€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ACTA MEDICA PHILIPPINA***** Angeles LT Canlas BD Concha JA Sotto AS Aligaen PL TOXICITY STUDIES ON ARISTOLOCHIC ACID ISOLATED FROM ARISTOLOCHIA TAGALA, CHAM In: Acta Med Philipp (1970) 6(2):139-148 ISSN: 0001-6071 In mice treated with aristolochic acid I (AA-I; 10-80 mg/kg ip), the acute toxic manifestations were tachycardia, increased respiration, ataxia, sedation and marked vasodilatation. No deaths were seen at doses below 40 mg/kg. After admin of the LD50 (15.80 mg/kg), the mice died of respiratory arrest on d 3-5. Autopsy examination showed the heart fixed in diastole, the lungs engorged with blood, pale liver and kidneys and many hemorrhagic foci in the viscera. The short-term chronic toxic effects of AA-I (1.0-2.0 mg/kg/d x 11 ip) included hepatotoxicity, marked renal damage and mild hematological dyscrasias (with a decrease in lymphocytes and an increase in granulocytes). Cell division was inhibited in WBC from treated mice. Females were more sensitive than males to the toxic effects of AA. It is suggested that the toxic effects of AA-I (8-methoxy-6-nitrophenanthro+3,4-d1- 1,3-dioxole-5-carboxylic acid) may be related to the presence of both the nitrophenanthrene nucleus of the opium alkaloids and the benzylisoquinoline moiety of papaverine in the AA molecule. The cytotoxicity of AA may be related to the presence of an epoxide moiety; however, the cytotoxicity and the nephrotoxic effects (the principal side effects of AA in man) of AA might also result from an effect of AA on membrane transport. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ANTICANCER RESEARCH***** Voloudakis-Baltatzis IE Karydas I Pateras C Experimental applications of herbs of Greek flora with anticancer properties in breast cancer in vitro and in rats in vivo (Meeting abstract). In: Anticancer Res (1992) 12(6A):1883 ISSN: 0250-7005 This study concerns the experimental Greek herb substances, with anticancer properties, named IBV-BK (Aristolochia, Iska). We tested the IBV-BK drugs, first on human primary cultures, derived from malignant and nonmalignant breast tissues in vitro, second, in vivo on rats with Walker carcinoma. The cells of nonmalignant breast cultures remained unchanged after treatment with IBV-BK, while the malignant cells were killed in 1 or 2 days after treatment with IBV- BK drugs. In a number of rats with Walker carcinoma, the tumor of these rats disappeared after 2-wk treatment with IBV-BK drugs. Control rats with Walker carcinoma without IBV-BK treatment died in approx 28 days. So, our interesting results observed by IBV-BK drugs, both in vitro and in vivo direct us to study in detail the organic elements of these herbs. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BULLETIN ET MEMOIRES DE L ACADEMIE ROYALE DE MEDECINE DE BELGIQUE***** Vanherweghem JL [A new form of nephropathy secondary to the absorption of Chinese herbs] Une nouvelle forme de nephropathie secondaire a l'absorption d'herbes chinoises. In: Bull Mem Acad R Med Belg (1994) 149(1-2):128-35; discussion 135-40 ISSN: 0377-8231 (Published in French) An outbreak of rapidly progressive renal failure was observed in Belgium in 1992-1993 and was related to a slimming regimen involving chinese herbs, namely Stephania tetrandra and Magnolia officinalis. Seventy one cases were registered on january 1994, 35 of whom being on renal replacement therapy. Renal failure has been progressing in most of the cases despite the withdrawal of the exposure to the chinese herbs. Renal biopsies showed an extensive interstitial fibrosis with loss of tubes, predominantly in the outer cortex. Chemical analyses of the chinese herbs powdered extracts delivered in Belgium demonstrated a misidentification between Stephania tetrandra and another chinese herb, Aristolochia Fang-chi, potentially nephrotoxic. These observations indicate the need of intensive search of nephrotoxins in cases of interstitial nephritis of unknown origin. Also, they underline the necessity of the introduction of measures allowing the control of correct identification of herbs preparations. