Food Reviews International

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Coix Seed: A Review of Its Physicochemical

Composition, Bioactivity, Processing, Application,
Functionality, and Safety Aspects

Chidimma Juliet Igbokwe, Ming Wei, Yuqin Feng, Yuqing Duan, Haile Ma &
Haihui Zhang

To cite this article: Chidimma Juliet Igbokwe, Ming Wei, Yuqin Feng, Yuqing Duan, Haile Ma
& Haihui Zhang (2021): Coix Seed: A Review of Its Physicochemical Composition, Bioactivity,
Processing, Application, Functionality, and Safety Aspects, Food Reviews International, DOI:
10.1080/87559129.2021.1892129

To link to this article: https://doi.org/10.1080/87559129.2021.1892129

Published online: 17 Mar 2021.

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FOOD REVIEWS INTERNATIONAL
https://doi.org/10.1080/87559129.2021.1892129

REVIEW

Coix Seed: A Review of Its Physicochemical Composition,

Bioactivity, Processing, Application, Functionality, and Safety
Aspects
a,b
Chidimma Juliet Igbokwe , Ming Weia, Yuqin Fenga, Yuqing Duana,c, Haile Maa,c,
and Haihui Zhanga
a
School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China; bDepartment of Food Science and
Technology, University of Nigeria Nsukka, Enugu State, Nigeria; cInstitute of Food Physical Processing, Jiangsu
University, Zhenjiang, China

ABSTRACT KEYWORDS
Coix seed (also known as adlay, Job’s tears) is a cereal grain mainly popular in Coix seed; isolation;
tropical Asia. It is used in Chinese traditional medicine to treat various types of functionality; safety;
diseases and also consumed as food. It is rich nutritionally and contains a wide bioactivity
range of bioactive compounds and phytochemicals. The functionality of coix
seed has been explored to the extent that it may provide a basis for its use as
a food ingredient. Several studies have demonstrated the biological activity of
coix seed. Published reviews on coix seed are scattered and not systematic.
This review gives a comprehensive summary of the physicochemical compo­
sition, bioactivity, processing, application, and safety aspects of coix seed.

Introduction
Coix seed (Coix lachryma-jobi L. var. ma-yuen Stapf) is a minor annual cereal grain that belongs to the
Gramineae family. It has a long history of use in China, serves as a food source and is used as
a medicinal herb. Coix seed origin can be traced back to tropical Asia, in particular China. It has other
common names, including adlay (Philippines), Job’s tears (English) or pearl barley, hatomugi (Japan),
and “da wan si” or “yi yi ren” (China). The seeds are hard oval or egg-shaped structures, with a pearly
white outer surface and slightly sweet to tasteless .[1] It is covered by a hard, shiny dark brown to the
grayish-black hull.
Coix seed from diverse species differs in size and appearance (mostly color). Translucent coix seed,
big coix seed, and small coix seed are the predominant types. Fig. 1 shows a pictorial representation of
varieties of coix seed grain. Dehulled coix seed can be polished, boiled, and eaten in the same way as
rice or as an ingredient in fermented beverages and tea. It can also be ground into flour as a composite
or used whole for baking pastry products. Coix seeds are used to treat arthritis, diarrhea, remove heat,
diuresis, help the drainage of pus, stimulate the lung’s function and spleen in traditional Chinese
medicine.[2]
Coix seed is nutritionally rich and has unique biological activities. It contains 65% carbohydrates,
14% protein, 3% crude fiber, 5% fat, 0.242% phosphorus, 0.07% calcium and 0.001% iron.[3] Evidence-
based research has shown that coix seed contains bioactive components including phenolic com­
pounds, [4] polysaccharides, [5] coixol, [6] coixenolide, [7] flavonoids, and lactams.[8,9] These bioactive
components have been shown to confer various health-promoting and pharmacological properties,
namely anti-inflammatory, anti-cancer, antidiabetes, antioxidant, and anti-obesity. Moreover, an
extract of coix seed oil of pharmaceutical grade is marketed under the trade name “Kanglaite”

CONTACT Yuqing Duan [email protected] School of Food and Biological Engineering, Jiangsu University, Zhenjiang
212013, China.
© 2021 Taylor & Francis
2 C. J. IGBOKWE ET AL.

Figure 1. Photograph of different varieties of Coix seed grains. A – big coix seed, B – coix seed with bran, C – small coix seed, D –
translucent coix seed.

(KLT). It has undergone Phase I, II, and III clinical trials as approved by the Food and Drug
Administration (FDA) due to its proven efficacy in treating various types of cancer.[10–12] However,
the active components responsible for these health claims and the action mechanism need to be
further studied and elucidated.
Studies on bioactive food components as an alternative to disease prevention or treatment has
plummeted over the last decade. Bioactive food compounds are secondary plant metabolites that occur
in small quantities which demonstrate specific pharmacological or toxicological effects in man.[13] As
emphasis on the role diet and nutrition play in disease mitigation and prevention, intake of bioactive
rich foods such as fruits, vegetables, whole grains among others is strongly encouraged. Coix seed
contains an affluent reserve of these bioactive compounds which has potentials to promote physiolo­
gical or cellular effects in human health besides its basic nutritional function. This review gives
a comprehensive summary of the physicochemical composition, application, bioactivity, processing,
functionality, and coix seed’s safety aspects. This concise and indepth contribution will act as reference
material for better understanding the potentials of coix seed grain, which may open up more areas
requiring further research.

