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Molecules 2018, 23(7), 1674; https://doi.org/10.3390/molecules23071674

Efficacy of Prosopilosidine from Prosopis glandulosa var. glandulosa against Cryptococcus neoformans Infection in a Murine Model

1
National Center for Natural Product Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA
2
Faculty of Pharmacy, Al-Azhar University, Cairo 11651, Egypt
3
Department of Arts and Sciences, Keiser University, 2085 Vista Pkwy, West Palm Beach, FL 33411, USA
4
Department of Pharmacy, University of Rajshahi, Rajshahi 6205, Bangladesh
*
Authors to whom correspondence should be addressed.
Received: 1 June 2018 / Revised: 29 June 2018 / Accepted: 6 July 2018 / Published: 10 July 2018
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Abstract

In this study, 2,3-dihydro-1H-indolizinium alkaloid-prosopilosidine (PPD), that was isolated from Prosopis glandulosa, was evaluated against C. neoformans in a murine model of cryptococcosis. In vitro and in vivo toxicity of indolizidines were also evaluated. Mice were infected via the tail vein with live C. neoformans. Twenty-four hours post-infection, the mice were treated with PPD once a day (i.p.) or twice a day (bid) orally, or with amphotericin B (Amp B) intraperitoneally (IP), or with fluconazole (Flu) orally for 5 days. The brains of all of the animals were aseptically removed and the numbers of live C. neoformans were recovered. In vitro toxicity of indolizidine alkaloids was determined in HepG2 cells. PPD showed to be potent in vivo activity against C. neoformans at a dose of 0.0625 mg/kg by eliminating ~76% of the organisms compared to ~83% with Amp B (1.5 mg/kg). In addition, PPD was found to be equally efficacious, but less toxic, at either 0.125 or 0.0625 mg/kg compared to Amp B (1.5 mg/kg) when it was administered bid (twice a day) by an i.p. route. When tested by an oral route, PPD (10 mg/kg) showed potent activity in this murine model of cryptococcosis with ~82% of organisms eliminated from the brain tissue, whereas Flu (15 mg/kg) reduced ~90% of the infection. In vitro results suggest that quaternary indolizidines were less toxic as compared to those of tertiary bases. PPD (20 mg/kg) did not cause any alteration in the plasma chemistry profiles. These results indicated that PPD was active in eliminating cryptococcal infection by oral and i.p. routes at lower doses compared to Amp B. or Flu. View Full-Text
Keywords: Cryptococcus neoformans; cryptococcosis; HepG2; Prosopis glandulosa; prosopilosidine; amphotericin B; fluconazole Cryptococcus neoformans; cryptococcosis; HepG2; Prosopis glandulosa; prosopilosidine; amphotericin B; fluconazole
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Ashfaq, M.K.; Abdel-Bakky, M.S.; Tahir Maqbool, M.; Samoylenko, V.; Abdur Rahman, A.; Muhammad, I. Efficacy of Prosopilosidine from Prosopis glandulosa var. glandulosa against Cryptococcus neoformans Infection in a Murine Model. Molecules 2018, 23, 1674.

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