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Arthur P. Grollman - One of the best experts on this subject based on the ideXlab platform.

  • Aristolochia Herbs and Iatrogenic Disease: The Case of Portland's Powders.
    The Yale journal of biology and medicine, 2020
    Co-Authors: Tristan Tomlinson, Andrea Fernandes, Arthur P. Grollman
    Abstract:

    Aristolochia herbals have a 2500-year history of medicinal use. We focused this article on Portland's Powders, an 18th-century British gout medicine containing Aristolochia herbs. The powders constitute an 18th-century iteration of an herbal remedy, which was used, with variations, since at least the fifth century BCE. The use of Portland's Powders in Great Britain may appear to be an unusual choice for investigating a public health problem currently widespread in Asia. Yet it exemplifies long-term medicinal use of Aristolochia herbs, reflecting our argument that aristolochic acid nephropathy (AAN) is a historically persistent iatrogenic disease. Moreover, we provide compelling evidence that individuals taking Portland's Powders for gout would have ingested toxic quantities of aristolochic acid, which causes AAN and cancer. Several factors, including long history of use, latency of toxic effects, and lack of effective regulation, perpetuate usage of Aristolochia herbals to the present day.

  • human formalin fixed paraffin embedded tissues an untapped specimen for biomonitoring of carcinogen dna adducts by mass spectrometry
    Analytical Chemistry, 2013
    Co-Authors: Thomas A. Rosenquist, Arthur P. Grollman, Bojan Jelakovic, Jovan Nikolic, Dejan Dragicevic, Karla Tomic, Kathleen G Dickman, Robert J Turesky
    Abstract:

    DNA adducts represent internal dosimeters to measure exposure to environmental and endogenous genotoxicants. Unfortunately, in molecular epidemiologic studies, measurements of DNA adducts often are precluded by the unavailability of fresh tissue. In contrast, formalin-fixed paraffin embedded (FFPE) tissues frequently are accessible for biomarker discovery. We report here that DNA adducts of aristolochic acids (AAs) can be measured in FFPE tissues at a level of sensitivity comparable to freshly frozen tissue. AAs are nephrotoxic and carcinogenic compounds found in Aristolochia herbaceous plants, many of which have been used worldwide for medicinal purposes. AAs are implicated in the etiology of aristolochic acid nephropathy and upper urinary tract carcinoma. 8-Methoxy-6-nitrophenanthro-[3,4-d]-1,3-dioxole-5-carboxylic acid (AA-I) is a component of Aristolochia herbs and a potent human urothelial carcinogen. AA-I reacts with DNA to form the aristolactam (AL-I)-DNA adduct 7-(deoxyadenosin-N6-yl) aristolactam...

  • biomonitoring of aristolactam dna adducts in human tissues using ultra performance liquid chromatography ion trap mass spectrometry
    Chemical Research in Toxicology, 2012
    Co-Authors: Byeong Hwa Yun, Viktoriya S. Sidorenko, Thomas A. Rosenquist, Arthur P. Grollman, Kathleen G Dickman, Charles R Iden, Chunghsin Chen, Radha Bonala, Francis Johnson, Robert J Turesky
    Abstract:

    Aristolochic acids (AAs) are a structurally related family of nephrotoxic and carcinogenic nitrophenanthrene compounds found in Aristolochia herbaceous plants, many of which have been used worldwide for medicinal purposes. AAs have been implicated in the etiology of so-called Chinese herbs nephropathy and of Balkan endemic nephropathy. Both of these disease syndromes are associated with carcinomas of the upper urinary tract (UUC). 8-Methoxy-6-nitrophenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic acid (AA-I) is a principal component of Aristolochia herbs. Following metabolic activation, AA-I reacts with DNA to form aristolactam (AL-I)-DNA adducts. We have developed a sensitive analytical method, using ultraperformance liquid chromatography–electrospray ionization/multistage mass spectrometry (UPLC-ESI/MSn) with a linear quadrupole ion-trap mass spectrometer, to measure 7-(deoxyadenosin-N6-yl) aristolactam I (dA-AL-I) and 7-(deoxyguanosin-N2-yl) aristolactam I (dG-AL-I) adducts. Using 10 μg of DNA for measuremen...

