Review on NMR spectroscopic data and recent analytical methods of aristolochic acids and derivatives in Aristolochia herbs

doi:10.1007/s13659-025-00506-x

Natural Products and Bioprospecting ›› 2025, Vol. 15 ›› Issue (5): 41-41.DOI: 10.1007/s13659-025-00506-x

Review on NMR spectroscopic data and recent analytical methods of aristolochic acids and derivatives in Aristolochia herbs

Phan Minh Giang¹, Nguyen Nghia Vu^1,2, Vu Thanh Loc^1,3, Dong Ngoc Phuc¹, Ngiem Duc Trong⁴, To Phuong Linh⁵, Tran Thi Thu Thuy³

1. Faculty of Chemistry, VNU University of Science, Vietnam National University, Hanoi, 19 Le Thanh Tong Street, Hanoi, Vietnam;
2. Center for Research and Production of Vaccines and Biologicals, Ministry of Health, 135 Lo Duc Street, Hanoi, Vietnam;
3. Institute of Chemistry of Natural Products, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Street, Hanoi, Vietnam;
4. Department of Botany, Hanoi University of Pharmacy, 13-15 Le Thanh Tong Street, Hanoi, Vietnam;
5. Institute of New Technology, Academy of Military Science and Technology, 17 Hoang Sam Street, Hanoi, Vietnam

Received:2024-10-19 Online:2025-11-06
Contact: Phan Minh Giang,E-mail:giangpm@vnu.edu.vn
Supported by:
This research is funded by Vietnam National Foundation for Science and Technology Development (NAFOSTED) under Grant Number 104.01-2021.09.

Review on NMR spectroscopic data and recent analytical methods of aristolochic acids and derivatives in Aristolochia herbs

Phan Minh Giang¹, Nguyen Nghia Vu^1,2, Vu Thanh Loc^1,3, Dong Ngoc Phuc¹, Ngiem Duc Trong⁴, To Phuong Linh⁵, Tran Thi Thu Thuy³

1. Faculty of Chemistry, VNU University of Science, Vietnam National University, Hanoi, 19 Le Thanh Tong Street, Hanoi, Vietnam;
2. Center for Research and Production of Vaccines and Biologicals, Ministry of Health, 135 Lo Duc Street, Hanoi, Vietnam;
3. Institute of Chemistry of Natural Products, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Street, Hanoi, Vietnam;
4. Department of Botany, Hanoi University of Pharmacy, 13-15 Le Thanh Tong Street, Hanoi, Vietnam;
5. Institute of New Technology, Academy of Military Science and Technology, 17 Hoang Sam Street, Hanoi, Vietnam

通讯作者: Phan Minh Giang,E-mail:giangpm@vnu.edu.vn
基金资助:
This research is funded by Vietnam National Foundation for Science and Technology Development (NAFOSTED) under Grant Number 104.01-2021.09.

Abstract

Abstract: Aristolochic acids (AAs) are an important group of secondary metabolites in the genus Aristolochia. The presence of aristolochic acids infers the potency of many Aristolochia herbs used for ages in traditional medicine of China, Europe, Central America, India, and some other countries. Although being moderately cytotoxic, intake of AAs is associated with serious health problems, such as nephrotoxicity and carcinogenicity. Analyzing AAs in Aristolochia herbs is crucial for regulating their efficacy and toxicity because phytochemistry works have shown the occurrence of AAs in almost all Aristolochia herbs studied. Using two-dimensional parameters, chemical shifts and coupling constants, NMR spectroscopy is a modern, accurate, and reliable method in the analysis of secondary metabolites. Comparing experimental spectroscopic data with those of known and related compounds helps simplify the structural identification of secondary metabolites. The compilation of an NMR database of AAs from scattered sources would also be useful in NMR-based metabolomics. The present review provides updated information on sources and NMR spectroscopic data of 54 aristolochic acid derivatives, including AAs and their methyl esters, denitroaristolochic acids and their derivatives, and sesqui- and diterpene esters of AAs. The report also covers the newest development of analytical and preparative methods used in separation, identification, and quantification of AAs in Aristolochia herbal samples.

