€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****AMERICAN JOURNAL OF GASTROENTEROLOGY***** Nadir A Agrawal S King PD Marshall JB Acute hepatitis associated with the use of a Chinese herbal product, ma-huang [see comments] In: Am J Gastroenterol (1996 Jul) 91(7):1436-8 ISSN: 0002-9270 Herbal medicines are widely perceived by the public as being healthful and innocuous. A number of herbal medicines have now been linked with hepatotoxicity. We report a case of acute hepatitis associated with the use of ma-huang, a herbal product derived from plants of the Ephedra species, which is advertised as being useful for causing weight loss and enhancing energy levels. Given the lack of reports in the literature of hepatotoxicity with ma-huang and ephedrine, we speculate that the ma-huang product our patient took contained some other ingredient or contaminant or was misidentified. Our report and others in the literature, which we review, indicate that the clinician should consider herbal medicines as a possible cause of unexplained liver injury. Registry Numbers: 299-42-3 (Ephedrine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****EMBO JOURNAL***** Malek O Lattig K Hiesel R Brennicke A Knoop V RNA editing in bryophytes and a molecular phylogeny of land plants. In: EMBO J (1996 Mar 15) 15(6):1403-11 ISSN: 0261-4189 RNA editing has been observed to date in all groups of vascular plants, but not in bryophytes. Its occurrence was therefore assumed to correlate with the evolution of tracheophytes. To gain more insight into both the phylogeny of early land plants and the evolution of mitochondrial RNA editing we have investigated a number of vascular and non-vascular plant species. Contrary to the belief that editing is absent from bryophytes, here we report mitochondrial RNA editing in cox3 mRNA of the liverwort Pellia epiphylla, the mosses Tetraphis pellucida and Ceratodon purpureus and the hornwort Anthroceros crispulus. RNA editing in plants consequently predates the evolution of tracheophytes. Editing is also found in the eusporangiate ferns Ophioglossum petiolatum and Angiopteris palmiformis, the whisk fern Tmesipteris elongata and the gnetopsid Ephedra gerardiana, but was not detected in Gnetum gnemon.cox3 mRNA of the lycopsid Isoetes lacustris shows the highest frequency of RNA editing ever observed in a plant, with 39% of all cytidine residues converted to uridines. The frequency of RNA editing correlates with the genomic GC content rather than with the phylogenetic position of a species. Phylogenetic trees derived from the slowly evolving mitochondrial sequences find external support from the assessments of classical systematics. Registry Numbers: EC 1.9.3.1 (Cytochrome-c Oxidase) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ADVANCES IN BIOCHEMICAL ENGINEERING/BIOTECHNOLOGY***** Rogers PL Shin HS Wang B Biotransformation for L-ephedrine production. In: Adv Biochem Eng Biotechnol (1997) 56:33-59 ISSN: 0724-6145 L-ephedrine is widely used in pharmaceutical preparations as a decongestant and anti-asthmatic compound. One of the key intermediates in its production is L-phenylacetylcarbinol (L-PAC) which can be obtained either from plants (Ephedra sp.), chemical synthesis involving resolution of a racemic mixture, or by biotransformation of benzaldehyde using various yeasts. In the present review, recent significant improvements in the microbial biotransformation are assessed for both fed-batch and continuous processes using free and immobilised yeasts. From previous fed-batch culture data, maximal levels of L-PAC of 10-12 gl-1 were reported with yields of 55-60% theoretical based on benzaldehyde. However, recently concentrations of more than 22 gl-1 have been obtained using a wild-type strain of Candida utilis. This has been achieved through optimal control of yeast metabolism (via microprocessor control of the respiratory quotient, RQ) in order to enhance substrate pyruvate production and induce pyruvate decarboxylase (PDC) activity. Processes involving purified PDC have also been evaluated and it has been demonstrated that L-PAC levels up to 28 gl-1 can be obtained with yields of 90-95% theoretical based on the benzaldehyde added. In the review the advantages and disadvantages of the various strategies for the microbial and enzymatic production of L-PAC are compared. In view of the increasing interest in microbial biotransformations, L- PAC production provides an interesting example of enhancement through on-line control of a process involving both toxic substrate (benzaldehyde) and end-product (L-PAC, benzyl alcohol) inhibition. Registry Numbers: EC 4.1.1.1 (Pyruvate Decarboxylase) 100-52-7 (benzaldehyde) 299-42-3 (Ephedrine) 67-64-1 (Acetone) 90-63-1 (1-hydroxy-1-phenyl-2-propanone) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****AMERICAN JOURNAL OF CHINESE MEDICINE***** Mahdihassan S Mehdi FS Soma of the Rigveda and an attempt to identify it. In: Am J Chin Med (1989) 17(1-2):1-8 ISSN: 0192-415X Ephedra juice is used as the drink of longevity given even to the new born. This is an Aryan custom mentioned in Rigveda and followed even by the Romans. To trace the history of this custom would lead to identifying Soma = Ephedra. The original species of Ephedra or Soma proper would be Ephedra sinica, the Chinese plant. It is the one species with yellow stalks. This has been illustrated so that it confirms Rigveda speaking of Soma as "golden yellow." The name Soma is also a loan word from Chinese meaning "fire-yellow fibers of hemp." The plant Soma is described as "thousand boughs" and photographic evidence has been offered in support. Each stalk is rod- like resembling an arrow as Rigveda speaks of it. An illustration has been offered to show the plant with stalks which are straight and rod- like, comparable with an arrow. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****AMERICAN JOURNAL OF NEPHROLOGY***** Chan EL Ahmed TM Wang M Chan JC History of medicine and nephrology in Asia. In: Am J Nephrol (1994) 14(4-6):295-301 ISSN: 0250-8095 The beginning of Chinese medicine has been attributed to 3 mythical emperors who gathered herbs for medicines. During the 2nd century BC, Han dynasty physicians developed cranial trephining and sedation with wine and herbs for anesthesia. Chiang Chung-Ching (142-212 AD) used the appearance of rashes in diagnosis, treated infections with anthelmintics and asthma with ephedra, described the symptoms of diabetes mellitus and expanded medical ethics. The specialties of obstetrics, pediatrics, ophthalmology and dentistry were described in the records of the Han and Tang dynasties, and methods of setting fractures and treating trauma were comparable with those of Roman military doctors. Shen Tua (1031-1095 AD) compiled a pharmacopeia and studied acupuncture and the pulses. Forensic medicine was developed during the 10th century by Sung Tse, who also advocated hand washing with sulfur and vinegar to avoid infection during autopsies. The Daoist physicians used androgens and estrogens to treat hypogonadism with therapeutic preparations of placentas. They also had an advanced knowledge of alchemy, claiming to achieve 'immortality' by their preservation techniques. Qualifying examinations for physicians were conducted by the Chinese state as early as the 1st century AD, and later incorporated philosophy and art to conform with the Confucian ideal. Throughout these eras, Chinese medicine profited from contact with western Asia. In ancient Chinese medicine, the excretory function of the kidney was attributed to the bladder. 'Kidney weakness', which refers to somatized depression, was treated by acupuncture along the 'kidney channel'. Pulse examination was also used to give a measure of the imbalance of renal Yin and Yang.(ABSTRACT TRUNCATED AT 250 WORDS) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARCHIV FUR EXPERIMENTELLE VETERINARMEDIZIN***** Shabana MM Mirhom YW Genenah AA Aboutabl EA Amer HA Study into wild Egyptian plants of potential medicinal activity. Ninth communication: hypoglycaemic activity of some selected plants in normal fasting and alloxanised rats. In: Arch Exp Veterinarmed (1990) 44(3):389-94 ISSN: 0003-9055 31 desert plants belonging to 17 families were collected from different Egyptian localities. 21 plants extracts were orally given to normal rats, and 15 were tested on fasted and to alloxanised rats. The results were compared with a standard oral hypoglycaemic drug (Daonil, Hoechst) used as a positive control. The following findings were obtained: 8 plants exhibited persistent hypoglycaemic effects, Lycium shawii, Salvia (S.) aegyptiaca, Pergularia tomentosa, Convolvulus (C.) althaeoides, Haloxylon salicornicum, Ephedra alata, Scrophularia deserti, and Crotalaria aegyptiaca. Transient hypoglycaemic effects appeared only 1 hour after administration in response to 4 plants, Silena succulenta, Lygos raetam, C. lanatus, and Pulicaria incisa. In the cases of Ochradenus baccatus and Zygophyllum album, slow hypoglycaemic activity was produced and appeared 3 hours after administration. 5 plants showed hypoglycaemic effects viz, Thymus capitatus, Launaea nudicaulis, Conyza dioscorides, Nitraria retusa, and Limonium tubiflorum. Among the 15 plant extracts tested on alloxanised diabetic rats only 4 showed hypoglycaemic effects more potent than those of the administered dose of Daonil. These were Matthiola livida, S. aegyptiaca, Astragalus species, and Arthrocnemum glaucum. The hypoglycaemic effect of S. aegyptiaca in fasting rats has been confirmed also in alloxanised diabetic animals. This emphasises the importance of conducting both experiments in order to obtain a reliable conclusion. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BIOCHIMICA ET BIOPHYSICA ACTA***** Melekhovets YuF Troitsky AV Comparative analysis of 5.8 S rRNA from Ephedra kokanica Regl. (Gymnospermae) and other plant species. In: Biochim Biophys Acta (1990 Apr 6) 1048(2-3):294-6 ISSN: 0006-3002 5.8 S rRNA from the gymnosperm Ephedra kokanica Regl. (EMBL Data Library accession No. X15676) has been sequenced. It is 161 nucleotides long and contains three 2'-O-methylated residues--two adenosines and one guanosine. No pseudouridine have been detected. E. kokanica 5.8 S rRNA, as those from other plant species, can form a secondary structure with paired 5'- and 3'-terminal regions. 5.8 S rRNAs of seed plants differ from the moss Mnium reguicum 5.8 S rRNA in that they have longer variable 'GC-rich' hairpins with insertions in the loop region. 5.8 S rRNA of E. kokanica reveals 69 and 82% of homology with that of moss and five angiosperm species, respectively. The posttranscriptional modification pattern of plant 5.8 S rRNAs is not strictly conservative. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CANCER LETTERS***** Tricker AR Wacker CD Preussmann R Nitrosation products from the plant Ephedra altissima and their potential endogenous formation. In: Cancer Lett (1987 May) 35(2):199-206 ISSN: 0304-3835 The plant species Ephedra is commonly used in both folk medicine and for the preparation of health teas. Nitrosation of a tea made from Ephedra altissima yielded N-nitrosoephedrine (NEP), N- nitrosopseudoephedrine (NPEP), N-nitrosoproline (NPRO), N- nitrosomethylbenzylamine (NMBA), trace quantities of 2 unidentified non-volatile nitrosamines and the new nitroso compound 2-(N-nitroso-N- methylamino)propiophenone (NMAP). Incubation of a tea extract at 37 degrees C and pH 2.0 under conditions simulating the normal fasting stomach with a constant nitrite concentration (25 microM) for 1 h produced NEP, NPEP, NMAP and NPRO. The synthesis and preliminary results for the mutagenic effect of NMAP on the reversion of Salmonella typhimurium strains TA100 and TA1535 in the Ames test are reported. Registry Numbers: 110505-04-9 (2-(N-nitroso-N-methylamino)propiophenone) 17608-59-2 (N-nitrosoephedrine) 62-75-9 (Dimethylnitrosamine) 7519-36-0 (nitrosoproline) 937-40-6 (nitrosobenzylmethylamine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Alwan SM Al-Hindawi MK Abdul-Rahman SK Al-Sarraj S Production of nitrosamines from ephedrine, pseudoephedrine and extracts of Ephedra foliata under physiological conditions. In: Cancer Lett (1986 May) 31(2):221-6 ISSN: 0304-3835 N-Nitrosoephedrine (NEP) and N-nitrosopseudoephedrine (NPEP) were synthesised at 5 degrees C using different concentrations of various acids. The reaction with acetic acid gave the highest yield (85%) of N-nitrosamine. Ephedrine and pseudoephedrine were reacted with nitrite under physiological conditions (37 degrees C, pH 1-3) to form NEP and NPEP. The yield of NEP, which is a known carcinogen, and NPEP were the highest (18.5%) at pH 2. Aqueous and alcoholic extracts of Ephedra foliata (100 g dry wt), nitrosated under physiological conditions, produced 0.77 mg and 8.3 mg, respectively, as total nitrosamines. This indicated the potential of the nitrosamine formation from the plant extracts specified. Registry Numbers: 299-42-3 (Ephedrine) 7632-00-0 (Sodium Nitrite) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CHUNG-KUO CHUNG HSI I CHIEH HO TSA CHIH***** Wang GZ Hikokichi O [Experimental study in treating chronic renal failure with dry extract and tannins of herba ephedra] In: Chung Kuo Chung Hsi I Chieh Ho Tsa Chih (1994 Aug) 14(8):485-8 ISSN: 1003-5370 (Published in Chinese) The effects of dry extract and tannin of Herba Ephedra on adenine- induced chronic renal failure in rats and their mechanisms of action have been studied. Dry extract of Herba Ephedra in dose of 10 mg, 20 mg and 30 mg/d with adenine (for 24 days) were administered to rats. After inducing renal failure (34 days), it reduced toxins in blood significantly. The action of 30 mg-dose was highly significant, BUN decreased by 37%, creatinine (Cr) 35%, methylguanidine (MG) 76%, guanidinosuccinic acid 83%, blood phosphate 39%, while blood calcium raised for 28%. But in 25mg and 45mg-dose, MG in urine decreased by 49%-65%. The mechanisms of action might be including (1) Inhibiting the production of Cr; (2) Inhibiting the production of hydroxyl free radical, blocking the conversion of Cr into creatol, thereby reducing, the production of MG from creatol. In conclusion, dry extract of Herba ephedra could improve renal function in adenine- induced chronic renal failure in rats, correct Ca and P disorder, and especially inhibit the production of MG. Fraction 2 and fraction 3 of Ephedra tannin had no effect on this renal failure model. Registry Numbers: 471-29-4 (Methylguanidine) 73-24-5 (Adenine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ **CHUNG-KUO CHUNG YAO TSA CHIH CHINA JOURNAL OF CHINESE MATERIA MEDICA* Zeng Q Liu C Lou G Zheng L Jiang H [Volatile oil in Ephedra sinica Stapf. and its processed products by GC-MS] In: Chung Kuo Chung Yao Tsa Chih (1992 Feb) 17(2):83-7, 126 ISSN: 1001-5302 (Published in Chinese) This paper deals with the changes in contents and chemical composition in the volatile oil of Ephedra sinica before and after processing. The results indicate that after processing, the more the substances of low boiling point, the higher their contents and vice versa. The changes are particularly obvious in yellow-fried Ephedra sinica. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CLINICAL AND EXPERIMENTAL IMMUNOLOGY***** Ling M Piddlesden SJ Morgan BP A component of the medicinal herb ephedra blocks activation in the classical and alternative pathways of complement. In: Clin Exp Immunol (1995 Dec) 102(3):582-8 ISSN: 0009-9104 Extracts of the herb Ephedra sinica have long been used in traditional Chinese medicine for the treatment of, among other conditions, acute nephritis. In preliminary studies it was shown that extracts of ephedra caused inhibition of complement in vitro. We thus set out to isolate the active component(s) of this herb, to examine the complement-inhibiting capacity in sera from different species, and to characterize the mechanism(s) by which it inhibits complement. Aqueous extraction of the herb followed by fractionation using thin layer chromatography (TLC) demonstrated that complement-inhibiting activity resided within a single band, hereafter termed the complement-inhibiting component (CIC), which represents an as yet uncharacterized polyanionic carbohydrate molecule. TLC-purified CIC inhibited the classical complement pathway in all species tested (human, pig, guinea pig, rat and rabbit). Using erythrocyte intermediates and sera specifically depleted of individual components it was apparent that CIC inhibited C2. This finding was confirmed using purified human C2, CIC causing a dose-dependent loss of C2 haemolytic activity. At much higher doses, CIC also showed some inhibiting effect in the terminal pathway, and this was shown to be due to inhibition of C9. In the alternative pathway CIC also showed inhibitory activity, although its site of action in this pathway remains unresolved. In Chinese medicine the herb is taken orally, though no studies of complement levels in patients taking the herb have been reported. Preliminary data indicate that oral administration in rats causes a partial inhibition of serum complement activity. Given the current enthusiasm for complement inhibition as a therapy for inflammatory diseases, this non-toxic, naturally occurring agent might be of therapeutic value. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF AOAC INTERNATIONAL***** Betz JM Gay ML Mossoba MM Adams S Portz BS Chiral gas chromatographic determination of ephedrine-type alkaloids in dietary supplements containing Ma Huang. In: J AOAC Int (1997 Mar-Apr) 80(2):303-15 ISSN: 1060-3271 Ma Huang is a traditional Chinese medicine derived from the aerial parts of several Ephedra species (Ephedraceae). These plants produce (-)-ephedrine, (+)-pseudoephedrine, (-)-norephedrine, (+)- norpseudoephedrine, (-)-N-methylephedrine, and (+)-N- methylpseudoephedrine. Racemic and (-)-ephedrine, (+)- pseudoephedrine, and (+/-)-norephedrine (phenylpropanolamine) are used clinically in the United States and are largely synthetic in origin. Current interest in Ma Huang is spurred by reports describing a "thermogenic" (calorie burning) effect provided by mixtures of ephedrine, caffeine, and aspirin. Products providing the key thermogenic compounds from natural sources are available as dietary supplements in retail outlets. Reports of potentially unsafe levels of the alkaloids, as well as possible fortification of Ma Huang- containing products with synthetic Ephedra alkaloids, prompted the development of a chiral gas chromatographic (GC) method that allows determination of alkaloid patterns and identification of isomerically impure synthetic alkaloids. Nine products were analyzed on a gamma- cyclodextrin capillary GC column. Identity of the alkaloids was verified by GC/mass spectrometry (MS) and GC/matrix isolation/Fourier transform infrared spectroscopy. No synthetic isomers were found in the dietary supplements analyzed. Three products contained only one of the ephedrine-type alkaloids. One product that listed Ma Huang as an ingredient contained no detectable ephedrine-type alkaloid. In products containing measurable quantities of these compounds, total alkaloid levels ranged from 0.3 to 56 mg/g. Registry Numbers: 299-42-3 (Ephedrine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hanna GM Determination of ephedrine, pseudoephedrine, and norephedrine in mixtures (bulk and dosage forms) by proton nuclear magnetic resonance spectroscopy. In: J AOAC Int (1995 Jul-Aug) 78(4):946-54 ISSN: 1060-3271 A simple, specific, and accurate 1H nuclear magnetic resonance (NMR) spectroscopic method has been developed for quantitative determination of the Ephedra alkaloids (-)-ephedrine, (+)- pseudoephedrine, and (+/-)-norephedrine, either singly or in mixtures with each other. Determination of individual alkaloids was carried out in D2O solution, with acetamide as internal standard. Although calculations were based on integrals for the C-CH3 protons, those for the N-CH3 and -CH-O- protons may also be useful, depending on the compound. Determination of diastereomeric cross-contamination of ephedrine and pseudoephedrine--or of the concentrations of these alkaloids in the presence or absence of (+/-)-norephedrine--was feasible by using the integrals for the -CH-O- protons after addition of a trace of DCl. Mean recoveries for ephedrine and pseudoephedrine from their respective synthetic mixtures with the internal standard (acet- amide) were > or = 99.9 +/- 0.6% (n = 10) and 99.6 +/- 0.8% (n = 10) of the amount added. Recovery for pseudoephedrine from diastereomeric mixtures with ephedrine was > 99.4 +/- 0.7% (n = 10) of the amount added, with as little as 1.92% still being measurable. Mean recovery of (+/-)-norephedrine from mixtures with ephedrine and pseudoephedrine was > 99.7 +/- 2.5% (n = 4) of the amount added, with about 1% still being measurable. Application of the proposed NMR spectroscopic method to commercial dosage forms, including ephedrine sulfate injections and pseudoephedrine hydrochloride tablets, yielded assay results ranging from 97.8 to 100.2% (mean, 99.2%) and from 98.7 to 100.5% (mean, 99.7%) of declared, respectively. Registry Numbers: 14838-15-4 (Phenylpropanolamine) 299-42-3 (Ephedrine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF CHROMATOGRAPHY. B, BIOMEDICAL APPLICATIONS***** Flurer CL Lin LA Satzger RD Wolnik KA Determination of ephedrine compounds in nutritional supplements by cyclodextrin-modified capillary electrophoresis. In: J Chromatogr B Biomed Appl (1995 Jul 7) 669(1):133-9 ISSN: 0378-4347 Capillary electrophoresis was utilized for the separation, identification, and quantitation of ten stereoisomers in the ephedrine family. Chiral discrimination was accomplished through the use of hydroxypropyl-beta-cyclodextrin, and separation was enhanced at pH 2 in the presence of tetramethylammonium chloride and sodium dodecyl sulfate. Calibration plots of the ephedrines were linear over the range 4-100 micrograms/ml. This method was used in the analysis of nutritional supplements that contain Ma Huang, a Chinese herbal preparation that is made from plants in the genus Ephedra. Registry Numbers: 299-42-3 (Ephedrine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF ETHNOPHARMACOLOGY***** Lietava J Medicinal plants in a Middle Paleolithic grave Shanidar IV? In: J Ethnopharmacol (1992 Jan) 35(3):263-6 ISSN: 0378-8741 This paper deals with phytopharmacological evaluation of the therapeutic potential of the plants found in the Neanderthal grave of a Shanidar IV individual (Iraq), where the palynological analysis of some other authors discovered the following flowers: Achillea-type, Centaurea solstitialis, Senecio-type, Muscari-type, Ephedra altissima, Althea-type. The purpose of our theoretical analysis was to evaluate the objective healing activity of the flowers. The result of the research revealed that Shanidar IV flowers possess considerable therapeutic effects with marked medical activity, which could be an intentional reason for the selection of the flowers in Middle Paleolithic Shanidar Neanderthals. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Kalix P The pharmacology of psychoactive alkaloids from ephedra and catha. In: J Ethnopharmacol (1991 Apr) 32(1-3):201-8 ISSN: 0378-8741 Ever since the introduction of the alkaloid ephedrine as an anti- asthmatic, the CNS stimulatory effects of this sympathomimetic have been a problem in therapy. Indeed, the use of ephedrine is not only limited by its cardiovascular effects, but also by the occurrence of insomnia, restlessness and anxiety. Exceptionally, ephedrine may even induce toxic psychosis, and the possibility of this side effect has recently received renewed attention. Besides ephedrine, the ephedra plant contains some norpseudoephedrine. This substance is also called cathine, because it is a major alkaloid of Catha edulis or khat, a plant that is widely used as a stimulant in certain countries of East Africa and of the Arab Peninsula. The effects of khat have been explained formerly by those of cathine; some time ago, however, the labile alkaloid cathinone was discovered in khat. This substance is the keto-analog of cathine; it is therefore more lipophilic and penetrates easily to its sites of action in the central nervous system. Indeed, cathinone has been found to be a highly potent CNS stimulant and it is now known to be the main psychoactive constituent of khat; the results of various in vitro and in vivo studies indicate that cathinone must be considered a natural amphetamine. In confirmation of this view, it has recently been demonstrated that cathinone has in humans marked euphorigenic and psychostimulant effects. As the case may be, these findings may lead, together with epidemiological data, to a reconsideration of the use of khat as a stimulant and social drug. Registry Numbers: 299-42-3 (Ephedrine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF MOLECULAR EVOLUTION***** Troitsky AV Melekhovets YuF Rakhimova GM Bobrova VK Valiejo-Roman KM Antonov AS Angiosperm origin and early stages of seed plant evolution deduced from rRNA sequence comparisons. In: J Mol Evol (1991 Mar) 32(3):253-61 ISSN: 0022-2844 Complete or partial nucleotide sequences of five different rRNA species, coded by nuclear (18S, 5.8S, and 5S) or chloroplast genomes (5S, 4.5S) from a number of seed plants were determined. Based on the sequence data, the phylogenetic dendrograms were built by two methods, maximum parsimony and compatibility. The topologies of the trees for different rRNA species are not fully congruent, but they share some common features. It may be concluded that both gymnosperms and angiosperms are monophyletic groups. The data obtained suggest that the divergence of all the main groups of extant gymnosperms occurred after the branching off of the angiosperm lineage. As the time of divergence of at least some of these gymnosperm taxa is traceable back to the early Carboniferous, it may be concluded that the genealogical splitting of gymnosperm and angiosperm lineages occurred before this event, at least 360 million years ago, i.e., much earlier than the first angiosperm fossils were dated. Ancestral forms of angiosperms ought to be searched for among Progymnospermopsida. Genealogical relationships among gymnosperm taxa cannot be deduced unambiguously on the basis of rRNA data. The only inference may be that the taxon Gnetopsida is an artificial one, and Gnetum and Ephedra belong to quite different lineages of gymnosperms. As to the phylogenetic position of the two Angiospermae classes, extant monocotyledons seem to be a paraphyletic group located near the root of the angiosperm branch; it emerged at the earliest stages of angiosperm evolution. We may conclude that either monocotyledonous characters arose independently more than once in different groups of ancient Magnoliales or that monocotyledonous forms rather than dicotyledonous Magnoliales were the earliest angiosperms. Judging by the rRNA trees, Magnoliales are the most ancient group among dicotyledons. The most ancient lineage among monocotyledons leads to modern Liliaceae. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Kolukisaoglu HU Marx S Wiegmann C Hanelt S Schneider-Poetsch HA Divergence of the phytochrome gene family predates angiosperm evolution and suggests that Selaginella and Equisetum arose prior to Psilotum. In: J Mol Evol (1995 Sep) 41(3):329-37 ISSN: 0022-2844 Thirty-two partial phytochrome sequences from algae, mosses, ferns, gymnosperms, and angiosperms (11 of them newly released ones from our laboratory) were analyzed by distance and character-state approaches (PHYLIP, TREECON, PAUP). In addition, 12 full-length sequences were analyzed. Despite low bootstrap values at individual internal nodes, the inferred trees (neighbor-joining, Fitch, maximum parsimony) generally showed similar branching orders consistent with other molecular data. Lower plants formed two distinct groups. One basal group consisted of Selaginella, Equisetum, and mosses; the other consisted of a monophyletic cluster of frond-bearing pteridophytes. Psilotum was a member of the latter group and hence perhaps was not, as sometimes suggested, a close relative of the first vascular plants. The results further suggest that phytochrome gene duplication giving rise to a- and b- and later to c-types may have taken place within seedfern genomes. Distance matrices dated the separation of mono- and dicotyledons back to about 260 million years before the present (Myr B.P.) and the separation of Metasequoia and Picea to a fossil record-compatible value of 230 Myr B.P. The Ephedra sequence clustered with the c- or a-type and Metasequoia and Picea sequences clustered with the b-type lineage. The "paleoherb" Nymphaea branched off from the c-type lineage prior to the divergence of mono- and dicotyledons on the a- and b-type branches. Sequences of Piper (another "paleoherb") created problems in that they branched off from different phytochrome lineages at nodes contradicting distance from the inferred trees' origin. Registry Numbers: 11121-56-5 (Phytochrome) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF PHARMACOBIO-DYNAMICS***** Harada M Nishimura M Contribution of alkaloid fraction to pressor and hyperglycemic effect of crude Ephedra extract in dogs. In: J Pharmacobiodyn (1981 Sep) 4(9):691-9 In anesthetized dogs, pressor and hyperglycemic effects of Ephedra aqueous extract as well as its alkaloid fraction and adsorption of alkaloid from the digestive tract were studied in order to investigate how closely effects of the alkaloid fraction relate to those of the Ephedra extract itself. Blood pressure, heart rate, and blood glucose concentration