The anti-cancer activity and potential clinical application of rice bran extracts and fermentation products

Abstract

Rice bran is the main by-product of rice processing and contains approximately 64% of the nutrients in rice. Its various nutrient elements include rice bran proteins, oil, oryzanol, vitamins, polysaccharides, etc. The use of fermented technology can increase the content of bioactive peptides, promote the absorption efficiency, and further improve the functionality and added value of rice bran. In recent years, the nutritional value and function of the extracts and fermented products of rice bran have been emphatically studied. Rice bran extracts and fermentation products serve a critical role in the anti-inflammatory reaction, reducing the plasma lipid effect and increasing anti-cancer activity. Moreover, few review studies have been reported on the anti-cancer activity and potential mechanism of action of rice bran extract and its fermentation products. In this review, we focused on the anti-cancer function, mechanisms, and potential clinical usage of rice bran extracts and fermentation products in the adjuvant therapy of cancer patients.

Full text

The anti-cancer activity and potential clinical
application of rice bran extracts and fermentation
products
Yonghui Yu, †
a
Jingjie Zhang,†
b
Jing Wang*
a
and Baogao Sun
a
Rice bran is the main by-product of rice processing and contains approximately 64% of the nutrients in rice.
Its various nutrient elements include rice bran proteins, oil, oryzanol, vitamins, polysaccharides, etc. The use
of fermented technology can increase the content of bioactive peptides, promotethe absorption efficiency,
and further improve the functionality and added value of rice bran. In recent years, the nutritional value and
function of the extracts and fermented products of rice bran have been emphatically studied. Rice bran
extracts and fermentation products serve a critical role in the anti-inflammatory reaction, reducing the
plasma lipid effect and increasing anti-cancer activity. Moreover, few review studies have been reported
on the anti-cancer activity and potential mechanism of action of rice bran extract and its fermentation
products. In this review, we focused on the anti-cancer function, mechanisms, and potential clinical
usage of rice bran extracts and fermentation products in the adjuvant therapy of cancer patients.
Introduction
Rice bran, which consists of a combination of aleurone and
pericarp, is the hard outer layer that is obtained during rice
milling. Rice bran is rich in essential fatty acids and dietary
ber and contains proteins, dietary minerals, and vitamins.
1
Approximately 12–18.5% of rice bran is healthy oil, which
contains 47% monounsaturated, 33% polyunsaturated, and
20% saturated fats as well as highly unsaponiable ingredients
including gamma-oryzanol, tocotrienols, and beta-sitosterol.
2
However, the high oil content of rice bran leads to easy rancidity
by endogenous lipase, and stabilization is an effective way to
avoid rancidication.
3
Heat (dry or damp), microwave applica-
tion, refrigeration, and proteasome treatment to inactivate
endogenous lipase are useful methods to stabilize rice bran and
mitigate its rancidication.
3,4
The protein content comprises
approximately 10–15% of rice bran, and it is increased to 18% in
defatted rice bran.
5
The protein content includes albumin
(water soluble), globulin (salt soluble), prolamin (alcohol
soluble), and glutelin (alkali soluble).
6
The rice bran protein
contains all the essential amino acids. Compared with that of
rice protein, the amino acid composition of rice bran is closer to
the recommended model of the Food and Agriculture
Organization (FAO)/World Health Organization (WHO), and its
nutritional value is comparable to those of soybeans and egg
proteins.
7
Moreover, researchers are striving to isolate bioactive
components from rice bran and reveal their functions.
Multiple isolation methods have been applied for the
purication of rice bran fractions, and the method selection
is based on the different physicochemical properties of the
rice bran components. Rice bran oil (RBO) can be extracted
using an aqueous method,
8
an enzymatic method,
9
and
a screw press method.
10
Subsequently, modied methods
such as ultrasound and microwave-assisted aqueous
extraction of RBO have been used.
11,12
Rice bran protein
(RBP) can be extracted using an alkali solution,
13
enzy-
matic,
14
or physical method.
15
With the development of the
extraction technology, the yield and purity of the rice bran
components will be further improved.
