Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
J Biol Chem ; 290(52): 31138-50, 2015 Dec 25.
Article in English | MEDLINE | ID: mdl-26546678

ABSTRACT

Cystine knot α-amylase inhibitors are cysteine-rich, proline-rich peptides found in the Amaranthaceae and Apocynaceae plant species. They are characterized by a pseudocyclic backbone with two to four prolines and three disulfides arranged in a knotted motif. Similar to other knottins, cystine knot α-amylase inhibitors are highly resistant to degradation by heat and protease treatments. Thus far, only the α-amylase inhibition activity has been described for members of this family. Here, we show that cystine knot α-amylase inhibitors named alstotides discovered from the Alstonia scholaris plant of the Apocynaceae family display antiviral activity. The alstotides (As1-As4) were characterized by both proteomic and genomic methods. All four alsotides are novel, heat-stable and enzyme-stable and contain 30 residues. NMR determination of As1 and As4 structures reveals their conserved structural fold and the presence of one or more cis-proline bonds, characteristics shared by other cystine knot α-amylase inhibitors. Genomic analysis showed that they contain a three-domain precursor, an arrangement common to other knottins. We also showed that alstotides are antiviral and cell-permeable to inhibit the early phase of infectious bronchitis virus and Dengue infection, in addition to their ability to inhibit α-amylase. Taken together, our results expand membership of cystine knot α-amylase inhibitors in the Apocynaceae family and their bioactivity, functional promiscuity that could be exploited as leads in developing therapeutics.


Subject(s)
Alstonia/chemistry , Antiviral Agents , Coronavirus Infections/drug therapy , Dengue Virus , Dengue , Glycoside Hydrolase Inhibitors , Infectious bronchitis virus/drug effects , Plant Proteins , Alstonia/genetics , Animals , Antiviral Agents/chemistry , Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Chlorocebus aethiops , Coronavirus Infections/metabolism , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Glycoside Hydrolase Inhibitors/pharmacology , Infectious bronchitis virus/metabolism , Plant Proteins/chemistry , Plant Proteins/genetics , Plant Proteins/isolation & purification , Plant Proteins/pharmacology , Protein Structure, Tertiary , Vero Cells
2.
J Ethnopharmacol ; 125(3): 461-70, 2009 Sep 25.
Article in English | MEDLINE | ID: mdl-19619631

ABSTRACT

The uses of medicinal plants have always been part of human culture. The World Health Organization estimates that up to 80% of the world's population relies on traditional medicinal system for some aspect of primary health care. However, there are few reports on the toxicological properties of most medicinal plants especially, their mutagenicity and carcinogenicity. Therefore, this research is to determine the mutagenic potentials of Morinda lucida [Oruwo (Root)], Azadirachta indica [Dongoyaro (Leaf)], Terapluera tetraptera [Aridan (Fruit)], Plumbago zeylanica [Inabiri (Root)], Xylopia aethiopica [Erunje (Fruit)], Newbouldia laevis [Akoko (Leaf)], Alstonia boonei [Ahun (Bark)], Enantia chlorantha [Awopa (Bark)], and Rauvolfia vomitoria [Asofeyeje (Root)] using the Allium cepa Linn. model and the modified Ames assay. Allium cepa model was used to determine the mean root length, mitotic index and chromosomal aberrations effects of these plants on onion bulbs using 0.1, 1, 5 and 10mg/ml concentration of the plant extracts. The modified Ames test which is a modification of the standard Ames test as described by Ames et al. [Ames, B.N., McCann, J., Yamasaki, E., 1975. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test. Mutation Research 31, 347-364] was done using Escherichia coli (0157:H7) that has the phenotypic characteristics of glucose and lactose fermentation, motile, urease negative, indole positive and citrate negative. The results obtained from Allium cepa assay showed increasing root growth inhibition with increased concentration, decreasing mitotic index with increased concentration and chromosomal aberrations. The modified Ames test showed an alteration in the biochemical characteristics of Escherichia coli (0157:H7) for all plants except Rauvolfia vomitoria and Plumbago zeylanica. Three of the medicinal plants altered at least three of the normal biochemical characteristics thus demonstrating mutagenic potentials. The results of internationally accepted Allium cepa were comparable with the modified Ames test. However, a long term in vivo and dose dependent study should be carried out to validate these results and the findings should be communicated to drug and food regulatory body and also to the general public.


Subject(s)
Mutagens/pharmacology , Plants, Medicinal/chemistry , Alstonia/genetics , Animals , Azadirachta/genetics , Chromosome Aberrations/drug effects , Chromosomes, Plant/drug effects , Dose-Response Relationship, Drug , Humans , Medicine, African Traditional , Microsomes, Liver/metabolism , Mitotic Index , Morinda/genetics , Mutagenicity Tests/methods , Mutation , Nigeria , Onions/cytology , Onions/drug effects , Onions/genetics , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Plants, Medicinal/classification , Plumbaginaceae/genetics , Rats , Rats, Sprague-Dawley , Salmonella typhimurium/drug effects , Xylopia/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...