Aristolochic acid nephropathy in a Chinese patient: time to abandon the term "Chinese herbs nephropathy"?

The causal role of aristolochic acid (AA) in the so-called Chinese herbs nephropathy (CHN) has been conclusively demonstrated only in the Belgian epidemic. We report a biopsy-proven hypocellular interstitial fibrosing nephropathy in a Chinese patient who had ingested a Chinese herbal preparation bought in Shanghai. The identification of AA in the preparation and of AA-DNA adducts in the kidney tissue unequivocally demonstrates, for the first time, the causal role of AA outside the Belgian epidemic. Because the ingested preparation is very popular in China as an over-the-counter product, our observation raises the possibility that many such cases due to AA might be currently unrecognized in China. AA should be banned from herbal preparations worldwide. All cases of the so-called CHN, in which the causal role of AA has been thoroughly documented, should be further identified as aristolochic acid nephropathy (AAN). The term phytotherapy-associated interstitial nephritis (PAIN) might refer to the other cases associated with phytotherapy without identification, as yet, of the causal agent.

Toxicity of complementary therapies: an eastern perspective.

Chinese traditional medicine is used extensively in Chinese populations, and other Asian countries employ similar therapies. Herbal treatments have a major role in these systems, and although most have a well-established safety record, occasional adverse effects are seen. Problems arise when toxic herbs are used in excessive doses, with improper preparation, or when they are substituted erroneously. There may also be adulteration with Western drugs or heavy metals, and interactions between herbs and Western drugs may also occur. It is always prudent to obtain a complete history of the use of herbal medications during any clinical assessment, particularly in Asian patients.

Encephalopathy and neuropathy following ingestion of a Chinese herbal broth containing podophyllin.

Two patients developed podophyllin intoxication following ingestion of a broth of the Chinese herb guijiu. The neurological manifestations are described and the pathology of the peripheral neuropathy is fully documented with ultrastructural and quantitative studies.

Furanoditerpenoid lactones from the seeds of Caesalpinia minax Hance.

Two furanoditerpenoid lactones, were isolated from the seeds of Caesalpinia minax Hance. Their structures and stereochemistry have been established by spectral data and single crystal X-ray analysis.

Secoiridoid constituents from the fruits of Ligustrum lucidum.

Two secoiridoid glucosides, lucidumosides A and B, as well as six known glucosides, oleoside dimethyl ester, ligustroside, oleuropein, nuezhenide, isonuezhenide, and neonuezhenide, were isolated from the fruits of Ligustrum lucidum. Their structures were elucidated by spectroscopic methods.

Vasorelaxing effects of Caesalpinia sappan involvement of endogenous nitric oxide.

Methanolic extract and two purified compounds (brazilin and hematoxylin) from Caesalpinia sappan were examined for their relaxant effects in isolated rat thoracic aorta. The methanolic extract significantly and dose-dependently relaxed the alpha1-receptor agonist phenylephrine-precontracted aortic rings, without affecting passive tension of these vessels. Removal of the vascular endothelium, inhibition of nitric oxide (NO) synthase with 0.1 mM Nomega-nitro-L-arginine and of cGMP biosynthesis with 10 microM methylene blue abolished the vasorelaxant effects of the herbal extract at doses up to 30 microg/ml. Similar vasorelaxant effects were observed with brazilin and hematoxylin. Therefore, these results suggest that brazilin and hematoxylin may be responsible for the vascular relaxant effects of C. sappan, via endogenous NO and subsequent cGMP formation. The vascular relaxant effects of the plant may contribute to its therapeutic actions.

Determination of quinolizidine alkaloids in traditional Chinese herbal drugs by nonaqueous capillary electrophoresis.

A rapid method for the determination of quinolizidine alkaloids by nonaqueous capillary electrophoresis was developed. A total of 10 alkaloids (matrine, sophocarpine, oxymatrine, oxysophocarpine, sophoridine, cytisine, sophoramine, aloperine, lehmannine and dauricine) could be easily separated within 18 min. A running buffer composed of 50 mM ammonium acetate, 10% tetrahydrofuran and 0.5% acetic acid in methanol was found to be the most suitable for this separation. Five of these alkaloids were selected for further studies. The linear calibration ranges were 2.51-50.1 microg/ml for sophoridine and sophocarpine, 2.71-54.2 microg/ml for matrine, 3.30-65.9 microg/ml for oxymatrine, and 3.10-62.0 microg/ml for oxysophocarpine. The recovery of the five alkaloids was 98.0-101.3% with relative standard deviations from 1.03 to 2.68% (n=5). The limits of detection for all 10 alkaloids were over the range 0.93-2.31 microg/ml. The method was successfully applied to the phytochemical analysis of alkaloid extracts from three commonly used traditional Chinese herbal drugs: Sophora flavescens Ait. (Kushen), S. alopecuroides L. (Kudouzi or Kugancao) and S. tonkinensis Gapnep (Shandougen).