Key words: Aristolochia, Aristolochiaceae, Aristolochic acid (AA), Denitroaristolochic acid, LC analysis, NMR data

摘要： Aristolochic acids (AAs) are an important group of secondary metabolites in the genus Aristolochia. The presence of aristolochic acids infers the potency of many Aristolochia herbs used for ages in traditional medicine of China, Europe, Central America, India, and some other countries. Although being moderately cytotoxic, intake of AAs is associated with serious health problems, such as nephrotoxicity and carcinogenicity. Analyzing AAs in Aristolochia herbs is crucial for regulating their efficacy and toxicity because phytochemistry works have shown the occurrence of AAs in almost all Aristolochia herbs studied. Using two-dimensional parameters, chemical shifts and coupling constants, NMR spectroscopy is a modern, accurate, and reliable method in the analysis of secondary metabolites. Comparing experimental spectroscopic data with those of known and related compounds helps simplify the structural identification of secondary metabolites. The compilation of an NMR database of AAs from scattered sources would also be useful in NMR-based metabolomics. The present review provides updated information on sources and NMR spectroscopic data of 54 aristolochic acid derivatives, including AAs and their methyl esters, denitroaristolochic acids and their derivatives, and sesqui- and diterpene esters of AAs. The report also covers the newest development of analytical and preparative methods used in separation, identification, and quantification of AAs in Aristolochia herbal samples.

关键词: Aristolochia, Aristolochiaceae, Aristolochic acid (AA), Denitroaristolochic acid, LC analysis, NMR data

Phan Minh Giang, Nguyen Nghia Vu, Vu Thanh Loc, Dong Ngoc Phuc, Ngiem Duc Trong, To Phuong Linh, Tran Thi Thu Thuy. Review on NMR spectroscopic data and recent analytical methods of aristolochic acids and derivatives in Aristolochia herbs[J]. Natural Products and Bioprospecting, 2025, 15(5): 41-41.