  • A fluorescence-based analysis of aristolochic acid-derived DNA adducts.
    Analytical biochemistry, 2012
    Co-Authors: Victor Romanov, Viktoriya S. Sidorenko, Thomas A. Rosenquist, Terry Whyard, Arthur P. Grollman
    Abstract:

    Aristolochic acids (AAs), major components of plant extracts from Aristolochia species, form (after metabolic activation) pro-mutagenic DNA adducts in renal tissue. The DNA adducts can be used as biomarkers for studies of AA toxicity. Identification of these adducts is a complicated and time-consuming procedure. We present here a fast, nonisotopic, fluorescence-based assay for the detection of AA–DNA adducts in multiple samples. This approach allows analysis of AA adducts in synthetic DNA with known nucleotide composition and analysis of DNA adducts formed from chemically diverse AAs in vitro. The method can be applied to compare AA–DNA adduct formation in cells and tissues.

  • dna adducts of aristolochic acid ii total synthesis and site specific mutagenesis studies in mammalian cells
    Nucleic Acids Research, 2010
    Co-Authors: Sivaprasad Attaluri, Arthur P. Grollman, Charles R Iden, Radha Bonala, Inyoung Yang, Mark Lukin, Yujing Wen, Masaaki Moriya, Francis Johnson
    Abstract:

    Aristolochic acids I and II (AA-I, AA-II) are found in all Aristolochia species. Ingestion of these acids either in the form of herbal remedies or as contaminated wheat flour causes a dose-dependent chronic kidney failure characterized by renal tubulointerstitial fibrosis. In � 50% of these cases, the condition is accompanied by an upper urinary tract malignancy. The disease is now termed aristolochic acid nephropathy (AAN). AA-I is largely responsible for the nephrotoxicity while both AA-I and AA-II are genotoxic. DNA adducts derived from AA-I and AA-II have been isolated from renal tissues of patients suffering from AAN. We describe the total synthesis, de novo, of the dA and dG adducts derived from AA-II, their incorporation site-specifically into DNA oligomers and the splicing of these modified oligomers into a plasmid construct followed by transfection into mouse embryonic fibroblasts. Analysis of the plasmid progeny revealed that both adducts blocked replication but were still partly processed by DNA polymerase(s). Although the majority of coding events involved insertion of correct nucleotides, substantial misincorporation of bases also was noted. The dA adduct is significantly more mutagenic than the dG adduct; both adducts give rise, almost exclusively, to misincorporation of dA, which leads to AL-II-dA!T and AL-II-dG!T transversions.

Michael Heinrich - One of the best experts on this subject based on the ideXlab platform.

  • medicinally used asarum species high resolution lc ms analysis of aristolochic acid analogs and in vitro toxicity screening in hk 2 cells
    Frontiers in Pharmacology, 2017
    Co-Authors: Johanna Michl, Olusheyi Bello, Geoffrey C Kite, Monique S J Simmonds, Michael Heinrich
    Abstract:

    Species of Asarum are used in traditional Chinese medicine and, similar to members of the genus Aristolochia, they contain aristolochic acid analogs (AAAs). These compounds are known for their nephrotoxic and carcinogenic effects. So far, the phytochemistry and nephrotoxicity of species of Asarum is not well studied. A high-resolution LC-MS-based metabolomic approach was used to study the phytochemical variation in medicinally used Asarum species. The cytotoxicity of the samples was assessed using human kidney (HK-2) cells. The majority of samples contained potentially nephrotoxic AAAs, including 9-methoxy aristolactam (AL) IV, AL I, and AL IV. These compounds were present in methanol as well as water extracts. AAAs were detected in all parts of the plant. The majority of the extracts were not cytotoxic to HK-2 cells at the doses tested. However, other mechanisms relating to aristolochic acid nephropathy and cancer development, such as DNA adduct formation may occur. The results of this study provide a model for assessing lesser-known plant species for toxicity.

