JOURNAL OF MEDICINAL FOOD

J Med Food 00 (0) 2018, 1–12

FULL COMMUNICATION
# Mary Ann Liebert, Inc., and Korean Society of Food Science and Nutrition
DOI: 10.1089/jmf.2017.4093

The Effects of Curcuma longa L., Purple Sweet Potato, and Mixtures
of the Two on Immunomodulation in C57BL/6J Mice Infected
with LP-BM5 Murine Leukemia Retrovirus
Soo-Jeung Park,1 Dasom Lee,1 Minhee Lee,1 Han-Ol Kwon,2 Hyesook Kim,3 Jeongjin Park,4
Woojin Jeon,4 Minseok Cha,5 Suhwa Jun,5 Kwangjin Park,5 and Jeongmin Lee1
1
Department of Medical Nutrition, Kyung Hee University, Yongin, Korea.
2
Korea Ginseng Corporation Research Institute, Korea Ginseng Corporation, Daejeon, Korea.
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3
Department of East-West Medicine, Kyung Hee University, Yongin, Korea.
4
Department of Food and Nutrition, Chonnam National University, Gwangju, Korea.
5
SDC Research & Development Center, Damyang-gun, Korea.

ABSTRACT The immune response is stimulated to protect the body from external antigens and is controlled by several types
of immune cells. In the present study, the immunomodulatory effects of Curcuma longa L., purple sweet potato, and
mixtures of the two (CPM) were investigated in C57BL/6 mice infected with LP-BM5 murine leukemia virus (MuLV).
Mice were divided into seven groups as follows: normal control, infected control (LP-BM5 MuLV infection), positive control
(LP-BM5 MuLV infection+dietary supplement of red ginseng 300 mg/kg body weight), the original powder of C. longa
L. (C; LP-BM5 MuLV infection+dietary supplement of C 189 mg/kg body weight), the original powder of purple sweet
potato (P; LP-BM5 MuLV infection+dietary supplement of P 1811 mg/kg body weight), CPM Low (CPL; LP-BM5 MuLV
infection+CPM 2 g/kg body weight), and CPM High (CPH; LP-BM5 MuLV infection+CPM 5 g/kg body weight). Dietary
supplementation lasted for 12 weeks. Dietary supplementation of CPM inhibited LP-BM5 MuLV-induced lymphadenop-
athy and splenomegaly and inhibited reduction of messenger RNA (mRNA) expression of major histocompatibility
complex (MHC) I and II. Moreover, CPM reduced the decrease in T- and B cell proliferation, reduced the population of
CD4(+)/CD8(+) T cells, and remedied the unbalanced production of T helper-1 (Th1)/T helper-2 (Th2) cytokines in LP-BM5
MuLV-infected mice. In addition, CPM inhibited reduction of phagocytosis in peritoneal macrophages and decreased serum
levels of immunoglobulin A (IgA), immunoglobulin E (IgE), and immunoglobulin G (IgG). These results suggest that CPM
had a positive effect on immunomodulation in C57BL/6 mice induced by LP-BM5 leukemia retrovirus infection.

KEYWORDS:  Curcuma longa L002E  immunomodulation  LP-BM5 murine leukemia viruses

INTRODUCTION T helper-2 (Th2)-type cytokines such as IL-4, IL-6, IL-10,

and TNF-a result in an imbalance of cytokines. This imbal-
H omeostasis of the immune system is maintained by
regulation of the immune response to the current
physiological condition at any given time.1 Failure of ap-
ance decreases the function of T cells and suppresses the
immune response to antigens; it also stimulates the activity
of B cells, which in turn increases the production of immu-
propriate self-regulation of the immune system can cause
noglobulins.5,6 Furthermore, this imbalance in Th1/Th2 lym-
uncontrollable situations and even lead to acquired immune
phocytes causes abnormalities in the number and function of
deficiency syndrome (AIDS). AIDS is known to be caused
CD4+ T helper cells and CD8+ T helper cells, which bind to the
by human immunodeficiency virus (HIV) infection.2 If the
major histocompatibility complex (MHC) molecules, and in-
HIV virus is not removed and AIDS develops over a latent
creases macrophages and natural killer (NK) cells. The number
period, the immune system will collapse, and the body will
of macrophages is known through the expression of CD11b(+),
be vulnerable to a number of infectious diseases.3
and the number of NK cell is known through the expression of
Indeed, AIDS is known to cause many changes in cells.4
CD49b(+).7–9
Increased pro-inflammatory cytokines, reduced T helper-1
LP-BM5 murine leukemia virus (MuLV)-induced murine
(Th1)-type cytokines such as IL-2 and IFN-c, and increased
AIDS induces symptoms very similar to the HIV infection.10
About 12 weeks after mice are infected with MuLV, symp-
Manuscript received 29 December 2017. Revision accepted 10 April 2018. toms of AIDS appear, including lymphadenopathy syndrome,
Address correspondence to: Jeongmin Lee, PhD, Department of Medical Nutrition,
splenomegaly, alopecia, and hypergammaglobulinemia.
Kyung Hee University, Yongin 17104, Korea, E-mail: jlee2007@khu.ac.kr Further progression of these symptoms diminishes the function

