Trends in Food Science & Technology 108 (2021) 58–70

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Trends in Food Science & Technology

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Litchi (Litchi chinenis) seed: Nutritional profile, bioactivities, and its

industrial applications
Sneh Punia a, *, Manoj Kumar b, c, **
a
Department of Food Science and Technology, Chaudhary Devi Lal University, Sirsa, India
b
ICAR-Central Institute for Research on Cotton Technology, Mumbai, India
c
Division of Biochemistry, ICAR – Indian Agricultural Research Institute, New Delhi, India

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Litchi fruit, belongs to Sapindaceae family, is commercially grown for its sweet, juicy, and nutri­
Litchi seed extract tional arils in tropical to subtropical parts of the world. During the processing of litchi fruit into beverages, jellies,
Biological activities wine, and squash; litchi seeds, are get rid of as waste. Seeds are a remarkably rich source of phytochemicals
Food ingredient
(flavonoids), polysaccharides (starch), oil (high unsaturated fatty acids), and proteins (bioactive peptides).
Food safety and regulation
Scope and approach: This review article firstly narrates the nutritional composition of the litchi seed which in­
cludes its phenolic compounds, bioactive and starchy polysaccharides (40.7%), proteins (4.93%), oil content
(3.2%), and minerals. The review also unfolds bioactivities (anticancer, neuro-protective, antioxidant, anti-viral,
anti-microbial, hepato-protective, lipid lowering) of the litchi seed extract (LSE). In addition, review also
highlighted the safety and regulatory issues for consumption of litchi seeds as food ingredient. This compre­
hensive systematic review also gives insights into developing litchi seed as a potential and novel ingredient for its
versatile food and non-food applications along with the latest researches conducted worldwide.
Key findings and conclusions: The extracts obtained from the litchi seed can act as a premium source of starch for
application in foods. The bioactive properties recommend the use of bioactive components in the development of
innovative food and pharma products. Utilization of these components can improve the economic feasibility of
litchi processing industry and it will also help in preventing the environmental pollution caused by the litchi
seeds.

1. Introduction
Litchi (Litchi chinensis), one of the important fruit crops, belongs to
soapberry family (Sapindaceae) and extensively cultivated in the trop­
ical to sub-tropical regions of the globe. Reports in the literature sug­
gests that litchi possibly originated in Southern China and Northern
Vietnam and later on spread to at least 20 nations (Fig. 1; Menzel, 2001).
China ranks first in the production (69.9% of total produce) of litchi
followed by Thailand, India, and Vietnam (Qi, Chen, Li, & Zhan, 2016;
Pareek, 2016). Although major portion of litchi fruit is constituted by
water (76–91%), the presence of bioactive compounds (pheno­
lics/antioxidants), minerals (P, Fe, Ca), vitamins (thiamine, niacin,
riboflavin, vitamin C), sugars (glucose, fructose, sucrose), fats, protein,
and flavoring components (limonene, geraniol, neral) makes it a super
fruit (Pareek, 2016). However, highly perishable nature of litchi
instigates the need for preparation of processed litchi products. Few
examples of the processed litchi products are litchi pulp (wet/dehy­
drated), squash, RTS, wine, honey, and canned litchi (https://www.
nrclitchi.org/value-added-products-of-litchi, accessed on August 07,
2020). Intervention of processing techniques have not only reduced the
post-harvest losses of the litchi but also open up the ways of employment
generation and increased the farmers’ income. At the same time, con­
current generation of the litchi waste such as seeds (10–20% depending
on variety) and pericarp (15%) has posed significant problem to the
environment and economic feasibility processing industries (Bhushan
et al., 2015, 2019; Pandey & Sharma, 1989).
Litchi processing generates 30–40% of by-product which is
frequently discarded by the industry. Litchi seeds are dark brown or
chocolaty in color and oblong to concave in shape with dimensions of
1–3.3 cm long and 0.6–1.2 cm wide. It is estimated that total global

* Corresponding author.
** Corresponding author. ICAR-Central Institute for Research on Cotton Technology, Mumbai, India.
E-mail addresses: dimplepoonia@gmail.com, snehpunia69@gmail.com (S. Punia), manojkumarpuniya114@gmail.com, manoj.kumar13@icar.gov.in (M. Kumar).

https://doi.org/10.1016/j.tifs.2020.12.005
Received 21 September 2020; Received in revised form 1 November 2020; Accepted 6 December 2020
Available online 9 December 2020
0924-2244/© 2020 Elsevier Ltd. All rights reserved.
S. Punia and M. Kumar
production of litchi is ~2.7 million tons which can generate as much as
~0.54 million tons of seeds per year (Chen & Huang, 2012). This huge
amount of seeds during the processing of litchi is intractable problem for
the food industries. Seeds are traditionally used in the Chinese medicine
to eliminate pathogenic cold, release stagnant humor and also it serves
as analgesic agent comforting orchitis, neuralgia, testicular swelling,
hernia, abdominal pains (Guo et al., 2017; Zhu et al., 2019). Therefore,
litchi seeds can potentially be used as active ingredient in different
pharma and food formulations. Litchi seed is rich source of starch
Fig. 1. Diagram showing the litchi producing countries and overall nutritional profile of litchi seed.
59
Trends in Food Science & Technology 108 (2021) 58–70
polysaccharides (40.7%), proteins (4.93%), crude fibres (24.5%), oil
content (3.2%) and minerals (Magnesium: 0.28%; Calcium: 0.21%;
Phosphorus: 0.11%) (Anwar, Mahmood, Mehmood, & Aladedunye,
2014; Koul & Singh, 2017).
Being a non-conventional source and higher availability as industrial
waste, litchi seed is emerging source of starch in food application. Starch
can be isolated in higher purity with excellent water holding capacity
(WHC), thermal stability and structural morphology, suggesting its
application in food industry (Jaiswal & Kumar, 2015). Litchi seed’s fatty
S. Punia and M. Kumar Trends in Food Science & Technology 108 (2021) 58–70