  • lc ms and 1h nmr based metabolomic analysis and in vitro toxicological assessment of 43 Aristolochia species
    Journal of Natural Products, 2016
    Co-Authors: Johanna Michl, Geoffrey C Kite, Monique S J Simmonds, Stefan Wanke, Oliver Zierau, G Vollmer, Christoph Neinhuis, Michael Heinrich
    Abstract:

    Species of Aristolochia are used as herbal medicines worldwide. They cause aristolochic acid nephropathy (AAN), a devastating disease associated with kidney failure and renal cancer. Aristolochic acids I and II (1 and 2) are considered to be responsible for these nephrotoxic and carcinogenic effects. A wide range of other aristolochic acid analogues (AAAs) exist, and their implication in AAN may have been overlooked. An LC-MS- and 1H NMR-based metabolomic analysis was carried out on 43 medicinally used Aristolochia species. The cytotoxicity and genotoxicity of 28 Aristolochia extracts were measured in human kidney (HK-2) cells. Compounds 1 and 2 were found to be the most common AAAs. However, AA IV (3), aristolactam I (4), and aristolactam BI (5) were also widespread. No correlation was found between the amounts of 1 or 2 and extract cytotoxicity against HK-2 cells. The genotoxicity and cytotoxicity of the extracts could be linked to their contents of 5, AA D (8), and AA IIIa (10). These results undermine...

  • is aristolochic acid nephropathy a widespread problem in developing countries a case study of Aristolochia indica l in bangladesh using an ethnobotanical phytochemical approach
    Journal of Ethnopharmacology, 2013
    Co-Authors: Johanna Michl, Geoffrey C Kite, Monique S J Simmonds, Michael Heinrich, Hannah Jennings, Martin J Ingrouille
    Abstract:

    Species of Aristolochia are associated with aristolochic acid nephropathy (AAN), a renal interstitial fibrosis and upper urinary tract cancer (UUC). Aristolochic acid nephropathy has been reported in ten countries but its true incidence is unknown and most likely underestimated. By combining an ethnobotanical and phytochemical approach we provide evidence for the risk of AAN occurring in Bangladesh. More specifically, we assess the intra-specific variation of aristolochic acid analogues in medicinally used A. indica samples from Bangladesh.

  • local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2 a global assessment based on bibliographic sources
    Journal of Ethnopharmacology, 2009
    Co-Authors: Michael Heinrich, Monique S J Simmonds, Stefan Wanke, Christoph Neinhuis, Jennifer Chan
    Abstract:

    Abstract Aims of the study More than 100 cases of nephropathy over the last 10 years caused by the systemic and longer term application of Chinese snakeroot ( Aristolochia fangchi ) highlighted the risk of using preparations which contain aristolochic acids. On the other hand anecdotal evidence highlights the widespread use of Aristolochia species (Aristolochiaceae) in many regions of the world. Therefore, it was our objective to systematically assess the scientific literature available on the local and traditional use of Aristolochia spp. on a worldwide scale. Our review identifies core species which need to be investigated and which may need monitoring (esp. in national and international trade). Methods An extensive review of the literature available in libraries in London on the uses of species of Aristolochia was undertaken. Relevant information was extracted and entered into a database for analysis. Results Based on the assessment of 566 reference sources 685 individual sets of data were recorded. Seven species – Aristolochia indica L. (Asia), Aristolochia serpentaria L. (North America), Aristolochia debilis Sieb & Zucch. (China), Aristolochia acuminata Lam (India), Aristolochia trilobata L. (Central/South America, Caribbean), Aristolochia clematitis L. (Europe) and Aristolochia bracteolata Lam. (Africa) – are reported widely as being used medicinally. The medical uses vary, but of particular interest are uses in case of gastrointestinal problems, which is likely to result in repeated exposure to the botanical drugs by an individual. About half of all records relate to uses of Aristolochia species in Asia, one-third to the Americas, a continent which has so far received practically no attention in terms of assessing the risk of using species of Aristolochia . Of the 99 species (plus several identified at genus level only) for which we were able to summarise ethnobotanical information, preliminary phytochemical information is only available for 24 species and some of the most common ones including Aristolochia acuminata have so far not been studied phytochemically. Conclusions Species of Aristolochia are used medicinally in many regions of the world and both from an ethnopharmacological and a public health perspective this poses a risk. A systematic assessment of the content of aristolochic acids in the most widely used species is needed to evaluate whether their uses pose a potential health risk. In China and Europe species of Aristolochia have been associated with nephropathy and it is important to evaluate whether nephropathy occurs in other parts of the world, especially India and Central America where the use of species of Aristolochia are reported to be commonly used in traditional medicine.