1
 2 PARK ET AL.
of T cells and B cells and causes an imbalance in Th1/Th2
cytokines.11 Therefore, LP-BM5 MuLV-infected mice have
been widely used as a model for understanding the pathogenesis
of AIDS and for evaluating immunomodulatory effects.12 A
cure for AIDS has not yet been developed, and continued ad-
ministration of anti-HIV drugs causes side effects. However,
many studies report an increase in patient immunoregulatory
ability through diet and natural product administration.13
Recently, several natural products have been reported
to have various physiological activities such as antioxi-
dant,14,15 anti-inflammation,16,17 immunomodulation,18,19
antiobesity,15 and antitumor.20 Curcuma longa L. and purple
sweet potato (Ipomoea batatas L.) are representative ex-
amples. These natural products have been shown to be ef-
fective in immunomodulation in the LP-BM5 MuLV
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infection model,19,21 but a study has not yet been conducted
to confirm whether these two individual substances have
interactive immunomodulatory effects.
In this study, we investigated the effects of C. longa L.
and purple sweet potato mixtures on immunomodulation in
a LP-BM5 murine leukemia retrovirus-infected animal
model, as measured by cytokine production by splenocytes,
immunoglobulin concentration in the plasma, proliferation
of T cells and B cells, and expression of CD4(+), CD8(+),
CD11b(+), and CD49b(+).
MATERIALS AND METHODS
Preparation of the plant materials
C. longa L. (C) and purple sweet potato (P) were obtained
from SDC Research & Development Center (Damyang,
Korea). C was produced in Jindo, Korea, and unnecessary
parts of the raw materials were removed after harvesting.
The parts to be used in the experiment were washed, cut,
dried, and pulverized by a crusher. P was produced in
Haenam, Korea. The parts to be used in the experiment were
washed, sliced, hot air dried at 50–60C, and then crushed
by a pin-type mill (DK201; Sejung Tech, Daegu, Korea).
The mixture (CPM) ratio of C and P was 1:9.6. The mixing
ratio of C and P was confirmed to be within a safe con-
centration range after determining the safety standard of
intake of samples. The powders of C, P, and CPM were
sealed from air and light and stored at -20C until use.
Experimental mice and treatment
The protocol of the animal experiment was approved by the
Institutional Animal Care and Use Review Committee of
Kyung Hee University (KHUASP[SE]-16-007). Male
C57BL/6J mice (6 weeks old, 23 – 1 g) were purchased from
Saeronbio, Inc. (Uiwang, Korea). The housing facility was
maintained at 24C – 1C, 55–60% relative humidity with a
12-h light/12-h dark cycle. Experimental mice were accli-
mated for 1 week before starting the experiment and were
provided with standard pellet chow and fresh water ad libitum.
A total of 56 mice were randomly assigned to 7 groups
with 8 animals per group: normal control, infected control
(LP-BM5 MuLV infection), positive control (LP-BM5
MuLV infection+dietary supplement of red ginseng 300 mg/
kg body weight),19,22 C (LP-BM5 MuLV infection+dietary
supplement of C 189 mg/kg body weight), P (LP-BM5
MuLV infection+dietary supplement of P 1811 mg/kg body
weight), C + P low (CPL; LP-BM5 MuLV infection+a
mixture of C + P (CPM) 2 g/kg body weight), and C + P high
(CPH; LP-BM5 MuLV infection+CPM 5 g/kg body weight).
On the day that mice were injected with LP-BM5 MuLV, diets
were provided for each group; the experiment was conducted
for 12 weeks. All experimental diets were manufactured based
on the AIN93G diet and provided to mice ad libitum.
Infection with LP-BM5 MuLV
LP-BM5 MuLV (100 lL; donated from the National In-
stitute of Allergy and Infectious Diseases [NIAID], National
Institutes of Health [NIH], Bethesda, MD, USA) was in-
jected into mice intraperitoneally with an ecotropic titer of
4.5 log10 plaque-forming unit (PFU) · 10-3/L.8 Twelve
weeks later, all mice were sacrificed by cervical dislocation.
The peritoneal macrophages were collected into culture
medium (Dulbecco’s modified Eagle’s medium [DMEM],
10% fetal bovine serum) for phagocytosis assay. In addition,
the spleens of the mice were separated for primary spleno-
cyte culture, and blood samples from the mice were col-
lected for enzyme-linked immunosorbent assay (ELISA).
Real-time polymerase chain reaction
The primary splenocyte culture was prepared as follows.
Splenocytes were gently isolated with a strainer (40 mesh)
from the spleen in culture medium (RPMI 1640, 10% fetal
bovine serum, 1 · 105 U/L penicillin/streptomycin, 2 mM
glutamine). Red blood cell lysing buffer (Sigma-Aldrich, St.
Louis, MO, USA) was used to lyse the red blood cells in the
spleen at 37C for 3 min. Splenocytes were washed twice
using the culture medium, and 1 · 107 cells were lysed using
a QIAzol Lysis Reagent (Qiagen, Gaithersburg, MD,
USA). To extract the total RNA, an RNeasy Extraction Kit
(Qiagen) was used, and the experiment was conducted ac-
cording to the protocol of the manufacturer. Purified RNA
concentrations were quantified using a Q5000 UV-Vis
spectrophotometer (Quawell, San Jose, CA, USA). Exactly
500 ng of purified total RNA was used to synthesize com-
plementary DNA (cDNA) in 20 lL of Master Mix buffer,
using the iScript cDNA Synthesis Kit (Bio-Rad Labora-
tories, Hercules, CA, USA). Real-time polymerase chain
reaction (PCR; Applied Biosystems, Foster City, CA, USA)
was performed with selected primer sets using 2 lL cDNA
and the iQ SYBR Green Supermix (Bio-Rad Labora-
tories, Singapore, Singapore). Then, amplification of the
cDNA was carried out with 40 cycles of denaturation (95C
for 15 sec), annealing (57C for 60 sec), and extension (72C
for 30 sec), and the primer pair sequences used for the PCR
were as follows: GAPDH, 50 -CATGGCCTTCCGTGTTC
