Ann N Y Acad Sci. 2005 Nov;1056:279-92.
Novel Drugs and Vaccines Based on the Structure and
Function of HIV Pathogenic Proteins Including Nef.
Faculty of Health Sciences, Medical School, University of Cape Town, Anzio Road, Observatory, 7925, Cape Town, South Africa.
Evidence is presented to suggest that HIV-1 accessory protein Nef could be involved in AIDS pathogenesis. When present
in extracellular medium, Nef
causes the death of a wide variety of cells in vitro and may therefore be
responsible for the depletion of bystander cells in lymphoid tissues during
HIV infection. When present inside the cell, Nef
could prevent the death of infected cells and thereby contribute to increased
viral load. Intracellular Nef does this by preventing
apoptosis of infected cells by either inhibiting proteins involved in
apoptosis or preventing the infected cells from being recognized by CTLs. Neutralization of extracellular
Nef could prevent the death of uninfected immune
cells and thereby the destruction of the immune system. Neutralization of
intracellular Nef could hasten the death of
infected cells and help reduce the viral load. Nef
is therefore a very important molecular target for developing therapeutics
that slow progression to AIDS. The N-terminal region of Nef
and the naturally occurring bee venom mellitin have
very similar primary and tertiary structures, and they both act by destroying
membranes. Chemical analogs of a mellitin inhibitor prevent Nef-mediated
cell death and inhibit the interaction of Nef with
cellular proteins involved in apoptosis. Naturally occurring bee propolis also contains substances that prevent Nef-mediated cell lysis and
increases proliferation of CD4 cells in HIV-infected cultures. These chemical
compounds and natural products are water soluble and nontoxic
and are therefore potentially very useful candidate drugs.
2: J Ethnopharmacol. 2005 Nov 14;102(2):158-63. Epub 2005 Jul
Anti-HIV-1 activity of propolis in CD4(+) lymphocyte and microglial
Gekker G, Hu S, Spivak M, Lokensgard JR, Peterson PK.
Neuroimmunology Laboratory, Minneapolis Medical
Research Foundation, Minneapolis, MN 55415, USA; Centre for Infectious Diseases
and Microbiology Translational Research, University of Minnesota Medical
School, Minneapolis, MN 55415, USA.
An urgent need for additional agents to treat human immunodeficiency virus
type 1 (HIV-1) infection led us to assess the anti-HIV-1 activity of the
natural product propolis in CD4(+)
lymphocytes and microglial cell cultures. Propolis inhibited viral expression in a
concentration-dependent manner (maximal suppression of 85 and 98% was
observed at 66.6mug/ml propolis in CD4(+) and microglial cell
cultures, respectively). Similar anti-HIV-1 activity was observed with propolis samples from several geographic regions. The
mechanism of propolis antiviral property in CD4(+) lymphocytes appeared to involve, in part,
inhibition of viral entry. While propolis had an
additive antiviral effect on the reverse transcriptase inhibitor zidovudine, it had no noticeable effect on the protease
inhibitor indinavir. The results of this in vitro
study support the need for clinical trials of propolis
or one or more of its components in the treatment of HIV-1 infection.
3: J Oral Sci. 2002 Mar;44(1):41-8.
Effect of commercial ethanol propolis
extract on the in vitro growth of Candida albicans collected
from HIV-seropositive and HIV-seronegative
Brazilian patients with oral candidiasis.
RS, Pereira ES Jr, Lima SM, Senna
RA, Santos VR.
of Clinical Pathology and Surgery, School
of Dentistry, Minas
Gerais Federal University,
The present study assessed the susceptibility of Candida albicans strains, collected from HIV-positive patients
with oral candidiasis, to a commercial 20% ethanol propolis extract (EPE) and compare it to the
inhibitory action of the standardized antifungal agents nystatin
(NYS), clotrimazole (CL), econazole
(EC), and fluconazole (FL). Twelve C. albicans strains collected from HIV-positive patients
with oral candidiasis were tested. The inhibition
zones were measured with a pachimeter and the
results are reported as means and standard deviation (M +/- SD). Data were
analyzed statistically by the non-parametric Kruskal-Wallis
test. EPE inhibited all the C. albicans strained
tested. No significant difference was observed between the results obtained
with NYS and EPE, while significant differences were observed between EPE and
other antifungals. The C. albicans
strains tested showed resistance to the remaining antifungal agents. The propolis extract used in this study inhibited the in
vitro growth of C. albicans collected from HIV-seropositive Brazilian patients, creating/forming
inhibition zones like those ones formed by NYS. This fact suggests that
commercial EPE could be an alternative medicine in the treatment of candidiasis from HIV-positive patients. However, in vivo
studies of the effect of EPE are needed to determine its possible effects on
the oral mucosa.