Joelle Nortier - One of the best experts on this subject based on the ideXlab platform.

  • substitution between Aristolochia and bryonia genus in north eastern morocco toxicological implications
    Journal of Ethnopharmacology, 2015
    Co-Authors: Amal Yamani, Valerian Bunel, Mariehelene Antoine, Cecile Husson, Caroline Stevigny, Pierre Duez, Mostafa Elachouri, Joelle Nortier
    Abstract:

    Abstract Ethnopharmacological relevance Although acknowledged as toxic herbs, Aristolochia species are still widely used worldwide. The aristolochic acids (AA) they contain can induce the so-called “aristolochic acid nephropathy”, leading to renal fibrosis and upper urinary tract cancer. Traditional Moroccan medicine still often uses Aristolochia species under the vernacular name of Bereztem for the treatment of numerous ailments, notably cancer, diabetes or digestive tract disorders. As the botanical identity and renal toxicity of used species remain unexplored, the safety of patients may be threatened. Material and methods Ethnopharmacological data were collected from herbalists from the provinces of Oujda and Berkane, located in North-Eastern Morocco. Samples of Bereztem were collected at herbalist shops and checked for their content in AA using TLC and LC-MS methods. The toxicity of crude methanolic extracts of each herb was assessed on a HK-2 cell-based in vitro model by measurement of the cell survival to evaluate cytotoxicity and by assessment of renal-specific toxicity via (i) the evaluation of genes (E-cadherin and α-smooth muscle actin) expression by RT-qPCR; (ii) the quantities of β-catenin and vimentin by immunofluorescence microscopy; (iii) the secretion of fibronectin; and (iv) the excretion of interleukin-6. Results The survey indicated that, among 42 herbalists visited, 33 were retailers of Bereztem, which was generally sold as a cancer treatment. Botanical investigations revealed that Aristolochia longa was frequently substituted by Bryonia dioica, which was associated with a higher cytotoxicity. Parameters specific to renal toxicity were also found to be enhanced, as compared to Aristolochia baetica and A. longa: down-regulation of β-catenin and E-cadherin and up-regulation of vimentin and α-smooth muscle actin, and secretion of fibronectin and interleukin-6. Conclusion In accordance with the Moroccan regulations, the use of so-called Aristolochia species should be discontinued. On one hand, the correctly identified Aristolochia contain nephrotoxic aristolochic acids; on the other hand, Aristolochia are massively substituted in North-Eastern Morocco and adulterated by a well-known toxic herb, B. dioica. Our data indicate that the bryony renal toxicity may be deleterious in shorter time periods than Aristolochia. Reinforced on-site controls are needed to remind herbalists and harvesters that these herbs should be prohibited.

  • exceptionally long term persistence of dna adducts formed by carcinogenic aristolochic acid i in renal tissue from patients with aristolochic acid nephropathy
    International Journal of Cancer, 2014
    Co-Authors: Heinz H Schmeiser, Joelle Nortier, Rajinder Singh, Goncalo Gamboa Da Costa, Jacques Sennesael, Elisabeth Cassutoviguier, Damien Ambrosetti, Sandrine Rorive, Agnieszka Pozdzik, David H Phillips
    Abstract:

    Aristolochic acid (AA) causes aristolochic acid nephropathy (AAN), first described in women in Belgium accidently prescribed Aristolochia fangchi in a slimming treatment, and also Balkan endemic nephropathy (BEN), through probable dietary contamination with Aristolochia clematitis seeds. Both nephropathies have a high risk of urothelial cancer, with AA being the causative agent. In tissues of AAN and BEN patients, a distinct DNA adduct, 7-(deoxyadenosin-N6-yl)-aristolactam I (dA-AAI), has been detected. DNA adducts can be removed through DNA repair, they can result in mutations through erroneous DNA replication or they can cause cell death. The dA-AAI adduct induces AT to TA transversions in the tumor-suppressor TP53 gene in experimental systems, matching TP53 mutations observed in urothelial tumors from AAN cancer cases. Using thin-layer chromatography 32P-postlabeling and mass spectrometric analysis we report the detection of dA-AAI in renal DNA from 11 Belgian AAN patients over 20 years after exposure to AA had ceased. Our results showed that dA-AAI is an established biomarker of AA exposure, and that this biomarker can be demonstrated to be persistent decades after a distinct AA exposure. Further, the persistence of dA-AAI adducts appears to be a critical determinant for the AA mutational fingerprint frequently found in oncogenes and tumor suppressor genes recently identified by whole genome sequencing of AA-associated urothelial tumors. The potential for exposure to AA worldwide is high; the unprecedented long-term persistence of dA-AAI provides a useful long-term biomarker of exposure and attests to the role of AA in human urothelial malignancy.