Chemical profile of coix seed

The chemical composition of coix seed is influenced by variety, extraction solvent, pretreatment, and
geographical differences. A significant proportion of the endosperm contains starch.
 FOOD REVIEWS INTERNATIONAL 3

Starch
Starch is a polysaccharide made up of linear amylose and branched amylopectin. It can be isolated
from various plant parts, including tubers, roots, seeds, and they perform multifunctional roles in both
food and non-food industries. Starch isolated from wheat, corn, and rice grains is the commonest
cereal starches that have been exploited for use as a binder, adhesive, thickener, gel, among others, in
industries. Focus on exploring other starch sources is ongoing to increase variety and functionality,
and coix starch can compete in this regard. Liu et al.[14] assessed the crude starch content in three types
of coix (big coix, small coix, and translucent coix) seed, and the results show a significant variation
among the cultivars. The translucent coix seed (TCS) variety contained significantly higher amylose
content (20.33%) among the three types.
Native starch from plant sources can be modified physically, chemically, or enzymatically to
improve and extend its functionality. Heat moisture treatment was used to physically modify coix
starch, which increased the amylose content from 6.32% to 8.10%, [15] although the species of coix seed
used in the study was not specified. Kim et al.[8] modified adlay starch with glutaric acid; resistant
starch of the glutarate starch ranged from 13.5 to 66.5%. The authors observed an increase in glutaric
acid content, with reaction time, and reaction temperature causing a significant increase in the
resistant starch levels.

Coix polysaccharide
Polysaccharide from natural sources has gained global attention owing to its diverse pharmacological
activities. Some schools of thought believe that sugar composition and molecular weight significantly
influence polysaccharide’s biological function. Emerging research evidence has shown that coix
polysaccharides possess biological activities in modulating gut microbiota, antioxidative, anti-
cancer, hypolipidaemic, and immunological properties. Yao et al.[16] isolated and purified alkali-
extractable polysaccharide, two polysaccharide sub-fractions (AAP-1 and AAP-2), and ultrasonically
treated fractions (AAP-1ʹ and AAP-2ʹ) from coix seed. In the study, average molecular weights were
reported as 63.1 kDa, 94.2 kDa, 60.4 kDa, and 82.3 kDa and for AAP-1ʹ, AAP-1, AAP-2ʹ and AAP-2,
respectively. Rha, Ara, Glc, and Gal were indicated as the monosaccharide composition of AAP-1 and
AAP-1ʹ in a molar ratio of 1.1:0.4:0.7:0.5 and 1.4:1.6:0.4:0.7. Xyl, Rha, Gal, and Glc were the
constituents of AAP-2 and AAP-2ʹ in a molar ratio of 0.4:1.6:0.5 and 0.3:1.6:1.1:0.7.
Apirattananusorn et al.[17] studied the alkali extractable non-starch polysaccharides (arabinoxylans)
of polished dark and white husk types of coix seed. In the study, the ratio of arabinose to xylose (Ara/
Xyl) was 1.25 and 1.24 in the two alkali extractable arabinoxylans, which indicates a highly branched
structure. The average molecular weights were 741 kDa and 1,449 kDa for the arabinoxylan of the dark
and white husk type, respectively, which reduced tremendously after protease treatment.

Protein
Plant proteins have been an object of extensive research over the last decade, other than their
nutritional properties. They are also sought after in food product formulation and development of
nutraceutical products due to their techno-functional properties (foams, gels, emulsifiers, films, etc.)
and bioactivity. Plant proteins find application in meat products to act as fillers and fat replacers.[18–20]
They are also used to encapsulate bioactive substances and nutrient supplements due to their
hydrophobic and hydrophilic nature (amphiphilic character).[21]
Coix seed contains superior essential amino acids compared to other cereals such as rice. The
prolamins (also called coixin) are the major components of coix grain protein. Leite et al.[22] separated
coix prolamins into four classes: α-, β- and γ- using differential solubility. The α-prolamins of coix are
naturally rich in proline, alanine, glutamine, and leucine residues. However, they observed that lysine
and tryptophan contents were relatively low due to the high content of prolamins in the total grain
4 C. J. IGBOKWE ET AL.

protein. Lin et al.[23] identified 10 coixins; calculated amino acid compositions show that all 10 coixins
are rich in glutamine (>20% in R-coixin isoforms, 13.3% in δ-coixin, and 31.2% in γ-coixin). However,
the δ-coixin is a sulfur-rich protein (9.1% cysteine and 18.2% methionine), and the γ-coixin is
a nutritious protein composed of 2.6% lysine, 6.6% cysteine, 2.0% methionine, and 8.9% histidine.
Genetic differences and variety can affect the protein content of coix seed. Liu et al.[24] observed
differences in the protein content of three types of coix seed - translucent coix seed (TCS), big coix
seed (BCS), and small coix seed (SCS). In the study, SCS grain was found to contain the highest protein
content of 16.16% among the three kinds of cereal, the prolamins of TCS recorded the highest protein
content of 95.24% and 7.73% in terms of extraction yield, while BCS had the lowest protein content
(13.64%) and extraction yield among the three varieties.
Germination has also been observed to enhance the nutritional quality of cereal grains. Xu et al.
(2017a)[25] observed that the coixol content of coix seed germinated over 60 hours increased from
30.08 to 109.59 µg/g, although there was a decrease in the first 24 hours. The authors further noted that
the germination process resulted in protein breakdown, SDS soluble protein increased, and low
molecular weight (LMW) protein changed.