were increased by intraduodenal administration of the extract and the alkaloid fraction on the bases of the same alkaloid content (20 mg/Kg). In respect to the pressor and hyperglycemic effects, changes in time course of the effects produced by these two drug preparations were similar and in either of the two physiological parameters the maximal value given by the extract was about a half that given by the alkaloid fraction. A maximal level of blood pressure and blood glucose concentration was reached 10-15 min after the administration of the two drug preparations, while the amount of alkaloid absorbed in the portal vein until this time was about 2-3 times as much under administration of the alkaloid fraction as under administration of the extract. Absorption of alkaloid in the extract occurred slowly and lasted longer compared with that of the alkaloid fraction itself. On the contrary, the alkaloid-free extract administered intraduodenally showed no virtual effects on blood pressure and blood glucose concentration except producing tachycardia. It seems that the effect of Ephedra extract on blood pressure and blood glucose concentration was mostly qualitatively and quantitatively represented by that of alkaloid contained and that effect of the extract mainly depended on that of alkaloid absorbed early after its application. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****MOLECULAR PHYLOGENETICS AND EVOLUTION***** Boivin R Richard M Beauseigle D Bousquet J Bellemare G Phylogenetic inferences from chloroplast chlB gene sequences of Nephrolepis exaltata (Filicopsida), Ephedra altissima (Gnetopsida), and diverse land plants. In: Mol Phylogenet Evol (1996 Aug) 6(1):19-29 ISSN: 1055-7903 The chloroplast chlB gene, involved in light-independent protochlorophyllide reduction, has been reported present in algae, in one bryophyte and some gymnosperms, but absent from various angiosperms. In this study, the complete or nearly complete chlB gene sequences from the fern Nephrolepis exaltata and the seed plant Ephedra altissima were determined. Comparison of five available land plant chlB sequences with a similar set of rbcL sequences, encoding the large subunit of ribulose 1,5-bisphosphate carboxylase, showed that the chlB rate of nonsynonymous substitution was about fourfold higher than for rbcL, while the chlB phylogeny resulted in a better resolution of the clades surveyed. The presence of chlB in other lineages of land plants was determined by amplification and sequencing of a chlB internal fragment, which was recovered from all the nonangiosperm taxa surveyed except Psilotum and Gnetum. The phylogenies derived from 23 land plant chlB sequences were largely congruent with the relationships inferred from other analyses. Neighbor-joining analysis supported the view that bryophytes are paraphyletic, with mosses as sister group to vascular plants. Within lycopodiophytes, Selaginella clustered with Lycopodium, but Isoetes was located basally to the other land plants. The various ferns surveyed were found to form a coherent group which derived after horsetails and which was sister group to seed plants. Our results strongly supported monophyly of the conifers-Ginkgo-cycads clade, where conifers were sister group to Ginkgo and cycads. The various phylogenies suggested an early divergence of the seed plant lineage leading to Ephedra. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****MUTAGENESIS***** Horikawa K Mohri T Tanaka Y Tokiwa H Moderate inhibition of mutagenicity and carcinogenicity of benzo[a]pyrene, 1,6-dinitropyrene and 3,9-dinitrofluoranthene by Chinese medicinal herbs. In: Mutagenesis (1994 Nov) 9(6):523-6 ISSN: 0267-8357 The activity of six Chinese medicinal herbs against the environmental mutagens and carcinogens benzo[a]pyrene (B[a]P), 1,6-dinitropyrene (1,6-diNP) and 3,9-dinitrofluoranthene (3,9-diNF) was determined. Samples of Prunella spica, Rheum palmatum, Polygonum multiflorum, Agrimonia pilosa, Ephedra sinica and Teitoutou were tested in an in vitro system. Antimutagenic activity against B[a]P was marked in the presence of extracts (boiled for 2 h in a water bath) whereas that against 1,6-diNP and 3,9-diNF varied from 20 to 86%. The differences in inhibition might be due to inactivation of metabolic enzymes. An extract of P. multiflorum was divided into ether, ethyl acetate and water soluble fractions, which were tested for antimutagenic activity against B[a]P. The antimutagenic action of the ethyl acetate soluble fraction was substantial and dose-dependent. Tannins and related compounds were the major components of the extract, of which epigallocatechin, epigallocatechin gallate, epicatechin gallate and tannic acid strongly inhibited the mutagenicity of B[a]P (2.5 micrograms/plate) in Salmonella typhimurium TA98 with S9 mix. To confirm the results of the in vitro test system, F344/DuCrj male rats were given a subcutaneous injection of B[a]P. Thereafter, they received water extracts of the six Chinese medicinal herbs for 50 weeks and were examined for tumors. The P. multiflorum extract significantly reduced the tumor incidence. Registry Numbers: 22506-53-2 (3,9-dinitrofluoranthene) 42397-64-8 (1,6-dinitropyrene) 50-32-8 (Benzo(a)pyrene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****TOXICOLOGY LETTERS***** Tricker AR Wacker CD Preussmann R 2-(N-nitroso-N-methylamino)propiophenone, a direct acting bacterial mutagen found in nitrosated Ephedra altissima tea. In: Toxicol Lett (1987 Sep) 38(1-2):45-50 ISSN: 0378-4274 A new N-nitroso compound identified in a nitrosated tea extract made from the plant Ephedra altissima and shown to be formed under in vivo conditions was identified as 2-(N-nitroso-N-methylamino)propiophenone (NMAP). N-Nitrosoephedrine (NEP), another N-nitroso compound detected in nitrosated Ephedra altissima tea and NMAP are shown to exert mutagenic activity in the Salmonella/mammalian microsome mutagenicity (Ames) test. Base-pair