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The naturally-occurring anthraquinones (AQs), alizarin (1,2-dihydroxyanthraquinone) and lucidin (1,3-dihydroxy-2-hydroxymethylanthraquinone), were incubated with DNA in the presence of S9 mix. The isolated DNA was analysed by 32P-postlabelling for the presence of aromatic adducts. Only lucidin formed up to five different DNA adducts in the range from 0.995 to 3.05 adducts/10(8) nucleotides. Lucidin was also incubated with polynucleotides poly[d(A-T)] and polydG*polydC in the presence of S9 mix. Analysis of polydG*polydC revealed a similar adduct pattern to that obtained with lucidin-modified DNA. Alizarin, lucidin, a glycoside mixture containing alizarinprimeveroside and lucidinprimeveroside, and Rubia Teep (a herbal drug made from Rubia tinctorum containing lucidin) were incubated with primary rat hepatocytes for 24 h and the isolated DNA was analysed by 32P-postlabelling. Lucidin, the glycoside mixture and Rubia Teep gave rise to DNA adducts, but alizarin did not. Male Parkes mice were treated orally for 4 days with alizarin (10 mg/d), lucidin (2 mg/d), the glycoside mixture (20 mg/d) or Rubia Teep (1/2 tablet/d) and DNA was isolated from liver, kidney, duodenum and colon. Analysis by 32P-postlabelling revealed that lucidin, the glycoside mixture and Rubia Teep, but not alizarin, formed DNA adducts in all the tissues examined but that the adduct patterns were organ-specific.

Bioassay-directed fractionation of the n-hexane extract of the stem of Rhus semialata Murr. var. roxburghii DC (Anacardiaceae) has led to the isolation of 6-pentadecylsalicylic acid. It showed antithrombin activity at 50 micrograms/ml in the amidolytic method. It also prolonged the clotting time in a dose-dependent manner in the clotting assay of thrombin-fibrinogen interaction.

A reinvestigation of the aerial parts of Calendula arvensis afforded, in addition to the oleanolic acid glycosides 1-4 (4), the new glycoside 5 whose structure was elucidated by spectral and chemical studies and determined as 3-O-(beta-D-galactopyranosyl-(1----3) [beta-D-glucopyranosyl-(1----4)]-beta-D-glucopyranosyl) oleanolic acid (28----1)-beta-D-glucopyranosyl ester. Furthermore, some antiviral tests were performed on glycosides 1-5 and on 5a, the hydrolysis product of 5, towards vesicular stomatitis virus (VSV) and rhinovirus (HRV) infection in cell cultures. An inhibitory effect against VSV multiplication was observed for all the compounds tested while HRV replication was significantly affected only by compound 3.

The chemical constituents of the aerial parts of six species of Bupleurum genus (B. kunmingense, B. polyclonum, B. wenchuanense, B. longicaule var. franchetii, B. rockii and B. chaishoui) medicinally used in south-west region of China have been investigated with the results of obtaining eight flavonoid compounds and six triterpenoid saponins. The aglycones of these eight flavonoid compounds are quercetin and isorhamnetin, which are different from the aglycones of the flavonoid compounds isolated from the aerial parts of B. chinense, the official species in Chinese Pharmacopoeia. In the latter case, the aglycone is kaempferol. This difference may be of chemotaxonomic value in Bupleurum genus.

Essential oils were extracted from the pericarp of Zanthoxylum bungeanum and Z. schinifolium. The chemical constituents were analysed by means of GC-MS and 33 compounds were identified. Their contents in the essential oil were also determined.

A lyophilised hydroalcoholic extract of Melissa officinalis L. (Lamiaceae) has been evaluated for behavioral effects in mice. According to the traditional use of M. officinalis, sedative properties have been confirmed for low doses by the decrease of behavioral parameters measured in a non-familiar environment test (staircase test) and in a familiar environment test (two compartment test). With high doses, a peripheral analgesic activity was obtained by reducing the acetic acid-induced pain (writhing test); moreover, the plant extract induced the sleep in mice after treatment with an infrahypnotic dose of pentobarbital and potentialised the sleep induced by a hypnotic dose of pentobarbital.