Coix seed oil

Coix seed oil is the most economical and functional component of coix seed, representing the
principal constituent of the cancer drug Kangliate (KLT). In line with the principles of drug safety,
KLT is the only Traditional Chinese Medicine (TCM) that has gone through various clinical trials both
in the USA and Russia for treatment of multiple types of tumors, most especially non-small cell lung
cancer (NSCLC).[26] Coix seed contains a relatively higher amount of lipids compared to other cereal
grains. Coixenolide and a rich source of fatty acids have been identified as the bioactive components of
coix seed oil responsible for its potency in cancer treatment. Xi et al.[27] reported ample quantities of
fatty acids, namely oleic acid, linoleic acid, palmitic acid, and stearic acid from different accessions of
coix seed oil, the unsaturated fatty acid (oleic and linoleic acid) was significantly high in the different
accessions ranging from 74.08% to 82.28% of the total fatty acids. Furthermore, Numata et al.[28] had
earlier demonstrated that palmitic acid, stearic acid, oleic acid, and linoleic acid have strong anti-
tumor activity in mice models.
Moreover, thin layer chromatography shows that neutral lipids (>90%, triacylglyceroles and about
5% diacylglyceroles) are the main components of coix seed oil[29]. Li[30] identified 11 triglycerides in
coix seed oil namely 1-olein-2, 3-dilinolein (13.00 -\18.69%), trilinolein (4.87–6.99%), 1-palmitin-2,
3-dilinolein (5.25–7.54%), 1-palmiitin-2,3-dilinolein (5.25–7.%), 1-olein-2,3-dilinolein (13–18.69%),
1, 3-diolein-2-linolein (13.23–19.02%), 1, 3-dipalmitin-2-linolein (2.28–20.76%) and 1-palmitin-2,
3-diolein (8.06–11.52%), 1, 3 dipalmitin-2-olein (1.52–2.19%), 1-olein-2-linolein-3-stearin (1.37–­
1.97%) and 1,2-diolein-3-stearin (1.29–1.86%).

Phenolic compounds
There is a linear relationship between total phenolic content and antioxidant activities. It has been
postulated that phenolic compounds can potentially play a role in protecting the body against
oxidative stress and its effects because of their well-known antioxidant properties. It is generally
measured as milligrams of gallic acid equivalent per gram of a sample on a dry weight basis. Phenolic
compounds are one of the most critical coix seed constituents, influencing some of its biological
activity. There is growing evidence on the phenolic composition of coix seed and its extracts. Lin
et al.[31] identified a total of 20 phenolics, including 10 phenolic acids, two coumarins, two phenolic
aldehydes, and six flavonoids in adlay bran using a phenolic compound-guided separation technique.
For the first time, sinapic acid was also identified in adlay bran in the study. It exhibited strong
xanthine oxidase (XOD) inhibitory activity in a mixed non-competitive manner and displayed
synergistic effects with other adlay phenolics.
 FOOD REVIEWS INTERNATIONAL 5

The phenolic content of coix seed has been divided into free and bound phenolics, varying
depending on the seed and geographical location. Zhao et al.[32] reported that free and bound
phenolics of coix seed bran exhibited significant antioxidant activities (oxygen radical absorbance
capacities, xanthine oxidase inhibition activities, superoxide radical scavenging activities, and
2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities) when compared with the coix
seed hull, brown coix seed, and polished adlay. Wang et al.[33] compared the total polyphenol and
antioxidant activity of coix seed varieties selected from three locations in China. In the study, the free
and bound phenolics did not differ much among the coix seed varieties, and total phenol content was
in the range of 59.30 to 76.04 mg of gallic acid equivalent GAE/100 g.
In a recent study, Yao et al.[34] used Sephadex LH-20 to separate and purify crude insoluble-bound
polyphenol extracts (CEAE) from coix seed into three fractions in a time-dependent manner. Fraction
2 (collection time 11–12 h) was reported to have the highest total polyphenol content
(216.21 ± 10.99 mg GAE/g) among the three fractions. Ferulic acid was also identified as the active
component of insoluble bound polyphenol content of coix seed. Wang et al.[35] reported that
n-butanol fractions extracted from defatted adlay meal recorded the highest total phenolic compound
(43.83 mg GAE/g DW) among three fractions. A similar trend was also reported in the sub-fractions of
n-butanol (6.34–183.42 mg GAE/g).
In most of the studies, detection and quantification of adlay phenolics seem to be the main thrust of
the studies. It will be interesting in future studies to apply ultrasonics and other green extraction
technologies for recovery and extraction of phenolic compounds from coix seed due to its advantages
over traditional extraction techniques.

Coix seed processing

Oil extraction
Coix seed oil is an important constituent of coix seed and it has some medicinal functions for human
health. Extraction of oil from coix seed can be affected by particle size, extraction solvent, solid–liquid
ratio, time and method of extraction. Conventional oil extraction methods such as solvent processes,
supercritical fluid extraction and ultrasonic procedures are employed to extract oil from coix seed. The
solvent process may be potentially toxic to human health and may also affect the flavor of the
resultant oil.
However, supercritical fluid extraction (SFE) is a clean, non-toxic, and effective technique that has
been developed in the last decade. Carbon dioxide (CO2) is the solvent that is commonly used due to
its low critical pressure (7.8 MPa) and temperature (31.1o C), low cost, and availability. It also has the
advantage of the ease of removal from a product. Hu et al.[36] compared the extraction efficiency of
ultrasound-assisted supercritical fluid extraction (USFE) and SFE, and they concluded that the
differences between SFE and USFE were not significant. The extracted oil met the quality standard
requirements for coix seed oil.
Ultrasonics is also a novel emerging technology that acts through the cavitation phenomenon. The
cavitation, mechanical and thermal effects enhance the cell wall’s penetration, leading to the release of
their contents into the medium. Ultrasound-assisted extraction of coix seed oil increased the oil yield
(14%) and could reduce the CO2 flow rate, pressure, temperature, and time used in the extraction
process.[36] It also has the potential to conserve and protect the bioactive components of the
resultant oil.

Isolation of starch
Starch is a significant component of coix seed (58% dry weight) and an essential structural component
in many coix seed products.[15] Its starch properties may be suitable for food product development and
formulation similar to other cereal grains. Repetitively, some authors adopted the method described
6 C. J. IGBOKWE ET AL.

by Kim et al.[8] for starch isolation from coix seed using the alkaline steeping method. The process
involves steeping the grains in excess water for 18 hours at room temperature, grinding in a milling
machine, and stepwise filtering in 50-, 100- and 200-mesh sieves. Centrifugation of the filtrate at
5000 g for 10 minutes was used for isolation of starch. The supernatant was discarded, and the top,
yellowish layer of protein removed. Repeated washing using NaOH and centrifugation was used to
neutralize starch slurry and starch cake drying was at room temperature.
However, some authors[37] adopted a different method, steeping with 0.45% Na2S2O5 in a water
bath at 40°C for 48 hours. Removal of the germ and the grinding of the endosperm. Filtration of the
slurry was carried out, and the residue was reground and rescreened several times. Purification of
extracted starch granules was achieved with 0.05 M NaCl and one-fifth volume toluene. Purified starch
granules were washed twice with distilled water and once with acetone. Finally, starch cakes were dried
at 40°C. Native coix seed starch shows polygonal, irregular, or spherical shapes that varied with size
.[15] Native granules display relatively smooth surfaces except for slight pits on their granular surfaces.
Schematic presentation of isolation of coix starch is shown in Fig. 2.

