown to have anti hyperlipidemic activity and anti atherogenic effects. To determine its efficacy and safety, we examined whether TXL improves PWV, ABI, Framingham score, blood pressure, and lipid profile in high risk group of cardiovascular diseases. Subjects and methods: 49 subjects with the high risk of cardiovascular diseases were recruited. Subjects were administered TXL with the dose of 1110mg three times a day for 8 weeks. baPWV, ABI, Framingham risk score, Blood pressure and serum lipid profile were assessed at baseline and after 4 and 8weeks. Results: Total cholesterol, LDL cholesterol, triglyceride, total lipid and phospolipid significantly decreased after 4 weeks of medication. Total cholesterol, total lipid and phospolipid significantly decreased after 8 weeks of medication. There were no significant changes in Framingham risk scores, ABI, PWV and blood pressure. On safety assessment, there were no adverse effects, hepatic or renal toxicity. Conclusion: We suggest that TXL is a safe and useful herbal medicine for hyperlipidemia and as for anti-atherognic effects, further research would be necessary.

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Biotransformation of Diterpenoids From Aralia continentalis Roots by the Genus Fusarium (곰팡이 Fusarium 속을 이용한 독활 뿌리 추출물로부터 디테르페노이드의 생물전환)

  • Keumok Moon;Seola Lee;Eunhye Jo;Areum Lee;Jaeho Cha
    • Journal of Life Science
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    • v.34 no.4
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    • pp.215-226
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    • 2024
  • Aralia continentalis is widely distributed in Far East Asian countries such as Korea, China, and Japan. A. continentalis has traditionally been used as an herbal remedy for various conditions, including analgesia, headache, inflammation, lameness, lumbago, rheumatism, and dental diseases in Korea. Previously, epi-continentalic acid, continentalic acid, and kaurenoic acid as major active biological compounds belonging to the diterpenoid class were identified. To synthesize diterpenoid derivatives with enhanced bioavailability, Fusarium fujikuroi was employed to biotransform diterpenoids due to its known antibacterial activity. This yielded two derivatives of kaurenoic acid, namely 16α-hydroxyent-kauran-2-on-19-oic acid and 2β, 16α-dihydroxy-ent-kauran-19-oic acid, with their chemical structures elucidated via NMR analysis. These derivatives exhibited increased polarity compared to kaur- enoic acid, as evidenced by their retention time on preparative HPLC using the ODS-A column and structural modifications. Evaluation of their antidiabetic activity targeting PTP1B, a negative regulator of the insulin signaling pathway, revealed inhibitory activities of 30.8% and 27.6%, respectively, at a concentration of 4 ㎍/ml. Additionally, both derivatives demonstrated low cytotoxicity, with an IC50 value 18 times higher than kaurenoic acid. Therefore, the augmented water solubility and reduced toxicity of 16α-hydroxy-ent-kauran-2-on-19-oic acid and 2β, 16α-dihydroxy-ent-kauran-19-oic acid, resulting from biotransformation by F. fujikuroi, render them promising candidates for industrial applications.

Antioxidative Effects of Lycium chinense Miller on Cisplatin-induced Nephrotoxicity in Rats (Cisplatin으로 유도된 급성신부전증에 대한 지골피(地骨皮)의 항산화효과)

  • Jung, Yu-Sun;Park, Chan-Hum;Shin, Hyeon-Cheol
    • The Journal of Internal Korean Medicine
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    • v.35 no.1
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    • pp.92-105
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    • 2014
  • Objectives : Cisplatin is a widely used cancer therapy drug. However, nephrotoxicity resulting in increased oxidative stress is a major side effect of cisplatin chemotherapy, thereby limiting its chemotherapeutic use. Lycium chinense Miller (LCM) has been used as a traditional herbal medicine in various febrile and inflammatory diseases such as night sweat, cough, nosebleed, bronchitis, pulmonary tuberculosis, etc. In this study we investigated the protective and antioxidative potential of LCM against cisplatin-induced nephrotoxicity in rats. Methods : Twenty-four 8-week-old male Wistar rats were divided into four groups: normal untreated; cisplatin treatment only; LCM 10 mg/kg plus cisplatin treatment; and LCM 30 mg/kg plus cisplatin treatment. Twenty-four hours after the last cisplatin injection, all the rats were sacrificed, and serological changes were evaluated. The levels of NF-${\kappa}B$ activity and NOX-4, $p47^{phox}$, $p22^{phox}$, COX-2, iNOS, SOD, catalase expressions were analyzed in Western blot analysis. Results : Cisplatin injection caused an increase in the BUN level, which is a reliable indicator of renal toxicity. The levels of BUN, renal ROS, and renal TBARS were significantly reduced in the LCM groups compared with the cisplatin-only groups. The levels of $p47^{phox}$ and $p22^{phox}$, which are NADPH oxidase subunits, were increased in the cisplatin-only groups, whereas they were decreased in the LCM groups. The levels of renal NF-${\kappa}B$ activity and COX-2, iNOS expressions were increased significantly in the cisplatin-only groups compared with the normal groups, whereas they were decreased in the LCM groups. Compared with the cisplatin-only groups, renal GSH and GSH/GSSG increased in the LCM groups. Also, the administration of LCM increased levels of SOD and catalase as compared with the cisplatin-only groups. Conclusions : These results suggest that LCM protects cisplatin-induced nephrotoxicity via a mechanism that may involves the inhibition of oxidative stress by the activation of antioxidants.