China, one of the developing countries with approx. one-fifth of the world population, has been making great efforts in controlling her population size. One of the efforts being stressed is to look into the practicability of employing Chinese herbal medicine for fertility control. The rich ethnopharmacological descriptions in the ancient books of herbal remedy and those scattered in the folklore medicine contribute the possibility of this approach. After a discussion concerning the facets of antifertility drugs linked with male or female fertility regulation, several selected examples are presented, which include yuehchukene (isolated from Murraya paniculata), pseudolarix acids A and B (from Pseudolarix kaempferi), mardekoside A (from Mardenia koi), gardenic acid and gardenodic acid A (from Gardenia jasminoides) as early pregnancy terminating agent, for fertility regulation in females; whereas gossypol (from cottonseed oil) and total glycosides of Tripterygium wilfordii (GTW) as antispermatogenic agent for fertility regulation in males. Further research and development strategies of antifertility drugs from herbal medicines have also been discussed based on a collective research data in this field worldwide.

Virosecurinine (1) and viroallosecurinine (2) were isolated as two cytotoxic alkaloids from the leaves of Securinega virosa. A comparison of the cytotoxicity of 1 and several of its derivatives indicates that an alpha,beta- and a gamma,delta-unsaturated lactone located in a strained ring system, such as rings -B, -C, and -D of 1, is structurally required for significant cytotoxicity.

The in vitro effects of griffonin and ouabain on erythrocyte sodium content have been investigated in 6 normal subjects and 6 sickle cell patients. Intracellular sodium contents of normal or sickle cells incubated for 8 h in tris buffer, griffonin/tris buffer, or ouabain/tris buffer were determined. Incubation of normal cells in tris buffer or 0.5 mmol/l griffonin had little effect on the cell sodium content. However, 1.0 mmol/l griffonin/tris buffer raised the cell sodium level (P less than 0.05) over the incubation period. Ouabain/tris buffer (0.5 mmol/l or 1.0 mmol/l) also raised the sodium content (P less than 0.05 to P less than 0.001). Incubation of sickle cells in tris buffer raised the cell sodium (P less than 0.05) as did 0.5 mmol/l or 1.0 mmol/l griffonin (P less than 0.05 to P less than 0.001). Ouabain/tris buffer (0.5 mmol/l or 1.0 mmol/l) raised the intra-erythrocyte sodium level (P less than 0.01 to P less than 0.001). These findings suggest that ouabain and griffonin both have similar actions on intra-erythrocyte sodium content although ouabain was more potent. It is suggested therefore that griffonin could be a useful anti-sickling drug for sickle cell disease crisis.

Taspine has been isolated as a cytotoxic substance from Sangre de Grado, sap of Croton palanostigma (Euphorbiaceae), by bioassay guided fractionation. The cytotoxicity (IC50) of taspine was found to be 0.39 microgram/ml against KB cells and 0.17 microgram/ml against V-79 cells.

Dried hydro-alcoholic extract of Peumus boldus (Monimiaceae) has been evaluated for hepatoprotective, choleretic and anti-inflammatory effects in mice and rats, in order to validate or to invalidate traditional therapeutic indications. This extract exerted a significant hepatoprotection of tert-butyl hydroperoxide-induced hepatotoxicity in isolated rat hepatocytes (in vitro technique) by reducing the lipid peroxidation and the enzymatic leakage of LDH; this in vitro efficacy was reinforced by a significant hepatoprotection on CCl4-induced hepatotoxicity in mice (in vivo technique), the plant extract reducing the enzymatic leakage of ALAT. Boldine, the main alkaloid of P. boldus appears to be implicated in this hepatoprotective activity. Choleretic effects, often mentioned in traditional indications, have not been confirmed in rats. Finally, significant and dose-dependent anti-inflammatory effects were obtained on an acute inflammatory process (carrageenan-induced edema test in rats). Boldine does not appear to be involved in such properties.

The resistance of Plasmodium falciparum, the cause of tertian malaria, to synthetic antimalarials, together with the resistance of the vector mosquitoes to insecticides, has resulted in a resurgence in the use of quinine and a search for new antimalarial agents. In recent years, artemisinin, isolated from Artemisia annua which is used in Chinese traditional medicine for the treatment of malaria, has proved to be effective in the treatment of cerebral malaria due to chloroquine-resistant strains of P. falciparum. The development of in vitro tests utilising P. falciparum obtained from malaria patients means that it is possible to use bioassay guided fractionation of active extracts in order to isolate active principles. A number of laboratories throughout the world are currently investigating plants used in traditional medicine for their active constituents. Some of their results will be described and in particular two aspects of our investigations with species of Simaroubaceae and Menispermaceae will be discussed. There is every possibility that such approaches which use leads from Ethnopharmacology will result in the development of new antimalarial agents. It is vitally important to those populations relying on traditional medicines for the treatment of malaria that the safety and efficacy of such medicines be established, their active principles determined and that reproducible dosage forms be prepared and made available for use.