Figure 2. Schematic flow diagram showing isolation of coix seed starch.

 FOOD REVIEWS INTERNATIONAL 7

Extraction of coix proteins

Dehulled coix seed grain is rich in protein, 14.8 g per 100 g edible portion compared to other cereal
grains. There is very limited information on the extraction of protein from coix seed, although
opportunities exist to explore its protein extraction using green extraction techniques. Alkaline and
salt extraction methods are among the most effective and feasible protein extraction methods. Cao
et al.[38] compared two extraction methods using an alkaline method and salt method for protein
extraction from coix seeds. The alkaline extraction method, based on the extraction rate of protein
from coix seed, single factor, and orthogonal array design, was used to optimize the extraction
parameters: pH, temperature, extraction time, and solid-to-liquid ratio. By the same design, tempera­
ture, salt concentration, solid-to-liquid ratio, and extraction time were optimized in the salt extraction
method. The results showed that the optimum solid-to-liquid ratio, extraction time, temperature, and
pH for the alkaline extraction of coix seed protein were 1:12, 5 h, 35°C, and 11, respectively. The
extraction rate of protein was up to 43.56% under these conditions, and the authors concluded that the
alkaline extraction method was the most preferred relative to the salt extraction method.

Food application of coix seed

The grains are typically pounded, threshed, winnowed, and polished. Due to the rich starch content of
coix seed, the pounded kernel can be used in broths, soups, porridge, and pastries, which serve as food
ingredients.[39] Fried and sugar-coated pounded coix seed kernel can also be made into a sweet snack,
and dehulled coix seed grains can be boiled and eaten like boiled peanuts. When ground into flour, the
kernels serve as a composite with wheat flour for baking pastry products such as biscuits and cakes.
Pounded coix seed flour can be used to brew tea, beverages, and herbal teas mixed with other herbs.
Coix seed kernels can be roasted and used to make a coffee-like drink. It can also be fermented into
wine and beers. In India, the pounded grain is fermented into beer known as zhu or dhu in the
Philippines. Okroju is a South Korean liquor prepared from rice and ground coix seed. Fermented
glutinous wine can also be produced with rice and coix seed. Yu et al.[40] explained that for glutinous
wine production, the ratio of coix seed to glutinous rice is 1:4. Herbal wines can also be produced from
coix seed mixed with other herbs depending on the needed application.
Other food applications of coix seed involve consuming it as a medicinal food combined with other
ingredients taken as a meal during the day to treat a particular ailment. Dharmananda[41] described
a recipe that involves boiling coix seed and other ingredients to make a gruel for treatment of ascites
secondary to liver cirrhosis, which includes: coix seed (30 grams), polished round-grained rice (30
grams), red kidney beans (30 grams), tangerine peel (3 grams).

Coix seed functionality

In simple terms, functionality connotes the different non-nutritive functions and food constituents
behavior and interaction in a food system. Food constituents functionality is vital to predict and assess
how starch, proteins, fat, and fiber can affect the quality of a finished product during processing,
storage, and ultimately sensory attributes. The coix seed functionality is mainly derived from the
starch content, and several studies have explored this angle ranging from rheology, pasting, and
thermal properties, among others.
Differential scanning calorimetry (DSC) is commonly used for evaluating thermal properties.
Thermal transitions are defined in terms of onset (To), peak (Tp), and end set (Tc) transition
temperature, the peak transition temperature (Tp) gives a measure of crystalline quality (double
helix length). In contrast, gelatinization enthalpy (ΔH) provides an overall measure of crystallinity
(quantity and quality) and indicates the loss of molecular order within the granule when gelatinization
occurs. Liu et al.,[42] evaluated the effect of heat moisture treatment on three varieties of coix seed
starch. The authors observed that gelatinization temperatures (To, Tp, Tc) of all heat moisture treated
8 C. J. IGBOKWE ET AL.

(HMT) starches were higher than those of the native starches, indicating more ordered crystallites
resulting from interactions between amylase-amylose, amylose-amylopectin, or amylopectin-
amylopectin chains might have formed during HMT. They further stated that enthalpy (ΔH) values
of varieties of the coix seed HMT starches decreased, which shows that the double helices of HMT
starches were weak and less energy would be required to unravel and melt them during gelatinization.
Rheological studies show that all the starch samples exhibited non-Newtonian shear-thinning flow
behavior in that the apparent viscosity of the starches decreased as the shear rate increased. The
evident viscosity values of the three native starches were higher than those of the corresponding HMT
starches.
Pasting properties of starch refer to changes in viscosity during the heating and cooling of starch-
water mixtures. It is commonly measured using a Rapid Visco Analyzer (RVA), which records the
peak viscosity (PV), breakdown (BD) setback (initial retrogradation of the starch paste on cooling),
and the final viscosity (FV) during a cycle of heating and cooling. Xu et al.[44] reported that the pasting
viscosity of raw adlay had the highest peak viscosity (PV) and final viscosity (FV) at 1,002.0 and 1,501.0
cP, respectively. However, the authors noted that germinated adlay had a much lower PV (65–261 cP)
and FV (13–57 cP) than the raw adlay due to the degradation of starch α-amylase during the
germination process. (Table 2) shows a summary of the pasting properties of coix seed starch. The
starch concentration in the starches’ pasting properties was not reported in all the studies (Table 1),
making it difficult for comparison since it is a crucial index relating to the pasting behavior of starch.
(Table 1) shows the pasting properties of coix seed starches.
X-ray diffractogram (XRD) is commonly used to study the crystallinity pattern of starch; the starch
crystal structure can be divided into four types: A, B, C, and V. The A-type polymorph has more tightly
packed crystals than the B-type. The C-type polymorph is generally considered as a mixture of the A-
and B-types. Zhang et al.[64] observed diffraction peaks at 15.1°, 17.2°, 18.0°, and 23.1° in native adlay
flour, and the degree of relative crystallinity was 24.59%. Wang et al.[15] also reported similar
diffraction peaks for heat moisture treated (HMT) starches, which is expected for A-type polymorph
and is a significant characteristic of cereal starches.[42,44,64,66] observed that germination process did
not affect the crystalline starch pattern of adlay flour. Fig. 2 and Fig. 3 show the XRD patterns of two
small and big coix seed starches.