Fermentation is an important method for the deep pro-
cessing of rice bran; thus, the fermentation products can be
used as high-quality feed
16
and raw materials for food and
beverage production.
17
The traditional zymogenous micro-
organisms include yeast, Aspergillus oryzae,lacticacid
bacteria, and Lentinus edodes.
18–21
Fermentation contributes
to an increased amino acid content and a decreased fatty
acid content.
22
Moreover, the bioactive components ob-
tained from fermented rice bran (FRB) exert various bio-
logical activities (Table 1).
With the development of nutraceuticals, researchers and
consumers are currently paying increasing interest to the
possible preventive/therapeutic effects of rice bran on
pathological conditions;
24–27
nutraceuticals have attracted
signicant attention due to their abilities to regulate the
a
Beijing Advanced Innovation Center for Food Nutrition and Human Health,
China-Canada Joint Lab of Food Nutrition and Health (Beijing), Beijing Engineering
and Technology Research Center of Food Additives, Beijing Technology & Business
University, Beijing 100048, China. E-mail: wangjing@th.btbu.edu.cn
b
Institute of Food and Nutrition Development, Ministry of Agriculture, Beijing 100081,
China
†Yonghui Yu and Jingjie Zhang contributed equally to this work.
Cite this: RSC Adv.,2019,9, 18060
Received 1st April 2019
Accepted 25th May 2019
DOI: 10.1039/c9ra02439e
rsc.li/rsc-advances
18060 |RSC Adv.,2019,9,18060–18069 This journal is © The Royal Society of Chemistry 2019
RSC Advances
REVIEW

Table 1 Rice bran fermentation and function
Raw material
Type of fermentation
microorganism Model Function Reference
Brown rice and rice bran Aspergillus oryzae Mice bearing tumors derived
from QR-32 cells, ApcMin/+
mice, female A/J mice, male
F344 rats, or female LEC rats
Fermented brown rice and rice
bran administration reduced
the expression of the
inammation-related genes
TNF-a,Mac-1,CCL3and
CXCL2 in tumor-bearing mice;
suppressed the multiplicity of
colontumorsinApcMin/+
mice exposed to dextran
sodium sulfate; inhibited
NNK-induced lung
tumorigenesis and NMBA-
induced esophageal
tumorigenesis; protected
against the development of
hepatitis; and suppressed
diethylnitrosoamine (DEN)-
and phenobarbital (PB)-
induced hepatocarcinogenesis
22,34–38
Rice bran Fungi and lactic acid
bacteria
Colitis in mice Dietary supplementation
with fermented rice bran
attenuated dextran sodium
sulfate-induced intestinal
inammation via elevating
short-chain fatty acids and
tryptamine production
19
Rice bran along with
Angelicae gigantis, Cnidium
officinale,Artemisia princeps,
and Camellia sinensis
Lactobacillus rhamnosus and
Pichia deserticola
Atopic dermatitis in mice Fermented rice bran combined
with Angelicae gigantis,
Cnidium officinale,Artemisia
princeps,andCamellia sinensis
mitigated 1-chloro-2,4-
dinitrobenzene-induced atopic
dermatitis through inhibiting
the expression of cytokines and
Cox-2
1
Rice bran Lentinus edodes Healthy participants Supplementation with
fermented rice bran
signicantly increased IFN-g
secretion without causing
obvious adverse effects and
with no signicant effects on
the production of IL-2, IL-4,
IL-10, IL-12, or TNF-a
21
Rice bran Issatchenkia orientalis MFST1 3T3-L1 adipocytes Fermented rice bran
treatment reduced reactive
oxygen species generation
and oxidative stress-induced
insulin resistance
39
Neptune rice bran Saccharomyces boulardii Raji B lymphomas Treatment with fermented
Neptune rice bran extracts
signicantly inhibited the
viability of Raji B lymphomas
23
Rice bran Lactobacillus rhamnosus and
Saccharomyces cerevisiae
B16F1 melanoma Fermented rice bran extracts
reduced the expression of
microphthalmia-associated
transcription factor and
inhibited the melanogenesis
of B16F1 melanoma cells
20
Rice bran Saccharomyces cerevisiae Rats or mice Oral administration of
fermented rice bran induced
an anti-stress and anti-
fatigue response
40
This journal is © The Royal Society of Chemistry 2019 RSC Adv.,2019,9,18060–18069 | 18061
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immune response, glucose and lipid metabolism. Black rice
bran, which is rich in gamma-oryzanol, could promote the
expression of CD14 and toll-like receptor 4 and enhance the
phagocytic activity of the macrophages RAW264.7.