acid composition showed the presence of palmitic acid (12%), linoleic researchers is depicted in Table 1.
acid (27%), linolenic acid (11%), and cyclo propanoic acid (42%) (Ding,
1999). The unique fatty acids of the litchi seed oil makes it a suitable
2.1. Polysaccharides
candidate for the functional foods development. Apart from this, litchi
seeds have been found to have sterol derivatives and crude saponins
Polysaccharides are biological polymers made of one or several
which have role in membrane dynamics and various biological activ­
different monosaccharide units linked by glycosidic bonds. The func­
ities, respectively (Koul & Singh, 2017). Further, appreciable amount of
tional or biological properties of the polysaccharides are dependent on
vitamin E (tocopherol) (9.4%) and unsaturated fatty acids were identi­
the type of monomeric units, degree of polymerization, and glycosidic
fied in oil (Matthaus, Vosmann, Pham, & Aitzetmüller, 2003). The
bonds. The polysaccharide fractions from the plants have been reported
proteins of litchi seeds were found to have all essential amino acids
to exhibit functional activities, including antioxidant, antimicrobial,
(Huang & Chen, 2007) with two unusual amino acid known as
anti-inflammatory, anti-hyperlipidemic and anti-cancer (Kakar et al.,
α-methylenecyclopropylglycine (α-MCPG) and hypoglycin A (HGA)
2020). Among the various active ingredients of litchi seeds, bioactive
which restricts application of litchi seeds in food due to their hypogly­
polysaccharides have recently attracted attention by virtue of their
cemic effect in human body (Ding, 1999).
excellent biological properties and pharmacological functions (Ema­
The phytochemical profile of ethanolic extract of litchi seed depicted
nuele, Lauricella, Calvaruso, D’Anneo, & Giuliano, 2017). However,
the presence of major 5 phenolic compound namely (− )-epicatechin,
polysaccharides from the litchi seeds are scarcely researched concerning
(− )-gallocatechin, (− )-epicatechin-3-gallate, gallic acid, and procyani­
to its recovery and structural characterization. Chen, Luo, Gao, and Zhu
din B2 whereas protocatechuic acid, protocatechuic aldehyde, 5-O-
(2011) studied the impact of ultrasound for extraction of poly­
coumaroyl methyl quinate and daucosterol are the other minor pheno­
saccharides from litchi seeds using response surface methodology as
lics (Yan & Liu, 2009; Yang et al., 2011; Prasad, Yang, Zhao, Ruen­
statistical tool. Authors found maximum yield at ultrasound power 222
roengklin, & Jiang, 2009). The nutritional and phytochemical
W, incubation time 45 min and solvent-to-solid ratio 15 mL/g. They
components act as strong antioxidants and responsible for various bio­
obtained two fractions of litchi seed polysaccharides namely LSP I (litchi
logical activities which make it a potential candidate for use in foods.
seed polysaccharides I, precipitated using 40% ethanol) and LSP II
Litchi seeds extracts have demonstrated multifaceted bioactivities viz.
(precipitated using 80% ethanol) for structural characterization. LSP I
antioxidant, antimicrobial anticancer (lung, colorectal, liver, cervical,
consist of glucose, arabinose, galactose, fructose and mannose whereas
nasopharyngeal cancers), anti-diabetes, hypoglycemic, antivirus,
LSP II has additional fucose monosaccharide in small concentration. Gas
anti-inflammation, anti-hyperlipidemia, and immuno-regulation (Guo
chromatography (GC) analysis established that sum of molar percent­
et al., 2017). The exceptional profile including polysaccharides, anti­
ages of glucose and galactose was highest (87%) in LSP I whereas
oxidants, fatty acids, and protein make litchi seed a suitable candidate
galactose and fructose was highest (62.5%) in LSP II. These neutral
for application in development of functional foods. For example,
monosaccharides are well linked with various glycosidic linkages (viz.
aqueous extract of litchi seeds act as a natural additive and enhanced the
→5)-Ara-(1→, →2)-Man-(1→, →3)-Man-(1→, →3,6-Man-(1→, →3)-Fuc
safety and quality of meat paste by inhibiting the lipid peroxidation and
terminal, →3)-Fru-(1→, →3)-Gal-(1→, →6)-Gal-(1→, →2,4)-Glc termi­
adipogenesis (Qi, Huang, Huang, Wang, & Wei, 2015).
nal, and →6)-Glc-(1→,confirmed with methylation and gas chromatog­
This review highlights nutritional and phytochemical profile of the
raphy/mass chromatography (GC/MS) (Chen et al., 2011)).
litchi seeds (section 2) with an aim to improve its utilization as food
Polysaccharides have drawn special attention of food technologists due
ingredient. Further, the biological activities (section 3) of litchi seed
to its antioxidant activities (AOAs) and comparatively safer use in food
extract (LSE) and application of litchi seed as a functional ingredient in
matrices. AOA is regarded as crucial criterion for application of any
the foods (section 4) will be comprehensively discussed. To further
polysaccharide as functional food ingredient. The LSEs were evaluated
clarify the overview of the current review, various components dis­
for AOA using DPPH assay. Both LSP I and LSP II displayed radical
cussed in the review are illustrated in Fig. 2.
scavenging behavior in a dose-dependent manner while LSP I possessed
higher antioxidant activity than LSP II.
2. Nutritional and phytochemical profiles
In another research, a novel neutral polysaccharide, LSP-W-4 (mo­
lecular weight: 6.70 kDa), consists of monosaccharides, arabinose,
Litchi has a rough indehiscent pericarp surrounding the succulent
mannose, glucose and galactose with molar ratio of 6.33: 3.88: 10.35:
aril (edible) surrounds a single shell of hardened endocarp with a seed. It
1.00 was identified and purified from litchi seeds (Wu et al., 2020). The
has been reported that litchi seeds contain a significant number of
novel polysaccharide was assayed for its inhibitory action against
nutritional and biological substances especially starch, proteins, crude
α-glucosidase with acarbose (pseudo tetrasaccharide: inhibitor of
fibre, minerals, phytochemicals (Kessy, Hu, Zhao, & Zhou, 2016; Koul &
α-glucosidase) as positive control. This enzyme hydrolyses disaccharides
Singh, 2017). The composition of the litchi seed reported by various
and other polysaccharides and increases blood sugar concentration thus

Fig. 2. Various components discussed in the review i.e. nutritional profile, bioactivities, and possible application of litchi seeds.