Bioactivity of coix seed

Several studies have demonstrated the pharmacological potential and health-promoting properties of
coix seed, both invivo and invitro.[45,67] The numerous health claims ascribed to coix seed could be
attributed to its unique bioactive components such as coixan, coixol, lactams, [68] and coixenolide .[69]
Furthermore, coix seed has been shown to have a higher proportion of lipids and proteins than other
cereals that possess some pharmacological functions. The wide range of biological activities and health
benefits of coix seed are discussed below and summarized in (Table 2).

Anti-inflammatory activity
Inflammation is a natural defense response of the body to stimuli. When the response is continuously
triggered and sustained, it may predispose the body to various diseases such as cancer, depression, etc.
The application of dietary components, among other factors, has gained popularity among researchers
as a fundamental tool to stimulate pro-inflammatory pathways. Several studies have demonstrated the
efficacy of coix seed and its extract to inhibit inflammation.[49] studied the anti-inflammatory effects,
and chemical analysis of a flavonoid enriched fraction from coix seed bran. It was reported that
fractions with high phenolic and flavonoid contents from the ethanol extract of coix seed bran
suppressed lipopolysaccharide (LPS) stimulated interleukin 6 (IL-6) and tumor necrosis factor-α
(TNF-α) secretions in a concentration-dependent manner in RAW 264.7 cells and murine peritoneal
 FOOD REVIEWS INTERNATIONAL 9

Table 1.: Pasting properties of native and modified coix seed starch.

Native adlay RVA 1664 82 498 73.50 NR

[65]
Adlay extrudate RVA NR NR NR NR NR
[44]
Native adlay RVA 1844 569 483 76.07 1758
G12 RVA 1577 515 459 76.17 1521
G24 RVA 822 302 208 76.17 728
G36 RVA 303 178 84 76.65 210
G48 RVA 67 26 12 76.57 52
G60 RVA 48 21 10 76.60 32
[43]
Native adlay RVA NR 1.002 NR 76.55 1.501
Germinated adlay RVA 65–261 NR NR 75.55–75.85 13–57
[65]
Native adlay BVA 318.5 88 115 62.75 ND
S15 BVA 372.0 126.0 81.5 60.90 ND
S25 BVA 363.5 126.0 75.5 61.00 ND
S35 BVA 342.0 112.0 66.5 62.10 ND
S45 BVA 368.0 128.5 72.0 62.40 ND
S/S15 BVA 262.0 68.00 65.5 57.10 ND
S/S25 BVA 218.0 44.50 59.0 52.60 ND
S/S35 BVA 176.5 25.00 54.5 49.60 ND
S/S45 BVA 184.5 27.00 57.5 48.55 ND
Key: PV – Peak viscosity, BD – Breakdown viscosity, SB – Setback, PT – Pasting temperature, FV – Final viscosity, G12-G60
= Germination time (hours), S15-S45 = Steam time (minutes), S/S15-S/S45 = Steam/Soak time (minutes), RVA – Rapid Visco
Analyzer, BVA – Brabenda viscograph, NR – Not reported, ND – Not determined.

macrophages. The authors suggested that flavonoids in the coix seed bran could partially contribute to
its anti-inflammatory effect.
Three sub-fractions of ethyl acetate fraction of ethanol extract of adlay seed hull had a potent
inhibitory effect on nitric oxide (NO) production, inducible nitric oxide synthase (INOS), and
cyclooxygenase-2 (COX-2) expressions and pro-inflammatory cytokines IL-6 and TNF-α secretion
in lipopolysaccharide activate RAW 264.7 cells system [50]. Nobiletin, tangeretin, and p-hydroxyben­
zoic acid were reported as the main active compounds responsible for the anti-inflammatory proper­
ties. The methanolic extract of coix seed showed significant inhibition of NO and O2 by activated
RAW 264.7 cells in a dose and time-dependent manner through suppression of inducible NO synthase
messenger ribonucleic acd (mRNA) expression and probably by interfering with the mechanism of
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase of macrophages respectively[51].
Choi et al.[70] observed that fractions of dehulled adlay had inhibitory activity on LPS-induced NO
production with IC50 values of 12 µg/mL compared to hulled adlay, which showed no activity.

Antioxidant activity
Free radicals are typical by-products of cellular redox processes in the body, usually in reactive oxygen
species (ROS) or reactive nitrogen species (RNS). Oxidative stress induced by ROS at high concentra­
tions has adverse effects on all organisms. In humans, oxidative modification of cellular macromole­
cules by ROS underlies various degenerative diseases such as cancer and aging .[71] It is believed that in
addition to the human endogenous antioxidant system, antioxidants from natural sources may inhibit
oxidative stress. Therefore, antioxidant activity from natural resources has been the focus of various
researches. Coix seed and its different parts, including endosperm, bran, hull, and testa, coix seed has
been investigated for its antioxidant functions.
Polyphenolic extracts of adlay administered orally on high cholesterol diet-fed rats (HCD) for
28 days showed enhanced dose-dependent activities of antioxidant enzymes malondialdehyde (MDA)
and superoxide dismutase (SOD) of serum and antioxidant activities of the liver (glutathione perox­
idase and catalase and) relative to the control.[61] Adlay seed extracted using supercritical fluid
 10

Table 2. Some bioactivity and health-promoting properties of coix seed.