Structural elucidation of bioactive compounds has always been and remains a field of interest for organic chemists. Tools have constantly evolved over the past fifty years and the field has become so sophisticated and relies so heavily on instruments and computers that is becoming an area for specialists. Specialization has become such that the natural product chemist now faces X-ray professionals, mass spectrometry specialists, not to speak of NMR experts; all these people use different tools, different quantities of material and it may happen that once our natural product chemists opens the door of one of their laboratories, he is not welcome in the others anymore. The purpose of this paper is to discuss briefly what can be done best with each of the tools. It will be also shown that chemistry may still find a use, especially when problems are very difficult to tackle. Examples will be chosen among terpenes, antibiotics and toxins.

Ginkgolides are unique twenty-carbon terpenes, occurring naturally only in the roots and leaves of Ginkgo biloba. The molecules incorporate a tert-butyl group and six 5-membered rings, and are specific and potent antagonists of platelet-activating factor (PAF), a potent inflammatory autacoid. Studies in animal models with the most potent ginkgolide, BN 52021, and other specific PAF antagonists have demonstrated that PAF plays an important role in pathologies such as asthma, shock, ischemia, anaphylaxis, graft rejection, renal disease, CNS disorders and numerous inflammatory conditions. Ginkgolides are now being developed as therapeutic agents and very promising results have been obtained in clinical trials on shock, organ preservation and thermal injury. In addition to ginkgolides, several other types of natural PAF antagonists have been identified from various medicinal plants. These compounds have not only helped to explain the pharmacological basis of several traditional medicines, but have also provided man with a valuable new class of therapeutic agents.

A xanthone was isolated from the hexane fraction of the Swertia chirayita plant and identified as 1,8-dihydroxy-3,5-dimethoxyxanthone (swerchirin). It has a very significant blood sugar lowering effect in fasted, fed, glucose loaded, and tolbutamide pretreated albino rat models. The ED50 for 40% blood sugar lowering in CF male albino rats (body weight 140-165 g) is 23.1 mg/kg/oral. The possibility of its application in clinical therapy for diabetes mellitus needs exploration.

One traditional aspect of natural products in medical research has been their use in the identification and investigation of the physiological/pathological role of receptors and enzymes as possible targets for drug design programmes. Classical examples of this function of natural products in drug research can be seen in the investigation of the cholinergic system. For example, the importance of alkaloids such as nicotine, physostigmine and curare for research into the nicotine receptor and muscarine, pilocarpine and the tropane alkaloids on the muscarinic receptor. On binding of a ligand to its cell surface membrane receptor and prior to a physiological/pharmacological response two mechanisms are currently known to be involved in membrane signal transductance. In the minority of cases signal transductance involves the direct opening of an ion channel, for example sodium ion influx, but in the majority of cases involves stimulation of a family of G-proteins and subsequent activation of second messenger systems. For example, the cyclic-AMP/adenylate cyclase system and the phosphoinositol cycle. In this communication, the part played currently by the tumour-promoting and pro-inflammatory phorbol esters from the plant family Euphorbiaceae in furthering our understanding of the role of a group of related kinases from one arm of the phosphoinositol cycle as a signal transduction pathway will be illustrated. The possibilities of using these new receptors as targets for future drug development will also be described.

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.

How to look for new drugs? What guidelines to use? Have we to continue investigations on plant and marine organisms? These questions arise frequently today. A pharmacological effect results from the addition of many effects at a molecular level, i.e. the interaction between a ligand and a receptor. As long as the chemical structure of this receptor remains unknown, studies of Nature's resources will yield the largest reservoir of new drugs. Nature provides our imagination with the pattern of novel biologically active molecules. Criteria classically used in the past to select plants for study were chemotaxonomy, ethnopharmacology or pharmacotaxonomy. Examples will be taken from personal experience, to illustrate work done according to the chemotaxonomical approach (Ochrosia and ellipticines), and the ethnopharmacological approach (antiinflammatory properties of Euphorbiaceae from New Caledonia). Taking into account that one of the major problems we have to face is the unsatisfactory classical pharmacological testing procedure, we have tried to set up a network grouping biologists and chemists. Among many results obtained, one concerns the use of the mammalian hypothalamo-pituitary system to screen effects of alkaloids extracted from Psychotria oleoides, a Rubiaceae collected in New Caledonia. Psycholeine exhibits an intriguing activity on GH release. Another result concerns the influence of a Labiatae extract on the adenylate cyclase system: 9 HODE extracted from Glechoma hederacea stimulates the basal level of enzyme activity in platelets, this activity being possibly involved in the folk uses claimed. Using the tubulin test to screen antimitotic activities of plant extracts, the biological activity of rhazinilam has been demonstrated as responsible for the antitubulin activity of a Malaysian plant, Kopsia singapurensis.(ABSTRACT TRUNCATED AT 250 WORDS)