60
S. Punia and M. Kumar
Table 1
Phenolic profile of litchi seeds.
Compounds Phenolic compounds
Phenolic acid Coumaric acid
Protocatechuic acid
Flavonoids
Flavan-3-ols Procyanidin D
Epicatechin
Proanthocyanidin B2,
Proanthocyanidin B4
2a,3a-epoxy-5,7,30,40
-tetrahydroxyflavan-(4b-8-
catechin)
2a,3aepoxy-5,7,30,40
-tetrahydroxyflavan-(4b8)-
epicatechin
2b,3b-epoxy-5,7,30,40
-tetrahydroxyflavan-(4a-8-
epicatechin)
Flavanone Pinocembrin-7-rutinoside
Pinocembrin-7-neohesperidoside
Flavonoid glycosides Litchioside D
(− )-pinocembrin 7-O-
neohesperidoside
Pinocembrin 7-O-rutinoside
(− )-taxifolin 40 -O-β-D-
glucopyranoside
Kaempferol 7-O-neohesperidoside
Tamarixetin 3-O-rutinoside
Phlorizin
Flavanone-7-O- Narirutin
glycoside
Naringin
Anthocyanins Cyanidin-3-glucoside
Cyanidin 3-rutinoside
Quercetin 3-glucoside
Quercetin 3-rutinoside
A-type Litchitannin A1-1
proanthocyanidins
Litchitannin A2
Aesculitannin A
Epicatechin-(2βfOf7,4βf8)-
epiafzelechin- (4Rf8)-epicatechin
Proanthocyanidins A1
Proanthocyanidins A2
Proanthocyanidin A6
Epicatechin-(7,8-bc)-4β-(4-
hydroxyphenyl)-dihydro-2(3H)-
pyranone
Epicatechin
increasing the risk of type 2 diabetes (T2DM). It was found that LSP-W-4
reversibly inhibited the mammalian α-glucosidase enzyme action from
rat (half of maximal inhibitory concentration (IC50)) in a dose dependent
manner and showed a better inhibition compared to acarbose. LSP-W-4
is possessed to have a potential natural compound for development of
functional foods suitable for managing T2DM.
2.1.1. Starch
Extraction of starch from corn, rice wheat and potato (conventional
food sources) is straining their human consumption supply. Growing
Trends in Food Science & Technology 108 (2021) 58–70
food and market demand of starches and with different physicochemical
and functional properties as compared to conventional starch sources
References motivates the search for new starch sources. Scientists are exploring and
exploiting starch’s nonconventional sources including fruit kernels
Wang et al. (2011)
Wang et al. (2011) aiming to meet the starch demand commercially. Starch extraction from
non-conventional sources used as additives (stabilizers, thickeners, gel
Man et al. (2016) production) is gaining significant interest from scientists. Besides being
Xu et al. (2010); an important ingredient for food industries, starch plays major role in
Queiroz et al.
(2015a,b)
the paper, textile and cosmetic industries. Utilization of litchi seeds as a
Li and Jiang, 2007; source of starch will minimize the waste and will add value to fruit
Queiroz et al. processing industries.
(2015a,b) Among all the macromolecules, starch is the pre-eminent carbohy­
Li and Jiang, 2007;
drate and accounts 40–45% of total dry weight of litchi seed. Wet milling
Queiroz et al.
(2015a,b) method is generally opted for isolation of starches from litchi seeds. The
Wang et al. (2011) litchi seed starch isolated using alkaline method using 0.5% NaOH (w/
w) showed lower amylose content (7.6%) when compared with acidic
method (9.6%) using 0.3% citric acid because of disrupting amorphous
Wang et al. (2011)
regions (Jaiswal & Kumar, 2015). Litchi seed starch contains 19.2% of
amylose content, considerably equals that of corn, cassava, and barley
Wang et al. (2011) showing its applicability analogous to food crops (Thory and Sandhu,
2017). Litchi seed starch showed A-type X-ray diffraction pattern, which
is generally found in cereal starches. Swelling power (SP) and solubility
Wang et al. (2011)
Wang et al. (2011) provides an evidence of interaction between starch chains within the
Xu et al. (2010) crystalline and amorphous regions and determine the potential uses of
Xu et al. (2010) starch in the food industry (as a thickener, binding agent, gelling agent
and emulsifier). Litchi seed starch showed low clarity of paste, SP, peak
Xu et al. (2010)
viscosity, breakdown viscosity and high solubility and setback viscosity
Xu et al. (2010)
as compared with other fruits wastes (Kringel, Dias, Zavareze, & Gandra,
Xu et al. (2010) 2020). WHC is also is important to the quality and texture of food
Xu et al. (2010) products because it stabilize food products against effects such as syn­
Xu et al. (2010)
eresis. Alkali derived starch presented higher WHC (587.4%; w/w)
Wang et al. (2011)
compared to acid derived starch (462.5%; w/w). The higher WHC of
Wang et al. (2011) alkali extracted starch was associated with the formation of H-bond with
Li and Jiang, 2007; water molecule and hydroxyl group of pyranose ring of starch chains.
Queiroz et al. WHC was influenced by loose connection of amylopectin and amylose in
(2015a,b)
the starch granules. SEM of litchi seed starch revealed the presence of
Li and Jiang, 2007;
Queiroz et al. round to oval shaped starch granules with smooth surfaces and no sign
(2015a,b) of clefts (Fig. 1). The size of citric acid isolated starch granules is larger
Li and Jiang, 2007; with diameter of 4.22–10.18 μm whereas alkali extracted starch gran­
Queiroz et al.
ules have smaller diameter varying from of 3.01–7.88 μm (Jaiswal &
(2015a,b)
Li and Jiang, 2007;
Kumar, 2015). It was inferred from the findings that the extraction
Queiroz et al. medium imparts different properties to the isolated starch.
(2015a,b) Thermogravimetric analysis demonstrated higher temperature sta­
Xu et al. (2010) bility suggesting its application in the thermally processed foods
(Jaiswal & Kumar, 2015). Drug release studies indicate that litchi kernel
Xu et al. (2010)
Xu et al. (2010) starch tablets showed 42–67% of drug release in 5 h and can act as an
Xu et al. (2010) entrapment material for delayed nutrient and drug deliver for specific
therapies. This novel property of litchi starch prevents release of drugs in
Xu et al. (2010)
stomach and small intestine eventually targeting drugs to colon (Jaiswal
Xu et al. (2010)
Xu et al. (2010)
& Kumar, 2015). The amylopectin content in the starch assisted in the
Xu et al. (2010) WHC of the starch ultimately contributing to slow release of drugs. In
the same way, litchi starch polysaccharides can be utilized as encapsu­
lant material for the delivery of nutrients (mineral and vitamins) in
digestive tract for improving the bioavailability.
2.2. Protein
Litchi seeds are good source of carbohydrates and fibers whereas
proteins are scarce varying from 1 to 5% on dry weight basis depending
on the variety and region of cultivation. The results of proximate anal­
ysis show that litchi seed contains 4.97% of protein (Koul & Singh,
2017). Of the total essential amino acids, aspartic acid has the highest
value (0.45%), followed by lysine, glutamic acid, and leucine in litchi
seeds (Saisavoey, Sangtanoo, Reamtong, & Karnchanatat, 2018).
Further, protein bands in the range of 15.5 kDa (Bhat & Al-daihan,
2014) and 61 kDa (Mhatre, Bhagit, & Yadav, 2019) measured by
61
S. Punia and M. Kumar
Tris–glycine sodium dodecyl sulphate-poly acrylamide gel electropho­
resis (SDS–PAGE) were reported in LSEs. Despite of lesser volume of
protein in the litchi seed, specific lectins have been registered for its high
value application as antiviral, anti-inflammatory, pro-inflammatory,
and antitumor agent. Legumes lectins are consisting of 0.1–5% of total
seed protein of legumes and these lectins are resistant against enzymatic
and heat denaturation. In vegetarian diet, the digestive tract is most
commonly exposed with these lectins present in the legumes (Mur­
amoto, 2017). Lectins consumed in higher concentration reacts with the
lining of intestine and causes physiological disorders in humans by
acting as enzyme inhibitors and anti-nutritional factors (Muramoto,
2017). The extensive research proved that lectin from plants sources can
have antimicrobial, immunomodulating, and selective cytotoxicity
against cancerous cells (Clement, Pramod, Yeldur, & Venkatesh, 2010).
Waste from fruit processing, litchi seed in present context is sustainable
and environmentally friendly source for the production of specific lec­
tins. A novel lectin namely ‘glucose/mannose binding lectin’ was
extracted from the litchi-seeds and studied for the antimicrobial activity
against a food borne bacteria Pseudomonus aeruginosa (Bose et al., 2016).
Lectins are class of glycoproteins with non-catalytic domain (at least
one) that attach with peculiar monosaccharide or oligosaccharide. The
lectins were purified using Sephadex G 100 and Con A-Sepharose 4 B
affinity chromatography. The purified homo-dimer lectin (54 kDa) binds
with mannobiose with high specificity and demonstrated antibiofilm
activity against P. aeruginosa (Bose et al., 2016). In another report,
protein rich aqueous extract of litchi seed inhibited the growth of both
Gram-positive including S. aureus, Streptococcus pyogenes, Bacilllus sub­
tillis and Gram-negative bacteria (E. coli and P. aeruginosa) (Bhat &
Al-daihan, 2014). Antimicrobial lectins/peptides have cationic charge
which interacts anionic microbial phospholipids membrane by electro­
static interactions creating transient pores leading to ion of leakage and
cell lysis. These lectins may play an important role in the development of
the active packaging materials for fruits and vegetables having high
antimicrobial activity against the food spoiling pathogens.
2.3. Lipid profile
Plant lipids are predominantly utilized for food and non-food in­
dustrial application. Edible oils quality and digestibility are determined
by the composition and concentration of fatty acids (FAs), most
importantly unsaturated fatty acids (UFAs). The total amount of UFAs in
litchi seed was 80.02%, mono-unsaturated (MUFA) of 14.67% and poly-
unsaturated fatty acid of 65.35% (PUFA; Luzia & Jorge, 2011). GC–MS
analysis of litchi seed oil revealed the presence of palmitic acid (hex­
adecanoic acid) (C16:0; 9%), oleic acid (C18:1 n–9; 14.7%), stearic acid
(C18:0; 4.8%), linoleic acid (C18:2 n–6; 64%), arachidic acid (C20:0;
1.825%), α-linolenic (C18:3 n–3; 1.34%), behenic acid (C22:0; 1.11%),
and lignoceric acid (C22:0; 4.21%) (Luzia & Jorge, 2011). Therefore, the
most abundant fatty acid in litchi seed is linoleic acid followed by oleic
and palmitic acid (9.09%). In another study, GC-MS profile of LSE
showed higher concentration of oleic acid (37.9%). Earlier in 1993, a
study published in the Journal of Agricultural and Food Chemistry re­
ported a contrasting profile of fatty acid i.e. palmitic acid (12%), oleic
acid (27%), linoleic acid (11%), and cyclopropanoic fatty acids (42%)
(Gaydou, Ralaimanarivo, & Bianchini, 1993). The diversity in the fatty
acid profile may be due to modification in the extraction protocol and
differences in the variety of litchi used for the analysis (Paliga et al.,
2017). The ratio of saturated to UFA was 1/4.0 make this oil suitable for
frying due to higher oxidative stability (Takemoto, Okada, Garbelotti,
Tavares, & Aued-Pimentel, 2001). The litchi seed oil also presented a
similar profile to that of sunflower oil with respect to α-linolenic fatty
acid (Tuberoso, Kowalczyk, Sarritzu, & Cabras, 2007). The consumption
of MUFAs and PUFAs from plant sources has been proven to have many
health benefits by preventing coronary heart diseases, diabetes, and
various type of cancers. Hence, litchi seed can be selectively targeted for
exploiting the potential of useful fatty acids for the formulation of the
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Trends in Food Science & Technology 108 (2021) 58–70
functional foods. Some unusual fatty acids such as cyclopropanoic fatty
acids (Gontier et al., 2000) namely dihydrosterculic acid (cis-9,
l0-methyleneoctadecanoic acid) accumulates to over 41–60% (Ahmad,
Ali, Ahmad, Sheikh, & Ahmad, 2017; Jie & Chan, 1977) and 2-hexyl-cy­
clopropaneoctanoic acid (cis-7,8-methylenehexadecanoic acid) which
accounted for 2.3–4% of the of the total fatty acids in litchi seeds (Anwar
et al., 2014) were also identified. These cyclo fatty acids are highly
reactive inside the human system but cyclopropene ring is disintegrated
during the process of refining and degradation so to make the oil good
for the consumption.
2.4. Minerals
Two-thirds of the world’s population lack one or more essential
minerals. Appreciable amount of essential minerals in litchi seeds are
fundamentally important to human and animal nutrition. Owing to its
high nutritional profile, litchi seed have been examined as an important
part of human nutrition. The mineral constituents include magnesium
(0.28%), calcium (0.21%) and phosphorus (0.11%) (Koul & Singh,
2017). Calcium, phosphate, and magnesium are multivalent cations that
are important for many biological and cellular functions.
2.5. Phytochemicals
Due to the government policies concerning to environmental pollu­
tion and improving awareness about the nutritional components of fruit
processing waste including seeds, pomace, peels; research trends has
shifted towards the valorization of these wastes in past few years. Litchi
seeds are considered a superior source of antioxidant phenolic com­
pounds (PCs) for human body as these PCs play an effective role man­
aging numerous metabolic and physiological activities. As discussed in
section 2.1–2.4, it has superior quality of starch, lipids, proteins and
bioactive polysaccharides. Apart from these biological macromolecules,
seeds are abundant in antioxidants viz. PCs (phenolic acids, flavonoids,
anthocyanins, dihydrochalcones, coumarins), ascorbic acid, volatile
constituents, terpenoids (sesquiterpenes, triterpenes) (Ibrahim &
Mohamed, 2015; Queiroz et al., 2015). Among all, PCs performs
numerous biological tasks like acting as shield against oxidative stress,
induce lower adipogenesis, anti-microbial, anticancer,
anti-hyperglycemic and anti-inflammatory properties (Kumar et al.,
2019; Kumar et al., 2020a; b). They perform these actions alone or in
synergy with other components of the litchi seeds. PCs induces protec­
tive mechanism by regulating the various cell signaling and by acti­
vating endogenous defense mechanism. Bioactivities of phytochemicals
exemplify their importance in development of functional foods (Paliga
et al., 2017). Phytochemicals reported in litchi seeds are well presented
in Table 2.
PCs including flavonoids are widely distributed bioactive secondary
metabolites that hold an aromatic ring bearing at least one hydroxyl
group. PCs can influence sensory characteristics of foods by altering
flavor, color, and astringency. Total AOAs of the LSE were found to be
higher than butylated hydroxytoluene (BHT) which are attributed to
chemical composition and PCs. Extraction yields and PCs content of
litchi seeds using different solvents were reported to be 23.3–26.8% and
158–244 μg GAE/g, respectively. The PCs namely gallic acid, procya­
nidin B2, (− )-gallocatechin, (− )-epicatechin and (− )-epicatechin-3-
gallate compounds were firstly identified in litchi seeds by using RP-
HPLC (Prasad et al., 2009).
Flavonoids are the main and the bulkiest group accounting for then
50% of established PCs. Anthocyanidins, flavones, flavan-3-ols, and
flavanols are the major flavonoids in litchi seeds (Singh, Singh, Kaur, &
Singh, 2017). Litchi seeds are excellent in procyanidins (flavan-3-ols)
and are predominantly composed procyanidin trimers and dimers (Lv
et al., 2015). Ethanolic LSEs were partitioned between H2O, petroleum
ether and ethyl acetate sequentially. Further, the fractions were sepa­
rated using silica gel columns and HPLC. 7 A-type proanthocyanidins
S. Punia and M. Kumar Trends in Food Science & Technology 108 (2021) 58–70

