title: In vitro antifungal activities of amphotericin B in combination with acteoside, a phenylethanoid glycoside from Colebrookea oppositifolia.
abstract: This study was undertaken to investigate the synergistic interaction between amphotericin B (AmB) and acteoside, isolated from the aerial parts of the shrub Colebrookea oppositifolia (Lamiaceae). Acteoside alone exhibited no intrinsic antifungal activity but showed a potent synergism in combination with AmB against selected pathogenic species, with fractional inhibitory concentration indices in the range of 0.0312-0.1562. The combination of acteoside at 3.12 and 12.5 µg ml(-1) with subinhibitory concentrations of AmB resulted in a potent fungicidal effect and also exhibited a significantly extended post-antifungal effect. Furthermore, the combination also reduced the minimum biofilm reduction concentration values of AmB (2-16-fold) in preformed biofilms of Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. There was decreased viability of the cells, increased uptake of propidium iodide and enhanced leakage of 260 nm-absorbing material by Candida albicans cells when exposed to AmB in the presence of acteoside. The reason for potentiation is likely to be that the subinhibitory concentrations of AmB facilitated the uptake of acteoside, which resulted in increased killing of the fungal cells. Administration of acteoside in mice at up to 2000 mg (kg body weight)(-1) by the intraperitoneal or oral route produced no overt toxicity. The data presented here support synergism between acteoside and AmB, and it is therefore proposed that a prospective new management strategy for therapeutic application of this combination should be explored.
authors.affiliation: Clinical Microbiology Division, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180 001, India.
authors.forename: Intzar
authors.initials: I
authors.lastname: Ali
authors.affiliation: Natural Product Chemistry Division, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180 001, India.
authors.forename: Punita
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Natural Product Chemistry Division, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180 001, India.
authors.forename: Krishan Avtar
authors.initials: KA
authors.lastname: Suri
authors.affiliation: Natural Product Chemistry Division, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180 001, India.
authors.forename: Naresh Kumar
authors.initials: NK
authors.lastname: Satti
authors.affiliation: Natural Product Chemistry Division, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180 001, India.
authors.forename: Prabhu
authors.initials: P
authors.lastname: Dutt
authors.affiliation: Department of Biotechnology, Faculty of Science, Hamdard University, Hamdard Nagar, New Delhi 110 062, India.
authors.forename: Farhat
authors.initials: F
authors.lastname: Afrin
authors.affiliation: Clinical Microbiology Division, Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180 001, India.
authors.forename: Inshad Ali
authors.initials: IA
authors.lastname: Khan
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects*; D003455:Cryptococcus neoformans / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*; D019686:Lamiaceae / Q000737:chemistry; D008297:Male; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*; D059808:Polyphenols
chemical_list: D000666:Amphotericin B; D000935:Antifungal Agents; D005960:Glucosides; D010636:Phenols; C058956:acteoside; D059808:Polyphenols