References

[1] Heinrich M, Chan J, Wanke S, Neinhuis C, Simmonds MSJ. Local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2-a global assessment based on bibliographic sources. J Ethnopharmacol. 2009;125:108-44.
[2] Holzbach JC, Lopes LXM. Aristolactams and alkamides of Aristolochia giganta. Molecules. 2010;15:9462-72.
[3] Shi LS, Kuo PC, Tsai YL, Damu AG, Wu TS. The alkaloids and other constituents from the root and stem of Aristolochia elegans. Bioorg Med Chem. 2004;12:439-46.
[4] Wang X, Jin M, Jin C, Sun J, Zhou W, Li G. A new sesquiterpene, a new monoterpene and other constituents with anti-inflammatory activities from the roots of Aristolochia debilis. Nat Prod Res. 2020;34:351-8.
[5] Lu JZ, Wei F, Cai Y. A new aristolactam-type from the roots of Aristolochia fangchi. J Asian Nat Prod Res. 2012;14:276-80.
[6] Zhou Z, Luo J, Pan K, Kong L. A new alkaloid glycoside from the rhizomes of Aristolochia fordiana. Nat Prod Res. 2015;28:1065-9.
[7] Jiménez-Arellanes A, León-Díaz R, Meckes M, Tapia A, Molina-Salinas GM, Luna-Herrera J, Yépez-Mulia L. Antiprotozoal and antimycobacterial activities of pure compounds from Aristolochia elegans rhizomes. Evid Based Complement Alternat Med. 2012;2012:593403.
[8] Desai DC, Jacob J, Almeida A, Kshirsagar R, Manju SL. Isolation, structural elucidation and anti-inflammatory activity of astragalin, (-)-hinokinin, aristolactam I and aristolochic acids (I & II) from Aristolochia indica. Nat Prod Res. 2014;28:141301417.
[9] Chen YG, Yu LL, Huang R, Liu JC, Lu YP, Zhao Y. 3″-Hydroxyamentoflavone ant its 7-O-methyl ether, two new bioflavonoids from Aristolochia contorta. Arch Pharm Res. 2005;2025:1233-5.
[10] Zhang G, Shimokawa S, Mochizuki M, Kumamoto T, Nakanishi W, Watanabe T, Ishikawa T, Matsumoto K, Tashima K, Horie S, Higuchi Y, Dominguez OP. Chemical constituents of Aristolochia constricta: antiplasmodic effects of its constituents in Guinea-pig ileum and isolation of a diterpeno-lignan hybrid. J Nat Prod. 2008;71:1167-72.
[11] Lerma-Herrera MA, Beiza-Granados L, Ochoa-Zarzosa A, López-Meza JE, Navarro-Santos P, Herrera-Bucio R, Avirna-Verduzco J, Gariciá-Gutiérrez HA. Biological activities of organic extracts of the genus Aristolochia: a review from 2005 to 2021. Molecules. 2022;27:3937.
[12] Wu TS, Damu AG, Su CR, Kuo PC. Terpenoids of Aristolochia and their biological activities. Nat Prod Rep. 2004;21:594-624.
[13] Pacheco AG, de Oliveira PM, Piló-Veloso D, Alcântara AFC. ¹³C-NMR data of diterpenes isolated from Aristolochia species. Molecules. 2009;14:1245-62.
[14] Michl J, Ingrouille MJ, Simmonds MSJ, Heinrich M. Naturally occurring aristolochic acid analogues and their toxicities. Nat Prod Rep. 2014;31:676-93.
[15] Attaluri S, Iden CR, Bonala RR, Johnson F. Total synthesis of aristolochic acids, their major metabolites, and related compounds. Chem Res Toxicol. 2014;27:1236-42.
[16] Houghton PJ, Ogutveren M. Aristolochic acids and aristolactams from Aristolochia auricularia. Phytochemistry. 1991;30:253-4.
[17] Cai Y, Cai TG. Two new aristolochic acid derivatives from the roots of Aristolochia fangchi and their cytotoxicities. Chem Pharm Bull. 2010;58:1093-5.
[18] Ji HJ, Li JY, Wu SF, Wu WY, Yao CL, Yao S, Zhang JQ, Guo DA. Two new aristolochic acid analogues from the roots of Aristolochia contorta with significant cytotoxic activity. Molecules. 2021;26:44.
[19] Priestap HA, Barbieri MA. Conversion of aristolochic acid I into aristolic acid by reaction with cysteine and glutathione: biological implications. J Nat Prod. 2013;76:965-8.
[20] Priestap HA, de Santos C, Quirke JM. Identification of a reduction product of aristolochic acid: implication for the metabolic activation of carcinogenic aristolochic acid. J Nat Prod. 2010;73:1979-86.
[21] Krell D, Stebbing J. Aristolochia: the malignant truth. Lancet. 2013;14:25-6.
[22] Achenbach H, Waibel R, Zwanzger M. 9-Methoxy- and 7,9-dimethoxytariacuripyrone, natural nitro-compounds with a new basic skeleton from Aristolochia brevipes. J Nat Prod. 1992;55:918-22.
[23] Schimmer O, Drewello U. 9-Methoxytariacuripyrone, a naturally occurring nitro-aromatic compound with strong mutagenicity in Salmonella typhimurium. Mutagenesis. 1994;9:547-51.