28
The
extracts, such as phenolic, avonoid, anthocyanin, and
proanthocyanidin extracts, obtained from rice bran inhibit
alpha-glucosidase activity and promote glucose uptake in
3T3-L1 adipocytes, which are critical factors for glucose
homeostasis.
29
Monacolins (present in large amounts in red
yeast rice, which is produced by the fermentation of Mon-
ascus purpureus mold) have been shown to be bioactive for
cholesterol reduction.
30
Studies have demonstrated that rice bran extracts and
FRB serve critical roles in the regulation of oxidative
response, inammatory reaction, immune function,
cholesterol metabolism, and tumor suppression.
31–33
In this
study, we emphasized the potential function of rice bran
extracts and FRB in cancer prevention and therapy.
Anti-cancer activity: mechanism of
action and chemopreventive effects
Reducing inammatory reaction
Inammation is an important inducer of tumor progression,
and many cancers arise from infection and inammation.
41
Inammation also aids in cancer cell proliferation and
promotes angiogenesis and cell mobility.
42
Thus, reducing
inammation is a promising therapeutic target for treating
cancer.
43
Recent data demonstrate that rice bran extracts and
FRB are helpful in attenuating inammation (Fig. 1). A high-
fat diet results in chronic intestinal inammation,
44
and rice
bran enzymatic extract supplements mitigate high-fat diet-
induced inammatory factor secretion.
45
The rice bran
protein hydrolysate also contributes to the suppression of
proinammatory cytokine expression in rats fed a high-
carbohydrate, high-fat diet.
46
RBO also exerts an anti-
inammatory response and can reduce the inammatory
response of rats fed partially hydrogenated vegetable fat.
47
A
subsequent study has shown that the gamma-oryzanol
componentofRBOservesanessentialroleintheanti-
inammatory activity.
48
Gamma-tocotrienol is another
important component of rice bran extracts that represses
pancreatic tumor growth by reducing the NF-kB-mediated
inammatory microenvironment.
49
The colitis effect is a crit-
ical inducer of colon cancer,
50
and a dietary supplement of FRB
effectively inhibits dextran sodium sulfate-induced colitis via
reducing inammatory cell inltration and inammatory
cytokine production.
19
Overall,thericebranextractsandFRB
might serve essential roles in preventing cancer development
via downregulation of the inammatory reaction.
Fig. 1 The role of rice bran extracts and FRB in reducing inflammation. Supplementation of RBP hydrolysate and RBO inhibited the production of
proinflammatory factors. Gamma-oryzanol inactivated the NF-kB signaling pathway and reduced inflammatory reactions. FRB effectively
mitigated dextran sodium sulfate-induced colitis by suppressing the infiltration of inflammatory cells and the secretion of inflammatory factors.
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RSC Advances Review

Cell cycle arrest
Aberrant cell cycle protein expression leads to uncontrolled cell
proliferation, which is one of the critical factors for cancer
occurrence.
51
Cell cycle blockers are ideal targets for cancer
therapy.
52
As shown in Fig. 2, tricin is an important avone
component of rice bran. A study has indicated that tricin arrests
the human malignant breast cancer cell line MDA-MB-468 at
the G2/M phase. Furthermore, the volume of tumors is signi-
cantly decreased in nude mice implanted with tricin-pretreated
MDA-MB-468 cells as compared to that in the control group.
53
Thus, tricin treatment results in arrest of the cancer cell cycle
and inhibition of the tumor growth. Gamma-tocotrienol also
inhibits human gastric adenocarcinoma SGC-7901 cell prolif-
eration via arresting the cell cycle at the G0/G1 phase.
