Revisiting the ancient concept of botanical therapeutics
Nature Chemical Biology 3, 360-366 (2007)
doi:10.1038/nchembio0707-360
Barbara M Schmidt1, David M Ribnicky1, Peter E Lipsky2 and Ilya Raskin1
Barbara M. Schmidt, David M. Ribnicky and Ilya Raskin are at Rutgers University, School of Environmental and Biological Sciences, Biotech Center, 59 Dudley Road, New Brunswick, New Jersey 08901, USA.
Email: raskin@AESOP.Rutgers.edu
Peter E. Lipsky is at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Autoimmunity Branch, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
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Mixtures of interacting compounds produced by plants may provide important combination therapies that simultaneously affect multiple pharmacological targets and provide clinical efficacy beyond the reach of single compound–based drugs. Developing innovative scientific methods for discovery, validation, characterization and standardization of these multicomponent botanical therapeutics is essential to their acceptance into mainstream medicine.
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Historically, natural products have provided an endless source of medicine, and despite the diversification of drug discovery technology and reduced funding for natural product–based drug discovery, natural products from plants and other biological sources remain an undiminished source of new pharmaceuticals. Indeed, even though industrial funding specifically allocated for natural product–based drug discovery declined from 1984 to 2003, the percentage of natural product–derived, small-molecule patents has remained relatively unchanged1. A comprehensive review of human drugs introduced since 1981 suggests that, out of 847 small-molecule drugs, 5% were natural products, 27% were derived from natural products (usually semisynthetically) and the remaining 572 were synthetic molecules2. However, 262 of the synthetic molecules had a natural product–inspired pharmacophore or could be considered natural-product analogs. Natural products continue to make the most dramatic impact in the area of cancer. Of 155 anticancer drugs developed since the 1940s only 27% could not be traced to natural products, with 47% being either a natural product or a direct derivation thereof2. Only one drug, the anticancer compound sorafenib, could be traced to completely de novo combinatorial chemistry2. The above analysis does not include biologics and vaccines, which are by definition derived from nature.
Why plants?
It is often noted that 25% of all drugs prescribed today come from plants3,4. This estimate suggests that plant-derived drugs make up a significant segment of natural product–based pharmaceuticals. Out of many families of secondary metabolites, or compounds on which the growth of a plant is not dependent, nitrogen-containing alkaloids have contributed the largest number of drugs to the modern pharmacopeia, ranging in effects from anticholinergics (atropine) to analgesics (opium alkaloids) and from antiparasitics (quinine) to anticholinesterases (galantamine) to antineoplastics (vinblastine/vincristine)5. Although not as plentiful as alkaloids in the modern pharmacopeia, terpenoids (including steroids) have made an equally important contribution to human health. They range from Na+/K+ pump-inhibiting cardiac glycosides from Digitalis spp. (recognized as a treatment for congestive heart failure by William Withering in 1775)6, to antineoplastic paclitaxel (Taxol, isolated from the Pacific yew in 1967 by Monroe E. Wall and Mansukh C. Wani)7 to antimalarial artemisinin8 (isolated by Tu Youyou in 1972, a component of Artemisia annua extract used for centuries in traditional Chinese medicine), to anti-inflammatory triptolide (isolated in 1972)9,10. Phenolics (mostly phenylpropanoids) contributed aspirin and podophyllotoxin to modern medicine. Figure 1 summarizes the most important structural classes of pharmacologically active secondary metabolites from plants. It is important to note, however, that the activity of some natural products has yet to be certified by extensive testing or clinical trials; we anticipate that these cases will benefit from the same rigorous attention as those described below for multicomponent botanical therapeutics (MCBTs).
Developing innovative scientific methods for discovery, validation, characterization and standardization of these multicomponent botanical therapeutics is essential to their acceptance into mainstream medicine.
哪里在做这方面的研究,有进展了吗?
Nature Chemical Biology 3, 360-366 (2007)
doi:10.1038/nchembio0707-360
Barbara M Schmidt1, David M Ribnicky1, Peter E Lipsky2 and Ilya Raskin1
Barbara M. Schmidt, David M. Ribnicky and Ilya Raskin are at Rutgers University, School of Environmental and Biological Sciences, Biotech Center, 59 Dudley Road, New Brunswick, New Jersey 08901, USA.
Email: raskin@AESOP.Rutgers.edu
Peter E. Lipsky is at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Autoimmunity Branch, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
--------------------------------------------------------------------------------
Mixtures of interacting compounds produced by plants may provide important combination therapies that simultaneously affect multiple pharmacological targets and provide clinical efficacy beyond the reach of single compound–based drugs. Developing innovative scientific methods for discovery, validation, characterization and standardization of these multicomponent botanical therapeutics is essential to their acceptance into mainstream medicine.
--------------------------------------------------------------------------------
Historically, natural products have provided an endless source of medicine, and despite the diversification of drug discovery technology and reduced funding for natural product–based drug discovery, natural products from plants and other biological sources remain an undiminished source of new pharmaceuticals. Indeed, even though industrial funding specifically allocated for natural product–based drug discovery declined from 1984 to 2003, the percentage of natural product–derived, small-molecule patents has remained relatively unchanged1. A comprehensive review of human drugs introduced since 1981 suggests that, out of 847 small-molecule drugs, 5% were natural products, 27% were derived from natural products (usually semisynthetically) and the remaining 572 were synthetic molecules2. However, 262 of the synthetic molecules had a natural product–inspired pharmacophore or could be considered natural-product analogs. Natural products continue to make the most dramatic impact in the area of cancer. Of 155 anticancer drugs developed since the 1940s only 27% could not be traced to natural products, with 47% being either a natural product or a direct derivation thereof2. Only one drug, the anticancer compound sorafenib, could be traced to completely de novo combinatorial chemistry2. The above analysis does not include biologics and vaccines, which are by definition derived from nature.
Why plants?
It is often noted that 25% of all drugs prescribed today come from plants3,4. This estimate suggests that plant-derived drugs make up a significant segment of natural product–based pharmaceuticals. Out of many families of secondary metabolites, or compounds on which the growth of a plant is not dependent, nitrogen-containing alkaloids have contributed the largest number of drugs to the modern pharmacopeia, ranging in effects from anticholinergics (atropine) to analgesics (opium alkaloids) and from antiparasitics (quinine) to anticholinesterases (galantamine) to antineoplastics (vinblastine/vincristine)5. Although not as plentiful as alkaloids in the modern pharmacopeia, terpenoids (including steroids) have made an equally important contribution to human health. They range from Na+/K+ pump-inhibiting cardiac glycosides from Digitalis spp. (recognized as a treatment for congestive heart failure by William Withering in 1775)6, to antineoplastic paclitaxel (Taxol, isolated from the Pacific yew in 1967 by Monroe E. Wall and Mansukh C. Wani)7 to antimalarial artemisinin8 (isolated by Tu Youyou in 1972, a component of Artemisia annua extract used for centuries in traditional Chinese medicine), to anti-inflammatory triptolide (isolated in 1972)9,10. Phenolics (mostly phenylpropanoids) contributed aspirin and podophyllotoxin to modern medicine. Figure 1 summarizes the most important structural classes of pharmacologically active secondary metabolites from plants. It is important to note, however, that the activity of some natural products has yet to be certified by extensive testing or clinical trials; we anticipate that these cases will benefit from the same rigorous attention as those described below for multicomponent botanical therapeutics (MCBTs).
Developing innovative scientific methods for discovery, validation, characterization and standardization of these multicomponent botanical therapeutics is essential to their acceptance into mainstream medicine.
哪里在做这方面的研究,有进展了吗?