Bioactivity
property Extraction medium IC50/Dosage Methodology Key Findings References
[9,45–48]
Anti-cancer activity Hexane fraction of adlay testa 0.067 µM ATE-Hex Chemosensitizing effect on ATE-Hex alone or in combination with doxorubicin
ethanolic extracts (ATE-Hex). 10–300 µg/mL drug resistant uterine resistant significantly inhibited the growth of cancer cells and
Polysaccharide fraction was 1 mg/mL carcinoma cells. induced apoptosis.
extracted from coix seed (CP- 5.0 µg Western blot and MTT assay were used CP-1 inhibited A549 cell
1). Between 28.6 & to assess the effect of CP-1 on the proliferation and induced apoptosis.
Coix seed sprout extract (CLSE). 72.6 µg/mL viability of A549 cells. Migration, invasion, and adhesion of colon cancer cells were
C. J. IGBOKWE ET AL.

Coix extract emulsion. Anti-metastatic effect of Coix seed inhibited by CLSE.

Methanol extracts of adlay bran sprout extract (CLSE) in colorectal Coix seed oil extract attenuated NFKB signaling including
fractionated serially with cancer. down regulation of COX-2 and matrix metalloproteins.
various solvents. Anti-neoplastic activity of coix extract Inhibitory effect of fractionated adlay bran extracts on
emulsion in xenografts of MDA-MB human lung cancer, human colorectal carcinoma cells.
-231 breast cancer cells.
Antiproleferative effect of adlay bran
fractions on human lung cancer,
human colorectal carcinoma cells.
[49,50]
Anti-inflammatory Fraction and purification of 50 µg/mL Murine peritoneal microphages were Fractions of coix seed bran suppressed LPS – stimulated IL –
activity adlay bran components. 24.3 µg/mL collected from the peritoneal cavities 6 and TNF-α secretions in RAW 264.7 cells and murine
Sixteen fractions of ethyl of normal BALB/c mice. peritoneal macrophages.
acetate and ethanol extract RAW 264.7 cells were seeded in 96 well ABE-Ea-B had the most potent inhibitory effect on nitric
of adlay seed hull. plates in serum free medium oxide (NO) production, INOS and COX-2 expressions and
overnight and treated with only pro-inflammatory IL-6 and TNF-α secretion in
carrier vehicle. lipopolysaccharide activate RAW 264.7 cells system
[32,34,35,52,53]
Antioxidant Insoluble-bound polyphenols 0.5 mg/mL Intracellular activities, protein Ferulic acid, the main active component exerted protection
activity from adlay seed. 0.940–1.116 mg/mL expression levels of antioxidant in HepG2 cells against H2O2-induced oxidative stress and
Coix seed oil extracted from the for ABTS enzymes and apoptosis were increased the activity levels of antioxidant enzymes.
coix seed samples obtained 0.282–0.414 mg/mL determined to investigate effects of Coix seed oil exhibited considerable levels of ABTS radical
from four main-producing for β-Carotene- the main active components against H2 scavenging activity, FRAP activity, and β-Carotene-linoleic
areas of China. linoleic acid O2-induced oxidant stress in HepG2 acid bleaching activity.
Fructooligosaccharides (FOS) bleaching activity. cells. The antioxidant activity by DPPH free radical scavenging of
hot water extraction from –1.00 mg/mL Antioxidant scavenging activities of FOS containing extract was comparable to vitamin C.
coix grain Not reported coix seed oil were evaluated. Strong correlation between total phenolic content and
Phenolic rich fraction from 4.75 µg/ml Antioxidant and cytotoxicity of the FOS antioxidant activity.
defatted adlay meal. containing extract was determined. Adlay seed and derivatives contained significant amounts of
Polished adlay, brown adlay, Assay the effect of adlay meal on free or bound phenolics, possessing strong antioxidant
adlay bran, and adlay hull antioxidant enzyme activities. activities.
extracts. In vitro and In vivo studies on adlay-
derived seed extracts on antioxidant
activities.
(Continued)
Table 2. (Continued).
Bioactivity
property Extraction medium IC50/Dosage Methodology Key Findings References
[54–56]
Modulation of gut Dehulled adlay 20 and 40 g/kg diet Culture counts of groups of intestinal Adlay had an effect on the growth of intestinal bacteria,
microbiota Polyphenol extract of adlay Not reported bacteria and their metabolism in the which may affect the physiology of GI tracts of rats.
(PEA). 0.5 g/100 kg gastrointestinal (GI) tract of rats. PEA had a positive effect in ameliorating gut microbiota
Coix seed powder diet Polyphenol extract of adlay (PEA) on disorders rats.
gut microbiota in rats fed a high Structural alterations of gut microbiota by enriching some
cholesterol diets. beneficial bacteria in the gut by coix seed
Modulation of microbial composition
and function in response to coix seed
treatment in rat,
[57–59]
Anti-diabetic Water soluble polysaccharide 12 and 24 mg/kg/ Anti-diabetic activity of PAS from adlay PAS decreased blood glucose and insulin levels.
activity extracted from adlay seed day seed. PAS decreased blood glucose and serum insulin levels in
(PAS). 24 mgKg−1day−1 Anti-diabetic and gut microbiota of diabetic mice. Diversity and composition of the gut
Polysaccharides from adlay 100 mg/Kg/day adlay seed in streptozocin mice. microbiota changed as a result of PAS treatment.
seed (PAS). Coixan was extracted from Coix seed, Coixan has an effect on reducing postprandial blood glucose
Coixan from coix seed and administered to diabetic mice. from 10th week.
[31]
Antihyperuricemia Adlay bran free phenolic 2.88 µM Investigate the structure-activity Sinapic acid, identified from adlay bran, possessed strong
activity extract. relationship and interaction of XOD inhibitory activity.
phenolic acids as XOD inhibitors.
[60,61]
Hypolipidaemic Crude extracts of adlay seed 50 mg/100 g/day Effect of TNF-α and leptin gene Treatment of ACE modulated expressions of leptin and TNF-
activity (ACE). 2 ml expression in rat adipose tissue and α, and serum hyperlipidaemia in rats.
Polyphenol extract of adlay concentrations of serum lipid. Administration of APE decreased the levels of serum lipids.
(APE). Effect of polyphenols extract of adlay
(APE) on high cholesterol diet fed
rats (HCD)
[62,63]
Antiosteoporosis Water extract of adlay 0.3 g/kg/day Effect of adlay on osteoporosis using an Adlay alleviated the osteoporotic status in ovariectomized
activity Fractions of adlay hull extracts. 175 µg/mL ovariectomized mouse model. mice.
Antidysmenorrhea Evaluation of uterine contraction Hull extracts and its fractions inhibited uterine contraction in
activity activity. a concentration dependent manner.
FOOD REVIEWS INTERNATIONAL
11
12 C. J. IGBOKWE ET AL.