CTA-30 and 50 -GCGGCACGTCAGATCCA-30 ; MHC I, 50 -
CTGTGGTCGCCAAATGGTT-30 and 50 -CTCGAAGGAT
GTCCCCTGATT-30 ; and MHC II, 50 -AGTCTGCGATCGC
TTCTGAAC-30 and 50 -CAGCAGGGCTCCAATTGTG-30 .
 IMMUNOMODULATION OF PURPLE SWEET POTATO MIXTURE
Data analysis of the relative quantitation values was per-
formed using the 7500 System SDS software, version 1.3.1
(Applied Biosystems).
Flow cytometry (fluorescence-activated cell sorting)
The separated splenocytes were seeded at a concentration
of 1 · 106 cells/well in 24-well tissue culture dishes and
reacted with each of Anti-Mouse CD8a FITC, Anti-Mouse
CD4 PE, Anti-mouse CD11b CY7, and Anti-mouse CD49b
PE (eBioscience, San Diego, CA, USA), with light blocked
for 30 min on ice. Then, cells were centrifuged for 5 min,
and the supernatant was removed. Subsequently, the pellet
was suspended in fluorescence-activated cell sorting (FACS)
buffer (1 · phosphate-buffered saline, 1% bovine serum al-
bumin) and measured by a FACStar plus (Becton Dickinson,
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Mountain View, CA, USA).
T and B cell proliferation of splenocytes
The separated splenocytes were seeded at a concentration
of 1 · 106 cells/well in 96-well tissue culture dishes and
incubated for 12 h. Then, the cells were treated with Con-
canavalin A (Con A, 5 lg/mL; Sigma-Aldrich) for T cell
proliferation and lipopolysaccharide (LPS, 5 lg/mL; Gibco-
BRL, Grand Island, NY, USA) for B cell proliferation for
48 h in the incubator (37C, 5% CO2). After incubation, T
and B cell proliferation of splenocytes was measured using
EZ-CyTox (Daeil Lab Service, Seoul, Korea) following the
manufacturer’s protocol.
ELISA for cytokines in splenocytes
The separated splenocytes were seeded at a concentration
of 1 · 106 cells/well in 96-well tissue culture dishes and
incubated for 12 h. Then, the splenocytes were stimulated
with Con A (5 lg/mL) to induce IL-2, IL-4, IL-10, IL-12,
IL-15, and IFN-c production. In addition, the splenocytes
were stimulated with LPS (5 lg/mL) to induce IL-6 and
TNF-a production. After a 24-h incubation, the supernatants
of splenocytes were collected for assessment of IL-2, IL-4,
IL-6, IL-10, and TNF-a concentration. After a 48-h incu-
bation, the supernatants of the splenocytes were collected
for IL-12 and IL-15 concentration and analyzed. After a 72-
h incubation, the supernatants of the splenocytes were col-
lected for IFN-c concentration and analyzed. We used the
R&D DuoSet ELISA Development Kit (R&D Systems,
Minneapolis, MN, USA) to measure the concentrations of
cytokines according to the manufacturer’s protocol.
Determination of immunoglobulin concentration
The blood collected by sacrificing all the experimental
animals was centrifuged (14,000 g at 4C for 20 min) to
collect serum samples. The concentrations of immunoglob-
ulin E (IgE), immunoglobulin A (IgA), and immunoglobulin
G (IgG) were measured using IgE, IgA, and IgG Mouse
ELISA Kits (Abcam, Cambridge, United Kingdom), respec-
tively, and the experiment was conducted according to the
manufacturer’s protocol.
3
ELISA of phagocytosis
The separated peritoneal macrophages were seeded with
culture medium at a concentration of 1 · 106 cells/well in
96-well tissue culture dishes and incubated for 24 h. Then,
the phagocytosis of peritoneal macrophages was assessed
using the CytoSelect 96-well Phagocytosis Assay (zymosan
substrate) Kit (Cell Biolabs, Inc., San Diego, CA, USA). For
the activation of macrophages, zymosan substrate contained
in the kit was used, and the experiment was conducted ac-
cording to the manufacturer’s protocol.
Statistical analysis
All results are presented as mean – standard deviation.
We analyzed the significance of experimental results with
Duncan’s multiple-range test after conducting a one-way
analysis of variance using the SPSS statistical program
(SPSS PASW Statistics 22.0; SPSS, Inc., Chicago, IL,
USA). Statistical significance was considered at P < .05.
RESULTS
Effects of CPM on body weight and organ weights
of LP-BM5 MuLV-infected mice
This study showed a significant attenuation of weight gain
in the LP-BM5 MuLV-infected groups compared to the
normal controls. There was no significant difference in
weight gain among the LP-BM5 MuLV-infected groups,
except the CPH group. In addition, there was no significant
difference in food efficiency rate (FER) among any of the
groups. Spleen and lymph node weights of the infected
control group (0.30 – 0.05 g and 0.60 – 0.05 g) were signifi-
cantly higher than the normal control group (0.09 – 0.02 g
and 0.01 – 0.00 g). Positive control, C, P, CPL, and CPH
groups showed a significant decrease in lymph node weight
compared to the infected group, whereas there was no sig-
nificant difference in spleen weight among the LP-BM5
MuLV-infected groups. However, there was no significant
difference in liver, kidney, or heart weight among any of the
experimental groups (P < .05) (Table 1).
Effects of CPM on messenger RNA expression
of MHC I and II in primary splenocytes
of LP-BM5 MuLV-infected mice
The messenger RNA (mRNA) expression of MHC I was
decreased in the infected control group compared to the
normal control group. But there was no significant differ-
ence between the normal control and the infected control
groups. Compared with the infected control group, the
groups receiving CPL- and CPH-containing diets signifi-
cantly increased mRNA expression of MHC I, but there was
no significant difference between the two groups. The
mRNA expression of MHC II was significantly decreased
in the infected control group compared to the normal
control group. Compared with the infected control group,
the groups receiving CPL- or CPH-containing diets showed
significantly increased mRNA expression of MHC II, but
 4 PARK ET AL.