Two new indole alkaloid glycosides, 10-hydroxystrictosamide and 6'-O-acetylstrictosamide, as well as the known alkaloids strictosamide and vincosamide were isolated from the leaves of Nauclea orientalis L. The structures of the isolated compounds were determined using spectroscopic methods, mainly 1D- and 2D-NMR spectroscopy.

In recent years, many compounds having potent antiviral activity in cell cultures and in experimental animals have been detected, but only a few have been approved by Western health authorities for clinical use. Nevertheless, some of these compounds are currently undergoing either preclinical or clinical evaluation, and perspectives for finding new interesting antiviral drugs are promising. Among these antiviral substances are several natural compounds isolated from plants used in traditional medicine including polysaccharides, flavonoids, terpenes, alkaloids, phenolics and amino acids. Some of these plant compounds exhibit a unique antiviral mechanism of action and are good candidates for further clinical research. What follows is a brief summary of the selection methods of plants for antiviral screening and in vitro and in vivo assays, which are currently used for detecting this activity in plant extracts. The importance of the plant kingdom as a source of new antiviral substances will be illustrated by presenting a survey on plant-derived antirhinovirus and anti-HIV agents.

The injudicious use of a systemically administered herb containing psoralens derived from the fruits of Ammi majus in combination with exposure of the skin to the sun caused a severe phototoxic dermatitis in a Moroccan patient with vitiligo. She was disappointed in the treatment by the dermatologist. A family member advised her to start the treatment with herbs. The identification of the herbs by microscopic, chromatographic and biological techniques demonstrated that they contained the linear furanocoumarins (psoralens) 5-MOP, 8-MOP and oxypeucedanin each in a concentration of approx. 1%. Because of the large immigrant population in our country we expect to see more cases in the future.

Skin infections are common diseases in developing countries, of which dermatophytoses are of particular concern in the tropics, especially in infants. Through ethnobotanical surveys and literature review 100 plants were detected as being used in Guatemala for the treatment of dermatophytoses. Of these, 44 plants were screened for in vitro activity against the most common dermatophytes (Epidermophyton floccosum, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes and Trichophyton rubrum). Results showed that aqueous extracts from 22 of the plants tested inhibit one or more of the dermatophytes. The most commonly inhibited dermatophytes were E. floccosum (43.2%), T. rubrum (36.0%), and T. mentagrophytes (31.8%); the less inhibited were M. canis (22.7%) and M. gypseum (24.0%). Plants of American origin which exhibited anti-dermatophyte activity were: Byrsonima crassifolia, Cassia grandis, Cassia occidentalis, Diphysa carthagenensis, Gliricidia sepium, Piscidia piscipula, Sambucus mexicana, Smilax regelii, Solanum americanum and Solanum nigrescens. Fungicidal and fungistatic activities as well as the minimal inhibitory concentration were demonstrated. These results provide a scientific basis for the use of these plants for the treatment of dermatophyte infections in man.

A chloroform-soluble fraction from Calotropis procera roots showed significant dose-related antiinflammatory activity in rats using the pharmacologic models of carrageenin-induced pedal oedema, cotton pellet granuloma and formaldehyde-induced arthritis. In addition, significant analgesic potential was demonstrated using acetic acid-induced writhing in mice.

An alcoholic extract of whole plant Boerhaavia diffusa given orally exhibited hepatoprotective activity against experimentally induced carbon tetrachloride hepatotoxicity in rats and mice. The extract also produced an increase in normal bile flow in rats suggesting a strong choleretic activity. The extract does not show any signs of toxicity up to an oral dose of 2 g/kg in mice.

Two active sites responsible for antitumor activity, an oxirane ring and an alpha-methylene-cyclopentanone moiety, have been extracted from studies on the structure-activity relationship of the cytotoxic diterpenoids isolated from Rabdosia shikokiana. Series of the simplified cyclopentanone derivatives containing both of the two active sites in the molecule have been synthesized and evaluated for cytotoxicity against P 388 cells. The compounds possessing both of two active sites displayed cytotoxicity at a concentration of 1 microgram/ml, while those possessing a single active site showed no activity.

