Current Topics in Medicinal Chemistry - Volume 3, Issue 2, 2003

Jalap, a pre-Hispanic herbal remedy still considered a useful laxative, is an ingredient in some over-the-counter products sold by herbalists in contemporary Mexico. The purgative crude drugs are prepared from the roots of several morning glories species which all have been identified as members of the Ipomoea genus (Convolvulaceae). Their incorporation as therapeutical agents into Europe is an outstanding example of the assimilation of botanical drugs from the Americas as substitutes for traditional Old World remedies. Phytochemical investigations on the resin glycosides, main constituents of these drugs, were initiated during the second half of the XIX century; however, the structures of their active ingredients had remained poorly known, and still are for some members of these purgative root species. Modern analytical techniques with higher resolution capabilities (HPLC) for the isolation of the active principles of these crude drugs used in conjunction with powerful spectroscopic methods (high field NMR) have facilitated the investigation of these relevant, to the herbal product market, convolvulaceous species during the last decade. The advantages and limitations of theses techniques will be discussed. This review will also describe the ethnobotanical information associated with the Mexican morning glory species and how the traditional usages of these plants have played an important role in the selection of these materials for chemical studies.Little is as yet known about either the mechanism of purge action caused by the resin glycosides or the ecological significance of these same compounds for the producing plants. Over the five centuries of Mexican herbal medicine, one hundred years of phytochemistry has only partially elucidated the active ingredients of the jalap roots but has exemplified how to further contemporary drug discoveries through the investigation of those plants traditionally held to be economically and medicinally important in developing countries.

A quantitative ethnobotanical approach to antimalarial drug discovery led to the identification of Lansium domesticum Corr. Ser. (Meliaceae) as an important antimalarial used by Kenyah Dyak healers in Indonesian Borneo. Triterpenoid lansiolides with antimalarial activity were isolated from the bark and shown to have activity in both in vitro bioassays with Plasmodium falciparum, and in mice infected with P. berghei. A survey of African and tropical American Meliaceae led to further development of the limonoid gedunin from the traditionally used medicinal plants, tropical cedar, Cedrela odorata L., and neem, Azadirachta indica A. Juss. Gedunin has significant in vitro activity but initially showed poor in vivo activity. In vivo activity was improved by (1) incorporation into an easy to absorb suspension, (2) preparation of a more stable compound, 7-methoxygedunin, and (3) synergism with dillapiol, a cytochrome P450 3A4 inhibitor. The results show the potential for both antimalarial drug and phytomedicine development from traditionally used plants.

Results of various projects on Mexican Indian ethnobotany and some of the subsequent pharmacological and phytochemical studies are summarised focusing both on chemical-pharmacological as well as anthropological (ethnopharmacological) aspects of our research. We have identified taste and smell properties of medicinal (vs. non-medicinal) plants as important indigenous selection criteria. There exist welldefined criteria specific for each culture, which lead to the selection of a plant as a medicine. This field research has also formed a basis for studies on bioactive natural products from selectedspecies. The bark of Guazuma ulmifolia showed antisecretory activity (cholera toxin-induced chloride secretion in rabbit distal colon in an USSING chamber). Active constituents are procyanidins with a polymerisation degree of eight or higher. Byrsonima crassifolia yielded proanthocyanidins with (+) epicatechin units and Baccharis conferta showed a dose-dependant antispasmodic effect with the effect being particularly strong in flavonoid-rich fractions. Our ethnopharmacological research led to the identification of sesquiterpene lactones (SLs) like parthenolide as potent and relatively specific inhibitors of the transcription factor NF-κB, an important mediator of the inflammatory process. The inhibitory effect of SLs is very strongly enhanced by the presence of such groups as the isoprenoid ring system, a lactone ring containing a conjugated exomethylene group (α- methylene-γ-lactone) and an α,β-unsaturated cyclopentenone or a conjugated ester moieties. Our work also elucidated the NF-κB inhibiting activity of the photosensitiser phaeophorbide A from Solanum diflorum (Solanaceae) in PMA induced HeLa cells. Hyptis verticillata yielded a series of lignans as well as sideritoflavone, rosmarinic acid and (R)-5-hydroxypyrrolidin-2-one and is rich in essential oil (rich in α- pinene, β-pinene and thymol). Other species investigated include Begonia heracleifolia, Crossopetalum gaumerii, Epaltes mexicana, Pluchea symphytifolia and Xanthosoma robustum.