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ ***CHUNG HSI I CHIEH HO TSA CHIH CHINESE JOURNAL OF MODERN DEVELOPMENTS*** Zheng M [Experimental study of 472 herbs with antiviral action against the herpes simplex virus] In: Chung Hsi I Chieh Ho Tsa Chih (1990 Jan) 10(1):39-41, 6 ISSN: 0254-9034 (Published in Chinese) Using tissue culture method, the present work with its first-hand observation was primarily concerned with evaluating the antiviral effect of 472 traditional medicinal herbs (comprising raw material 10 mg/ml), through both initial (qualitative) and repeated (quantitative) screens, on type 1 herpes simplex virus. When dealing with water and alcoholic extracts, the effective herbs during initial screens were reduced after repeated screens by a range of 28.8-80.0%. Employing the basic value attained by the simultaneous route of drug administration, a stepwise declining of effective herbs would be: extratube route greater than simultaneous route greater than therapeutic route greater than preventive route. The more the routes of drug administration, the less the multiple-route simultaneous efficacy of a herb. Through repeated screens, 10 highly effective herbs were Aristolochia debilis, Artemisia anomala, Lindera strychnifolia, Patrinia villosa, Pinus massoniana, Prunella vulgaris, Pyrrosia lingua, Rhus chinensis, Sargussum fusiforme and Taraxacum mongolicum. Clinically, among the 78 cases of herpetic keratitis due to HSV1 treated by Pyrrosia lingua and Prunella vulgaris eye drops, a cure was effected in 38 and an improvement in 37, with 3 being of no benefit. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CONTRACEPTION***** Pakrashi A Pakrasi P Antifertility efficacy of the plant Aristolochia indica linn on mouse. In: Contraception (1979 Jul) 20(1):49-54 ISSN: 0010-7824 Two compounds isolated from the alcoholic extract of the roots of Aristolochia indica Linn were tested on day 6 pregnant mice. One of the compounds, p-coumaric acid showed 100% interceptive activity at the single oral dose of 50 mg/kg of body weight. The antifertility efficacy of these two compounds is discussed. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Ganguly T Pakrashi A Pal AK Disruption of pregnancy in mouse by aristolic acid: I. Plausible explanation in relation to early pregnancy events. In: Contraception (1986 Dec) 34(6):625-37 ISSN: 0010-7824 Aristolic acid (AA), obtained from Aristolochia indica Linn, disrupted nidation in mice when administered on Day 1 of pregnancy. The implantation inhibiting effect of the compound was assessed with respect to certain parameters which are characteristics of early pregnancy, such as tubal transport of ova into the uterus, hyperpermeability of the endometrial capillaries, increase in uterine weight and total protein content, endometrial bed preparation and changes in uterine phosphatase enzymes during Days 4-6 of pregnancy. The compound did not affect tubal transport of eggs, but the uterine blue reaction, caused by extravasation of the dye, pontamine blue, at future implantation sites was inhibited significantly in treated mice. Histological picture of the uterus revealed AA-induced impairment of development (i.e. decidualization) and reconciled with decreases found in uterine weight and its total protein contents in treated animals. In control untreated mice, specific uterine alkaline phosphatase (ALP) activity increased significantly from Days 4 through 6 of pregnancy, but this was prevented in treated mice. On the other hand, specific uterine acid phosphatase (AP) activity was high on Day 5, while in treated mice uterine AP activity remained low during Days 4 and 5 and increased significantly thereafter. It was inferred that AA interferes with steroidal conditioning of the uterus and renders it hostile to ovum implantation. Registry Numbers: EC 3.1.3.1 (Alkaline Phosphatase) EC 3.1.3.2 (Acid Phosphatase) 35142-05-3 (aristolic acid) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****EXPERIENTIA***** Pakrashi A Shaha C Effect of methyl ester of aristolic acid from Aristolochia indica Linn. on fertility of female mice. In: Experientia (1978 Sep 15) 34(9):1192-3 ISSN: 0014-4754 Methyl ester of aristolic acid, a pure compound isolated from the roots of Aristolochia indica (Linn.), was found to exert 100% abortifacient activity at a single oral dose of 60 mg/kg b. wt when administered on 6th or 7th day of pregnancy; 20 and 25% abortifacient effect were observed at the same dose on day 10 and 12, respectively. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Pakrashi A Shaha C Effect of a sesquiterpene from Aristolochia indica Linn. on fertility in female mice. In: Experientia (1977 Nov 15) 33(11):1498-9 ISSN: 0014-4754 A sesquiterpene isolated from the roots of Aristolochia indica (Linn.) was found to exert 100% interceptive activity and 91.7% anti- implantation activity in mice at a single oral dose of 100 mg/kg b. wt. No toxic effect was found at the dose levels used. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Pakrashi A Chakrabarty B Dasgupta A Effect of the extracts from Aristolochia indica Linn. on interception in female mice. In: Experientia (1976 Mar 15) 32(3):394-5 ISSN: 0014-4754 The crude petroleum ether, chloroform and alcoholic extracts from the roots of Aristolochia indica (Linn.) showed 100% interceptive activity in mature female mice at the single dose of 100 mg/kg body wt. The follow-up studies with the chloroform extract showed the most significant effect in the basic part and two acidic fractions at the single dose levels of 50 mg/kg body wt. No toxic effect was observed at the dose levels used. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****INFLAMMATION***** Vishwanath BS Fawzy AA Franson RC Edema-inducing activity of phospholipase A2 purified from human synovial fluid and inhibition by aristolochic acid. In: Inflammation (1988 Dec) 12(6):549-61 ISSN: 0360-3997 A neutral-active, Ca2+-dependent phospholipase A2 (PLA2) purified 11,000-fold from human synovial fluid (HSF) induced edema when injected into the mouse foot pad. The edema produced by HSF-PLA2 was dose-dependent and was positively correlated with the dose-dependent in vitro expression of PLA2 activity. Maximum edema was achieved within 45 min after the injection and persisted for at least 6 h. Aristolochic acid [8-methoxy-6-nitrophenanthro(3,4-d)-1,3-dioxole-5- carboxylic acid], a major chemical component derived from various species of Aristolochia plant, produced a dose-dependent inhibition of in vitro phospholipid hydrolysis by HSF-PLA2, porcine pancreatic PLA2, snake venom (Naja naja) PLA2, and PLA2 isolated from human platelet. The sensitivity of these PLA2s to inhibition by aristolochic acid varied markedly: HSF-PLA2 greater than N. naja PLA2 greater than human platelet PLA2 greater than porcine pancreatic PLA2. The inhibition of HSF-PLA2 by aristolochic acid was independent of substrate concentration (18-144 microM) and Ca2+ concentration (0.1-4.0 mM). These observations indicate that inhibition of HSF-PLA2 by aristolochic acid may result from direct interaction with the enzyme. When aristolochic acid was mixed with HSF-PLA2 and then injected into the mouse foot pad, edema was inhibited in a dose- dependent manner and was positively correlated with in vitro inhibition of PLA2 activity. Alkylation of HSF-PLA2 with p- bromophenacyl bromide concomitantly inhibited both enzyme and edema- inducing activity. These results clearly demonstrate that the neutral- active, Ca2+-dependent PLA2 isolated from human synovial fluid is proinflammatory and that catalytic activity is positively correlated with in vivo proinflammatory effects. Registry Numbers: EC 3.1.- (Phospholipases) 313-67-7 (aristolochic acid I) 99-73-0 (4-bromophenacyl bromide) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF ETHNOPHARMACOLOGY***** Lemos VS Thomas G Barbosa Filho JM Pharmacological studies on Aristolochia papillaris Mast. (Aristolochiaceae). In: J Ethnopharmacol (1993 Oct) 40(2):141-5 ISSN: 0378-8741 The non-specific and reversible smooth muscle relaxant activities of the ethanolic extract (EE) of Aristolochia papillaris Mast., a fraction of EE containing tertiary alkaloids (TAF) and of 3 compounds isolated from TAF are reported. In the non-pregnant rat uterus, EE and TAF inhibited both the oxytocin-induced contractions and the amplitude of rhythmic spontaneous contractions. The IC50 values for EE and TAF were 0.91 and 0.22 microgram/ml, respectively in the first experiments while the corresponding values were 1.0 and 0.17 microgram/ml in the second case. The rhythmic contractions of the uterus obtained from 21-day pregnant rats were also reduced by EE and TAF with IC50 values of 25.5 and 11.2 micrograms/ml, respectively. The relaxation of isolated guinea pig trachea produced by EE and TAF were also observed with the compounds moupinamide, coclaurine and isoboldine isolated from TAF. The IC50 values of these compounds were 1.58 x 10(-4) M, 3.98 x 10(-4) M and 7.10 x 10(-4) M, respectively. Propranolol significantly antagonized the effects of coclaurine and isoboldine but failed to inhibit the responses to moupinamide which suggests that the plant constituents produce muscle relaxation by beta-adrenoceptor-dependent and -independent mechanisms. Registry Numbers: 50-56-6 (Oxytocin) 525-66-6 (Propranolol) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF NATURAL PRODUCTS***** Che CT Ahmed MS Kang SS Waller DP Bingel AS Martin A Rajamahendran P Bunyapraphatsara N Lankin DC Cordell GA et al Studies on Aristolochia III. Isolation and biological evaluation of constituents of Aristolochia indica roots for fertility-regulating activity. In: J Nat Prod (1984 Mar-Apr) 47(2):331-41 ISSN: 0163-3864 An ethanol extract of Aristolochia indica roots decreased fertility in both rats and hamsters when administered postcoitally (days 1-10 and 1-6, respectively). Petroleum ether (A), CHCl3 (B), and aqueous (C) fractions, tested similarly in rats, were inactive and/or toxic. Partition of fraction B afforded non-acidic (D) and acidic (E) fractions. Savinin (1), isolated from fraction D and not