A group of flavonoids isolated from medicinal plants and which are selective inhibitors of lipoxygenase activity in vitro: sideritoflavone, cirsiliol, hypolaetin-8-O-beta-D-glucoside, hypolaetin, oroxindin, quercetagetin-7-O-beta-D-glucoside, gossypin, hibifolin and gossypetin, besides leucocyanidol, have been studied for their effects on acute responses induced by carrageenin in mice. The oral administration of flavonoids to mice inhibited dose-dependently the development of paw oedema at 1, 3 and 5 h after carrageenin injection. A similar administration of flavonoids induced a dose-dependent inhibition of leukocyte accumulation in inflammatory exudates following intraperitoneal injection of carrageenin into mice. Some of the flavonoids exhibited a potency against leukocyte infiltration similar to that seen for inhibition of carrageenin oedema at 3 h of induction. In agreement with data reported in rats, indomethacin was much more effective on inhibition of prostaglandin E2 (PGE2) formation than on leukocyte infiltration in mice. The selectivity of flavonoids towards lipoxygenase is not retained in vivo since they behave as dual inhibitors of PGE2 and leukotriene B4 (LTB4) formation in peritoneal exudates. Our data support the inhibition of arachidonic acid metabolism as one of the mechanisms by which flavonoids exert their anti-inflammatory effects.

Investigations were carried out to evaluate the effects of hot-water extracts of Artocarpus heterophyllus leaves and Asteracanthus longifolia whole plant material on the glucose tolerance of normal human subjects and maturity-onset diabetic patients. The extracts of both Artocarpus heterophyllus and Asteracanthus longifolia significantly improved glucose tolerance in the normal subjects and the diabetic patients when investigated at oral doses equivalent to 20 g/kg of starting material.

Casearins G-R, new cytotoxic clerodane diterpenes have been isolated from the leaves of Casearia sylvestris Sw. (Flacourtiaceae). Their structures have been elucidated by spectroscopic methods and chemical conversions, and their structure-activity relationships have been discussed.

An ELISA-assay for the detection and the semi-quantitative determination of taxane diterpenoids structurally related to taxol found in Taxus sp. has been developed. The antiserum was raised in rabbits using a 2'-succinyltaxol-bovine serum albumin conjugate as immunogen. The working range of the assay was from 1 to 100 ng of taxol. In order to improve the production of taxol, preliminary experiments have been performed on crude extracts of several Taxus sp.; the results indicate that the present immunoassay is an useful tool for the rapid screening of species, varieties or individual plants out of a large population as well as for tissue cultures analysis.

From the herb of Luffa acutangula ROXB. (Cucurbitaceae), seven oleanane-type triterpene saponins, acutosides A--G, were isolated and their structures were determined. Acutoside A is oleanolic acid 3-O-beta-D-glucopyranosyl-(1----2)-beta-D-glucopyranoside. Acutosides B, D, E, F and G have a common prosapogenin structure, acutoside A, and only differ in the structures of the ester-linked sugar moieties. Acutoside B is a 28-O-[O-beta-D-xylopyranosyl-(1----4)-O-alpha-L-rhamnopyranosyl-(1----2) -alpha-L-arabinopyranosyl] ester, D is a 28-O-[O-beta-D-xylopyranosyl-(1----3)-O-beta-D-xylopyranosyl-(1----4)-O- alpha-L-rhamnopyranosyl-(1----2)-alpha-L-arabinopyranosyl] ester, E is a 28-O-[O-alpha-L-arabinopyranosyl-(1----3)-O-beta-D-xylopyranosyl-( 1----4)-O-alpha-L-rhamnopyranosyl-(1----2)-alpha-L-arabinopyranosyl] ester, F is a 28-O-[O-beta-D-xylopyranosyl-(1----3)-[O-beta-D-xylopyranosyl-(1----4)-O -alpha-L-rhamnopyranosyl-(1----2)-alpha-L-arabinopyranosyl] ester, and G is a 28-O-beta-D-xylopyranosyl-(1----3)-[O-alpha-L-arabinopyranosyl-(1- ---3)-O-beta-D-xylopyranosyl-(1----4)]-O-alpha-L- rhamnopyranosyl-(1----2)-alpha-L-arabinopyranosyl] ester. Acutoside C is a machaelinic acid (=21 beta-hydroxyoleanolic acid) saponin having the same sugar moiety as that of acutoside B.