Table 2
Highlights of biological activities of litchi seed extracts.
Source/ Region Compounds/component Bioactivities Key findings References
Variety

Litchi seeds Shanghai, China LSP-W-4, a heteropolysaccharide Anti-diabetic LSP-W-4 is a natural compound with α -glucosidase inhibitory Wu et al.
potential suitable for Type II diabetes mellitus. (2020)
Litchi seeds Sichuan, China Litchi seeds extract Neuroprotective Seeds of litchi prevent hippocampal neuronal injury in AD rats Sun et al.
effect through the AKT/GSK-3β signalling pathway, therefore LSE an (2020)
effective drug against Alzheimer’s disease
Litchi seeds China Litchi seeds water extract Anti-cancer High concentration of aqueous Litchi seeds extract serves as a Ma et al.
antitumor medicine breast cancer (MCF-7, BT474 and MDS-MB- (2020)
231) treatment
Litchi seeds Guangzhou Methyl jasmonate analogs, Anti- Methyl jasmonates in litchi seed are responsible for anti- Dong et al.
lignanoside and flavonoids inflammation inflammatory activity (2019)
Litchi seeds Navi Mumbai, Protein Anti-obesity Litchi seed protein has been proven as inhibitor of pancreatic Mhatre et al.
India lipase. (2019)
Litchi seeds Luzhou, China, Polyphenols Neuroprotection Prevented neuronal injury and improves cognitive functions Tang et al.
through reducing blood glucose, improving IR and inhibiting the (2018)
formation of Aβ.
Litchi seeds Nakornpathom, Peptide hydrolysates Anti- Litchi seeds peptide hydrolysate have anti-inflammatory Saisavoey
Thailand inflammation activities et al. (2018)
Litchi seeds Luzhou (Sichuan, Saponins Neuroprotection Improved cognitive function and prevented neuronal injury Wang et al.
saponins China) induced by Aβ25–35 (2017a)
Litchi seeds Luzhou, (Sichuan, Saponins Neuroprotection Litchi seed extract inhibited apoptosis induced by Aβ25-35 Wang et al.
saponins China) through regulation of the apoptotic and NF-κB pathways in (2017b)
PC12 cells
Sicilian Sicily, italy Polyphenols Anti-cancer Litchi seed extracts display anti-tumor and pro-apoptotic effects Emanuele
Litchi in vitro et al. (2018)
Litchi seed Brazil Phytochemicals Anti-obesity Litchi seed flour controls dyslipidemia and hepatic steatosis. Queiroz et el.
flour (2018)
Litchi seeds Yunnan Oligomeric procyanidins Hypoglycaemic Seeds possessed antihypoglycaemic effects on type 2 diabetes by Man et al.
effects reducing glucagon mRNA level and increased the protein (2017).
expression of glucose transporter type 2 diabetes rats
Seeds China procyanidin A2, Anti-diabetic α-Glucosidase inhibitory activity Choi et al.
Protocatechuic acid, pavetannin (2017)
B2,
5-q-coumaroylquinic acid
Chinese Southern China Coumaric acid, Anti-cancer Treating prostate cancer PC3, DU145, RM1 and C4–2B cells Guo et al.
Cherry Protocatechuic aldehyde, (2017)
2α,3α-Epoxy-5,7,3′ ,4′ -
tetrahydroxyflavan- (4β-8-
catechin),
(− )-Epicatechin, Rutin,
Pterodontriol-D-6-O-β-D-
glucopyranoside,
2β,3β-Epoxy-5,7,3′ ,4′
-tetrahydroxyflavan-(4α-8-
epicatechin),
2α,3α-Epoxy-5,7,3′ , 4′ -
tetrahydroxyflavan-(4β-8-
epicatechin),
Tamarixetin3-O-rutinoside,
Litchioside C
Hei Yeh Taiwan Phenolics Anti-cancer Suppressed EGFR signaling in non-small cell lung cancer Chung et al.
Litchi (2017)
Litchi seeds Jinan, China Litchi seeds water extract Anti-obesity Litchi seed water extract is capable of preventing obesity and Qi et al.
retarding lipid oxidation (2015)
Litchi seeds China Litchitannin A2, A-type Anti-viral Litchitannin A2 extracted from litchi seed displayed in vitro anti- Xu et al.
proanthocyanidins, coxsackie virus B3 (CVB3) activity and aesculitannin A, and (2010)
proanthocyanidins A2 were active against herpes simplex virus 1
(HSV-1).

including 4 trimers: epicatechin, aesculitannin A, litchitannin A1, A2
along with 3 dimers: proanthocyanidin A1, A2, and A6 were identified
(Xu, Xie, Wang, & Wei, 2010). Among which, trimers, proanthocyanidin
A6 and other 3 are newly characterized compounds and showed strong
AOA like L-ascorbic acid.
Seven flavonoid glycosides were isolated from litchi seeds and their
structure was identified using nuclear magnetic resonance (NMR) and high-
resolution electrospray ionization mass spectrometry (HRESIMS) (Xu et al.,
2011). Authors identified one new flavonone triglycoside i.e. litchioside D
(1), one known i.e. (− )-pinocembrin 7-O-neohesperidoside (2) and five
previously uncharacterized, tamarixetin 3-O-rutinoside, kaempferol
7-O-neohesperidoside, taxifolin 4-O-β-D-glucopyranoside, phlorizin, and
(− )-pinocembrin 7-O-rutinoside using repetitive column chromatography
and HPLC (Xu et al., 2011). Wang, Lou, Ma, & Liu (2011) investigated 95%
ethanolic LSEs and isolated 4 unknown PCs i.e. litchiol A, litchiol B, 2α,
3α-epoxy-5,7,3՛,4՛-tetrahydroxyflavan-(4b-8-catechin) and 2β,3β-epoxy-5,
7,3՛,4՛-tetrahydroxyflavan-(4a-8-epicatechin). Eleven other known com­
pounds such as coumaric acid, soscopoletin, naringin, narirutin, proto­
catechuic acid, pinocembrin-7-rutinoside, 2,5-dihydroxy-hexanoic acid,
2α,3α-epoxy-5,7,3՛,4՛-tetrahydroxyflavan-(4b-8-catechin), pinocembrin-7-
neohesperidoside, dihydrocharcone-40՛-O-β-D-glucopyranoside, pterodon­
triol D-6-O-β-D-glucopyranoside. LSE also contained numerous pinocembrin
glycosides and catechin-rich compounds. Extracts were found to be consti­
tuted with phlorizin, rutin, procyanidin A1, procyanidin D, cinnamtannin
B1, cianidanol, 3,5-dihydroxybenzoic acid, scopoletin, 3,4-dihydroxyben­
zaldehyde, and epicatechin–epicatechin–catechin determined by