previously reported from the Aristolochiaceae , was inactive when administered postcoitally to rats. Aristolochic acid-I (2), reported previously from A. indica and isolated from fraction E, was inactive when administered postcoitally to rats and toxic when administered postcoitally to hamsters. (12S)-7,12- Secoishwaran -12-ol (3), previously reported from A. indica and isolated from fraction A, did not interrupt pregnancy when administered to mice on day 6 of pregnancy. Four additional compounds, aristolic acid (4) [prepared from aristolochic acid-I (2)], methyl aristolate (5) [prepared by methylating aristolic acid (4)], and cis- and trans-p-coumaric acid (both oblate commercially), were similarly tested in mice and found to be inactive. Aristolic acid (4), and the cis- and trans-p-coumaric acids also were inactive when administered postcoitally (days 1-10) to rats. Seven compounds reported previously from A. indica were also isolated, as were a new naphthoquinone, aristolindiquinone (6) (fraction E), and magnoflorine (fraction C). €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Pistelli L Nieri E Bilia AR Marsili A Scarpato R Chemical constituents of Aristolochia rigida and mutagenic activity of aristolochic acid IV. In: J Nat Prod (1993 Sep) 56(9):1605-8 ISSN: 0163-3864 Two aristolochic acids [2 and 3] and a flavonol glycoside 1 have been isolated from Aristolochia rigida (Aristolochiaceae). Aristolochic acid IV [2], the most abundant constituent, has shown a weak direct mutagenic activity in the Ames test: this action seems to be inhibited, at least in part, by metabolic reactions. Registry Numbers: 313-67-7 (aristolochic acid I) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Lee HS Han DS A new acylated N-glycosyl lactam from Aristolochia contorta. In: J Nat Prod (1992 Sep) 55(9):1165-9 ISSN: 0163-3864 A new acylated glycoside isolated from the roots of Aristolochia contorta (Aristolochiaceae), has been characterized as aristolactam N- (6'-trans-p-coumaroyl)-beta-D-glucopyranoside [2]. Aristolactam-N- beta-D-glucopyanoside [1] was also isolated from the same source. Compound 2 showed relatively significant antibacterial activity against Gram-positive bacteria, based on disc diffusion and dilution methods. Registry Numbers: 145613-84-9 (N-((6'-p-coumaroyl)glucopyranosyl)aristolactam) 56-75-7 (Chloramphenicol) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL DE PHARMACIE DE BELGIQUE***** Violon C Belgian (Chinese herb) nephropathy: why? In: J Pharm Belg (1997 Jan-Feb) 52(1):7-27 ISSN: 0047-2166 During the last years several patients with renal failure were admitted in Brussels hospitals. The progressive interstitial fibrosis with tubular atrophy seen in these patients has been ascribed to the slimming therapy preceding the pathology. The nephropathy was remarkable with regard to its extensive fibrotic process and the rapidity of its evolution. The ingestion of Aristolochia fangchi instead of the prescribed Stephania tetrandra, one of the components of the slimming therapy, was put forward as hypothesis for the etiology of the nephropathies in the literature. Questions however remain unanswered: Why have certain persons, among thousands similarly treated including ingestion of Aristolochic acids, not withstood the treatment? Why is there no correlation between the length of treatment and the occurrence nor the degree of illness? Last but not least: Is it in the actual conditions possible to be confident again in slimming treatments as the concerned one? We made an overview of the pharmacological action and possible (nephro) toxicity of the known components of the concerned therapy. Concerning the Chinese plants we have described and commented on the procedures for quality control actually at disposal and the difficulties in differentiation between resembling species and possible substitute herbs. We have described largely the traditional and medicinal use of the involved Chinese plants as to evaluate their implication in the nephrotoxicity. The elements of the therapy possibly relevant in the etiology of the disease are mentioned. The overview shows that different elements of the therapy are hazardous. Attention is caught to the danger of the use of (Chinese) herbs of unknown origin when nor the indications nor the form of preparation--in this case decoctions--are respected and when the quality cannot be assured, due to lack of (official) operating procedures. Medicinal plants as those implied contain secondary metabolites (bis)-benzylisoquinoline- alkaloids, dihydroxy-diallyl-biphenyls, aristolochic acids) with strong pharmacological (and possibly toxic) actions. Attention is caught to the danger of alternative therapies as mesotherapy. Products are injected which are not