The aqueous extract of Albizzia anthelmintica bark at 10-150 g/kg orally showed no toxicity and high anthelmintic activity (68-100%) against experimental Hymenolepis diminuta infection in albino rats. The water extract from A. lebbek bark at 10-100 g/kg orally was less effective against the cestode and was toxic to rats at the highest dose tested (150 g/kg).

A microdilution technique was developed for the assessment of in vitro cytotoxicity against KB cells derived from a human epidermoid carcinoma of the nasopharynx. The test was used to determine the cytotoxicity of a series of quassinoids, isolated from Brucea javanica, and which have previously been shown to demonstrate activity against Plasmodium falciparum. The 50% effective dose (ED50) for 7 quassinoids tested against KB ranged from 0.008 microgram/ml for bruceantin, the most cytotoxic of the compounds tested to greater than 5 micrograms/ml for bruceolide, the least toxic tested. The activities of the quassinoids against KB did not parallel the known activities of the quassinoids against Plasmodium falciparum suggesting that the quassinoid mode of antimalarial action is not a simple cytotoxic effect and lends support to further investigation of the structure activity relationships within this group of compounds.

The analgesic principles from Aralia cordata Thunb, were identified with (ent)-kaur-16-en-19-oic acid (KA) and (ent)-pimara-8(14),15-dien-19-oic acid (PA), respectively. Both compounds were significantly effective regarding analgesics, hypothermia, duration of pentobarbital-induced anesthesia, and depression of locomotor activity enhanced by methamphetamine at doses of 300 mg/kg (KA) and 500 mg/kg (PA) by oral administration.

The role of the substituents at C3 and C8 of jesaconitine (1) on jesaconitine-induced analgesia and toxicity was examined. 3-O-Acetyljesaconitine (2), 3-O-anisoyljesaconitine (3), and 3-deoxyjesaconitine (6) showed dose-dependent analgesic action, and the potency of their compound-induced analgesia and toxicity was lower than those of 1. The most remarkable difference was found in the toxicity. The results indicate that the C3 hydroxy function of 1 participate in the induction of toxicity rather than of analgesia. 8-O-Linoleoyl-14-anisoylaconine (5), 8-O-methyl-14-anisoylaconine (7), 8-O-ethyl-14-anisoylaconine (8), 14-anisoylaconine (4) and 8-deoxy-14-anisoylaconine (9) showed lower activities than jesaconitine-induced analgesia and toxicity. The analgesic activity of 7 was almost the same as that of 8, but the toxicity of 7 was lower than that of 8. The analgesic activity of 9 was lower than that of 4, but the toxicities of both derivatives were not apparent. These facts indicate that the C8 function of 1 is important to the induction of analgesia and toxicity, and also that this function participates differently in the induction of the analgesia and toxicity. Subsequently, it was suggested that substituents at C3 and C8 of 1 played important roles of the induction of the analgesia and toxicity, and that the modes of this participation were not the same in analgesia and toxicity.

Acridone alkaloids isolated from plants of the family Rutaceae have antiplasmodial activity in rodent models of malaria. Because a variety of antimalarial agents have also been shown to have activity against Pneumocystis carinii, we tested six of these alkaloids in an established culture model for P. carinii. Atalaphillinine and glycobismine A inhibited growth of cultured P. carinii at concentrations of 2.7 and 1.7 microM, respectively. This potency of effect is similar to that of chloroquine (3 microM) but somewhat less than that of primaquine (0.4 microM), which was previously evaluated in the same system.

Echinacea belongs to the most usable plants in medical treatment since many years. It is applicable in the fields of homoepathy and allopathy, however, there are many different ways of treatment. Two species are listed in the European Pharmacopoea: Echinacea angustifolia and Echinacea purpurea. They differ in morphology and their chemical composition. There have been chemical and biological analyses of Echinacea for about 80 years. After exact investigations of these reports, the following result were found: Most chemical analyses were done with Echinacea angustifolia, especially the older ones, whereas biological activity was tested with Echinacea purpurea. In almost all of these experiments, proprietaries were preferred to use in contrast to any plant extracts. Most of the reports, which declared the stimulating biological activity of Echinacea could not resist any critical opinion. So the frequency of medical application of this drug is mainly due to delivered practical knowledge. The experiments described in this study were practised with a water-soluble plant extract of Echinacea angustifolia. Echinacosid one of its low-molecular compounds and proprietaries which contains this plant. Their influence on the unspecified cellular immunity of the mouse after intraperitoneal, intravenous or peroral application was investigated. Under various conditions no effects on the immuno system could be found using the carbon clearance test.