Table 1. Effects of CPM on Body Weight and Organ Weights of C57BL/6 Mice With or Without LP-BM
5 Murine Leukemia Virus Infection

LP-BM5 MuLV infection

Groups Normal control Infected control Positive control C P CPL CPH
a b ab ab ab ab
Weight gain (g)* 12.63 – 1.36 8.38 – 3.08 10.67 – 1.58 10.45 – 2.45 11.87 – 1.75 10.14 – 1.64 12.73 – 1.84a
Food intake (g/day/mouse) 3.60 – 0.25a 3.44 – 0.32a 3.48 – 0.32a 3.46 – 0.30a 3.46 – 0.41a 3.53 – 0.50a 3.44 – 0.39a
FER** 8.23 – 0.87a 8.35 – 0.51a 7.37 – 1.09a 7.63 – 1.93a 8.24 – 1.22a 7.65 – 0.76a 7.83 – 0.87a
Tissue weight (g)
Spleen 0.09 – 0.02b 0.3 – 0.05a 0.27 – 0.03a 0.26 – 0.02a 0.32 – 0.10a 0.31 – 0.01a 0.28 – 0.05a
Lymph node 0.01 – 0.00c 0.6 – 0.05a 0.34 – 0.06b 0.35 – 0.07b 0.37 – 0.08b 0.37 – 0.04b 0.34 – 0.03b
Liver 1.11 – 0.03a 1.23 – 0.11a 1.2 – 0.09a 1.2 – 0.08a 1.19 – 0.08a 1.11 – 0.05a 1.24 – 0.02a
Heart 0.14 – 0.02a 0.14 – 0.01a 0.14 – 0.01a 0.14 – 0.01a 0.14 – 0.01a 0.14 – 0.01a 0.14 – 0.00a
Kidney 0.34 – 0.06a 0.33 – 0.02a 0.34 – 0.01a 0.36 – 0.01a 0.35 – 0.06a 0.34 – 0.02a 0.34 – 0.05a

Values are presented as mean – standard deviation (n = 8), and different superscript letters indicate significance at P < .05. Normal control; Infected control, LP-
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BM5 MuLv infection group; Positive control, LP-BM5 MuLV infection with dietary supplementation of red ginseng 300 mg/kg body weight; C, LP-BM5 MuLV
infection with dietary supplementation of Curcuma longa L. 189 mg/kg body weight; P, LP-BM5 MuLV infection with dietary supplementation of purple sweet
potato 1811 mg/kg body weight; CPL, LP-BM5 MuLV infection with dietary supplementation of C. longa L. and purple sweet potato mixture 2 g/kg body weight;
CPH, LP-BM5 MuLV infection with dietary supplementation of C. longa L. and purple sweet potato mixture 5 g/kg body weight.
*Weight gain (g/12 weeks) = final body weight (g) - initial body weight (g).
**FER = weight gain (g)/total food consumption (g) · 100.
FER, food efficiency rate; MuLV, murine leukemia virus.

there was no significant difference between the two groups
(P < .05) (Fig. 1).
Effects of CPM on expression of CD4(+), CD8(+),
CD11b(+), and CD49b(+) in primary splenocytes
of LP-BM5 MuLV-infected mice
The quantity of CD4(+) T cells in the infected control group
was not significantly different compared to the normal control
group, and the CPH group (17.52% – 0.50%) showed a signifi-
cantly lower amount compared to that of the infected control
group (26.38% – 1.87%). However, there was no significant
difference in the other LP-BM5 MuLV-infected groups. The
quantity of CD8(+) T cells in the infected control group
(1.80% – 0.23%) was significantly less than the normal control
group (17.74% – 1.76%), and the CPH group (6.94% – 2.47%)
had significantly more CD8(+) T cells than the infected control
group. However, there was no significant difference in the other
LP-BM5 MuLV-infected groups (P < .05) (Fig. 2). The quantity
of CD11b(+) cells in the infected control group (3.22% – 0.26%)
was significantly higher than the normal control group (0.46% –
0.39%), and the positive control group (2.19% – 0.43%) had
significantly less than the infected control group. However, the
CPL and CPH groups (3.22% – 0.67% and 3.43% – 0.80%, re-
spectively) did not show any significant difference compared to
the infected control. CD49b(+) in the infected control group
(2.83% – 0.26%) was higher than the normal control group
(2.15% – 0.79%), but there was no significant difference

FIG. 1. Effects of Curcuma longa L. and pur-

ple sweet potato mixtures on the mRNA ex-
pression of MHC I and II in C57BL/6 mice with
or without LP-BM5 MuLV infection. Normal
control; Infected control, LP-BM5 MuLV infec-
tion group; Positive control, LP-BM5 MuLV
infection with dietary supplementation of red
ginseng 300 mg/kg body weight; C, LP-BM5
MuLV infection with dietary supplementation of
C. longa L. 189 mg/kg body weight; P, LP-BM5
MuLV infection with dietary supplementation of
purple sweet potato 1811 mg/kg body weight;
CPL, LP-BM5 MuLV infection with dietary
supplementation of C. longa L. and purple sweet
potato mixture 2 g/kg body weight; CPH, LP-
BM5 MuLV infection with dietary supplemen-
tation of C. longa L. and purple sweet potato
mixture 5 g/kg body weight. Values are presented
as mean – standard deviation (n = 8), and differ-
ent superscript letters indicate significance at
P < .05. MHC, major histocompatibility complex;
mRNA, messenger RNA.
 IMMUNOMODULATION OF PURPLE SWEET POTATO MIXTURE 5
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FIG. 2. Effects of C. longa L. and purple sweet potato mixtures on the proportion of CD4(+) and CD8(+) T cells in splenocytes prepared from
C57BL/6 mice with or without LP-BM5 MuLV infection. Normal control; Infected control, LP-BM5 MuLV infection group; Positive control, LP-
BM5 MuLV infection with dietary supplementation of red ginseng 300 mg/kg body weight; C, LP-BM5 MuLV infection with dietary supple-
mentation of C. longa L. 189 mg/kg body weight; P, LP-BM5 MuLV infection with dietary supplementation of purple sweet potato 1811 mg/kg
body weight; CPL, LP-BM5 MuLV infection with dietary supplementation of C. longa L. and purple sweet potato mixture 2 g/kg body weight;
CPH, LP-BM5 MuLV infection with dietary supplementation of C. longa L. and purple sweet potato mixture 5 g/kg body weight. Values are
presented as mean – standard deviation (n = 8), and different superscript letters indicate significance at P < .05.