proved safe for this administration way. The administration during long periods of cocktails with anorectics (fenfluramine and diethylpropion) in association with a diuretic, a tranquilizer, plants with laxative and atropinergic action are alike to be at the origin of susceptibility in the excretion system. Under these circumstances exposure to any toxic product might cause renal failure. Several years have passed after the scientific reports of the first nephropathy cases in Belgium. We are afraid that prohibiting (temporarily) three Chinese herbs (Stephania tetrandra, Aristolochia fangchi and Magnolia officinalis) does not provide enough safety in order to assume responsibilities for common health care. Keeping in mind that these treatments were not meant to cure any disease but only for slimming, we ask Belgian authorities to regulate strictly the use of (Chinese) herbal medicines, the products and practices in alternative practices as mesotherapy and cocktail-treatments. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF PHARMACEUTICAL SCIENCES***** Ionescu F Jolad SD Cole JR Dehydrodiisoeugenol: a naturally occurring lignan from Aristolochia taliscana (Aristolochiaceae). In: J Pharm Sci (1977 Oct) 66(10):1489-90 ISSN: 0022-3549 The ethanol-water extract of Aristolochia taliscana Hook and Arn (Aristolochiaceae) yielded a compound which was identified as dehydrodiisoeugenol by means of elemental analysis, IR, UV, NMR, and mass spectra, and direct comparison with a synthetic sample. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Ionescu F Jolad SD Cole JR DEHYDRODIISOEUGENOL: A NATURALLY OCCURRING LIGNAN FROM ARISTOLOCHIA TALISCANA (ARISTOLOCHIACEAE) In: J Pharm Sci (1977) 66(10):1489-1490 ISSN: 0022-3549 The ethanol-water extract of Aristolochia taliscana Hook and Arn (Aristolochiaceae) yielded a compound which was identified as dehydrodiisoeugenol by means of elemental analysis, infrared, UV, nuclear magnetic resonance, and mass spectra, and direct comparison with a synthetic sample. (Author abstract) (2 Refs) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****MEMORIAS DO INSTITUTO OSWALDO CRUZ***** Mendes NM de Souza CP Araujo N Pereira JP Katz N [Molluscicide activity of some natural products on Biomphalaria glabrata] Atividade moluscicida de alguns produtos naturais sobre Biomphalaria glabrata. In: Mem Inst Oswaldo Cruz (1986 Jan-Mar) 81(1):87-91 ISSN: 0074-0276 (Published in Portuguese) The molluscicide activity of aqueous (macerated and boiled), hexanic and ethylic extracts of Aristolochia brasiliensis, Caesalpinia peltophoroides, Caesalpinia pulcherrima, Delonix regia, Spathodea campanulata and Tibouchina scrobiculata was evaluated in the laboratory. The solutions obtained from those extracts were tested on adults and egg masses of Biomphalaria glabrata reared in the laboratory at 1, 10, 20, 100 and 1000 ppm concentrations. The most active of the extracts studied was D. regia flowers' (flamboyant) ethylic extracts which presented molluscicidal activity on adult snails at 20 ppm. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****MUTATION RESEARCH***** Pezzuto JM Swanson SM Mar W Che CT Cordell GA Fong HH Evaluation of the mutagenic and cytostatic potential of aristolochic acid (3,4-methylenedioxy-8-methoxy-10-nitrophenanthrene-1-carboxylic acid) and several of its derivatives. In: Mutat Res (1988 Dec) 206(4):447-54 ISSN: 0027-5107 Aristolochic acid (1), a constituent of Aristolochia species, has been used for medicinal purposes since the Graeco-Roman period. Following the observation that the compound was mutagenic and carcinogenic, it was removed from pharmaceutical products. Consistent with previous reports, we have found that 1 serves as a direct-acting mutagen in Salmonella typhimurium strains TA100, TA102, TA1537 and TM677, but was not active in the nitroreductase-deficient strains TA98NR and TA100NR. However, aristolic acid (2), a compound that differs in structure only by the absence of the nitro group, was also found to be a direct-acting mutagen in Salmonella strains TA98, TA100, TA102, TA1537, and TM677, as well as strains TA98NR and TA100NR. Both compounds (1 and 2) were active mutagens when evaluated with cultured Chinese hamster ovary cells. Thus, in contrast to previous suggestions, the nitro group at position 10 is not required to induce a mutagenic response. Also, a series of structural relatives (the methyl esters of 1 and 2 (3 and 4, respectively), aristolochic acid-D (5), aristolactam (6), aristolactam A-II (7), and aristolactam-N-beta-D-glucoside (8)) were evaluated for mutagenic potential with Salmonella typhimurium strain TM677 and found to be inactive. Since compounds 3 and 4 were found to be active mutagens with Salmonella typhimurium