Identification of aristolochic acid in Chinese herbs

Vanhaelen, Maurice; Vanhaelen-Fastré, Renée; But, Paul Pui‐Hay; Vanherweghem, Jean‐Louis

doi:10.1016/s0140-6736(94)90964-4

Cited by 318 publications

(207 citation statements)

References 3 publications

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“…The most widely publicised reports were the cluster of cases of rapidly progressive interstitial nephritis in Belgium (Vanhaelen et al, 1994). Following investigation, this problem was attributed to the substitution of Aristolochia fangchi instead of the CM herb Stephania tetrandra in a combined slimming regimen that included some orthodox medications.…”

Section: Authenticity or Poor Quality Of CM Herbsmentioning

confidence: 99%

Some aspects of toxic contaminants in herbal medicines

2003

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A World Health Organisation survey indicated that about 70-80% of the world populations rely on non-conventional medicine mainly of herbal sources in their primary healthcare. In recent years, we have witnessed the increasing growth in popularity of over-the-counter (OTC) health foods, nutraceuticals, and medicinal products from plants or other natural sources in developed countries. This indirectly indicates that the public is not satisfied with their orthodox medical (OM) treatment. Such increase in popularity has also brought concerns and fears over the professionalism of practitioners, and quality, efficacy and safety of their treatment methods and products from herbal and natural sources available in the market. Over the past decade several news-catching episodes in developed communities indicated adverse effects, sometimes life threatening, allegedly arisen consequential to taking of OTC herbal products or traditional medicines from various ethnic groups. These OTC products may be contaminated with excessive or banned pesticides, microbial contaminants, heavy metals, chemical toxins, and for adulterated with orthodox drugs. Excessive or banned pesticides, heavy metals and microbial contaminants may be related to the source of these herbal materials, if they are grown under contaminated environment or during collection of these plant materials. Chemical toxins may come from unfavourable or wrong storage conditions or chemical treatment due to storage. The presence of orthodox drugs can be related to unprofessional practice of manufacturers. Some of these environment related factors can be controlled by implementing standard operating procedures (SOP) leading to Good Agricultural Practice (GAP), Good Laboratory Practice (GLP), Good Supply Practice (GSP) and Good Manufacturing Practice (GMP) for producing these medicinal products from herbal or natural sources. The publicÕs belief that herbal and natural products are safer than synthetic medicines can only be ascertained by imposing regulatory standards on these products that should be manufactured using these Good Practices.Using Chinese medicines, as examples, this paper illustrate how advances in chemical and biomedical analysis would help to detect intentional and unintentional toxic contaminants in herbal substances. The paper also summarises how modernization and progress are being carried out to get the best out of Chinese medicines for public healthcare.

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Section: Authenticity or Poor Quality Of CM Herbsmentioning

confidence: 99%

Some aspects of toxic contaminants in herbal medicines

2003

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“…Thin-layer chromatography detection of AAs in these herbal preparations failed however [19]. Afterwards AAs were found in 11 of the 12 batches of S. tetrandra powder delivered to Belgian pharmacies during the treatment period [20]. The disease became known as Chinese herb nephropathy (CHN).…”

Section: Introductionmentioning

confidence: 99%

Enforcement of the ban on aristolochic acids in Chinese traditional herbal preparations on the Dutch market

et al. 2007

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In traditional chinese medicine several Aristolochia species are used. Aristolochia spp. contain a mixture of aristolochic acids (AAs), mainly AA I and AA II which are nephrotoxicants and carcinogens. After AA-related nephropathy (AAN) and urothelial cancer were described in female patients in Belgium following intake of AA-contaminated herbal preparations, herbs with AAs were prohibited worldwide. Confusing nomenclature can cause AA contamination of certain Chinese traditional herbal preparations (THPs). Here we report the results of investigations by the Dutch Food and Consumer Product Safety Authority (VWA) into the presence of AAs in THPs sampled on the Dutch market using a liquid-chromatography--mass spectrometry method. Between 2002 and 2006 we sampled 190 Chinese THPs using recent information on Chinese THPs potentially containing AAs. AA I was found in 25 samples up to a concentration of 1,676 mg/kg. AA II was also found in 13 of these samples up to 444 mg/kg. All 25 positive samples including Mu Tong, Fang Ji, Tian Xian Teng and Xi Xin were part of a group of 68 THPs identified as possibly containing AAs. In a worst-case scenario, use of a sample of Mu Tong with the highest AA content over a 7-day period would result in the same intake levels of AAs which significantly raised the cancer risk in the Belgian AAN cases. Our results show that contaminated THPs still can be found on the market following worldwide publicity. Therefore, it can be concluded that testing of possibly AAcontaminated THPs is still essential.