[24] Wang X, Shi GR, Liu YF, Li L, Chen RY, Yu DQ. Aristolochic acid derivatives from the rhizome of Aristolochia championii. Fitoterapia. 2017;118:63-8.
[25] Maggini V, Menniti-Ippolito F, Firenzuoli F. Aristolochia, a nephrotoxic herb, still surfs on the Web, 15 years later. Intern Emerg Med. 2018. https://doi.org/10.1007/s111739-018-1813-2.
[26] Wen YJ, Su T, Tang JW, Zhang CY, Wang X, Cai SQ, Li XM. Cytotoxicity of phenanthrenes extracted from Aristolochia contorta in human proximal tubular epithelial cell line. Nephron Exp Nephrol. 2006;103:e95.
[27] Mix DB, Guinaudeau H, Shamma M. The aristolochic acids and aristolactams. J Nat Prod. 1982;45:657-66.
[28] Achari B, Bandyopadhyay S, Chakravarty AK, Pakrashi SC. Carbon ¹³C NMR spectra of some phenanthrene derivatives from Aristolochia indica and their analogues. Org Magn Reson. 1984;22:741-6.
[29] Priestap HA. ¹³C NMR spectroscopy of aristolochic acids and aristololactams. Mag Res Chem. 1989;27:460-9.
[30] Michl J, Kite GC, Wanke S, Zierau O, Vollmer G, Neinhuis C, Simmonds MSJ, Heinrich M. LC-MS- and ¹H NMR-based metabolomic analysis and in vitro toxicological assessment of 43 Aristolochia species. J Nat Prod. 2016;9:30-7.
[31] Nakanishi T, Iwasaki K, Nasu M, Miura I, Yoneda K. Aristoloside, an aristolochic acid derivative from stems of Aristolochia manshuriensis. Phytochemistry. 1981;21:1759-62.
[32] De P, Teresa J, Urones JG, Fernandez A. An aristolochic acid derivative from Aristolochia longa. Phytochemistry. 1983;22:2745-7.
[33] Wu TS, Chan YY, Leu YL. The constituents of the root and stem of Aristolochia cucurbitifolia Hayata and their biological activity. Chem Pharm Bull. 2000;48:1006-9.
[34] Che CT, Ahmed MS, Kang SS, Waller DP, Bingel AS, Martin A, Rajamahendran P, Bunyapraphatsara N, Lankin DC, Cordell GA, Soejarto DD, Wijesekera ROB, Fong HHS. Studies on Aristolochia III Isolation and biological evaluation of constituents of Aristolochia indica roots for fertility-regulating activity. J Nat Prod. 1984;47:331-41.
[35] Mizuno M, Oka M, Iinuma M, Tanaka T. An aristolochic acid derivative of Aristolochica liukiuensis. J Nat Prod. 1990;53:179-81.
[36] Wu TS, Ou LF, Teng CM. Aristolochic acids, aristolactam alkaloids and amides from Aristolochia kankauensis. Phytochemistry. 1994;36:1063-8.
[37] Hong L, Sakagami Y, Marumo S, Xinmin C. Eleven aristolochic acid derivatives from Aristolochia cinnabarina. Phytochemistry. 1994;37:237-9.
[38] Leu YL, Chan YY, Wu TS. Sodium aristolochate derivatives from leaves of Aristolochia foveolata. Phytochemistry. 1998;48:743-5.
[39] Nascimento IR, Lopes LMX. Diterpene etsers of aristolochic acids from Aristolochia pubescens. Phytochemistry. 2003;63:953-7.
[40] Wu TS, Leu YL, Chan YY. Constituents of the fresh leaves of Aristolochia cucurbitifolia. Chem Pharm Bull. 1999;47:571-3.
[41] Wu TS, Chan YY, Leu YL. The constituents of the root and stem of Aristolochia heterophylla Hemsl. Chem Pharm Bull. 2000;48:357-61.
[42] Wu TS, Leu YL, Chan YY. Constituents from the stem and root of Aristolochia kaempferi. Biol Pharm Bull. 2000;23:1216-9.
[43] Al-Busafi S, Al-Harthi M, Al-Sabahi B. Isolation of aristolochic acids from Aristolochia bracteolata and studies of their antioxidant activities. SQU J Sci. 2004;9:19-23.
[44] Al-Barham MB, Al-Jaber HI, Al-Qudah MA, Abu Zarga MH. New aristolochic acid and other chemical constituents of Aristolochia maurorum growing wild in Jordan. Nat Prod Res. 2017;31:245-52.
[45] Wu TS, Leu YL, Chan YY. Aristofolin-A, a denitro-aristolochic acid glycoside and other constituents form Aristolochia kaempferi. Phytochemistry. 1998;49:2509-10.
[46] Wu TS, Leu YL, Chan YY. Denitroaristolochic acids from the leaves of Aristolochia cucurbitifolia. Chem Pharm Bull. 1998;46:1301-2.
[47] Wu PL, Su GC, Wu TS. Constituents from the stems of Aristolochia manshuriensis. J Nat Prod. 2003;66:996-8.
[48] Pakrashi SC, Ghosh-Dastidar P, Basu S, Achari B. New phenanthrene derivatives from Aristolochia indica. Phytochemistry. 1977;16:1103-4.
