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EGCG and HIV Treatment
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Green Tea Compound Being Developed as Potential HIV-1
Therapy
Therapy
"It is refreshing to deal with
someone who is both professional
and courteous."
someone who is both professional
and courteous."
| | Copyright © 2008 Jing Tea Brisbane Australia | |
By Marcus A. Cohen
Researchers at the Baylor College of Medicine (BCM) and the Texas
Children's Hospital (TCH), both in Houston, have been evaluating the
ability of epigallocatechin gallate (EGCG) to inhibit infection by HIV-1.
EGCG is among a group of natural polyphenols, called catechins,
found in green tea; it is the most prevalent and active catechin. A report
on this evaluation appeared in The Journal of Allergy and Clinical
Immunology (February 2009;123[2]:459-465). There were three
coauthors: Christina L. Nance, PhD; Edward B. Siwak, PhD; and
William T. Shearer, MD, PhD. For this column, I questioned Dr. Nance
about certain findings and points.
Researchers at the Baylor College of Medicine (BCM) and the Texas
Children's Hospital (TCH), both in Houston, have been evaluating the
ability of epigallocatechin gallate (EGCG) to inhibit infection by HIV-1.
EGCG is among a group of natural polyphenols, called catechins,
found in green tea; it is the most prevalent and active catechin. A report
on this evaluation appeared in The Journal of Allergy and Clinical
Immunology (February 2009;123[2]:459-465). There were three
coauthors: Christina L. Nance, PhD; Edward B. Siwak, PhD; and
William T. Shearer, MD, PhD. For this column, I questioned Dr. Nance
about certain findings and points.
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Studies have indicated that EGCG inhibits replication of HIV-1 by targeting several steps in
the life cycle of HIV-1. In high nonphysiologic concentrations, EGCG reportedly interferes
with reverse transcriptase (RT) and protease activity.
RT is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded
DNA. A protease is any of numerous enzymes that hydrolyze, or decompose, proteins. In AIDS,
drugs termed protease inhibitors are used to prevent cleavage of viral proteins into mature
infectious particles.
Nance et al. showed that EGCG acts as an entry inhibitor by blocking the binding of HIV-1 gp120
to CD4 on the T cell. A glycoprotein exposed on the surface of the HIV envelope, gp120 is
essential for entry of the virus into cells, seeking specific cell surface receptors for entry. CD4 is
a large glycoprotein found especially on the surface of helper T cells; it is the primary receptor
for HIV.
What's of further importance about EGCG's blocking capability, Dr. Nance explained to me, is
the level of EGCG needed to block binding; physiologic levels suffice – levels that can be safely
and significantly utilized by the body.
In a previous study by Nance and other investigators, a physiologic concentration of merely
0.170 micromols/L of EGCG was found to reduce binding of gp120 to CD4 by a factor of
between 10-fold and 20-fold.1 That's a physiologic concentration equivalent to what a human
can obtain drinking two cups of green tea. Physiologic in the term physiologic concentration
means characteristic of or appropriate to an organism's healthy or normal functioning. The
Baylor researchers used a compound of EGCG standardized elsewhere in phase 1 trials of the
safety and pharmacokinetics of EGCG in healthy individuals and cancer patients.
The research team from BCM and TCH pointed out that almost all previous reports of inhibition
of HIV replication by EGCG were based on high nonphysiologic concentrations of EGCG. Their
recent evaluation, in contrast, sought to determine if physiologic concentrations of EGCG would
be capable of inhibiting infection by HIV-1. A second, related objective of their evaluation was to
begin preclinical development of EGCG as an alternative, low-cost, nontoxic therapy for HIV-1
infection.
For their evaluation in the paper published in 2009, the BMC-TCH researchers isolated CD4 T
cells and macrophages from the blood of donors not infected with HIV. The researchers chose
these key components of the immune system, Dr. Nance stressed to me, because HIV-1
targets them for infection.
Exposing these immune cells in the lab to HIV, they assessed the inhibitory ability of EGCG via
an HIV-1 p24 ELISA test. P24 is the core protein in the HIV particle. It's the "capsid" of HIV, the
"case" in which HIV's RNA genome is kept. The level of p24 in blood serum is an indicator of
HIV progression.
A summary of the findings in the abstract of this paper says: "Epigallocatechin gallate inhibited
HIV-1 infectivity on human CD4 T cells and macrophages in a dose-dependent manner. At a
physiologic concentration of 6 micromols/L , EGCG significantly inhibited HIV-1 p24 antigen
production across a broad spectrum of both HIV-1 clinical isolates and laboratory-adapted
subtypes." (An antigen is any substance foreign to the body that evokes an immune response.)
