• 한국식품영양과학회지
• /
• 제32권7호
• /
• pp.1164-1167
• /
• 2003

국내 유통 중인 한약재에 발암물질로 알려진 aristolochic acid 함유 여부를 검사하고자 방기, 목통, 목향, 마두령, 세신, 철목향 등을 대상으로 aristolochic acid 검출 유무 및 정량분석을 수행하였다. 시료에 대한 TLC와 $C_{18}$ column을 이용한 HPLC의 aristolochic acid 최적 분석 조건을 수립하였고 aristolochic acid 정량분석 결과 방기 type II에는 3.9 mg/g, 마두령에는 2.3 mg/g이 함유되어 있는 것으로 나타났다. 그외 목향, 목통, 세신, 청목향 등 시료에서는 aristolochic acid가 검출되지 않았다.

• 생약학회지
• /
• 제20권1호
• /
• pp.1-5
• /
• 1989

Two phenanthrene nitrocarboxylic acid derivatives were isolated from the root of Aristolochia contorta Bunge. They were identified as aristolochic acid I and aristolochic acid II, respectively.

• 한국식품저장유통학회:학술대회논문집
• /
• 한국식품저장유통학회 2003년도 제23차 추계총회 및 국제학술심포지움
• /
• pp.136.1-136
• /
• 2003

Aristolochic acid has been known to be a carcinogenic compound and to cause Chinese herbs nephrophathy. To determine the content of aristolochic acid in various medicinal herbs marketed domestically, samples of Aristolochia fangchi, Aristolochia fructus, Aristolochia radix, Asiasari radix, Saussureae radix, and Akebia caulis were analyzed using TLC and HPLC. The optimal conditions for TLC and HPLC were established for the quantitative analysis of aristolochic acid. This study showed that Aristolochia fangchi and Aristolochia fructus examined in this study contain aristolochic acid of 3.9 and 2.3 mg/g sample, respectively. In contrast, aristolochic acid was not detected in other samples.

• 한국수정란이식학회:학술대회논문집
• /
• 한국수정란이식학회 2002년도 국제심포지엄
• /
• pp.110-110
• /
• 2002

Rapidly progressive interstitial renal fibrosis has recently been reported in young women who have been on a slimming regimen including chinese herbs. Aristolochic acid, suspected as the causal factor of this renal disease, is a well known carcinogen. It has been known that Madouling (Aristolochiae fructus) contains aristolochic acid. The objective of this study was to investigate the effects of Madouling, Madouling-tang, which are the extract mixture from 10 different chinese herbs including Madouling, and aristolochic acid on reproductive and developmental toxicity. Female rats were administered orally with the extracts of Madouling, madouling-tang, and aristolochic acid from 14 days before mating to day 17 of gestation. Madouling (8mg/kg) decreased fertility in the 8mg/kg group, but Madouling-tang and aristolochic acids did not. Significant decrease of mean fetal body weights were observed in the 16mg/kg group of aristolochic acids. External, visceral and skeletal malformation of fetuses were not observed with treatment. Histopathological examination showed the discrete damage of kidney in the 8mg/kg group of Madouling and 16mg/kg groups of aristolochic acid. In whole embryo culture, Madouling and Madouling-tang caused the retardation of growth and development of embryo in the dose of 1 $\mu$g/ml and 0.02 $\mu\textrm{g}$/kg, respectively while aristolochic acids showed the similar effect in the dose of 300 $\mu\textrm{g}$/kg. These results indicate that Madouling, up to 0.05mg/kg (prescription dose to human) has no adverse effects on the fertility, reproduction and development of Sprague-Dawley rats.

• 생약학회지
• /
• 제38권2호통권149호
• /
• pp.123-127
• /
• 2007

Aristolochic acid (AA) included in the plants Aristolochiaceae have been well known to be nephrotoxic and carcinogenic inducer and to cause renal disease such as Chinese Herb Nephropathy (CHN). In this study, we used a high performance liquid chromatopaphy-mass spectrometry (HPLC-MS) under the positive ion detection mode for the quantitative change of aristolochic acid-I and-II (AA-I and AA-II) in Aristolochiaceae (Aristolochia contorta Bunge, Aristolochia debilis Sieb. et Zucc., Aristolochia fangchi Wu), some related plants (Cocculus trilobus De candolle, Inula helenium Linne, Saussurea lappa Clarke), and its prescriptions (防己茯笭湯, 定喘散) with or without processing. Here, the processing methods and prescriptions in oriental medicine were generally used to alleviate toxicity or alter property of herbal medicines. However, the concentrations of AA-I and AA-II were highly determined in processed material extracts rather than unprocessed those, not measured in some related plants. Also, the concentrations of AA-I and AA-II even at the prescriptions mixed the plants of Aristolochiaceae were detected to range from 0.73 to 2.53 ppm. Thus, the present results suggest that the content of AA-I and AA-II contained to plants of Aristolochiaceae was not reduced by the processing methods or prescriptions which can induce the physico-chemical change and pharmacological transformation in traditional herbal medicines.