[49] Chung YM, Chang FR, Tseng TF, Hwang TL, Chen LC, Wu SF, Lee CL, Lin ZY, Chuang LY, Su JH, Wu YC. A novel alkaloid, aristopyridinone A and anti-inflammatory phenanthrenes isolated from Aristolochia manshuriensis. Bioorg Med Chem Lett. 2011;21:1792-4.
[50] Wu TS, Leu YL, Chan YY. Aristolochic acids as a defentive substance for the Aristolochiaceous plant-feeding swallowtail butterfly, Pachliopta aristolochiae interpositus. J Chin Chem Soc. 2000;47:221-6.
[51] Mukhopadhyay S, Funayama S, Cordell GA, Fong HHS. Studies on Aristolochia, I. Conversion of aristolochic acid-I to aristolic acid-one step removal of a nitro group. J Nat Prod. 1983;46:507-9.
[52] Wu TS, Chan YY, Leu YL, Chen ZT. Sesquiterpene esters of aristolochic acid from the root and stem of Aristolochia heterophylla. J Nat Prod. 1999;62:415-8.
[53] Wu TS, Chan YY, Leu YL, Wu PL, Li CY, Mori Y. Four aristolochic acid ester of rearranged ent-elemane sesquiterpenes from Aristolochia heterophylla. J Nat Prod. 1999;6:348-51.
[54] Wu TS, Tsai YL, Damu AG, Kuo PC, Wu PL. Constituents form the root and stem of Aristolochia elegans. J Nat Prod. 2002;65:1522-5.
[55] Hashimoto K, Higuchi M, Makino B, Sakakibara I, Kubo M, Komatsu Y, Maruno M, Okada M. Quantitative analysis of aristolochic acids, toxic compounds, contained in some medicinal plants. J Ethnopharm. 1999;64:185-9.
[56] Bartha GS, Tóth G, Horváth P, Kiss E, Papp N, Kerényi M. Analysis of aristolochic acids and evaluation of antibacterial activity of Aristolochia clematitis L. Biol Futura. 2019;70:323-9.
[57] Li W, Li R, Bo T, Liu H, Feng X, Hu S. Rapid determination of aristolochic acids I and II in some medicinal plants by high-perfomance liquid chromatography. Chromatographia. 2004;59:233-6.
[58] Alali FO, Tawaha K, Shehadeh MB, Telfah S. Phytochemical and biological investigation of Aristolochia maurorum L. Z Naturforsch. 2006;2006:685-91.
[59] Zhang C, Wang X, Shang M, Yu J, Xu Y, Li Z, Lei L, Li X, Cai S, Namba T. Simultaneous determination of five aristolochic acids and two aristolactmas in Aristolochia plants by high-perfomance liquid chromatography. Biomed Chromatogr. 2006;20:309-18.
[60] Abdelgadir AA, Ahmed EM, Eltohami MS. Isolation, characterization and quality determination of aritolochic acids, toxic compounds in Aristolochia bracteolata L. Environ Health Insights. 2011;5:1-8.
[61] Araya M, García S, Gonzaslez-Teuber M. Rapid identification and simultaneous quantification of aristolochic acids by HPLC-DAD and confirmation by MS in Aristolochia chilensis using a limited biomass. J Anal Methods Chem. 2018;2018:5036542.
[62] Rodríguez IIG, Francisco AF, Moreira-Drill LS, Quintero A, Guimarães CLS, Fernandes CAH, Takeda AAS, Zanchi FB, Caldeira CAS, Pereira PS, Fontes MRM, Zuliani JP, Soares AM. Isolation and structural characterization of bioactive compound from Aristolochia spruce aqueous extract with anti-myotic activity. Toxicon: X. 2020;2020:100049.
[63] Zhang SH, Wang Y, Yang J, Zhang DD, Wang YL, Li SH, Pan YN, Zhang HM, Sun Y. Comparative analysis of aristolochic acids in Aristolochia medicinal herbs and evaluation of their toxicities. Toxins. 2022;14:879.
[64] Zhou X, Zheng C, Sun J, You T. Analysis of nephroloxic and carcinogenic aristolochic acids in Aristolochia plants by capillary electrophoresis with electrochemical detection at a carbon fiber microdisk electrode. J Chromatg A. 2006;1109:152-9.
[65] Zhang J, Xiao Y, Feng J, Wu SL, Xue X, Zhang X, Liang X. Selective preparative purification of aristolochic acids and aristolactams from Aristolochia plants. J Pharm Biomed Anal. 2010;52:446-51.
[66] Duan W, Li Y, Dong H, Yang G, Wang W, Wang X. Isolation and purification of six aristolochic acids with similar structures from Aristolochia manshuriensis Kom stems by pH-zone-refining counter-current chromatography. J Chromatog A. 2020;1613:460657.

Review on NMR spectroscopic data and recent analytical methods of aristolochic acids and derivatives in Aristolochia herbs

Review on NMR spectroscopic data and recent analytical methods of aristolochic acids and derivatives in Aristolochia herbs

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