Figure 3. X-ray diffraction patterns of adlay seed starches[66]. Key: Q-2 and P-6 = two small adlay seed starches and BW = big adlay
seed starch.

extraction (SFE) technique exhibited antioxidant characteristics such as free radical scavenging
capacity and reducing power and it also effectively reduced ROS levels in B16F10 cells .[72]
Polished brown adlay, adlay bran, and adlay hull were evaluated for invivo and invitro antioxidant
activity. Zhao et al.[32] reported that all the adlay seed types and derived materials contain significant
amounts of free or bound phenolics that possess strong DPPH radical scavenging activities, oxygen
radical absorbance capacities (ORAC), and antioxidant activities in scavenging xanthine/xanthine
oxidase-derived superoxide radicals. Fructooligosaccharides (FOS) extracted from coix grain by hot
water extraction exhibited antioxidant activity by 2,2–diphenyl-1-picrylhydrazyl (DPPH) free radical
scavenging activity is comparable to vitamin C.[53] Water extracts of adlay seed germinated at different
periods have been shown to increase the ferric-reducing antioxidant power (FRAP) and total phenolic
content (TPC).[25]

Anti-cancer activity
The anti-tumor effect is one of the essential biological functions of the coix seed. In Chinese medicine,
coix seed extract and emulsion are potent in the treatment of various types of cancers, including lung
cancer, [73] colon cancer, [74] breast cancer, [75] hepatocellular carcinoma, [67,76] singly or in combina­
tion with other cancer drugs with minimal side effects compared to chemotherapy. Woo et al.[48]
reported a significant reduction in several functionally related genes related to cell growth, invasion,
and metastasis for breast cancer when experimental rats were treated with 50 µg of coix seed oil. The
coix seed oil extract attenuated nuclear factor kappa B (NFKB) signaling, including down-regulation of
COX-2 and matrix metalloproteins. Coix seed water extract attenuated the migration, invasion, and
adhesion of colon cancer cells and tube formation by human umbilical vein endothelial cells
(HUVECs) under hypoxic conditions by repressing the extracellular signal-regulated kinase (ERK1/
2) and protein kinase b (AKT) pathways.[47]
A novel polysaccharide extracted from coix seed inhibited growth, metabolism, and proliferation of
non-small cell lung cancer A549 cell proliferation and activated apoptosis through a mechanism that
 FOOD REVIEWS INTERNATIONAL 13

primarily involved the activation of the intrinsic mitochondrial pathway.[46] Similarly, a more recent
study showed that ethanolic extract of coix seed testa could inhibit human uterine sarcoma cells by
inducing apoptosis and increasing the human’s multidrug-resistant chemosensitivity uterine sarcoma
cell MES-SA/Dx5 to Doxorubicin, a chemotherapeutic drug.[45] Combining ethanolic extract of coix
seed testa and doxorubicin may reduce multi-drug resistance and increase the synergistic effect.

Modulation of gut microbiota

Gut microbiota exists in the intestinal tract in a mutually beneficial relationship with its hosts, assisting
the host to perform a variety of physiological and biochemical functions by engaging in a variety of
complex metabolic processes, as well as in the development and regulation of the immune system.[77]
Food is a significant factor that can significantly affect the composition and function of the human
microbiota. There is evidence that coix seed can create a balance of intestinal flora, crucial for human
health and disease prevention. In hypercholesterolemic rats, polyphenols extracted from coix seed had
a significant effect on alleviating gut microbiota disorders.[55] P-coumaric acid, ferulic acid, and
sinapinic acid were suggested as polyphenols that are responsible for the beneficial effects on the gut
microbial ecology. Chiang et al.[54] evaluated the impact of dehulled adlay on microbiota’s culture
count and metabolism in rats’ gastrointestinal tract. They observed that animals on adlay diets (20%
and 40%) had higher lactic acid bacteria populations and fewer enterics in their faeces. Caecal and fecal
short-chain fatty acid concentrations were also higher, which are beneficial to health. Liu et al.[56]
suggested that anti-obesity and anti-diabetic effects of coix seed are associated with structural altera­
tions in gut microbiota. Moreover, coix seed enriched some beneficial bacteria such as A. muciniphila
in the intestine.