between the two groups. In addition, the CPL and CPH groups
(3.66% – 1.33% and 2.86% – 0.57%) showed no significant dif-
ference compared to the infected control group (P < .05) (Fig. 3).
Effects of CPM on T and B cell proliferation in primary
splenocytes of LP-BM5 MuLV-infected mice
T cell proliferation from mitogen (Con A)-stimulated
splenocytes of the infected control group (58.86% – 2.60%)
was significantly decreased compared to the normal control
group. T cell proliferation was significantly increased in the
positive control, C, P, CPL, and CPH groups (80.29% –
1.30%, 71.41% – 3.66%, 73.85% – 6.37%, 76.66% – 2.78%,
and 93.09% – 4.52%, respectively) compared to the infected
control group. Specifically, the CPH group showed the highest
significance compared with the infected control group. In ad-
dition, B cell proliferation from mitogen (LPS)-stimulated
splenocytes of the infected control group (150.00% – 27.11%)
 6 PARK ET AL.
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FIG. 3. Effects of C. longa L. and purple sweet potato mixtures on the proportion of CD11b(+) and CD49b(+) in splenocytes prepared from
C57BL/6 mice with or without LP-BM5 MuLV infection. Normal control; Infected control, LP-BM5 MuLV infection group; Positive control, LP-
BM5 MuLV infection with dietary supplementation of red ginseng 300 mg/kg body weight; C, LP-BM5 MuLV infection with dietary supple-
mentation of C. longa L. 189 mg/kg body weight; P, LP-BM5 MuLV infection with dietary supplementation of purple sweet potato 1811 mg/kg
body weight; CPL, LP-BM5 MuLV infection with dietary supplementation of C. longa L. and purple sweet potato mixture 2 g/kg body weight;
CPH, LP-BM5 MuLV infection with dietary supplementation of C. longa L. and purple sweet potato mixture 5 g/kg body weight. Values are
presented as mean – standard deviation (n = 8), and different superscript letters indicate significance at P < .05.