54
Momilactone B, a terpenoid phytoalexin derived from rice bran,
exerts its anti-cancer effect by arresting the human leukemia
U937 cells at the G1 phase.
55
Gamma-oryzanol can arrest the cell
cycle of the prostate cell lines PC3 and LNCaP (at the G2/M
phase) and DU145 (at the G0/G1 phase).
56
Phytic acid, which
is also known as inositol hexakisphosphate (IP6), is a bioactive
compound existing in rice bran, and it induces cell cycle arrest
at the G0/G1 phase of the human colon cancer cell line HT-29
and breast cancer cell line MCF-7.
57,58
In summary, rice bran
extracts play an important role in suppressing cancer cell
proliferation by blocking cell cycle progression.
Promoting cell apoptosis
Dysregulation of cell apoptosis is one of the vital aspects of
cancer development. Promotion of cancer cell apoptosis
serves a critical role in cancer prevention and therapy.
Moreover, rice bran extracts and FRB exhibit a role in regu-
lating cancer cell apoptosis. Water-based extracts of rice bran
dramatically induce colon cancer cell apoptosis.
59
Phytic acid
from rice bran elicits a proapoptotic effect on the colon
cancer cells HT-29 through the regulation of Bax and Bcl-xl
protein expression.
60
Moreover, phytic acid induces the
apoptosis of the liver cancer cells HepG2 by upregulating the
expression of the proapoptotic genes p53 and Bax and
downregulating the expression of the antiapoptotic gene Bcl-
2.
61
Cycloartenyl ferulate, one of the phenolic compounds
from rice bran, promotes the activity of the death receptors
DR4 and DR5, suppresses the antiapoptotic Bcl-2 expression,
elevates the proapoptotic Bak expression, and leads to the
apoptosis of the colon cancer cells SW480.
62
Tocotrienol is
Fig. 2 Rice bran extracts arrest the cancer cell cycle. Gamma-tocotrienol, gamma-oryzanol, and phytic acid (IP6) arrested the cell cycle at the
G0/G1 phase of gastric adenocarcinoma SGC-7901 cells; prostate cells DU145, colon cancer cells HT-29, and breast cancer cells MCF-7.
Momilactone B treatment resulted in human leukemia cell U937 arrest at the G1 phase. Tricin and gamma-oryzanol could also arrest the breast
cancer cells MDA-MB-468 and prostate cell lines (PC3 and LNCaP) at the G2/M phase.
This journal is © The Royal Society of Chemistry 2019 RSC Adv.,2019,9,18060–18069 | 18063
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also involved in mediating cancer cell apoptosis. Gamma-
tocotrienol induces caspase 3 activation and contributes to
the apoptosis of the gastric adenocarcinoma SGC-7901
cells,
54
whereas delta-tocotrienol elevates the expression of
p21, p27, and caspases 3 and 9, represses Akt phosphoryla-
tion, and results in human colorectal adenocarcinoma DLD-1
cell apoptosis.
63
Administration of MGN-3/Biobran, a modi-
ed arabinoxylan rice bran, can promote tumor cell
apoptosis and reduce tumor volume and weight in mice
bearing a solid Ehrlich carcinoma.
64
MGN-3/Biobran also
enhances yeast-induced breast cancer cell apoptosis via
activating the caspases 8 and 9 in the MCF-7 cells and cas-
pases3,8,and9intheHCC70cells.
65
Other studies indicate
that MGN-3/Biobran exhibits a proapoptotic effect on the
human leukemic HUT78 cells in a death receptor CD95-
dependent manner
66
and induces the human multiple
myeloma cell line U266 cell apoptosis by decreasing the Bcl-2
expression and increasing the Bax expression.
67
A recent
study has also showed that FRB with Aspergillus oryzae
activates the expression of the death receptor DR5 and Fas
protein, promotes the protein levels of caspases 3, 8, and 9,
reduces the Bcl-2 expression, and leads to the human acute
lymphoblastic leukemia Jurkat cell apoptosis.
68
In general,
rice bran extracts and FRB might promote cancer cell
apoptosis by enhancing the proapoptotic protein expression
and repressing the antiapoptotic protein expression (Fig. 3).
