TY  - JOUR
A1  - Montoya Peláez, Guillermo L.
A1  - Sierra, Jelver A.
A1  - Alzate, Fernando
A1  - Holzgrabe, Ulrike
A1  - Ramirez-Pineda, José R.
T1  - Pentacyclic triterpenes from Cecropia telenitida with immunomodulatory activity on dendritic cells
JF  - Revista Brasileira de Farmacognosia - Brazilian Journal of Pharmacognosy
N2  - Pentacyclic triterpenes are a large family of plant metabolites that exhibit a wide array of biological activities. The genus Cecropia, which encompasses many plant species, has been used as traditional medicine for the treatment of inflammatory diseases and is known to produce many active pentacyclic triterpenes. In this study we investigated the chemical composition of a pentacyclic triterpene fraction from the roots of Cecropia telenitida Cuatrec., Urticaceae. A novel compound, which we termed yarumic acid, and four known molecules (serjanic acid, spergulagenic acid A, 20-hydroxy-ursolic acid and goreishic acid I) were isolated and characterised. In a dendritic cell (DC)-based assay, we demonstrated that non-toxic doses of these pentacyclic triterpenes inhibited the secretion of at least one of the proinflammatory cytokines tested (IL-1 beta, IL-12p40, IL-12p70, TNF-alpha). Spergulagenic acid A also inhibited nitric oxide production in lipopolysaccharide-stimulated dendritic cell. Serjanic acid and spergulagenic acid A, which were the most potent abundant compounds in the pentacyclic triterpene fraction, showed the most activity in the dendritic cell-based assay. These results show that all pentacyclic triterpenes might contribute to the anti-inflammatory activities of C. telenitida. Moreover, yarumic acid as well as the four known pentacyclic triterpenes, can be exploited as potential immunomodulatory/anti-inflammatory agents.
KW  - psidium guajava;
KW  - oleanane saponins
KW  - kappa-B activation
KW  - cytokine production
KW  - chenopodium quinoa
KW  - obtusifolia bertol
KW  - nitric oxide
KW  - ursolic acid
KW  - bone marrow
KW  - macrophages
KW  - pentacyclic triterpene
KW  - dendritic cells
KW  - anti-inflammatory activity
KW  - cytokine modulation
KW  - natural product
KW  - cecropia telenitida
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131851
VL  - 23
ER  - 
TY  - JOUR
A1  - Firdessa, Rebuma
A1  - Good, Liam
A1  - Amstalden, Maria Cecilia
A1  - Chindera, Kantaraja
A1  - Kamaruzzaman, Nor Fadhilah
A1  - Schultheis, Martina
A1  - Röger, Bianca
A1  - Hecht, Nina
A1  - Oelschlaeger, Tobias A.
A1  - Meinel, Lorenz
A1  - Lühmann, Tessa
A1  - Moll, Heidrun
T1  - Pathogen- and host-directed antileishmanial effects mediated by polyhexanide (PHMB)
JF  - PLoS Neglected Tropical Diseases
N2  - Background 
Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. 

Methodology/Principal 
Findings Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. 

Conclusions 
Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators.
KW  - resistance
KW  - activation
KW  - dendritic cells
KW  - Cutaneous leishmaniasis
KW  - topical treatment
KW  - biocide polyhexamethylene biguanide
KW  - experimental visceral leishmaniasis
KW  - drug-delivery systems
KW  - therapy
KW  - paromomycin
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148162
VL  - 9
IS  - 10
ER  -