was significantly greater compared to the normal control
group. B cell proliferation was significantly less in the positive
control, C, P, CPL, and CPH groups (66.83% – 8.95%,
66.12% – 7.81%, 63.92% – 8.35%, 69.34% – 12.86%, 58.98% –
12.17%, and 74.14% – 15.61%) compared to the infected control
group. Specifically, the positive control group showed the
highest significance compared to the infected control
group. However, there were no significant differences in
the other LP-BM5 MuLV-infected groups (P < .05) (Fig. 4).
Effects of CPM on Th1-type cytokine production
in primary splenocytes of LP-BM5 MuLV-infected mice
The levels of Th1-type cytokine (IL-2, IFN-c, IL-12, IL-
15) production are shown in Figure 4. IL-2 and IFN-c pro-
duction levels from Con A-stimulated splenocytes in the
infected group (IL-2: 127.00 – 29.64 pg/mL, IFN-c: 165.75 –
15.63 pg/mL) were significantly decreased compared to
the normal control (IL-2: 235.49 – 5.66 pg/mL, IFN-c:
 IMMUNOMODULATION OF PURPLE SWEET POTATO MIXTURE
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853.04 – 67.16 pg/mL). However, there was no significant
difference between LP-BM5 MuLV-infected groups for either
IL-2 or IFN-c (Fig. 5A). IL-12 and IL-15 production levels
from Con A-stimulated splenocytes in the infected group (IL-
12: 44.54 – 0.38 pg/mL, IL-15: 280.67 – 23.09 pg/mL) were
significantly decreased compared to the normal control (IL-12:
65.37 – 2.88 pg/mL, IL-15: 494.67 – 23.09 pg/mL). IL-12 pro-
duction levels of the positive control and the CPH group
(51.85 – 0.77 pg/mL and 54.15 – 1.54 pg/mL) were signifi-
cantly increased compared to the infected control group, but
there was no significant difference between C, P, and CPL
groups. In addition, IL-15 production levels of CPL and CPH
groups were significantly greater than the infected control
group, but there was no significant difference between the LP-
BM5 MuLV-infected groups (Fig. 5B).
Effects of CPM on Th2-type cytokine production
in primary splenocytes of LP-BM5 MuLV-infected mice
The levels of Th2-type cytokine (IL-4, IL-10, IL-6, TNF-a)
production are shown in Figure 5. IL-4 and IL-10 production
levels from Con A-stimulated splenocytes in the infected group
(IL-4: 1663.50 – 745.05 pg/mL, IL-10: 1924.50 – 53.07 pg/mL)
were significantly greater than the normal control (IL-4:
213.50 – 34.70 pg/mL, IL-10: 359.50 – 30.00 pg/mL). IL-4
production levels of the CPL and CPH groups (456.00 –
20.41 pg/mL and 531.00 – 20.41 pg/mL) were significantly less
than those of the infected control group, but there was no sig-
nificant difference between the positive control (474.33 –
20.14 pg/mL), C (591.00 – 257.20 pg/mL), P (468.50 –
59.20 pg/mL), CPL, and CPH groups. IL-10 production level
of the CPH group (1312.00 – 217.50 pg/mL) was significantly
decreased compared to the infected control group, but there
was no significant difference between the positive control
(1416.17 – 23.09 pg/mL), C (1492.00 – 107.50 pg/mL), P
(1432.83 – 68.98 pg/mL), and CPH groups (Fig. 6A). IL-6 and
TNF-a production levels from LPS-stimulated splenocytes in
7
FIG. 4. Effects of C. longa L. and purple sweet
potato mixtures on the T and B cell proliferation
from mitogen (Con A or LPS)-stimulated spleno-
cytes prepared from C57BL/6 mice with or without
LP-BM5 MuLV infection. Normal control; Infected
control, LP-BM5 MuLV infection group; Positive
control, LP-BM5 MuLV infection with dietary
supplementation of red ginseng 300 mg/kg body
weight; C, LP-BM5 MuLV infection with dietary
supplementation of C. longa L. 189 mg/kg body
weight; P, LP-BM5 MuLV infection with dietary
supplementation of purple sweet potato 1811 mg/kg
body weight; CPL, LP-BM5 MuLV infection with
dietary supplementation of C. longa L. and purple
sweet potato mixture 2 g/kg body weight; CPH, LP-
BM5 MuLV infection with dietary supplementation
of C. longa L. and purple sweet potato mixture 5 g/kg
body weight. Values are presented as mean – standard
deviation (n = 8), and different superscript letters in-
dicate significance at P < .05. Con A, concanavalin A;
LPS, lipopolysaccharide.
the infected group (IL-6: 218.11 – 9.14 pg/mL, TNF-a:
567.25 – 113.45 pg/mL) were significantly higher com-
pared to the normal control (IL-6: 73.37 – 4.94 pg/mL, TNF-a:
111.00 – 37.12 pg/mL). IL-6 production levels of CPL and
CPH groups (131.40 – 4.04 pg/mL and 127.05 – 7.52 pg/mL)
were significantly decreased compared to the infected
control group, but there was no significant difference in
C (137.58 – 3.19 pg/mL), P (130.21 – 3.68 pg/mL), CPL, or
CPH groups. TNF-a production levels of CPL and CPH
groups (91.42 – 12.58 pg/mL and 124.75 – 75.00 pg/mL)
were significantly lower compared to the infected control
group. However, there was no significant difference be-
tween the positive control (227.25 – 20.00 pg/mL), C
(178.92 – 109.04 pg/mL), P (118.50 – 33.75 pg/mL), CPL,
and CPH groups (Fig. 6B).
Effects of CPM on immunoglobulins
of LP-BM5 MuLV-infected mice
This study shows that the serum IgE, IgA, and IgG con-
centrations of the infected group (14.03 – 0.71 ng/mL,
210.96 – 9.43 ng/mL, and 579.05 – 53.68 ng/mL) were sig-
nificantly higher than those of the normal control group
(2.18 – 0.11 ng/mL, 161.55 – 14.29 ng/mL, and 86.01 –
36.48 ng/mL). In addition, serum IgE, IgA, and IgG con-
centrations of the positive control group (6.90 – 0.44 ng/
mL, 165.50 – 11.38 ng/mL, and 257.41 – 11.49 ng/mL, re-
spectively) were significantly decreased compared to those
of the infected control group. The IgE levels of CPL and
CPH groups (5.37 – 1.01 ng/mL and 3.84 – 0.09 ng/mL)
were significantly lower than those of the infected control
group, but there was no significant difference between the
positive control, C (6.95 – 1.11 pg/mL), P (5.17 – 2.65 pg/mL),
CPL, and CPH groups. The IgA levels of the CPL and CPH
groups (173.96 – 6.35 ng/mL and 168.01 – 3.29 ng/mL) were
significantly decreased compared to the infected control
group, but there was no significant difference between the
 8 PARK ET AL.
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positive control, C (180.89 – 5.16 pg/mL), P (181.09 –
6.71 pg/mL), CPL, and CPH groups. In addition, the IgG
level of the CPH group (279.92 – 13.45 ng/mL) was signifi-
cantly decreased compared to that of the infected control
group (P < .05) (Table 2).
Effects of CPM on phagocytosis of LP-BM5
MuLV-infected mice
The activity of the zymosan-treated group (100% – 0.74%;
zymosan activates macrophages) was significantly increased
compared to the cell-only group (8.96% – 0.35%). In addition,
these data show that the phagocytosis in the group treated with
zymosan and inhibitor (10.35% – 2.21%) was significantly in-
hibited compared to the zymosan-treated group. Phagocytosis
of the infected control group (85.52% – 2.05%) was signifi-
cantly decreased compared to the zymosan-treated group. The
positive control, C, P, and CPH groups (95.73% – 2.84%,
92.77% – 2.12%, 91.61% – 2.34%, and 93.33% – 1.59%, re-
FIG. 5. Effects of Curcuma long L. and purple
sweet potato mixtures on Th1-type cytokine [(A);
IL-2 and IFN-c, (B); IL-12 and IL-15] production
from mitogen (Con A)-stimulated splenocytes pre-
pared from C57BL/6 mice with or without LP-BM5
MuLV infection. Normal control; Infected control,
LP-BM5 MuLV infection group; Positive control,
LP-BM5 MuLV infection with dietary supplemen-
tation of red ginseng 300 mg/kg body weight; C, LP-
BM5 MuLV infection with dietary supplementation
of C. longa L. 189 mg/kg body weight; P, LP-BM5
MuLV infection with dietary supplementation of
purple sweet potato 1811 mg/kg body weight; CPL,
LP-BM5 MuLV infection with dietary supplemen-
tation of C. longa L. and purple sweet potato mix-
ture 2 g/kg body weight; CPH, LP-BM5 MuLV
infection with dietary supplementation of C. longa
L. and purple sweet potato mixture 5 g/kg body
weight. Values are presented as mean – standard
deviation (n = 8), and different superscript letters
indicate significance at P < .05. Th1, T helper-1.
spectively) showed significantly increased phagocytosis com-
pared to the infected control. Specifically, the CPH group
showed the highest significance. However, the CPL group
(82.55% – 4.29%) showed no significant difference compared
to the infected control group (P < .05) (Fig. 7).
DISCUSSION
The LP-BM5 MuLV-infected animal model exhibits symp-
toms very similar to an HIV-infected person and is well-
suited for assessing the immunomodulatory effects of
CPM.12 In addition, red ginseng is known to be helpful for
immune regulation and enhancement and was an effective
positive control for this experiment.23
In this experiment, the spleen and lymph node weights
and volumes were significantly greater in the LP-BM5
MuLV-infected group compared to the normal control
group. The spleen, which works with the immune system
and attacks external antibodies and infections, plays a very
 IMMUNOMODULATION OF PURPLE SWEET POTATO MIXTURE 9

