Antimalarial drug discovery: old and new approaches.
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New drugs against malaria are greatly needed. Many approaches to antimalarial drug discovery are available. These approaches must take into account specific concerns, in particular the requirement for very inexpensive and simple to use new therapies and the need to limit the cost of drug discovery. Among important efforts that are currently ongoing are the optimization of therapy with available drugs, including the use of combination therapy, the development of analogs of existing agents, the discovery of natural products, the use of compounds that were originally developed against other diseases, the evaluation of drug resistance reversers, and the consideration of new chemotherapeutic targets. The last category benefits from recent advances in malaria research technologies and genomics and is most likely to identify new classes of drugs. A number of new antimalarial therapies will likely be needed over the coming years, so it is important to pursue multiple strategies for drug discovery. (+info)
cis-hinokiresinol, a norlignan from Anemarrhena asphodeloides, inhibits angiogenic response in vitro and in vivo.
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cis-Hinokiresinol (CHR) is a norlignan constituent from Anemarrhena asphodeloides BUNGE (Liliaceae), which shows hyaluronidase inhibitory activity. In the present studies, we have demonstrated that CHR selectively inhibited endothelial cell proliferation compared with cancer cells, and especially basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation. Furthermore, endothelial cell migration and tube formation, two important steps in the angiogenic process, were also inhibited by CHR. Moreover, CHR reduced the vessel growth induced by VEGF in the mouse corneal neovascularization model. These results suggest that CHR may prove useful for the development of a novel angiogenesis inhibitor. (+info)
Screening of the inhibitory effect of vegetable constituents on the aryl hydrocarbon receptor-mediated activity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
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The aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear transcription factor that mediates responses to environmental contaminants such as dioxins, which have many adverse health effects. We performed a preliminary screening of the inhibitory effects of vegetable constituents on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of AhR using the AhR-based bioassay for dioxins, the Ah-Immunoassay. Ninety vegetable constituents including flavonoids, tannins, saponins, terpenes, etc., were assayed in vitro. Among them, flavones, flavonols, anthraquinones, piperine, coumestrol, brevifolincarboxylic acid, and resveratrol showed marked inhibitory effects on AhR-based bioassay activation by TCDD, and their effects were dose dependent. Curcumin, carnosol, and capsaicin also inhibited the activation of AhR in this assay, although to a lesser degree. These results suggest that several vegetable constituents might play a role in protection against dioxin toxicity. (+info)
The pharmacognosy of Humulus lupulus L. (hops) with an emphasis on estrogenic properties.
(4/15)
As the population ages, there is an ever-increasing need for therapeutic agents that can be used safely and efficaciously to manage symptoms related to postmenopausal estrogen deficiency. Endogenous estrogens, e.g., 17beta-estradiol, of exogenous mammalian origin, e.g., horses, have long been used to manage such symptoms. There are more than 20 different classes of phytochemicals that have demonstrated affinity for human estrogen receptors in vitro. Some studies on exogenous estrogenic substances of botanical origin (phytoestrogens), such as standardized formulations of plant extracts with in vitro and in vivo estrogenic activity from soy (Glycine max Merill.) and red clover (Trifolium pratense L.), suggest clinical efficacy. Few clinical data for phytoestrogens other than isoflavonoids are available. In an exhaustive review of the literature through 2003, only two clinical trials were identified that were designed to evaluate the effect of hops (Humulus lupulus L.) on symptoms related to menopause. Folkloric, chemical, and biological literature relating primarily to the use of hops for their estrogenic activity, and two human clinical trials, are reviewed. (+info)
Healing with animals in the Levant from the 10th to the 18th century.
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Animals and products derived from different organs of their bodies have constituted part of the inventory of medicinal substances used in various cultures since ancient times. The article reviews the history of healing with animals in the Levant (The Land of Israel and parts of present-day Syria, Lebanon, and Jordan, defined by the Muslims in the Middle Ages as Bilad al-Sham) in the medieval and early Ottoman periods. Intensive research into the phenomenon of zootherapy in the medieval and early Ottoman Levant has yielded forty-eight substances of animal origin that were used medicinally. The vast majority of these substances were local and relatively easy to obtain. Most of the substances were domestic (honey, wax, silkworm, etc.), others were part of the local wildlife (adder, cuttle fish, flycatcher, firefly, frog, triton, scorpion, etc.), part of the usual medieval household (milk, egg, cheese, lamb, etc.), or parasites (louse, mouse, stinkbug, etc.). Fewer substances were not local but exotic, and therefore rare and expensive (beaver testicles, musk oil, coral, ambergris, etc.). The range of symptoms that the substances of animal origin were used to treat was extensive and included most of the known diseases and maladies of that era: mainly hemorrhoids, burns, impotence, wounds, and skin, eye, and stomach diseases. Changes in the moral outlook of modern societies caused the use of several substances of animal origin to cease in the course of history. These include mummy, silkworm, stinkbug, scarabees, snail, scorpion, and triton. (+info)
A systematic study on confused species of Chinese materia medica in the Hong Kong market.
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As more and more people worldwide begin using Chinese herbs, authentication of these herbs becomes an increasingly critical, international problem. Mistakes, misidentification, or willful deception can cause illness and even death. Questionable authenticity with regard to Chinese herbs arises for a number of historical, geographical and nomenclatural reasons, which will be described in this paper. The current situation in the Hong Kong market and some suggestions for alleviating the problem are also discussed. (+info)
In silico target fishing for rationalized ligand discovery exemplified on constituents of Ruta graveolens.
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Synthetic analogs of natural glycosides in drug discovery and development.
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Secondary metabolites, which have vital environmental and allelopathic functions for a host, and long tradition of ethnopharmacological applications preceding modern medicinal use, often occur in their native state as glycosides. The role of sugar moiety looks completely different from plant physiology point of view and from drug discovery and development perspective. Based on a short survey of cases, in which structural modification of natural glycone (saccharide part of a low molecular weight secondary metabolite) resulted in advantageous pharmacological changes, we postulate that glycosides of natural origin can be quite promising as drug leads, based on general rules of drug design. In particular, polyfunctional sugar moieties offer ample opportunities for almost continuous changes in shape, electron density and polarity. By the same token, glycosylation of other biologically active natural products, which are not natively glycosylated, can be viewed as a tool for tune up of their activity in direction of higher efficacy and better selectivity. Despite of considerable advances towards turning enzymatic glycosylations into biotechnological processes, chemical transformations still remain more practical, particularly for synthesis of modified glycosides, both: in research laboratory and in industry. (+info)