The pharmacological effects of norathyriol on isolated rat thoracic aorta were examined. In the high-K+ (60 mM) medium, Ca2+ (0.03 to 3 mM)-induced vasocontraction was inhibited concentration dependently by norathyriol. Given as pretreatment norathyriol (20 to 200 microM) also inhibited the norepinephrine (NE, 3 microM)-induced tonic contraction. However, the phasic contraction was inhibited only by high concentrations of norathyriol (200 and 400 microM). The tonic contraction elicited by NE was also relaxed by the addition of norathyriol. This relaxing effect of norathyriol was not antagonized by methylene blue (50 microM) or indomethacin (20 microM) and was still seen in denuded rat aorta. Although the cAMP level was not changed by norathyriol, the cGMP level was increased by a high concentration of norathyriol (400 microM). [3H]Inositol monophosphate formation caused by NE was not affected by norathyriol at concentration of either 100 or 400 microM. The 45Ca2+ influx caused by either NE or high K+ was inhibited by norathyriol in a concentration-dependent manner. It is concluded that norathyriol relaxed the rat thoracic aorta mainly by suppressing the Ca2+ influx through both voltage-dependent and receptor-operated calcium channels.

A thermospray high-performance liquid chromatography-mass spectrometry method for analysis of hyoscyamine and scopolamine in plant cell culture samples is described. The alkaloids were separated on a polymeric reversed-phase column with an alkaline ammonium acetate buffer-acetonitrile eluent. Selected-ion recording of the protonated molecular ions was used for quantitation of the compounds. The compounds were fragmented by discharge-assisted ionization and elevated thermospray capillary temperatures or ion repeller potentials.

The four major C-glycosidic flavonoids isolated from Passiflora incarnata were identified as schaftoside, isoschaftoside, isovetexin-2''-O-glucopyranoside and isoorientin-2''-O-glucopyranoside on the basis of mass spectral and 13C NMR data. The daughter ion spectra of [M + H]+ ions of schaftoside and isoschaftoside showed differences for the [M + H - 104]+ ions, which could be rationalized by hydrogen bonding effects. In the negative-ion mode, pronounced differences were found for the [M - H - 90]- and [M - H - 120]- ions, formed by prevalent fragmentation in the C-6-linked sugar moiety. With respect to isovitexin-2''-O-beta-glucopyranoside and isoorientin-2''-O-beta-glucopyranoside, the daughter ion spectra of both the [M + H]+ and [M - H]- ions provided evidence for a 1----2 linkage in the diglucosidic moiety. Support for C-6 glucosylation was obtained by recording the daughter ion spectra of [M - H - 162]- ions, which were in good agreement with that obtained for [M - H]- ions of isovitexin.

The effect of nine dibenzo[a,c]cyclooctene lignans isolated from Fructus schizandrae on in vitro and in vivo lipid peroxidation of liver microsomes as well as on anti-oxidative enzyme activities were studied. Seven of the nine lignans (1 mM) were shown to inhibit Vit C/NADPH induced lipid peroxidation (malondialdehyde (MDA) formation) of rat liver microsomes. Of these compounds, schisanhenol (Sal), S(-)schizandrin C (S(-)sin C) and S(-)schizandrin B (S(-)sin B) were shown to be more potent than Vit E at the same concentration. Sal and Sin B were able to inhibit gossypol-induced superoxide anion generation in rat liver microsomes. In addition, oral administration of Sal and Sin B markedly reduced liver MDA formation induced by ethanol, 15 ml/kg in mice, and increased superoxide dismutase and catalase activities in rat liver cytosol. The data of this paper are in favor of the conclusion that some lignans, like Sal, have strong anti-oxidant activity. The mechanisms of anti-oxidant activity of the lignans were discussed.

Inhibitory effects of magnosalin and magnoshinin, compounds from the crude drug "Shin-i" (Flos magnoliae), on angiogenesis and pouch granuloma formation in mice induced by an adjuvant containing croton oil were investigated. The anti-chronic inflammatory effect of "shin-i" was caused by selective inhibition of angiogenesis by magnosalin and of granuloma formation by magnoshinin.