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S. Punia and M. Kumar Trends in Food Science & Technology 108 (2021) 58–70

UPLC-Q/TOF-MS (Man et al., 2016). The compounds and nutritional mol­
ecules discussed in this section are tested to have various biological activities
which is discussed in section 4.
3. Analytical chemistry techniques for isolation, purification
and characterization of biological molecules from litchi seed
Isolation is the first most crucial step for the recovery of the bio­
logical molecules (polysaccharide, phenolics, proteins). Wet milling
with acid and alkaline steeping conditions is most commonly used
method for isolation of starchy polysaccharides from the litchi seeds.
Purification of starch is usually performed by repetitive centrifugation.
Amylose content of starches from litchi seed is estimated using calori­
metric methods (Thory and Sandhu, 2017; Williams et al., 1970).
Structural elucidation of these polysaccharides is performed using X-ray
diffraction technique and scanning electron microscopy.
Crude proteins (lectins) extracted using saline solution are purified
using centrifugation, dialysis and gel filtration on Sephadex G-100. The
protein content is measured using Bradford method and amino acid
composition may be performed using HPLC with the help amino acid
standards. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis
is commonly used to determine the molecular weight of the litchi seed
proteins (Bose et al., 2016). Phenolic extracts from litchi seeds were
most commonly obtained using organic solvents (butane, ethanol,
methanol, and acetone) (Rosales et al., 2019). Total phenolic contents
(gallic acid equivalents) from litchi seeds are estimated using UV-VIS
spectrophotometric method i.e. Folin-Ciocaulteu method. Chromato­
graphic analysis is performed using gas chromatography–mass spec­
trometer (for lipid components) and HPLC (water soluble components or
phenolic components) for elucidation of chemical profile of the LSE
(Paliga et al., 2017). The associated antioxidant activity is determined
using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing anti­
oxidant power (FRAP) assay (Rosales et al., 2019).
4. Bioactivities of the litchi seed extract (LSE)
Currently, litchi seeds have emerged as an attractive ingredient for
development of functional foods because of its important nutraceutical
properties and phytochemical composition. The development of inno­
vative foods by integrating the active ingredients from litchi seeds are
well-endowed with novel biological and therapeutic properties. These
properties of the litchi seed have been extensively studied for the anti­
oxidant, antitumor, antibacterial, antivirus, anti-hyperglycemic, hepato-
protective, and immune-stimulating activities (Fig. 3). The important

Fig. 3. Bioactivities of litchi seed extract (LSEs). A) Saponins present in the LSEs protects the neurons from the injuries and have preventive effect on Alzheimer’s
disease. B) LSEs showing anticancer activity in oral, lung, colorectal, and prostate cancer. The main pathway operating for killing of all type cancer cells is stimulation
of apoptosis and inhibiting the cell cycle at various phases of cell division. C) Specific lectins extracted from the litchi seeds have demonstrated the antimicrobial
activity by inhibiting the biofilm in bacterial cells. D) LSEs inhibits the activity of intestinal and pancreatic lipases resulting in anti-obesity effects. E) Various phenolic
compounds a) protocatechuic acid, b) pavetannin B2, c) procyanidin A2, d) 5-q- coumaroylquinic acid & e) litchi seed polysaccharides inhibits α-glucosidase
resulting in reduction of blood sugar, hence, showing anti-diabetic effect. E) LSEs prevents lipid peroxidation and protects lever cells from damage caused by
free radicals.