  • renal interstitial fibrosis and urothelial carcinoma associated with the use of a chinese herb Aristolochia fangchi
    Toxicology, 2002
    Co-Authors: Joelle Nortier, Jeanlouis Vanherweghem
    Abstract:

    A new renal disease called 'Chinese-herb nephropathy' (CHN) has been reported to occur in women who have ingested slimming pills containing powdered extracts of the Chinese herb Stephania tetrandra (ST). Moderate to end-stage renal disease developed, requiring renal replacement therapy by dialysis or transplantation. Phytochemical analyses of the pills revealed the presence of aristolochic acids (AA) instead of tetrandrine, suggesting the substitution of ST (Han fang ji) by Aristolochia fangchi containing nephrotoxic and carcinogenic AA. A typical histological feature of CHN is a progressive interstitial fibrosis leading to a severe atrophy of the proximal tubules, as documented by the urinary excretion rates of markers of tubular integrity (reduction of neutral endopeptidase enzymuria and high levels of microproteinurias). Removal of the native kidneys and ureters in end-stage CHN patients provided a high prevalence of urothelial carcinoma (46%). Tissue samples contained AA-related DNA adducts, which are not only specific markers of prior exposure to AA but are also directly involved in tumorigenesis. Exposure to Aristolochia species (spp.) is associated with the development of renal interstitial fibrosis (CHN) and urothelial cancer in humans. Health professionals should be aware that in traditional Chinese medicine, Aristolochia spp. are considered interchangeable with certain other herbal ingredients and are also sometimes mistaken for ST, Akebia, Asarum, Clematis spp. and Cocculus spp. in herbal remedies.

  • progression rate of chinese herb nephropathy impact of Aristolochia fangchi ingested dose
    Nephrology Dialysis Transplantation, 2002
    Co-Authors: M C Martinez, Joelle Nortier, P Vereerstraeten, Jeanlouis Vanherweghem
    Abstract:

    Background. Renal failure after ingestion of Chinese herbs between 1990 and 1992 was related to the replacement of Stephania tetrandra by Aristolochia fangchi (ST=AF ), containing nephrotoxic and carcinogenic aristolochic acids. However, the relationship between ST=AF and renal failure is still a matter of debate. We therefore tested the impact of the ST=AF ingested dose on the progression of renal function deterioration. Methods. Analysis of medical charts and prescriptions between 1990 and 1992 was carried out to determine the presence of risk factors for kidney failure and the cumulative dose of pill components. Individual progression rate of renal impairment was studied by the time-course of the inverse of blood creatinine level (1uPcreat). Results. Patients were divided into an end-stage renal disease (ESRD) group (ns 44) and a chronic renal failure (CRF) group (ns 27) according to their Pcreat at the time of this study. The mean number of risk factors ("SD) was equally distributed within both groups (1.50"0.18 vs 1.59"0.17, Ps0.74). Patients from the ESRD group ingested significantly higher cumulative doses of ST=AF (192"13.1 g vs 138" 16.3 g), Magnolia officinalis, (80.1"6.3 g vs 59.8" 11.7 g), diethylpropion (14.7"1.4 g vs 10.0"1.4 g) and fenfluramine (14.1"1.6 g vs 8.7"1.3 g). In the ESRD group, some patients who had received steroids had a slower progression to ESRD than the others. In multiple regression analysis, ST=AF emerged as the only significant drug predicting the slope of the progression of renal failure. Moreover, hypothesizing a linear dose=response relationship, the risk of developing ESRD linearly increased with ST=AF doses. Conclusions. The relationship between the cumulative ST=AF dose and the renal failure progression rate confirms that regular ingestion of Aristolochia sp. extracts is causally involved in the onset of chronic interstitial nephropathy leading to ESRD.