strains TA98, TA100, TA102 and TA1537 (sufficient quantities of compounds 5-8 were not available for testing), differential sensitivity of the tester strains unrelated to mutagenic potential is suggested. Further, compounds 1, 2, and 6-8 were evaluated for potential to inhibit growth with cultured KB or P388 cells. P388 cells were substantially more sensitive, and compound 1 was the most active of the materials tested (ED5 = 0.58 microM). Compound 6 also demonstrated appreciable activity (ED50 = 4.2 microM), as did compound 8 (ED50 = 6.0 microM). It therefore appears that phenanthrene-ring substituents, in addition to the nitro group at position 10, serve important roles for biological potential. In considering the carcinogenic event induced by aristolochic acid, these functionalities should also be taken into account. Registry Numbers: 313-67-7 (aristolochic acid I) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHYTOCHEMISTRY***** Li H Sakagami Y Marumo S Chen X Eleven aristolochic acid derivatives from Aristolochia cinnabarina. In: Phytochemistry (1994 Sep) 37(1):237-9 ISSN: 0031-9422 Three new compounds, aristolochic acid IIIa-6-O-beta-D-glucoside, cepharanone-A N-beta-D-glucoside and 2-hydroxy-8-methyloxycepharanone- A, were isolated together with eight known compounds from methanolic extracts of fresh roots of Aristolochia cinnabarina. Registry Numbers: 313-67-7 (aristolochic acid I) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Wu TS Ou LF Teng CM Aristolochic acids, aristolactam alkaloids and amides from Aristolochia kankauensis. In: Phytochemistry (1994 Jul) 36(4):1063-8 ISSN: 0031-9422 Fourteen aristolochic acid derivatives: ariskanins A-E, 3-hydroxy-4- methoxy-10-nitrophenanthrene-1-carboxylic acid methyl ester, aristolochic acid-II methyl ester, aristolochic acid-IV methyl ester, aristolochic acid-C, -I, -II, -III, -IV, -IVa; nine aristolactam alkaloids: aristolactam, aristolactam-AII, -BIII, -AIII, -III, cepharanone-A, 9-methoxy-aristolactam-I, aristolactam-N-beta-D- glucoside and aristolactam-C-N-beta-D-glucoside; a 4,5-dioxoaporphine alkaloid: cepharadione-A, together with 12 other compounds: methyl-p- coumarate, N-trans-feruloyltyramine, N-cis-feruloyltyramine, methyl vanillate, methyl paraben, allantoin, an octadecyl- and eicosyl ferulate mixture, cis- and trans-p-coumaric acid, N-p- coumaroyltyramine, N-p-cis-coumaroyltyramine, methyl ferulate and isorhamnetin-3-O-rutinoside were isolated and characterized from the fresh root and stem of Aristolochia kankauensis. Their structures were elucidated by spectral and chemical methods. Among them, ariskanins-A-E and N-p-cis-coumaroyltyramine are reported for the first time from a natural source. The cytotoxicity and antiplatelet activity of the compounds isolated are also discussed. Registry Numbers: 313-67-7 (aristolochic acid I) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PROCEEDINGS / ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR***** Schmeiser HH Bieler CA Stiborova M Wiessler M van Ypersele de Strihou C Cosyns JP (32)P-postlabeling analysis of DNA adducts derived from aristolochic acid in patients with Chinese herbs nephropathy (Meeting abstract). In: Proc Annu Meet Am Assoc Cancer Res (1996) 37:A681 ISSN: 0197-016X Recently we reported the detection of a major DNA adduct found in kidneys from patients with Chinese herbs nephropathy (CHN). This adduct was identified as the deoxyadenosine adduct of aristolochic acid I (AAI), the major adduct formed by the plant carcinogen aristolochic acid (AA). The 32P-postlabeling analyses were now extended and showed the presence of 3 additional minor adduct spots. Chromatographic analyses by HPLC resulted in the identification of 2 minor spots being the guanosine adduct of AAI (dG-AAI) and the adenosine adduct of AAII (dA-AAII). Adduct levels in the 6 patients tested ranged from 0.2 to 1.5/10(8) nucleotides for dG-AAI and from 0.2 to 4.3/10(8) nucleotides for dA-AAII. The results confirm the high persistence of the adenosine adducts in kidney and indicate that indeed Stefania tetrandra had been mistakenly substituted with Aristolochia fangchi in the Chinese herbs preparation ingested by the patients. Registry Numbers: 313-67-7 (aristolochic acid I) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****REVUE D ELEVAGE ET DE MEDECINE VETERINAIRE DES PAYS TROPICAUX***** Kela SL Ogunsusi RA Ogbogu VC Nwude N Screening of some Nigerian plants for molluscicidal activity. In: Rev Elev Med Vet Pays Trop (1989) 42(2):195-202 ISSN: 0035-1865 Methanolic (MEOH), evaporated crude water (ECW) and unevaporated crude water (UECW) extracts of 25 Nigerian plants, used for different medicinal and domestic purposes were screened for molluscacidal activity on laboratory-reared