In discussing the results of their investigation, the researchers indicate that they tried a range of
concentrations, observing a "50% inhibitory concentration of 4.5 micromols/L." This percentage
falls within the range of physiologic concentrations (levels that can be significantly utilized by the
body).
They start the "Results" section by stating that EGCG "inhibited p24 antigen production."
Curious to know what else EGCG may have inhibited, I asked Dr. Nance: Would it also show
that EGCG is inhibiting viral activity once HIV is inside the cells? She said the research team did
no testing in this area.
Nance et al. are clear about the clinical implications of their findings in this report:
"Development of the green tea catechin EGCG as an alternative therapy in HIV-1 infection may
result in a potentially nontoxic effective treatment across a broad spectrum of HIV-1 isolates".
A paragraph in the "Discussion" section elaborates: This broad specificity of EGCG for HIV-1
subtype suggests that EGCG may be an effective alternative therapy against HIV-1 infection.
Like vaccines, current HIV treatments such s nucleoside and non-nucleoside RT inhibitors as
well as protease inhibitors were developed in Western countries based on an HIV-1 subtype B
model. As these and other medications become available in the developing world, the efficacy
of these drugs for non-B subtypes becomes a significant issue. Both the natural resistance of
the different viruses in drug-naïve individuals and the propensity of the virus for developing drug
resistance after treatment are major concerns.
The Baylor team also note: "Subtype C HIV-1 seems to be spreading more rapidly worldwide
than other subtypes." (In speaking to her while writing this column, Dr. Nance informed me that
subtype C is now most prevalent globally, specifically in Africa and Asia.) In conclusion they
follow with: "Thus, EGCG may represent a low-cost inhibitor of global HIV-1 infection".
Toward the end of the "Discussion" section, the researchers remark that no studies to date
have evaluated the efficacy, safety, and pharmacokinetic characteristics of EGCG in individuals
infected by HIV-1.
When I contacted Dr. Nance, I asked if she and her co-researchers had plans to conduct such a
study. She replied: "We are now poised to begin a phase 1 clinical trial." In closing, I should say
that Nance et al. cite in their footnotes two studies of the antiviral effects of EGCG from green tea
on hepatitis B virus and influenza virus.2,3
Notes
1. Williamson MP et al. Epigallocatechin gallate, the main polyphenol in green tea, binds to the
T-cell receptor, CD4: potential for HIV-1 therapy. J Allergy Clin Immunol. 2006;118:1369–1374.
2. Xu J et al. Green tea extract and its major component epigallocatechin gallate inhibits
hepatitis B virus in vitro. Antiviral Res 2008;78:242–249.
3. Song JM et al. Antiviral effect of catechins in green tea on influenza virus. Antiviral Res 2005;
68:66–74.
Marcus A. Cohen's "baptism" in the whirlpools of medical politics dates to 1984, when he
served as government and media liaison for patients under alternative cancer therapy.
Subsequently, he has advocated broadening plausible treatment options for patients
unresponsive to conventional care.
A Townsend Letter columnist since 2004, he has reported and commented on a wide range of
health-care topics; he is also the author of a paperback, Lyme Disease Update, published by
the Lyme Disease Association in 2004.
the life cycle of HIV-1. In high nonphysiologic concentrations, EGCG reportedly interferes
with reverse transcriptase (RT) and protease activity.
RT is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded
DNA. A protease is any of numerous enzymes that hydrolyze, or decompose, proteins. In AIDS,
drugs termed protease inhibitors are used to prevent cleavage of viral proteins into mature
infectious particles.
Nance et al. showed that EGCG acts as an entry inhibitor by blocking the binding of HIV-1 gp120
to CD4 on the T cell. A glycoprotein exposed on the surface of the HIV envelope, gp120 is
essential for entry of the virus into cells, seeking specific cell surface receptors for entry. CD4 is
a large glycoprotein found especially on the surface of helper T cells; it is the primary receptor
for HIV.
What's of further importance about EGCG's blocking capability, Dr. Nance explained to me, is
the level of EGCG needed to block binding; physiologic levels suffice – levels that can be safely
and significantly utilized by the body.
In a previous study by Nance and other investigators, a physiologic concentration of merely
0.170 micromols/L of EGCG was found to reduce binding of gp120 to CD4 by a factor of
between 10-fold and 20-fold.1 That's a physiologic concentration equivalent to what a human
can obtain drinking two cups of green tea. Physiologic in the term physiologic concentration
means characteristic of or appropriate to an organism's healthy or normal functioning. The
Baylor researchers used a compound of EGCG standardized elsewhere in phase 1 trials of the
safety and pharmacokinetics of EGCG in healthy individuals and cancer patients.