FIG. 6. Effects of C. longa L. and purple sweet

potato mixtures on Th2-type cytokine [(A); IL-4 and
IL-10, (B); IL-6 and TNF-a] production from mi-
togen (Con A or LPS)-stimulated splenocytes pre-
pared from C57BL/6 mice with or without LP-BM5
MuLV infection. Normal control; Infected control,
LP-BM5 MuLV infection group; Positive control,
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LP-BM5 MuLV infection with dietary supplemen-

tation of red ginseng 300 mg/kg body weight; C, LP-
BM5 MuLV infection with dietary supplementation
of C. longa L. 189 mg/kg body weight; P, LP-BM5
MuLV infection with dietary supplementation of
purple sweet potato 1811 mg/kg body weight; CPL,
LP-BM5 MuLV infection with dietary supplemen-
tation of C. longa L. and purple sweet potato mix-
ture 2 g/kg body weight; CPH, LP-BM5 MuLV
infection with dietary supplementation of C. longa
L. and purple sweet potato mixture 5 g/kg body
weight. Values are presented as mean – standard
deviation (n = 8), and different superscript letters
indicate significance at P < .05. Th2, T helper-2.

important role in immune system function along with the nificant attenuation in lymph node growth compared to the
lymph nodes. Spleen and lymph node hyperplasia, com- infected control group (P < .05). These results show that
monly known as splenomegaly and lymphadenopathy, are dietary supplementation with CPM alleviates symptoms of
caused by diseases such as infection, leukemia, and can- lymphadenopathy syndrome induced by infection of LP-
cer.24–26 Dietary supplementation of CPM induced a sig- BM5 MuLV.
Table 2. Effects of CPM on Immunoglobulin Concentrations from Serum of C57BL/6 Mice
With or Without LP-BM5 Murine Leukemia Virus Infection

LP-BM5 MuLV infection

Groups Normal control Infected control Positive control C P CPL CPH
IgE (ng/mL) 2.18 – 0.11d 14.03 – 0.71a 6.90 – 0.44b 6.95 – 1.11b 5.17 – 2.65bc 5.37 – 1.01bc 3.84 – 0.09cd
IgA (ng/mL) 161.55 – 14.29c 210.96 – 9.43c 165.50 – 11.38bc 180.89 – 5.16b 181.09 – 6.71b 173.96 – 6.35bc 168.01 – 3.29bc
IgG (ng/mL) 86.01 – 36.48d 579.05 – 53.68b 257.41 – 11.49c 677.72 – 12.38a 517.65 – 99.99bc 543.38 – 91.11b 279.92 – 13.45c

Values are presented as mean – standard deviation (n = 8), and different superscript letters indicate significance at P < .05. Normal control; Infected control, LP-
BM5 MuLV infection group; Positive control, LP-BM5 MuLV infection with dietary supplementation of red ginseng 300 mg/kg body weight; C, LP-BM5 MuLV
infection with dietary supplementation of C. longa L. 189 mg/kg body weight; P, LP-BM5 MuLV infection with dietary supplementation of purple sweet potato
1811 mg/kg body weight; CPL, LP-BM5 MuLV infection with dietary supplementation of C. longa L. and purple sweet potato mixture 2 g/kg body weight; CPH,
LP-BM5 MuLV infection with dietary supplementation of C. longa L. and purple sweet potato mixture 5 g/kg body weight.
IgA, immunoglobulin A; IgE, immunoglobulin E; IgG, immunoglobulin G; MuLV, murine leukemia virus.
 10 PARK ET AL.
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FIG. 7. Effects of C. longa L. and purple sweet potato mixtures on phagocytic activity in peritoneal macrophage from C57BL/6 mice with or
without LP-BM5 MuLV infection. Cell only; cell+in, cell+zymosan inhibitor; cell+zy+in, cell+zymosan+zymosan inhibitor; cell+zy, cell+zy-
mosan, normal control; Infected control, LP-BM5 MuLV infection group; Positive control, LP-BM5 MuLV infection with dietary supplemen-
tation of red ginseng 300 mg/kg body weight; C, LP-BM5 MuLV infection with dietary supplementation of C. longa L. 189 mg/kg body weight; P,
LP-BM5 MuLV infection with dietary supplementation of purple sweet potato 1811 mg/kg body weight; CPL, LP-BM5 MuLV infection with
dietary supplementation of C. longa L. and purple sweet potato mixture 2 g/kg body weight; CPH, LP-BM5 MuLV infection with dietary
supplementation of C. longa L. and purple sweet potato mixture 5 g/kg body weight. Values are presented as mean – standard deviation (n = 8),
and different superscript letters indicate significance at P < .05.

