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

• Biomolecules & Therapeutics
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• 제31권1호
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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.

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

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.198-198
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• 2002

Occurrence of Chinese Herbs Nephropathy (CHN) has been reported in young women who had taken a slimming pills containing some chinese herbs. Aristolochic acid (AA) known as a carcinogen, was suspected as the major causal factor of CHN. AA is major component of fruit of A. contorta was used in Korean Traditional Medicine.(omitted)

• 대한수의학회지
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• 제45권1호
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• pp.29-37
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• 2005

13-week orally repeated dose toxicity was investigated to ascertain the toxic effects of Aristolochiae radix in F344 rats at dose levels of 0, 1 (0.003 AA, aristolochic acid, mg/kg), 5 (0.014 AA mg/kg), 25 (0.068 AA mg/kg), 125 (0.34 AA mg/kg), and 500mg/kg (AA 1.36 mg/kg). No mortalities were found in any of the dose groups including vehicle control groups of both sexes during the study period. Hematologic and serum biochemical examinations revealed no changes related to the test item in any of the dose groups of both sexes. However, gross findings at necropsy implicated thickening of the stomach wall. In histopathological examinations, prominent findings related to the test item treatment were observed in the stomach and urinary bladder. There were squamous cell papilloma, squamous cell hyperplasia, ulceration and erosion observed in the non-glandular stomach. Squamouse cell hyperplasia was observed at dose levels of more than 125 mg/kg in both sexes and squamous cell papilloma was observed at dose level of 500 mg/kg in both sexes. The incidence and severity of these proliferating lesions including squamous cell hyperplasia and squamous cell papilloma increased with dose dependency. Transitional cell hyperplasia was also observed in the urinary bladder at dose levels of more than 25 mg/kg in both sexes and the incidence and severity of the lesion increased with dose dependency. In conclusion, the toxic changes related to the test item treatment were observed in the stomach and urinary bladder, and the no-observed-adverse-effect level (NOAEL) was estimated to be 5 mg/kg/day for both males and females in F344 rats.