Lymnaea natalensis Krauss. Seven of the plants were not active; extracts from 18 (72 per cent) of the plants, some of which are renowned fish poisons, had molluscicidal activity. These were Acacia nilotica, Aristolochia albida, Balanites aegyptiaca, Blighia sapida, Boswellia dalzielii, Detarium microcarpum, Gnidia kraussiana, Kigelia africana, Nauclea latifolia, Opilia celtidefolia, Parkia clappertoniana, Polygonum limbatum, Pseudocedrela kotschyi, Sclerocarya birrea, Securidaca longipedunculata, Ximenia americana, Vetiveria nigritana and Ziziphus abyssinica. The LC50 of these extracts were determined. It is strongly recommended that the toxic effects of these extracts against fish, cercariae, snail eggs and mammals be further investigated so as to determine the right concentration, especially for use in fish ponds. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****TOXICON***** Vishwanath BS Appu Rao AG Gowda TV Interaction of phospholipase A2 from Vipera russelli venom with aristolochic acid: a circular dichroism study. In: Toxicon (1987) 25(9):939-46 ISSN: 0041-0101 The interaction of aristolochic acid, an alkaloid from Aristolochia species, with phospholipase A2 (PLA2) from Vipera russelli venom was followed by circular dichroism measurements. Aristolochic acid is a non-competitive inhibitor of PLA2. The binding of aristolochic acid to PLA2 induces an extrinsic CD band at 320 nm. The association constant was determined by following the intensity of the extrinsic CD band. Aristolochic acid forms a 1:1 complex with PLA2, with an association constant K, of 5.4 X 10(3) M-1 and a Gibb's free energy change (delta G0) for the reaction of -5.1 kcal/mole. The values of association constant and delta G0 suggest that the interaction is weak. Binding of aristolochic acid causes a change in the secondary structure of the protein which is characterized by an increase in the apparent content of alpha-helix, without any detectable change in the tertiary structure of PLA2. Registry Numbers: EC 3.1.- (Phospholipases) EC 3.1.1.- (Phospholipases A) 313-67-7 (aristolochic acid I) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Vishwanath BS Gowda TV Interaction of aristolochic acid with Vipera russelli phospholipase A2: its effect on enzymatic and pathological activities. In: Toxicon (1987) 25(9):929-37 ISSN: 0041-0101 Aristolochic acid, an alkaloid from the plant Aristolochia species, interacts with the major basic phospholipase A2 from Vipera russelli venom. It is an uncompetitive inhibitor with a Ki of 9.9 X 10(-4)M when phosphatidylcholine is used as substrate. The inhibition of direct and indirect hemolysis is higher compared to the inhibition of phosphatidylcholine hydrolysis. Edema-inducing activity of Vipera russelli phospholipase A2 is inhibited by aristolochic acid when injected either as a mixture or separately. Both i.m. and i.p. administration of aristolochic acid following phospholipase injection are equally effective in inhibiting edema. The alkaloid inhibits the edema-inducing activity as soon as it reaches the site, but does not aid in recovery. Aristolochic acid failed to inhibit other pathological activities of the enzyme. Registry Numbers: EC 3.1.- (Phospholipases) EC 3.1.1.- (Phospholipases A) 313-67-7 (aristolochic acid I) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Vishwanath BS Kini RM Gowda TV Characterization of three edema-inducing phospholipase A2 enzymes from habu (Trimeresurus flavoviridis) venom and their interaction with the alkaloid aristolochic acid. In: Toxicon (1987) 25(5):501-15 ISSN: 0041-0101 A basic phospholipase A2 (PLA2) enzyme, TFV PL-X (pI 9.2) and two acidic PLA2 enzymes, TFV PL-Ia (pI 4.9) and TFV PL-Ib (pI 4.5) were purified from Trimeresurus flavoviridis venom on CM-Sephadex C-25 and QAE-Sephadex A-25 columns, respectively. The basic enzyme exists as a monomer, whereas the acidic enzymes are dimers. These enzymes differ in properties such as molecular weight, Km, optimum pH and temperature and pharmacological properties. The basic enzyme hydrolysed purified phospholipids in the order of PC greater than PE greater than PS greater than PI = 0, while for TFV PL-Ia and TFV PL- Ib the order was PC greater than PE greater than PS = PI = 0. TFV PL- X was comparatively more toxic, with an LD50 value of 4.2 micrograms/g (i.p.), while the acidic PLA2 enzymes had LD50 values above 8 micrograms/g (i.p.). All three enzymes induced edema when injected into the mouse foot pad. Aristolochic acid, an alkaloid (8- methoxy-6-nitrophenanthro(3,4-d)-1,3-dioxole-5-carboxylic acid) from the medicinal plant Aristolochia radix, interacts with these PLA2 enzymes. It is a competitive inhibitor with varying affinity when PC is used as substrate. Aristolochic acid inhibits direct and indirect hemolytic activity, as well as edema-inducing activity, of TFV PL-X, but fails to neutralize the lethal potency of the enzyme. On the other hand, it inhibits direct and indirect lytic activity of TFV PL- Ia and TFV PL-Ib only at 10-fold higher concentrations and it enhances the edema-inducing activity of these enzymes. Such effects of aristolochic acid indicates that (1) different mechanisms may be involved in the edema-inducing activity of PLA2 enzymes and (2) catalytic and pharmacological sites are separate on the PLA2 molecule. Registry Numbers: EC 3.1.