In adaptive immunity, T cells are classified as CD8(+) T
helper cells or CD4(+) T helper cells, which cause apoptosis.
When reacting with an antigen, MHC molecules interact with
CD8(+) or CD4(+) T helper cell coreceptors and play an im-
portant role in T cell selection.27 MHC class I molecules are
expressed continuously in all nucleated cells, whereas MHC
class II molecules are expressed only in antigen-presenting cells
(APCs) such as macrophages, dendritic cells, B cells, and thy-
mic epithelial cells. The functions of MHC class I and II mol-
ecules are similar, but they bind to CD8(+) T helper cells and
CD4(+) T helper cells, respectively, and respond to the antigen.28
Viruses and tumors inhibit the adaptive immune response by
decreasing the MHC class molecules bound at the cell sur-
face.29,30 In this study, the expressions of MHC class I and II in
the infected group were significantly decreased compared to the
normal control group. Furthermore, dietary supplementation of
CPH induced a significant increase in the expression of MHC
class I compared to the infected control group (P < .05).
CD8(+) T helper cells are cytotoxic T cells that directly
attack NK cells, virus-infected cells, tumor cells, and abnormal
cells.31 We found that the proportion of CD8(+) T helper cells
was significantly reduced in the virus-infected group com-
pared to the normal control group, and dietary supplementa-
tion of CPH significantly increased the proportion of CD8(+) T
helper cells compared to the infected control group (P < .05).
CD4(+) T helper cells are divided into Th1 cells, which pro-
duce Th1-type cytokines, and Th2 cells, which produce Th2-
type cytokines. Th1-type cytokines stimulate phagocytosis
mainly by increasing macrophage activity, and Th2-type cy-
tokines stimulate B cell activity and increase antibody pro-
duction. The balance of immunity is maintained by
complementary regulation of these Th1- and Th2-type cyto-
kines.32 However, LP-BM5 MuLV infection decreases the
production of Th1-type cytokines and increases the production
of Th2-type cytokines, resulting in an imbalance between them
and impaired immunoregulatory ability.33 IL-2, a Th1-type
cytokine, stimulates proliferation of CD8(+) T helper cells, and
IFN-c stimulates CD4(+) T helper cell differentiation and
macrophage function.34,35 As a result of confirming the ratio of
macrophages using CD11b(+) antibody herein, it is difficult to
discuss the activity of macrophages. However, the phagocy-
tosis assay showed that the phagocytic activity of the infected
control group was significantly decreased compared to the
normal control group, and dietary supplementation of CPH
significantly increased compared to the infected control group
(P < .05). IL-12 and IL-15, which are Th1-type cytokines,
stimulate and control the activity of NK cells and recognize
and kill virus-infected cells, tumor cells, and abnormal cells in
endogenous immunity. NK cells bind to virus-infected cells
through active and inhibitory signals and attack cells by re-
ceiving active signals.36 However, infection with HIV inhibits
the production of IL-12 and reduces the activity of NK cells.
This causes an attack on the virus-infected cells to be in-
activated.37 As a result of confirming the ratio of NK cells
using CD49b(+) antibody, it is difficult to discuss the activity of
NK cells. However, the activity of IL-12 and IL-15 cytokines
 IMMUNOMODULATION OF PURPLE SWEET POTATO MIXTURE
was significantly inhibited in the infected control group
compared with that of the normal control group, and dietary
supplementation of CPH significantly increased compared to
the infected control group (P < .05). These results suggest that
CPH increased the production of IL-12 and IL-15, which were
reduced by LP-BM5 MuLV, and increased the activity of NK
cells. IL-4, a Th2-type cytokine, inhibits HIV replication in
human macrophages and is produced at an abnormally high
level in mice inducing LP-BM5 MuLV with IL-10.38 IL-6 and
TNF-a, which are inflammatory cytokines and function as
Th2-type cytokines, activate NFjB and cause replication of
HIV. In particular, TNF-a is known to be an important cyto-
kine for the regulation of immune cell activity because it is
mainly degraded by activated macrophages, induces inflam-
matory responses, and induces apoptosis.39 We confirmed that
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dietary supplementation of CPM significantly decreased the
production of IL-4, IL-10, IL-6, and TNF-a, increased with
LP-BM5 MuLV (P < .05). Therefore, we hypothesized that
CPM could also improve immunomodulating ability by
modulating the balance between Th1- and Th2-type cytokines.
Several studies have reported that HIV infection decreases
the proliferation of T cells and increases the proliferation of B
cell as the HIV infection progresses.40,41 Recently, studies on
the relationship between HIV infection and B cells have shown
that the B cell replacement rate is increased in response to HIV
infection, and the plasma cell survival time is shortened, re-
sulting in hypergammaglobulinemia. It is known that HIV
decreases production of the B cell CD21 protein and interferes
with B cell function.42 In this study, LP-BM5 MuLV infection
significantly decreased T cell proliferation and significantly
increased B cell proliferation; IgE and IgG concentrations were
higher compared to those in the normal control group. The
dietary supplement CPM significantly increased T cell prolif-
eration and significantly decreased B cell proliferation com-
pared to the infected control group. Specifically, the dietary
supplement CPH significantly decreased the concentration of
IgE and IgG compared to the infected control group (P < .05).
According to our findings, CPH can improve B cell dysfunc-
tion caused by LP-BM5 MuLV infection and prevent hy-
pergammaglobulinemia.
In summary, we investigated the interactive effects
of CPM on immunomodulation in the LP-BM5 MuLV-
infected animal model. It is presumed that the interaction of
curcumin18 and anthocyanins,19 which are active ingredients
of CPM, improves the function of CD8(+) T helper cells in
LP-BM5 MuLV-infected animal models. This suggests that
macrophages acting as APCs promote the activation of NK
cells and T cells, which may explain the mechanism by
which naive CD4(+) T cells mature and increase Th1 cyto-
kines. Increased Th1 type cytokines in this mechanism ac-
tivate CD8(+) T helper cells leading to the elimination of the
virus.34,35 In particular, we found that dietary supplemen-
tation of CPH increased the expression of MHC class I and
CD8(+) T helper cells, T cell proliferation, and phagocytic
activity and improved the imbalance of Th1/Th2 type cy-
tokines in an LP-BM5 MuLV-infected animal model. These
results suggest that CPH is effective for immunomodulatory
function and shows promise as a natural functional material.
11
ACKNOWLEDGMENTS
This research was supported by the Ministry of Trade,
Industry, and Energy (MOTIE) and The Korea Institute for
Advancement of Technology (KIAT) through the Research
and Development for Regional Industry.
AUTHOR DISCLOSURE STATEMENT
No competing financial interests exist.
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