From the bark of Uncaria guianensis, two new quinovic acid glycosides, quinovic acid 3 beta-O-beta-D-quinovopyranoside and quinovic acid 3 beta-O-beta-D-fucopyranosyl-(27----1)-beta-D-glucopyranosylester, have been isolated, in addition to known quinovic acid 3 beta-O-[beta-D-glucopyranosyl-(1----3)-beta-D-fucopyranosyl]-(27----1)- beta-D-glucopyranosylester and quinovic acid 3 beta-O-beta-D-fucopyranoside. Their structures were elucidated by spectral and chemical studies.

1. The effects of the oxyaporphine alkaloid thalicminine on guinea-pig isolated ileum, trachea, aorta and pulmonary artery and on blood pressure and heart rate of anesthetized guinea-pigs were studied. 2. Thalicminine (1-300 microM) caused the relaxation of the longitudinal ileal segments. The relaxation induced by 300 microM was followed by vigorous contractions. 3. Thalicminine caused only mild relaxation of the trachea. 4. Thalicminine (0.3-300 microM) caused concentration-dependent relaxation of epinephrine-precontracted aorta and main pulmonary artery. 5. Propranolol (1 microM) failed to reduce the relaxation or to affect the EC50 value of thalicminine on the ileum or the pulmonary artery. 6. Quinacrine (10 microM), on the other hand, potentiated thalicminine-induced relaxation and reduced the EC50 on the aorta and the pulmonary artery suggesting the interference of thalicminine with arachidonic acid metabolism. 7. In anesthetized animals, intravenous injections of 0.37-1.1 mg kg of thalicminine caused transient reduction of systolic and diastolic blood pressure and heart rate. Both parameters returned to their normal values in about 10 min.

From a cytotoxic Et2O-soluble extract of Muntingia calabura roots, twelve new flavonoids were isolated, constituting seven flavans 1-7, three flavones 8, 10, and 12, and two biflavans 9 and 11. The structures of compounds 1-12 were established by the interpretation of spectral data, with the nmr assignments of these constituents being based on 1H-1H COSY, 1H-13C HETCOR, and selective INEPT experiments. This is the first report of the occurrence of 7,8-di-O-substituted flavans, biflavans, and flavones. Most of the isolates demonstrated cytotoxic activity when tested against cultured P-388 cells, with the flavans being more active than the flavones. Furthermore, certain of these structurally related flavonoids exhibited somewhat selective activities when evaluated with a number of human cancer cell lines.

Traditional experience calls for the skinning of Radix Adenophorae. Depending on the chemical compositions, this paper presents a comparative study on the skin, the radix with skin and the skinned radix. The experimental results show that the contents of beta-sitosterol, saponins, amino acids and trace elements are highest in the radix with skin, and that the radix with skin and the skinned radix are similar in the contents of polysaccharides.

Four new bisdesmosidic saponins each containing eight carbohydrate units were isolated from Solidago canadensis. GC, GC-MS, FABMS analysis and mainly the use of 2D NMR techniques allowed their identification as bayogeninglycosides (canadensissaponins 1-4) 3-O- [beta-D-glucopyranosyl-(1----3)-beta-D-glucopyranosyl]-28-O-[alpha-L- rhamnopyranosyl-(1----3)-beta-D-xylopyranosyl-(1----4)-[beta-D- xylopyranosyl-(1----3)]-alpha-L-rhamnopyranosyl-(1----2)-[beta-D- apio-D-furanosyl-(1----3)]-beta-D-6-deoxyglucopyranosyl- (1----]-bayogenin; -(1----2)-[beta-D-apio-D-furanosyl-(1----3)]-ara- binopyranosyl-(1----]-bayogenin; -[alpha-L-rhamnopyranosyl-(1----3)]-beta- D-6-deoxyglucopyranosyl-(1----]-bayogenin and - [alpha-L-rhamnopyranosyl- (1----3)]-arabinopyranosyl-(1----]-bayogenin.

Many bioactive phytochemicals have been shown in recent years to be photosensitizers, i.e. their toxic activities against viruses, micro-organisms, insects or cells are dependent on or are augmented by light of certain wavelengths. These activities are often selective, and this has led to the concept of therapeutic prospects in the control of infectious diseases, pests and cancer. Reaction mechanisms commonly involve singlet oxygen and radicals, which are thought to cause photodamage to membranes or macromolecules. The main classes of plant photosensitizers reviewed here are polyyines (acetylenes, thiophenes and related compounds); furanyl compounds; beta-carbolines and other alkaloids; and complex quinones. We propose that within each group of phytochemicals there are several representatives that merit further study for therapeutic abilities in appropriate animal models.