The plant-derived terpenoids and analogues are reviewed with respect to their anti-HIV activity, structure-activity relationships, and mechanism of action. The active compounds include diterpenoid lactones, phenolic diterpenes, atisane and kaurane diterpenes, phorbol diterpenes, triterpene glycosides, friedelane triterpenes, taraxerane triterpenes, ursane triterpenes, lanostane triterpene, lupane triterpenes, seco-ring A triterpenes, degraded triterpenes, and cucurbitacin triterpenes. Positive new leads for drug development will be highlighted.

Natural products research has lately undergone exponential growth owing to advances in isolation techniques and in synthetic methods design, as well as for the identification of a wide range of biological properties exhibited by these compounds. In the present review, general remarks on the chemical features, biosynthetic pathways, isolation and structure elucidation of terpenoids are briefly discussed. In addition to this, recent work done on anti-inflammatory terpenoids (diterpenoids, triterpenoids and sesquiterpene lactones) with special emphasis on the last new molecular targets evaluated is presented.

Although St. John's wort has been known for thousands of years and has been used for a variety of medicinal purposes, understanding of its activity and mechanisms of action is relatively new and not well understood. While researchers originally thought the naphthodianthrone hypericin was responsible for Hypericum's antidepressant activity, it is now believed some other compound or a combination of constituents exerts their antidepressant activity on the body. Hypericum is unique in that it seems to impact all known neurotransmitters at some level, directly, or indirectly through receptor sensitivity and regulation.There has been a proliferation of clinical studies on Hypericum in the last ten years, and even though some of these studies might be methodologically flawed, the preponderance of the evidence proves Hypericum to be beneficial for the treatment of mild-to-moderate depression, with a very favorable side effect profile.One clinical trial carried out using two extracts with different hyperforin content indicate this constituent as (one of) the main active principle responsible for the antidepressant activity.

The seeds of Alpinia blepharocalyx K. Schum. (Zingiberaceae) is used in Chinese traditional medicine for the treatment of stomach disorders. From the ether fraction of a 95% ethanolic extract, which showed hepatoprotective and antiproliferative activities, we isolated 16 novel diarylheptanoids bearing a chalcone or a flavanone moiety [calyxins A-H, epicalyxins B-D, G, and H, 6-hydroxycalyxin F, and blepharocalyxins A and B] together with seven known compounds, while the residual fraction of the ethanolic extract gave 32 novel diarylheptanoids namely, calyxins A, E-G, and I-M, epicalyxins B, F, I-K, and M, deoxycalyxin A, blepharocalyxins C-E, neocalyxins A and B, (3S,5S)- and (3S,5R)-3-hydroxy-1-(4- hydroxyphenyl)-5-methoxy-7-phenyl-6E-heptene, (3S,5S)- and (3S,5R)-3-hydroxy-1-(4-hydroxyphenyl)-5- ethoxy-7-phenyl-6E-heptene, (3S)-3-methoxy-1,7-bis(4-hydroxyphenyl)-6E-hepten-5-one, 1,7-bis(4- hydroxyphenyl)-hepta-4E,6E-dien-3-one, (3S,7R)-5,6-dehydro-1,7-bis(4-hydroxy-phenyl)-4“-de-O-methylcentrolobine, (3S,5S,6S,7R)-5,6-dihydroxy-1,7-bis(4-hydroxyphenyl)-4“-de-O-me-thylcentrol obine, (3S,5R,6S,7R)- and (3S,5S,6R,7R)-5,6-dihydroxy-1,7-bis(4-hydroxyphenyl)-4“-de-O-methyl-centrol obine, 1,2- dihydro-bis(de-O-methyl)curcumin, and (3S,7S)-5,6-dehydro-4' ' -de-O-methylcentrolobine, and one known diarylheptanoid [(3S,5S)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane] together with 12 other known phenolic compounds. Moreover, in vitro NO inhibitory and antiproliferative activities of the isolated compounds were also tested and the active constituents identified.

Every country has its own traditional medicine system originated from ancient times. Vietnam, a Southeast Asian country, has a unique traditional medicine system. Several medicinal plants are still used by different ethnic societies of Vietnam for treating several diseases due to their easy availability. Combretum quadrangulare, Panax vietnamensis (Vietnamese Ginseng), Dracaena angustifolia (Nam Ginseng) and Orthosiphon stamineus are among the popular medicinal plants used in Vietnamese traditional medicine for curing various diseases and to improve physical strength. In this review article, we discuss the chemical analysis as well as biological activities of these Vietnamese medicinal plants in order to establish the relation between their therapeutic uses and scientific findings.