Enhancing the chemopreventive effects
Chemoprevention is the use of natural or synthetic agents to
inhibit, delay, or reverse carcinogenesis.
69
As shown in Fig. 4,
studies have demonstrated that rice bran extracts and FRB can
be effective natural agents for chemoprevention. Diethylni-
trosamine (DEN) and 2-acetylaminouorene (AAF) are carcino-
gens that can induce the development of liver cancer. An in vivo
study has indicated that DEN/AFF exposure elevates hepatic
lipid peroxidation and low-density lipoprotein oxidation and
leads to liver carcinogenesis in Sprague-Dawley rats.
70
However,
Fig. 3 Rice bran extracts and FRB promote cancer cell apoptosis. Rice bran extracts (phytic acid, cycloartenyl ferulate, gamma/delta-tocotrienol,
and MGN-3/Biobran) and FRB administration dramatically induced cancer cell apoptosis via promoting the expression of proapoptosis proteins
(Bax, Bcl-xl, Bak, P21, P27, P53, and caspase 3/8/9), activating apoptosis-related receptors (DR4/5, CD95, and Fas) or inhibiting the expression of
the anti-apoptotic protein Bcl-2.
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treatment with tocotrienol-rich fraction reduced the DEN/AFF-
induced activation of the abovementioned parameters and
hepatocarcinogenesis.
70
The total phenolics and gamma-
tocotrienol in rice bran have a positive correlation with
reduced colorectal cancer cell growth.
71
N-Nitrosobis(2-
oxopropyl)amine (BOP), N-butyl-N-(4-hydroxybutyl)-
nitrosamine (OH-BBN), N-methyl-N0-nitro-N-nitrosoguanidine
(MNNG) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
(NNK) are well-known carcinogens. Diets with 5% or 10% fer-
mented brown rice and rice bran have signicantly inhibited
BOP-induced pancreatic cancer,
72
OH-BBN-induced bladder
carcinogenesis,
73
MNNG-induced gastric cancer,
74
NNK-
induced lung cancer,
35
and prostate carcinogenesis in the
transgenic rat adenocarcinoma of the prostate (TRAP) strain.
75
In addition to directly reducing chemical-induced carcino-
genesis, the rice bran extracts can enhance the sensitivity of
cancer cells to chemotherapy drugs. MGN-3/Biobran treatment
signicantly increases the susceptibility of the human non-
metastatic breast cancer cells MCF-7 and metastatic murine
breast cancer cells 4T1 to paclitaxel.
76
Another study showed
that MGN-3/Biobran contributes to enhanced sensitivity of the
breast cancer cells MCF-7 and HCC-70 to daunorubicin.
77
Overall, rice bran extracts and FRB are potential chemo-
preventive agents that act by reducing carcinogen-related
cancer induction and enhancing the susceptibility of cancer
cells to chemotherapy drugs (Fig. 4).
Clinical trials
In addition to studies that have focused on the function of rice
bran extracts and FRB in cell or animal models, increasing
research is being concentrated on their clinical effects. Dietary
supplementation of rice bran dramatically downregulates the
level of the inammatory factor IL-6 in overweight and obese
adults.
78
In patients with type II diabetes, the dietary
consumption of rice bran oil signicantly reduces the blood
levels of total cholesterol, triglyceride, and low-density lipo-
protein cholesterol.
79,80
In addition, RBO containing gamma-
oryzanol
81
or rice bran extract containing an acylated steryl
glucoside fraction
82
effectively decreases low-density lipoprotein
cholesterol levels. Thus, rice bran administration could miti-
gate the inammatory reaction and reduce the level of blood
lipids in obese and hyperlipidemic subjects. Rice bran extracts
still play a crucial role in regulating innate immune activity.
MGN-3/Biobran consumption for 30 days dramatically
increased the NK cell activity in geriatric subjects (over 65 years
old).
83
A study that enrolled patients with multiple myeloma has
also indicated that dietary supplementation with MGN-3/
Biobran contributes to elevated NK cell activity.
84
The function
of activated NK cells is to help recognize and kill cancer cells,
which is critical for cancer prevention and immunotherapy.