Fatal accidental aconitine poisoning following ingestion of Chinese herbal medicine: a report of two cases.

Two Hong Kong Chinese adults were prescribed aconitine-containing herbal preparations by Chinese herbal practitioners for relief of minor musculoskeletal pain. After ingestion both quickly developed ventricular tachycardia followed by ventricular fibrillation and cardiac arrest refractory to resuscitation; death in both cases occurred within 12 h of ingestion. Neither had a history of cardiac disease. Coroners' autopsies showed no significant macroscopic or microscopic findings, with no evidence of ischaemic heart disease or other cardiac disease. Toxicological examination of stomach contents showed a trace of hydrolysed aconitine in one case but was negative in the other. Analysis of the herbal preparations consumed, however, confirmed the presence of the aconitine-containing herbs in quantities greatly in excess of the maximum recommended in the P.R. China pharmacopoeia. Both patients therefore consumed an accidental overdose of aconitine, which has a narrow safety margin between therapeutic analgesic effect and its known cardiotoxic effect. These particular herbal medicines are controlled substances in mainland China and Taiwan, but no controls on their dispensing exist in Hong Kong. Together with reported non-fatal cases of aconitine poisoning, these cases emphasise that legal controls of the dispensing and use of aconitine-containing herbal preparations are necessary in Hong Kong.

Ethnopharmacology of rhinoceros horn. I: Antipyretic effects of rhinoceros horn and other animal horns.

Intraperitoneal administration of an aqueous extract of rhinoceros horn at 5, 2.5 and 1 g/ml, showed a significant antipyretic effect in rats with hyperthermia induced by subcutaneous injection of terpentine oil. Similar assays with extracts of the horns of saiga antelope, water buffalo and cattle at 5 g/ml also caused a significant drop in fever; however, at 1 g/ml, only saiga antelope horn produced an antipyretic action.

Ethnopharmacology of rhinoceros horn. II: Antipyretic effects of prescriptions containing rhinoceros horn or water buffalo horn.

Aqueous extracts of rhinoceros horn or water buffalo horn demonstrated significant antipyretic action at 2.5 g/ml i.p. (1 ml/animal) in rats with hyperthermia induced by subcutaneous injection of turpentine oil. Qingying Decoction, a classic compound prescription composed of rhinoceros horn and eight herbs, showed significant antipyretic action at dosages equivalent to 0.5 g/ml of rhinoceros horn extract. Comparable action was obtained by Qingying Decoction prepared with water buffalo horn. It is suggested that water buffalo horn can be used as a substitute for rhinoceros horn in treating hyperthermia, especially when prepared with other herbal materials according to the principles of compound prescriptions of Chinese medicine.

Fertility regulating agents from traditional Chinese medicines.

Chinese scientists have capitalized on the rich flora and the ethnomedical experience in China, in their pursuit of fertility regulating agents from natural products. Discoveries range from anti-implantation agents to abortifacient and pregnancy-terminating compounds, as well as a male contraceptive. Chemistry and bioactivity of these compounds and materials are reviewed in this paper, with the hope that further research and collaboration will take place to help solve the problem of population explosion.

Antipruritic and antinociceptive effects of Chenopodium album L in mice.

The ethanolic extract from the fruits of Chenopodium album L. (FCAL), orally administered at doses of 100-400 mg/kg, dose-dependently inhibited scratching behavior induced by 5-HT (10 micro g per mouse, s.c.) or compound 48/80 (50 micro g per mouse, s.c.) in mice. But it failed to affect hind paw swelling induced by 5-HT or compound 48/80 in mice at doses of 100 and 200 mg/kg and only showed a relatively weak inhibition on the swelling at a higher dose of 400 mg/kg. In addition, FCAL (200 and 400 mg/kg) significantly attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and the inflammatory pain response induced by an intraplantar injection of formalin in mice. At a dose of 400 mg/kg, it also inhibited the neurogenic pain response of formalin test. In conclusion, FCAL possesses antipruritic and antinociceptive activities and the antinociceptive effects are not secondary to anti-inflammatory effects. The findings support evidence for the clinical use of FCAL to treat cutaneous pruritus.

