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1.
Phytother Res ; 29(4): 582-90, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25640812

ABSTRACT

Kava is a soporific, anxiolytic and relaxant in widespread ritual and recreational use throughout the Pacific. Traditional uses of kava by indigenous Pacific Island peoples reflect a complex pharmacopeia, centered on GABA-ergic effects of the well-characterized kavalactones. However, peripheral effects of kava suggest active components other than the CNS-targeted kavalactones. We have previously shown that immunocytes exhibit calcium mobilization in response to traditionally prepared kava extracts, and that the kavalactones do not induce these calcium responses. Here, we characterize the complex calcium-mobilizing activity of traditionally prepared and partially HPLC-purified kava extracts, noting induction of both calcium entry and store release pathways. Kava components activate intracellular store depletion of thapsigargin-sensitive and -insensitive stores that are coupled to the calcium release activated (CRAC) current, and cause calcium entry through non-store-operated pathways. Together with the pepper-like potency reported by kava users, these studies lead us to hypothesize that kava extracts contain one or more ligands for the transient receptor potential (TRP) family of ion channels. Indeed, TRP-like conductances are observed in kava-treated cells under patch clamp. Thus TRP-mediated cellular effects may be responsible for some of the reported pharmacology of kava.


Subject(s)
Calcium Signaling/drug effects , Calcium/metabolism , Kava/chemistry , Plant Extracts/pharmacology , Transient Receptor Potential Channels/metabolism , Animals , Cell Line, Tumor , Chromatography, High Pressure Liquid , Ligands , Patch-Clamp Techniques , Rats , Thapsigargin/chemistry
2.
J Ethnopharmacol ; 51(1-3): 29-38, 1996 Apr.
Article in English | MEDLINE | ID: mdl-9213624

ABSTRACT

Natural products research continues to provide a tremendous variety of lead structures which are used as templates for the development of new drugs by the pharmaceutical industry. Advances in bioassay technology and in chemical methodology have combined to make natural products a cost effective source for new leads. While microbial products have been the mainstay of industrial natural products discovery, in recent years phytochemistry has again become a field of active interest. Drug discovery programs based on microbial products and phytochemicals are discussed and contrasted.


Subject(s)
Drug Evaluation, Preclinical , Drug Industry , Pharmacognosy , Animals , Biological Assay , Culture Techniques , Drug Evaluation, Preclinical/economics , Drug Evaluation, Preclinical/methods , Drug Industry/economics , Drug Industry/methods , Drug-Related Side Effects and Adverse Reactions , Humans , Investigational New Drug Application , Pharmaceutical Preparations/isolation & purification , Pharmacognosy/economics , Pharmacognosy/methods , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/toxicity , Plants, Medicinal/chemistry , Research , Specimen Handling , United States , United States Food and Drug Administration
3.
J Nat Prod ; 58(9): 1325-57, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7494142

ABSTRACT

Until recently, the prevailing attitude in developed nations regarded the world's genetic resources, which are mainly concentrated in the developing world, as a common resource of humankind, to be exploited freely irrespective of national origin. With the devastation being wreaked in the tropical rainforests and the resurgence in interest in recent years in the discovery of novel drugs from natural sources, particularly plants and marine organisms, the international scientific community has realized that the conservation of these global genetic resources and the indigenous knowledge associated with their use are of primary importance if their potential is to be fully explored. With this realization has come a recognition that these goals must be achieved through collaboration with, and fair and equitable compensation of, the scientists and communities of the genetically rich source countries. The signing of the United Nations Convention on Biological Diversity by nearly all of the World's nations has emphasized the need for the implementation of such policies. In this review, the articles of the Convention of relevance to the activities and practices of the natural products scientific community are briefly discussed. This discussion is followed by a summary of policies for international collaboration and compensation being implemented by several developed country organizations, and the perspectives on the current developments given by representatives of some of the source countries located in the regions of greatest biodiversity.


Subject(s)
Biological Products/isolation & purification , Bioethics , Drug Industry , Ecosystem , International Cooperation , Plants, Medicinal , United Nations , United States
4.
J Nat Prod ; 57(6): 755-60, 1994 Jun.
Article in English | MEDLINE | ID: mdl-7931364

ABSTRACT

gamma-Pyrone-3-acetic acid (L-741,494) is a novel metabolite produced by a culture of the fungal genus Xylaria. This substance is a water-soluble, competitive, irreversible inhibitor of Interleukin-1 beta Converting Enzyme that is inactive against papain and trypsin. It has a mol wt of 154 and an empirical formula of C7H6O4. We propose the name xylaric acid for this compound.


Subject(s)
Acetates/pharmacology , Cysteine Endopeptidases/chemistry , Metalloendopeptidases/chemistry , Pyrones/pharmacology , Xylariales/metabolism , Acetates/chemistry , Acetates/isolation & purification , Amino Acid Sequence , Caspase 1 , Chromatography, Ion Exchange , Magnetic Resonance Spectroscopy , Molecular Sequence Data , Pyrones/chemistry , Pyrones/isolation & purification
5.
J Nat Prod ; 57(2): 230-5, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8176399

ABSTRACT

Curcuma comosa is a member of the economically important plant family, Zingiberaceae. A methanolic extract of C. comosa was shown to be nematocidal when tested against the free-living nematode Caenorhabditis elegans. Five diphenylheptanoids [1-5], one new and four known, have been isolated and shown to be responsible for the activity. This is the first report of three of these compounds [1, 2, 4] being isolated from a natural source.


Subject(s)
Antinematodal Agents/isolation & purification , Curcumin/analogs & derivatives , Curcumin/isolation & purification , Plants/chemistry , Animals , Antinematodal Agents/analysis , Antinematodal Agents/toxicity , Caenorhabditis elegans/drug effects , Curcumin/analysis , Curcumin/toxicity , Magnetic Resonance Spectroscopy , Mass Spectrometry , Plant Extracts/analysis , Plant Extracts/toxicity , Spectrophotometry, Ultraviolet
7.
J Ethnopharmacol ; 24(1): 41-91, 1988 Sep.
Article in English | MEDLINE | ID: mdl-3059068

ABSTRACT

The ethnobotany, ethnopharmacology and phytochemistry of the Thymelaeaceae are reviewed. Some members of this family find wide use commercially whilst others are used as deadly poisons or possess extreme irritant properties. The phytochemical evidence thus far available indicates that the daphnane and tigliane diterpene esters are clearly responsible for the toxic reactions observed, but chemotaxonomically it is not possible to predict which additional genera are likely to contain these toxins. Caution should therefore be exercised when studying members of this plant family.


Subject(s)
Medicine, Traditional , Plants, Medicinal , Animals , Drug-Related Side Effects and Adverse Reactions , Humans , Pharmaceutical Preparations/isolation & purification
8.
J Nat Prod ; 47(2): 270-8, 1984.
Article in English | MEDLINE | ID: mdl-6736968

ABSTRACT

The acetone and methanol extracts of Gnidia kraussiana roots displayed activity against the P-388 lymphocytic leukemia. Bioactivity-directed fractionation led to the isolation of five daphnane orthoesters , all possessing potent antineoplastic activity. Four of these isolates, gnidilatin (1), gnidilatidin (2), Excoecaria toxin (3), and Pimelea factor P2 (4) have been isolated previously from plants in the Thymelaeaceae and Euphorbiaceae. The fifth compound, kraussianin (5), is a new member of the macrocyclic daphnane orthoester series of compounds.


Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Plants, Medicinal/analysis , Animals , Cell Line , Chemical Phenomena , Chemistry , Leukemia P388/drug therapy , Mice , Plant Extracts/pharmacology
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