64
S. Punia and M. Kumar
bioactivities are well discussed in the following sub-sections (3.1–3.7).
4.1. Anti-cancer activity
Globally, cancer is a leading and common cause of mortality and
morbidity accounting for an estimated 9.6 million deaths in 2018 (WHO,
2018). Harmful effects encountered due to chemo- and radiation-
therapies during cancer treatment, have encouraged researchers to
develop new herbal formulae-based therapies effective in limiting the
growth of cancerous cells. A significant number of information from
human and animal cell line studies has supplied evidence that utilization
of litchi seeds or their active components display the anti-tumor activ­
ities towards many cancers including prostate (Wang, 2011), lung
(Chung et al., 2017), and colorectal cancer (Emanuele et al., 2018) by
affecting the proliferation, apoptosis, autophagy, metastasis, chemo­
therapy and radiotherapy sensitivity, stemness, metabolism, angiogen­
esis, and immunity via multiple targeting (Cao et al., 2020). LSEs
inhibited the cancerous cells growth by destroying them through cas­
pases induced apoptosis and cell division arresting at various phases by
targeting key regulatory proteins of cell division i.e. cyclins (D1, A, B).
The members of Bcl-2 family (Bax, Bcl-2) plays critical role in apoptosis
regulation in cancerous cells (Khodapasand, Jafarzadeh, Farrokhi,
Kamalidehghan, & Houshmand, 2015). Bax factors promotes the
apoptosis whereas Bcl-2 inhibits it, hence ratio of both the factors de­
cides the fate of cancerous cells (Guo et al., 2017). n-Butanol extract of
litchi seeds (NLS) containing 13 polyphenols showed potent inhibition
towards the prostate cancer cell line (PC3 and DU145) growth, their
migration, and invasion by encouraging cell apoptosis by
caspases-3/7/9, cell cycle arrests at G1/S phase by decreasing the
expression of cyclins-D1/E2 and CDKs2/4/6, and phenotypic inversion
of epithelial-mesenchymal transition by inhibiting the Akt signaling
pathway responsible for the cell proliferation, survival and migration in
human cancers (Guo et al., 2017). NLS enhanced the Bax/Bcl-2 ratio by
enhancing the Bax expression and downregulating the Bcl-2 expression,
resulting in stimulation of extrinsic apoptosis inducing the death of
cancerous prostate cells. The findings were further confirmed by
examining the tumor volume and body weight. It was found NLS
reduced the growth of tumor by ~53% at a concentration of 52 mg/kg
without significant loss in body weight compared to the vehicle control
on 29th day. Hence, NLS acts as excellent adjuvant for the treatment of
the prostate cancer (Guo et al., 2017).
Animal-based experiments showed LSEs treat tumor either by
increasing both innate immunity and acquired immunity (Chen, Hu, &
Xiao, 2009) or by increasing Bax/Bcl-2 ratio in sarcoma S180 tumor cells
of mouse xenograft (Lv et al., 2008). Flavonoid glycosides purified from
litchi seeds, including litchioside D, taxifolin 4′ -O-β-D-glucopyranoside,
tamarixetin 3-O-rutinoside, (− )-pinocembrin 7-O-neohesperidoside,
(− )-pinocembrin 7-O-rutinoside, and kaempferol 7-O-neohesperidoside,
exert strong anti-proliferative effects and cytotoxic activity towards
human pulmonary (LAC), lung (A549), liver (Hep G2), and cervical
(HeLa) cancer cell lines in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,
5-diphenyltetrazolium bromide assay (Xu et al., 2011). Among all the
glycosides, kaempferol 7-O-neohesperidoside demonstrated excellent
cytotoxic action compared to reference compound admycin against all
the tested cell lines with IC50 values of 7.93, 0.53, 0.020, and 0.051 μM,
respectively. Polyphenol-rich ethanolic LSE may significantly induce
apoptotic cell death by increasing the expression of Bax or reduce the
expression of Bcl-2 in a dose-dependent manner and arrest G2/M phase
in colorectal carcinoma SW480 and Colo320DM cells (Hsu, Lin, &
Huang, 2012). Saponins, terpenic glycosides extracted from the litchi
seeds, inhibited mammary gland’s hyperplasia and affected pathways of
estrogen-mediated signaling in rats with dose of 0.1 g/kg and 0.2 g/kg,
respectively (Lin, Qiu, He, & Guan, 2015).
LSE (25–150 μg/mL) inhibited epidermal growth factor receptor
(EGFR) activity and protein expression in two non-small cell lung cells
(NSCLC; A549 and NCI–H661), concomitantly decreased the
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Trends in Food Science & Technology 108 (2021) 58–70
downstream Akt and Erk-1/-2 signaling resulting in inhibition of
cancerous cell growth. Downregulation of Bcl-2, cyclin B1, cyclin E and
elevated Kip1/p27 and Bax further inhibited the proliferation of NSCLC
cell lines by arresting cell division at G2/M phase and promoting the
apoptosis of cancerous cells (Chung et al., 2017). They further revealed
the cytotoxic activity of LSE against human hepatocellular carcinoma
HepG2 cells and inhibited the growth of lung cancer cell lines. High
concentration of aqueous LSE (220 and 400 μg/mL) inhibits the hall­
mark of the cancer progression i.e. epithelial-mesenchymal transition
(EMT) process, suppressing breast cancer cells (MCF-7, BT474 and
MDS-MB-231) growth, invasion, and migration while promoting cell
apoptosis in a dose dependent manner (Ma et al., 2020). Therefore,
aqueous LSEs could serve as a possible antitumor medicine in breast
cancer treatment. It is also speculated that the use of optimized con­
centration of LSEs as functional food ingredient may help in suppression
of the cancerous cells during early stage of cancer.
4.2. Anti-diabetic activity
Diabetes is the 3rd biggest cause of mortality globally after cancer
and heart diseases. It is a chronic disease characterised by hyper­
glycaemic condition either have a complete lack of insulin (type 1 dia­
betes) due to inadequate secretion of insulin from the β-cells of the
pancreatic islets or have very little insulin or fails to respond to secreted
insulin (type 2 diabetes; T2D). T2D accounts for over 90% of all diabetic
cases, therefore became the growing public health problem throughout
the world (Ashwini & Mahalingam, 2020). One therapeutic approach to
manage the T2D is to decelerate the glucose absorption via enzymes
inhibition, such as α-glucosidase in the gastrointestinal tract (Zhong
et al., 2019). Inhibitors impede the activity of α-glucosidase delaying
carbohydrate absorption and slows the elevation of blood glucose levels,
showing anti-hyperglycemic action. In-vivo examination displayed
anti-diabetic potency of LSE successfully to regulate carbohydrate
metabolism by inhibiting pancreatic α-amylase and intestinal α-gluco­
sidase. These are the key enzymes that catalyzes the final step of
digestion of carbohydrate, hence, targeted for diabetes management
(Choi et al., 2017; Ren, Xu, Gao, Ma, & Gao, 2013).
LSP-W-4 is a polysaccharide with MW of 6.70 kDa was extracted
from litchi seeds. The kinetic enzymatic analysis demonstrated that LSP-
W-4 non-competitively inhibited laboratory rats (IC50 = 66.97 μM; KM
= 0.53 mmol/L) and yeast’s (IC50 = 75.24 μM; KM = 0.43 mmol/L)
α-glucosidase activity. Results implied that novel polysaccharide have
low cytotoxicity with high efficiency to inhibit α-glucosidase and is a
deserving candidate for managing T2D (Wu et al., 2020). In another
study, α-methylenecyclopropylglycine was found adequate to drop
down the sugar in blood and glucagon in mice liver injected with alloxan
(a glucose analogue) (Huang, 1994) whereas others supported that litchi
saponins also possess anti-diabetic property (Guo et al., 2003; Yang &
Liang, 2004). PCs of litchi seeds have potential to alleviate the symptoms
of polydipsia, polyuria, and hyperphagia in streptozotocin (a drug
particularly toxic to insulin producing cells) induced diabetes in rats
(Man, Ma, Wang, Gao, & Lu, 2016). Choi et al. (2017) through an in
vitro study detected the four bioactive substances, 5-q-coumaroylquinic
acid, pavetannin B2 & C, procyanidin A2 & D, protocatechuic acid B and
concluded that these compounds have potential to inhibit α-glucosidase
activity and treat T2D. LSEs are reported to inhibit protein tyrosine
phosphatase 1B activity to reduce postprandial hyperglycemia. LSE
contained catechin-associated compounds and pinocembrin glycosides
including 3,5-dihydroxybenzoic acid, scopoletin and rutin (Man et al.,
2016). These glycosides acted as anti-diabetic and antiglycation agents
in T2D management in rats (Chang et al., 2015; Dhanya et al., 2014;
Scazzocchio et al., 2015).
Man et al. (2017) stated that LSE had the hypoglycaemic conse­
quences on T2D through inhibition of the glycogenesis, proteolysis and
lipogenesis. Considering the beneficial properties of litchi seeds, it can
be a cost-effective and sustainable food ingredient in the food industry
S. Punia and M. Kumar
and an effective strategy for management of diabetes in pharma
industry.
4.3. Antioxidant activity (AOA)
Oxygen play an important role in the energy metabolism of living
organisms. However, oxygen derived free radicals participates in chain
of reactions, consequently ending in numerous life-style complications
including diabetes, cardiovascular disease, neurodegenerative disor­
ders, respiratory diseases, and cancers. Phytochemical analysis has
suggested that litchi seeds contain biologically active components
including flavonoids, phenolics, oligosaccharides, (Xu et al., 2011),
which could be employed as a natural antioxidant for maintaining
health as evident from in vitro and in vivo studies (Prasad et al., 2009).
The antioxidant compounds inhibit or quench free radical reactions and
delay or inhibit cellular damage. Five A-type proanthocyanidins with
two novel, litchitannin A1 and A2, in litchi seeds by silica gel column
chromatography, and HPLC. These compounds showed more AOA than
L-ascorbic acid with FRAP values of 3.7–24.2 mmol/g and IC50 values of
5.25–20.07 μM toward DPPH radicals (Xu et al., 2010). AOA found in
litchi seed was high (Emanuele et al., 2017), which is due to ascorbic
acid and β-carotene, as demonstrated by PCA, allowing the uses of seeds
as source of natural oxidant (Queiroz, Abreu, Oliveira, Ramos, &
Fráguas, 2015). A set of bioactive compounds were isolated from the
litchi seeds which includes 4 methyl jasmonate analogs, one lignanoside,
along with 15 flavonoids and results strongly demonstrated the anti­
oxidant potential of the lignanoside and flavonoids (Dong, Huang,
Wang, & He, 2019). The peptide fractions (hydrolyzed using neutralase)
with lowest molecular weight (MW; < 650 Da) demonstrated highest
radical scavenging activity (IC50 = 8.32 μg/mL) whereas highest MW >
10000 Da showed minimum activity (37 μg/mL). Further, four purified