Studies on effect and Safety of various Aqua-acupunctures from Scutellariae Radix (다양(多樣)한 황금약침제제(黃芩藥鍼製劑)의 안전성(安定性) 및 효능(效能)에 관한 연구(硏究))

  • Kim, Ho-Kyoung;Ma, Jin-Yeul;Cheon, Won-Kyung;Yun, Su-Young;Kang, Eun-Jung;Joo, Hye-Jeong;Ko, Byoung-Seob
    • Korean Journal of Oriental Medicine
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    • v.3 no.1
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    • pp.183-197
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    • 1997
  • In order to detect the safety and effect of various aqua-acupunctures from Scutellariae Radix, the modifications of boiling, filtration and dilution were employed for the manufacture of aqua-acupunctures. We injected 0.2cc of aqua-acupunctures into Joksamri (足三里) of rat, repeatedly. We compared subacute toxicity of them with saline group, distilled water(D.W.) group, acupuncture group and control group. The results were summarized as follows: 1. The groups were all healthy and alive, and there was no special abnormality in physical condition and autopsy. And there were not any toxic symptoms in repeating application of aqua-acupunctures to the rat, including changes of body weight, organ weight, haematological examination and serum biochemical test. 2. There was slight change of body weight in acupuncture group : We could see significance after 3 days(p<0.05) and after 7 days(p<0.001) in body weight loss. After 9 days, all tested groups were suppressed in body weight increment. 3. Result of organ weight : In Palkang aqua-acupuncture(D-2 group), saline group and acupuncture group there were some statistical significance. Especially, acupuncture group revealed significant result in liver and spleen than aqua-acupunctures. From this result, we could suggest that the efficacy of acupuncture was preceded herbal medicine. 4. In serum biochemical test, we examined glucose(GLU), triglyceride(TG) and cholesterol(CHOL). In comparison with control group, the diluted 10 times of Hwanggum aqua-aqupuncture$({\times}10\;group)$ was recognized significant decrease of glucose, but the diluted 100 times of Hwanggum aqua-acupuncture$({\times}100\;group)$, D-2 group, saline group were confirmed significant increment. There was not any meaningful change of CHOL in all of tested group, excepting the acupuncture group was exhibited statistically significant decrease(p<0.05). In TG level all tested group except complex injection of standard compound(CPA group) and HG, there were significant value iii statistically. The diluted solution was more significant decrease than Hwanggum aqua-acupuncture(HG). The mutual relationship of components of aqua-acupunture tended to decrease level of TG, regardless of its concentration. In acupunture guoup, we gained some interesting result In meaningful decrease in 7G. 5. Haematological examination showed significant increment of granulocytes(GR) in all tested groups except Hwanggum aqua-acupuncture. And the diluted solutions of HG expressed very high increment of them(p<0.001). The GR and Mean Corpuscular Volume(MCV) of acupuncture group showed statistical significance.

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Inhibition Effect of Phenolic Compounds from Ultra-fine Ground Chrysanthemum indicum L. on Xanthine Oxidase (초미세 분쇄한 감국으로부터 추출된 phenolic 화합물의 xanthine oxidase 저해 효과)

  • Cho, Young-Je;Kim, Byung-Oh;Park, Hye-Jin;Lee, Eun-Ho;Jo, Jae-Bum;Lee, Jae-Eun;Lim, Su-Bin;Kim, Ye-Jin;Park, Ki-Tae;Choi, Moo-Young
    • Journal of Life Science
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    • v.27 no.8
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    • pp.902-908
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    • 2017
  • In this study, the extracted phenolic compounds from 98 species of oriental herbal medicine were examined for biological activities to be used as functional resources. In particular, the anti-gout effect by xanthine oxidase (XOase) inhibition was determined using water and ethanol as extraction solvents because of their non-toxicity in the human body. The extracts of Chrysanthemum indicum L. (83.45%), Cuscuta chinensis (60.22%), Asiasarum sieboldi F. Maekawa (51.66%), Acorus gramineus (67.8%), Aconitum pseudo-laeve var. erectum (75.23%), Thuja orientalis (47.27%), Polygonum aviculare (53.98%), Carthami semen (63.99%), and Syzygium aromaticum (40.22%) showed relatively high XOase inhibitory activity. Chrysanthemum indicum L. was selected for its high XOase inhibitory activity. The biological compounds in Chrysanthemum indicum L. were identified to contain phenolics included in extracts of solids. Ultra-fine grind technology showed a higher extraction yield than normal grind and fine grind technology. Ethanol extracts showed relatively higher XOase inhibitory activity than water extracts. XOase inhibitory activity increased in a dependent manner as phenolic concentration increased. Therefore, ultra-fine grind technology was confirmed for use in increasing the extraction yield of XOase inhibitory compounds from Chrysanthemum indicum L.. Extracts from Chrysanthemum indicum L. are expected to be a useful functional resource for the prevention or treatment of gout.