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“…1,2 About 100 cases have been identified so far in Belgium, half of which needed renal replacement therapy, mostly including renal transplantation. [3][4][5] The observed nephrotoxicity has been traced to the ingestion of Aristolochia fangchi containing carcinogenic and nephrotoxic aristolochic acid (AA) inadvertently included in slimming pills.…”

mentioning

confidence: 99%

“…[3][4][5] The observed nephrotoxicity has been traced to the ingestion of Aristolochia fangchi containing carcinogenic and nephrotoxic aristolochic acid (AA) inadvertently included in slimming pills. 2 Chinese herbs nephropathy has been described in patients in other European and in Asian countries as well as in the United States (about 170 cases), 6 who were exposed to Aristolochia species containing AA and had no relationship with the Belgian slimming clinic. Therefore, it has been proposed to designate the interstitial nephropathy in which the unequivocal role of AA has been fully documented as aristolochic acid nephropathy.…”

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confidence: 99%

Human hepatic and renal microsomes, cytochromes P450 1A1/2, NADPH:Cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid‐DNA adducts found in patients with urothelial cancer

Stiborová

Frei

Hodek

et al. 2004

Intl Journal of Cancer

135

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Aristolochic acid (AA), a naturally occurring nephrotoxin and carcinogen, has been associated with the development of urothelial cancer in humans. Understanding which human enzymes are involved in AA activation and/or detoxication is important in the assessment of an individual's susceptibility to this plant carcinogen. Using the 32 P postlabeling assay, we examined the ability of microsomal samples from 8 human livers and from 1 human kidney to activate AAI, the major component of the plant extract AA, to metabolites forming adducts in DNA. Microsomes of both organs generated DNA adduct patterns reproducing those found in renal tissues from humans exposed to AA. 7-(deoxyadenosin-N 6 -yl)aristolactam I, 7-(deoxyguanosin-N 2 -yl)aristolactam I and 7-(deoxyadenosin-N 6 -yl)aristolactam II were identified as AA-DNA adducts formed from AAI by all human hepatic and renal microsomes. To define the role of human microsomal enzymes in the activation of AAI, we investigated the modulation of AAI-DNA adduct formation by cofactors and selective inhibitors of microsomal reductases, cytochrome P450 (CYP) enzymes, NADPH:CYP reductase and NADH:cytochrome b 5 reductase. We also determined whether the activities of CYP and NADPH:CYP reductase in different human hepatic microsomal samples correlated with the levels of AAI-DNA adducts formed by the same microsomal samples. On the basis of these studies, we attribute most of the activation of AAI in human hepatic microsomes to CYP1A2. In contrast to human hepatic microsomes, in human renal microsomes NADPH:CYP reductase is more effective in AAI activation. In addition, prostaglandin H synthase is another enzyme activating AAI in renal microsomes. The results demonstrate for the first time the potential of microsomal enzymes in human liver and kidney to activate AAI by nitroreduction.

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Identification of aristolochic acid in Chinese herbs

Cited by 318 publications

References 3 publications

Some aspects of toxic contaminants in herbal medicines

Some aspects of toxic contaminants in herbal medicines

Enforcement of the ban on aristolochic acids in Chinese traditional herbal preparations on the Dutch market

Human hepatic and renal microsomes, cytochromes P450 1A1/2, NADPH:Cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid‐DNA adducts found in patients with urothelial cancer

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