litchi seed fractions (H1–4) with high AOAs were separated using
RP-HPLC (Saisavoey et al., 2018). The fractions were analyzed for amino
acid sequence, MWs and radical scavenging activity in H1 (KVRTKLLPP;
1051 Da; IC50: 10.9 μg/mL), H2 (MKLCWQKSIHGS; 1417 Da IC50: 5.35
μg/mL), H3 (XDVDRIDK; 970 Da IC50: 2.81 μg/mL), and H4 (RPLVTHK;
850Da; IC50 = 4.42 μg/mL). H3 fraction reported the highest as lower
MW peptides are reported to cross the intestinal barriers which assist
them to show biological effects by interacting more effectively with the
free radicals (Wang et al., 2013). Methyl jasmonate analogs, flavonoids
and lignanoside was isolated and purified from the litchi seeds and
evaluated for the anti-inflammatory activity (AIA) and AOA. It was
found that flavonoid fractions contributed towards the antioxidant
properties (DPPH radical scavenging activity with IC50 < 10 μM) of LSE
(Dong e al., 2019). Therefore, LSE may serve as important antioxidant
agent in functional foods.
4.4. Anti-inflammatory activity (AIA)
Inflammatory actions play an important role in the body’s defense
mechanism to hazardous stimuli including allergens and tissues injury;
however, uncontrolled inflammatory actions are responsible for al­
lergies, CVDs, metabolic syndrome, cancer, and autoimmune diseases
imposing an immense economic burden on the society (Bagad, Joseph,
Bhaskaran, & Agarwal, 2013). Catechin rich compounds, procyanidin D
in litchi seeds also protect against the diabetic pancrease damage by
exerting anti-inflammatory effects (Yin et al., 2015). Four purified litchi
seed fractions (H1–4) with high AIAs were separated using RP-HPLC
(Saisavoey et al., 2018). Findings suggested that the presence of posi­
tively charged amino acids in peptide sequence contributed towards the
AIAs by inhibiting the production of inflammatory cytokines and NO
(Rajasekaran et al., 2015; Saisavoey et al., 2018). Aconitase (H3 frac­
tion), a Fe–S cluster enzyme forms dinitrosyl iron complexes on reaction
with NO and demonstrated AIAs by down-regulating pro-inflammatory
cytokines (tumor necrosis factor alpha and IL-6) in RAW 264.7 macro­
phage cells (Saisavoey et al., 2018; Skodje, Kwon, Chung, & Kim, 2014).
66
Trends in Food Science & Technology 108 (2021) 58–70
In another study, it was found that methyl jasmonate analogs are
responsible for AIAs (IC50 = 43–61μM) through NO inhibition induced
by lipopolysaccharides (LPS) in RAW 264.7 macrophage cells (Dong
et al., 2019). Litchi seeds hydrolysate with LPS showed AIA in macro­
phage cell line, RAW 264.7 cells by downregulation of inducible nitric
oxide synthase (iNOS) and interleukin-6 (IL-6) (Saisavoey et al., 2018).
Amino acid composition of the litchi seeds has high concentration of
leucine and lysine which contributes to its higher AIA potential (Nan
et al., 2007). Litchi seed peptides exhibited potent AIAs, suggests that
the peptides could be useful as additives to dietary supplements and
functional foods.
4.5. Neuroprotection
Neurodegenerative disorders are characterized by slow progressive
and irreversible neurons loss related with proteins depositions showing
altered physicochemical characteristics in the brain and in peripheral
organs (Kovacs, 2018). Therapeutic approaches for treating neurode­
generative diseases like Alzheimer’s disease (AD) are limited because of
protective behavior of the blood–brain barrier that hinders drug tar­
geting towards neurons (Sardoiwala, Kaundal, & Choudhury, 2018).
Neuronal apoptosis is determined by multiple key regulators, such as
activation of mitochondrial permeability transition (Kang et al., 2011),
tumor necrosis factor-α (Sharma, Thakur, Singh, & Guleria, 2012), ROS
(Radi et al., 2014), enzymes (Zhang et al., 2014), and other apoptotic
factors namely Bcl-2, Bax, and caspases (Mei & Niu, 2014). Pharmaco­
logical studies have mentioned an important role of litchi seeds in
neuro-protection. In vivo study suggested litchi seeds saponins (LSS)
inhibited apoptosis which improving cognitive function and attenuated
neuronal injury in the hippocampus of AD rats (Rattus norvegicus) by
down-regulating the caspase-3 mRNA expression and Bax protein
expression and enhanced the Bcl-2 protein expression (Wang et al.,
2017a). LSS has started to develop as a novel supplement for preventing
and/or treating AD by inhibiting apoptosis in pheochromocytoma 12
(PC12) cells induced by Aβ25-35 (Amyloid-β25-35) through apoptotic
regulation and NF-κB (nuclear factor κB) pathways (Wang et al., 2017b).
Additionally, LSS reduced the formation of Aβ, tau protein, and
advanced glycosylation end products (AGEs), and the release of mito­
chondrial cytochrome C, to execute its anti-apoptosis effect in AD rats’s
brain (Wan, 2010). Catechin, procyanidin A1 and procyanidin A2 pre­
sent in litchi seeds were manifested to be the bioactive compounds
responsible to inhibit hyper-phosphorylated Tau through the
IRS-1/PI3K/Akt/GSK-3β signaling pathway (Xiong et al., 2020) and for
the inhibition effect of neuro-inflammation in Aβ (1–42)-induced BV-2
cells by modulating the NF-κB signaling pathway (Tang et al., 2018).
LSE also prevent hippocampal neuronal injury in AD rats through the
AKT/GSK-3β signalling pathway, thereby helping as evidence for the
potential utilization of seeds of litchi fractions as an effective drug
against AD (Sun et al., 2020).
4.6. Anti-microbial activities
Bacterial biofilms play an important role in sustaining growth and
pathology by aiding their surface linking to different interfaces and at
the same time provides safety against determinantal biotic and abiotic
factors of the environment (Parsek and Singh, 2003). Recently, natural
bio-actives have been increasingly investigated for their anti-bacterial
and anti-fungal properties and showed higher efficiency to prevent the
infection by microbes. The presence of biofilm in pathogenic microbes
makes these pathogens hard to treat. Hence, inhibition of biofilms by
employing a suitable inhibitor is very important to prevent the infection
cycle. LSEs reported to inhibit the growth of food borne microbes
including Gram positive bacteria such as Streptococcus pyogenes,
S. aureus and Bacillus subtillis as well as Pseudomonas aeruginosa and
Escherichia coli (Gram negative bacteria) (Bhat & Al-daihan, 2014) with
the highest inhibitory activity of 15 ± 0.55 mm against S. pyogenes. A
S. Punia and M. Kumar
novel αD-glucose/mannose specific lectin from litchi seeds, antibiofilm
activity and their effectiveness at preventing biofilm formation was
tested in bacterial assays involving Pseudomonas aeruginosa (Bose et al.,
2016). Therefore, litchi seeds can be employed as a sustainable source
for producing antimicrobial peptides for preparation of innovative
pharma and food products.
4.7. Antiviral activities
Natural products have considerably more structural and chemical
diversities than artificially synthesized molecules (Pertino, Petrera,
Alché, & Schmeda-Hirschmann, 2018). In the past few decades, plant
derived compounds have attracted widespread interest pertaining to its
antiviral effects. In vitro tests confirmed that LSE contain remarkable
amounts of PCs which inhibits proliferation and replication of viruses.
Using the cytopathic effect (CPE) inhibitory assay and the plaque
reduction assay, A-type proanthocyanidins, litchitannin A2 extracted
from litchi seed was reported to have in vitro anti-coxsackie virus B3
(CVB3) activity with IC50 and TI (CC50/IC50) values of 35.2 μg/mL and
3.2, which was comparable to virazole (an antiviral drug) with IC50 and
TI values were 69.2 μg/mL and 6.2. Whereas aesculitannin A, and
proanthocyanidins A2 were active against herpes simplex virus 1
(HSV-1) with IC50 values of 27.1 and 18.9 μg/mL and TI values of 2.0
and 3.0, respectively, which were much weaker than acyclovir with
IC50 and TI values were 1.3 μg/mL and 506.9 (Xu et al., 2010). In
another study, CPE, reduction assay and MTT assay were used to detect
the antiviral activity of LSE on Cox B3, respiratory syncytial virus (RSV)
long strain and herpes simplex virus type 1 and type 2 (HSV-1 and
HSV-2) standard strain. Litchi seeds reported to have no inhibition on
Cox B3 in HeLa cells, but showed potent antiviral action on RSV long
strain, HSV-1 and HSV-2 standard strain in concentration dependent
manner with IC50 value of 32.3, 27.9 and 20.4 μg/mL. In addition, litchi
seeds inhibited the replication of HSV-1 in Vero cells thereby showing a
high anti-HSV effect (Wang et al., 2008). These findings may provide
important insights for the potential discovery and development of litchi
seed based novel therapeutic agents against virus strains.
4.8. Anti-obesity and lipid-lowering effects
Obesity is major epidemiologic challenge in the developed and
developing nations. Hyperlipidemia is medical condition which may
also develop into obesity and other associated diseases. It is primarily
indicated by increased concentration of triacylglycerols, total choles­
terol and LDL, along with decreased HDL (Chen et al., 2014). This sit­
uation consequently results into deposition of fats in arteries which
ultimately risks cardiovascular health. Studies on high-fat rat model
revealed the lipid-lowering capability of litchi seeds was attributed to its
copious unsaturated fatty acid profile and other compounds (saponins)
(Guo et al., 2003).
Pancreatic lipase is an enzyme present within the small intestine and
is responsible for cleaving the components of dietary triglycerides
yielding the obesity causing saturated, polyunsaturated long chain fatty
acids and β-monoglyceride (Mhatre et al., 2019; Pirahanchi & Sharma,
2019). Hence, inhibiting the pancreatic lipase activity is a fascinating
attempt towards the development of anti-obesity drugs for managing
obesity or overweight. Numerous drugs (example: orlistat) inhibits
gastrointestinal and pancreatic lipases showing anti-obesity effects but
at the same time these drugs exhibit ill effects on gastrointestinal health.
This intensifies the need of the development of safe and natural
compound-based management of the obesity. Litchi seed protein (MW:
61 ± 2 kDa) obtained from precipitation using 70% saturated ammo­
nium sulphate is proved to have potential of inhibiting pancreatic lipase
with IC50 of 73.1 μg/mL (Mhatre et al., 2019). Litchi seed protein
demonstrated its inhibitory activity on pancreatic lipase on broader
range of pH varying from 3 to 8 with maximum at 8 pH (59%) and
minimum at 3 pH (23%). Aqueous LSE (200 μ g/mL) assists in
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Trends in Food Science & Technology 108 (2021) 58–70
preventing obesity by down-regulating the adipogenesis-specific genes