Another clinical effect of rice bran extracts is the regulation of
gastrointestinal function. Administration of MGN-3/Biobran
remarkably attenuates the clinical symptoms of patients with
diarrhea-predominant or mixed-type irritable bowel
syndrome.
85
A heat-stabilized rice bran diet offers the benets of
bacterial richness and diversity in the gut, helps with microbial
metabolism, modulates stool metabolite proles, and contrib-
utes to chemoprevention in colorectal cancer survivors.
86–88
The
function of rice bran in altering gut microbiota might
contribute to the relief of adverse gastrointestinal effects in
cancer patients during chemotherapy. A study that enrolled
patients with cervical cancer indicated that the oral intake of
hydrolyzed rice bran effectively attenuated the diarrheal side
effects of chemotherapy.
89
Rice bran extracts also exert an
adjuvant therapeutic effect on cancer patients. A study of
hepatocellular carcinoma patients receiving interventional
therapy demonstrated that dietary supplementation of MGN-3/
Biobran signicantly decreased the recurrence and increased
the two-year survival rate.
90
Therefore, rice bran extracts play
Fig. 4 Rice bran extracts and FRB have chemopreventive effects. Tocotrienol treatment reduced DEN/AFF-induced liver carcinogenesis. A diet
of FRB effectively inhibited BOP-induced pancreatic cancer, OH-BBN-induced bladder cancer, MNNG-induced gastric cancer, and NNK-
induced lung cancer. MGN-3/Biobran supplementation enhanced the susceptibility of breast cancer cells to paclitaxel and daunorubicin.
This journal is © The Royal Society of Chemistry 2019 RSC Adv.,2019,9,18060–18069 | 18065
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Table 2 Detailed information of rice bran extracts in clinical trials
Types of extract Types of trial Registration number
Target
enroll
number Disease type Conclusion Reference
Rice husk powder or
rice bran
Randomized
trial
IRCT2015040721652N1 105 Overweight and
obese adults
Rice husk powder and rice bran
consumption combined with an energy-
restricted diet signicantly reduced the
levels of inammatory factor IL-6 in
overweight and obese subjects
78
Rice bran oil (RBO) or
canola oil (CO)
Randomized,
controlled,
parallel-group
trial
IRCT2014050417568N1 75 Postmenopausal
women with type 2
mellitus
RBO or CO treatment attenuated lipid
disorders in type 2 diabetic women. RBO
improved the lipid prole more efficiently
than CO
79
Rice bran and sesame
blend oil
Open-label
randomized
trial
300 Patients with type
2 mellitus
A novel blend of 20% cold-pressed
unrened sesame oil and 80% physically
rened rice bran oil, when used as cooking
oil, lowered hyperglycemia and improved
the lipid prole in type 2 diabetes mellitus
patients
80
Rice bran oil (RBO)
containing gamma-
oryzanol
Randomized,
double-blind,
controlled trial
59 Hyperlipidemic
subjects
RBO with gamma-oryzanol decreased LDL-C
levels and increased the antioxidant
capacity in hyperlipidemic subjects. Thus,
RBO consumption may reduce
cardiovascular disease risk factors
81
Rice bran extract
containing acylated
steryl glucoside
fraction (RB-ASG)
Randomized,
double-blinded
trial
51 Obese men RB-ASG fraction might reduce the blood
LDL cholesterol levels and the risk of
arteriosclerosis in obese Japanese men
82
MGN-3/Biobran Randomized,
double-blind,
placebo-
controlled trial
12 Healthy geriatric
subjects
Biobran/MGN-3 induced a signicant
increase in NK activity, which may increase
resistance to viral infections and cancers in
the geriatric population
83
MGN-3/Biobran Randomized,
placebo-
controlled trial
48 Multiple myeloma
patients
MGN-3 might represent an immunologically
relevant product for activating innate
immunity in multiple myeloma patients
and warrants further testing to demonstrate
clinical efficacy
84
MGN-3/Biobran Pilot,
randomized,
controlled trial
40 Diarrhea-
predominant or
mixed-type
irritable bowel