The research team from BCM and TCH pointed out that almost all previous reports of inhibition
of HIV replication by EGCG were based on high nonphysiologic concentrations of EGCG. Their
recent evaluation, in contrast, sought to determine if physiologic concentrations of EGCG would
be capable of inhibiting infection by HIV-1. A second, related objective of their evaluation was to
begin preclinical development of EGCG as an alternative, low-cost, nontoxic therapy for HIV-1
infection.
For their evaluation in the paper published in 2009, the BMC-TCH researchers isolated CD4 T
cells and macrophages from the blood of donors not infected with HIV. The researchers chose
these key components of the immune system, Dr. Nance stressed to me, because HIV-1
targets them for infection.
Exposing these immune cells in the lab to HIV, they assessed the inhibitory ability of EGCG via
an HIV-1 p24 ELISA test. P24 is the core protein in the HIV particle. It's the "capsid" of HIV, the
"case" in which HIV's RNA genome is kept. The level of p24 in blood serum is an indicator of
HIV progression.
A summary of the findings in the abstract of this paper says: "Epigallocatechin gallate inhibited
HIV-1 infectivity on human CD4 T cells and macrophages in a dose-dependent manner. At a
physiologic concentration of 6 micromols/L , EGCG significantly inhibited HIV-1 p24 antigen
production across a broad spectrum of both HIV-1 clinical isolates and laboratory-adapted
subtypes." (An antigen is any substance foreign to the body that evokes an immune response.)
In discussing the results of their investigation, the researchers indicate that they tried a range of
concentrations, observing a "50% inhibitory concentration of 4.5 micromols/L." This percentage
falls within the range of physiologic concentrations (levels that can be significantly utilized by the
body).
They start the "Results" section by stating that EGCG "inhibited p24 antigen production."
Curious to know what else EGCG may have inhibited, I asked Dr. Nance: Would it also show
that EGCG is inhibiting viral activity once HIV is inside the cells? She said the research team did
no testing in this area.
Nance et al. are clear about the clinical implications of their findings in this report:
"Development of the green tea catechin EGCG as an alternative therapy in HIV-1 infection may
result in a potentially nontoxic effective treatment across a broad spectrum of HIV-1 isolates".
A paragraph in the "Discussion" section elaborates: This broad specificity of EGCG for HIV-1
subtype suggests that EGCG may be an effective alternative therapy against HIV-1 infection.
Like vaccines, current HIV treatments such s nucleoside and non-nucleoside RT inhibitors as
well as protease inhibitors were developed in Western countries based on an HIV-1 subtype B
model. As these and other medications become available in the developing world, the efficacy
of these drugs for non-B subtypes becomes a significant issue. Both the natural resistance of
the different viruses in drug-naïve individuals and the propensity of the virus for developing drug
resistance after treatment are major concerns.
The Baylor team also note: "Subtype C HIV-1 seems to be spreading more rapidly worldwide
than other subtypes." (In speaking to her while writing this column, Dr. Nance informed me that
subtype C is now most prevalent globally, specifically in Africa and Asia.) In conclusion they
follow with: "Thus, EGCG may represent a low-cost inhibitor of global HIV-1 infection".
Toward the end of the "Discussion" section, the researchers remark that no studies to date
have evaluated the efficacy, safety, and pharmacokinetic characteristics of EGCG in individuals
infected by HIV-1.
When I contacted Dr. Nance, I asked if she and her co-researchers had plans to conduct such a
study. She replied: "We are now poised to begin a phase 1 clinical trial." In closing, I should say
that Nance et al. cite in their footnotes two studies of the antiviral effects of EGCG from green tea
on hepatitis B virus and influenza virus.2,3
Notes
1. Williamson MP et al. Epigallocatechin gallate, the main polyphenol in green tea, binds to the
T-cell receptor, CD4: potential for HIV-1 therapy. J Allergy Clin Immunol. 2006;118:1369–1374.
2. Xu J et al. Green tea extract and its major component epigallocatechin gallate inhibits
hepatitis B virus in vitro. Antiviral Res 2008;78:242–249.
3. Song JM et al. Antiviral effect of catechins in green tea on influenza virus. Antiviral Res 2005;
68:66–74.
Marcus A. Cohen's "baptism" in the whirlpools of medical politics dates to 1984, when he
served as government and media liaison for patients under alternative cancer therapy.
Subsequently, he has advocated broadening plausible treatment options for patients
unresponsive to conventional care.
A Townsend Letter columnist since 2004, he has reported and commented on a wide range of
health-care topics; he is also the author of a paperback, Lyme Disease Update, published by
the Lyme Disease Association in 2004.
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