such as CCAAT/enhancer binding proteins α (C/EBP α), C/EBP β, C/EBP
δ, peroxisome proliferator-activated receptors (PPARγ) and Krüppel-like
factor 9 (KLF9) in 3T3-L1 preadipocyte cells (Qi et al., 2015). Almeida
et al. (2018) incorporated litchi seed flour in hypercaloric diet and
observed a lower visceral adipose tissue mass resulting in maintaining
body weight.
5. Applications as ingredient in functional foods
Litchi seeds nutritional (polysaccharide, fats, protein, minerals and
fibers) and phytochemical (PCs) profile (as discussed in section 2) make
them an emerging candidate for the formulation of functional foods. The
application of litchi seeds in food is still juvenile and biological activities
of its extracts are explored recently to establish the beneficial effects on
human body in prevention of diseases and promoting health as
comprehensively described in section 3.
The exploration studies have suggested that various components of
the litchi seeds can be maneuvered for application the food industry.
One of the major constituents of the litchi seeds is starchy poly­
saccharide which may found enormous application in food industry as
thickener, emulsifier, and gelling agent. Litchi starchy seeds are used in
brewing sweets and fragrant wine (Bhalla-Sarin, Prasad, Kantharajah, &
Jain, 2003). The characteristics low paste clarity, SP, peak viscosity,
breakdown viscosity and high solubility along with setback viscosity of
litchi seed starch also supported its application in the treating the colon
cancer by delaying the drug delivery (Kringel et al., 2020). The func­
tionality of the native litchi seeds starch can be further improvised as per
desired application using the chemical/biological modifications. Bio­
logical active polysaccharide (LSP-W-4) from the litchi seeds inhibits
α-glucosidase showing its possible application in development of func­
tional foods suitable for managing T2D. The utilization of the litchi seed
waste as functional ingredient will not only solve the issue of environ­
mental pollution but also adds in profit of the food industry.
PCs in the litchi seeds imparts the strong antioxidant properties to
the litchi seeds. The higher radical scavenging activities of LSEs allows
its use as excellent antioxidant in formulation of value added new
products in the food industries. Aqueous LSE notably improved the meat
paste quality and safety in the post-preservation period by inhibiting
adipogenesis and lipid oxidation (Qi et al., 2015), therefore, these ex­
tracts are added to meat products as a natural additive. The lipid
lowering ability/anti-adipogenesis activity may open up an avenue for
the preparation of cardio-protective and anti-obesity promoting inno­
vative foods. Antioxidant, antimicrobial, and antiviral nature of litchi
seeds offer its application in enhancing the functionality of natural
biopolymers including chitosan, alginate, starch, and pectins for active
edible packaging of food items. However, the use of LSEs in the active
edible packaging of foods need further research.
Litchi seeds processed into flour can serve as an alternative sources of
nutrients and bioactive substances in the manufacturing of breads,
cakes, and cookies (Queiroz, Abreu, Santos, & Simão, 2015b). Food
processing industries or food-contact surfaces are very prone to biofilm
formation and possible contamination source which may led to major
hygiene problems and economic losses. Purified peptide, glucose/­
mannose specific lectin extracted from litchi seeds demonstrated
anti-biofilm activity towards food borne pathogens for example
P. aeruginosa, therefore lectin can be used as a food preservative (Bose
et al., 2016). Considering the food safety and regulatory issues as dis­
cussed in section 5, it is suggested that LSE could be engaged as func­
tional food ingredient, due to the high starch, phenolic content,
antioxidant potential, and other bioactivities.
Apart from the food applications, litchi seeds may have non-food
utilization in pharmaceutical applications. Litchi seed starch served as
drug delivery excipient and binding, suspending and emulsifying agent.
Increasing demand for natural and value-added healthy ingredients,
litchi seeds may be used as an important ingredient to the personal care
S. Punia and M. Kumar
and cosmetics industry due to its high antioxidant properties and
excellent bioactivities. As a cosmeceutical, LSE prevents collagen elastin
and hyaluronic acid degradation by inhibiting enzymes responsible for
these degradation as well as prevents wrinkles by maintaining tension
and skin moisture.
6. Food safety and regulation
Litchi seeds are higher in unusual fatty acids i.e. cyclopropanoic fatty
acids (Gontier et al., 2000) namely dihydrosterculic acid (cis-9,
l0-methyleneoctadecanoic acid) which accumulates to over 41–60%
(Ahmad et al., 2017; Jie & Chan, 1977) and 2-hexyl-cyclopropaneocta­
noic acid (cis-7,8-methylenehexadecanoic acid) which accounts for
2.3–4% of the of the total fatty acids in litchi seeds (Anwar et al., 2014).
These cyclo fatty acid are highly reactive inside the human system but
cyclopropene ring is disintegrated during the process of refining and
degradation so to make the oil good for the consumption. Apart from
unusual fatty acids, litchi seeds have varying concentration of the MCPG
and hypoglycin A (HGA) which is critical index to assess the safety for
consumption as nutraceutical source. A potent hypoglycaemic amino
acid, MCPG isolated first in 1962 from litchi kernel by Gray and Fowden,
1962. MCPG is metabolised to a toxic compound,
Methylenecyclopropyl-formyl-CoA (MCPF-CoA) is reported to possess
hypoglycemic activity because of its potential to disrupt fatty acid
β-oxidation (Ding, 1999). These toxic amino acids in litchi seeds is
responsible for hypoglycaemic effect in animal models by retarding
gluconeogenesis and fatty acids β-oxidation, making them inedible for
the direct consumption for human nutrition (Spencer & Palmer, 2017;
Sander, Terhardt, Sander, & Janzen, 2017). Studies confirmed that both
MCPG and HGA toxins are responsible for the acute encephalopathy and
other gastrointestinal complications in India, Vietnam and Bangladesh
(Shrivastava et al., 2017). Hence, utilization of litchi seeds as health
ingredient needs optimization of its ratio in food or pharma formulations
depending on the concentration of the MCPG and HGA. Therefore, LSEs
are assessed for its cytotoxic concentration in normal cells while eval­
uating them for various bioactivities (anticancer, anti-obesity, neuro-­
protection, antioxidant) in specific cell lines. For instance, in the 3-(4,
5-dimethyl-2-thiazolyl)-2,5-diphenyl-2Htetrazolium bromide assay at a
concentration (30 μg/mL), the litchi seed fraction was not cytotoxic to
the macrophage-like RAW 264.7 transformed murine cell line (Saisa­
voey et al., 2018). Hence, concentration lesser than 30 μg/mL can be
used safely for the development of health promoting products from the
litchi seed active ingredients. Despite the known fact that litchi fruits
and seeds are associated with toxins there is no regulatory restrictions on
import, however, ackee fruit which belongs from same family (Sapin­
daceae) have import restriction in United States with HGA concentration
not more than 100 mg/kg (Yang et al., 2020). An excessive amount of
litchi seed or aril may lead to a toxic situation in humans. It was esti­
mated that maximum tolerant dose (MTD) of HGA for a rat weighing
230 g was 1.5 mg/kg while it could be 0.22 mg/kg for human weighing
60 kg which suggests that ingestion of more than 13.2 mg of HGA may
result in acute toxic encephalopathy, however no such estimates are
available for MCPG till date (Blake, Bennink, & Jackson, 2006; Yang
et al., 2020). A case-control study published in the Lancet Global Health
recommended an evening meal throughout the litchi consumption sea­
son as glucose correction to avoid the situation of hypoglycaemia in
children (Shrivastava et al., 2017). A both synergistic and independent
toxic effect of MCPG and HGA need to be investigated to understand the
MTD of LSE for formulations of innovative bioactive products. Further,
increasing production of litchi in Asian countries and imports in
non-producing countries have hasten the need of laying guidance for the
consumer for consumption of litchi seed or arils based on the concen­
tration of MCPG and HPA.
68
Trends in Food Science & Technology 108 (2021) 58–70
7. Conclusion and future perspectives
Litchi is widely cultivated and consumed in the Asian countries while
exported to other parts of the globe due to its delicious taste, nutritional
profile, and numerous beneficial biological activities in the human body.
It has been shown in the review the that seed remnant of the litchi fruit
also exhibits an excellent composition of bioactive polysaccharides,
peptides, PCs with higher in beneficial unsaturated fatty acids. The in
vivo and in vitro experiments on human cell lines along with animal
model using LSEs has proved its beneficial effects as a strong anticancer,
anti-diabetes, antioxidant, anti-microbe, anti-virus, anti-obesity, and
anti-inflammation agent. Based on the nutritional and beneficial bio­
activities, this review also highlighted the potential application of litchi
seeds in active edible packaging, preservative in meats, and as func­
tional ingredient in specialized foods for the diabetic, cancer and Alz­
heimer patients. Various studies on the clinical trials has been conducted
to ensure the safe consumption of the litchi fruit, however, information
on metabolism and mechanism of action in humans is scanty.
It is evident that intervention of multidisciplinary research has
facilitated the conversion of litchi seed waste to healthful ingredient for
industry. However, further research on understanding of molecular
mechanism of bioactivities of LSEs is essential. More exploration on
pharmacological activities and safety of specific compounds from LSEs
for food and pharma application is need of time. Further, there is
insufficient data on the bioavailability of the various compounds from
litchi seeds in human system. In addition, starch polysaccharides from
litchi seed must be evaluated for application in the food system. Clinical
trials of litchi seed-based products on humans by considering all the
safety issues will boost the valorization potential of the litchi seeds for
the application in food, pharma and cosmeceutical industries.
Declaration of competing interest
None.
Acknowledgments
This research did not receive any specific grant.
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