  • urothelial carcinoma associated with the use of a chinese herb Aristolochia fangchi
    The New England Journal of Medicine, 2000
    Co-Authors: Joelle Nortier, Heinz H Schmeiser, M C Martinez, Volker M Arlt, Christian A Bieler, Michel Petein, Michel Depierreux, L De Pauw, Daniel Abramowicz, P Vereerstraeten
    Abstract:

    Background Chinese-herb nephropathy is a progressive form of renal fibrosis that develops in some patients who take weight-reducing pills containing Chinese herbs. Because of a manufacturing error, one of the herbs in these pills (Stephania tetrandra) was inadvertently replaced by Aristolochia fangchi, which is nephrotoxic and carcinogenic. Methods The diagnosis of a neoplastic lesion in the native urinary tract of a renal-transplant recipient who had Chinese-herb nephropathy prompted us to propose regular cystoscopic examinations and the prophylactic removal of the native kidneys and ureters in all our patients with end-stage Chinese-herb nephropathy who were being treated with either transplantation or dialysis. Surgical specimens were examined histologically and analyzed for the presence of DNA adducts formed by aristolochic acid. All prescriptions written for weight-reducing compounds during the period of exposure (1990 to 1992) in these patients were obtained, and the cumulative doses were calculated...

Monique S J Simmonds - One of the best experts on this subject based on the ideXlab platform.

  • medicinally used asarum species high resolution lc ms analysis of aristolochic acid analogs and in vitro toxicity screening in hk 2 cells
    Frontiers in Pharmacology, 2017
    Co-Authors: Johanna Michl, Olusheyi Bello, Geoffrey C Kite, Monique S J Simmonds, Michael Heinrich
    Abstract:

    Species of Asarum are used in traditional Chinese medicine and, similar to members of the genus Aristolochia, they contain aristolochic acid analogs (AAAs). These compounds are known for their nephrotoxic and carcinogenic effects. So far, the phytochemistry and nephrotoxicity of species of Asarum is not well studied. A high-resolution LC-MS-based metabolomic approach was used to study the phytochemical variation in medicinally used Asarum species. The cytotoxicity of the samples was assessed using human kidney (HK-2) cells. The majority of samples contained potentially nephrotoxic AAAs, including 9-methoxy aristolactam (AL) IV, AL I, and AL IV. These compounds were present in methanol as well as water extracts. AAAs were detected in all parts of the plant. The majority of the extracts were not cytotoxic to HK-2 cells at the doses tested. However, other mechanisms relating to aristolochic acid nephropathy and cancer development, such as DNA adduct formation may occur. The results of this study provide a model for assessing lesser-known plant species for toxicity.

  • lc ms and 1h nmr based metabolomic analysis and in vitro toxicological assessment of 43 Aristolochia species
    Journal of Natural Products, 2016
    Co-Authors: Johanna Michl, Geoffrey C Kite, Monique S J Simmonds, Stefan Wanke, Oliver Zierau, G Vollmer, Christoph Neinhuis, Michael Heinrich
    Abstract:

    Species of Aristolochia are used as herbal medicines worldwide. They cause aristolochic acid nephropathy (AAN), a devastating disease associated with kidney failure and renal cancer. Aristolochic acids I and II (1 and 2) are considered to be responsible for these nephrotoxic and carcinogenic effects. A wide range of other aristolochic acid analogues (AAAs) exist, and their implication in AAN may have been overlooked. An LC-MS- and 1H NMR-based metabolomic analysis was carried out on 43 medicinally used Aristolochia species. The cytotoxicity and genotoxicity of 28 Aristolochia extracts were measured in human kidney (HK-2) cells. Compounds 1 and 2 were found to be the most common AAAs. However, AA IV (3), aristolactam I (4), and aristolactam BI (5) were also widespread. No correlation was found between the amounts of 1 or 2 and extract cytotoxicity against HK-2 cells. The genotoxicity and cytotoxicity of the extracts could be linked to their contents of 5, AA D (8), and AA IIIa (10). These results undermine...