• 대한한방내과학회지
• /
• 제21권4호
• /
• pp.543-548
• /
• 2000

After Vanherweghem J-L reported the rapidly progressive interstitial renal fibrosis that developed in patients taking the slimming preparation compounded with chinese Herb in Belgium 1993. Chinese Herb Nephropathy(CHN) has become known as a new renal disease, CHN is described as the decrease of urinary renal enzyme, neutral endopeptidase(NEP). N-acetyl-${\beta}$-Dglucosaminidase(NAG). increase of urinary low molecular protein, ${\alpha}$1-microglobulin, ${\beta}$2-microglobulin. clara cell protein(CC16), retinol-binding protein(RBP) in clinical findings, and the proximal tubular atrophy, interstitial fibrosis. urothelial atrophy. glomerular sclerosis in histology, Because CHN was caused by Chinese herb contained in slimming preparation, western medical doctors have thought that all Herb medicine might have caused renal disease and prohibit the taking of any Herb medicine, However. CHN was actually caused by the aristolochic acid contained in some Herb medicines. Aristolochia manshuriensis, Aristolochia fang chi, which is the substitutions of Akebia quinata, Stephania tetrandra has being used in clinical. Aristolochia manshuriensis. Aristolochia fang chi were different with Akebia quinata. Stephania tetrandra in botany, and it have not been classified with medicines in Oriental medicine, That is, the aristolochic acid, not Herb medicines. causes CHN, So, Chinese Herb Nephropathy should be changed to Aristolochic acid Nephropathy.

• 생약학회지
• /
• 제40권2호
• /
• pp.89-98
• /
• 2009

The toxicity of aristolochic acid (ArA) has attracted considerable attention since the case of nephropathy regarding diet pill preparations was reported. The present study was performed to determine the reproductive toxicity of ArA in female SD rats. ArA was administered orally to female rats at 2, 8 or 16 mg/kg b.w./day and the females were mated with untreated males and their reproductive status was determined. ArA is well known as PLA2 inhibitor, toxic effects of such a relationship are not yet clear, and in vivo study on this matter are scarce. For this study, ArA was administered to pregnant rats at 10 or 20 mg/kg b.w./day, because premating treatments were not conducted. Administration of 20 mg/kg b.w./day caused infertility or abortion. In ArA-treated groups, PGF2a productions were inhibited and apoptosis were suppressed. Collectively, this study may help to further define the roles of sPLA2 in reproductive organs and to determine the toxic mechanisms of ArA.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
• /
• pp.158-158
• /
• 2002

The potential toxicological effects of aristolochic acid (AA), a natural component in Aristolochiaceae family, were investigated. The 13-week toxicity study consisted of groups of 10 SD rat/sex administrated water containing 0, 0.05, 0.5, or 5 mg/kg per day AA (Study 1). The tested groups were terminated on Test Day 90 due to mortality and overt clinical signs of toxicity.(omitted)

• BMB Reports
• /
• 제52권9호
• /
• pp.554-559
• /
• 2019

Despite reports suggesting that tissue-resident natural killer (trNK) cells cause ischemic kidney injury, their contribution to the development of tubulointerstitial fibrosis has not been determined. This study hypothesized that the depletion of trNK cells may ameliorate renal fibrosis by affecting transglutaminase 2/syndecan-4 interactions. Aristolochic acid nephropathy (AAN) was induced in C57BL/6 mice as an experimental model of kidney fibrosis. The mice were treated with anti-asialo GM1 (ASGM1) or anti-NK1.1 antibodies to deplete NK cells. Although both ASGM1 and NK1.1 antibodies suppressed renal $NKp46^+DX5^+$ NK cells, renal $NKp46^+DX5^-$ cells were resistant to suppression by ASGM1 or NK1.1 antibodies during the development of tubulointerstitial fibrosis in the AAN-induced mouse model. Western blot analysis showed that both antibodies increased the expression of fibronectin, transglutaminase 2, and syndecan-4. These findings indicate that trNK cells played an exacerbating role in tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in the AAN-induced mouse model.

• Biomolecules & Therapeutics
• /
• 제31권1호
• /
• pp.97-107
• /
• 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.