4: J Nat Prod. 2001 Oct;64(10):1278-81.
Anti-AIDS agents. 48.(1) Anti-HIV activity of
moronic acid derivatives and the new melliferone-related
triterpenoid isolated from Brazilian propolis.
Ito J, Chang FR, Wang HK, Park YK, Ikegaki M, Kilgore N, Lee KH.
Natural Products Laboratory, School
of Pharmacy, University of North Carolina, NC
A new triterpenoid named melliferone
(1), three known triterpenoids, moronic acid (2), anwuweizonic acid (3), and betulonic
acid (4), and four known aromatic compounds (5-8) were isolated from
Brazilian propolis and tested for anti-HIV activity
in H9 lymphocytes. Moronic acid (2) showed significant anti-HIV activity (EC(50) <0.1 microg/mL, TI
>186) and was modified to develop more potent anti-AIDS agents.
5: In Vivo. 2001 Jan-Feb;15(1):17-23.
Diverse biological activities of healthy foods.
N, Unten S, Kakuta
Fujimi Bee House, Shiki, Saitama,
Diverse biological activities of 7 healthy foods [powdered pine needle,
citrate-fermented sesame, powdered coffee, royal jelly, propolis,
pollen and white sesame oil (extracted by super critical state (40 degrees C,
350 atmospheric pressure))] were investigated. The
pine needle, sesame and powdered coffee was also extracted successively by
ethanol and hot water, and lyophilized. The pine needle and coffee extracts,
and propolis showed higher in vitro cytotoxic, bactericidal and oxidation activity, as
compared with other 4 lipophilic healthy foods.
However, propolis showed slightly lower, but
significant cytotoxic and bactericidal activity
with much reduced oxidation potential. ESR spectroscopy demonstrated that the
cytotoxic activity of these extracts was closely
related to their radical generation and O2- scavenging activities. Healthy
food components may have both pro-oxidant and anti-oxidant properties.
Pre-treatment of mice with pine needle, sesame or powdered coffee extract
significantly reduced the lethality of bacterial infection, possibly due to
their host-mediated action. These extracts failed to reduce the cytophatic effect of HIV-1 (human immunodeficiency virus)
infection in MT-4 cells. No apparent acute toxicity was detected in mice by
oral administration of 10 g/kg of these extracts. This data suggest the
medicinal efficacy of healthy foods.
6: Drugs Exp Clin
Suppression of HIV-1 replication by propolis
and its immunoregulatory effect.
Harish Z, Rubinstein A, Golodner M, Elmaliah M, Mizrachi Y.
College of Medicine, Department of Pediatrics, Microbiology and Immunology, Bronx, New York
In the current study we show that propolis, a
non-toxic natural bee-hive product, suppresses HIV-1
replication and modulates in vitro immune responses. CEM cells were treated
with propolis at nontoxic
concentrations prior to or following infection with HIV-1. Propolis abolished syncytium
formation at 4.5 micrograms/ml and inhibited it at lower doses in a
concentration-dependent manner. Propolis decreased
p24 antigen production by as much as 90-100% in a concentration-dependent manner.
Furthermore, modulation of peripheral blood mononuclear cells (PBMCs) mitogenic responses upon
the addition of propolis was noted, reducing the
elevated responses to Concanavalin A (Con A) and
enhancing suppressed mitogenic responses to
pokeweed mitogen (PWM). In summary, propolis may constitute a non-toxic natural product with
both anti HIV-1 and immunoregulatory effects.
7: J Am Acad
Dermatol. 1996 Oct;35(4):644.
allergy in an HIV-positive patient.
IJ, Ferrara R, Scala
of Clinical Medicine, University La Sapienza, Rome, Italy.
· Case Reports