syndrome
The administration of Biobran/MGN-3
improved IBS symptoms. The anti-
inammatory and/or immune modulatory
effects of Biobran might be useful in IBS
patients
85
Heat-stabilized rice
bran or cooked navy
bean powder
Randomized-
controlled pilot
trial
NCT01929122 29 Colorectal cancer
survivors
Dietary supplementation of heat-stabilized
rice bran or cooked navy bean powder had
benets for gut microbiotic richness and
microbial metabolism
86
Heat-stabilized rice
bran
Randomized
controlled trial
NCT01929122 29 Colorectal cancer
survivors
Heat-stabilized rice bran consumption
favorably modulated the stool metabolome
of colorectal cancer survivors
87
Heat-stabilized rice
bran or cooked navy
bean powder
Randomized
controlled trial
NCT01929122 29 Colorectal cancer
survivors
Increased dietary heat-stabilized rice bran
or cooked navy bean powder consumption
contributed to colorectal cancer
chemoprevention
88
Hydrolyzed rice bran Randomized,
double-blind
pilot trial
UMIN000004350 20 Cervical cancer
patients
Hydrolyzed rice bran administration may
relieve diarrhea, an acute-phase
gastrointestinal side effect of
chemoradiotherapy
89
MGN-3/Biobran Three-year
randomized
trial
NCT01018381 68 Patients with
hepatocellular
carcinoma
Biobran/MGN-3, in conjunction with
intervention therapy, may be useful for the
treatment of hepatocellular carcinoma; this
treatment showed lower recurrence and an
increased the two-year survival rate
90
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RSC Advances Review

a large role in regulating inammation, lipid metabolism, and
clinical cancer therapy via the modulation of gastrointestinal
function, chemotherapy effects, and interventional therapy
effects (Table 2).
Conclusion
Rice bran extracts and FRB are promising adjuvant therapeutic
agents for cancer prevention and therapy. They might play
a critical role in suppressing local inammation, arresting the
cancer cell cycle, promoting cancer cell apoptosis, and
enhancing the chemopreventive effects (Fig. 5). Furthermore,
the benets of dietary supplementation of rice bran include
modulation of the microbiota richness of the gut, maintenance
of the gastrointestinal function, attenuation of the side effects
and enhancement of the therapeutic effects in cancer patients.
In general, as potential nutraceuticals, rice bran extracts and
fermentation products are greatly expected to contribute health
benets to those suffering from pathological conditions.
Furthermore, nutraceutical supplementation is a new clinically
auxiliary strategy for the prevention or therapeutic treatment of
acute and chronic diseases.
Conflicts of interest
The authors declare no conict of interest.
Abbreviations
RBO Rice bran oil
RBP Rice bran protein
FRB Fermented rice bran
DR Death receptor
Bcl-2 B-cell lymphoma-2
Bax BCL2-associated X protein
Bak Bcl-2 homologous antagonist/killer
Bcl-xl B-cell lymphoma-extra large
MGN-3/
Biobran
Arabinoxylan rice bran
DEN Diethylnitrosamine
AAF 2-Acetylaminouorene
BOP N-Nitrosobis(2-oxopropyl) amine
OH-BBN N-Butyl-N-(4-hydroxybutyl)-nitrosamine
MNNG N-Methyl-N0-nitro-N-nitrosoguanidine
NNK 4-(Methylnitrosamino)-1-(3-pyridyl)-1-
butanone
CD95 Cluster of differentiation 95
IL Interleukin
NK Natural killer
TNF Tumor necrosis factor
Mac-1 Macrophage-1
CCL Chemokine (C–C motif) ligand
CXCL Chemokine (C–X–C motif) ligand
LDL Low-density lipoprotein
Acknowledgements
This work was supported by the Beijing Natural Science Foun-
dation (7172210), the Beijing Nova Program
(Z181100006218043), the National Natural Science foundation
of China (NSFC 81471873), the Beijing Excellent Talents Fund-
ing for Youth Scientist Innovation Team (No.
2016000026833TD01), the High-level Teachers in Beijing
Municipal Universities (IDHT20180506), the Shenzhen Munic-
ipal Commission Science and Technology Innovation
JSGG20170413151359491.
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