- (Phospholipases) EC 3.1.1.- (Phospholipases A) 313-67-7 (aristolochic acid I) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Martz W Plants with a reputation against snakebite. In: Toxicon (1992 Oct) 30(10):1131-42 ISSN: 0041-0101 Many plants are recommended in traditional medicine as active against various effects of snakebite. Few attempts have been made to investigate the veracity of these assertions in controlled experiments. Several workers, mainly Oriental, have investigated the reputation of such plants by performing in vitro and in vivo experiments in order to demonstrate whether there was any protective effect, using drugs or mixtures of drugs prepared using traditional formulae. In some studies, these extracts were administered to mice before or after treatment with different elapid or crotalid venoms. Other papers deal with selected compounds isolated from Schumanniophyton magnificum, Eclipta prostrata or Aristolochia shimadai, and their capacity to inhibit phospholipase A2 or other enzymes (e.g. ATPase) or for physiological and biochemical properties (such as effects on uterine tone or the protection of mitochondrial membranes). Japanese workers have described the antihaemorrhagic effect of persimmon tannin from Diospyros kaki. Atropine has been attributed a life-prolonging effect after black mamba venom treatment. Prolonged survival was also observed after pretreatment with extracts of Diodia scandens and Andrographis paniculata. Some authors have found little or no beneficial effects. The papers collected so far show that there are no systematic investigations in this field. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****VETERINARY PATHOLOGY***** Barakat SE Wasfi IA Adam SE The toxicity of Aristolochia bracteata in goats. In: Vet Pathol (1983 Sep) 20(5):611-6 ISSN: 0300-9858 Diarrhea, dyspnea, tympany, arching of the back, loss of condition, and loss of hair from the back were the prominent signs when Aristolochia bracteata was given orally to goats. The main lesions were hemorrhages in the lungs, heart, and kidneys, fatty change and congestion in the liver, mucoid abomasitis and enteritis and straw- colored fluid in serous cavities. An increase in aspartate aminotransferase activity, ammonia and urea concentrations and a decrease in the concentrations of total protein and magnesium were detected in detected in the serum. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****YAO HSUEH HSUEH PAO [ACTA PHARMACEUTICA SINICA]***** Zhang J He LX Xue HZ Feng R Pu QL [The structure of versicolactone A from Aristolochia versicolar S.M. Hwang] In: Yao Hsueh Hsueh Pao (1991) 26(11):846-51 ISSN: 0513-4870 (Published in Chinese) A novel sesquiterpene lactone, versicolactone A, with 12-carbon ring skeleton, was isolated from the roots of Aristolochia versicolar S. M. Hwang. Versicolactone A, C15H20O2, colorless prisms, mp 130-132 degrees C, [alpha]6D +486 degrees (c 0.1276, CHCl3). Its structure was established by spectroscopic methods, mainly 2D-NMR (1H-1H COSY, 1H-13C COSY, COLOC), HRMS and metastable ion measurement. Registry Numbers: 136315-17-8 (versicolactone A) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Xue HZ Zhang J He LX He CH Zheng QT Feng R [The structure of versicolactone D] In: Yao Hsueh Hsueh Pao (1989) 24(12):917-22 ISSN: 0513-4870 (Published in Chinese) The extracts of Aristolochia versicolar S.M. Huang root afforded a new dimeric sesquiterpene lactone, versicolactone D, with a novel skeleton. Its structure was established by spectroscopic methods, mainly X-ray and 2D-NMR. Registry Numbers: 126770-37-4 (versicolactone D) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Lou FC Ding LS Waterman PG [Chemical studies on Aristolochia mollissima V] In: Yao Hsueh Hsueh Pao (1989) 24(4):305-7 ISSN: 0513-4870 (Published in Chinese) Two new phenanthrene compounds, 9-ethoxyaristololactam and 9-ethoxy- aristolactone, were isolated from the root of Aristolochia mollissima. Their structures were identified by means of spectral analysis. Registry Numbers: 122739-09-7 (9-ethoxyaristololactam) 122739-10-0 (9-ethoxyaristolactone) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€