Ethnopharmacology of bear gall bladder: I.

Both bear and pig bile solutions were shown to have anti-inflammatory, anticonvulsion and analgesic effects, and also to prolong the survival time of mice in hypoxic conditions. It is possible that pig gall bladders could be developed as an alternative to bear gall bladders for uses in certain prescriptions of Chinese medicine.

Sources of the anti-implantation alkaloid yuehchukene in the genus Murraya.

The genus Murraya has been widely used in traditional medicine in east Asia. In view of the recent isolation of the anti-implantation alkaloid yuehchukene from M. paniculata a search has now been made for other natural sources of this alkaloid within the genus. In this paper we report findings for nine taxa of Murraya.

The induction of liver microsomal cytochrome P450 by Glycyrrhiza uralensis and glycyrrhetinic acid in mice.

The effect of Glycyrrhiza uralensis Fisch (GRZ) aqueous extract and one of its active principles Glycyrrhetinic acid (GRT) on hepatic cytochrome P450 in mice were investigated. Oral administration of GRZ at 10 g/kg/d or GRT at 50 mg/kg/d for 7 days was found to increase the P450 contents up to 4.6 fold compared with the controls. The activities of aryl hydrocarbon hydroxylase (AHH, 3.1 and 3.3 fold), aminopyrine N-demethylase (ADM, 4.2 and 3.2 folds), and 7-ethoxycumarin O-deethylase (ECOD, 2.8 and 2.5 fold) were also shown to be increased. Western blot analysis showed that the subtypes of P450 isoforms induced selectively by GRZ and GRT included CYP1A1 (1.8 and 1.5 fold over that of the control, respectively), CYP2B1 (both 1.3 fold), and CYP2C11 (3.2 and 3.0 fold). Moreover, significant positive correlation between the P450 content or the isoforms and the corresponding enzyme activities mentioned above was observed.

Quantitative analysis of ginsenosides in fresh Panax ginseng.

TLC, DCC and HPLC were used to study the ginsenoside composition of the main root, lateral root, rhizome, leaves and seeds of Panax ginseng cultivated in Jilin, China. Each of these methods has advantages of its own and the ensemble reveal the special features of Jilin ginseng. Total saponin content of various plant parts in Jilin ginseng showed a mid-range value as compared to those in ginsengs reported in literature. Fresh as well as sun-dried specimens from the same batch possessed a high percentage of Rg1 in the main root and this might account for the traditional preference of this plant part despite its lowest percentage of saponin in the whole plant. Large amounts of polar saponins were also observed in roots and rhizome of fresh Jilin ginseng, the nature and significance of which remained to be investigated.

Authentication of the Chinese drug "ku-di-dan" (herba elephantopi) and its substitutes using random-primed polymerase chain reaction (PCR).

DNA fingerprinting and polymorphism among the Chinese drug "Ku-Di-Dan" and its substitutes were demonstrated with arbitrarily primed polymerase chain reaction (AP-PCR) and random amplified polymorphic DNA (RAPD). Distinctive, reproducible genomic fingerprints from DNA of the Chinese drug Ku-Di-Dan and 9 species of Compositae were generated with six long (18-24 mer) and one short (10 mer) random-chosen primers with PCR. Ku-Di-Dan samples can be distinguished according to the banding patterns of their amplified DNA on agarose gels. Results showed that AP-PCR and RAPD fingerprints of the commercial samples of Ku-Di-Dan retailed in Fujian, Taiwan, Hong Kong and Macau markets are identical with that of Elephantopus scaber L. The relatedness of Ku-Di-Dan among 9 plants may also be estimated by the Similarity Indexes values of the genomic DNA fingerprints.

[Identification of herba taraxaci and its adulterants in Hong Kong market by DNA fingerprinting with random primed PCR].

DNA fingerprinting for Taraxacum mongolicum and its adulterants of six species of Compositae was demonstrated with random-primed polymerase chain reaction (PCR) including arbitrarily-primed PCR (AP-PCR) and random-amplified polymorphic DNA(RAPD). Distinctive genomic fingerprints from DNA of Taraxacum mongolicum and its adulterants were generated with two long (20-24 mer) and one short (10 mer) random-chosen primers Taraxacum mongolicum can be distinguished from six adulterants according to the banding patterns of their amplified DNA on agarose gels. Moreover, that Taraxacum mongolicum and its adulterant are unrelated. The Similarity Indexes values of the genomic fingerprints. Results showed AP-PCR and RAPD might be used for identifying Chinese drugs.