Hypolipidaemic activity
It is well known that hyperlipidemia is the leading cause of chronic diseases such as atherosclerosis,
which can cause heart disease. Among other factors, an unhealthy diet seems to play a significant role
in the disease’s initiation and buildup. Various plant parts and their derivatives are being assayed on
their role in lipid management. Coix seed is no exception; polyphenol extract and oil emulsion from
coix seed have shown potentials in reducing total serum cholesterol, low-density lipoprotein, and
triglyceride levels with an accompanying increase in high-density cholesterol (good cholesterol) in
hypercholesterolemic rats.[61,78] A rich source of unsaturated fats (oleic and linoleic) may play a role in
coix seed oil’s hypolipidaemic activity since consuming saturated fats is known to cause elevated
plasma lipids.
Yeh et al.[79] demonstrated that dehulled coix seed could stimulate insulin production, leading to
lower plasma glucose levels and hypoglycaemic effect streptozotocin-induced diabetic rats. Kim
et al.[60] showed that crude extracts of coix seed significantly reduced leptin mRNA expression and
TNF-α in white adipose tissue of induced obese rats, which play a role in body weight control and lipid
metabolism, among others, respectively.

Skin treatment, anti-osteoporosis activity and anti-obesity activity

Enzymolysis products of adlay “Super Hamatogi” (SPH) have positively affected human skin improve­
ment in a double-blind placebo-controlled study. The number of nucleated epidermal cells reduced
due to SPH intake, which was correlated with a change in intestinal flora population.[80] The
mechanism of hydrolysis products of adlay on skin improvement and its association with intestinal
flora needs to be studied further.
Yang et al.[62] reported a reverse of osteoporotic conditions in ovariectomized (OVA) mouse
models fed adlay diet and extracts in a dose-dependent manner. Decreased calcium contents, alkaline
phosphatase activity, and bone mineral density levels were reversed after adlay diet and extract
14 C. J. IGBOKWE ET AL.

administration. Liu et al.[56] demonstrated that coix seed could be used as a prebiotic in weight
management and obesity-related disorder through the structural alteration of gut microbiota. The
authors asserted that coix seed achieves this by promoting lipid metabolism pathways such as
unsaturated fatty acid biosynthesis, glycerolipid metabolism, sulfate transport system, glutathione,
and manganese/iron transport system.

Antifungal activity, Antihyperuricemia activity, allergy suppressant

A novel chymotrypsin inhibitor (ClCl) was isolated and purified from coix seed. Invitro antifungal
activity of ClCl shows that it has varying levels of inhibition on mycelial growth and spore germination
of six plant pathogenic fungi.[81] Furthermore, hyphal morphology was affected, thereby leading to
stunted growth with reduced volume in some plant pathogenic fungi as observed in a microtiter plate
assay. To date, the mechanism by which plant protease inhibitors induce resistance to plant diseases
has not been systematically studied. Brown adlay extract has been shown to effectively control serum
uric levels among other adlay derivatives in oxonate-induced hyperuricemic rats.[32]
Hsu et al.,[82] showed that oral administration of methanolic extract of dehulled adlay could reduce
the serum levels of antigen-specific immunoglobulin E (IgE) in OVA immunized mice and elevated
serum levels of antigen-specific immunoglobulin (IgG2a) through the mechanism of reviving of
T helper cell (Th cell) responses from a T2-dominant to a Th1-dominant structure.

Toxicity and safety aspects of coix seed

There is paucity of information on the toxicity or safety in the use of coix seed and its extract to treat
diseases. Woo et al.[48] carried out a post-mortem examination of all animals used to study coix seed
extract for cancer treatment. The results showed no organ-specific toxicity in any of the animals
treated with coix seed oil emulsion. The authors further explained that dosing in the experiments was
limited only by the emulsion volume injected into the peritoneum daily. Kangliate (KLT)’s safety and
efficacy plus gemcitabine in patients with locally advanced or metastatic pancreatic cancer was studied
by.[83] No negative safety signal was identified with the addition of Kanglaite. Also, quality of life
(QOL) improved. Due to the lack of incremental toxicity and potential attenuation of hematological
toxicity, the authors concluded that KLT could also be added to a combination chemotherapy
regimen.
Oral acute toxicity tests showed that the lethal dose of hot water extract of whole-grain coix seed is
> 2000 mg/kg in male and female rats.[84] This implies that no adverse effect was observed in the
experimental rats at a dosage greater than 2000 mg/kg. Furthermore, no significant toxicity nor
abnormality on body weight, urinalysis, hematological and histopathological examination was
observed in the experimental rats.

Conclusion
Generally, research on coix seed and its derivatives is still emerging relative to other cereal grains.
However, the information generated so far has shed light on the rich health-promoting potentials of
the grain. Although coix seed is mainly used and consumed due to its health benefits, it has
considerable potential for industrial application; for instance, it can be used as whole flour or
composite in food product development based on its functional properties. Furthermore, due to its
heat stability, digestibility, and low solubility, coix starch can function as texturizers, humectants,
among others in food products. Future research should be geared towards using non-thermal
technologies, including high hydrostatic pressure, ozone, cold plasma, ultrasound, and combination
methods to isolate the chemical components of coix seed such as starch. Compounds responsible for
specific biological activities, including anti-cancer, antifungal, antidiabetic, antioxidant activity among
others should be studied further to explore their maximum therapeutic potentials. Possible synergistic
 FOOD REVIEWS INTERNATIONAL 15

or antagonistic interactions in both experimental and clinical studies bothering on safety, bioavail­
ability and bioaccessibility should be well defined in future studies. Coix seed can be explored as an
alternative grain in culinary cuisine, which can enhance human health by delaying or preventing some
pathological and dietetic conditions, and improving the population’s dietary diversity, which can
popularize the grain in the long run.

Acknowledgments
This work was supported by the National Natural Science Foundation of China (32072354), National Key R & D Project
of China (2016YFD0400303), and the Priority Academic Program Development of Jiangsu Higher Education
Institutions (PAPD).

Declaration of conflict of interest

The authors declare that there are no conflicts of interest.

Funding
This work was supported by the National Natural Science Foundation of China (32072354), National Key R & D Project
of China (2016YFD0400303) and the Priority Academic Program Development of Jiangsu Higher Education Institutions
(PAPD). [2016YFD0400303,32072354].

ORCID
Chidimma Juliet Igbokwe http://orcid.org/0000-0003-0245-1297

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