  • is aristolochic acid nephropathy a widespread problem in developing countries a case study of Aristolochia indica l in bangladesh using an ethnobotanical phytochemical approach
    Journal of Ethnopharmacology, 2013
    Co-Authors: Johanna Michl, Geoffrey C Kite, Monique S J Simmonds, Michael Heinrich, Hannah Jennings, Martin J Ingrouille
    Abstract:

    Species of Aristolochia are associated with aristolochic acid nephropathy (AAN), a renal interstitial fibrosis and upper urinary tract cancer (UUC). Aristolochic acid nephropathy has been reported in ten countries but its true incidence is unknown and most likely underestimated. By combining an ethnobotanical and phytochemical approach we provide evidence for the risk of AAN occurring in Bangladesh. More specifically, we assess the intra-specific variation of aristolochic acid analogues in medicinally used A. indica samples from Bangladesh.

  • local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2 a global assessment based on bibliographic sources
    Journal of Ethnopharmacology, 2009
    Co-Authors: Michael Heinrich, Monique S J Simmonds, Stefan Wanke, Christoph Neinhuis, Jennifer Chan
    Abstract:

    Abstract Aims of the study More than 100 cases of nephropathy over the last 10 years caused by the systemic and longer term application of Chinese snakeroot ( Aristolochia fangchi ) highlighted the risk of using preparations which contain aristolochic acids. On the other hand anecdotal evidence highlights the widespread use of Aristolochia species (Aristolochiaceae) in many regions of the world. Therefore, it was our objective to systematically assess the scientific literature available on the local and traditional use of Aristolochia spp. on a worldwide scale. Our review identifies core species which need to be investigated and which may need monitoring (esp. in national and international trade). Methods An extensive review of the literature available in libraries in London on the uses of species of Aristolochia was undertaken. Relevant information was extracted and entered into a database for analysis. Results Based on the assessment of 566 reference sources 685 individual sets of data were recorded. Seven species – Aristolochia indica L. (Asia), Aristolochia serpentaria L. (North America), Aristolochia debilis Sieb & Zucch. (China), Aristolochia acuminata Lam (India), Aristolochia trilobata L. (Central/South America, Caribbean), Aristolochia clematitis L. (Europe) and Aristolochia bracteolata Lam. (Africa) – are reported widely as being used medicinally. The medical uses vary, but of particular interest are uses in case of gastrointestinal problems, which is likely to result in repeated exposure to the botanical drugs by an individual. About half of all records relate to uses of Aristolochia species in Asia, one-third to the Americas, a continent which has so far received practically no attention in terms of assessing the risk of using species of Aristolochia . Of the 99 species (plus several identified at genus level only) for which we were able to summarise ethnobotanical information, preliminary phytochemical information is only available for 24 species and some of the most common ones including Aristolochia acuminata have so far not been studied phytochemically. Conclusions Species of Aristolochia are used medicinally in many regions of the world and both from an ethnopharmacological and a public health perspective this poses a risk. A systematic assessment of the content of aristolochic acids in the most widely used species is needed to evaluate whether their uses pose a potential health risk. In China and Europe species of Aristolochia have been associated with nephropathy and it is important to evaluate whether nephropathy occurs in other parts of the world, especially India and Central America where the use of species of Aristolochia are reported to be commonly used in traditional medicine.

Jongki Hong - One of the best experts on this subject based on the ideXlab platform.

  • Simultaneous Determination of Structurally Diverse Compounds in Different Fangchi Species by UHPLC-DAD and UHPLC-ESI-MS/MS
    Molecules, 2013
    Co-Authors: Jongki Hong
    Abstract:

    Abstract: Two bisbenzylisoquinoline alkaloids, two morphine alkaloids, one aporphine alkaloid, syringaresinol and aristolochic acid І were selected as marker compounds and simultaneously analyzed using an ultra-high pressure liquid chromatography-diode array detection (UHPLC-DAD) method. These marker compounds were used for the quality control of Fangchi species of different origins, including Sinomenium acutum , Stephania tetrandra , Cocculus trilobus and Aristolochia fangchi . A reversed-phase UHPLC-DAD method was developed and validated for the simultaneous quantification of structurally diverse markers in different Fangchi species. In addition, an UHPLC-electrospray ionization tandem mass spectrometry (ESI-MS/MS) method was used for marker identification in Fangchi species, which provided diagnostic MS/MS spectral patterns that were dependent upon the marker structures. The UHPLC-MS/MS data were used to confirm and complement the UHPLC-DAD quality evaluation results. Additionally, magnoflorine and syringaresinol were observed for the first time in