substitution mutation-detecting strains (TA100 and TA1535) showed both compounds to be weak direct-acting mutagens without the addition of S9-mix. The identification, synthesis and mutagenicity of NMAP are discussed. Registry Numbers: 110505-04-9 (2-(N-nitroso-N-methylamino)propiophenone) 17608-59-2 (N-nitrosoephedrine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****YAKUBUTSU, SEISHIN, KODO [JAPANESE JOURNAL OF PSYCHOPHARMACOLOGY]***** Furuya I Watanabe S [Discriminative stimulus properties of ephedra herb (Ephedra sinica) in rats] In: Yakubutsu Seishin Kodo (1993 Feb) 13(1):33-8 ISSN: 0285-5313 (Published in Japanese) The stimulus properties of ephedra herb (drug of Chinese medicine) were demonstrated in rats trained to discriminate between 2.5 ml/kg extract of ephedra herb and same volume of distilled water (p.o.). On the discrimination training, animals were shaped on an FR20 schedule to respond to one of two levers for food reinforcement when they were administrated ephedra herb extract, and to respond to the other lever when they were treated with distilled water. Cumulative dosing tests for the discriminative stimulus properties consisted of two to five trials of FR20 schedule; responses for both levers were reinforced. d- Methamphetamine 1.43 mg/kg p.o. indicated complete generalization to the ephedra herb. Nicotine and caffeine indicated modest generalization, but some animals generalized completely. These results suggest that the ephedra herb has d-methamphetamine-like, but unique discriminative stimulus properties. Registry Numbers: 537-46-2 (Methamphetamine) 54-11-5 (Nicotine) 58-08-2 (Caffeine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****YAKUGAKU ZASSHI. JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN***** Nikaido T Iizuka S Okada N Kuge T Ohmoto T [The study of Chinese herbal medicinal prescription with enzyme inhibitory activity. VI. The study of makyo-kanseki-to with adenosine 3',5'-cyclic monophosphate phosphodiesterase] In: Yakugaku Zasshi (1992 Feb) 112(2):124-8 ISSN: 0031-6903 (Published in Japanese) A Chinese herbal medicinal prescription, Makyo-kanseki-to, was studied for the inhibitory activity of adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase. The effect for the inhibitory activity of cAMP phosphodiesterase by combination with constituent crude drugs of the prescription was studied. Gypsum acted as a mitigatory component for Ephedra herb and Glycyrrhiza in cAMP phosphodiesterase inhibition test. Registry Numbers: EC 3.1.4.17 (3',5'-Cyclic-Nucleotide Phosphodiesterase) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Nikaido T Ohmoto T Kuge T Yanagisawa A Teinozawa K Takeda H Tsukamoto H [The study on Chinese herbal medicinal prescription with enzyme inhibitory activity. III. The study of mao-to with adenosine 3',5'- cyclic monophosphate phosphodiesterase] In: Yakugaku Zasshi (1990 Jul) 110(7):504-8 ISSN: 0031-6903 (Published in Japanese) Mao-to, a Chinese herbal medicinal prescription was studied for the inhibitory activity of adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase. The inhibitory activity for this enzyme depended mainly on Ephedra herb and Glycyrrhiza in this prescription. Apricot kennel acted as a mitigatory component for Ephedra herb in cAMP phosphodiesterase inhibitory test. In ephedrine and the related compounds the inhibitory activity of cAMP phosphodiesterase was not shown. Registry Numbers: EC 3.1.4.17 (3',5'-Cyclic-Nucleotide Phosphodiesterase) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****YAO HSUEH HSUEH PAO [ACTA PHARMACEUTICA SINICA]***** Cui JF Niu CQ Zhang JS [Determination of six Ephedra alkaloids in Chinese Ephedra (Ma Huang) by gas chromatography] In: Yao Hsueh Hsueh Pao (1991) 26(11):852-7 ISSN: 0513-4870 (Published in Chinese) Six Ephedra alkaloids, namely ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedrine and methylpseudoephedrine, in 12 species of Chinese Ephedra were successfully separated and determined by gas chromatography with the highly specific and sensitive nitrogen phosphorus detector (GC/NPD). The column used (HP-5) had a cross linked 5% phenylmethylsilicone phase. Diphenylamine was used as the internal standard to check the reproducibility of the extraction yields of the alkaloids, the stability of the detector response and to quantify the alkaloids. The contents of the six alkaloids were calculated according to their regression equations. The way for the preparation of crude drug samples was improved, the diethyl ether extract of the alkalized crude sample was directly analysed by GC. The method is simple, rapid and sensitive. The results are in agreement with those of the HPLC method. Registry Numbers: 14838-15-4 (Phenylpropanolamine) 17605-71-9 (N-methylephedrine) 299-42-3 (Ephedrine) 36393-56-3 (norpseudoephedrine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Zhang JS Li SH Lou ZC [Morphological and histological studies of Chinese Ephedra, ma huang. II. Species produced in southwestern China and other species] In: Yao Hsueh Hsueh Pao (1990) 25(1):54-65 ISSN: 0513-4870 (Published in Chinese) In this paper, the morphological and histological characters of crude drugs derived from Ephedra likiangensis Florin, E. likiangensis f. mairei (Florin) C. Y. Cheng, E. saxatilis Royle ex Florin, E. gerardiana Wall, E. gerardiana var. congesta C. Y. Cheng, E. minuta Florin, E. minuta var. dioeca C. Y. Cheng, E. lepidosperma C. Y. Cheng, E. lomatolepis Schrenk and E. intermedia var. tibetica Stapf are described, compared and illustrated with line drawings. It was found that all the Ephedra spp. growing in southwester nChina possess the following features in common, viz. (1) numerous distinct longitudinal ridges are present on the stem; (2) xylem fibres and tracheids possess steep, tertiary spiral thickenings; (3) stone cells (sclereids) are absent from the nodes. According to the above characters, the drugs produced in southwestern China can be differentiated from those produced in northern China. The results also show that the histological characters of E. intermedia var tibetica Stapf produced in southeast ern Xizang (Tibet) are different from those produced in north western Xizang. The former possesses the xylem fibres and tracheids with steep, tertiary spiral thickenings, while the latter possesses sclereids at stem-nodes. It may be related to their habitat factors and interspecies hybridization. A key for identification of all the crude drugs derived from Chinese Ephedra spp. studied in this series of paper, including thirteen species, three varieties and one form is presented. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Zhang JS Li SH Lou ZC [Morphological and histological studies of Chinese Ephedra mahuang. I. Seven species produced in north China] In: Yao Hsueh Hsueh Pao (1989) 24(12):937-48 ISSN: 0513-4870 (Published in Chinese) The Chinese drug Ma Huang, Herba Ephedrae, is well known in the East and West. The botanical origin specified in the Chinese Pharmacopoeia (1985 edition) includes the dried herbaceous stems of Ephedra sinica Stapf, E. equisetina Bunge and E. intermedia Schrenk ex Mey. A survey of the botanical origin of this drug, however, revealed that other Eqhedra spp. are also used in certain districts in China. In order to find means for the identification of drugs derived from different plant origins, it is necessary to make a comparative study of the morphology and histology of all the Eqhedra spp. growing in China. In this paper, the morphological and histological characters of the crude drugs derived from the Eqhedra spp. chiefly growing in north China, viz. E. sinica Stapf, E. equisetina Bunge, E. intermedia Schrenk ex Mey., E. qrzewaskiistaqs E. monosperma Gmel. ex Mey., E. fedtschenkoae Pauls, and E. regeliana Florin are described, compared and illustrated with line drawings. It is discovered that the following characters are useful for their differentiation, viz. (1) the presence, shape and height of cuticular papillae of the stem; (2) the presence, amount and arrangement of sclereids at stem-nodes; (3) vessels and tracheids with bordered pits and spiral thickenings, tracheids with bordered pits and reticulate thickenings, and xylem parenchyma cells with reticulate thickenings, (4) the ratios of longitudinal and transverse diameters of stomata on the epidermis of stem and leaf. Observation with scanning electron microscope (SEM) revealed that the perforations of the end walls of vessel element in Eqherda spp. are bordered. It is also found that the degree of lignification of fibres and medullary cells of the herbaceous stems is related to the positions and diameters of the stems. It is therefore unsuitable as a diagnostic feature for the differentiation of Eqhedrra species. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Zhang JS Tian Z Lou ZC [Quality evaluation of twelve species of Chinese Ephedra (ma huang)] In: Yao Hsueh Hsueh Pao (1989) 24(11):865-71 ISSN: 0513-4870 (Published in Chinese) The contents of six Ephedra alkaloids, namely ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedrine and methyl-pseudoephedrine, in 12 species of Chinese Ephedra collected in 24 districts were determined by high performance liquid chromatography (HPLC). Zorbax CN column (25 cm x 4.6 mm I.D.) was used and the temperature of column oven was 23-25 degrees C. Dibutylamine phosphate solution 0.0009 mol/L (pH 2.2) was used as the mobile phase at flow rates: 0.8 ml/min for the first 7 minutes, raised to 1.5 ml/min in 30 sec and maintained for 16 minutes. The alkaloids eluted were detected at wave-length 210 nm. The results showed that ephedrine and pseudoephedrine are the main components in these Ephedra herbs, but the contents of the six Ephedra alkaloids vary greatly with the plant species. The contents of total alkaloids are higher and ephedrine is the main component in samples derived from Ephedra sinica, E. equisetina, E. monosperma and E. intermedia var. tibetica; but in E. intermedia and E. lomatolepis, the content of pseudoephedrine is higher than that of ephedrine. Methylephedrine content is higher in E. intermedia var. tibetica produced in Xizang (Tibet) and in E. sinica produced in north-eastern China than that in other species. The results also showed that the samples derived from E. przewalskii and E. lepidosperma contain so little alkaloids (less than 0.1%) that they are considered not suitable to be used as the drug Ma Huang. It is of interest that the cultivated Ephedra sinica showed lower alkaloids content compared with that growing wild. Registry Numbers: 14838-15-4 (Phenylpropanolamine) 299-42-3 (Ephedrine) 36393-56-3 (norpseudoephedrine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Shao G Wu F Wang DS Zhu R Luo X Quantitative analysis of (l)-ephedrine and (d)-pseudoephedrine in plasma by high-performance liquid chromatography with fluorescence detection. In: Yao Hsueh Hsueh Pao (1995) 30(5):384-9 ISSN: 0513-4870 Quantitative analysis of (l)-ephedrine (l-Ep) and (d)-pseudoephedrine (d-Ps) in plasma by high-performance liquid chromatography (HPLC) is described. The newly developed method is based on a precolumn derivatization with 5-dimethyl-aminonaphthalene-1-sulfonyl chloride (DNSC1) in acetonitrile. The diastereomers formed were separated on a reversed phase column by HPLC with fluorescence detection employing 0.6% phosphate buffer (pH 6.5)-methanol (3:8, v/v) as mobile phase. The detection limit of each Ephedra alkaloid stereoisomer was 0.5 ng at a signal-to-noise ratio of 3:1, the linear response to each stereoisomer being 1-800 ng.ml-1. The plasma level profile of l-Ep and d-Ps in guinea pig was investigated by this method. The determination of l-Ep and d-Ps in plasma of a volunteer after oral administration of Xiao Qinglong Heji was also performed. Registry Numbers: 299-42-3 (Ephedrine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€